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  • gabapentin enacarbil - Drug Summary

  • CLASSES

    Anticonvulsants, Gabapentinoids
    Neuropathic Pain and Peripheral Neuropathy Agents

    DEA CLASS

    Rx

    DESCRIPTION

    Oral analog of GABA.
    Used for restless legs syndrome, postherpetic and other neuralgias, and adjunctively for partial seizures; orphan drug for amyotrophic lateral sclerosis (ALS).
    Monitor for emerging or worsening suicidal thoughts or actions and/or depression.

    COMMON BRAND NAMES

    Active-PAC with Gabapentin, Gralise, Horizant, Neurontin

    HOW SUPPLIED

    Active-PAC with Gabapentin/Gabapentin/Neurontin Oral Cap: 100mg, 300mg, 400mg
    Gabapentin/Gralise/Neurontin Oral Tab: 300mg, 600mg, 800mg
    Gabapentin/Neurontin Oral Sol: 5mL, 250mg
    Horizant Oral Tab ER: 300mg, 600mg

    DOSAGE & INDICATIONS

    For the adjunctive treatment of partial seizures with or without secondary generalized tonic-clonic seizures.
    Oral dosage (immediate-release formulations ONLY; e.g., Neurontin)
    Adults and Adolescents

    Initially, 300 mg PO 3 times per day. May increase using 300, 400, 600, or 800 mg dosage forms PO given 3 times per day. Effective dose is 900—1800 mg/day, but up to 2400 mg/day has been used long-term. Dosages of 3600 mg/day have been given to limited patients for a relatively short duration. Do not give doses less frequently than every 12 hours. Dosage adjustments of other anticonvulsants are not necessary. Doses should be based on CrCl if indicated.

    Children 3—12 years (adjunctive treatment)

    Initially, 10—15 mg/kg/day PO in 3 divided doses; titrate upward to effective dose over a period of 3 days. If > 5 years, the effective dose is 25—35 mg/kg/day PO, given in 3 divided doses. If 3—4 years of age, the effective dose is 40 mg/kg/day PO, given in 3 divided doses. Do not give doses less frequently than every 12 hours. Depending on the clinical response, titration may continue as needed up to 50 mg/kg/day PO; higher dosages have occasionally been used. In one study, if clinically indicated, doses were further increased to a maximum of 50 mg/kg/day in refractory patients.

    For neuropathic pain associated with postherpetic neuralgia (PHN).
    Oral dosage (immediate-release formulations; e.g., Neurontin)
    Adults

    Initiate therapy at 300 mg PO as a single dose on day 1, then 600 mg/day (300 mg PO twice daily) on day 2, and 900 mg/day (300 mg PO three times per day) on day 3. The dose can then be titrated up as needed for pain relief to a dose of 1800 mg/day (600 mg PO three times per day). In most clinical studies, efficacy was demonstrated over a range of doses from 1800 mg/day to 3600 mg/day with comparable effects across the dose range. Additional benefit of using doses greater than 1800 mg/day has not been demonstrated in at least 2 randomized, placebo-controlled trials. In one trial performed prior to FDA approval for postherpetic neuralgia, an initial dose of 100 mg PO three times per day was rapidly titrated to 300 mg PO three times per day the first week, followed by an increase by 300 mg/day at weekly intervals up to 3600 mg/day in 3 divided doses by the fourth week, as tolerated. A minimum dose of 400 mg PO three times per day was allowed. At the end of the 8-week study, 83% of gabapentin treated patients had achieved a dose of 2400—3600 mg/day. Patients receiving gabapentin reported an average 33% reduction in pain as assessed by self-reporting of a 10-point pain scale. The difference versus placebo was statistically significant. In another similarly designed trial the difference in the pain score vs. placebo was 18.8% for the 1800 mg dose and 18.7% for the 2400 mg dose. There were significant differences in favor of gabapentin for a number of patients reporting >50% reduction in their pain intensity.

    Oral dosage (extended-release tablets; Gralise ONLY)

    NOTE: Do not interchange Gralise with other immediate-release or extended-release gabapentin formulations; pharmacokinetic differences between immediate- and extended-release products necessitate differing dosing regimens.

    Adults

    Initiate therapy with 300 mg PO with evening meal on Day 1, then titrate once daily dosage as follows: 600 mg on Day 2, 900 mg on Days 3—6, 1200 mg on Days 7—10, 1500 mg on Days 11—14, and 1800 mg on Day 15 and thereafter. Advise patients to swallow tablets whole and to take dose with the evening meal.

    Oral dosage (extended-release tablets; Horizant ONLY)

    NOTE: Do not interchange Horizant with other immediate-release or extended-release gabapentin formulations; pharmacokinetic differences between immediate- and extended-release products necessitate differing dosing regimens.

    Adults

    Initiate therapy at a dose of 600 mg PO in the morning for 3 days. On day 4, increase the dose to 600 mg twice daily. Advise patients to swallow tablets whole. If a dose is missed, the dose should be skipped and the next dose should be taken at the next scheduled time. A dose > 1200 mg/day provides no additional benefit, and may be associated with increased risk of adverse effects.

    For the treatment of moderate to severe primary restless legs syndrome (RLS).
    Oral dosage (gabapentin enacarbil extended-release tablets; Horizant ONLY)
    Adults

    600 mg PO once daily with food in the evening at about 5 PM each day. If the dose is missed at the recommended time, the next dose should be taken the following day as prescribed. A dose of 1,200 mg/day has been studied, but provided no additional benefit and an increase in adverse reactions was observed. LIMITS of USE: Not recommended for patients who are required to sleep during the day and remain awake at night. Different formulations of gabapentin are not interchangeable due to differing chemical forms and pharmacokinetic properties. 

    For the treatment of amyotrophic lateral sclerosis (ALS)†.
    NOTE: Gabapentin has been granted orphan drug status by the FDA for this indication.
    Oral dosage
    Adults

    In one case-control study of 110 patients, gabapentin 1000 mg/day PO, given in divided doses for 6 months, slowed decline of muscle strength and showed a trend of increased survival versus control subjects.

    For the treatment of tremor†.
    For the treatment of orthostatic tremor†.
    Oral dosage
    Adults

    100 mg PO 3 times daily initially, titrated up to 2400 mg/day PO given in divided doses, was effective in reducing orthostatic tremor in a limited trial of 4 patients. Cross-over to placebo resulted in the reappearance of tremor in all patients.

    For the treatment of essential tremor†.
    Oral dosage
    Adults

    Clinical practice guidelines of the American Academy of Neurology consider gabapentin, as monotherapy, as probably effective for the treatment of essential tremor. Initial doses have ranged from 300—400 mg/day PO (in single or divided doses). Doses are then titrated over 4—7 days to 400—600 mg PO 3 times daily, then further titrated to a maximum target dosage of 1800—3600 mg/day PO, given in 3 divided doses. Gabapentin treatment has demonstrated mixed-efficacy in these small trials; however, the data suggest overall modest clinical and functional improvements. The drug may provide a treatment option for patients with inadequate response or intolerance to standard therapies, such a beta-blockers (e.g., propranolol). At the studied doses, gabapentin improved tremor clinical rating scales and other clinical measures of tremor compared to placebo. There was no significant difference between gabapentin and propranolol with regard to these outcomes. One study demonstrated improved activities of daily living (ADL) and global ratings with higher-dose gabapentin at 3600 mg/day PO versus lower total daily doses. Common side effects included nausea, fatigue, and drowsiness. Larger, well-controlled trials are needed to determine the role of gabapentin in treating essential tremor and optimal dosing strategies.

    For the treatment of nystagmus†.
    For the treatment of acquired pendular nystagmus†.
    Oral dosage
    Adults

    Limited, short-term data suggest a dose of 300 mg PO once daily titrated to 300 mg PO 3 to 4 times daily may be effective. Gabapentin has decreased oscillopsia and the frequency of ocular oscillations and improved visual acuity.

    For the treatment of congenital nystagmus†.
    Oral dosage
    Adults and Adolescents 16 years and older

    In a small retrospective analysis, 900 mg/day PO (given in divided doses) was initially administered and increased as therapeutically indicated up to 2400 mg/day PO. Nystagmus amplitude was reduced following treatment in patients with infantile nystagmus (n = 2) and nystagmus associated with ocular pathology (n = 5). Visual acuity improved in all patients with infantile nystagmus; acuity improvements in patients with ocular pathology were seen in 4 patients.

    For the treatment of paroxysmal symptoms and spasticity† due to multiple sclerosis†.
    Oral dosage
    Adults

    In one open label trial, 18 of 21 multiple sclerosis patients who received 600—1200 mg/day PO in divided doses reported improvement of trigeminal neuralgia, paresthesia, spasticity and ocular ataxia. The authors concluded that further study of gabapentin use for treating paroxysmal symptoms in multiple sclerosis was warranted.

    For the treatment of hot flashes† due to menopause† or in women who have been treated for breast cancer.
    For reducing hot flashes† associated with natural menopause†.
    Oral dosage
    Adult females

    Initially, 300 mg/day PO is recommended, with titration to 300 mg three times daily PO if the patient still has hot flashes at lower doses. The North American Menopause Society (NAMS) Guidelines for non-hormonal therapy indicate that gabapentin is an effective choice for treating vasomotor symptoms of menopause when hormonal therapy is not desired or is contraindicated. Doses up to 2700 mg/day have been studied. Data from a small, randomized controlled trial of 59 postmenopausal women indicate that treatment with gabapentin for 12 weeks significantly reduces the frequency of hot flashes (45% reduction with gabapentin vs. 29% reduction with placebo, p = 0.02) and the frequency plus severity of hot flashes (54% reduction with gabapentin vs. 31% reduction with placebo, p = 0.01). A study of 60 postmenopausal women indicates that there is no difference in the frequency or severity of hot flashes in patients taking conjugated estrogens 0.625 mg/day vs. gabapentin 2400 mg/day (reduction in composite hot flush score by 72% for conjugated estrogens vs. 71% for gabapentin, p = 0.63), but there is a significant difference for both treatment groups vs. placebo. The overall frequency of adverse events are similar between the 2 treatments; however, gabapentin use is associated with a higher frequency in the group of symptoms including headache, dizziness, and disorientation. When the data from the available studies are compiled, the use of gabapentin 900 mg/day PO is associated with an overall decrease of 2 hot flashes/day versus placebo (mean difference -2.05, 95% CI -2.80 to -1.30).

    For reducing hot flashes† in women with breast cancer.
    Oral dosage
    Adult females

    Initially, 300 mg/day PO is recommended, with titration to 300 mg three times daily PO if the patient still has hot flashes at lower doses. The North American Menopause Society (NAMS) Guidelines for non-hormonal therapy indicate that gabapentin is an effective choice for treating vasomotor symptoms of menopause when hormonal therapy is not desired or is contraindicated. Doses up to 2700 mg/day have been studied. Data from a randomized clinical trial of 420 women with breast cancer (71% on tamoxifen therapy) indicate that gabapentin significantly reduces the mean daily frequency of hot flashes by -2.10 (90% CI -2.95 to -1.23, p less than 0.0001) and the mean percent change in severity of hot flashes by -30% (95% CI -44% to-16%, p less than 0.0001) as compared to placebo after 8 weeks; these effects can be seen as early as 4 weeks after drug initiation. A dose of 300 mg/day PO of gabapentin did not have any effects on frequency or severity of hot flashes compared to placebo. In a trial of vitamin E vs. gabapentin, the use of gabapentin was associated with a significantly greater reduction in hot flashes vs. vitamin E and 35% of the vitamin E group discontinued the trial due to lack of efficacy. When the data from the available studies are compiled, the use of gabapentin 900 mg/day PO is associated with an overall decrease of 2 hot flashes/day versus placebo (mean difference -2.05, 95% CI -2.80 to -1.30).

    For the treatment of pruritus†, including chronic kidney disease-associated pruritus (CKD-aP)†.
    For the treatment of chronic kidney disease-associated pruritus (CKD-aP) in patients undergoing hemodialysis†.
    Oral dosage (immediate-release)
    Adults

    300 mg PO 3 times weekly after hemodialysis.

    For the treatment of brachioradial pruritus†.
    Oral dosage (immediate-release)
    Adults

    300 to 1,800 mg/day PO in divided doses.

    For the treatment of fibromyalgia†.
    Oral dosage
    Adults

    Initiate treatment at 300 mg at bedtime over 1 week. After 1 week, gradually increase to target dosage (2400 mg/day) according to the following schedule: 300 mg twice daily for 1 week, 300 mg twice daily with 600 mg at bedtime for 2 weeks, 600 mg 3 times daily for 2 weeks, and 600 mg twice daily with 1200 mg at bedtime. To discontinue, taper dosage by 300 mg/day. The safety and efficacy of gabapentin for the treatment of fibromyalgia was evaluated in a randomized, double-blind, placebo-controlled, parallel-group trial. Adult patients who met the American College of Rheumatology criteria for fibromyalgia who scored >=4 on the average pain severity item of the Brief Pain Inventory (BPI) assessment were randomized in a 1:1 ratio to 12 weeks of treatment with gabapentin (n = 75) or placebo (n = 75). Acetaminophen, over-the-counter NSAIDs, and episodic use of sedating antihistamines were allowed during the trial. Antidepressants were not allowed and required a 2-week washout period prior to study entry; fluoxetine required a 30-day washout period. The primary outcome was pain severity, measured by average BPI pain severity scores (0—10, none to severe); a positive response to treatment required a score reduction >= 30%. The interference of pain on activities such as general mood, relationships, work, and sleep was also assessed. Various other secondary outcomes were evaluated, including the overall impact of fibromyalgia on many components of health status as assessed by the Fibromyalgia Impact Questionnaire (FIQ) (0—80, higher score = more negative impact). An intention-to-treat analysis was used. Thirty-one patients withdrew from the study (21%) prior to completion. The average daily gabapentin dose was 1800 mg/day. Pain severity scores decreased significantly more with gabapentin treatment at 12 weeks (from approximately 5.7 to 3.2) compared to placebo (6 to 4.6). The estimated difference between groups was -0.92 (95% CI -1.75 to -0.71, p = 0.015). Pain interference scores were also significantly lower with gabapentin (decrease from approximately 4.7 to 2.2) vs. placebo (5.3 to 3.6); the estimated difference between groups was -0.81 (95% CI -1.56 to -0.07, p = 0.032). A total of 51% vs. 31% of patients (p = 0.014) achieved a response to treatment in the gabapentin and placebo groups, respectively. FIQ total scores also favored gabapentin (26.2 +/- 15.1 vs. 37.3 +/- 18.1), with an estimated difference of -8.4 (95% CI -13 to -3.3, p = 0.001). A total of 19 patients discontinued treatment during the trial due to adverse reactions (12 with gabapentin vs. 7 with placebo). The most frequent adverse reactions associated with gabapentin were headache (26.7%), dizziness (25.3%), sedation (24%), and nausea (21.3%).

    For the treatment of singultus (hiccups)†.
    Oral dosage
    Adults

    300 mg PO 3 times daily and titrated to response up to 1200 mg/day, or alternately, 400 mg PO 3 times daily for 3 days followed by 400 mg PO once daily for 3 days.

    For the treatment of dysautonomia† following severe traumatic brain injury.
    Oral dosage (immediate-release formulations)
    Adults

    300 mg PO twice daily. Titrate to desired clinical effect. Dosages up to 600 mg PO 3 times daily have been used.

    For long-term prophylaxis of short-lasting unilateral neuralgiform headache with conjunctival injection and tearing (SUNCT)†.
    Oral dosage
    Adults

    Limited case series and case reports have suggested doses ranging from 300 mg PO twice daily up to 300 mg to 1200 mg PO three times daily may be effective in reducing or eliminated SUNCT symptoms. Most patients have required a dose of at least 900 mg/day PO. Titrate to response and tolerability.

    For the treatment of painful diabetic neuropathy†.
    Oral dosage (immediate-release formulations)
    Adults

    Initially, 300 mg PO three times per day. Titrate dosage based on clinical response and drug tolerance up to a maximum of 3600 mg/day PO, given in divided doses. In clinical trials, a mean effective and tolerated daily dosage of approximately 1500 mg/day, in divided doses, has been reported. The American Academy of Neurology considers gabapentin probably effective for the treatment of painful diabetic neuropathy. The guideline stance is based on one higher quality trial where gabapentin-treated patients' mean daily pain score at the study end point was significantly lower (p < 0.001) compared with placebo. Additional statistically significant differences favoring gabapentin were observed in secondary measures of pain and with measures of quality of life. Adverse events of gabapentin included dizziness, somnolence, and confusion. The scientific published and unpublished data regarding the off-label use of gabapentin for PDN have been scrutinized, and the use of gabapentin has been controversial due to potential bias in publication of research. However, published randomized, controlled trials and meta-analyses suggest that gabapentin is efficacious for the treatment of PDN and has a favorable safety profile.

    For the treatment of alcohol dependence†.
    Oral dosage (immediate-release products)
    Adults

    Initially, 300 mg PO at bedtime on day 1; then 300 mg PO twice daily on day 2; then 300 mg PO 3 times per day on Day 3; and then titrated upward over days 4 to 7 to reach final dosing regimen. Doses ranging from 600 mg/day to 1,800 mg/day PO have been beneficial in treating symptoms of alcohol dependence such as improving the rates of abstinence and no heavy drinking, reducing the number of heavy drinking days, and reducing the number of drinks per day. While overall quality of the studies is low, according to a review co-authored by the National Institute on Alcohol Abuse and Alcoholism (NIAAA), the efficacy of gabapentin for alcohol use disorder (AUD) is good, particularly at higher dosages, and may be considered as a treatment option. The American Psychiatric Association evidence-based practice guideline for The Pharmacological Treatment of Patients with Alcohol Use Disorder suggests that gabapentin may be offered to patients with moderate to severe alcohol use disorder who have a goal of reducing alcohol consumption or achieving abstinence, prefer gabapentin or are intolerant to or have not responded to naltrexone and acamprosate, and have no contraindications to the use of gabapentin.

    †Indicates off-label use

    MAXIMUM DOSAGE

    Adults

    3600 mg/day PO (immediate-release products, e.g., Neurontin); 1800 mg/day PO (extended-release tablets; Gralise ONLY); 1200 mg/day PO (extended-release tablets; Horizant ONLY).

    Geriatric

    3600 mg/day PO (immediate-release products, e.g., Neurontin); 1800 mg/day PO (extended-release tablets; Gralise ONLY); 1200 mg/day PO (extended-release tablets; Horizant ONLY).

    Adolescents

    3600 mg/day PO (immediate-release products, e.g., Neurontin); safety and efficacy of extended-release gabapentin products have not been established.

    Children

    3—12 years: 50 mg/kg/day PO immediate-release products has been suggested, higher dosages occasionally used in refractory patients. Safety and efficacy of extended-release gabapentin products have not been established.
    < 3 years: Safety and efficacy have not been established.

    Infants

    Safety and efficacy have not been established.

    Neonates

    Safety and efficacy have not been established.

    DOSING CONSIDERATIONS

    Hepatic Impairment

    It appears no dosage adjustment is needed, unless renal dysfunction exists concurrently. Gabapentin is not metabolized.

    Renal Impairment

    •Dose adjustment for immediate-release formulations in adult and adolescent patients >= 12 years:
    NOTE: The use of immediate-release gabapentin in children < 12 years of age with compromised renal function has not been studied.
    CrCl >= 60 mL/min: No dose adjustment needed.
    CrCl > 30—59 mL/min: Total dose range 400—1400 mg/day PO in 2 evenly divided doses.
    CrCl > 15—29 mL/min: Total dose range 200—700 mg/day PO given in one daily dose.
    CrCl = 15 mL/min: Total dose range 100—300 mg/day PO given in one daily dose as 100, 125, 150, 200, or 300 mg.
    CrCl < 15 mL/min: Reduce daily dose in proportion to CrCl (e.g., CrCl = 7.5 mL/min should receive one-half the dose that patients with CrCl of 15 mL/min receive).
    •Dose adjustment for extended-release tablets (Gralise tablets only, adult recommendations):
    CrCl >= 60 mL/min: No dose adjustment needed.
    CrCl 30—59 mL/min: 600—1800 mg/day PO daily based on tolerability and desired clinical benefit.
    CrCl < 30 mL/min: Use not recommended.
    •Dose adjustment for extended-release tablets (Horizant tablets only, adult recommendations):
    CrCl >= 60 mL/min: No dose adjustment needed. For dose tapering prior to discontinuation, reduce the dose to 600 mg PO once daily for 1 week before stopping the drug.
    CrCl 30—59 mL/min: For RLS, start at 300 mg/day PO and increase to 600 mg/day PO as needed. For PHN, start at 300 mg PO in the morning for 3 days, then increase to 300 mg PO twice daily. Increase to 600 mg PO twice daily as needed. For dose tapering prior to discontinuation, reduce the maintenance dose to once daily in the morning for 1 week before stopping the drug.
    CrCl 15—29 mL/min: For RLS, 300 mg/day PO. For PHN, 300 mg PO on day 1 and day 3, followed by a maintenance dose of 300 mg PO once daily in the morning. Increase dose to 300 mg PO twice daily as needed. For dose tapering, if the patient is taking 300 mg twice daily, reduce the dose to 300 mg PO once daily in the morning for 1 week before discontinuation. If the patient is taking 300 mg once daily no taper is required.
    CrCl < 15 mL/min: For RLS and PHN, 300 mg PO every other day. For PHN, the dose can be increased to 300 mg PO once daily in the morning if needed. No dose taper is required prior to discontinuation.
     
    Intermittent hemodialysis
    •Immediate-release formulations (adults):
    Patients on hemodialysis should receive PO maintenance doses based on CrCl as indicated for patients with renal impairment. A supplemental post-hemodialysis dose ranging from 125—350 mg PO (and based on maintenance dose and CrCl) should be given after each 4 hours of hemodialysis (see manufacturer's package label).
    •Extended-release tablets (Gralise tablets only, adults):
    Use not recommended.
    •Extended-release tablets (Horizant tablets only, adults):
    Patients should receive 300 mg PO after each dialysis. Dosage may be increased to 600 mg PO following each dialysis if needed.

    ADMINISTRATION

     
    A MedGuide is available that discusses the proper use and precautions of gabapentin as well as the risk of suicidal thoughts and behaviors associated with the use of anticonvulsant medications. This MedGuide should be dispensed with each new prescription and refill.

    Oral Administration
    Oral Solid Formulations

    Immediate-release capsule or tablet (e.g., Neurontin) administration:
    May be administered without regard to meals; however, administration with meals may minimize adverse GI effects.
    In the treatment of epilepsy the maximum time between doses should not exceed 12 hours.
    600 mg and 800 mg tablets may be broken along score line if needed. Advise patients to take the unused half-tablet with the next dose as prescribed. Half-tablets not used within 28 days of breaking the scored tablet should be discarded.
    Oral capsules should be swallowed whole with plenty of water.
    For Patients with Difficulty Swallowing: In one study, gabapentin capsules were opened, and the contents mixed with drinks (e.g., orange juice) or food (e.g., applesauce) for patients who could not swallow the capsule. Alternately, scored tablets may be cut in half with the second half-tablet used or discarded within 28 days.
     
    Extended-release tablets (e.g., Gralise or Horizant) administration:
    NOTE: Due to differing pharmacokinetic profiles and chemical formulations, do not interchange Gralise or Horizant with one another.
    Administer with meals; bioavailability is substantially lower if taken on an empty stomach. Patients taking once daily regimens should be instructed to take tablets with the evening meal (around 5 PM).
    Swallow extended-release tablets whole; do not split, crush, or chew the tablets.

    Oral Liquid Formulations

    Measure with calibrated device prior to administration to ensure accurate dosage.
    May be administered without regard to meals; however, administration with meals may minimize adverse GI effects.
    In the treatment of epilepsy the maximum time between doses should not exceed 12 hours.

    STORAGE

    Active-PAC with Gabapentin:
    - Store at controlled room temperature (between 68 and 77 degrees F)
    Gabarone :
    - Store at 77 degrees F; excursions permitted to 59-86 degrees F
    Gralise:
    - Store at 77 degrees F; excursions permitted to 59-86 degrees F
    Horizant:
    - Protect from moisture
    - Store at 77 degrees F; excursions permitted to 59-86 degrees F
    Neurontin:
    - Store at controlled room temperature (between 68 and 77 degrees F)

    CONTRAINDICATIONS / PRECAUTIONS

    General Information

    Gabapentin is contraindicated in patients who have demonstrated gabapentin hypersensitivity or hypersensitivity to any of the products' components.
     
    Neither Gralise or Horizant extended-release tablets are interchangeable with each other or other gabapentin products because of differing chemical and pharmacokinetic profiles.

    Depression, suicidal ideation

    Monitor all patients beginning treatment with antiepileptic drugs (AEDs) or currently receiving gabapentin closely for emerging or worsening depression or suicidal ideation. Advise patients and caregivers of the increased risk of suicidal thoughts and behaviors and to immediately report the emergence of new or worsening of depression, suicidal thoughts or behavior, thoughts of self-harm, or other unusual changes in mood or behavior. AEDs should be prescribed in the smallest quantity consistent with good patient management in order to reduce the risk of overdose. Epilepsy and many other illnesses for which AEDs are prescribed are themselves associated with an increased risk of suicidal thoughts and behavior. If suicidal thoughts and behavior emerge during treatment, consider whether the emergence of these symptoms in any patient may be related to the illness being treated. There is an increased risk of suicidal ideation and behavior in patients receiving AEDs to treat epilepsy, psychiatric disorders, or other conditions (e.g., migraine, neuropathic pain). The primary analysis consisted of 199 placebo-controlled clinical studies with a total of 27,863 patients in drug treatment groups and 16,029 patients in placebo groups (5 years of age and older). There were 4 completed suicides among patients in drug treatment groups versus none in the placebo groups. Patients receiving AEDs had approximately twice the risk of suicidal behavior or ideation as patients receiving placebo (0.43% vs. 0.24%, respectively; RR 1.8, 95% CI: 1.2 to 2.7). The relative risk for suicidality was higher in patients with epilepsy compared to those with other conditions; however, the absolute risk differences were similar in trials for epilepsy and psychiatric indications. Age was not a determining factor. The increased risk of suicidal ideation and behavior was observed between 1 and 24 weeks after therapy initiation. However, a longer duration of therapy should not preclude the possibility of an association to the drug since most studies included in the analysis did not continue beyond 24 weeks.

    Dialysis, renal failure, renal impairment

    Gabapentin is known to be substantially excreted by the kidney. Adjust the gabapentin dose in patients with renal impairment or renal failure undergoing dialysis, such as hemodialysis.

    Driving or operating machinery

    Because gabapentin causes somnolence and dizziness, advise patients against driving or operating machinery until they have gained enough experience on gabapentin to assess whether gabapentin impairs their ability to perform such tasks. Driving performance studies conducted with a prodrug of gabapentin (gabapentin enacarbil) indicate that gabapentin may cause significant driving impairment. The patients' ability to assess their own driving competence, as well as their ability to assess the degree of somnolence caused by gabapentin, can be imperfect. The duration of driving impairment after starting therapy with gabapentin is unknown. Whether the impairment is related to somnolence or other effects of gabapentin is unknown.

    Abrupt discontinuation

    Avoid abrupt discontinuation of gabapentin to limit drug withdrawal and the possibility of increasing seizure frequency. Gradually discontinue gabapentin over a minimum of 1 week or longer. Patients receiving gabapentin encarbil 600 mg or less may discontinue the drug without tapering.

    Substance abuse

    When using gabapentin, carefully evaluate patients for a history of substance abuse and monitor for signs and symptoms of gabapentin misuse or abuse (e.g., development of tolerance, self-dose escalation, and drug-seeking behavior). A small number of postmarketing cases report gabapentin misuse and abuse. These individuals were taking higher than recommended doses of gabapentin for unapproved uses. Most of the individuals described in these reports had a history of polysubstance abuse or used gabapentin to relieve symptoms of withdrawal from other substances.

    Chronic obstructive pulmonary disease (COPD), coadministration with other CNS depressants, pulmonary disease, respiratory depression

    Initiate gabapentin at the lowest recommended dose and monitor for symptoms of respiratory depression and sedation in elderly patients, patients with underlying pulmonary disease, such as chronic obstructive pulmonary disease (COPD), and during coadministration with other CNS depressants. Serious, life-threatening, and fatal respiratory depression has been reported with gabapentin. Most cases involved coadministration of another CNS depressant, particularly opioids, in patients with underlying respiratory impairment or advanced age. Respiratory depression, if left untreated, may cause respiratory arrest and death. Management of respiratory depression should include observation, necessary supportive measures, and reduction or withdrawal of CNS depressants, including gabapentin. Taper the dose of gabapentin used for analgesia or seizure control before discontinuation.

    Geriatric

    Initiate gabapentin at the lowest recommended dose and monitor for symptoms of respiratory depression and sedation in geriatric patients. Serious, life-threatening, and fatal respiratory depression has been reported with gabapentin. Most cases involved coadministration of another CNS depressant, particularly opioids, in patients with underlying respiratory impairment or advanced age. Respiratory depression, if left untreated, may cause respiratory arrest and death. Management of respiratory depression should include observation, necessary supportive measures, and reduction or withdrawal of CNS depressants, including gabapentin. Taper the dose of gabapentin used for analgesia or seizure control before discontinuation. Overall, clinical trials and other reported clinical experience for the various uses of gabapentin suggest that no overall differences in safety and efficacy of gabapentin occur in geriatric vs. younger adults. Some clinical trials, such as those for epilepsy or restless legs syndrome (RLS) did not include a sufficient number of patients 65 years and older to determine whether they respond differently from younger adults. Gabapentin is known to be almost exclusively excreted by the kidney, and the risk of adverse reactions to this drug may be greater in patients with impaired renal function. Adjust dosing based on estimated creatinine clearance; it may be useful to monitor renal function. According to the Beers Criteria, anticonvulsants are considered potentially inappropriate medications (PIMs) in geriatric patients with a history of falls or fractures and should be avoided in these patient populations, except for treating seizure and mood disorders, since anticonvulsants can produce ataxia, impaired psychomotor function, syncope, and additional falls. If gabapentin must be used, consider reducing the use of other CNS-active medications that increase the risk of falls and fractures and implement strategies to reduce fall risk.[63923] The federal Omnibus Budget Reconciliation Act (OBRA) regulates medication use in residents of long-term care facilities; the use of any anticonvulsant for any condition should be based on confirmation of the condition and its potential cause(s). Determine effectiveness and tolerability by evaluating symptoms, and use these as the basis for dosage adjustment for most patients. Therapeutic drug monitoring is not required or available for most anticonvulsants. Serum medication concentrations (when available) may assist in identifying toxicity. Monitor the treated patient for drug efficacy and side effects. Anticonvulsants can cause a variety of side effects; some adverse reactions can increase the risk of falls. When an anticonvulsant is being used to manage behavior, stabilize mood, or treat a psychiatric disorder, the facility should attempt periodic tapering of the medication or provide documentation of medical necessity as outlined in the OBRA guidelines.[60742]

    Pregnancy

    There are no adequate and well-controlled studies of gabapentin in pregnant women. Data from cohort studies describing the neonatal risks of gabapentin treatment during pregnancy are inconclusive. Gabapentin actively crosses the placenta. Among 6 neonates born to mothers who were taking gabapentin (doses ranging from 900 to 3,200 mg/day), umbilical cord-to-maternal plasma concentration ratios ranged from 1.3 to 2.11 (mean, 1.74) at delivery. Gabapentin concentrations in the neonates declined to an average of 27% (range, 12% to 36%) of cord blood concentrations at 24 hours postpartum. One infant was born premature at 33 weeks; however, all deliveries were uneventful and all neonates were born in healthy condition. In a prospective cohort study, rates of major malformations among neonates were similar between 223 pregnancies with gabapentin exposure and 223 unexposed pregnancies (4.1% exposed vs. 2.5% unexposed, p = 0.555). Major malformations included 2 ventricular septal defects, anencephaly, macrocephaly, microretrognathism, cutis marmorata, pyloric stenosis, bilateral varus clubfoot, and cryptorchidism. In all cases of major malformations, women received concomitant treatment with other medications during pregnancy; therefore, a causal relationship to gabapentin cannot be established. No major malformations occurred in neonates born to women exposed to gabapentin monotherapy during pregnancy (n = 36). There were higher rates of preterm births (10.5% vs. 3.9%, p = 0.019), low birth weight (less than 2,500 g) (10.5% vs. 4.4%, p = 0.033), and admission to neonatal intensive care or special care nursery (38% vs. 2.9%, p less than 0.001) among neonates with gabapentin exposure compared to unexposed neonates. Two cases of possible poor neonatal adaptation syndrome occurred in neonates with gabapentin exposure late in pregnancy compared to no cases among unexposed infants; these 2 neonates were also exposed to other psychotropic medications. In a cohort of 39 women who were exposed to gabapentin during their first trimester (97%) and throughout gestation (81.8%), malformations occurred in 3 of 44 live births. Hypospadia was reported in a neonate exposed to gabapentin and valproate; a missing kidney occurred in a neonate exposed to gabapentin and phenobarbital, and a minor malformation of the left external ear canal and 2 small skin tags at the jaw occurred in a neonate exposed to gabapentin and lamotrigine. Since exposure to multiple antiepileptic drugs occurred during these pregnancies, a causal relationship to gabapentin cannot be established. No malformations occurred in 11 patients exposed to gabapentin monotherapy during pregnancy. In animal studies, gabapentin has been fetotoxic during organogenesis at doses of 1 to 4 times the maximum recommended human dose on a mg/m2 basis. Delayed ossification of bones in the skull, limbs, and vertebrae were reported when pregnant mice received oral gabapentin (500, 1,000, or 3,000 mg/kg/day) during organogenesis. The no-effect dose for toxicity (500 mg/kg/day) is less than the maximum human recommended dose (MRHD) of 3,600 mg/kg on a body surface area (mg/m2) basis. Increased incidences of hydroureter and/or hydronephrosis were observed at all doses tested in studies in which rats received oral gabapentin (500 to 2,000 mg/kg/day). An increased incidence of fetal loss was also noted at all doses tested when pregnant rabbits were treated with oral gabapentin (60, 300, or 1,500 mg/kg) during organogenesis. There is a pregnancy exposure registry that monitors outcomes in pregnant patients exposed to gabapentin; information about the registry can be obtained at www.aedpregnancyregistry.org or by calling 1-888-233-2334.

    Breast-feeding

    Gabapentin is excreted in human breast milk; however, it is not known if gabapentin derived from gabapentin enacarbil is excreted in human milk. A breast-feeding infant could be exposed to a maximum gabapentin dose of approximately 1 mg/kg/day. There are no data on the effects of gabapentin on the breast-fed infant or milk production. Consider the developmental and health benefits of breast-feeding along with the mother's clinical need for gabapentin and any potential adverse effects on the breast-fed infant from gabapentin or the underlying maternal condition. Only use gabapentin in breast-feeding women if the benefits clearly outweigh the risks.[27986] [43322] [43905] The infant dose of gabapentin excreted in breast milk was examined in 4 infants, 3 of which were 2 to 3 weeks of age and 1 who was approximately 3 months old. The average daily maternal dosage of gabapentin was 1,575 mg (range: 600 to 2,100 mg/day). A single milk sample was obtained approximately 10 to 15 hours after the last dose. Assuming a breast milk consumption of 150 mL/kg/day, the relative infant dose of gabapentin was estimated to be 0.2 to 1.3 mg/kg/day, which approximates 1.3% to 3.8% of the weight-adjusted maternal dose. At 2 to 3 weeks after delivery, 2 infants had detectable gabapentin plasma concentrations that were under the normal range of quantification, and 1 had an undetectable concentration. At 3 months, the gabapentin plasma concentration in another infant was under the normal range of quantification. No adverse effects were reported.[62571]

    ADVERSE REACTIONS

    Severe

    suicidal ideation / Delayed / 0-0.1
    teratogenesis / Delayed / Incidence not known
    angioedema / Rapid / Incidence not known
    Stevens-Johnson syndrome / Delayed / Incidence not known
    anaphylactoid reactions / Rapid / Incidence not known
    erythema multiforme / Delayed / Incidence not known
    Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS) / Delayed / Incidence not known
    rhabdomyolysis / Delayed / Incidence not known

    Moderate

    ataxia / Delayed / 3.0-13.0
    peripheral edema / Delayed / 0-8.0
    nystagmus / Delayed / 8.0-8.0
    hostility / Early / 5.2-8.0
    blurred vision / Early / 0-5.0
    constipation / Delayed / 1.4-4.0
    amblyopia / Delayed / 3.0-4.0
    impaired cognition / Early / 1.7-2.7
    amnesia / Delayed / 2.0-2.0
    dysarthria / Delayed / 2.0-2.0
    peripheral vasodilation / Rapid / 1.1-1.1
    dystonic reaction / Delayed / 0.1-1.0
    conjunctivitis / Delayed / 1.0-1.0
    hyperglycemia / Delayed / 1.0-1.0
    withdrawal / Early / 0-1.0
    tolerance / Delayed / 0-1.0
    choreoathetosis / Delayed / 0-0.1
    depression / Delayed / 1.8
    involuntary movements / Delayed / 0.1
    confusion / Early / 1.0
    memory impairment / Delayed / 1.0
    hepatitis / Delayed / 1.0
    dyspnea / Early / 1.0
    hypertension / Early / 1.0
    dehydration / Delayed / Incidence not known
    jaundice / Delayed / Incidence not known
    hyponatremia / Delayed / Incidence not known
    eosinophilia / Delayed / Incidence not known
    bullous rash / Early / Incidence not known
    respiratory depression / Rapid / Incidence not known

    Mild

    dizziness / Early / 3.0-30.0
    drowsiness / Early / 4.5-27.0
    headache / Early / 0-15.0
    fatigue / Early / 3.0-11.0
    asthenia / Delayed / 4.0-10.0
    nausea / Early / 4.0-8.0
    vomiting / Early / 3.0-8.0
    insomnia / Early / 0-7.0
    tremor / Early / 0-7.0
    diarrhea / Early / 3.3-6.0
    diplopia / Early / 1.0-6.0
    weight gain / Delayed / 2.0-5.0
    lethargy / Early / 0-2.0
    libido decrease / Delayed / 0-2.0
    back pain / Delayed / 1.0
    irritability / Delayed / 2.0
    vertigo / Early / 1.4
    appetite stimulation / Delayed / 2.0
    dyspepsia / Early / 1.0
    anorexia / Delayed / 2.0
    xerostomia / Early / 2.0
    flatulence / Early / 2.0
    cough / Delayed / 2.0
    rhinitis / Early / 1.0
    infection / Delayed / 1.0
    pharyngitis / Delayed / 1.0
    rash / Early / 1.0
    emotional lability / Early / Incidence not known
    restlessness / Early / Incidence not known
    fever / Early / Incidence not known
    skin irritation / Early / Incidence not known

    DRUG INTERACTIONS

    Acetaminophen; Caffeine; Dihydrocodeine: (Major) Concomitant use of opioid agonists with gabapentin may cause excessive sedation, somnolence, and respiratory depression. Avoid prescribing opioid cough medications in patients taking gabapentin. Limit the use of opioid pain medications with gabapentin to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, initiate gabapentin at the lowest recommended dose and monitor patients for symptoms of respiratory depression and sedation. Use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Educate patients about the risks and symptoms of excessive CNS depression and respiratory depression.
    Acetaminophen; Chlorpheniramine: (Moderate) Monitor for excessive sedation and somnolence during coadministration of chlorpheniramine and gabapentin. Concurrent use may result in additive CNS depression.
    Acetaminophen; Chlorpheniramine; Dextromethorphan: (Moderate) Monitor for excessive sedation and somnolence during coadministration of chlorpheniramine and gabapentin. Concurrent use may result in additive CNS depression.
    Acetaminophen; Chlorpheniramine; Dextromethorphan; Phenylephrine: (Moderate) Monitor for excessive sedation and somnolence during coadministration of chlorpheniramine and gabapentin. Concurrent use may result in additive CNS depression.
    Acetaminophen; Chlorpheniramine; Dextromethorphan; Pseudoephedrine: (Moderate) Monitor for excessive sedation and somnolence during coadministration of chlorpheniramine and gabapentin. Concurrent use may result in additive CNS depression.
    Acetaminophen; Chlorpheniramine; Phenylephrine : (Moderate) Monitor for excessive sedation and somnolence during coadministration of chlorpheniramine and gabapentin. Concurrent use may result in additive CNS depression.
    Acetaminophen; Chlorpheniramine; Phenylephrine; Phenyltoloxamine: (Moderate) Monitor for excessive sedation and somnolence during coadministration of chlorpheniramine and gabapentin. Concurrent use may result in additive CNS depression.
    Acetaminophen; Codeine: (Major) Concomitant use of opioid agonists with gabapentin may cause excessive sedation, somnolence, and respiratory depression. Avoid prescribing opioid cough medications in patients taking gabapentin. Limit the use of opioid pain medications with gabapentin to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, initiate gabapentin at the lowest recommended dose and monitor patients for symptoms of respiratory depression and sedation. Use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Educate patients about the risks and symptoms of excessive CNS depression and respiratory depression.
    Acetaminophen; Dextromethorphan; Doxylamine: (Moderate) Monitor for excessive sedation and somnolence during coadministration of doxylamine and gabapentin. Concurrent use may result in additive CNS depression.
    Acetaminophen; Diphenhydramine: (Moderate) Monitor for excessive sedation and somnolence during coadministration of diphenhydramine and gabapentin. Concurrent use may result in additive CNS depression.
    Acetaminophen; Hydrocodone: (Major) Concomitant use of opioid agonists with gabapentin may cause excessive sedation, somnolence, and respiratory depression. Avoid prescribing opioid cough medications in patients taking gabapentin. Limit the use of opioid pain medications with gabapentin to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, initiate gabapentin at the lowest recommended dose and monitor patients for symptoms of respiratory depression and sedation. Use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Also, coadministration of gabapentin with hydrocodone decreases hydrocodone exposure in a dose-dependent manner. Consider the potential for decreased hydrocodone exposure and effect when gabapentin is started or discontinued in a patient taking hydrocodone. Hydrocodone (10 mg; n = 50) Cmax and AUC values were 3% to 4% lower, respectively, after administration of gabapentin (n = 48) 125 mg and 21% to 22% lower, respectively, after administration of gabapentin 500 mg. Hydrocodone increases gabapentin AUC values by 14%. The magnitude of interaction at other doses and the mechanism of the interaction are unknown.
    Acetaminophen; Oxycodone: (Major) Concomitant use of opioid agonists with gabapentin may cause excessive sedation, somnolence, and respiratory depression. Limit the use of opioid pain medications with gabapentin to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, initiate gabapentin at the lowest recommended dose and monitor patients for symptoms of respiratory depression and sedation. Use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Educate patients about the risks and symptoms of excessive CNS depression and respiratory depression.
    Acetaminophen; Pamabrom; Pyrilamine: (Moderate) Monitor for excessive sedation and somnolence during coadministration of pyrilamine and gabapentin. Concurrent use may result in additive CNS depression.
    Acetaminophen; Pentazocine: (Major) Concomitant use of pentazocine with gabapentin may cause excessive sedation, somnolence, and respiratory depression. Limit the use of pentazocine with gabapentin to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, initiate gabapentin at the lowest recommended dose and monitor patients for symptoms of respiratory depression and sedation. Use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Educate patients about the risks and symptoms of excessive CNS depression and respiratory depression.
    Acetaminophen; Propoxyphene: (Moderate) Concomitant use of opioid agonists with gabapentin may cause excessive sedation and somnolence. Limit the use of opioid pain medications with gabapentin to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Educate patients about the risks and symptoms of excessive CNS depression.
    Acrivastine; Pseudoephedrine: (Major) Avoid coadministration of acrivastine with gabapentin because of the risk of additive CNS depression. If concurrent use cannot be avoided, initiate gabapentin at the lowest recommended dose and monitor patients for symptoms of sedation and somnolence during coadministration. Educate patients about the risks and symptoms of excessive CNS depression.
    Alfentanil: (Major) Concomitant use of opioid agonists with gabapentin may cause excessive sedation, somnolence, and respiratory depression. Limit the use of alfentanil with gabapentin to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, initiate gabapentin at the lowest recommended dose and monitor patients for symptoms of respiratory depression and sedation. Use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. The magnitude and duration of CNS and cardiovascular effects of alfentanil may be enhanced. Monitor patients for hypotension or prolonged respiratory depression and sedation. The respiratory depressant effect of alfentanil may persist longer than the measured analgesic effect; consider the total dose of all opioid agonists before ordering opioid analgesics during recovery from anesthesia. Educate patients about the risks and symptoms of excessive CNS depression and respiratory depression.
    Alprazolam: (Major) Concomitant use of benzodiazepines with gabapentin may cause excessive sedation, somnolence, and respiratory depression. If concurrent use is necessary, initiate gabapentin at the lowest recommended dose and monitor patients for symptoms of respiratory depression and sedation. Educate patients about the risks and symptoms of excessive CNS depression and respiratory depression.
    Aluminum Hydroxide: (Moderate) Gabapentin should be taken at least 2 hours after the administration of antacids. Antacids have been shown to reduce the oral bioavailability of gabapentin by roughly 20%. This decrease in bioavailability was about 5% when gabapentin was administered 2 hours after the antacid.bb
    Aluminum Hydroxide; Magnesium Carbonate: (Moderate) Gabapentin should be taken at least 2 hours after the administration of antacids. Antacids have been shown to reduce the oral bioavailability of gabapentin by roughly 20%. This decrease in bioavailability was about 5% when gabapentin was administered 2 hours after the antacid.bb
    Aluminum Hydroxide; Magnesium Hydroxide: (Moderate) Gabapentin should be taken at least 2 hours after the administration of antacids. Antacids have been shown to reduce the oral bioavailability of gabapentin by roughly 20%. This decrease in bioavailability was about 5% when gabapentin was administered 2 hours after the antacid.bb
    Aluminum Hydroxide; Magnesium Hydroxide; Simethicone: (Moderate) Gabapentin should be taken at least 2 hours after the administration of antacids. Antacids have been shown to reduce the oral bioavailability of gabapentin by roughly 20%. This decrease in bioavailability was about 5% when gabapentin was administered 2 hours after the antacid.bb
    Aluminum Hydroxide; Magnesium Trisilicate: (Moderate) Gabapentin should be taken at least 2 hours after the administration of antacids. Antacids have been shown to reduce the oral bioavailability of gabapentin by roughly 20%. This decrease in bioavailability was about 5% when gabapentin was administered 2 hours after the antacid.bb
    Amobarbital: (Major) Concomitant use of barbiturates with gabapentin may cause excessive sedation, somnolence, and respiratory depression. If concurrent use is necessary, initiate gabapentin at the lowest recommended dose and monitor patients for symptoms of respiratory depression and sedation. Educate patients about the risks and symptoms of excessive CNS depression and respiratory depression.
    Amoxapine: (Major) Initiate gabapentin at the lowest recommended dose and monitor patients for symptoms of sedation and somnolence during coadministration of gabapentin and amoxapine. Concomitant use of gabapentin with amoxapine may cause additive CNS depression. Educate patients about the risks and symptoms of excessive CNS depression.
    Antacids: (Moderate) Gabapentin should be taken at least 2 hours after the administration of antacids. Antacids have been shown to reduce the oral bioavailability of gabapentin by roughly 20%. This decrease in bioavailability was about 5% when gabapentin was administered 2 hours after the antacid.bb
    Apomorphine: (Major) Initiate gabapentin at the lowest recommended dose and monitor patients for symptoms of sedation and somnolence during coadministration of gabapentin and apomorphine. Concomitant use of gabapentin with apomorphine may cause additive CNS depression. Educate patients about the risks and symptoms of excessive CNS depression. Dopaminergic agents, such as apomorphine, have also been associated with sudden sleep onset during activities of daily living such as driving, which has resulted in accidents in some cases. Reassess patients for drowsiness or sleepiness regularly throughout treatment, especially since events may occur well after the start of treatment.
    Aripiprazole: (Moderate) Monitor for excessive sedation and somnolence during coadministration of aripiprazole and gabapentin. Concurrent use may result in additive CNS depression.
    Asenapine: (Moderate) Monitor for excessive sedation and somnolence during coadministration of asenapine and gabapentin. Concurrent use may result in additive CNS depression.
    Aspirin, ASA; Butalbital; Caffeine: (Major) Concomitant use of barbiturates with gabapentin may cause excessive sedation, somnolence, and respiratory depression. If concurrent use is necessary, initiate gabapentin at the lowest recommended dose and monitor patients for symptoms of respiratory depression and sedation. Educate patients about the risks and symptoms of excessive CNS depression and respiratory depression.
    Aspirin, ASA; Butalbital; Caffeine; Codeine: (Major) Concomitant use of barbiturates with gabapentin may cause excessive sedation, somnolence, and respiratory depression. If concurrent use is necessary, initiate gabapentin at the lowest recommended dose and monitor patients for symptoms of respiratory depression and sedation. Educate patients about the risks and symptoms of excessive CNS depression and respiratory depression. (Major) Concomitant use of opioid agonists with gabapentin may cause excessive sedation, somnolence, and respiratory depression. Avoid prescribing opioid cough medications in patients taking gabapentin. Limit the use of opioid pain medications with gabapentin to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, initiate gabapentin at the lowest recommended dose and monitor patients for symptoms of respiratory depression and sedation. Use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Educate patients about the risks and symptoms of excessive CNS depression and respiratory depression.
    Aspirin, ASA; Caffeine; Dihydrocodeine: (Major) Concomitant use of opioid agonists with gabapentin may cause excessive sedation, somnolence, and respiratory depression. Avoid prescribing opioid cough medications in patients taking gabapentin. Limit the use of opioid pain medications with gabapentin to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, initiate gabapentin at the lowest recommended dose and monitor patients for symptoms of respiratory depression and sedation. Use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Educate patients about the risks and symptoms of excessive CNS depression and respiratory depression.
    Aspirin, ASA; Caffeine; Orphenadrine: (Major) Initiate gabapentin at the lowest recommended dose and monitor patients for symptoms of sedation and somnolence during coadministration of gabapentin and orphenadrine. Concomitant use of gabapentin with orphenadrine may cause additive CNS depression. Educate patients about the risks and symptoms of excessive CNS depression.
    Aspirin, ASA; Carisoprodol: (Major) Initiate gabapentin at the lowest recommended dose and monitor patients for symptoms of sedation and somnolence during coadministration of gabapentin and carisoprodol. Concomitant use of gabapentin with carisoprodol may cause additive CNS depression. Educate patients about the risks and symptoms of excessive CNS depression.
    Aspirin, ASA; Carisoprodol; Codeine: (Major) Concomitant use of opioid agonists with gabapentin may cause excessive sedation, somnolence, and respiratory depression. Avoid prescribing opioid cough medications in patients taking gabapentin. Limit the use of opioid pain medications with gabapentin to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, initiate gabapentin at the lowest recommended dose and monitor patients for symptoms of respiratory depression and sedation. Use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Educate patients about the risks and symptoms of excessive CNS depression and respiratory depression. (Major) Initiate gabapentin at the lowest recommended dose and monitor patients for symptoms of sedation and somnolence during coadministration of gabapentin and carisoprodol. Concomitant use of gabapentin with carisoprodol may cause additive CNS depression. Educate patients about the risks and symptoms of excessive CNS depression.
    Aspirin, ASA; Citric Acid; Sodium Bicarbonate: (Moderate) Antacids have been shown to reduce the oral bioavailability of gabapentin by roughly 20%. This decrease in bioavailability was about 5% when gabapentin was administered 2 hours after the antacid. It is recommended that gabapentin be taken at least 2 hours following the administration of antacids in order to avoid a significant interaction.
    Aspirin, ASA; Oxycodone: (Major) Concomitant use of opioid agonists with gabapentin may cause excessive sedation, somnolence, and respiratory depression. Limit the use of opioid pain medications with gabapentin to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, initiate gabapentin at the lowest recommended dose and monitor patients for symptoms of respiratory depression and sedation. Use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Educate patients about the risks and symptoms of excessive CNS depression and respiratory depression.
    Atropine: (Moderate) Monitor for excessive sedation and somnolence during coadministration of atropine and gabapentin. Concurrent use may result in additive CNS depression.
    Atropine; Benzoic Acid; Hyoscyamine; Methenamine; Methylene Blue; Phenyl Salicylate: (Moderate) Monitor for excessive sedation and somnolence during coadministration of atropine and gabapentin. Concurrent use may result in additive CNS depression.
    Atropine; Difenoxin: (Moderate) Monitor for excessive sedation and somnolence during coadministration of atropine and gabapentin. Concurrent use may result in additive CNS depression.
    Atropine; Edrophonium: (Moderate) Monitor for excessive sedation and somnolence during coadministration of atropine and gabapentin. Concurrent use may result in additive CNS depression.
    Azelastine: (Major) Initiate gabapentin at the lowest recommended dose and monitor patients for symptoms of sedation and somnolence during coadministration of gabapentin and azelastine. Concomitant use of gabapentin with azelastine may cause additive CNS depression. Educate patients about the risks and symptoms of excessive CNS depression.
    Azelastine; Fluticasone: (Major) Initiate gabapentin at the lowest recommended dose and monitor patients for symptoms of sedation and somnolence during coadministration of gabapentin and azelastine. Concomitant use of gabapentin with azelastine may cause additive CNS depression. Educate patients about the risks and symptoms of excessive CNS depression.
    Baclofen: (Major) Initiate gabapentin at the lowest recommended dose and monitor patients for symptoms of sedation and somnolence during coadministration of gabapentin and baclofen. Concomitant use of gabapentin with baclofen may cause additive CNS depression. Educate patients about the risks and symptoms of excessive CNS depression.
    Barbiturates: (Major) Concomitant use of barbiturates with gabapentin may cause excessive sedation, somnolence, and respiratory depression. If concurrent use is necessary, initiate gabapentin at the lowest recommended dose and monitor patients for symptoms of respiratory depression and sedation. Educate patients about the risks and symptoms of excessive CNS depression and respiratory depression.
    Belladonna Alkaloids; Ergotamine; Phenobarbital: (Major) Concomitant use of barbiturates with gabapentin may cause excessive sedation, somnolence, and respiratory depression. If concurrent use is necessary, initiate gabapentin at the lowest recommended dose and monitor patients for symptoms of respiratory depression and sedation. Educate patients about the risks and symptoms of excessive CNS depression and respiratory depression.
    Belladonna; Opium: (Major) Concomitant use of opioid agonists with gabapentin may cause excessive sedation, somnolence, and respiratory depression. Limit the use of opioid pain medications with gabapentin to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, initiate gabapentin at the lowest recommended dose and monitor patients for symptoms of respiratory depression and sedation. Use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Educate patients about the risks and symptoms of excessive CNS depression and respiratory depression.
    Benzhydrocodone; Acetaminophen: (Major) Concomitant use of opioid agonists with gabapentin may cause excessive sedation, somnolence, and respiratory depression. Limit the use of opioid pain medications with gabapentin to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, initiate gabapentin at the lowest recommended dose and monitor patients for symptoms of respiratory depression and sedation. Use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Educate patients about the risks and symptoms of excessive CNS depression and respiratory depression.
    Benzodiazepines: (Major) Concomitant use of benzodiazepines with gabapentin may cause excessive sedation, somnolence, and respiratory depression. If concurrent use is necessary, initiate gabapentin at the lowest recommended dose and monitor patients for symptoms of respiratory depression and sedation. Educate patients about the risks and symptoms of excessive CNS depression and respiratory depression.
    Brexpiprazole: (Major) Initiate gabapentin at the lowest recommended dose and monitor patients for symptoms of sedation and somnolence during coadministration of gabapentin and brexpiprazole. Concomitant use of gabapentin with brexpiprazole may cause additive CNS depression. Educate patients about the risks and symptoms of excessive CNS depression.
    Brompheniramine: (Moderate) Monitor for excessive sedation and somnolence during coadministration of brompheniramine and gabapentin. Concurrent use may result in additive CNS depression.
    Brompheniramine; Carbetapentane; Phenylephrine: (Moderate) Monitor for excessive sedation and somnolence during coadministration of brompheniramine and gabapentin. Concurrent use may result in additive CNS depression.
    Brompheniramine; Dextromethorphan; Guaifenesin: (Moderate) Monitor for excessive sedation and somnolence during coadministration of brompheniramine and gabapentin. Concurrent use may result in additive CNS depression.
    Brompheniramine; Dextromethorphan; Phenylephrine: (Moderate) Monitor for excessive sedation and somnolence during coadministration of brompheniramine and gabapentin. Concurrent use may result in additive CNS depression.
    Brompheniramine; Guaifenesin; Hydrocodone: (Major) Concomitant use of opioid agonists with gabapentin may cause excessive sedation, somnolence, and respiratory depression. Avoid prescribing opioid cough medications in patients taking gabapentin. Limit the use of opioid pain medications with gabapentin to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, initiate gabapentin at the lowest recommended dose and monitor patients for symptoms of respiratory depression and sedation. Use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Also, coadministration of gabapentin with hydrocodone decreases hydrocodone exposure in a dose-dependent manner. Consider the potential for decreased hydrocodone exposure and effect when gabapentin is started or discontinued in a patient taking hydrocodone. Hydrocodone (10 mg; n = 50) Cmax and AUC values were 3% to 4% lower, respectively, after administration of gabapentin (n = 48) 125 mg and 21% to 22% lower, respectively, after administration of gabapentin 500 mg. Hydrocodone increases gabapentin AUC values by 14%. The magnitude of interaction at other doses and the mechanism of the interaction are unknown. (Moderate) Monitor for excessive sedation and somnolence during coadministration of brompheniramine and gabapentin. Concurrent use may result in additive CNS depression.
    Brompheniramine; Hydrocodone; Pseudoephedrine: (Major) Concomitant use of opioid agonists with gabapentin may cause excessive sedation, somnolence, and respiratory depression. Avoid prescribing opioid cough medications in patients taking gabapentin. Limit the use of opioid pain medications with gabapentin to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, initiate gabapentin at the lowest recommended dose and monitor patients for symptoms of respiratory depression and sedation. Use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Also, coadministration of gabapentin with hydrocodone decreases hydrocodone exposure in a dose-dependent manner. Consider the potential for decreased hydrocodone exposure and effect when gabapentin is started or discontinued in a patient taking hydrocodone. Hydrocodone (10 mg; n = 50) Cmax and AUC values were 3% to 4% lower, respectively, after administration of gabapentin (n = 48) 125 mg and 21% to 22% lower, respectively, after administration of gabapentin 500 mg. Hydrocodone increases gabapentin AUC values by 14%. The magnitude of interaction at other doses and the mechanism of the interaction are unknown. (Moderate) Monitor for excessive sedation and somnolence during coadministration of brompheniramine and gabapentin. Concurrent use may result in additive CNS depression.
    Brompheniramine; Phenylephrine: (Moderate) Monitor for excessive sedation and somnolence during coadministration of brompheniramine and gabapentin. Concurrent use may result in additive CNS depression.
    Brompheniramine; Pseudoephedrine: (Moderate) Monitor for excessive sedation and somnolence during coadministration of brompheniramine and gabapentin. Concurrent use may result in additive CNS depression.
    Brompheniramine; Pseudoephedrine; Dextromethorphan: (Moderate) Monitor for excessive sedation and somnolence during coadministration of brompheniramine and gabapentin. Concurrent use may result in additive CNS depression.
    Buprenorphine: (Major) Concomitant use of buprenorphine with gabapentin may cause excessive sedation, somnolence, and respiratory depression. Limit the use of buprenorphine with gabapentin to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, initiate gabapentin at the lowest recommended dose and monitor patients for symptoms of respiratory depression and sedation. Use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Educate patients about the risks and symptoms of excessive CNS depression and respiratory depression.
    Buprenorphine; Naloxone: (Major) Concomitant use of buprenorphine with gabapentin may cause excessive sedation, somnolence, and respiratory depression. Limit the use of buprenorphine with gabapentin to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, initiate gabapentin at the lowest recommended dose and monitor patients for symptoms of respiratory depression and sedation. Use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Educate patients about the risks and symptoms of excessive CNS depression and respiratory depression.
    Bupropion: (Moderate) A reduction in seizure threshold has been reported following concomitant administration of pemoline with anticonvulsant agents.
    Bupropion; Naltrexone: (Moderate) A reduction in seizure threshold has been reported following concomitant administration of pemoline with anticonvulsant agents.
    Butabarbital: (Major) Concomitant use of barbiturates with gabapentin may cause excessive sedation, somnolence, and respiratory depression. If concurrent use is necessary, initiate gabapentin at the lowest recommended dose and monitor patients for symptoms of respiratory depression and sedation. Educate patients about the risks and symptoms of excessive CNS depression and respiratory depression.
    Butalbital; Acetaminophen: (Major) Concomitant use of barbiturates with gabapentin may cause excessive sedation, somnolence, and respiratory depression. If concurrent use is necessary, initiate gabapentin at the lowest recommended dose and monitor patients for symptoms of respiratory depression and sedation. Educate patients about the risks and symptoms of excessive CNS depression and respiratory depression.
    Butalbital; Acetaminophen; Caffeine: (Major) Concomitant use of barbiturates with gabapentin may cause excessive sedation, somnolence, and respiratory depression. If concurrent use is necessary, initiate gabapentin at the lowest recommended dose and monitor patients for symptoms of respiratory depression and sedation. Educate patients about the risks and symptoms of excessive CNS depression and respiratory depression.
    Butalbital; Acetaminophen; Caffeine; Codeine: (Major) Concomitant use of barbiturates with gabapentin may cause excessive sedation, somnolence, and respiratory depression. If concurrent use is necessary, initiate gabapentin at the lowest recommended dose and monitor patients for symptoms of respiratory depression and sedation. Educate patients about the risks and symptoms of excessive CNS depression and respiratory depression. (Major) Concomitant use of opioid agonists with gabapentin may cause excessive sedation, somnolence, and respiratory depression. Avoid prescribing opioid cough medications in patients taking gabapentin. Limit the use of opioid pain medications with gabapentin to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, initiate gabapentin at the lowest recommended dose and monitor patients for symptoms of respiratory depression and sedation. Use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Educate patients about the risks and symptoms of excessive CNS depression and respiratory depression.
    Butorphanol: (Major) Concomitant use of butorphanol with gabapentin may cause excessive sedation, somnolence, and respiratory depression. Limit the use of butorphanol with gabapentin to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, initiate gabapentin at the lowest recommended dose and monitor patients for symptoms of respiratory depression and sedation. Use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Educate patients about the risks and symptoms of excessive CNS depression and respiratory depression.
    Calcium Carbonate: (Moderate) Antacids (e.g., aluminum hydroxide; magnesium hydroxide) have been shown to reduce the oral bioavailability of gabapentin by roughly 20%. This decrease in bioavailability was about 5% when gabapentin was administered 2 hours after the antacid. It is recommended that gabapentin be taken at least 2 hours following the administration of antacids in order to avoid a significant interaction.
    Calcium Carbonate; Famotidine; Magnesium Hydroxide: (Moderate) Antacids (e.g., aluminum hydroxide; magnesium hydroxide) have been shown to reduce the oral bioavailability of gabapentin by roughly 20%. This decrease in bioavailability was about 5% when gabapentin was administered 2 hours after the antacid. It is recommended that gabapentin be taken at least 2 hours following the administration of antacids in order to avoid a significant interaction.
    Calcium Carbonate; Magnesium Hydroxide: (Moderate) Antacids (e.g., aluminum hydroxide; magnesium hydroxide) have been shown to reduce the oral bioavailability of gabapentin by roughly 20%. This decrease in bioavailability was about 5% when gabapentin was administered 2 hours after the antacid. It is recommended that gabapentin be taken at least 2 hours following the administration of antacids in order to avoid a significant interaction.
    Calcium Carbonate; Magnesium Hydroxide; Simethicone: (Moderate) Antacids (e.g., aluminum hydroxide; magnesium hydroxide) have been shown to reduce the oral bioavailability of gabapentin by roughly 20%. This decrease in bioavailability was about 5% when gabapentin was administered 2 hours after the antacid. It is recommended that gabapentin be taken at least 2 hours following the administration of antacids in order to avoid a significant interaction.
    Calcium Carbonate; Risedronate: (Moderate) Antacids (e.g., aluminum hydroxide; magnesium hydroxide) have been shown to reduce the oral bioavailability of gabapentin by roughly 20%. This decrease in bioavailability was about 5% when gabapentin was administered 2 hours after the antacid. It is recommended that gabapentin be taken at least 2 hours following the administration of antacids in order to avoid a significant interaction.
    Calcium Carbonate; Simethicone: (Moderate) Antacids (e.g., aluminum hydroxide; magnesium hydroxide) have been shown to reduce the oral bioavailability of gabapentin by roughly 20%. This decrease in bioavailability was about 5% when gabapentin was administered 2 hours after the antacid. It is recommended that gabapentin be taken at least 2 hours following the administration of antacids in order to avoid a significant interaction.
    Calcium, Magnesium, Potassium, Sodium Oxybates: (Major) Concomitant use of sodium oxybate with gabapentin may cause excessive sedation, somnolence, and respiratory depression. If concurrent use is necessary, initiate gabapentin at the lowest recommended dose and monitor patients for symptoms of respiratory depression and sedation. Educate patients about the risks and symptoms of excessive CNS depression and respiratory depression.
    Calcium; Vitamin D: (Moderate) Antacids (e.g., aluminum hydroxide; magnesium hydroxide) have been shown to reduce the oral bioavailability of gabapentin by roughly 20%. This decrease in bioavailability was about 5% when gabapentin was administered 2 hours after the antacid. It is recommended that gabapentin be taken at least 2 hours following the administration of antacids in order to avoid a significant interaction.
    Cannabidiol: (Moderate) Monitor for excessive sedation and somnolence during coadministration of cannabidiol and gabapentin. Concurrent use may result in additive CNS depression.
    Capsaicin; Metaxalone: (Major) Initiate gabapentin at the lowest recommended dose and monitor patients for symptoms of sedation and somnolence during coadministration of gabapentin and metaxalone. Concomitant use of gabapentin with metaxalone may cause additive CNS depression. Educate patients about the risks and symptoms of excessive CNS depression.
    Carbetapentane; Chlorpheniramine: (Moderate) Monitor for excessive sedation and somnolence during coadministration of chlorpheniramine and gabapentin. Concurrent use may result in additive CNS depression.
    Carbetapentane; Chlorpheniramine; Phenylephrine: (Moderate) Monitor for excessive sedation and somnolence during coadministration of chlorpheniramine and gabapentin. Concurrent use may result in additive CNS depression.
    Carbetapentane; Diphenhydramine; Phenylephrine: (Moderate) Monitor for excessive sedation and somnolence during coadministration of diphenhydramine and gabapentin. Concurrent use may result in additive CNS depression.
    Carbetapentane; Phenylephrine; Pyrilamine: (Moderate) Monitor for excessive sedation and somnolence during coadministration of pyrilamine and gabapentin. Concurrent use may result in additive CNS depression.
    Carbetapentane; Pyrilamine: (Moderate) Monitor for excessive sedation and somnolence during coadministration of pyrilamine and gabapentin. Concurrent use may result in additive CNS depression.
    Carbidopa; Levodopa: (Major) Initiate gabapentin at the lowest recommended dose and monitor patients for symptoms of sedation and somnolence during coadministration of gabapentin and levodopa. Concomitant use of gabapentin with levodopa may cause additive CNS depression. Educate patients about the risks and symptoms of excessive CNS depression. Dopaminergic agents, such as levodopa, have also been associated with sudden sleep onset during activities of daily living such as driving, which has resulted in accidents in some cases. Reassess patients for drowsiness or sleepiness regularly throughout treatment, especially since events may occur well after the start of treatment.
    Carbidopa; Levodopa; Entacapone: (Major) Initiate gabapentin at the lowest recommended dose and monitor patients for symptoms of sedation and somnolence during coadministration of gabapentin and entacapone. Concomitant use of gabapentin with entacapone may cause additive CNS depression. Educate patients about the risks and symptoms of excessive CNS depression. Dopaminergic agents, such as entacapone, have also been associated with sudden sleep onset during activities of daily living such as driving, which has resulted in accidents in some cases. Reassess patients for drowsiness or sleepiness regularly throughout treatment, especially since events may occur well after the start of treatment. (Major) Initiate gabapentin at the lowest recommended dose and monitor patients for symptoms of sedation and somnolence during coadministration of gabapentin and levodopa. Concomitant use of gabapentin with levodopa may cause additive CNS depression. Educate patients about the risks and symptoms of excessive CNS depression. Dopaminergic agents, such as levodopa, have also been associated with sudden sleep onset during activities of daily living such as driving, which has resulted in accidents in some cases. Reassess patients for drowsiness or sleepiness regularly throughout treatment, especially since events may occur well after the start of treatment.
    Carbinoxamine: (Moderate) Monitor for excessive sedation and somnolence during coadministration of carbinoxamine and gabapentin. Concurrent use may result in additive CNS depression.
    Carbinoxamine; Dextromethorphan; Pseudoephedrine: (Moderate) Monitor for excessive sedation and somnolence during coadministration of carbinoxamine and gabapentin. Concurrent use may result in additive CNS depression.
    Carbinoxamine; Hydrocodone; Phenylephrine: (Major) Concomitant use of opioid agonists with gabapentin may cause excessive sedation, somnolence, and respiratory depression. Avoid prescribing opioid cough medications in patients taking gabapentin. Limit the use of opioid pain medications with gabapentin to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, initiate gabapentin at the lowest recommended dose and monitor patients for symptoms of respiratory depression and sedation. Use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Also, coadministration of gabapentin with hydrocodone decreases hydrocodone exposure in a dose-dependent manner. Consider the potential for decreased hydrocodone exposure and effect when gabapentin is started or discontinued in a patient taking hydrocodone. Hydrocodone (10 mg; n = 50) Cmax and AUC values were 3% to 4% lower, respectively, after administration of gabapentin (n = 48) 125 mg and 21% to 22% lower, respectively, after administration of gabapentin 500 mg. Hydrocodone increases gabapentin AUC values by 14%. The magnitude of interaction at other doses and the mechanism of the interaction are unknown. (Moderate) Monitor for excessive sedation and somnolence during coadministration of carbinoxamine and gabapentin. Concurrent use may result in additive CNS depression.
    Carbinoxamine; Hydrocodone; Pseudoephedrine: (Major) Concomitant use of opioid agonists with gabapentin may cause excessive sedation, somnolence, and respiratory depression. Avoid prescribing opioid cough medications in patients taking gabapentin. Limit the use of opioid pain medications with gabapentin to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, initiate gabapentin at the lowest recommended dose and monitor patients for symptoms of respiratory depression and sedation. Use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Also, coadministration of gabapentin with hydrocodone decreases hydrocodone exposure in a dose-dependent manner. Consider the potential for decreased hydrocodone exposure and effect when gabapentin is started or discontinued in a patient taking hydrocodone. Hydrocodone (10 mg; n = 50) Cmax and AUC values were 3% to 4% lower, respectively, after administration of gabapentin (n = 48) 125 mg and 21% to 22% lower, respectively, after administration of gabapentin 500 mg. Hydrocodone increases gabapentin AUC values by 14%. The magnitude of interaction at other doses and the mechanism of the interaction are unknown. (Moderate) Monitor for excessive sedation and somnolence during coadministration of carbinoxamine and gabapentin. Concurrent use may result in additive CNS depression.
    Carbinoxamine; Phenylephrine: (Moderate) Monitor for excessive sedation and somnolence during coadministration of carbinoxamine and gabapentin. Concurrent use may result in additive CNS depression.
    Carbinoxamine; Pseudoephedrine: (Moderate) Monitor for excessive sedation and somnolence during coadministration of carbinoxamine and gabapentin. Concurrent use may result in additive CNS depression.
    Cariprazine: (Moderate) Monitor for excessive sedation and somnolence during coadministration of cariprazine and gabapentin. Concurrent use may result in additive CNS depression.
    Carisoprodol: (Major) Initiate gabapentin at the lowest recommended dose and monitor patients for symptoms of sedation and somnolence during coadministration of gabapentin and carisoprodol. Concomitant use of gabapentin with carisoprodol may cause additive CNS depression. Educate patients about the risks and symptoms of excessive CNS depression.
    Celecoxib; Tramadol: (Major) Concomitant use of opioid agonists with gabapentin may cause excessive sedation, somnolence, and respiratory depression. Limit the use of opioid pain medications with gabapentin to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, initiate gabapentin at the lowest recommended dose and monitor patients for symptoms of respiratory depression and sedation. Use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Educate patients about the risks and symptoms of excessive CNS depression and respiratory depression.
    Cenobamate: (Moderate) Monitor for excessive sedation and somnolence during coadministration of cenobamate and gabapentin. Concurrent use may result in additive CNS depression.
    Cetirizine: (Moderate) Monitor for excessive sedation and somnolence during coadministration of cetirizine and gabapentin. Concurrent use may result in additive CNS depression.
    Cetirizine; Pseudoephedrine: (Moderate) Monitor for excessive sedation and somnolence during coadministration of cetirizine and gabapentin. Concurrent use may result in additive CNS depression.
    Chlophedianol; Dexbrompheniramine: (Moderate) Monitor for excessive sedation and somnolence during coadministration of dexbrompheniramine and gabapentin. Concurrent use may result in additive CNS depression.
    Chlophedianol; Dexchlorpheniramine; Pseudoephedrine: (Moderate) Monitor for excessive sedation and somnolence during coadministration of dexchlorpheniramine and gabapentin. Concurrent use may result in additive CNS depression.
    Chloral Hydrate: (Major) Initiate gabapentin at the lowest recommended dose and monitor patients for symptoms of sedation and somnolence during coadministration of gabapentin and chloral hydrate. Concomitant use of gabapentin with chloral hydrate may cause additive CNS depression. Educate patients about the risks and symptoms of excessive CNS depression.
    Chlorcyclizine: (Moderate) Monitor for excessive sedation and somnolence during coadministration of chlorcyclizine and gabapentin. Concurrent use may result in additive CNS depression.
    Chlordiazepoxide: (Major) Concomitant use of benzodiazepines with gabapentin may cause excessive sedation, somnolence, and respiratory depression. If concurrent use is necessary, initiate gabapentin at the lowest recommended dose and monitor patients for symptoms of respiratory depression and sedation. Educate patients about the risks and symptoms of excessive CNS depression and respiratory depression.
    Chlordiazepoxide; Amitriptyline: (Major) Concomitant use of benzodiazepines with gabapentin may cause excessive sedation, somnolence, and respiratory depression. If concurrent use is necessary, initiate gabapentin at the lowest recommended dose and monitor patients for symptoms of respiratory depression and sedation. Educate patients about the risks and symptoms of excessive CNS depression and respiratory depression.
    Chlordiazepoxide; Clidinium: (Major) Concomitant use of benzodiazepines with gabapentin may cause excessive sedation, somnolence, and respiratory depression. If concurrent use is necessary, initiate gabapentin at the lowest recommended dose and monitor patients for symptoms of respiratory depression and sedation. Educate patients about the risks and symptoms of excessive CNS depression and respiratory depression.
    Chlorpheniramine: (Moderate) Monitor for excessive sedation and somnolence during coadministration of chlorpheniramine and gabapentin. Concurrent use may result in additive CNS depression.
    Chlorpheniramine; Codeine: (Major) Concomitant use of opioid agonists with gabapentin may cause excessive sedation, somnolence, and respiratory depression. Avoid prescribing opioid cough medications in patients taking gabapentin. Limit the use of opioid pain medications with gabapentin to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, initiate gabapentin at the lowest recommended dose and monitor patients for symptoms of respiratory depression and sedation. Use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Educate patients about the risks and symptoms of excessive CNS depression and respiratory depression. (Moderate) Monitor for excessive sedation and somnolence during coadministration of chlorpheniramine and gabapentin. Concurrent use may result in additive CNS depression.
    Chlorpheniramine; Dextromethorphan: (Moderate) Monitor for excessive sedation and somnolence during coadministration of chlorpheniramine and gabapentin. Concurrent use may result in additive CNS depression.
    Chlorpheniramine; Dextromethorphan; Phenylephrine: (Moderate) Monitor for excessive sedation and somnolence during coadministration of chlorpheniramine and gabapentin. Concurrent use may result in additive CNS depression.
    Chlorpheniramine; Dextromethorphan; Pseudoephedrine: (Moderate) Monitor for excessive sedation and somnolence during coadministration of chlorpheniramine and gabapentin. Concurrent use may result in additive CNS depression.
    Chlorpheniramine; Dihydrocodeine; Phenylephrine: (Major) Concomitant use of opioid agonists with gabapentin may cause excessive sedation, somnolence, and respiratory depression. Avoid prescribing opioid cough medications in patients taking gabapentin. Limit the use of opioid pain medications with gabapentin to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, initiate gabapentin at the lowest recommended dose and monitor patients for symptoms of respiratory depression and sedation. Use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Educate patients about the risks and symptoms of excessive CNS depression and respiratory depression. (Moderate) Monitor for excessive sedation and somnolence during coadministration of chlorpheniramine and gabapentin. Concurrent use may result in additive CNS depression.
    Chlorpheniramine; Dihydrocodeine; Pseudoephedrine: (Major) Concomitant use of opioid agonists with gabapentin may cause excessive sedation, somnolence, and respiratory depression. Avoid prescribing opioid cough medications in patients taking gabapentin. Limit the use of opioid pain medications with gabapentin to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, initiate gabapentin at the lowest recommended dose and monitor patients for symptoms of respiratory depression and sedation. Use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Educate patients about the risks and symptoms of excessive CNS depression and respiratory depression. (Moderate) Monitor for excessive sedation and somnolence during coadministration of chlorpheniramine and gabapentin. Concurrent use may result in additive CNS depression.
    Chlorpheniramine; Guaifenesin; Hydrocodone; Pseudoephedrine: (Major) Concomitant use of opioid agonists with gabapentin may cause excessive sedation, somnolence, and respiratory depression. Avoid prescribing opioid cough medications in patients taking gabapentin. Limit the use of opioid pain medications with gabapentin to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, initiate gabapentin at the lowest recommended dose and monitor patients for symptoms of respiratory depression and sedation. Use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Also, coadministration of gabapentin with hydrocodone decreases hydrocodone exposure in a dose-dependent manner. Consider the potential for decreased hydrocodone exposure and effect when gabapentin is started or discontinued in a patient taking hydrocodone. Hydrocodone (10 mg; n = 50) Cmax and AUC values were 3% to 4% lower, respectively, after administration of gabapentin (n = 48) 125 mg and 21% to 22% lower, respectively, after administration of gabapentin 500 mg. Hydrocodone increases gabapentin AUC values by 14%. The magnitude of interaction at other doses and the mechanism of the interaction are unknown. (Moderate) Monitor for excessive sedation and somnolence during coadministration of chlorpheniramine and gabapentin. Concurrent use may result in additive CNS depression.
    Chlorpheniramine; Hydrocodone: (Major) Concomitant use of opioid agonists with gabapentin may cause excessive sedation, somnolence, and respiratory depression. Avoid prescribing opioid cough medications in patients taking gabapentin. Limit the use of opioid pain medications with gabapentin to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, initiate gabapentin at the lowest recommended dose and monitor patients for symptoms of respiratory depression and sedation. Use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Also, coadministration of gabapentin with hydrocodone decreases hydrocodone exposure in a dose-dependent manner. Consider the potential for decreased hydrocodone exposure and effect when gabapentin is started or discontinued in a patient taking hydrocodone. Hydrocodone (10 mg; n = 50) Cmax and AUC values were 3% to 4% lower, respectively, after administration of gabapentin (n = 48) 125 mg and 21% to 22% lower, respectively, after administration of gabapentin 500 mg. Hydrocodone increases gabapentin AUC values by 14%. The magnitude of interaction at other doses and the mechanism of the interaction are unknown. (Moderate) Monitor for excessive sedation and somnolence during coadministration of chlorpheniramine and gabapentin. Concurrent use may result in additive CNS depression.
    Chlorpheniramine; Hydrocodone; Phenylephrine: (Major) Concomitant use of opioid agonists with gabapentin may cause excessive sedation, somnolence, and respiratory depression. Avoid prescribing opioid cough medications in patients taking gabapentin. Limit the use of opioid pain medications with gabapentin to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, initiate gabapentin at the lowest recommended dose and monitor patients for symptoms of respiratory depression and sedation. Use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Also, coadministration of gabapentin with hydrocodone decreases hydrocodone exposure in a dose-dependent manner. Consider the potential for decreased hydrocodone exposure and effect when gabapentin is started or discontinued in a patient taking hydrocodone. Hydrocodone (10 mg; n = 50) Cmax and AUC values were 3% to 4% lower, respectively, after administration of gabapentin (n = 48) 125 mg and 21% to 22% lower, respectively, after administration of gabapentin 500 mg. Hydrocodone increases gabapentin AUC values by 14%. The magnitude of interaction at other doses and the mechanism of the interaction are unknown. (Moderate) Monitor for excessive sedation and somnolence during coadministration of chlorpheniramine and gabapentin. Concurrent use may result in additive CNS depression.
    Chlorpheniramine; Hydrocodone; Pseudoephedrine: (Major) Concomitant use of opioid agonists with gabapentin may cause excessive sedation, somnolence, and respiratory depression. Avoid prescribing opioid cough medications in patients taking gabapentin. Limit the use of opioid pain medications with gabapentin to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, initiate gabapentin at the lowest recommended dose and monitor patients for symptoms of respiratory depression and sedation. Use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Also, coadministration of gabapentin with hydrocodone decreases hydrocodone exposure in a dose-dependent manner. Consider the potential for decreased hydrocodone exposure and effect when gabapentin is started or discontinued in a patient taking hydrocodone. Hydrocodone (10 mg; n = 50) Cmax and AUC values were 3% to 4% lower, respectively, after administration of gabapentin (n = 48) 125 mg and 21% to 22% lower, respectively, after administration of gabapentin 500 mg. Hydrocodone increases gabapentin AUC values by 14%. The magnitude of interaction at other doses and the mechanism of the interaction are unknown. (Moderate) Monitor for excessive sedation and somnolence during coadministration of chlorpheniramine and gabapentin. Concurrent use may result in additive CNS depression.
    Chlorpheniramine; Ibuprofen; Pseudoephedrine: (Moderate) Monitor for excessive sedation and somnolence during coadministration of chlorpheniramine and gabapentin. Concurrent use may result in additive CNS depression.
    Chlorpheniramine; Phenylephrine: (Moderate) Monitor for excessive sedation and somnolence during coadministration of chlorpheniramine and gabapentin. Concurrent use may result in additive CNS depression.
    Chlorpheniramine; Pseudoephedrine: (Moderate) Monitor for excessive sedation and somnolence during coadministration of chlorpheniramine and gabapentin. Concurrent use may result in additive CNS depression.
    Chlorpromazine: (Major) Initiate gabapentin at the lowest recommended dose and monitor patients for symptoms of sedation and somnolence during coadministration of gabapentin and chlorpromazine. Concomitant use of gabapentin with chlorpromazine may cause additive CNS depression. Educate patients about the risks and symptoms of excessive CNS depression.
    Chlorthalidone; Clonidine: (Major) Initiate gabapentin at the lowest recommended dose and monitor patients for symptoms of sedation and somnolence during coadministration of gabapentin and clonidine. Concomitant use of gabapentin with clonidine may cause additive CNS depression. Educate patients about the risks and symptoms of excessive CNS depression.
    Chlorzoxazone: (Major) Initiate gabapentin at the lowest recommended dose and monitor patients for symptoms of sedation and somnolence during coadministration of gabapentin and chlorzoxazone. Concomitant use of gabapentin with chlorzoxazone may cause additive CNS depression. Educate patients about the risks and symptoms of excessive CNS depression.
    Clemastine: (Moderate) Monitor for excessive sedation and somnolence during coadministration of clemastine and gabapentin. Concurrent use may result in additive CNS depression.
    Clobazam: (Major) Concomitant use of clobazam with gabapentin may cause excessive sedation, somnolence, and respiratory depression. If concurrent use is necessary, initiate gabapentin at the lowest recommended dose and monitor patients for symptoms of respiratory depression and sedation. Educate patients about the risks and symptoms of excessive CNS depression and respiratory depression.
    Clonazepam: (Major) Concomitant use of benzodiazepines with gabapentin may cause excessive sedation, somnolence, and respiratory depression. If concurrent use is necessary, initiate gabapentin at the lowest recommended dose and monitor patients for symptoms of respiratory depression and sedation. Educate patients about the risks and symptoms of excessive CNS depression and respiratory depression.
    Clonidine: (Major) Initiate gabapentin at the lowest recommended dose and monitor patients for symptoms of sedation and somnolence during coadministration of gabapentin and clonidine. Concomitant use of gabapentin with clonidine may cause additive CNS depression. Educate patients about the risks and symptoms of excessive CNS depression.
    Clorazepate: (Major) Concomitant use of benzodiazepines with gabapentin may cause excessive sedation, somnolence, and respiratory depression. If concurrent use is necessary, initiate gabapentin at the lowest recommended dose and monitor patients for symptoms of respiratory depression and sedation. Educate patients about the risks and symptoms of excessive CNS depression and respiratory depression.
    Clozapine: (Major) Initiate gabapentin at the lowest recommended dose and monitor patients for symptoms of sedation and somnolence during coadministration of gabapentin and clozapine. Concomitant use of gabapentin with clozapine may cause additive CNS depression. Educate patients about the risks and symptoms of excessive CNS depression.
    Codeine: (Major) Concomitant use of opioid agonists with gabapentin may cause excessive sedation, somnolence, and respiratory depression. Avoid prescribing opioid cough medications in patients taking gabapentin. Limit the use of opioid pain medications with gabapentin to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, initiate gabapentin at the lowest recommended dose and monitor patients for symptoms of respiratory depression and sedation. Use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Educate patients about the risks and symptoms of excessive CNS depression and respiratory depression.
    Codeine; Guaifenesin: (Major) Concomitant use of opioid agonists with gabapentin may cause excessive sedation, somnolence, and respiratory depression. Avoid prescribing opioid cough medications in patients taking gabapentin. Limit the use of opioid pain medications with gabapentin to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, initiate gabapentin at the lowest recommended dose and monitor patients for symptoms of respiratory depression and sedation. Use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Educate patients about the risks and symptoms of excessive CNS depression and respiratory depression.
    Codeine; Guaifenesin; Pseudoephedrine: (Major) Concomitant use of opioid agonists with gabapentin may cause excessive sedation, somnolence, and respiratory depression. Avoid prescribing opioid cough medications in patients taking gabapentin. Limit the use of opioid pain medications with gabapentin to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, initiate gabapentin at the lowest recommended dose and monitor patients for symptoms of respiratory depression and sedation. Use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Educate patients about the risks and symptoms of excessive CNS depression and respiratory depression.
    Codeine; Phenylephrine; Promethazine: (Major) Concomitant use of opioid agonists with gabapentin may cause excessive sedation, somnolence, and respiratory depression. Avoid prescribing opioid cough medications in patients taking gabapentin. Limit the use of opioid pain medications with gabapentin to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, initiate gabapentin at the lowest recommended dose and monitor patients for symptoms of respiratory depression and sedation. Use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Educate patients about the risks and symptoms of excessive CNS depression and respiratory depression. (Major) Initiate gabapentin at the lowest recommended dose and monitor patients for symptoms of sedation and somnolence during coadministration of gabapentin and promethazine. Concomitant use of gabapentin with promethazine may cause additive CNS depression. Educate patients about the risks and symptoms of excessive CNS depression.
    Codeine; Promethazine: (Major) Concomitant use of opioid agonists with gabapentin may cause excessive sedation, somnolence, and respiratory depression. Avoid prescribing opioid cough medications in patients taking gabapentin. Limit the use of opioid pain medications with gabapentin to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, initiate gabapentin at the lowest recommended dose and monitor patients for symptoms of respiratory depression and sedation. Use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Educate patients about the risks and symptoms of excessive CNS depression and respiratory depression. (Major) Initiate gabapentin at the lowest recommended dose and monitor patients for symptoms of sedation and somnolence during coadministration of gabapentin and promethazine. Concomitant use of gabapentin with promethazine may cause additive CNS depression. Educate patients about the risks and symptoms of excessive CNS depression.
    Colesevelam: (Moderate) The manufacturer for colesevelam suggests monitoring serum drug concentrations and/or clinical effects for those drugs for which alterations in serum blood concentrations have a clinically significant effect on safety or efficacy. To minimize potential for interactions, consider administering oral anticonvulsants such as gabapentin at least 1 hour before or at least 4 hours after colesevelam.
    Cyclizine: (Moderate) Monitor for excessive sedation and somnolence during coadministration of cyclizine and gabapentin. Concurrent use may result in additive CNS depression.
    Cyclobenzaprine: (Major) Initiate gabapentin at the lowest recommended dose and monitor patients for symptoms of sedation and somnolence during coadministration of gabapentin and cyclobenzaprine. Concomitant use of gabapentin with cyclobenzaprine may cause additive CNS depression. Educate patients about the risks and symptoms of excessive CNS depression.
    Cyproheptadine: (Moderate) Monitor for excessive sedation and somnolence during coadministration of cyproheptadine and gabapentin. Concurrent use may result in additive CNS depression.
    Dantrolene: (Major) Concomitant use of dantrolene with gabapentin may cause excessive sedation, somnolence, and respiratory depression. If concurrent use is necessary, initiate gabapentin at the lowest recommended dose and monitor patients for symptoms of respiratory depression and sedation. Educate patients about the risks and symptoms of excessive CNS depression and respiratory depression.
    Deutetrabenazine: (Moderate) Monitor for excessive sedation and somnolence during coadministration of deutetrabenazine and gabapentin. Concurrent use may result in additive CNS depression.
    Dexbrompheniramine: (Moderate) Monitor for excessive sedation and somnolence during coadministration of dexbrompheniramine and gabapentin. Concurrent use may result in additive CNS depression.
    Dexbrompheniramine; Pseudoephedrine: (Moderate) Monitor for excessive sedation and somnolence during coadministration of dexbrompheniramine and gabapentin. Concurrent use may result in additive CNS depression.
    Dexchlorpheniramine: (Moderate) Monitor for excessive sedation and somnolence during coadministration of dexchlorpheniramine and gabapentin. Concurrent use may result in additive CNS depression.
    Dexchlorpheniramine; Dextromethorphan; Pseudoephedrine: (Moderate) Monitor for excessive sedation and somnolence during coadministration of dexchlorpheniramine and gabapentin. Concurrent use may result in additive CNS depression.
    Dexmedetomidine: (Moderate) Monitor for excessive sedation, somnolence, and respiratory depression during coadministration of dexmedetomidine and gabapentin. Concurrent use may result in additive CNS and respiratory depression.
    Dextromethorphan; Diphenhydramine; Phenylephrine: (Moderate) Monitor for excessive sedation and somnolence during coadministration of diphenhydramine and gabapentin. Concurrent use may result in additive CNS depression.
    Diazepam: (Major) Concomitant use of benzodiazepines with gabapentin may cause excessive sedation, somnolence, and respiratory depression. If concurrent use is necessary, initiate gabapentin at the lowest recommended dose and monitor patients for symptoms of respiratory depression and sedation. Educate patients about the risks and symptoms of excessive CNS depression and respiratory depression.
    Dihydrocodeine; Guaifenesin; Pseudoephedrine: (Major) Concomitant use of opioid agonists with gabapentin may cause excessive sedation, somnolence, and respiratory depression. Avoid prescribing opioid cough medications in patients taking gabapentin. Limit the use of opioid pain medications with gabapentin to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, initiate gabapentin at the lowest recommended dose and monitor patients for symptoms of respiratory depression and sedation. Use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Educate patients about the risks and symptoms of excessive CNS depression and respiratory depression.
    Dimenhydrinate: (Moderate) Monitor for excessive sedation and somnolence during coadministration of dimenhydrinate and gabapentin. Concurrent use may result in additive CNS depression.
    Diphenhydramine: (Moderate) Monitor for excessive sedation and somnolence during coadministration of diphenhydramine and gabapentin. Concurrent use may result in additive CNS depression.
    Diphenhydramine; Hydrocodone; Phenylephrine: (Major) Concomitant use of opioid agonists with gabapentin may cause excessive sedation, somnolence, and respiratory depression. Avoid prescribing opioid cough medications in patients taking gabapentin. Limit the use of opioid pain medications with gabapentin to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, initiate gabapentin at the lowest recommended dose and monitor patients for symptoms of respiratory depression and sedation. Use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Also, coadministration of gabapentin with hydrocodone decreases hydrocodone exposure in a dose-dependent manner. Consider the potential for decreased hydrocodone exposure and effect when gabapentin is started or discontinued in a patient taking hydrocodone. Hydrocodone (10 mg; n = 50) Cmax and AUC values were 3% to 4% lower, respectively, after administration of gabapentin (n = 48) 125 mg and 21% to 22% lower, respectively, after administration of gabapentin 500 mg. Hydrocodone increases gabapentin AUC values by 14%. The magnitude of interaction at other doses and the mechanism of the interaction are unknown. (Moderate) Monitor for excessive sedation and somnolence during coadministration of diphenhydramine and gabapentin. Concurrent use may result in additive CNS depression.
    Diphenhydramine; Ibuprofen: (Moderate) Monitor for excessive sedation and somnolence during coadministration of diphenhydramine and gabapentin. Concurrent use may result in additive CNS depression.
    Diphenhydramine; Naproxen: (Moderate) Monitor for excessive sedation and somnolence during coadministration of diphenhydramine and gabapentin. Concurrent use may result in additive CNS depression.
    Diphenhydramine; Phenylephrine: (Moderate) Monitor for excessive sedation and somnolence during coadministration of diphenhydramine and gabapentin. Concurrent use may result in additive CNS depression.
    Diphenoxylate; Atropine: (Moderate) Monitor for excessive sedation and somnolence during coadministration of atropine and gabapentin. Concurrent use may result in additive CNS depression.
    Doxylamine: (Moderate) Monitor for excessive sedation and somnolence during coadministration of doxylamine and gabapentin. Concurrent use may result in additive CNS depression.
    Doxylamine; Pyridoxine: (Moderate) Monitor for excessive sedation and somnolence during coadministration of doxylamine and gabapentin. Concurrent use may result in additive CNS depression.
    Droperidol: (Major) Initiate gabapentin at the lowest recommended dose and monitor patients for symptoms of sedation and somnolence during coadministration of gabapentin and droperidol. Concomitant use of gabapentin with droperidol may cause additive CNS depression. Educate patients about the risks and symptoms of excessive CNS depression.
    Enflurane: (Major) Concomitant use of general anesthetics with gabapentin may cause excessive sedation, somnolence, and respiratory depression. If concurrent use is necessary, initiate gabapentin at the lowest recommended dose and monitor patients for symptoms of excessive respiratory depression. Educate patients about the risks and symptoms of excessive CNS depression and respiratory depression.
    Entacapone: (Major) Initiate gabapentin at the lowest recommended dose and monitor patients for symptoms of sedation and somnolence during coadministration of gabapentin and entacapone. Concomitant use of gabapentin with entacapone may cause additive CNS depression. Educate patients about the risks and symptoms of excessive CNS depression. Dopaminergic agents, such as entacapone, have also been associated with sudden sleep onset during activities of daily living such as driving, which has resulted in accidents in some cases. Reassess patients for drowsiness or sleepiness regularly throughout treatment, especially since events may occur well after the start of treatment.
    Esketamine: (Moderate) Closely monitor patients receiving esketamine and gabapentin for sedation and other CNS depressant effects. Instruct patients who receive a dose of esketamine not to drive or engage in other activities requiring alertness until the next day after a restful sleep.
    Estazolam: (Major) Concomitant use of benzodiazepines with gabapentin may cause excessive sedation, somnolence, and respiratory depression. If concurrent use is necessary, initiate gabapentin at the lowest recommended dose and monitor patients for symptoms of respiratory depression and sedation. Educate patients about the risks and symptoms of excessive CNS depression and respiratory depression.
    Eszopiclone: (Major) Initiate gabapentin at the lowest recommended dose and monitor patients for symptoms of sedation and somnolence during coadministration of gabapentin and eszopiclone. Concomitant use of gabapentin with eszopiclone may cause additive CNS depression and complex sleep-related behaviors (e.g., driving, talking, eating, or performing other activities while not fully awake). Educate patients about the risks and symptoms of excessive CNS depression. Instruct patients to contact their provider immediately if sleep-related symptoms or behaviors occur.
    Ethanol: (Major) Advise patients to avoid alcohol while taking gabapentin. Concomitant use of alcohol with gabapentin may cause excessive sedation, somnolence, and respiratory depression. Alcohol causes a more rapid release of gabapentin enacarbil from the extended-release tablets that may increase the risk for adverse events. In an in vitro dissolution study, 63% of the gabapentin enacarbil dose was released at 1 hour at the highest alcohol concentration studied (40%). At a 5% alcohol concentration, 43% of the dose was released at 1 hour.
    Etomidate: (Major) Concomitant use of general anesthetics with gabapentin may cause excessive sedation, somnolence, and respiratory depression. If concurrent use is necessary, initiate gabapentin at the lowest recommended dose and monitor patients for symptoms of excessive respiratory depression. Educate patients about the risks and symptoms of excessive CNS depression and respiratory depression.
    Fenfluramine: (Moderate) Monitor for excessive sedation and somnolence during coadministration of fenfluramine and gabapentin. Concurrent use may result in additive CNS depression.
    Fentanyl: (Major) Concomitant use of opioid agonists with gabapentin may cause excessive sedation, somnolence, and respiratory depression. Limit the use of opioid pain medications with gabapentin to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, initiate gabapentin at the lowest recommended dose and monitor patients for symptoms of respiratory depression and sedation. Use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Educate patients about the risks and symptoms of excessive CNS depression and respiratory depression.
    Flibanserin: (Moderate) Monitor for excessive sedation and somnolence during coadministration of flibanserin and gabapentin. Concurrent use may result in additive CNS depression.
    Fluphenazine: (Moderate) Monitor for excessive sedation and somnolence during coadministration of fluphenazine and gabapentin. Concurrent use may result in additive CNS depression.
    Flurazepam: (Major) Concomitant use of benzodiazepines with gabapentin may cause excessive sedation, somnolence, and respiratory depression. If concurrent use is necessary, initiate gabapentin at the lowest recommended dose and monitor patients for symptoms of respiratory depression and sedation. Educate patients about the risks and symptoms of excessive CNS depression and respiratory depression.
    Fospropofol: (Major) Concomitant use of general anesthetics with gabapentin may cause excessive sedation, somnolence, and respiratory depression. If concurrent use is necessary, initiate gabapentin at the lowest recommended dose and monitor patients for symptoms of excessive respiratory depression. Educate patients about the risks and symptoms of excessive CNS depression and respiratory depression.
    General anesthetics: (Major) Concomitant use of general anesthetics with gabapentin may cause excessive sedation, somnolence, and respiratory depression. If concurrent use is necessary, initiate gabapentin at the lowest recommended dose and monitor patients for symptoms of excessive respiratory depression. Educate patients about the risks and symptoms of excessive CNS depression and respiratory depression.
    Guaifenesin; Hydrocodone: (Major) Concomitant use of opioid agonists with gabapentin may cause excessive sedation, somnolence, and respiratory depression. Avoid prescribing opioid cough medications in patients taking gabapentin. Limit the use of opioid pain medications with gabapentin to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, initiate gabapentin at the lowest recommended dose and monitor patients for symptoms of respiratory depression and sedation. Use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Also, coadministration of gabapentin with hydrocodone decreases hydrocodone exposure in a dose-dependent manner. Consider the potential for decreased hydrocodone exposure and effect when gabapentin is started or discontinued in a patient taking hydrocodone. Hydrocodone (10 mg; n = 50) Cmax and AUC values were 3% to 4% lower, respectively, after administration of gabapentin (n = 48) 125 mg and 21% to 22% lower, respectively, after administration of gabapentin 500 mg. Hydrocodone increases gabapentin AUC values by 14%. The magnitude of interaction at other doses and the mechanism of the interaction are unknown.
    Guaifenesin; Hydrocodone; Pseudoephedrine: (Major) Concomitant use of opioid agonists with gabapentin may cause excessive sedation, somnolence, and respiratory depression. Avoid prescribing opioid cough medications in patients taking gabapentin. Limit the use of opioid pain medications with gabapentin to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, initiate gabapentin at the lowest recommended dose and monitor patients for symptoms of respiratory depression and sedation. Use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Also, coadministration of gabapentin with hydrocodone decreases hydrocodone exposure in a dose-dependent manner. Consider the potential for decreased hydrocodone exposure and effect when gabapentin is started or discontinued in a patient taking hydrocodone. Hydrocodone (10 mg; n = 50) Cmax and AUC values were 3% to 4% lower, respectively, after administration of gabapentin (n = 48) 125 mg and 21% to 22% lower, respectively, after administration of gabapentin 500 mg. Hydrocodone increases gabapentin AUC values by 14%. The magnitude of interaction at other doses and the mechanism of the interaction are unknown.
    Guanfacine: (Moderate) Monitor for excessive sedation and somnolence during coadministration of guanfacine and gabapentin. Concurrent use may result in additive CNS depression.
    Haloperidol: (Major) Initiate gabapentin at the lowest recommended dose and monitor patients for symptoms of sedation and somnolence during coadministration of gabapentin and haloperidol. Concomitant use of gabapentin with haloperidol may cause additive CNS depression. Educate patients about the risks and symptoms of excessive CNS depression.
    Halothane: (Major) Concomitant use of general anesthetics with gabapentin may cause excessive sedation, somnolence, and respiratory depression. If concurrent use is necessary, initiate gabapentin at the lowest recommended dose and monitor patients for symptoms of excessive respiratory depression. Educate patients about the risks and symptoms of excessive CNS depression and respiratory depression.
    Homatropine; Hydrocodone: (Major) Concomitant use of opioid agonists with gabapentin may cause excessive sedation, somnolence, and respiratory depression. Avoid prescribing opioid cough medications in patients taking gabapentin. Limit the use of opioid pain medications with gabapentin to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, initiate gabapentin at the lowest recommended dose and monitor patients for symptoms of respiratory depression and sedation. Use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Also, coadministration of gabapentin with hydrocodone decreases hydrocodone exposure in a dose-dependent manner. Consider the potential for decreased hydrocodone exposure and effect when gabapentin is started or discontinued in a patient taking hydrocodone. Hydrocodone (10 mg; n = 50) Cmax and AUC values were 3% to 4% lower, respectively, after administration of gabapentin (n = 48) 125 mg and 21% to 22% lower, respectively, after administration of gabapentin 500 mg. Hydrocodone increases gabapentin AUC values by 14%. The magnitude of interaction at other doses and the mechanism of the interaction are unknown.
    Hydrochlorothiazide, HCTZ; Methyldopa: (Moderate) Monitor for excessive sedation and somnolence during coadministration of methyldopa and gabapentin. Concurrent use may result in additive CNS depression.
    Hydrocodone: (Major) Concomitant use of opioid agonists with gabapentin may cause excessive sedation, somnolence, and respiratory depression. Avoid prescribing opioid cough medications in patients taking gabapentin. Limit the use of opioid pain medications with gabapentin to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, initiate gabapentin at the lowest recommended dose and monitor patients for symptoms of respiratory depression and sedation. Use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Also, coadministration of gabapentin with hydrocodone decreases hydrocodone exposure in a dose-dependent manner. Consider the potential for decreased hydrocodone exposure and effect when gabapentin is started or discontinued in a patient taking hydrocodone. Hydrocodone (10 mg; n = 50) Cmax and AUC values were 3% to 4% lower, respectively, after administration of gabapentin (n = 48) 125 mg and 21% to 22% lower, respectively, after administration of gabapentin 500 mg. Hydrocodone increases gabapentin AUC values by 14%. The magnitude of interaction at other doses and the mechanism of the interaction are unknown.
    Hydrocodone; Ibuprofen: (Major) Concomitant use of opioid agonists with gabapentin may cause excessive sedation, somnolence, and respiratory depression. Avoid prescribing opioid cough medications in patients taking gabapentin. Limit the use of opioid pain medications with gabapentin to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, initiate gabapentin at the lowest recommended dose and monitor patients for symptoms of respiratory depression and sedation. Use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Also, coadministration of gabapentin with hydrocodone decreases hydrocodone exposure in a dose-dependent manner. Consider the potential for decreased hydrocodone exposure and effect when gabapentin is started or discontinued in a patient taking hydrocodone. Hydrocodone (10 mg; n = 50) Cmax and AUC values were 3% to 4% lower, respectively, after administration of gabapentin (n = 48) 125 mg and 21% to 22% lower, respectively, after administration of gabapentin 500 mg. Hydrocodone increases gabapentin AUC values by 14%. The magnitude of interaction at other doses and the mechanism of the interaction are unknown.
    Hydrocodone; Phenylephrine: (Major) Concomitant use of opioid agonists with gabapentin may cause excessive sedation, somnolence, and respiratory depression. Avoid prescribing opioid cough medications in patients taking gabapentin. Limit the use of opioid pain medications with gabapentin to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, initiate gabapentin at the lowest recommended dose and monitor patients for symptoms of respiratory depression and sedation. Use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Also, coadministration of gabapentin with hydrocodone decreases hydrocodone exposure in a dose-dependent manner. Consider the potential for decreased hydrocodone exposure and effect when gabapentin is started or discontinued in a patient taking hydrocodone. Hydrocodone (10 mg; n = 50) Cmax and AUC values were 3% to 4% lower, respectively, after administration of gabapentin (n = 48) 125 mg and 21% to 22% lower, respectively, after administration of gabapentin 500 mg. Hydrocodone increases gabapentin AUC values by 14%. The magnitude of interaction at other doses and the mechanism of the interaction are unknown.
    Hydrocodone; Potassium Guaiacolsulfonate: (Major) Concomitant use of opioid agonists with gabapentin may cause excessive sedation, somnolence, and respiratory depression. Avoid prescribing opioid cough medications in patients taking gabapentin. Limit the use of opioid pain medications with gabapentin to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, initiate gabapentin at the lowest recommended dose and monitor patients for symptoms of respiratory depression and sedation. Use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Also, coadministration of gabapentin with hydrocodone decreases hydrocodone exposure in a dose-dependent manner. Consider the potential for decreased hydrocodone exposure and effect when gabapentin is started or discontinued in a patient taking hydrocodone. Hydrocodone (10 mg; n = 50) Cmax and AUC values were 3% to 4% lower, respectively, after administration of gabapentin (n = 48) 125 mg and 21% to 22% lower, respectively, after administration of gabapentin 500 mg. Hydrocodone increases gabapentin AUC values by 14%. The magnitude of interaction at other doses and the mechanism of the interaction are unknown.
    Hydrocodone; Potassium Guaiacolsulfonate; Pseudoephedrine: (Major) Concomitant use of opioid agonists with gabapentin may cause excessive sedation, somnolence, and respiratory depression. Avoid prescribing opioid cough medications in patients taking gabapentin. Limit the use of opioid pain medications with gabapentin to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, initiate gabapentin at the lowest recommended dose and monitor patients for symptoms of respiratory depression and sedation. Use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Also, coadministration of gabapentin with hydrocodone decreases hydrocodone exposure in a dose-dependent manner. Consider the potential for decreased hydrocodone exposure and effect when gabapentin is started or discontinued in a patient taking hydrocodone. Hydrocodone (10 mg; n = 50) Cmax and AUC values were 3% to 4% lower, respectively, after administration of gabapentin (n = 48) 125 mg and 21% to 22% lower, respectively, after administration of gabapentin 500 mg. Hydrocodone increases gabapentin AUC values by 14%. The magnitude of interaction at other doses and the mechanism of the interaction are unknown.
    Hydrocodone; Pseudoephedrine: (Major) Concomitant use of opioid agonists with gabapentin may cause excessive sedation, somnolence, and respiratory depression. Avoid prescribing opioid cough medications in patients taking gabapentin. Limit the use of opioid pain medications with gabapentin to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, initiate gabapentin at the lowest recommended dose and monitor patients for symptoms of respiratory depression and sedation. Use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Also, coadministration of gabapentin with hydrocodone decreases hydrocodone exposure in a dose-dependent manner. Consider the potential for decreased hydrocodone exposure and effect when gabapentin is started or discontinued in a patient taking hydrocodone. Hydrocodone (10 mg; n = 50) Cmax and AUC values were 3% to 4% lower, respectively, after administration of gabapentin (n = 48) 125 mg and 21% to 22% lower, respectively, after administration of gabapentin 500 mg. Hydrocodone increases gabapentin AUC values by 14%. The magnitude of interaction at other doses and the mechanism of the interaction are unknown.
    Hydromorphone: (Major) Concomitant use of opioid agonists with gabapentin may cause excessive sedation, somnolence, and respiratory depression. Limit the use of opioid pain medications with gabapentin to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, initiate gabapentin at the lowest recommended dose and monitor patients for symptoms of respiratory depression and sedation. Use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Educate patients about the risks and symptoms of excessive CNS depression and respiratory depression.
    Hydroxychloroquine: (Moderate) Caution is warranted with the coadministration of hydroxychloroquine and antiepileptic drugs, such as gabapentin. Hydroxychloroquine can lower the seizure threshold; therefore, the activity of antiepileptic drugs may be impaired with concomitant use.
    Hydroxyzine: (Major) Initiate gabapentin at the lowest recommended dose and monitor patients for symptoms of sedation and somnolence during coadministration of gabapentin and hydroxyzine. Reduce the gabapentin dose by 50% or more when used with hydroxyzine intramuscular injection. Concomitant use of gabapentin with hydroxyzine may cause additive CNS depression. Educate patients about the risks and symptoms of excessive CNS depression.
    Ibuprofen; Oxycodone: (Major) Concomitant use of opioid agonists with gabapentin may cause excessive sedation, somnolence, and respiratory depression. Limit the use of opioid pain medications with gabapentin to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, initiate gabapentin at the lowest recommended dose and monitor patients for symptoms of respiratory depression and sedation. Use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Educate patients about the risks and symptoms of excessive CNS depression and respiratory depression.
    Iloperidone: (Moderate) Monitor for excessive sedation and somnolence during coadministration of iloperidone and gabapentin. Concurrent use may result in additive CNS depression.
    Isocarboxazid: (Moderate) Monitor for excessive sedation and somnolence during coadministration of monoamine oxidase inhibitors (MAOIs) and gabapentin. Concurrent use may result in additive CNS depression. MAOIs can cause a variable change in seizure patterns, so careful monitoring of patients receiving gabapentin for epilepsy is required.
    Isoflurane: (Major) Concomitant use of general anesthetics with gabapentin may cause excessive sedation, somnolence, and respiratory depression. If concurrent use is necessary, initiate gabapentin at the lowest recommended dose and monitor patients for symptoms of excessive respiratory depression. Educate patients about the risks and symptoms of excessive CNS depression and respiratory depression.
    Ketamine: (Major) Concomitant use of general anesthetics with gabapentin may cause excessive sedation, somnolence, and respiratory depression. If concurrent use is necessary, initiate gabapentin at the lowest recommended dose and monitor patients for symptoms of excessive respiratory depression. Educate patients about the risks and symptoms of excessive CNS depression and respiratory depression.
    Lanthanum Carbonate: (Major) Oral compounds known to interact with antacids, like gabapentin, should not be taken within 2 hours of dosing with lanthanum carbonate. If these agents are used concomitantly, space the dosing intervals appropriately. Monitor serum concentrations and clinical condition.
    Lasmiditan: (Moderate) Monitor for excessive sedation and somnolence during coadministration of lasmiditan and gabapentin. Concurrent use may result in additive CNS depression.
    Lemborexant: (Moderate) Monitor for excessive sedation and somnolence during coadministration of lemborexant and gabapentin. Dosage adjustments of lemborexant and gabapentin may be necessary when administered together because of potentially additive CNS effects. The risk of next-day impairment, including impaired driving, is increased if lemborexant is taken with other CNS depressants.
    Levocetirizine: (Moderate) Monitor for excessive sedation and somnolence during coadministration of cetirizine and gabapentin. Concurrent use may result in additive CNS depression.
    Levodopa: (Major) Initiate gabapentin at the lowest recommended dose and monitor patients for symptoms of sedation and somnolence during coadministration of gabapentin and levodopa. Concomitant use of gabapentin with levodopa may cause additive CNS depression. Educate patients about the risks and symptoms of excessive CNS depression. Dopaminergic agents, such as levodopa, have also been associated with sudden sleep onset during activities of daily living such as driving, which has resulted in accidents in some cases. Reassess patients for drowsiness or sleepiness regularly throughout treatment, especially since events may occur well after the start of treatment.
    Levorphanol: (Major) Concomitant use of opioid agonists with gabapentin may cause excessive sedation, somnolence, and respiratory depression. Limit the use of opioid pain medications with gabapentin to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, initiate gabapentin at the lowest recommended dose and monitor patients for symptoms of respiratory depression and sedation. Reduce the initial dose of levorphanol by approximately 50% or more. Use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Educate patients about the risks and symptoms of excessive CNS depression and respiratory depression.
    Lithium: (Moderate) Caution is advisable during concurrent use of lithium and gabapentin since both drugs are renally eliminated. It is possible that competition for elimination may occur, possibly raising lithium or gabapentin concentrations. Although not systematically evaluated, it is possible that concurrent use of lithium and gabapentin may result in weight gain, memory disturbances, and ataxia. Monitor the patient clinically for evidence of the interaction, which may include monitoring lithium concentrations.
    Lofexidine: (Moderate) Monitor for excessive sedation and somnolence during coadministration of lofexidine and gabapentin. Concurrent use may result in additive CNS depression.
    Lorazepam: (Major) Concomitant use of benzodiazepines with gabapentin may cause excessive sedation, somnolence, and respiratory depression. If concurrent use is necessary, initiate gabapentin at the lowest recommended dose and monitor patients for symptoms of respiratory depression and sedation. Educate patients about the risks and symptoms of excessive CNS depression and respiratory depression.
    Loxapine: (Moderate) Monitor for excessive sedation and somnolence during coadministration of loxapine and gabapentin. Concurrent use may result in additive CNS depression.
    Lumateperone: (Moderate) Monitor for excessive sedation and somnolence during coadministration of lumateperone and gabapentin. Concurrent use may result in additive CNS depression.
    Lurasidone: (Moderate) Monitor for excessive sedation and somnolence during coadministration of lurasidone and gabapentin. Concurrent use may result in additive CNS depression.
    Magnesium Hydroxide: (Moderate) Gabapentin should be taken at least 2 hours after the administration of antacids. Antacids have been shown to reduce the oral bioavailability of gabapentin by roughly 20%. This decrease in bioavailability was about 5% when gabapentin was administered 2 hours after the antacid.bb
    Maprotiline: (Major) Initiate gabapentin at the lowest recommended dose and monitor patients for symptoms of sedation and somnolence during coadministration of gabapentin and maprotiline. Concomitant use of gabapentin with maprotiline may cause additive CNS depression. Educate patients about the risks and symptoms of excessive CNS depression.
    Meclizine: (Moderate) Monitor for excessive sedation and somnolence during coadministration of meclizine and gabapentin. Concurrent use may result in additive CNS depression.
    Mefloquine: (Moderate) It is not clear if mefloquine will alter the activity of gabapentin, as gabapentin is not appreciably metabolized nor does it typically interfere with the metabolism of other medications. Coadministration of mefloquine and certain anticonvulsants has been reported to result in lower than expected anticonvulsant concentrations and loss of seizure control. Monitoring of the anticonvulsant serum concentration, if the drug is monitored via therapeutic drug monitoring, is recommended. Gabapentin concentrations are not usually monitored. Mefloquine may additionally cause CNS side effects that may cause seizures or alter moods or behaviors.
    Melatonin: (Moderate) Monitor for excessive sedation and somnolence during coadministration of melatonin and gabapentin. Concurrent use may result in additive CNS depression.
    Meperidine: (Major) Concomitant use of opioid agonists with gabapentin may cause excessive sedation, somnolence, and respiratory depression. Limit the use of opioid pain medications with gabapentin to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, initiate gabapentin at the lowest recommended dose and monitor patients for symptoms of respiratory depression and sedation. Use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Educate patients about the risks and symptoms of excessive CNS depression and respiratory depression.
    Meperidine; Promethazine: (Major) Concomitant use of opioid agonists with gabapentin may cause excessive sedation, somnolence, and respiratory depression. Limit the use of opioid pain medications with gabapentin to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, initiate gabapentin at the lowest recommended dose and monitor patients for symptoms of respiratory depression and sedation. Use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Educate patients about the risks and symptoms of excessive CNS depression and respiratory depression. (Major) Initiate gabapentin at the lowest recommended dose and monitor patients for symptoms of sedation and somnolence during coadministration of gabapentin and promethazine. Concomitant use of gabapentin with promethazine may cause additive CNS depression. Educate patients about the risks and symptoms of excessive CNS depression.
    Mephobarbital: (Major) Concomitant use of barbiturates with gabapentin may cause excessive sedation, somnolence, and respiratory depression. If concurrent use is necessary, initiate gabapentin at the lowest recommended dose and monitor patients for symptoms of respiratory depression and sedation. Educate patients about the risks and symptoms of excessive CNS depression and respiratory depression.
    Meprobamate: (Moderate) Monitor for excessive sedation and somnolence during coadministration of meprobamate and gabapentin. Concurrent use may result in additive CNS depression.
    Metaxalone: (Major) Initiate gabapentin at the lowest recommended dose and monitor patients for symptoms of sedation and somnolence during coadministration of gabapentin and metaxalone. Concomitant use of gabapentin with metaxalone may cause additive CNS depression. Educate patients about the risks and symptoms of excessive CNS depression.
    Methadone: (Major) Concomitant use of opioid agonists with gabapentin may cause excessive sedation, somnolence, and respiratory depression. Limit the use of opioid pain medications with gabapentin to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, initiate gabapentin at the lowest recommended dose and monitor patients for symptoms of respiratory depression and sedation. Use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Educate patients about the risks and symptoms of excessive CNS depression and respiratory depression.
    Methocarbamol: (Major) Initiate gabapentin at the lowest recommended dose and monitor patients for symptoms of sedation and somnolence during coadministration of gabapentin and methocarbamol. Concomitant use of gabapentin with methocarbamol may cause additive CNS depression. Educate patients about the risks and symptoms of excessive CNS depression.
    Methohexital: (Major) Concomitant use of barbiturates with gabapentin may cause excessive sedation, somnolence, and respiratory depression. If concurrent use is necessary, initiate gabapentin at the lowest recommended dose and monitor patients for symptoms of respiratory depression and sedation. Educate patients about the risks and symptoms of excessive CNS depression and respiratory depression.
    Methyldopa: (Moderate) Monitor for excessive sedation and somnolence during coadministration of methyldopa and gabapentin. Concurrent use may result in additive CNS depression.
    Metoclopramide: (Moderate) Monitor for excessive sedation and somnolence during coadministration of metoclopramide and gabapentin. Concurrent use may result in additive CNS depression.
    Midazolam: (Major) Concomitant use of benzodiazepines with gabapentin may cause excessive sedation, somnolence, and respiratory depression. If concurrent use is necessary, initiate gabapentin at the lowest recommended dose and monitor patients for symptoms of respiratory depression and sedation. Educate patients about the risks and symptoms of excessive CNS depression and respiratory depression.
    Mirtazapine: (Major) Initiate gabapentin at the lowest recommended dose and monitor patients for symptoms of sedation and somnolence during coadministration of gabapentin and mirtazapine. Concomitant use of gabapentin with mirtazapine may cause additive CNS depression. Educate patients about the risks and symptoms of excessive CNS depression.
    Molindone: (Major) Initiate gabapentin at the lowest recommended dose and monitor patients for symptoms of sedation and somnolence during coadministration of gabapentin and molindone. Concomitant use of gabapentin with molindone may cause additive CNS depression. Educate patients about the risks and symptoms of excessive CNS depression.
    Monoamine oxidase inhibitors: (Moderate) Monitor for excessive sedation and somnolence during coadministration of monoamine oxidase inhibitors (MAOIs) and gabapentin. Concurrent use may result in additive CNS depression. MAOIs can cause a variable change in seizure patterns, so careful monitoring of patients receiving gabapentin for epilepsy is required.
    Morphine: (Major) Concomitant use of opioid agonists with gabapentin may cause excessive sedation, somnolence, and respiratory depression. Limit the use of opioid pain medications with gabapentin to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, initiate gabapentin at the lowest recommended dose and monitor patients for symptoms of respiratory depression and sedation. For extended-release morphine tablets (MS Contin and Morphabond), start with 15 mg every 12 hours. Morphine; naltrexone should be initiated at one-third to one-half the recommended starting dosage. Use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Also, coadministration of morphine and gabapentin may increase gabapentin concentrations and may require dosage adjustment. Mean gabapentin AUC increased by 44% when a 60 mg controlled-release morphine capsule was administered 2 hours prior to a 600 mg gabapentin capsule (n = 12). Morphine pharmacokinetic parameter values were not affected by administration of gabapentin 2 hours after morphine. The magnitude of interaction at other doses is not known.
    Morphine; Naltrexone: (Major) Concomitant use of opioid agonists with gabapentin may cause excessive sedation, somnolence, and respiratory depression. Limit the use of opioid pain medications with gabapentin to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, initiate gabapentin at the lowest recommended dose and monitor patients for symptoms of respiratory depression and sedation. For extended-release morphine tablets (MS Contin and Morphabond), start with 15 mg every 12 hours. Morphine; naltrexone should be initiated at one-third to one-half the recommended starting dosage. Use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Also, coadministration of morphine and gabapentin may increase gabapentin concentrations and may require dosage adjustment. Mean gabapentin AUC increased by 44% when a 60 mg controlled-release morphine capsule was administered 2 hours prior to a 600 mg gabapentin capsule (n = 12). Morphine pharmacokinetic parameter values were not affected by administration of gabapentin 2 hours after morphine. The magnitude of interaction at other doses is not known.
    Nabilone: (Major) Monitor for excessive sedation and somnolence during coadministration of nabilone and gabapentin. Concurrent use may result in additive CNS depression.
    Nalbuphine: (Major) Concomitant use of nalbuphine with gabapentin may cause excessive sedation, somnolence, and respiratory depression. Limit the use of nalbuphine with gabapentin to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, initiate gabapentin at the lowest recommended dose and monitor patients for symptoms of respiratory depression and sedation. Use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Educate patients about the risks and symptoms of excessive CNS depression and respiratory depression.
    Nefazodone: (Major) Initiate gabapentin at the lowest recommended dose and monitor patients for symptoms of sedation and somnolence during coadministration of gabapentin and nefazodone. Concomitant use of gabapentin with nefazodone may cause additive CNS depression. Educate patients about the risks and symptoms of excessive CNS depression.
    Olanzapine: (Major) Initiate gabapentin at the lowest recommended dose and monitor patients for symptoms of sedation and somnolence during coadministration of gabapentin and olanzapine. Concomitant use of gabapentin with olanzapine may cause additive CNS depression. Educate patients about the risks and symptoms of excessive CNS depression.
    Olanzapine; Fluoxetine: (Major) Initiate gabapentin at the lowest recommended dose and monitor patients for symptoms of sedation and somnolence during coadministration of gabapentin and olanzapine. Concomitant use of gabapentin with olanzapine may cause additive CNS depression. Educate patients about the risks and symptoms of excessive CNS depression.
    Olanzapine; Samidorphan: (Major) Initiate gabapentin at the lowest recommended dose and monitor patients for symptoms of sedation and somnolence during coadministration of gabapentin and olanzapine. Concomitant use of gabapentin with olanzapine may cause additive CNS depression. Educate patients about the risks and symptoms of excessive CNS depression.
    Oliceridine: (Major) Concomitant use of opioid agonists with gabapentin may cause excessive sedation, somnolence, and respiratory depression. Limit the use of opioid pain medications with gabapentin to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, initiate gabapentin at the lowest recommended dose and monitor patients for symptoms of respiratory depression and sedation. Use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect.
    Omeprazole; Sodium Bicarbonate: (Moderate) Antacids have been shown to reduce the oral bioavailability of gabapentin by roughly 20%. This decrease in bioavailability was about 5% when gabapentin was administered 2 hours after the antacid. It is recommended that gabapentin be taken at least 2 hours following the administration of antacids in order to avoid a significant interaction.
    Opicapone: (Major) Initiate gabapentin at the lowest recommended dose and monitor patients for symptoms of sedation and somnolence during coadministration of gabapentin and opicapone. Concomitant use of gabapentin with opicapone may cause additive CNS depression. Educate patients about the risks and symptoms of excessive CNS depression. Dopaminergic agents, such as opicapone, have also been associated with sudden sleep onset during activities of daily living such as driving, which has resulted in accidents in some cases. Reassess patients for drowsiness or sleepiness regularly throughout treatment, especially since events may occur well after the start of treatment.
    Orphenadrine: (Major) Initiate gabapentin at the lowest recommended dose and monitor patients for symptoms of sedation and somnolence during coadministration of gabapentin and orphenadrine. Concomitant use of gabapentin with orphenadrine may cause additive CNS depression. Educate patients about the risks and symptoms of excessive CNS depression.
    Oxazepam: (Major) Concomitant use of benzodiazepines with gabapentin may cause excessive sedation, somnolence, and respiratory depression. If concurrent use is necessary, initiate gabapentin at the lowest recommended dose and monitor patients for symptoms of respiratory depression and sedation. Educate patients about the risks and symptoms of excessive CNS depression and respiratory depression.
    Oxycodone: (Major) Concomitant use of opioid agonists with gabapentin may cause excessive sedation, somnolence, and respiratory depression. Limit the use of opioid pain medications with gabapentin to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, initiate gabapentin at the lowest recommended dose and monitor patients for symptoms of respiratory depression and sedation. Use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Educate patients about the risks and symptoms of excessive CNS depression and respiratory depression.
    Oxymorphone: (Major) Concomitant use of opioid agonists with gabapentin may cause excessive sedation, somnolence, and respiratory depression. Limit the use of opioid pain medications with gabapentin to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, initiate gabapentin at the lowest recommended dose and monitor patients for symptoms of respiratory depression and sedation. Use an initial dose of oxymorphone at 1/3 to 1/2 the usual dosage and titrate to clinical response. Use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Educate patients about the risks and symptoms of excessive CNS depression and respiratory depression.
    Paliperidone: (Moderate) Monitor for excessive sedation and somnolence during coadministration of paliperidone and gabapentin. Concurrent use may result in additive CNS depression.
    Pemoline: (Moderate) A reduction in seizure threshold has been reported following concomitant administration of pemoline with anticonvulsant agents.
    Pentazocine: (Major) Concomitant use of pentazocine with gabapentin may cause excessive sedation, somnolence, and respiratory depression. Limit the use of pentazocine with gabapentin to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, initiate gabapentin at the lowest recommended dose and monitor patients for symptoms of respiratory depression and sedation. Use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Educate patients about the risks and symptoms of excessive CNS depression and respiratory depression.
    Pentazocine; Naloxone: (Major) Concomitant use of pentazocine with gabapentin may cause excessive sedation, somnolence, and respiratory depression. Limit the use of pentazocine with gabapentin to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, initiate gabapentin at the lowest recommended dose and monitor patients for symptoms of respiratory depression and sedation. Use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Educate patients about the risks and symptoms of excessive CNS depression and respiratory depression.
    Pentobarbital: (Major) Concomitant use of barbiturates with gabapentin may cause excessive sedation, somnolence, and respiratory depression. If concurrent use is necessary, initiate gabapentin at the lowest recommended dose and monitor patients for symptoms of respiratory depression and sedation. Educate patients about the risks and symptoms of excessive CNS depression and respiratory depression.
    Perampanel: (Moderate) Monitor for excessive sedation and somnolence during coadministration of perampanel and gabapentin. Concurrent use may result in additive CNS depression.
    Perphenazine: (Moderate) Monitor for excessive sedation and somnolence during coadministration of perphenazine and gabapentin. Concurrent use may result in additive CNS depression.
    Perphenazine; Amitriptyline: (Moderate) Monitor for excessive sedation and somnolence during coadministration of perphenazine and gabapentin. Concurrent use may result in additive CNS depression.
    Phenelzine: (Moderate) Monitor for excessive sedation and somnolence during coadministration of monoamine oxidase inhibitors (MAOIs) and gabapentin. Concurrent use may result in additive CNS depression. MAOIs can cause a variable change in seizure patterns, so careful monitoring of patients receiving gabapentin for epilepsy is required.
    Phenobarbital: (Major) Concomitant use of barbiturates with gabapentin may cause excessive sedation, somnolence, and respiratory depression. If concurrent use is necessary, initiate gabapentin at the lowest recommended dose and monitor patients for symptoms of respiratory depression and sedation. Educate patients about the risks and symptoms of excessive CNS depression and respiratory depression.
    Phenobarbital; Hyoscyamine; Atropine; Scopolamine: (Major) Concomitant use of barbiturates with gabapentin may cause excessive sedation, somnolence, and respiratory depression. If concurrent use is necessary, initiate gabapentin at the lowest recommended dose and monitor patients for symptoms of respiratory depression and sedation. Educate patients about the risks and symptoms of excessive CNS depression and respiratory depression. (Moderate) Monitor for excessive sedation and somnolence during coadministration of atropine and gabapentin. Concurrent use may result in additive CNS depression. (Moderate) Monitor for excessive sedation and somnolence during coadministration of scopolamine and gabapentin. Concurrent use may result in additive CNS depression.
    Pimavanserin: (Moderate) Monitor for excessive sedation and somnolence during coadministration of pimavanserin and gabapentin. Concurrent use may result in additive CNS depression.
    Pimozide: (Major) Initiate gabapentin at the lowest recommended dose and monitor patients for symptoms of sedation and somnolence during coadministration of gabapentin and pimozide. Concomitant use of gabapentin with pimozide may cause additive CNS depression. Educate patients about the risks and symptoms of excessive CNS depression.
    Pramipexole: (Major) Initiate gabapentin at the lowest recommended dose and monitor patients for symptoms of sedation and somnolence during coadministration of gabapentin and pramipexole. Concomitant use of gabapentin with pramipexole may cause additive CNS depression. Educate patients about the risks and symptoms of excessive CNS depression. Dopaminergic agents, such as pramipexole, have also been associated with sudden sleep onset during activities of daily living such as driving, which has resulted in accidents in some cases. Reassess patients for drowsiness or sleepiness regularly throughout treatment, especially since events may occur well after the start of treatment.
    Pregabalin: (Major) Concomitant use of gabapentin with pregabalin may cause excessive sedation, somnolence, and respiratory depression. If concurrent use is necessary, initiate both pregabalin and gabapentin at the lowest recommended doses and monitor patients for symptoms of respiratory depression and sedation. Educate patients about the risks and symptoms of excessive CNS depression and respiratory depression.
    Primidone: (Major) Concomitant use of barbiturates with gabapentin may cause excessive sedation, somnolence, and respiratory depression. If concurrent use is necessary, initiate gabapentin at the lowest recommended dose and monitor patients for symptoms of respiratory depression and sedation. Educate patients about the risks and symptoms of excessive CNS depression and respiratory depression.
    Prochlorperazine: (Major) Initiate gabapentin at the lowest recommended dose and monitor patients for symptoms of sedation and somnolence during coadministration of gabapentin and prochlorperazine. Concomitant use of gabapentin with prochlorperazine may cause additive CNS depression. Educate patients about the risks and symptoms of excessive CNS depression. Concurrent administration of prochlorperazine is contraindicated in patients receiving large doses of CNS depressants.
    Promethazine: (Major) Initiate gabapentin at the lowest recommended dose and monitor patients for symptoms of sedation and somnolence during coadministration of gabapentin and promethazine. Concomitant use of gabapentin with promethazine may cause additive CNS depression. Educate patients about the risks and symptoms of excessive CNS depression.
    Promethazine; Dextromethorphan: (Major) Initiate gabapentin at the lowest recommended dose and monitor patients for symptoms of sedation and somnolence during coadministration of gabapentin and promethazine. Concomitant use of gabapentin with promethazine may cause additive CNS depression. Educate patients about the risks and symptoms of excessive CNS depression.
    Promethazine; Phenylephrine: (Major) Initiate gabapentin at the lowest recommended dose and monitor patients for symptoms of sedation and somnolence during coadministration of gabapentin and promethazine. Concomitant use of gabapentin with promethazine may cause additive CNS depression. Educate patients about the risks and symptoms of excessive CNS depression.
    Propofol: (Major) Concomitant use of general anesthetics with gabapentin may cause excessive sedation, somnolence, and respiratory depression. If concurrent use is necessary, initiate gabapentin at the lowest recommended dose and monitor patients for symptoms of excessive respiratory depression. Educate patients about the risks and symptoms of excessive CNS depression and respiratory depression.
    Propoxyphene: (Moderate) Concomitant use of opioid agonists with gabapentin may cause excessive sedation and somnolence. Limit the use of opioid pain medications with gabapentin to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Educate patients about the risks and symptoms of excessive CNS depression.
    Propranolol: (Minor) The combination of propranolol and gabapentin may induce dystonia via a pharmacodynamic interaction.
    Propranolol; Hydrochlorothiazide, HCTZ: (Minor) The combination of propranolol and gabapentin may induce dystonia via a pharmacodynamic interaction.
    Pseudoephedrine; Triprolidine: (Moderate) Monitor for excessive sedation and somnolence during coadministration of triprolidine and gabapentin. Concurrent use may result in additive CNS depression.
    Pyrilamine: (Moderate) Monitor for excessive sedation and somnolence during coadministration of pyrilamine and gabapentin. Concurrent use may result in additive CNS depression.
    Quazepam: (Major) Concomitant use of benzodiazepines with gabapentin may cause excessive sedation, somnolence, and respiratory depression. If concurrent use is necessary, initiate gabapentin at the lowest recommended dose and monitor patients for symptoms of respiratory depression and sedation. Educate patients about the risks and symptoms of excessive CNS depression and respiratory depression.
    Quetiapine: (Major) Initiate gabapentin at the lowest recommended dose and monitor patients for symptoms of sedation and somnolence during coadministration of gabapentin and quetiapine. Concomitant use of gabapentin with quetiapine may cause additive CNS depression. Educate patients about the risks and symptoms of excessive CNS depression.
    Ramelteon: (Moderate) Monitor for excessive sedation and somnolence during coadministration of ramelteon and gabapentin. Concurrent use may result in additive CNS depression.
    Rasagiline: (Major) Initiate gabapentin at the lowest recommended dose and monitor patients for symptoms of sedation and somnolence during coadministration of gabapentin and rasagiline. Concomitant use of gabapentin with rasagiline may cause additive CNS depression. Educate patients about the risks and symptoms of excessive CNS depression. Dopaminergic agents, such as rasagiline, have also been associated with sudden sleep onset during activities of daily living such as driving, which has resulted in accidents in some cases. Reassess patients for drowsiness or sleepiness regularly throughout treatment, especially since events may occur well after the start of treatment.
    Remifentanil: (Major) Concomitant use of opioid agonists with gabapentin may cause excessive sedation, somnolence, and respiratory depression. Limit the use of remifentanil with gabapentin to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, initiate gabapentin at the lowest recommended dose and monitor patients for symptoms of respiratory depression and sedation. Use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Educate patients about the risks and symptoms of excessive CNS depression and respiratory depression.
    Remimazolam: (Major) Concomitant use of benzodiazepines with gabapentin may cause excessive sedation, somnolence, and respiratory depression. If concurrent use is necessary, initiate gabapentin at the lowest recommended dose and monitor patients for symptoms of respiratory depression and sedation. Educate patients about the risks and symptoms of excessive CNS depression and respiratory depression.
    Risperidone: (Major) Initiate gabapentin at the lowest recommended dose and monitor patients for symptoms of sedation and somnolence during coadministration of gabapentin and risperidone. Concomitant use of gabapentin with risperidone may cause additive CNS depression. Educate patients about the risks and symptoms of excessive CNS depression.
    Ropinirole: (Major) Initiate gabapentin at the lowest recommended dose and monitor patients for symptoms of sedation and somnolence during coadministration of gabapentin and ropinirole. Concomitant use of gabapentin with ropinirole may cause additive CNS depression. Educate patients about the risks and symptoms of excessive CNS depression. Dopaminergic agents, such as ropinirole, have also been associated with sudden sleep onset during activities of daily living such as driving, which has resulted in accidents in some cases. Reassess patients for drowsiness or sleepiness regularly throughout treatment, especially since events may occur well after the start of treatment.
    Rotigotine: (Major) Initiate gabapentin at the lowest recommended dose and monitor patients for symptoms of sedation and somnolence during coadministration of gabapentin and rotigotine. Concomitant use of gabapentin with rotigotine may cause additive CNS depression. Educate patients about the risks and symptoms of excessive CNS depression. Dopaminergic agents, such as rotigotine, have also been associated with sudden sleep onset during activities of daily living such as driving, which has resulted in accidents in some cases. Reassess patients for drowsiness or sleepiness regularly throughout treatment, especially since events may occur well after the start of treatment.
    Safinamide: (Major) Initiate gabapentin at the lowest recommended dose and monitor patients for symptoms of sedation and somnolence during coadministration of gabapentin and safinamide. Concomitant use of gabapentin with safinamide may cause additive CNS depression. Educate patients about the risks and symptoms of excessive CNS depression. Dopaminergic agents, such as safinamide, have also been associated with sudden sleep onset during activities of daily living such as driving, which has resulted in accidents in some cases. Reassess patients for drowsiness or sleepiness regularly throughout treatment, especially since events may occur well after the start of treatment.
    Scopolamine: (Moderate) Monitor for excessive sedation and somnolence during coadministration of scopolamine and gabapentin. Concurrent use may result in additive CNS depression.
    Secobarbital: (Major) Concomitant use of barbiturates with gabapentin may cause excessive sedation, somnolence, and respiratory depression. If concurrent use is necessary, initiate gabapentin at the lowest recommended dose and monitor patients for symptoms of respiratory depression and sedation. Educate patients about the risks and symptoms of excessive CNS depression and respiratory depression.
    Selegiline: (Moderate) Monitor for excessive sedation and somnolence during coadministration of selegiline and gabapentin. Concurrent use may result in additive CNS depression.
    Sevoflurane: (Major) Concomitant use of general anesthetics with gabapentin may cause excessive sedation, somnolence, and respiratory depression. If concurrent use is necessary, initiate gabapentin at the lowest recommended dose and monitor patients for symptoms of excessive respiratory depression. Educate patients about the risks and symptoms of excessive CNS depression and respiratory depression.
    Sodium Bicarbonate: (Moderate) Antacids have been shown to reduce the oral bioavailability of gabapentin by roughly 20%. This decrease in bioavailability was about 5% when gabapentin was administered 2 hours after the antacid. It is recommended that gabapentin be taken at least 2 hours following the administration of antacids in order to avoid a significant interaction.
    Sodium Oxybate: (Major) Concomitant use of sodium oxybate with gabapentin may cause excessive sedation, somnolence, and respiratory depression. If concurrent use is necessary, initiate gabapentin at the lowest recommended dose and monitor patients for symptoms of respiratory depression and sedation. Educate patients about the risks and symptoms of excessive CNS depression and respiratory depression.
    Sufentanil: (Major) Concomitant use of opioid agonists with gabapentin may cause excessive sedation, somnolence, and respiratory depression. Limit the use of sufentanil with gabapentin to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, initiate gabapentin at the lowest recommended dose and monitor patients for symptoms of respiratory depression and sedation. Use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. The use of sufentanil with CNS depressants may result in decreased pulmonary artery pressure and hypotension. As postoperative analgesia, concomitant use increases the risk for hypotension, respiratory depression, profound sedation, coma, and death. Educate patients about the risks and symptoms of excessive CNS depression and respiratory depression.
    Suvorexant: (Moderate) Monitor for excessive sedation and somnolence during coadministration of suvorexant and gabapentin. Concurrent use may result in additive CNS depression.
    Tapentadol: (Major) Concomitant use of opioid agonists with gabapentin may cause excessive sedation, somnolence, and respiratory depression. Limit the use of opioid pain medications with gabapentin to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, initiate gabapentin at the lowest recommended dose and monitor patients for symptoms of respiratory depression and sedation. Use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Educate patients about the risks and symptoms of excessive CNS depression and respiratory depression.
    Tasimelteon: (Moderate) Monitor for excessive sedation and somnolence during coadministration of tasimelteon and gabapentin. Concurrent use may result in additive CNS depression.
    Temazepam: (Major) Concomitant use of benzodiazepines with gabapentin may cause excessive sedation, somnolence, and respiratory depression. If concurrent use is necessary, initiate gabapentin at the lowest recommended dose and monitor patients for symptoms of respiratory depression and sedation. Educate patients about the risks and symptoms of excessive CNS depression and respiratory depression.
    Tetrabenazine: (Moderate) Monitor for excessive sedation and somnolence during coadministration of tetrabenazine and gabapentin. Concurrent use may result in additive CNS depression.
    Thalidomide: (Major) Avoid coadministration of thalidomide with gabapentin because of the risk of additive CNS depression. If concurrent use cannot be avoided, initiate gabapentin at the lowest recommended dose and monitor patients for symptoms of sedation and somnolence during coadministration. Educate patients about the risks and symptoms of excessive CNS depression.
    Thiopental: (Major) Concomitant use of barbiturates with gabapentin may cause excessive sedation, somnolence, and respiratory depression. If concurrent use is necessary, initiate gabapentin at the lowest recommended dose and monitor patients for symptoms of respiratory depression and sedation. Educate patients about the risks and symptoms of excessive CNS depression and respiratory depression.
    Thioridazine: (Major) Initiate gabapentin at the lowest recommended dose and monitor patients for symptoms of sedation and somnolence during coadministration of gabapentin and thioridazine. Concomitant use of gabapentin with thioridazine may cause additive CNS depression. Educate patients about the risks and symptoms of excessive CNS depression.
    Thiothixene: (Moderate) Monitor for excessive sedation and somnolence during coadministration of thiothixene and gabapentin. Concurrent use may result in additive CNS depression.
    Tizanidine: (Major) Initiate gabapentin at the lowest recommended dose and monitor patients for symptoms of sedation and somnolence during coadministration of gabapentin and tizanidine. Concomitant use of gabapentin with tizanidine may cause additive CNS depression. Educate patients about the risks and symptoms of excessive CNS depression.
    Tolcapone: (Major) Initiate gabapentin at the lowest recommended dose and monitor patients for symptoms of sedation and somnolence during coadministration of gabapentin and tolcapone. Concomitant use of gabapentin with tolcapone may cause additive CNS depression. Educate patients about the risks and symptoms of excessive CNS depression. Dopaminergic agents, such as tolcapone, have also been associated with sudden sleep onset during activities of daily living such as driving, which has resulted in accidents in some cases. Reassess patients for drowsiness or sleepiness regularly throughout treatment, especially since events may occur well after the start of treatment.
    Tramadol: (Major) Concomitant use of opioid agonists with gabapentin may cause excessive sedation, somnolence, and respiratory depression. Limit the use of opioid pain medications with gabapentin to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, initiate gabapentin at the lowest recommended dose and monitor patients for symptoms of respiratory depression and sedation. Use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Educate patients about the risks and symptoms of excessive CNS depression and respiratory depression.
    Tramadol; Acetaminophen: (Major) Concomitant use of opioid agonists with gabapentin may cause excessive sedation, somnolence, and respiratory depression. Limit the use of opioid pain medications with gabapentin to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, initiate gabapentin at the lowest recommended dose and monitor patients for symptoms of respiratory depression and sedation. Use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Educate patients about the risks and symptoms of excessive CNS depression and respiratory depression.
    Tranylcypromine: (Moderate) Monitor for excessive sedation and somnolence during coadministration of monoamine oxidase inhibitors (MAOIs) and gabapentin. Concurrent use may result in additive CNS depression. MAOIs can cause a variable change in seizure patterns, so careful monitoring of patients receiving gabapentin for epilepsy is required.
    Trazodone: (Major) Initiate gabapentin at the lowest recommended dose and monitor patients for symptoms of sedation and somnolence during coadministration of gabapentin and trazodone. Concomitant use of gabapentin with trazodone may cause additive CNS depression. Educate patients about the risks and symptoms of excessive CNS depression.
    Triazolam: (Major) Concomitant use of benzodiazepines with gabapentin may cause excessive sedation, somnolence, and respiratory depression. If concurrent use is necessary, initiate gabapentin at the lowest recommended dose and monitor patients for symptoms of respiratory depression and sedation. Educate patients about the risks and symptoms of excessive CNS depression and respiratory depression.
    Tricyclic antidepressants: (Major) Initiate gabapentin at the lowest recommended dose and monitor patients for symptoms of sedation and somnolence during coadministration of gabapentin and tricyclic antidepressants. Concomitant use of gabapentin with tricyclic antidepressants may cause additive CNS depression. Educate patients about the risks and symptoms of excessive CNS depression.
    Trifluoperazine: (Moderate) Monitor for excessive sedation and somnolence during coadministration of trifluoperazine and gabapentin. Concurrent use may result in additive CNS depression.
    Triprolidine: (Moderate) Monitor for excessive sedation and somnolence during coadministration of triprolidine and gabapentin. Concurrent use may result in additive CNS depression.
    Valerian, Valeriana officinalis: (Moderate) Monitor for excessive sedation and somnolence during coadministration of valerian and gabapentin. Concurrent use may result in additive CNS depression.
    Valproic Acid, Divalproex Sodium: (Moderate) Monitor for excessive sedation and somnolence during coadministration of valproic acid and gabapentin. Concurrent use may result in additive CNS depression.
    Zaleplon: (Major) Initiate gabapentin at the lowest recommended dose and monitor patients for symptoms of sedation and somnolence during coadministration of gabapentin and zaleplon. Concomitant use of gabapentin with zaleplon may cause additive CNS depression and complex sleep-related behaviors (e.g., driving, talking, eating, or performing other activities while not fully awake). Educate patients about the risks and symptoms of excessive CNS depression. Instruct patients to contact their provider immediately if sleep-related symptoms or behaviors occur.
    Ziprasidone: (Moderate) Monitor for excessive sedation and somnolence during coadministration of ziprasidone and gabapentin. Concurrent use may result in additive CNS depression.
    Zolpidem: (Major) Initiate gabapentin at the lowest recommended dose and monitor patients for symptoms of sedation and somnolence during coadministration of gabapentin and zolpidem. The recommended dose of sublingual zolpidem tablets is 1.75 mg/night in patients receiving concomitant CNS depressants. Concomitant use of gabapentin with zolpidem may cause additive CNS depression and complex sleep-related behaviors (e.g., driving, talking, eating, or performing other activities while not fully awake). Educate patients about the risks and symptoms of excessive CNS depression. Instruct patients to contact their provider immediately if sleep-related symptoms or behaviors occur.

    PREGNANCY AND LACTATION

    Pregnancy

    There are no adequate and well-controlled studies of gabapentin in pregnant women. Data from cohort studies describing the neonatal risks of gabapentin treatment during pregnancy are inconclusive. Gabapentin actively crosses the placenta. Among 6 neonates born to mothers who were taking gabapentin (doses ranging from 900 to 3,200 mg/day), umbilical cord-to-maternal plasma concentration ratios ranged from 1.3 to 2.11 (mean, 1.74) at delivery. Gabapentin concentrations in the neonates declined to an average of 27% (range, 12% to 36%) of cord blood concentrations at 24 hours postpartum. One infant was born premature at 33 weeks; however, all deliveries were uneventful and all neonates were born in healthy condition. In a prospective cohort study, rates of major malformations among neonates were similar between 223 pregnancies with gabapentin exposure and 223 unexposed pregnancies (4.1% exposed vs. 2.5% unexposed, p = 0.555). Major malformations included 2 ventricular septal defects, anencephaly, macrocephaly, microretrognathism, cutis marmorata, pyloric stenosis, bilateral varus clubfoot, and cryptorchidism. In all cases of major malformations, women received concomitant treatment with other medications during pregnancy; therefore, a causal relationship to gabapentin cannot be established. No major malformations occurred in neonates born to women exposed to gabapentin monotherapy during pregnancy (n = 36). There were higher rates of preterm births (10.5% vs. 3.9%, p = 0.019), low birth weight (less than 2,500 g) (10.5% vs. 4.4%, p = 0.033), and admission to neonatal intensive care or special care nursery (38% vs. 2.9%, p less than 0.001) among neonates with gabapentin exposure compared to unexposed neonates. Two cases of possible poor neonatal adaptation syndrome occurred in neonates with gabapentin exposure late in pregnancy compared to no cases among unexposed infants; these 2 neonates were also exposed to other psychotropic medications. In a cohort of 39 women who were exposed to gabapentin during their first trimester (97%) and throughout gestation (81.8%), malformations occurred in 3 of 44 live births. Hypospadia was reported in a neonate exposed to gabapentin and valproate; a missing kidney occurred in a neonate exposed to gabapentin and phenobarbital, and a minor malformation of the left external ear canal and 2 small skin tags at the jaw occurred in a neonate exposed to gabapentin and lamotrigine. Since exposure to multiple antiepileptic drugs occurred during these pregnancies, a causal relationship to gabapentin cannot be established. No malformations occurred in 11 patients exposed to gabapentin monotherapy during pregnancy. In animal studies, gabapentin has been fetotoxic during organogenesis at doses of 1 to 4 times the maximum recommended human dose on a mg/m2 basis. Delayed ossification of bones in the skull, limbs, and vertebrae were reported when pregnant mice received oral gabapentin (500, 1,000, or 3,000 mg/kg/day) during organogenesis. The no-effect dose for toxicity (500 mg/kg/day) is less than the maximum human recommended dose (MRHD) of 3,600 mg/kg on a body surface area (mg/m2) basis. Increased incidences of hydroureter and/or hydronephrosis were observed at all doses tested in studies in which rats received oral gabapentin (500 to 2,000 mg/kg/day). An increased incidence of fetal loss was also noted at all doses tested when pregnant rabbits were treated with oral gabapentin (60, 300, or 1,500 mg/kg) during organogenesis. There is a pregnancy exposure registry that monitors outcomes in pregnant patients exposed to gabapentin; information about the registry can be obtained at www.aedpregnancyregistry.org or by calling 1-888-233-2334.

    Gabapentin is excreted in human breast milk; however, it is not known if gabapentin derived from gabapentin enacarbil is excreted in human milk. A breast-feeding infant could be exposed to a maximum gabapentin dose of approximately 1 mg/kg/day. There are no data on the effects of gabapentin on the breast-fed infant or milk production. Consider the developmental and health benefits of breast-feeding along with the mother's clinical need for gabapentin and any potential adverse effects on the breast-fed infant from gabapentin or the underlying maternal condition. Only use gabapentin in breast-feeding women if the benefits clearly outweigh the risks.[27986] [43322] [43905] The infant dose of gabapentin excreted in breast milk was examined in 4 infants, 3 of which were 2 to 3 weeks of age and 1 who was approximately 3 months old. The average daily maternal dosage of gabapentin was 1,575 mg (range: 600 to 2,100 mg/day). A single milk sample was obtained approximately 10 to 15 hours after the last dose. Assuming a breast milk consumption of 150 mL/kg/day, the relative infant dose of gabapentin was estimated to be 0.2 to 1.3 mg/kg/day, which approximates 1.3% to 3.8% of the weight-adjusted maternal dose. At 2 to 3 weeks after delivery, 2 infants had detectable gabapentin plasma concentrations that were under the normal range of quantification, and 1 had an undetectable concentration. At 3 months, the gabapentin plasma concentration in another infant was under the normal range of quantification. No adverse effects were reported.[62571]

    MECHANISM OF ACTION

    The exact mechanism by which gabapentin exerts its anticonvulsant activity is not known, but it does not appear to be related to its development as a GABA analog. Animal studies have shown that gabapentin binds with high affinity in the brain but does not act at GABA receptors, and does not inhibit sustained repetitive firing of sodium action potentials. Gabapentin does appear to interact with cortical neurons at auxillary subunits of voltage-sensitive calcium channels, but the relationship of this action to functional activity is unclear. Gabapentin crosses brain cell lipid membranes via L-system amino acid transporters. In vitro actions include the modulation of GABA synthetic enzyme, glutamate synthesizing enzyme, glutamic acid decarboxylase, and branched-chain amino acid transaminase. In animals, gabapentin increases GABA responses at non-synaptic sites in neuronal tissues, and reduces the release of mono-amine neurotransmitters. In humans, NMR spectroscopy has indicated that gabapentin increases GABA synthesis. In animal models, gabapentin is most effective in inhibiting seizures produced by maximal electroshock and was also found to decrease the median effective dose of phenytoin, carbamazepine, valproic acid, and primidone. Gabapentin reduces pain responses in several animal models of hyperalgesia, and prevents neuron death in models of amyotrophic lateral sclerosis (ALS). Animal models have also demonstrated anxiolytic activities of gabapentin.

    PHARMACOKINETICS

    Gabapentin is administered orally. Plasma concentrations > 2 mcg/mL are considered therapeutic; however, it is not necessary to monitor gabapentin plasma concentrations to optimize therapy. Protein binding of gabapentin is < 3%. Because of its high degree of lipid solubility, gabapentin readily distributes into the CNS. Gabapentin is not metabolized and is excreted intact in the urine. The elimination half-life in patients with normal renal function administered 1200 to 3000 mg/day of immediate-release gabapentin ranges 5—7 hours.
     
    Gabapentin enacarbil does not prolong QTc to a clinically relevant extent at doses of 6000 mg.

    Oral Route

    Gabapentin is rapidly absorbed within the proximal small bowel, in part by the saturable L-amino acid transport system. Bioavailability declines with higher doses. The absolute bioavailability of immediate-release gabapentin is 60% for a 300 mg dose and 35% for a 1600 mg dose; the bioavailability values of one extended-release tablet formulation (Gralise) are not stated. The mean bioavailability of Horizant (gabapentin enacarbil) extended-release tablets in the fed state is about 75%. One pharmacokinetic study assessed the bioavailability of immediate-release gabapentin following administration of the contents of opened capsules mixed with water, fruit juice, applesauce, or pudding. Food does not affect the absorption of immediate-release gabapentin, even when the capsules are opened for ease of administration. However, extended-release gabapentin should be taken with food; the rate and extent absorption are increased when administered with a fatty meal. Unlike immediate-release gabapentin, the Gralise extended-release tablets swell in gastric fluid, gradually releasing the medication and thus slowing drug absorption. The use of 1800 mg of extended-release gabapentin (Gralise), administered once daily, as compared to 1800 mg of immediate-release gabapentin, administered as 600 mg three times daily, resulted in higher Cmax (9.585 +/- 2.326 ng/mL vs 8.536 +/- 1.715 ng/mL) and longer median time to achieve maximal plasma concentrations (8 [range: 3—12] hours vs 2 [range: 1—5] hours). Steady-state of Horizant extended-release tablets is reached in 2 days with daily administration.
     
    NOTE: Neither Gralise or Horizant extended-release tablets are interchangeable with other gabapentin formulations or each other because of differing pharmacokinetic profiles.