CLASSES

Glycopeptide Antibiotics
Intestinal Antibiotics

DEA CLASS

Rx

DESCRIPTION

Glycopeptide antibiotic; only effective for gram-positive bacteria; poorly absorbed orally; however, used orally to treat GI infections such as pseudomembranous colitis; serum concentration monitoring with systemic use.

COMMON BRAND NAMES

FIRVANQ, Vancocin, Vancocin Powder, VANCOSOL

HOW SUPPLIED

FIRVANQ/Vancomycin/Vancomycin Hydrochloride Oral Pwd F/Recon: 3.8g, 5mL, 7.7g, 15.4g, 250mg
Vancomycin/Vancomycin Hydrochloride Intravenous Inj Pwd F/Sol: 1g, 1.25g, 1.5g, 5g, 10g, 100g, 250mg, 500mg, 750mg
Vancomycin/Vancomycin Hydrochloride Oral Cap: 125mg, 250mg
Vancomycin/Vancomycin Hydrochloride/Vancomycin Hydrochloride, Dextrose/Vancomycin Hydrochloride, Sodium Chloride/Vancomycin, Dextrose/Vancomycin, Sodium Chloride Intravenous Inj Sol: 1mL, 5mg, 1-0.9%, 1-5%, 500-0.9%, 500-5%, 750-0.9%, 750-5%
Vancomycin/Vancomycin Hydrochloride/VANCOSOL Intravenous Inj Pwd: 1g

DOSAGE & INDICATIONS

†Indicates off-label use

MAXIMUM DOSAGE

2 g/day IV/PO per FDA-approved labeling; individualize IV dosage to patient age, weight, indication for use, and serum drug concentration monitoring.

2 g/day IV/PO per FDA-approved labeling; individualize IV dosage to patient age, weight, indication for use, and serum drug concentration monitoring.

40 mg/kg/day IV and 2 g/day PO per FDA-approved product labeling; however, initial doses up to 60 mg/kg/day IV are recommended off-label for severe infections. Individualize IV dosage to patient age, weight, indication for use, and serum drug concentration monitoring.

40 mg/kg/day IV and 2 g/day PO per FDA-approved product labeling; however, initial doses up to 60 mg/kg/day IV are recommended off-label for severe infections. Individualize IV dosage to patient age, weight, indication for use, and serum drug concentration monitoring.

40 mg/kg/day IV/PO per FDA-approved product labeling; however, initial doses up to 60 mg/kg/day IV are recommended off-label for severe infections. Individualize IV dosage to patient age, weight, indication for use, and serum drug concentration monitoring.

8 days and older: 30 mg/kg/day IV per FDA-approved product labeling; however, doses should be individualized based on patient age, weight, indication for use, and serum drug concentration monitoring.
0 to 7 days: 20 mg/kg/day IV per FDA-approved product labeling; however, doses should be individualized based on patient age, weight, indication for use, and serum drug concentration monitoring.

DOSING CONSIDERATIONS

Specific guidelines for dosage adjustments in hepatic impairment are not available; it appears that no dosage adjustments are needed.

Oral dosing
Specific guidelines for dosage adjustments of the oral formulation in renal impairment are not available; it appears no dosage adjustment is needed.[28468] [62844]
 
Intravenous dosing
The manufacturer's renal adjustment recommendations and conventional IV dosing nomograms will likely not lead to an appropriate AUC/MIC target of 400 to 600 mg x hour/L as defined by guidelines. Individualize IV dosage based on patient-specific factors and modify based on therapeutic drug monitoring.[65262]
 
Adult patients† [65347] [65348] [65349]
CrCl more than 65 mL/min per 70 kg: No dosage adjustment necessary.
CrCl 40 to 65 mL/min per 70 kg: Extend IV dosing interval to every 12 hours.
CrCl 20 to 39 mL/min per 70 kg: Extend IV dosing interval to every 24 hours.
CrCl 10 to 20 mL/min per 70 kg: Extend IV dosing interval to every 48 hours.
 
Infants, Children, and Adolescents† [32569]
GFR more than 50 mL/minute/1.73 m2: No initial adjustment; monitor serum concentrations.
GFR 30 to 50 mL/minute/1.73 m2: Extend IV dosing interval to every 12 hours
GFR 10 to 29 mL/minute/1.73 m2: Extend IV dosing interval to every 18 to 24 hours.
GFR less than 10 mL/minute/1.73 m2: Dose as needed per serum concentration monitoring.
Neonates older than 28 weeks gestation†
SCr less than 0.7 mg/dL: 15 mg/kg/dose IV every 12 hours.
SCr 0.7 to 0.9 mg/dL: 20 mg/kg/dose IV every 24 hours.
SCr 1 to 1.2 mg/dL: 15 mg/kg/dose IV every 24 hours.
SCr 1.3 to 1.6 mg/dL: 10 mg/kg/dose IV every 24 hours.
SCr more than 1.6 mg/dL: 15 mg/kg/dose IV every 48 hours.
 
Neonates 28 weeks gestation and younger†
SCr less than 0.5 mg/dL: 15 mg/kg/dose IV every 12 hours.
SCr 0.5 to 0.7 mg/dL: 20 mg/kg/dose IV every 24 hours.
SCr 0.8 to 1 mg/dL: 15 mg/kg/dose IV every 24 hours.
SCr 1.1 to 1.4 mg/dL: 10 mg/kg/dose IV every 24 hours.
SCr more than 1.4 mg/dL: 15 mg/kg/dose IV every 48 hours.
 
Intermittent hemodialysis
For IV dosing, maintaining predialysis serum vancomycin concentrations between 15 and 20 mg/L is likely to attain the AUC target of 400 to 600 mg x hour/L in the previous 24 hours with higher AUC/MIC values occurring on days prior. Predialysis serum concentration monitoring should be performed at least weekly and should drive subsequent dosing. Loading and maintenance doses should be based on the timing of the dose and dialyzer permeability. Vancomycin dosing data are limited in pediatric patients receiving hemodialysis; therefore, recommendations are based on guideline recommendations for adult patients.[65262]
 
Adult and Pediatric patients - dosing after dialysis ends† [65262]
Low permeability dialyzer: 25 mg/kg/dose (actual body weight) IV loading dose; 7.5 mg/kg/dose (actual body weight) IV maintenance dose (generally 3 times per week).
High permeability dialyzer: 25 mg/kg/dose (actual body weight) IV loading dose; 10 mg/kg/dose (actual body weight) IV maintenance dose (generally 3 times per week).
 
Adult and Pediatric patients - intradialytic dosing† [65262]
Low permeability dialyzer: 30 mg/kg/dose (actual body weight) IV loading dose; 7.5 to 10 mg/kg/dose (actual body weight) IV maintenance dose (generally 3 times per week).
High permeability dialyzer: 35 mg/kg/dose (actual body weight) IV loading dose; 10 to 15 mg/kg/dose (actual body weight) IV maintenance dose (generally 3 times per week).
 
Peritoneal dialysis†
Adult and Pediatric patients
Serum concentrations above 15 mcg/mL are recommended when administered intraperitoneally. Clearance of vancomycin by intermittent peritoneal dialysis is highly variable.[53190] [61676]
 
Continuous renal replacement therapy (CRRT)†
NOTE: Various CRRT modalities include continuous venovenous hemofiltration (CVVH), continuous venovenous hemodialysis (CVVHD), continuous venovenous hemodiafiltration (CVVHDF), continuous venovenous high-flux hemodialysis (CVVHFD), continuous arteriovenous hemofiltration (CAVH), continuous arteriovenous hemodialysis (CAVHD), and continuous arteriovenous hemodiafiltration (CAVHDF). Dosing should take into consideration patient-specific factors (e.g. intrinsic renal function), type of infection, the duration of renal replacement therapy, the effluent flow rate, and the replacement solution administered.[42303] For CRRT operating in an uninterrupted fashion, vancomycin clearance is relatively constant over the dosing interval, although clearance may decline as the hemodiafilter clogs over time. Vancomycin clearance is related closely to the rate of ultrafiltrate/dialysate flow.[65262] Definitive dosage recommendations have not been established in pediatric patients; therefore, recommendations are based on guideline recommendations for adult patients.[24879] [41118] [41119] [41120] [42303]
 
Adult and Pediatric patients
Loading doses of 20 to 25 mg/kg/dose (actual body weight) IV should be used in patients receiving CRRT at conventional, KDIGO-recommended effluent rates of 20 to 25 mL/kg/h. Initial maintenance doses with these effluent rates should be 7.5 to 10 mg/kg/dose (actual body weight) IV every 12 hours. Further maintenance dosing should be based on serum concentration monitoring conducted within the first 24 hours. In fluid overloaded patients, doses may be reduced as patients become euvolemic and drug Vd decreases. Continuous infusion vancomycin may be considered in these patients, especially when high CRRT ultrafiltrate/dialysate flow rates are employed.[65262]
 
Hybrid hemodialysis†
NOTE: Hybrid treatments include prolonged intermittent renal replacement therapy (PIRRT), sustained low-efficiency dialysis (SLED), slow extended daily dialysis/diafiltration (SLEDD-f), and extended daily dialysis (EDD). Dosing should take into consideration patient-specific factors (e.g. intrinsic renal function), the type of infection, the duration of renal replacement therapy, the ultrafiltration rate, the dialysis flow rate, and how often dialysis sessions occur.[65397]
 
Adult and Pediatric patients
NOTE: Vancomycin dosing data are limited in pediatric patients receiving hybrid hemodialysis; therefore, recommendations are based on guideline recommendations for adult patients.[65262]
 
Loading doses of 20 to 25 mg/kg/dose (actual body weight) IV and initial doses should not be delayed until the end of the dialysis session. Maintenance doses of 15 mg/kg/dose (actual body weight) IV should be administered after the dialysis session ends or during the final 60 to 90 minutes of dialysis. Concentration monitoring should guide further maintenance doses. Serum concentrations obtained 2 hours after the vancomycin infusion and immediately prior to PIRRT can be used to calculate the AUC for dosing modifications.[65262]

ADMINISTRATION

Visually inspect parenteral products for particulate matter and discoloration prior to administration whenever solution and container permit.

STORAGE

Generic:
- Discard product if it contains particulate matter, is cloudy, or discolored
- Discard unused portion 4 hours after initial entry of container
- Store at controlled room temperature (between 68 and 77 degrees F)
FIRVANQ:
- Discard product if it contains particulate matter, is cloudy, or discolored
- Protect from freezing
- Protect from light
- Store between 36 to 46 degrees F
- Store reconstituted product in refrigerator (36 to 46 degrees F), discard after 14 days
Vancocin:
- Discard product if it contains particulate matter, is cloudy, or discolored
- Store reconstituted product in accordance with package insert instructions
- Store reconstituted product in refrigerator (36 to 46 degrees F), discard after 14 days
- Store unreconstituted product at 68 to 77 degrees F
Vancocin Powder:
- Discard product if it contains particulate matter, is cloudy, or discolored
- Discard unused portion 4 hours after initial entry of container
- Protect from direct sunlight
- Store at controlled room temperature (between 68 and 77 degrees F)
- Store in a cool, well ventilated, dry place
- Store in original container
- Store upright
VANCOSOL:
- Discard product if it contains particulate matter, is cloudy, or discolored
- Store at controlled room temperature (between 68 and 77 degrees F)

CONTRAINDICATIONS / PRECAUTIONS

Vancomycin is contraindicated in patients who have a history of vancomycin hypersensitivity. Vancomycin solutions containing dextrose may be contraindicated in patients with history of corn hypersensitivity or corn product hypersensitivity.

Vancomycin should be used with caution in patients with renal impairment because it can accumulate. Doses should be adjusted in patients with renal dysfunction. Vancomycin serum concentrations and renal-function tests should be performed during therapy, especially when concurrent nephrotoxic agents, such as aminoglycosides, are used. Nephrotoxicity (renal failure), principally manifested by azotemia (increased BUN) or increased serum creatinine, has been rarely reported with vancomycin. The risk for nephrotoxicity is increased in patients receiving large doses of vancomycin, in those receiving other nephrotoxic drugs such as aminoglycosides, or those who had preexisting renal disease or impairment. Historically, nephrotoxicity may be associated with product impurity. As monotherapy, nephrotoxicity associated with vancomycin in the literature is reported to be 5 to 7% or less. Vancomycin does potentiate the nephrotoxic effects of aminoglycosides and may increase that potential by 3- to 4-fold. Vancomycin exposure to renal proximal tubule epithelial cells results in increased oxygen consumption and ATP concentrations. Toxicity is not limited to the proximal tubules, but may also involve the medullary regions (loop of Henle and collecting duct) of the nephron. Vancomycin toxicity resulting in the destruction of glomeruli and proximal tubule necrosis may be due to oxidative stress. Nephrotoxicity due to vancomycin monotherapy is usually reversible. Higher doses have been associated with nephrotoxicity in some studies; however, concomitant nephrotoxic agents, severity of illness, patient hemodynamics, and the use of pressors may all complicate the interpretation of nephrotoxicity in these patients. Additionally, it is often difficult to determine if higher vancomycin concentrations preceded nephrotoxicity or were a result of worsening renal impairment.

Administer each intravenous vancomycin dose over at least 60 minutes. Larger loading doses may require extended infusion times of at least 2 to 3 hours. Infusion rates of 10 to 15 mg/minute are recommended. Too-rapid administration can lead to infusion-related reactions such as 'red man syndrome'. The frequency of infusion-related events may be higher with the concomitant administration of anesthetic agents. In addition, care must be taken to avoid extravasation because vancomycin is extremely irritating to tissues. Avoid intramuscular administration due to severe pain at the injection site. The safety and efficacy of intrathecal administration (intralumbar or intraventricular), intraperitoneal administration, intracameral administration, or intravitreal administration have not been established. Intraperitoneal administration of vancomycin has been associated with peritonitis. Hemorrhagic occlusive retinal vasculitis (HORV), including permanent loss of vision, has occurred in patients receiving intracameral or intravitreal administration of vancomycin during or after cataract surgery (ocular surgery).[40955] [40956] [62413] [65262]

Transient or permanent ototoxicity has occurred in patients receiving IV vancomycin. It has been reported mostly in patients who have been given excessive doses, who have an underlying hearing impairment or renal dysfunction, or who are receiving concomitant therapy with another ototoxic agent. Serial tests of auditory function may be helpful in order to minimize the risk of ototoxicity.

Consider pseudomembranous colitis in patients presenting with diarrhea after antibacterial use. Careful medical history is necessary as pseudomembranous colitis has been reported to occur over 2 months after the administration of antibacterial agents. Almost all antibacterial agents, including vancomycin, have been associated with pseudomembranous colitis or C. difficile-associated diarrhea (CDAD) which may range in severity from mild to life-threatening. Treatment with antibacterial agents alters the normal flora of the colon leading to overgrowth of C. difficile.

The clearance of vancomycin in neonates decreases as postconceptional age decreases, therefore, longer dosing intervals may be necessary in premature neonates.

There are no available data on vancomycin use in pregnant women to assess a risk of major birth defects or miscarriage. Available published data on intravenous vancomycin use in pregnancy during the second and third trimesters have not shown an association with adverse maternal or fetal outcomes.[28468] [63969] The fetal risk of ototoxic and/or nephrotoxic effects from vancomycin when administered during pregnancy is considered to be low.[27016] [33052] Certain formulations of injectable vancomycin contain excipients, such as polyethylene glycol (PEG) 400 and N-acetyl-D-alanine (NADA), which have caused fetal malformations in animal reproductive studies. If vancomycin use is needed during pregnancy, utilize other available formulations.[63968] Systemic absorption of vancomycin is low after oral administration; however, absorption may vary depending on various factors.[28468] [63969] Vancomycin crosses the placenta and can accumulate in amniotic fluid. Cord blood concentrations in 1 newborn were about 76% of the mother's serum concentrations after the mother received vancomycin 1 g IV every 12 hours for 13 days; no maternal nephrotoxicity or ototoxicity was noted.[33051] Congenital abnormalities were not noted in newborns of mothers who received vancomycin 1 g IV every 12 hours for at least 1 week.[33052] In a study evaluating hearing loss and nephrotoxicity in infants of 10 pregnant women treated with IV vancomycin in the second or third trimester, no infant had abnormal sensorineural hearing at 3 months or nephrotoxicity. In a study of 55 pregnant women who received IV vancomycin at the time of delivery, no major adverse reactions were noted in the newborns or the mothers, including no sensorineural hearing loss. Neonatal renal function was not examined.[28468] [63969] Animal data do not demonstrate any risk of teratogenic or toxic effects on the fetus.[28468] [33050] [33054] [28468] [33053]

There is insufficient data on the presence of vancomycin in human milk. There are no data on the effects of vancomycin on the breast-fed infant or milk production. Systemic absorption of vancomycin is low after oral administration; therefore, it is unlikely to result in clinically relevant exposure in nursing infants.[28468] [62844] [63969] In 1 woman treated with intravenous vancomycin 1 g every 12 hours, a single breast-milk concentration of 12.7 mcg/mL was measured at 4 hours after infusion. Her peak and trough serum vancomycin concentrations were 36.1 mcg/mL and12.5 mcg/mL, respectively.[33052] Consider the developmental and health benefits of breast-feeding along with the mother's clinical need for vancomycin and any potential adverse effects on the breast-fed infant from vancomycin or the underlying maternal condition.[28468] [62844] [63969]

Geriatric patients may need monitoring and/or initial dosage adjustments because of a higher risk of toxicity and drug accumulation secondary to age-related decrease in renal function. Clinical studies with oral vancomycin demonstrated that geriatric patients are at an increased risk of nephrotoxicity during or after completion of therapy for pseudomembranous colitis. Additionally, patients older than 65 years of age may take longer to respond to therapy for Clostridium difficile; therefore, it is important for clinicians to be aware of the appropriate duration of therapy to avoid discontinuation or switching to alternative therapy prematurely. The federal Omnibus Budget Reconciliation Act (OBRA) regulates medication use in residents of long-term care facilities (LTCFs). According to OBRA, use of parenteral vancomycin must be accompanied by monitoring of renal function tests, including a baseline value, and serum vancomycin concentrations, with the exception of single dose prophylactic administration. Serious consequences may occur insidiously if adequate monitoring does not occur; the drug may cause or worsen hearing loss and renal failure. Use of antibiotics should be limited to confirmed or suspected bacterial infections. Antibiotics are non-selective and may result in the eradication of beneficial microorganisms while promoting the emergence of undesired ones, causing secondary infections such as oral thrush, colitis, or vaginitis. Any antibiotic may cause diarrhea, nausea, vomiting, anorexia, and hypersensitivity reactions.

Due to the sodium content, avoid certain vancomycin products in patients with heart failure, requiring sodium restriction, and the elderly. Consult specific product labeling for precise sodium content.

Obesity may be associated with an increased risk of vancomycin-induced nephrotoxicity, partially due to supratherapeutic concentrations resulting from maintenance doses calculated using actual body weight. Actual body weight is used to calculate the vancomycin dose in obese patients; however, a maximum loading dose of 3,000 mg/dose and maintenance dose of 4,500 mg/day are recommended. Monitor vancomycin AUC to adjust dosing.

Serious rash events, including toxic epidermal necrolysis (TEN), Stevens-Johnson syndrome (SJS), drug reaction with eosinophilia and systemic symptoms (DRESS), acute generalized exanthematous pustulosis (AGEP), and linear IgA bullous dermatosis (LABD), have been reported with vancomycin therapy. Cutaneous signs or symptoms reported include skin rash, mucosal lesions, and blisters. Discontinue vancomycin at the first appearance of signs and symptoms of severe skin reaction.

ADVERSE REACTIONS

renal failure (unspecified) / Delayed / 0-7.0
hearing loss / Delayed / Incidence not known
ototoxicity / Delayed / Incidence not known
azotemia / Delayed / Incidence not known
interstitial nephritis / Delayed / Incidence not known
cardiac arrest / Early / Incidence not known
vasculitis / Delayed / Incidence not known
anaphylactoid reactions / Rapid / Incidence not known
agranulocytosis / Delayed / Incidence not known
exfoliative dermatitis / Delayed / Incidence not known
toxic epidermal necrolysis / Delayed / Incidence not known
Stevens-Johnson syndrome / Delayed / Incidence not known
Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS) / Delayed / Incidence not known
acute generalized exanthematous pustulosis (AGEP) / Delayed / Incidence not known
C. difficile-associated diarrhea / Delayed / Incidence not known
hemorrhagic occlusive retinal vasculitis / Delayed / Incidence not known
visual impairment / Early / Incidence not known

hypokalemia / Delayed / 13.0-13.0
neutropenia / Delayed / 2.0-12.0
peripheral edema / Delayed / 6.0-6.0
vancomycin infusion reaction / Rapid / Incidence not known
sinus tachycardia / Rapid / Incidence not known
hypotension / Rapid / Incidence not known
dyspnea / Early / Incidence not known
erythema / Early / Incidence not known
phlebitis / Rapid / Incidence not known
wheezing / Rapid / Incidence not known
thrombocytopenia / Delayed / Incidence not known
anemia / Delayed / Incidence not known
eosinophilia / Delayed / Incidence not known
constipation / Delayed / Incidence not known
superinfection / Delayed / Incidence not known
pseudomembranous colitis / Delayed / Incidence not known
depression / Delayed / Incidence not known

nausea / Early / 17.0-17.0
abdominal pain / Early / 15.0-15.0
fever / Early / 9.0-9.0
diarrhea / Early / 9.0-9.0
vomiting / Early / 9.0-9.0
flatulence / Early / 8.0-8.0
infection / Delayed / 8.0-8.0
headache / Early / 7.0-7.0
back pain / Delayed / 6.0-6.0
fatigue / Early / 5.0-5.0
dizziness / Early / Incidence not known
vertigo / Early / Incidence not known
tinnitus / Delayed / Incidence not known
pruritus / Rapid / Incidence not known
flushing / Rapid / Incidence not known
urticaria / Rapid / Incidence not known
paresthesias / Delayed / Incidence not known
injection site reaction / Rapid / Incidence not known
rash / Early / Incidence not known
chills / Rapid / Incidence not known
insomnia / Early / Incidence not known

DRUG INTERACTIONS

Acetaminophen; Ibuprofen: (Minor) It is possible that additive nephrotoxicity may occur in patients who receive NSAIDs concurrently with other nephrotoxic agents, including vancomycin.
Acyclovir: (Moderate) Closely monitor renal function if concomitant use with acyclovir and vancomycin is necessary. Both drugs can cause nephrotoxicity, which may be additive when used together.
Adefovir: (Moderate) Adefovir is eliminated renally by a combination of glomerular filtration and active tubular secretion; coadministration of adefovir dipivoxil with drugs that reduce renal function or compete for active tubular secretion, such as parenteral vancomycin, may decrease adefovir elimination by competing for common renal tubular transport systems, thereby increasing serum concentrations of adefovir and/or vancomycin. Additionally, chronic coadministration of adefovir with nephrotoxic drugs, such as vancomycin, may increase the risk of developing nephrotoxicity, even in patients who have normal renal function. Renal function should be monitored closely and vancomycin doses should be adjusted according to vancomycin serum concentrations.
Aldesleukin, IL-2: (Moderate) Aldesleukin may cause nephrotoxicity. Concurrent administration of drugs possessing nephrotoxic effects with Aldesleukin, such as vancomycin, may increase the risk of kidney dysfunction. In addition, reduced kidney function secondary to Aldesleukin treatment may delay elimination of concomitant medications and increase the risk of adverse events from those drugs.
Alfentanil: (Moderate) The concurrent administration of vancomycin and anesthetics, like alfentanil, has been associated with erythema, histamine-like flushing, and anaphylactoid reactions.
Amikacin: (Major) Concomitant use of parenteral vancomycin with other nephrotoxic drugs, such as aminoglycosides, can lead to additive nephrotoxicity. Both vancomycin and aminoglycosides may cause ototoxicity as well. In a clinical study, vancomycin coadministration, high aminoglycoside trough concentrations, and heart failure independently predicted acute kidney injury during aminoglycoside treatment. Renal function should be monitored closely, and vancomycin and aminoglycoside doses should be adjusted according to serum concentrations as clinically indicated.
Aminoglycosides: (Major) Concomitant use of parenteral vancomycin with other nephrotoxic drugs, such as aminoglycosides, can lead to additive nephrotoxicity. Both vancomycin and aminoglycosides may cause ototoxicity as well. In a clinical study, vancomycin coadministration, high aminoglycoside trough concentrations, and heart failure independently predicted acute kidney injury during aminoglycoside treatment. Renal function should be monitored closely, and vancomycin and aminoglycoside doses should be adjusted according to serum concentrations as clinically indicated.
Amlodipine; Celecoxib: (Minor) It is possible that additive nephrotoxicity may occur in patients who receive NSAIDs concurrently with other nephrotoxic agents, including vancomycin.
Amphotericin B lipid complex (ABLC): (Moderate) Concomitant use of parenteral vancomycin with other nephrotoxic drugs, such as Amphotericin B, can lead to additive nephrotoxicity. Amphotericin B dosage reduction may be necessary if renal impairment occurs.
Amphotericin B liposomal (LAmB): (Moderate) Concomitant use of parenteral vancomycin with other nephrotoxic drugs, such as Amphotericin B, can lead to additive nephrotoxicity. Amphotericin B dosage reduction may be necessary if renal impairment occurs.
Amphotericin B: (Moderate) Concomitant use of parenteral vancomycin with other nephrotoxic drugs, such as Amphotericin B, can lead to additive nephrotoxicity. Amphotericin B dosage reduction may be necessary if renal impairment occurs.
Aprotinin: (Moderate) The manufacturer recommends using aprotinin cautiously in patients that are receiving drugs that can affect renal function, such as vancomycin, as the risk of renal impairment may be increased.
Atracurium: (Moderate) Concomitant use of neuromuscular blockers and vancomycin may prolong neuromuscular blockade. The use of a peripheral nerve stimulator is strongly recommended to evaluate the level of neuromuscular blockade, to assess the need for additional doses of neuromuscular blocker, and to determine whether adjustments need to be made to the dose with subsequent administration.
Bacitracin: (Moderate) Additive nephrotoxicity may occur with concurrent use of systemic bacitracin and other nephrotoxic agents. When possible, avoid concomitant administration of systemic bacitracin and other nephrotoxic drugs such as vancomycin. Renal function should be monitored closely and vancomycin doses should be adjusted according to vancomycin serum concentrations if these drugs must be used together.
Beractant: (Major) Some surfactant-anti-infective mixtures have been shown to affect the in vivo activity of exogenous pulmonary surfactants when they are administered via inhalation. Pulmonary surfactants, such as beractant should not be mixed with anti-infectives that are commonly administered via nebulization such as vancomycin.
Bleomycin: (Minor) Previous treatment with nephrotoxic agents, like vancomycin, may result in decreased bleomycin clearance if renal function has been impaired. Monitor for signs/symptoms of bleomycin toxicity in patients with concomittant or prior vancomycin therapy.
Bupivacaine; Meloxicam: (Minor) It is possible that additive nephrotoxicity may occur in patients who receive NSAIDs concurrently with other nephrotoxic agents, including vancomycin.
Calfactant: (Major) Some surfactant-anti-infective mixtures have been shown to affect the in vivo activity of exogenous pulmonary surfactants when they are administered via inhalation. Pulmonary surfactants should not be mixed with anti-infectives that are commonly administered via nebulization such as vancomycin.
Capreomycin: (Major) Since capreomycin is eliminated by the kidney, coadministration of with other potentially nephrotoxic drugs, including vancomycin, may increase serum concentrations of either drug. Theoretically, the chronic coadministration of these drugs may increase the risk of developing nephrotoxicity, even in patients who have normal renal function. Monitor patients for changes in renal function if these drugs are coadministered.
Celecoxib: (Minor) It is possible that additive nephrotoxicity may occur in patients who receive NSAIDs concurrently with other nephrotoxic agents, including vancomycin.
Celecoxib; Tramadol: (Minor) It is possible that additive nephrotoxicity may occur in patients who receive NSAIDs concurrently with other nephrotoxic agents, including vancomycin.
Chlorpheniramine; Ibuprofen; Pseudoephedrine: (Minor) It is possible that additive nephrotoxicity may occur in patients who receive NSAIDs concurrently with other nephrotoxic agents, including vancomycin.
Cholestyramine: (Major) The concurrent use of anion-exchange resins and oral vancomycin is contraindicated by clinical practice guidelines. Per FDA-approved labeling, administer other drugs at least 1 hour before or 4 to 6 hours after cholestyramine (or as great an interval as possible). Cholestyramine can bind other drugs, such as oral vancomycin, when given concurrently.
Cidofovir: (Contraindicated) The administration of cidofovir other potentially nephrotoxic agents, such as IV vancomycin, is contraindicated. These agents should be discontinued at least 7 days prior to beginning cidofovir.
Cisatracurium: (Moderate) Concomitant use of neuromuscular blockers and vancomycin may prolong neuromuscular blockade. The use of a peripheral nerve stimulator is strongly recommended to evaluate the level of neuromuscular blockade, to assess the need for additional doses of neuromuscular blocker, and to determine whether adjustments need to be made to the dose with subsequent administration.
Cisplatin: (Moderate) Closely monitor renal function and audiometric testing if concomitant use with cisplatin and vancomycin is necessary. Both cisplatin and vancomycin can cause nephrotoxicity and ototoxicity, which may be additive when used together.
Clindamycin: (Moderate) Concomitant use of vancomycin and clindamycin may result in additive nephrotoxicity. Monitor for renal toxicity if concomitant use is required.
Colesevelam: (Major) The concurrent use of anion-exchange resins and oral vancomycin is contraindicated by clinical practice guidelines. Per FDA-approved labeling, administer other drugs at least 4 hours before colesevelam. Colesevelam can bind other drugs, such as oral vancomycin, when given concurrently.
Colestipol: (Major) The concurrent use of anion-exchange resins and oral vancomycin is contraindicated by clinical practice guidelines. Per FDA-approved labeling, administer other drugs at least 1 hour before or 4 hours after colestipol (or as great an interval as possible). Colestipol can bind other drugs, such as oral vancomycin, when given concurrently.
Colistimethate, Colistin, Polymyxin E: (Major) Since colistimethate sodium is eliminated by the kidney, coadministration with other potentially nephrotoxic drugs, including vancomycin, may increase serum concentrations of either drug. The chronic coadministration of these drugs may increase the risk of developing nephrotoxicity, even in patients who have normal renal function. Monitor patients for changes in renal function if these drugs must be coadministered.
Colistin: (Major) Since colistimethate sodium is eliminated by the kidney, coadministration with other potentially nephrotoxic drugs, including vancomycin, may increase serum concentrations of either drug. The chronic coadministration of these drugs may increase the risk of developing nephrotoxicity, even in patients who have normal renal function. Monitor patients for changes in renal function if these drugs must be coadministered.
Cyclosporine: (Minor) Additive nephrotoxicity can occur if cyclosporine is administered with other nephrotoxic drugs such as vancomycin. Renal function should be monitored closely and vancomycin doses should be adjusted according to vancomycin serum concentrations.
Deferasirox: (Moderate) Acute renal failure has been reported during treatment with deferasirox. Coadministration of deferasirox with other potentially nephrotoxic drugs, including vancomycin, may increase the risk of this toxicity. Monitor serum creatinine and/or creatinine clearance in patients who are receiving deferasirox and nephrotoxic drugs concomitantly.
Desogestrel; Ethinyl Estradiol: (Moderate) It would be prudent to recommend alternative or additional contraception when oral contraceptives (OCs) are used in conjunction with antibiotics. It was previously thought that antibiotics may decrease the effectiveness of OCs containing estrogens due to stimulation of metabolism or a reduction in enterohepatic circulation via changes in GI flora. One retrospective study reviewed the literature to determine the effects of oral antibiotics on the pharmacokinetics of contraceptive estrogens and progestins, and also examined clinical studies in which the incidence of pregnancy with OCs and antibiotics was reported. It was concluded that the antibiotics ampicillin, ciprofloxacin, clarithromycin, doxycycline, metronidazole, ofloxacin, roxithromycin, temafloxacin, and tetracycline did not alter plasma concentrations of OCs. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. Based on the study results, these authors recommended that back-up contraception may not be necessary if OCs are used reliably during oral antibiotic use. Another review concurred with these data, but noted that individual patients have been identified who experienced significant decreases in plasma concentrations of combined OC components and who appeared to ovulate; the agents most often associated with these changes were rifampin, tetracyclines, and penicillin derivatives. These authors concluded that because females most at risk for OC failure or noncompliance may not be easily identified and the true incidence of such events may be under-reported, and given the serious consequence of unwanted pregnancy, that recommending an additional method of contraception during short-term antibiotic use may be justified. During long-term antibiotic administration, the risk for drug interaction with OCs is less clear, but alternative or additional contraception may be advisable in selected circumstances. Data regarding progestin-only contraceptives or for newer combined contraceptive deliveries (e.g., patches, rings) are not available.
Diclofenac: (Minor) It is possible that additive nephrotoxicity may occur in patients who receive NSAIDs concurrently with other nephrotoxic agents, including vancomycin.
Diclofenac; Misoprostol: (Minor) It is possible that additive nephrotoxicity may occur in patients who receive NSAIDs concurrently with other nephrotoxic agents, including vancomycin.
Dienogest; Estradiol valerate: (Moderate) It would be prudent to recommend alternative or additional contraception when oral contraceptives (OCs) are used in conjunction with antibiotics. It was previously thought that antibiotics may decrease the effectiveness of OCs containing estrogens due to stimulation of metabolism or a reduction in enterohepatic circulation via changes in GI flora. One retrospective study reviewed the literature to determine the effects of oral antibiotics on the pharmacokinetics of contraceptive estrogens and progestins, and also examined clinical studies in which the incidence of pregnancy with OCs and antibiotics was reported. It was concluded that the antibiotics ampicillin, ciprofloxacin, clarithromycin, doxycycline, metronidazole, ofloxacin, roxithromycin, temafloxacin, and tetracycline did not alter plasma concentrations of OCs. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. Based on the study results, these authors recommended that back-up contraception may not be necessary if OCs are used reliably during oral antibiotic use. Another review concurred with these data, but noted that individual patients have been identified who experienced significant decreases in plasma concentrations of combined OC components and who appeared to ovulate; the agents most often associated with these changes were rifampin, tetracyclines, and penicillin derivatives. These authors concluded that because females most at risk for OC failure or noncompliance may not be easily identified and the true incidence of such events may be under-reported, and given the serious consequence of unwanted pregnancy, that recommending an additional method of contraception during short-term antibiotic use may be justified. During long-term antibiotic administration, the risk for drug interaction with OCs is less clear, but alternative or additional contraception may be advisable in selected circumstances. Data regarding progestin-only contraceptives or for newer combined contraceptive deliveries (e.g., patches, rings) are not available.
Diflunisal: (Minor) It is possible that additive nephrotoxicity may occur in patients who receive NSAIDs concurrently with other nephrotoxic agents, including vancomycin.
Diphenhydramine; Ibuprofen: (Minor) It is possible that additive nephrotoxicity may occur in patients who receive NSAIDs concurrently with other nephrotoxic agents, including vancomycin.
Diphenhydramine; Naproxen: (Minor) It is possible that additive nephrotoxicity may occur in patients who receive NSAIDs concurrently with other nephrotoxic agents, including vancomycin.
Donepezil; Memantine: (Moderate) Cationic drugs that are eliminated by renal tubular secretion, such as vancomycin, may compete with memantine for common renal tubular transport systems, thus possibly decreasing the elimination of one of the drugs. Although theoretical, careful patient monitoring of response to memantine and/or vancomycin is recommended to assess for needed dosage adjustments. In selected individuals, vancomycin serum concentration monitoring may be appropriate.
Doravirine; Lamivudine; Tenofovir disoproxil fumarate: (Moderate) Tenofovir should be avoided with concurrent or recent use of a nephrotoxic agent, such as vancomycin. Patients receiving these drugs together should be carefully monitored for changes in serum creatinine and phosphorus. Renal impairment, which may include hypophosphatemia, has been reported with the use of tenofovir; a majority of cases occurring in patients who have underlying systemic or renal disease or who are concurrently taking nephrotoxic agents.
Doxacurium: (Moderate) Concomitant use of neuromuscular blockers and vancomycin may prolong neuromuscular blockade. The use of a peripheral nerve stimulator is strongly recommended to evaluate the level of neuromuscular blockade, to assess the need for additional doses of neuromuscular blocker, and to determine whether adjustments need to be made to the dose with subsequent administration.
Drospirenone: (Moderate) It would be prudent to recommend alternative or additional contraception when oral contraceptives (OCs) are used in conjunction with antibiotics. It was previously thought that antibiotics may decrease the effectiveness of OCs containing estrogens due to stimulation of metabolism or a reduction in enterohepatic circulation via changes in GI flora. One retrospective study reviewed the literature to determine the effects of oral antibiotics on the pharmacokinetics of contraceptive estrogens and progestins, and also examined clinical studies in which the incidence of pregnancy with OCs and antibiotics was reported. It was concluded that the antibiotics ampicillin, ciprofloxacin, clarithromycin, doxycycline, metronidazole, ofloxacin, roxithromycin, temafloxacin, and tetracycline did not alter plasma concentrations of OCs. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. Based on the study results, these authors recommended that back-up contraception may not be necessary if OCs are used reliably during oral antibiotic use. Another review concurred with these data, but noted that individual patients have been identified who experienced significant decreases in plasma concentrations of combined OC components and who appeared to ovulate; the agents most often associated with these changes were rifampin, tetracyclines, and penicillin derivatives. These authors concluded that because females most at risk for OC failure or noncompliance may not be easily identified and the true incidence of such events may be under-reported, and given the serious consequence of unwanted pregnancy, that recommending an additional method of contraception during short-term antibiotic use may be justified. During long-term antibiotic administration, the risk for drug interaction with OCs is less clear, but alternative or additional contraception may be advisable in selected circumstances. Data regarding progestin-only contraceptives or for newer combined contraceptive deliveries (e.g., patches, rings) are not available.
Drospirenone; Estetrol: (Moderate) It would be prudent to recommend alternative or additional contraception when oral contraceptives (OCs) are used in conjunction with antibiotics. It was previously thought that antibiotics may decrease the effectiveness of OCs containing estrogens due to stimulation of metabolism or a reduction in enterohepatic circulation via changes in GI flora. One retrospective study reviewed the literature to determine the effects of oral antibiotics on the pharmacokinetics of contraceptive estrogens and progestins, and also examined clinical studies in which the incidence of pregnancy with OCs and antibiotics was reported. It was concluded that the antibiotics ampicillin, ciprofloxacin, clarithromycin, doxycycline, metronidazole, ofloxacin, roxithromycin, temafloxacin, and tetracycline did not alter plasma concentrations of OCs. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. Based on the study results, these authors recommended that back-up contraception may not be necessary if OCs are used reliably during oral antibiotic use. Another review concurred with these data, but noted that individual patients have been identified who experienced significant decreases in plasma concentrations of combined OC components and who appeared to ovulate; the agents most often associated with these changes were rifampin, tetracyclines, and penicillin derivatives. These authors concluded that because females most at risk for OC failure or noncompliance may not be easily identified and the true incidence of such events may be under-reported, and given the serious consequence of unwanted pregnancy, that recommending an additional method of contraception during short-term antibiotic use may be justified. During long-term antibiotic administration, the risk for drug interaction with OCs is less clear, but alternative or additional contraception may be advisable in selected circumstances. Data regarding progestin-only contraceptives or for newer combined contraceptive deliveries (e.g., patches, rings) are not available.
Drospirenone; Estradiol: (Moderate) It would be prudent to recommend alternative or additional contraception when oral contraceptives (OCs) are used in conjunction with antibiotics. It was previously thought that antibiotics may decrease the effectiveness of OCs containing estrogens due to stimulation of metabolism or a reduction in enterohepatic circulation via changes in GI flora. One retrospective study reviewed the literature to determine the effects of oral antibiotics on the pharmacokinetics of contraceptive estrogens and progestins, and also examined clinical studies in which the incidence of pregnancy with OCs and antibiotics was reported. It was concluded that the antibiotics ampicillin, ciprofloxacin, clarithromycin, doxycycline, metronidazole, ofloxacin, roxithromycin, temafloxacin, and tetracycline did not alter plasma concentrations of OCs. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. Based on the study results, these authors recommended that back-up contraception may not be necessary if OCs are used reliably during oral antibiotic use. Another review concurred with these data, but noted that individual patients have been identified who experienced significant decreases in plasma concentrations of combined OC components and who appeared to ovulate; the agents most often associated with these changes were rifampin, tetracyclines, and penicillin derivatives. These authors concluded that because females most at risk for OC failure or noncompliance may not be easily identified and the true incidence of such events may be under-reported, and given the serious consequence of unwanted pregnancy, that recommending an additional method of contraception during short-term antibiotic use may be justified. During long-term antibiotic administration, the risk for drug interaction with OCs is less clear, but alternative or additional contraception may be advisable in selected circumstances. Data regarding progestin-only contraceptives or for newer combined contraceptive deliveries (e.g., patches, rings) are not available.
Drospirenone; Ethinyl Estradiol: (Moderate) It would be prudent to recommend alternative or additional contraception when oral contraceptives (OCs) are used in conjunction with antibiotics. It was previously thought that antibiotics may decrease the effectiveness of OCs containing estrogens due to stimulation of metabolism or a reduction in enterohepatic circulation via changes in GI flora. One retrospective study reviewed the literature to determine the effects of oral antibiotics on the pharmacokinetics of contraceptive estrogens and progestins, and also examined clinical studies in which the incidence of pregnancy with OCs and antibiotics was reported. It was concluded that the antibiotics ampicillin, ciprofloxacin, clarithromycin, doxycycline, metronidazole, ofloxacin, roxithromycin, temafloxacin, and tetracycline did not alter plasma concentrations of OCs. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. Based on the study results, these authors recommended that back-up contraception may not be necessary if OCs are used reliably during oral antibiotic use. Another review concurred with these data, but noted that individual patients have been identified who experienced significant decreases in plasma concentrations of combined OC components and who appeared to ovulate; the agents most often associated with these changes were rifampin, tetracyclines, and penicillin derivatives. These authors concluded that because females most at risk for OC failure or noncompliance may not be easily identified and the true incidence of such events may be under-reported, and given the serious consequence of unwanted pregnancy, that recommending an additional method of contraception during short-term antibiotic use may be justified. During long-term antibiotic administration, the risk for drug interaction with OCs is less clear, but alternative or additional contraception may be advisable in selected circumstances. Data regarding progestin-only contraceptives or for newer combined contraceptive deliveries (e.g., patches, rings) are not available.
Drospirenone; Ethinyl Estradiol; Levomefolate: (Moderate) It would be prudent to recommend alternative or additional contraception when oral contraceptives (OCs) are used in conjunction with antibiotics. It was previously thought that antibiotics may decrease the effectiveness of OCs containing estrogens due to stimulation of metabolism or a reduction in enterohepatic circulation via changes in GI flora. One retrospective study reviewed the literature to determine the effects of oral antibiotics on the pharmacokinetics of contraceptive estrogens and progestins, and also examined clinical studies in which the incidence of pregnancy with OCs and antibiotics was reported. It was concluded that the antibiotics ampicillin, ciprofloxacin, clarithromycin, doxycycline, metronidazole, ofloxacin, roxithromycin, temafloxacin, and tetracycline did not alter plasma concentrations of OCs. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. Based on the study results, these authors recommended that back-up contraception may not be necessary if OCs are used reliably during oral antibiotic use. Another review concurred with these data, but noted that individual patients have been identified who experienced significant decreases in plasma concentrations of combined OC components and who appeared to ovulate; the agents most often associated with these changes were rifampin, tetracyclines, and penicillin derivatives. These authors concluded that because females most at risk for OC failure or noncompliance may not be easily identified and the true incidence of such events may be under-reported, and given the serious consequence of unwanted pregnancy, that recommending an additional method of contraception during short-term antibiotic use may be justified. During long-term antibiotic administration, the risk for drug interaction with OCs is less clear, but alternative or additional contraception may be advisable in selected circumstances. Data regarding progestin-only contraceptives or for newer combined contraceptive deliveries (e.g., patches, rings) are not available.
Efavirenz; Emtricitabine; Tenofovir Disoproxil Fumarate: (Moderate) Tenofovir should be avoided with concurrent or recent use of a nephrotoxic agent, such as vancomycin. Patients receiving these drugs together should be carefully monitored for changes in serum creatinine and phosphorus. Renal impairment, which may include hypophosphatemia, has been reported with the use of tenofovir; a majority of cases occurring in patients who have underlying systemic or renal disease or who are concurrently taking nephrotoxic agents.
Efavirenz; Lamivudine; Tenofovir Disoproxil Fumarate: (Moderate) Tenofovir should be avoided with concurrent or recent use of a nephrotoxic agent, such as vancomycin. Patients receiving these drugs together should be carefully monitored for changes in serum creatinine and phosphorus. Renal impairment, which may include hypophosphatemia, has been reported with the use of tenofovir; a majority of cases occurring in patients who have underlying systemic or renal disease or who are concurrently taking nephrotoxic agents.
Elagolix; Estradiol; Norethindrone acetate: (Moderate) It would be prudent to recommend alternative or additional contraception when oral contraceptives (OCs) are used in conjunction with antibiotics. It was previously thought that antibiotics may decrease the effectiveness of OCs containing estrogens due to stimulation of metabolism or a reduction in enterohepatic circulation via changes in GI flora. One retrospective study reviewed the literature to determine the effects of oral antibiotics on the pharmacokinetics of contraceptive estrogens and progestins, and also examined clinical studies in which the incidence of pregnancy with OCs and antibiotics was reported. It was concluded that the antibiotics ampicillin, ciprofloxacin, clarithromycin, doxycycline, metronidazole, ofloxacin, roxithromycin, temafloxacin, and tetracycline did not alter plasma concentrations of OCs. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. Based on the study results, these authors recommended that back-up contraception may not be necessary if OCs are used reliably during oral antibiotic use. Another review concurred with these data, but noted that individual patients have been identified who experienced significant decreases in plasma concentrations of combined OC components and who appeared to ovulate; the agents most often associated with these changes were rifampin, tetracyclines, and penicillin derivatives. These authors concluded that because females most at risk for OC failure or noncompliance may not be easily identified and the true incidence of such events may be under-reported, and given the serious consequence of unwanted pregnancy, that recommending an additional method of contraception during short-term antibiotic use may be justified. During long-term antibiotic administration, the risk for drug interaction with OCs is less clear, but alternative or additional contraception may be advisable in selected circumstances. Data regarding progestin-only contraceptives or for newer combined contraceptive deliveries (e.g., patches, rings) are not available.
Elvitegravir; Cobicistat; Emtricitabine; Tenofovir Disoproxil Fumarate: (Moderate) Tenofovir should be avoided with concurrent or recent use of a nephrotoxic agent, such as vancomycin. Patients receiving these drugs together should be carefully monitored for changes in serum creatinine and phosphorus. Renal impairment, which may include hypophosphatemia, has been reported with the use of tenofovir; a majority of cases occurring in patients who have underlying systemic or renal disease or who are concurrently taking nephrotoxic agents.
Emtricitabine; Rilpivirine; Tenofovir Disoproxil Fumarate: (Moderate) Tenofovir should be avoided with concurrent or recent use of a nephrotoxic agent, such as vancomycin. Patients receiving these drugs together should be carefully monitored for changes in serum creatinine and phosphorus. Renal impairment, which may include hypophosphatemia, has been reported with the use of tenofovir; a majority of cases occurring in patients who have underlying systemic or renal disease or who are concurrently taking nephrotoxic agents.
Emtricitabine; Tenofovir Disoproxil Fumarate: (Moderate) Tenofovir should be avoided with concurrent or recent use of a nephrotoxic agent, such as vancomycin. Patients receiving these drugs together should be carefully monitored for changes in serum creatinine and phosphorus. Renal impairment, which may include hypophosphatemia, has been reported with the use of tenofovir; a majority of cases occurring in patients who have underlying systemic or renal disease or who are concurrently taking nephrotoxic agents.
Entecavir: (Moderate) Vancomycin and entecavir both undergo renal tubular secretion. Monitor patients closely for adverse events when these drugs are coadministered. Elevated serum concentrations of either drug may occur.
Estradiol; Levonorgestrel: (Moderate) It would be prudent to recommend alternative or additional contraception when oral contraceptives (OCs) are used in conjunction with antibiotics. It was previously thought that antibiotics may decrease the effectiveness of OCs containing estrogens due to stimulation of metabolism or a reduction in enterohepatic circulation via changes in GI flora. One retrospective study reviewed the literature to determine the effects of oral antibiotics on the pharmacokinetics of contraceptive estrogens and progestins, and also examined clinical studies in which the incidence of pregnancy with OCs and antibiotics was reported. It was concluded that the antibiotics ampicillin, ciprofloxacin, clarithromycin, doxycycline, metronidazole, ofloxacin, roxithromycin, temafloxacin, and tetracycline did not alter plasma concentrations of OCs. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. Based on the study results, these authors recommended that back-up contraception may not be necessary if OCs are used reliably during oral antibiotic use. Another review concurred with these data, but noted that individual patients have been identified who experienced significant decreases in plasma concentrations of combined OC components and who appeared to ovulate; the agents most often associated with these changes were rifampin, tetracyclines, and penicillin derivatives. These authors concluded that because females most at risk for OC failure or noncompliance may not be easily identified and the true incidence of such events may be under-reported, and given the serious consequence of unwanted pregnancy, that recommending an additional method of contraception during short-term antibiotic use may be justified. During long-term antibiotic administration, the risk for drug interaction with OCs is less clear, but alternative or additional contraception may be advisable in selected circumstances. Data regarding progestin-only contraceptives or for newer combined contraceptive deliveries (e.g., patches, rings) are not available.
Estradiol; Norethindrone: (Moderate) It would be prudent to recommend alternative or additional contraception when oral contraceptives (OCs) are used in conjunction with antibiotics. It was previously thought that antibiotics may decrease the effectiveness of OCs containing estrogens due to stimulation of metabolism or a reduction in enterohepatic circulation via changes in GI flora. One retrospective study reviewed the literature to determine the effects of oral antibiotics on the pharmacokinetics of contraceptive estrogens and progestins, and also examined clinical studies in which the incidence of pregnancy with OCs and antibiotics was reported. It was concluded that the antibiotics ampicillin, ciprofloxacin, clarithromycin, doxycycline, metronidazole, ofloxacin, roxithromycin, temafloxacin, and tetracycline did not alter plasma concentrations of OCs. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. Based on the study results, these authors recommended that back-up contraception may not be necessary if OCs are used reliably during oral antibiotic use. Another review concurred with these data, but noted that individual patients have been identified who experienced significant decreases in plasma concentrations of combined OC components and who appeared to ovulate; the agents most often associated with these changes were rifampin, tetracyclines, and penicillin derivatives. These authors concluded that because females most at risk for OC failure or noncompliance may not be easily identified and the true incidence of such events may be under-reported, and given the serious consequence of unwanted pregnancy, that recommending an additional method of contraception during short-term antibiotic use may be justified. During long-term antibiotic administration, the risk for drug interaction with OCs is less clear, but alternative or additional contraception may be advisable in selected circumstances. Data regarding progestin-only contraceptives or for newer combined contraceptive deliveries (e.g., patches, rings) are not available.
Estradiol; Norgestimate: (Moderate) It would be prudent to recommend alternative or additional contraception when oral contraceptives (OCs) are used in conjunction with antibiotics. It was previously thought that antibiotics may decrease the effectiveness of OCs containing estrogens due to stimulation of metabolism or a reduction in enterohepatic circulation via changes in GI flora. One retrospective study reviewed the literature to determine the effects of oral antibiotics on the pharmacokinetics of contraceptive estrogens and progestins, and also examined clinical studies in which the incidence of pregnancy with OCs and antibiotics was reported. It was concluded that the antibiotics ampicillin, ciprofloxacin, clarithromycin, doxycycline, metronidazole, ofloxacin, roxithromycin, temafloxacin, and tetracycline did not alter plasma concentrations of OCs. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. Based on the study results, these authors recommended that back-up contraception may not be necessary if OCs are used reliably during oral antibiotic use. Another review concurred with these data, but noted that individual patients have been identified who experienced significant decreases in plasma concentrations of combined OC components and who appeared to ovulate; the agents most often associated with these changes were rifampin, tetracyclines, and penicillin derivatives. These authors concluded that because females most at risk for OC failure or noncompliance may not be easily identified and the true incidence of such events may be under-reported, and given the serious consequence of unwanted pregnancy, that recommending an additional method of contraception during short-term antibiotic use may be justified. During long-term antibiotic administration, the risk for drug interaction with OCs is less clear, but alternative or additional contraception may be advisable in selected circumstances. Data regarding progestin-only contraceptives or for newer combined contraceptive deliveries (e.g., patches, rings) are not available.
Ethacrynic Acid: (Major) Vancomycin should be used cautiously with other ototoxic drugs such as ethacrynic acid.
Ethinyl Estradiol: (Moderate) It would be prudent to recommend alternative or additional contraception when oral contraceptives (OCs) are used in conjunction with antibiotics. It was previously thought that antibiotics may decrease the effectiveness of OCs containing estrogens due to stimulation of metabolism or a reduction in enterohepatic circulation via changes in GI flora. One retrospective study reviewed the literature to determine the effects of oral antibiotics on the pharmacokinetics of contraceptive estrogens and progestins, and also examined clinical studies in which the incidence of pregnancy with OCs and antibiotics was reported. It was concluded that the antibiotics ampicillin, ciprofloxacin, clarithromycin, doxycycline, metronidazole, ofloxacin, roxithromycin, temafloxacin, and tetracycline did not alter plasma concentrations of OCs. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. Based on the study results, these authors recommended that back-up contraception may not be necessary if OCs are used reliably during oral antibiotic use. Another review concurred with these data, but noted that individual patients have been identified who experienced significant decreases in plasma concentrations of combined OC components and who appeared to ovulate; the agents most often associated with these changes were rifampin, tetracyclines, and penicillin derivatives. These authors concluded that because females most at risk for OC failure or noncompliance may not be easily identified and the true incidence of such events may be under-reported, and given the serious consequence of unwanted pregnancy, that recommending an additional method of contraception during short-term antibiotic use may be justified. During long-term antibiotic administration, the risk for drug interaction with OCs is less clear, but alternative or additional contraception may be advisable in selected circumstances. Data regarding progestin-only contraceptives or for newer combined contraceptive deliveries (e.g., patches, rings) are not available.
Ethinyl Estradiol; Levonorgestrel; Folic Acid; Levomefolate: (Moderate) It would be prudent to recommend alternative or additional contraception when oral contraceptives (OCs) are used in conjunction with antibiotics. It was previously thought that antibiotics may decrease the effectiveness of OCs containing estrogens due to stimulation of metabolism or a reduction in enterohepatic circulation via changes in GI flora. One retrospective study reviewed the literature to determine the effects of oral antibiotics on the pharmacokinetics of contraceptive estrogens and progestins, and also examined clinical studies in which the incidence of pregnancy with OCs and antibiotics was reported. It was concluded that the antibiotics ampicillin, ciprofloxacin, clarithromycin, doxycycline, metronidazole, ofloxacin, roxithromycin, temafloxacin, and tetracycline did not alter plasma concentrations of OCs. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. Based on the study results, these authors recommended that back-up contraception may not be necessary if OCs are used reliably during oral antibiotic use. Another review concurred with these data, but noted that individual patients have been identified who experienced significant decreases in plasma concentrations of combined OC components and who appeared to ovulate; the agents most often associated with these changes were rifampin, tetracyclines, and penicillin derivatives. These authors concluded that because females most at risk for OC failure or noncompliance may not be easily identified and the true incidence of such events may be under-reported, and given the serious consequence of unwanted pregnancy, that recommending an additional method of contraception during short-term antibiotic use may be justified. During long-term antibiotic administration, the risk for drug interaction with OCs is less clear, but alternative or additional contraception may be advisable in selected circumstances. Data regarding progestin-only contraceptives or for newer combined contraceptive deliveries (e.g., patches, rings) are not available.
Ethinyl Estradiol; Norelgestromin: (Moderate) It would be prudent to recommend alternative or additional contraception when oral contraceptives (OCs) are used in conjunction with antibiotics. It was previously thought that antibiotics may decrease the effectiveness of OCs containing estrogens due to stimulation of metabolism or a reduction in enterohepatic circulation via changes in GI flora. One retrospective study reviewed the literature to determine the effects of oral antibiotics on the pharmacokinetics of contraceptive estrogens and progestins, and also examined clinical studies in which the incidence of pregnancy with OCs and antibiotics was reported. It was concluded that the antibiotics ampicillin, ciprofloxacin, clarithromycin, doxycycline, metronidazole, ofloxacin, roxithromycin, temafloxacin, and tetracycline did not alter plasma concentrations of OCs. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. Based on the study results, these authors recommended that back-up contraception may not be necessary if OCs are used reliably during oral antibiotic use. Another review concurred with these data, but noted that individual patients have been identified who experienced significant decreases in plasma concentrations of combined OC components and who appeared to ovulate; the agents most often associated with these changes were rifampin, tetracyclines, and penicillin derivatives. These authors concluded that because females most at risk for OC failure or noncompliance may not be easily identified and the true incidence of such events may be under-reported, and given the serious consequence of unwanted pregnancy, that recommending an additional method of contraception during short-term antibiotic use may be justified. During long-term antibiotic administration, the risk for drug interaction with OCs is less clear, but alternative or additional contraception may be advisable in selected circumstances. Data regarding progestin-only contraceptives or for newer combined contraceptive deliveries (e.g., patches, rings) are not available.
Ethinyl Estradiol; Norethindrone Acetate: (Moderate) It would be prudent to recommend alternative or additional contraception when oral contraceptives (OCs) are used in conjunction with antibiotics. It was previously thought that antibiotics may decrease the effectiveness of OCs containing estrogens due to stimulation of metabolism or a reduction in enterohepatic circulation via changes in GI flora. One retrospective study reviewed the literature to determine the effects of oral antibiotics on the pharmacokinetics of contraceptive estrogens and progestins, and also examined clinical studies in which the incidence of pregnancy with OCs and antibiotics was reported. It was concluded that the antibiotics ampicillin, ciprofloxacin, clarithromycin, doxycycline, metronidazole, ofloxacin, roxithromycin, temafloxacin, and tetracycline did not alter plasma concentrations of OCs. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. Based on the study results, these authors recommended that back-up contraception may not be necessary if OCs are used reliably during oral antibiotic use. Another review concurred with these data, but noted that individual patients have been identified who experienced significant decreases in plasma concentrations of combined OC components and who appeared to ovulate; the agents most often associated with these changes were rifampin, tetracyclines, and penicillin derivatives. These authors concluded that because females most at risk for OC failure or noncompliance may not be easily identified and the true incidence of such events may be under-reported, and given the serious consequence of unwanted pregnancy, that recommending an additional method of contraception during short-term antibiotic use may be justified. During long-term antibiotic administration, the risk for drug interaction with OCs is less clear, but alternative or additional contraception may be advisable in selected circumstances. Data regarding progestin-only contraceptives or for newer combined contraceptive deliveries (e.g., patches, rings) are not available.
Ethinyl Estradiol; Norgestrel: (Moderate) It would be prudent to recommend alternative or additional contraception when oral contraceptives (OCs) are used in conjunction with antibiotics. It was previously thought that antibiotics may decrease the effectiveness of OCs containing estrogens due to stimulation of metabolism or a reduction in enterohepatic circulation via changes in GI flora. One retrospective study reviewed the literature to determine the effects of oral antibiotics on the pharmacokinetics of contraceptive estrogens and progestins, and also examined clinical studies in which the incidence of pregnancy with OCs and antibiotics was reported. It was concluded that the antibiotics ampicillin, ciprofloxacin, clarithromycin, doxycycline, metronidazole, ofloxacin, roxithromycin, temafloxacin, and tetracycline did not alter plasma concentrations of OCs. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. Based on the study results, these authors recommended that back-up contraception may not be necessary if OCs are used reliably during oral antibiotic use. Another review concurred with these data, but noted that individual patients have been identified who experienced significant decreases in plasma concentrations of combined OC components and who appeared to ovulate; the agents most often associated with these changes were rifampin, tetracyclines, and penicillin derivatives. These authors concluded that because females most at risk for OC failure or noncompliance may not be easily identified and the true incidence of such events may be under-reported, and given the serious consequence of unwanted pregnancy, that recommending an additional method of contraception during short-term antibiotic use may be justified. During long-term antibiotic administration, the risk for drug interaction with OCs is less clear, but alternative or additional contraception may be advisable in selected circumstances. Data regarding progestin-only contraceptives or for newer combined contraceptive deliveries (e.g., patches, rings) are not available.
Ethynodiol Diacetate; Ethinyl Estradiol: (Moderate) It would be prudent to recommend alternative or additional contraception when oral contraceptives (OCs) are used in conjunction with antibiotics. It was previously thought that antibiotics may decrease the effectiveness of OCs containing estrogens due to stimulation of metabolism or a reduction in enterohepatic circulation via changes in GI flora. One retrospective study reviewed the literature to determine the effects of oral antibiotics on the pharmacokinetics of contraceptive estrogens and progestins, and also examined clinical studies in which the incidence of pregnancy with OCs and antibiotics was reported. It was concluded that the antibiotics ampicillin, ciprofloxacin, clarithromycin, doxycycline, metronidazole, ofloxacin, roxithromycin, temafloxacin, and tetracycline did not alter plasma concentrations of OCs. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. Based on the study results, these authors recommended that back-up contraception may not be necessary if OCs are used reliably during oral antibiotic use. Another review concurred with these data, but noted that individual patients have been identified who experienced significant decreases in plasma concentrations of combined OC components and who appeared to ovulate; the agents most often associated with these changes were rifampin, tetracyclines, and penicillin derivatives. These authors concluded that because females most at risk for OC failure or noncompliance may not be easily identified and the true incidence of such events may be under-reported, and given the serious consequence of unwanted pregnancy, that recommending an additional method of contraception during short-term antibiotic use may be justified. During long-term antibiotic administration, the risk for drug interaction with OCs is less clear, but alternative or additional contraception may be advisable in selected circumstances. Data regarding progestin-only contraceptives or for newer combined contraceptive deliveries (e.g., patches, rings) are not available.
Etodolac: (Minor) It is possible that additive nephrotoxicity may occur in patients who receive NSAIDs concurrently with other nephrotoxic agents, including vancomycin.
Etonogestrel; Ethinyl Estradiol: (Moderate) It would be prudent to recommend alternative or additional contraception when oral contraceptives (OCs) are used in conjunction with antibiotics. It was previously thought that antibiotics may decrease the effectiveness of OCs containing estrogens due to stimulation of metabolism or a reduction in enterohepatic circulation via changes in GI flora. One retrospective study reviewed the literature to determine the effects of oral antibiotics on the pharmacokinetics of contraceptive estrogens and progestins, and also examined clinical studies in which the incidence of pregnancy with OCs and antibiotics was reported. It was concluded that the antibiotics ampicillin, ciprofloxacin, clarithromycin, doxycycline, metronidazole, ofloxacin, roxithromycin, temafloxacin, and tetracycline did not alter plasma concentrations of OCs. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. Based on the study results, these authors recommended that back-up contraception may not be necessary if OCs are used reliably during oral antibiotic use. Another review concurred with these data, but noted that individual patients have been identified who experienced significant decreases in plasma concentrations of combined OC components and who appeared to ovulate; the agents most often associated with these changes were rifampin, tetracyclines, and penicillin derivatives. These authors concluded that because females most at risk for OC failure or noncompliance may not be easily identified and the true incidence of such events may be under-reported, and given the serious consequence of unwanted pregnancy, that recommending an additional method of contraception during short-term antibiotic use may be justified. During long-term antibiotic administration, the risk for drug interaction with OCs is less clear, but alternative or additional contraception may be advisable in selected circumstances. Data regarding progestin-only contraceptives or for newer combined contraceptive deliveries (e.g., patches, rings) are not available.
Fenoprofen: (Minor) It is possible that additive nephrotoxicity may occur in patients who receive NSAIDs concurrently with other nephrotoxic agents, including vancomycin.
Fentanyl: (Moderate) The concurrent administration of vancomycin and anesthetics has been associated with erythema, histamine-like flushing, and anaphylactoid reactions. Infusion-related events may be minimized by the administration of vancomycin as a 60-minute infusion prior to anesthetic induction.
Flurbiprofen: (Minor) It is possible that additive nephrotoxicity may occur in patients who receive NSAIDs concurrently with other nephrotoxic agents, including vancomycin.
Foscarnet: (Major) The risk of renal toxicity may be increased if foscarnet is used in conjunction with other nephrotoxic agents such as parenteral vancomycin. Nephrotoxicity is also possible in patients receiving oral vancomycin for pseudomembranous colitis, should systemic absorption occur through significantly altered GI mucosa. Renal function should be monitored closely and vancomycin doses should be adjusted according to vancomycin serum concentrations.
Furosemide: (Moderate) Vancomycin should be used cautiously with other ototoxic drugs such as furosemide.
Ganciclovir: (Moderate) Concurrent use of nephrotoxic agents, such as vancomycin, with ganciclovir should be done cautiously to avoid additive nephrotoxicity. Renal function should be monitored closely and vancomycin doses should be adjusted according to vancomycin serum concentrations.
General anesthetics: (Moderate) The concurrent administration of vancomycin and anesthetics has been associated with erythema, histamine-like flushing, and anaphylactoid reactions.
Gentamicin: (Major) Concomitant use of parenteral vancomycin with other nephrotoxic drugs, such as aminoglycosides, can lead to additive nephrotoxicity. Both vancomycin and aminoglycosides may cause ototoxicity as well. In a clinical study, vancomycin coadministration, high aminoglycoside trough concentrations, and heart failure independently predicted acute kidney injury during aminoglycoside treatment. Renal function should be monitored closely, and vancomycin and aminoglycoside doses should be adjusted according to serum concentrations as clinically indicated.
Gold: (Minor) Both vancomycin and gold compounds can cause nephrotoxicity. Auranofin has been reported to cause a nephrotic syndrome or glomerulonephritis with proteinuria and hematuria. Monitor renal function carefully during concurrent therapy.
Hyaluronidase, Recombinant; Immune Globulin: (Moderate) Immune Globulin (IG) products have been reported to be associated with renal dysfunction, acute renal failure, osmotic nephrosis, and death. Patients predisposed to acute renal failure include patients receiving known nephrotoxic drugs like vancomycin. Coadminister IG products at the minimum concentration available and the minimum rate of infusion practicable. Also, closely monitor renal function.
Hydrocodone; Ibuprofen: (Minor) It is possible that additive nephrotoxicity may occur in patients who receive NSAIDs concurrently with other nephrotoxic agents, including vancomycin.
Ibandronate: (Moderate) Theoretically, coadministration of intravenous ibandronate with other potentially nephrotoxic drugs like vancomycin may increase the risk of developing nephrotoxicity.
Ibuprofen: (Minor) It is possible that additive nephrotoxicity may occur in patients who receive NSAIDs concurrently with other nephrotoxic agents, including vancomycin.
Ibuprofen; Famotidine: (Minor) It is possible that additive nephrotoxicity may occur in patients who receive NSAIDs concurrently with other nephrotoxic agents, including vancomycin.
Ibuprofen; Oxycodone: (Minor) It is possible that additive nephrotoxicity may occur in patients who receive NSAIDs concurrently with other nephrotoxic agents, including vancomycin.
Ibuprofen; Pseudoephedrine: (Minor) It is possible that additive nephrotoxicity may occur in patients who receive NSAIDs concurrently with other nephrotoxic agents, including vancomycin.
Immune Globulin IV, IVIG, IGIV: (Moderate) Immune Globulin (IG) products have been reported to be associated with renal dysfunction, acute renal failure, osmotic nephrosis, and death. Patients predisposed to acute renal failure include patients receiving known nephrotoxic drugs like vancomycin. Coadminister IG products at the minimum concentration available and the minimum rate of infusion practicable. Also, closely monitor renal function.
Indomethacin: (Minor) It is possible that additive nephrotoxicity may occur in patients who receive NSAIDs concurrently with other nephrotoxic agents, including vancomycin.
Inotersen: (Moderate) Use caution with concomitant use of inotersen and vancomycin due to the risk of glomerulonephritis and nephrotoxicity.
Ketoprofen: (Minor) It is possible that additive nephrotoxicity may occur in patients who receive NSAIDs concurrently with other nephrotoxic agents, including vancomycin.
Ketorolac: (Minor) It is possible that additive nephrotoxicity may occur in patients who receive NSAIDs concurrently with other nephrotoxic agents, including vancomycin.
Lamivudine; Tenofovir Disoproxil Fumarate: (Moderate) Tenofovir should be avoided with concurrent or recent use of a nephrotoxic agent, such as vancomycin. Patients receiving these drugs together should be carefully monitored for changes in serum creatinine and phosphorus. Renal impairment, which may include hypophosphatemia, has been reported with the use of tenofovir; a majority of cases occurring in patients who have underlying systemic or renal disease or who are concurrently taking nephrotoxic agents.
Lansoprazole; Naproxen: (Minor) It is possible that additive nephrotoxicity may occur in patients who receive NSAIDs concurrently with other nephrotoxic agents, including vancomycin.
Leuprolide; Norethindrone: (Moderate) It would be prudent to recommend alternative or additional contraception when oral contraceptives (OCs) are used in conjunction with antibiotics. It was previously thought that antibiotics may decrease the effectiveness of OCs containing estrogens due to stimulation of metabolism or a reduction in enterohepatic circulation via changes in GI flora. One retrospective study reviewed the literature to determine the effects of oral antibiotics on the pharmacokinetics of contraceptive estrogens and progestins, and also examined clinical studies in which the incidence of pregnancy with OCs and antibiotics was reported. It was concluded that the antibiotics ampicillin, ciprofloxacin, clarithromycin, doxycycline, metronidazole, ofloxacin, roxithromycin, temafloxacin, and tetracycline did not alter plasma concentrations of OCs. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. Based on the study results, these authors recommended that back-up contraception may not be necessary if OCs are used reliably during oral antibiotic use. Another review concurred with these data, but noted that individual patients have been identified who experienced significant decreases in plasma concentrations of combined OC components and who appeared to ovulate; the agents most often associated with these changes were rifampin, tetracyclines, and penicillin derivatives. These authors concluded that because females most at risk for OC failure or noncompliance may not be easily identified and the true incidence of such events may be under-reported, and given the serious consequence of unwanted pregnancy, that recommending an additional method of contraception during short-term antibiotic use may be justified. During long-term antibiotic administration, the risk for drug interaction with OCs is less clear, but alternative or additional contraception may be advisable in selected circumstances. Data regarding progestin-only contraceptives or for newer combined contraceptive deliveries (e.g., patches, rings) are not available.
Levonorgestrel: (Moderate) It would be prudent to recommend alternative or additional contraception when oral contraceptives (OCs) are used in conjunction with antibiotics. It was previously thought that antibiotics may decrease the effectiveness of OCs containing estrogens due to stimulation of metabolism or a reduction in enterohepatic circulation via changes in GI flora. One retrospective study reviewed the literature to determine the effects of oral antibiotics on the pharmacokinetics of contraceptive estrogens and progestins, and also examined clinical studies in which the incidence of pregnancy with OCs and antibiotics was reported. It was concluded that the antibiotics ampicillin, ciprofloxacin, clarithromycin, doxycycline, metronidazole, ofloxacin, roxithromycin, temafloxacin, and tetracycline did not alter plasma concentrations of OCs. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. Based on the study results, these authors recommended that back-up contraception may not be necessary if OCs are used reliably during oral antibiotic use. Another review concurred with these data, but noted that individual patients have been identified who experienced significant decreases in plasma concentrations of combined OC components and who appeared to ovulate; the agents most often associated with these changes were rifampin, tetracyclines, and penicillin derivatives. These authors concluded that because females most at risk for OC failure or noncompliance may not be easily identified and the true incidence of such events may be under-reported, and given the serious consequence of unwanted pregnancy, that recommending an additional method of contraception during short-term antibiotic use may be justified. During long-term antibiotic administration, the risk for drug interaction with OCs is less clear, but alternative or additional contraception may be advisable in selected circumstances. Data regarding progestin-only contraceptives or for newer combined contraceptive deliveries (e.g., patches, rings) are not available.
Levonorgestrel; Ethinyl Estradiol: (Moderate) It would be prudent to recommend alternative or additional contraception when oral contraceptives (OCs) are used in conjunction with antibiotics. It was previously thought that antibiotics may decrease the effectiveness of OCs containing estrogens due to stimulation of metabolism or a reduction in enterohepatic circulation via changes in GI flora. One retrospective study reviewed the literature to determine the effects of oral antibiotics on the pharmacokinetics of contraceptive estrogens and progestins, and also examined clinical studies in which the incidence of pregnancy with OCs and antibiotics was reported. It was concluded that the antibiotics ampicillin, ciprofloxacin, clarithromycin, doxycycline, metronidazole, ofloxacin, roxithromycin, temafloxacin, and tetracycline did not alter plasma concentrations of OCs. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. Based on the study results, these authors recommended that back-up contraception may not be necessary if OCs are used reliably during oral antibiotic use. Another review concurred with these data, but noted that individual patients have been identified who experienced significant decreases in plasma concentrations of combined OC components and who appeared to ovulate; the agents most often associated with these changes were rifampin, tetracyclines, and penicillin derivatives. These authors concluded that because females most at risk for OC failure or noncompliance may not be easily identified and the true incidence of such events may be under-reported, and given the serious consequence of unwanted pregnancy, that recommending an additional method of contraception during short-term antibiotic use may be justified. During long-term antibiotic administration, the risk for drug interaction with OCs is less clear, but alternative or additional contraception may be advisable in selected circumstances. Data regarding progestin-only contraceptives or for newer combined contraceptive deliveries (e.g., patches, rings) are not available.
Levonorgestrel; Ethinyl Estradiol; Ferrous Bisglycinate: (Moderate) It would be prudent to recommend alternative or additional contraception when oral contraceptives (OCs) are used in conjunction with antibiotics. It was previously thought that antibiotics may decrease the effectiveness of OCs containing estrogens due to stimulation of metabolism or a reduction in enterohepatic circulation via changes in GI flora. One retrospective study reviewed the literature to determine the effects of oral antibiotics on the pharmacokinetics of contraceptive estrogens and progestins, and also examined clinical studies in which the incidence of pregnancy with OCs and antibiotics was reported. It was concluded that the antibiotics ampicillin, ciprofloxacin, clarithromycin, doxycycline, metronidazole, ofloxacin, roxithromycin, temafloxacin, and tetracycline did not alter plasma concentrations of OCs. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. Based on the study results, these authors recommended that back-up contraception may not be necessary if OCs are used reliably during oral antibiotic use. Another review concurred with these data, but noted that individual patients have been identified who experienced significant decreases in plasma concentrations of combined OC components and who appeared to ovulate; the agents most often associated with these changes were rifampin, tetracyclines, and penicillin derivatives. These authors concluded that because females most at risk for OC failure or noncompliance may not be easily identified and the true incidence of such events may be under-reported, and given the serious consequence of unwanted pregnancy, that recommending an additional method of contraception during short-term antibiotic use may be justified. During long-term antibiotic administration, the risk for drug interaction with OCs is less clear, but alternative or additional contraception may be advisable in selected circumstances. Data regarding progestin-only contraceptives or for newer combined contraceptive deliveries (e.g., patches, rings) are not available.
Lithium: (Moderate) Moderate to significant dietary sodium changes, or changes in sodium and fluid intake, may affect lithium excretion. Systemic sodium chloride administration may result in increased lithium excretion and therefore, decreased serum lithium concentrations. In addition, high fluid intake may increase lithium excretion. For patients receiving sodium-containing intravenous fluids, symptom control and lithium concentrations should be carefully monitored. It is recommended that patients taking lithium maintain consistent dietary sodium consumption and adequate fluid intake during the initial stabilization period and throughout lithium treatment. Supplemental oral sodium and fluid should be only be administered under careful medical supervision.
Lorazepam: (Moderate) The concurrent administration of vancomycin and anesthetics has been associated with erythema, histamine-like flushing, and anaphylactoid reactions.
Mannitol: (Major) Avoid use of mannitol and vancomycin, if possible. Concomitant administration of nephrotoxic drugs, such as vancomycin, increases the risk of renal failure after administration of mannitol.
Meclofenamate Sodium: (Minor) It is possible that additive nephrotoxicity may occur in patients who receive NSAIDs concurrently with other nephrotoxic agents, including vancomycin.
Mefenamic Acid: (Minor) It is possible that additive nephrotoxicity may occur in patients who receive NSAIDs concurrently with other nephrotoxic agents, including vancomycin.
Meloxicam: (Minor) It is possible that additive nephrotoxicity may occur in patients who receive NSAIDs concurrently with other nephrotoxic agents, including vancomycin.
Memantine: (Moderate) Cationic drugs that are eliminated by renal tubular secretion, such as vancomycin, may compete with memantine for common renal tubular transport systems, thus possibly decreasing the elimination of one of the drugs. Although theoretical, careful patient monitoring of response to memantine and/or vancomycin is recommended to assess for needed dosage adjustments. In selected individuals, vancomycin serum concentration monitoring may be appropriate.
Mestranol; Norethindrone: (Moderate) It would be prudent to recommend alternative or additional contraception when oral contraceptives (OCs) are used in conjunction with antibiotics. It was previously thought that antibiotics may decrease the effectiveness of OCs containing estrogens due to stimulation of metabolism or a reduction in enterohepatic circulation via changes in GI flora. One retrospective study reviewed the literature to determine the effects of oral antibiotics on the pharmacokinetics of contraceptive estrogens and progestins, and also examined clinical studies in which the incidence of pregnancy with OCs and antibiotics was reported. It was concluded that the antibiotics ampicillin, ciprofloxacin, clarithromycin, doxycycline, metronidazole, ofloxacin, roxithromycin, temafloxacin, and tetracycline did not alter plasma concentrations of OCs. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. Based on the study results, these authors recommended that back-up contraception may not be necessary if OCs are used reliably during oral antibiotic use. Another review concurred with these data, but noted that individual patients have been identified who experienced significant decreases in plasma concentrations of combined OC components and who appeared to ovulate; the agents most often associated with these changes were rifampin, tetracyclines, and penicillin derivatives. These authors concluded that because females most at risk for OC failure or noncompliance may not be easily identified and the true incidence of such events may be under-reported, and given the serious consequence of unwanted pregnancy, that recommending an additional method of contraception during short-term antibiotic use may be justified. During long-term antibiotic administration, the risk for drug interaction with OCs is less clear, but alternative or additional contraception may be advisable in selected circumstances. Data regarding progestin-only contraceptives or for newer combined contraceptive deliveries (e.g., patches, rings) are not available.
Methohexital: (Moderate) The concurrent administration of vancomycin and anesthetics has been associated with erythema, histamine-like flushing, and anaphylactoid reactions.
Methotrexate: (Major) Avoid concomitant use of methotrexate with vancomycin due to the risk of additive nephrotoxicity as well as an increased risk of severe methotrexate-related adverse reactions. Recent exposure to vancomycin, in the absence of overt renal impairment, may also adversely affect methotrexate excretion and increase risk of toxicity. If concomitant use is unavoidable, closely monitor for adverse reactions. Vancomycin and methotrexate are both nephrotoxic drugs; methotrexate is also renally eliminated. Coadministration of methotrexate with vancomycin may result in decreased renal function as well as increased methotrexate plasma concentrations. In a case report, two patients who had received a methotrexate-containing chemotherapy regimen initially displayed appropriate methotrexate clearance. However, administration of vancomycin in between chemotherapy treatment cycles appears to have caused markedly prolonged methotrexate clearance (i.e., 170 to 231 hours to reach serum methotrexate concentrations of less than 0.2 micro-M). Subclinical renal impairment was documented in both cases following vancomycin administration, which eventually resolved; subsequent methotrexate cycles, of the same dose, showed appropriate clearance.
Mivacurium: (Moderate) Concomitant use of neuromuscular blockers and vancomycin may prolong neuromuscular blockade. The use of a peripheral nerve stimulator is strongly recommended to evaluate the level of neuromuscular blockade, to assess the need for additional doses of neuromuscular blocker, and to determine whether adjustments need to be made to the dose with subsequent administration.
Nabumetone: (Minor) It is possible that additive nephrotoxicity may occur in patients who receive NSAIDs concurrently with other nephrotoxic agents, including vancomycin.
Naproxen: (Minor) It is possible that additive nephrotoxicity may occur in patients who receive NSAIDs concurrently with other nephrotoxic agents, including vancomycin.
Naproxen; Esomeprazole: (Minor) It is possible that additive nephrotoxicity may occur in patients who receive NSAIDs concurrently with other nephrotoxic agents, including vancomycin.
Naproxen; Pseudoephedrine: (Minor) It is possible that additive nephrotoxicity may occur in patients who receive NSAIDs concurrently with other nephrotoxic agents, including vancomycin.
Neuromuscular blockers: (Moderate) Concomitant use of neuromuscular blockers and vancomycin may prolong neuromuscular blockade. The use of a peripheral nerve stimulator is strongly recommended to evaluate the level of neuromuscular blockade, to assess the need for additional doses of neuromuscular blocker, and to determine whether adjustments need to be made to the dose with subsequent administration.
Nonsteroidal antiinflammatory drugs: (Minor) It is possible that additive nephrotoxicity may occur in patients who receive NSAIDs concurrently with other nephrotoxic agents, including vancomycin.
Norethindrone Acetate; Ethinyl Estradiol; Ferrous fumarate: (Moderate) It would be prudent to recommend alternative or additional contraception when oral contraceptives (OCs) are used in conjunction with antibiotics. It was previously thought that antibiotics may decrease the effectiveness of OCs containing estrogens due to stimulation of metabolism or a reduction in enterohepatic circulation via changes in GI flora. One retrospective study reviewed the literature to determine the effects of oral antibiotics on the pharmacokinetics of contraceptive estrogens and progestins, and also examined clinical studies in which the incidence of pregnancy with OCs and antibiotics was reported. It was concluded that the antibiotics ampicillin, ciprofloxacin, clarithromycin, doxycycline, metronidazole, ofloxacin, roxithromycin, temafloxacin, and tetracycline did not alter plasma concentrations of OCs. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. Based on the study results, these authors recommended that back-up contraception may not be necessary if OCs are used reliably during oral antibiotic use. Another review concurred with these data, but noted that individual patients have been identified who experienced significant decreases in plasma concentrations of combined OC components and who appeared to ovulate; the agents most often associated with these changes were rifampin, tetracyclines, and penicillin derivatives. These authors concluded that because females most at risk for OC failure or noncompliance may not be easily identified and the true incidence of such events may be under-reported, and given the serious consequence of unwanted pregnancy, that recommending an additional method of contraception during short-term antibiotic use may be justified. During long-term antibiotic administration, the risk for drug interaction with OCs is less clear, but alternative or additional contraception may be advisable in selected circumstances. Data regarding progestin-only contraceptives or for newer combined contraceptive deliveries (e.g., patches, rings) are not available.
Norethindrone: (Moderate) It would be prudent to recommend alternative or additional contraception when oral contraceptives (OCs) are used in conjunction with antibiotics. It was previously thought that antibiotics may decrease the effectiveness of OCs containing estrogens due to stimulation of metabolism or a reduction in enterohepatic circulation via changes in GI flora. One retrospective study reviewed the literature to determine the effects of oral antibiotics on the pharmacokinetics of contraceptive estrogens and progestins, and also examined clinical studies in which the incidence of pregnancy with OCs and antibiotics was reported. It was concluded that the antibiotics ampicillin, ciprofloxacin, clarithromycin, doxycycline, metronidazole, ofloxacin, roxithromycin, temafloxacin, and tetracycline did not alter plasma concentrations of OCs. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. Based on the study results, these authors recommended that back-up contraception may not be necessary if OCs are used reliably during oral antibiotic use. Another review concurred with these data, but noted that individual patients have been identified who experienced significant decreases in plasma concentrations of combined OC components and who appeared to ovulate; the agents most often associated with these changes were rifampin, tetracyclines, and penicillin derivatives. These authors concluded that because females most at risk for OC failure or noncompliance may not be easily identified and the true incidence of such events may be under-reported, and given the serious consequence of unwanted pregnancy, that recommending an additional method of contraception during short-term antibiotic use may be justified. During long-term antibiotic administration, the risk for drug interaction with OCs is less clear, but alternative or additional contraception may be advisable in selected circumstances. Data regarding progestin-only contraceptives or for newer combined contraceptive deliveries (e.g., patches, rings) are not available.
Norethindrone; Ethinyl Estradiol: (Moderate) It would be prudent to recommend alternative or additional contraception when oral contraceptives (OCs) are used in conjunction with antibiotics. It was previously thought that antibiotics may decrease the effectiveness of OCs containing estrogens due to stimulation of metabolism or a reduction in enterohepatic circulation via changes in GI flora. One retrospective study reviewed the literature to determine the effects of oral antibiotics on the pharmacokinetics of contraceptive estrogens and progestins, and also examined clinical studies in which the incidence of pregnancy with OCs and antibiotics was reported. It was concluded that the antibiotics ampicillin, ciprofloxacin, clarithromycin, doxycycline, metronidazole, ofloxacin, roxithromycin, temafloxacin, and tetracycline did not alter plasma concentrations of OCs. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. Based on the study results, these authors recommended that back-up contraception may not be necessary if OCs are used reliably during oral antibiotic use. Another review concurred with these data, but noted that individual patients have been identified who experienced significant decreases in plasma concentrations of combined OC components and who appeared to ovulate; the agents most often associated with these changes were rifampin, tetracyclines, and penicillin derivatives. These authors concluded that because females most at risk for OC failure or noncompliance may not be easily identified and the true incidence of such events may be under-reported, and given the serious consequence of unwanted pregnancy, that recommending an additional method of contraception during short-term antibiotic use may be justified. During long-term antibiotic administration, the risk for drug interaction with OCs is less clear, but alternative or additional contraception may be advisable in selected circumstances. Data regarding progestin-only contraceptives or for newer combined contraceptive deliveries (e.g., patches, rings) are not available.
Norethindrone; Ethinyl Estradiol; Ferrous fumarate: (Moderate) It would be prudent to recommend alternative or additional contraception when oral contraceptives (OCs) are used in conjunction with antibiotics. It was previously thought that antibiotics may decrease the effectiveness of OCs containing estrogens due to stimulation of metabolism or a reduction in enterohepatic circulation via changes in GI flora. One retrospective study reviewed the literature to determine the effects of oral antibiotics on the pharmacokinetics of contraceptive estrogens and progestins, and also examined clinical studies in which the incidence of pregnancy with OCs and antibiotics was reported. It was concluded that the antibiotics ampicillin, ciprofloxacin, clarithromycin, doxycycline, metronidazole, ofloxacin, roxithromycin, temafloxacin, and tetracycline did not alter plasma concentrations of OCs. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. Based on the study results, these authors recommended that back-up contraception may not be necessary if OCs are used reliably during oral antibiotic use. Another review concurred with these data, but noted that individual patients have been identified who experienced significant decreases in plasma concentrations of combined OC components and who appeared to ovulate; the agents most often associated with these changes were rifampin, tetracyclines, and penicillin derivatives. These authors concluded that because females most at risk for OC failure or noncompliance may not be easily identified and the true incidence of such events may be under-reported, and given the serious consequence of unwanted pregnancy, that recommending an additional method of contraception during short-term antibiotic use may be justified. During long-term antibiotic administration, the risk for drug interaction with OCs is less clear, but alternative or additional contraception may be advisable in selected circumstances. Data regarding progestin-only contraceptives or for newer combined contraceptive deliveries (e.g., patches, rings) are not available.
Norgestimate; Ethinyl Estradiol: (Moderate) It would be prudent to recommend alternative or additional contraception when oral contraceptives (OCs) are used in conjunction with antibiotics. It was previously thought that antibiotics may decrease the effectiveness of OCs containing estrogens due to stimulation of metabolism or a reduction in enterohepatic circulation via changes in GI flora. One retrospective study reviewed the literature to determine the effects of oral antibiotics on the pharmacokinetics of contraceptive estrogens and progestins, and also examined clinical studies in which the incidence of pregnancy with OCs and antibiotics was reported. It was concluded that the antibiotics ampicillin, ciprofloxacin, clarithromycin, doxycycline, metronidazole, ofloxacin, roxithromycin, temafloxacin, and tetracycline did not alter plasma concentrations of OCs. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. Based on the study results, these authors recommended that back-up contraception may not be necessary if OCs are used reliably during oral antibiotic use. Another review concurred with these data, but noted that individual patients have been identified who experienced significant decreases in plasma concentrations of combined OC components and who appeared to ovulate; the agents most often associated with these changes were rifampin, tetracyclines, and penicillin derivatives. These authors concluded that because females most at risk for OC failure or noncompliance may not be easily identified and the true incidence of such events may be under-reported, and given the serious consequence of unwanted pregnancy, that recommending an additional method of contraception during short-term antibiotic use may be justified. During long-term antibiotic administration, the risk for drug interaction with OCs is less clear, but alternative or additional contraception may be advisable in selected circumstances. Data regarding progestin-only contraceptives or for newer combined contraceptive deliveries (e.g., patches, rings) are not available.
Norgestrel: (Moderate) It would be prudent to recommend alternative or additional contraception when oral contraceptives (OCs) are used in conjunction with antibiotics. It was previously thought that antibiotics may decrease the effectiveness of OCs containing estrogens due to stimulation of metabolism or a reduction in enterohepatic circulation via changes in GI flora. One retrospective study reviewed the literature to determine the effects of oral antibiotics on the pharmacokinetics of contraceptive estrogens and progestins, and also examined clinical studies in which the incidence of pregnancy with OCs and antibiotics was reported. It was concluded that the antibiotics ampicillin, ciprofloxacin, clarithromycin, doxycycline, metronidazole, ofloxacin, roxithromycin, temafloxacin, and tetracycline did not alter plasma concentrations of OCs. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. Based on the study results, these authors recommended that back-up contraception may not be necessary if OCs are used reliably during oral antibiotic use. Another review concurred with these data, but noted that individual patients have been identified who experienced significant decreases in plasma concentrations of combined OC components and who appeared to ovulate; the agents most often associated with these changes were rifampin, tetracyclines, and penicillin derivatives. These authors concluded that because females most at risk for OC failure or noncompliance may not be easily identified and the true incidence of such events may be under-reported, and given the serious consequence of unwanted pregnancy, that recommending an additional method of contraception during short-term antibiotic use may be justified. During long-term antibiotic administration, the risk for drug interaction with OCs is less clear, but alternative or additional contraception may be advisable in selected circumstances. Data regarding progestin-only contraceptives or for newer combined contraceptive deliveries (e.g., patches, rings) are not available.
Oral Contraceptives: (Moderate) It would be prudent to recommend alternative or additional contraception when oral contraceptives (OCs) are used in conjunction with antibiotics. It was previously thought that antibiotics may decrease the effectiveness of OCs containing estrogens due to stimulation of metabolism or a reduction in enterohepatic circulation via changes in GI flora. One retrospective study reviewed the literature to determine the effects of oral antibiotics on the pharmacokinetics of contraceptive estrogens and progestins, and also examined clinical studies in which the incidence of pregnancy with OCs and antibiotics was reported. It was concluded that the antibiotics ampicillin, ciprofloxacin, clarithromycin, doxycycline, metronidazole, ofloxacin, roxithromycin, temafloxacin, and tetracycline did not alter plasma concentrations of OCs. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. Based on the study results, these authors recommended that back-up contraception may not be necessary if OCs are used reliably during oral antibiotic use. Another review concurred with these data, but noted that individual patients have been identified who experienced significant decreases in plasma concentrations of combined OC components and who appeared to ovulate; the agents most often associated with these changes were rifampin, tetracyclines, and penicillin derivatives. These authors concluded that because females most at risk for OC failure or noncompliance may not be easily identified and the true incidence of such events may be under-reported, and given the serious consequence of unwanted pregnancy, that recommending an additional method of contraception during short-term antibiotic use may be justified. During long-term antibiotic administration, the risk for drug interaction with OCs is less clear, but alternative or additional contraception may be advisable in selected circumstances. Data regarding progestin-only contraceptives or for newer combined contraceptive deliveries (e.g., patches, rings) are not available.
Oxaliplatin: (Major) Avoid coadministration of oxaliplatin with vancomycin due to the risk of increased oxaliplatin-related adverse reactions. Vancomycin is known to be potentially nephrotoxic; because platinum-containing drugs like oxaliplatin are eliminated primarily through the kidney, oxaliplatin clearance may be decreased by coadministration with nephrotoxic agents.
Oxaprozin: (Minor) It is possible that additive nephrotoxicity may occur in patients who receive NSAIDs concurrently with other nephrotoxic agents, including vancomycin.
Pamidronate: (Moderate) Coadministration of pamidronate with other nephrotoxic drugs, like vancomycin, may increase the risk of developing nephrotoxicity following pamidronate administration, even in patients who have normal renal function.
Pancuronium: (Moderate) Concomitant use of neuromuscular blockers and vancomycin may prolong neuromuscular blockade. The use of a peripheral nerve stimulator is strongly recommended to evaluate the level of neuromuscular blockade, to assess the need for additional doses of neuromuscular blocker, and to determine whether adjustments need to be made to the dose with subsequent administration.
Paromomycin: (Major) Concomitant use of parenteral vancomycin with other nephrotoxic drugs, such as aminoglycosides, can lead to additive nephrotoxicity. Both vancomycin and aminoglycosides may cause ototoxicity as well. In a clinical study, vancomycin coadministration, high aminoglycoside trough concentrations, and heart failure independently predicted acute kidney injury during aminoglycoside treatment. Renal function should be monitored closely, and vancomycin and aminoglycoside doses should be adjusted according to serum concentrations as clinically indicated.
Pentamidine: (Major) Concomitant use of parenteral vancomycin with other nephrotoxic drugs, such as systemic pentamidine, can lead to additive nephrotoxicity. Renal function should be monitored closely and vancomycin doses should be adjusted according to vancomycin serum concentrations.
Piperacillin; Tazobactam: (Moderate) Piperacillin; tazobactam, when used concomitantly with vancomycin, may increase the risk of acute kidney injury. A limited number of retrospective studies have detected an increased incidence of acute kidney injury in patients administered concomitant piperacillin; tazobactam and vancomycin as compared to those who received vancomycin alone. Careful patient monitoring while on concurrent therapy with vancomycin is recommended.
Piroxicam: (Minor) It is possible that additive nephrotoxicity may occur in patients who receive NSAIDs concurrently with other nephrotoxic agents, including vancomycin.
Plazomicin: (Major) Concomitant use of parenteral vancomycin with other nephrotoxic drugs, such as aminoglycosides, can lead to additive nephrotoxicity. Both vancomycin and aminoglycosides may cause ototoxicity as well. In a clinical study, vancomycin coadministration, high aminoglycoside trough concentrations, and heart failure independently predicted acute kidney injury during aminoglycoside treatment. Renal function should be monitored closely, and vancomycin and aminoglycoside doses should be adjusted according to serum concentrations as clinically indicated.
Polymyxin B: (Major) Systemic polymyxin B should not be used concurrently or sequentially with other drugs that have the potential for nephrotoxicity or neurotoxicity such as vancomycin. Topical products containing polymyxin B, especially when they are applied over a large body surface area, should be used cautiously with any of the above drugs. If concurrent systemic use is necessary, renal function should be monitored closely and vancomycin doses should be adjusted according to vancomycin serum concentrations. Diminishing urine output and a rising BUN are indications to discontinue systemic polymyxin B therapy.
Poractant Alfa: (Major) Some surfactant-anti-infective mixtures have been shown to affect the in vivo activity of exogenous pulmonary surfactants when they are administered via inhalation. Pulmonary surfactants should not be mixed with anti-infectives that are commonly administered via nebulization such as vancomycin.
Rapacuronium: (Moderate) Concomitant use of neuromuscular blockers and vancomycin may prolong neuromuscular blockade. The use of a peripheral nerve stimulator is strongly recommended to evaluate the level of neuromuscular blockade, to assess the need for additional doses of neuromuscular blocker, and to determine whether adjustments need to be made to the dose with subsequent administration.
Relugolix; Estradiol; Norethindrone acetate: (Moderate) It would be prudent to recommend alternative or additional contraception when oral contraceptives (OCs) are used in conjunction with antibiotics. It was previously thought that antibiotics may decrease the effectiveness of OCs containing estrogens due to stimulation of metabolism or a reduction in enterohepatic circulation via changes in GI flora. One retrospective study reviewed the literature to determine the effects of oral antibiotics on the pharmacokinetics of contraceptive estrogens and progestins, and also examined clinical studies in which the incidence of pregnancy with OCs and antibiotics was reported. It was concluded that the antibiotics ampicillin, ciprofloxacin, clarithromycin, doxycycline, metronidazole, ofloxacin, roxithromycin, temafloxacin, and tetracycline did not alter plasma concentrations of OCs. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. Based on the study results, these authors recommended that back-up contraception may not be necessary if OCs are used reliably during oral antibiotic use. Another review concurred with these data, but noted that individual patients have been identified who experienced significant decreases in plasma concentrations of combined OC components and who appeared to ovulate; the agents most often associated with these changes were rifampin, tetracyclines, and penicillin derivatives. These authors concluded that because females most at risk for OC failure or noncompliance may not be easily identified and the true incidence of such events may be under-reported, and given the serious consequence of unwanted pregnancy, that recommending an additional method of contraception during short-term antibiotic use may be justified. During long-term antibiotic administration, the risk for drug interaction with OCs is less clear, but alternative or additional contraception may be advisable in selected circumstances. Data regarding progestin-only contraceptives or for newer combined contraceptive deliveries (e.g., patches, rings) are not available.
Remifentanil: (Moderate) The concurrent administration of vancomycin and anesthetics has been associated with erythema, histamine-like flushing, and anaphylactoid reactions.
Rocuronium: (Moderate) Concomitant use of neuromuscular blockers and vancomycin may prolong neuromuscular blockade. The use of a peripheral nerve stimulator is strongly recommended to evaluate the level of neuromuscular blockade, to assess the need for additional doses of neuromuscular blocker, and to determine whether adjustments need to be made to the dose with subsequent administration.
Salicylates: (Minor) Due to the inhibition of renal prostaglandins by salicylates, concurrent use of salicylates and other nephrotoxic agents, such as vancomycin, may lead to additive nephrotoxicity.
Segesterone Acetate; Ethinyl Estradiol: (Moderate) It would be prudent to recommend alternative or additional contraception when oral contraceptives (OCs) are used in conjunction with antibiotics. It was previously thought that antibiotics may decrease the effectiveness of OCs containing estrogens due to stimulation of metabolism or a reduction in enterohepatic circulation via changes in GI flora. One retrospective study reviewed the literature to determine the effects of oral antibiotics on the pharmacokinetics of contraceptive estrogens and progestins, and also examined clinical studies in which the incidence of pregnancy with OCs and antibiotics was reported. It was concluded that the antibiotics ampicillin, ciprofloxacin, clarithromycin, doxycycline, metronidazole, ofloxacin, roxithromycin, temafloxacin, and tetracycline did not alter plasma concentrations of OCs. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. Based on the study results, these authors recommended that back-up contraception may not be necessary if OCs are used reliably during oral antibiotic use. Another review concurred with these data, but noted that individual patients have been identified who experienced significant decreases in plasma concentrations of combined OC components and who appeared to ovulate; the agents most often associated with these changes were rifampin, tetracyclines, and penicillin derivatives. These authors concluded that because females most at risk for OC failure or noncompliance may not be easily identified and the true incidence of such events may be under-reported, and given the serious consequence of unwanted pregnancy, that recommending an additional method of contraception during short-term antibiotic use may be justified. During long-term antibiotic administration, the risk for drug interaction with OCs is less clear, but alternative or additional contraception may be advisable in selected circumstances. Data regarding progestin-only contraceptives or for newer combined contraceptive deliveries (e.g., patches, rings) are not available.
Sodium picosulfate; Magnesium oxide; Anhydrous citric acid: (Major) Prior or concomitant use of antibiotics with sodium picosulfate; magnesium oxide; anhydrous citric acid may reduce efficacy of the bowel preparation as conversion of sodium picosulfate to its active metabolite bis-(p-hydroxy-phenyl)-pyridyl-2-methane (BHPM) is mediated by colonic bacteria. If possible, avoid coadministration. Certain antibiotics (i.e., tetracyclines and quinolones) may chelate with the magnesium in sodium picosulfate; magnesium oxide; anhydrous citric acid solution. Therefore, these antibiotics should be taken at least 2 hours before and not less than 6 hours after the administration of sodium picosulfate; magnesium oxide; anhydrous citric acid solution.
Streptomycin: (Major) Concomitant use of parenteral vancomycin with other nephrotoxic drugs, such as aminoglycosides, can lead to additive nephrotoxicity. Both vancomycin and aminoglycosides may cause ototoxicity as well. In a clinical study, vancomycin coadministration, high aminoglycoside trough concentrations, and heart failure independently predicted acute kidney injury during aminoglycoside treatment. Renal function should be monitored closely, and vancomycin and aminoglycoside doses should be adjusted according to serum concentrations as clinically indicated.
Streptozocin: (Moderate) Concomitant use of parenteral vancomycin with other nephrotoxic drug, such as streptozocin, can lead to additive nephrotoxicity.
Succinylcholine: (Moderate) Concomitant use of neuromuscular blockers and vancomycin may prolong neuromuscular blockade. The use of a peripheral nerve stimulator is strongly recommended to evaluate the level of neuromuscular blockade, to assess the need for additional doses of neuromuscular blocker, and to determine whether adjustments need to be made to the dose with subsequent administration.
Sufentanil: (Moderate) The concurrent administration of vancomycin and anesthetics has been associated with erythema, histamine-like flushing, and anaphylactoid reactions.
Sulindac: (Minor) It is possible that additive nephrotoxicity may occur in patients who receive NSAIDs concurrently with other nephrotoxic agents, including vancomycin.
Sumatriptan; Naproxen: (Minor) It is possible that additive nephrotoxicity may occur in patients who receive NSAIDs concurrently with other nephrotoxic agents, including vancomycin.
Tacrolimus: (Moderate) Concomitant use of parenteral vancomycin with other nephrotoxic drugs, such as tacrolimus, can lead to additive nephrotoxicity. Monitor renal function closely and adjust vancomycin or tacrolimus doses according to serum concentrations.
Telbivudine: (Moderate) Drugs that alter renal function such as vancomycin may alter telbivudine plasma concentrations because telbivudine is eliminated primarily by renal excretion. Monitor renal function before and during telbivudine treatment.
Tenofovir Alafenamide: (Moderate) Monitor for changes in renal function if tenofovir alafenamide is administered in combination with a nephrotoxic agent, such as vancomycin. Tenofovir is primarily excreted via the kidneys by a combination of glomerular filtration and active tubular secretion. Coadministration of tenofovir alafenamide with a drug that reduces renal function or competes for active tubular secretion may increase concentrations of tenofovir and other renally eliminated drugs; thus, increasing the risk of developing renal-related adverse reactions.
Tenofovir Disoproxil Fumarate: (Moderate) Tenofovir should be avoided with concurrent or recent use of a nephrotoxic agent, such as vancomycin. Patients receiving these drugs together should be carefully monitored for changes in serum creatinine and phosphorus. Renal impairment, which may include hypophosphatemia, has been reported with the use of tenofovir; a majority of cases occurring in patients who have underlying systemic or renal disease or who are concurrently taking nephrotoxic agents.
Tobramycin: (Major) Concomitant use of parenteral vancomycin with other nephrotoxic drugs, such as aminoglycosides, can lead to additive nephrotoxicity. Both vancomycin and aminoglycosides may cause ototoxicity as well. In a clinical study, vancomycin coadministration, high aminoglycoside trough concentrations, and heart failure independently predicted acute kidney injury during aminoglycoside treatment. Renal function should be monitored closely, and vancomycin and aminoglycoside doses should be adjusted according to serum concentrations as clinically indicated.
Tolmetin: (Minor) It is possible that additive nephrotoxicity may occur in patients who receive NSAIDs concurrently with other nephrotoxic agents, including vancomycin.
Tolvaptan: (Moderate) Coadministration of tolvaptan and hypertonic saline (e.g., 3% NaCl injection solution) is not recommended. The use of hypertonic sodium chloride in combination with tolvaptan may result in a too rapid correction of hyponatremia and increase the risk of osmotic demyelination (i.e., central pontine myelinolysis).
Trospium: (Moderate) Both trospium and vancomycin are eliminated by active renal tubular secretion; coadministration has the potential to increase serum concentrations of trospium or vancomycin due to competition for the drug elimination pathway. Careful patient monitoring and dosage adjustment of trospium and/or vancomycin is recommended.
Valacyclovir: (Moderate) Closely monitor renal function if concomitant use with valacyclovir and vancomycin is necessary. Both drugs can cause nephrotoxicity, which may be additive when used together.
Valdecoxib: (Minor) It is possible that additive nephrotoxicity may occur in patients who receive NSAIDs concurrently with other nephrotoxic agents, including vancomycin.
Valganciclovir: (Moderate) Concurrent use of nephrotoxic agents, such as vancomycin, with valganciclovir should be done cautiously to avoid additive nephrotoxicity.
Vecuronium: (Moderate) Concomitant use of neuromuscular blockers and vancomycin may prolong neuromuscular blockade. The use of a peripheral nerve stimulator is strongly recommended to evaluate the level of neuromuscular blockade, to assess the need for additional doses of neuromuscular blocker, and to determine whether adjustments need to be made to the dose with subsequent administration.
Voclosporin: (Moderate) Concomitant use of voclosporin and vancomycin may result in additive nephrotoxicity. Monitor for renal toxicity if concomitant use is required.
Warfarin: (Moderate) The concomitant use of warfarin with many classes of antibiotics, including aminoglycosides, may result in an increased INR thereby potentiating the risk for bleeding. Inhibition of vitamin K synthesis due to alterations in the intestinal flora may be a mechanism; however, concurrent infection is also a potential risk factor for elevated INR. Monitor patients for signs and symptoms of bleeding. Additionally, increased monitoring of the INR, especially during initiation and upon discontinuation of the antibiotic, may be necessary.
Zoledronic Acid: (Moderate) Coadministration of zoledronic acid with other potentially nephrotoxic drugs, such as vancomycin, may increase serum concentrations of either drug and increase the risk of nephrotoxicity. Monitor patients for changes in renal function if these drugs are coadministered.

PREGNANCY AND LACTATION

There are no available data on vancomycin use in pregnant women to assess a risk of major birth defects or miscarriage. Available published data on intravenous vancomycin use in pregnancy during the second and third trimesters have not shown an association with adverse maternal or fetal outcomes.[28468] [63969] The fetal risk of ototoxic and/or nephrotoxic effects from vancomycin when administered during pregnancy is considered to be low.[27016] [33052] Certain formulations of injectable vancomycin contain excipients, such as polyethylene glycol (PEG) 400 and N-acetyl-D-alanine (NADA), which have caused fetal malformations in animal reproductive studies. If vancomycin use is needed during pregnancy, utilize other available formulations.[63968] Systemic absorption of vancomycin is low after oral administration; however, absorption may vary depending on various factors.[28468] [63969] Vancomycin crosses the placenta and can accumulate in amniotic fluid. Cord blood concentrations in 1 newborn were about 76% of the mother's serum concentrations after the mother received vancomycin 1 g IV every 12 hours for 13 days; no maternal nephrotoxicity or ototoxicity was noted.[33051] Congenital abnormalities were not noted in newborns of mothers who received vancomycin 1 g IV every 12 hours for at least 1 week.[33052] In a study evaluating hearing loss and nephrotoxicity in infants of 10 pregnant women treated with IV vancomycin in the second or third trimester, no infant had abnormal sensorineural hearing at 3 months or nephrotoxicity. In a study of 55 pregnant women who received IV vancomycin at the time of delivery, no major adverse reactions were noted in the newborns or the mothers, including no sensorineural hearing loss. Neonatal renal function was not examined.[28468] [63969] Animal data do not demonstrate any risk of teratogenic or toxic effects on the fetus.[28468] [33050] [33054] [28468] [33053]

There is insufficient data on the presence of vancomycin in human milk. There are no data on the effects of vancomycin on the breast-fed infant or milk production. Systemic absorption of vancomycin is low after oral administration; therefore, it is unlikely to result in clinically relevant exposure in nursing infants.[28468] [62844] [63969] In 1 woman treated with intravenous vancomycin 1 g every 12 hours, a single breast-milk concentration of 12.7 mcg/mL was measured at 4 hours after infusion. Her peak and trough serum vancomycin concentrations were 36.1 mcg/mL and12.5 mcg/mL, respectively.[33052] Consider the developmental and health benefits of breast-feeding along with the mother's clinical need for vancomycin and any potential adverse effects on the breast-fed infant from vancomycin or the underlying maternal condition.[28468] [62844] [63969]

MECHANISM OF ACTION

Vancomycin is bactericidal and appears to exert its effect by binding to the precursor units of bacterial cell walls, inhibiting their synthesis. It specifically binds with the D-alanyl-D-alanine terminus of the peptide precursor units, inhibiting peptidoglycan polymerase and transpeptidation reactions. This prevents cross-linking of the cell wall peptidoglycan during the second stage of cell synthesis. The net result is an alteration of bacterial cell wall permeability and cell death. In addition, RNA synthesis is inhibited. Vancomycin is not active in vitro to gram-negative organisms, mycobacteria, of fungi.[34153] [40937] [40938]
 
Vancomycin exhibits 'concentration-independent killing' in which there is saturation of the bacterial killing rate once the drug concentrations approach the minimum inhibitory concentration (MIC).[34142] [34143] [34144] [34145] An AUC/MIC ratio of 400 or more is necessary to achieve clinical effectiveness with vancomycin. In PK/PD models applicable to human methicillin-resistant S. aureus (MRSA) infection, bactericidal activity (i.e., a 1- to 2-log reduction in bacterial inoculum in the animal model) is achieved when the vancomycin AUC/MIC ratio approximates or exceeds 400. Additionally, in vitro data suggest that an AUC of less than 400 potentiates the emergence of MRSA resistance and vancomycin-intermediate S. aureus strains.[65262]
 
Most strains of S. aureus, S. epidermidis, Streptococcus sp., and Corynebacterium sp. are susceptible to vancomycin. Vancomycin is particularly useful against penicillin- and methicillin-resistant staphylococcal infections and for treating other gram-positive infections in beta-lactam-allergic patients. However, there are a few case reports of S. aureus strains that are insensitive to vancomycin.[34148] While, traditionally, vancomycin has been used to treat enterococcal infections, there is a significant resistance rate in these organisms. Vancomycin-resistant enterococci (VRE) rates up to 12.1% have been reported in bloodstream isolates and up to 25% of ICU enterococcal infections.[34149] [34150] Synergistic bactericidal effects can be achieved when vancomycin is combined with aminoglycosides against gram-positive organisms, but this increases possible toxicity. Vancomycin is useful against a wide variety of clinical infections due to these pathogens. When given orally, vancomycin is also useful in treating C. difficile.[62844]
 
The susceptibility interpretive criteria for vancomycin are delineated by pathogen. The MICs are defined for S. aureus as susceptible at 2 mcg/mL or less, intermediate at 4 to 8 mcg/mL, and resistant at 16 mcg/mL or more. The MICs are defined for Enterococcus sp. and Staphylococcus sp. other than S. aureus as susceptible at 4 mcg/mL or less, intermediate at 8 to 16 mcg/mL, and resistant at 32 mcg/mL or more.[63320] [63321] However, reports suggest that S. aureus isolates with vancomycin MICs of 1 to 2 mcg/mL may be less likely to be successfully treated with vancomycin.[35013] The MICs are defined for beta-hemolytic Streptococcus sp., viridans group Streptococcus sp., and S. pneumoniae as susceptible at 1 mcg/mL or less.[63320] [63321]
 
While vancomycin has been a predominant agent to treat gram-positive infections, increasing resistance has started to limit its utility. Vancomycin-resistant enterococci (VRE) is the most common resistant pathogen. There are 6 types of reported vancomycin resistance in enterococci (VanA, VanB, VanC, VanD, VanE, and VanG). Of these, 5 types are acquired resistance, while VanC is an intrinsic resistance found in E. gallinarum and E. casseliflavus. The most common type is VanA resistance. Once exposed to an inducer, like vancomycin, transcription of the enzymes that make the cell-wall precursors is altered. There is an increase in the cell-wall precursors ending in D-alanyl-D-lactate, to which vancomycin has a low binding affinity, and a decrease in the D-alanyl-D-alanine cell-wall precursors, to which vancomycin has a high binding affinity. This results in decreased binding of vancomycin to the receptor sites of the enterococcal cell wall. The genes for this resistance can potentially be spread to other bacteria via plasmids. Exposure to IV and oral vancomycin, antianaerobic antibiotics, and other broad-spectrum antibiotics have all been associated as factors contributing to VRE.[34152] [34153] S. aureus is another concerning organism with increasing resistance to vancomycin. Strains of vancomycin-intermediate S. aureus (VISA), heterogeneous vancomycin-intermediate S. aureus (hVISA), and vancomycin-resistance S. aureus (VRSA) have been described in the literature. Strains of VISA have shown an unusually thickened cell wall that prevents drug penetration. The cell wall also contains dipeptides that bind vancomycin. Fully resistant strains, VRSA, have acquired VanA resistance similar to Enterococcus sp.[34153] [34154] Guidelines suggest that exposure to vancomycin trough serum concentrations of less than 10 mg/L may produce S. aureus strains with VISA-like characteristics.[35013]

PHARMACOKINETICS

In general, vancomycin is only administered intravenously although oral administration is important in the treatment of some GI infections such as pseudomembranous colitis. Vancomycin is not administered intramuscularly due to severe pain at the injection site.
 
Systemically administered vancomycin is distributed into most body tissues and fluids including pericardial fluid, pleural fluid, ascitic fluid, synovial fluid, urine, peritoneal dialysis fluid, and atrial appendage tissue. Concentrations obtained in tissues and fluids are variable and somewhat dependent on the degree of inflammation present. The volume of distribution coefficient is reported by the manufacturer as 0.3 to 0.43 L/kg; however, literature reports give a range of 0.2 to 1.9 L/kg. Unless the meninges are inflamed, there is little diffusion into CSF (0 to 3.45 mg/L) with corresponding CSF:serum ratios of 0 to 0.18. Inflamed meninges improve penetration into the CSF with reported concentrations of 6.4 to 11.1 mg/L with corresponding CSF:serum ratio of 0.36 to 0.46. Vancomycin is about 55% (range: 44% to 82%) bound to serum protein in healthy volunteers with normal renal function. There is no apparent metabolism of vancomycin. Excretion is mainly by glomerular filtration, with about 80% of the drug excreted in 24 hours in the urine and only small amounts excreted in the feces. In patients with normal renal function, vancomycin has a serum half-life of about 4 to 6 hours. Mean plasma clearance is approximately 0.058 L/kg/hour and mean renal clearance is approximately 0.048 L/kg/hour.