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  • CLASSES

    Azole Antifungals
    Gynecological Antifungals
    Topical Dermatological Antifungals

    DEA CLASS

    OTC, Rx

    DESCRIPTION

    Imidazole antifungal; used topically, as a bioadhesive buccal tablet, and intravaginally for various fungal infections.

    COMMON BRAND NAMES

    Aloe Vesta, Antifungal, AZOLEN TINCTURE, Baza, Cruex, Desenex, Desenex Jock Itch, Fungoid, Lotrimin AF, Lotrimin AF Antifungal Liquid, Lotrimin AF Deodorant, Lotrimin AF Powder, Lotrimin AF Spray, Micaderm, Micatin, Miconazole 7, Micotrin AP, Micro-Guard, Mitrazol, Monistat 1 Day or Night Combination Pack, Monistat 1 Triple Action, Monistat 3, Monistat 3 Triple Action System Combination Pack, Monistat 3 Vaginal Cream (Prefilled), Monistat 3 Vaginal Cream Combination Pack, Monistat 3 Vaginal Cream Combination Pack (Prefilled), Monistat 3 Vaginal Ovule Combination Pack, Monistat 3 Vaginal Suppositories Combination Pack, Monistat 7, Monistat 7 Vaginal Cream Combination Pack, Monistat-Derm, Mycozyl AP, Neosporin AF, Novana Anti-Fungal, Oravig, Remedy, Soothe & Cool INZO, Ting Antifungal, Triple Paste AF, Vagistat-3, Zeasorb Athlete's Foot, Zeasorb Jock Itch

    HOW SUPPLIED

    Aloe Vesta/Antifungal/Baza/Micaderm/Micatin/Miconazole/Miconazole Nitrate/Monistat 3 Vaginal Cream Combination Pack (Prefilled)/Monistat 3 Vaginal Suppositories Combination Pack/Monistat 7/Monistat 7 Vaginal Cream Combination Pack/Monistat-Derm/Mycozyl AP/Neosporin AF/Novana Anti-Fungal/Remedy/Soothe & Cool INZO/Vagistat-3 Topical Cream: 2%, 2g, 2-200mg, 2-4%
    AZOLEN TINCTURE/Fungoid/Miconazole/Miconazole Nitrate Topical Sol: 2%
    Cruex/Lotrimin AF/Lotrimin AF Antifungal Liquid/Lotrimin AF Deodorant/Lotrimin AF Powder/Lotrimin AF Spray/Ting Antifungal Topical Spray: 2%
    Desenex/Lotrimin AF Powder/Miconazole/Miconazole Nitrate/Micotrin AP/Micro-Guard/Mitrazol/Remedy/Zeasorb Athlete's Foot/Zeasorb Jock Itch Topical Pwd: 2%
    Miconazole/Miconazole 7/Miconazole Nitrate/Monistat 1 Day or Night Combination Pack/Monistat 3 Triple Action System Combination Pack/Monistat 3 Vaginal Ovule Combination Pack/Monistat 3 Vaginal Suppositories Combination Pack/Vagistat-3 Vaginal Supp: 100mg, 200mg, 2-1200mg, 2-200mg
    Miconazole/Miconazole Nitrate/Monistat 1 Day or Night Combination Pack/Monistat 3 Triple Action System Combination Pack/Monistat 3 Vaginal Cream (Prefilled)/Monistat 3 Vaginal Cream Combination Pack (Prefilled)/Monistat 3 Vaginal Ovule Combination Pack/Monistat 3 Vaginal Suppositories Combination Pack/Monistat 7/Monistat 7 Vaginal Cream Combination Pack/Vagistat-3 Vaginal Cream: 2%, 4%, 2-1200mg, 2-200mg, 2-4%
    Miconazole/Oravig Buccal Tablet, SL: 50mg
    Triple Paste AF Topical Ointment: 2%

    DOSAGE & INDICATIONS

    For the topical treatment of tinea pedis and tinea corporis.
    Topical application
    Adults, Adolescents, and Children >= 2 years

    Apply 2% preparation to the cleansed, dry, infected area twice daily for 4 weeks.

    For the treatment of tinea cruris.
    Topical application
    Adults, Adolescents, and Children >= 2 years

    Apply 2% preparation to the cleansed, dry, infected area twice daily for 2 weeks.

    For the treatment of tinea versicolor.
    Topical application (skin cream only)
    Adults, Adolescents, and Children >= 2 years

    Apply 2% preparation to the cleansed, dry, infected area twice daily. An improvement is generally noted within 2 weeks of treatment.

    For the treatment of cutaneous candidiasis or mucocutaneous candidiasis (i.e., oropharyngeal candidiasis (thrush)).
    For the treatment of cutaneous candidiasis.
    Topical dosage (skin cream only)
    Adults

    Apply 2% preparation to the cleansed, dry, infected area twice daily. An improvement is generally noted within 2 weeks of treatment.

    Children and Adolescents 2 to 17 years

    Apply 2% preparation to the cleansed, dry, infected area twice daily. An improvement is generally noted within 2 weeks of treatment.

    For the local treatment of oropharyngeal candidiasis (thrush).
    Transmucosal dosage (adhesive buccal tablet)
    Adults

    Apply one 50 mg buccal tablet to the upper gum region, just above the incisor tooth (canine fossa) once daily for 14 days.

    Adolescents 16 to 17 years

    Apply one 50 mg buccal tablet to the upper gum region, just above the incisor tooth (canine fossa) once daily for 14 days.

    Adolescents 13 to 15 years†

    Apply one 50 mg buccal tablet to the upper gum region, just above the incisor tooth (canine fossa) once daily for 14 days.

    For the treatment of vulvovaginal candidiasis (VVC).
    For the treatment of uncomplicated VVC.
    Intravaginal dosage (1-day regimen, vaginal suppository)

    NOTE: The 1-day regimen is not recommended in persons living with HIV. Treatment for 3 to 7 days is recommended.

    Adults

    One suppository (1,200 mg miconazole) inserted intravaginally as a single dose at bedtime in non-pregnant patients.

    Children and Adolescents 12 to 17 years

    One suppository (1,200 mg miconazole) inserted intravaginally as a single dose at bedtime in non-pregnant patients.

    Intravaginal application (3-day regimen, vaginal suppository or cream)
    Adults

    One suppository (200 mg miconazole) or one applicatorful (200 mg miconazole/5 g cream) of cream intravaginally at bedtime for 3 days in non-pregnant patients.

    Children and Adolescents 12 to 17 years

    One suppository (200 mg miconazole) or one applicatorful (200 mg miconazole/5 g cream) of cream intravaginally at bedtime for 3 days in non-pregnant patients.

    Intravaginal dosage (7-day regimens, suppository or vaginal cream)
    Adults

    One suppository (100 mg miconazole) or one applicatorful (100 mg miconazole/5 g cream) of cream intravaginally once daily at bedtime for 7 days in pregnant or non-pregnant patients.

    Children and Adolescents 12 to 17 years

    One suppository (100 mg miconazole) or one applicatorful (100 mg miconazole/5 g cream) of cream intravaginally once daily at bedtime for 7 days in pregnant or non-pregnant patients.

    For the treatment of severe or recurrent VVC†.
    Intravaginal dosage
    Adults

    One suppository (100 mg miconazole) or one applicatorful (100 mg miconazole/5 g cream) of cream intravaginally once daily at bedtime for 7 to 14 days. Subsequent intermittent topical treatment may be considered for maintenance of recurrent VVC as an alternative to fluconazole.

    Adolescents

    One suppository (100 mg miconazole) or one applicatorful (100 mg miconazole/5 g cream) of cream intravaginally once daily at bedtime for 7 to 14 days. Subsequent intermittent topical treatment may be considered for maintenance of recurrent VVC as an alternative to fluconazole.

    MAXIMUM DOSAGE

    Adults

    50 mg/day PO; 1 applicatorful (100 or 200 mg miconazole/5 g cream) intravaginally/day; 1 suppository (100, 200, or 1,200 mg) intravaginally/day. Maximum dosage not available for topical products.

    Geriatric

    50 mg/day PO; 1 applicatorful (100 or 200 mg miconazole/5 g cream) intravaginally/day; 1 suppository (100, 200, or 1,200 mg) intravaginally/day. Maximum dosage not available for topical products.

    Adolescents

    16 to 17 years: 50 mg/day PO; 1 applicatorful (100 or 200 mg miconazole/5 g cream) intravaginally/day; 1 suppository (100, 200, or 1,200 mg) intravaginally/day. Maximum dosage not available for topical products.
    13 to 15 years: Safety and efficacy of oral formulation have not been established; however, 50 mg/day PO has been used off-label. 1 applicatorful (100 or 200 mg miconazole/5 g cream) intravaginally/day; 1 suppository (100, 200, or 1,200 mg) intravaginally/day. Maximum dosage not available for topical products.

    Children

    12 years: 1 applicatorful (100 or 200 mg miconazole/5 g cream) intravaginally/day; 1 suppository (100, 200, or 1,200 mg) intravaginally/day. Maximum dosage not available for topical products. Safety and efficacy of oral formulation have not been established.
    2 to 11 years: Maximum dosage not available for topical products. Safety and efficacy of other formulations have not been established.
    1 year: Safety and efficacy have not been established.

    Infants

    Safety and efficacy have not been established.

    Neonates

    Safety and efficacy have not been established.

    DOSING CONSIDERATIONS

    Hepatic Impairment

    No dosage adjustment needed for topical or vaginal products. While miconazole systemic exposure is minimal with buccal application and no specific dosage adjustments are recommended, adhesive buccal tablets should be administered with caution in patients with hepatic impairment.

    Renal Impairment

    No dosage adjustment needed for topical, adhesive buccal tablets, or vaginal products.

    ADMINISTRATION

     
    NOTE: Dosage and duration of therapy vary depending on the infecting organism and the product utilized.

    Oral Administration
    Other Oral Formulations

    Transmucosal Administration (adhesive buccal tablet)
    Apply tablet in the morning after brushing the teeth.
    Apply with dry hands.
    Place the rounded surface of the tablet against the upper gum just above the incisor tooth (canine fossa) and hold in place with a slight pressure over the upper lip for 30 seconds to assure adhesion.
    Although the tablet is rounded on one side for comfort, the flat side may also be applied to the gum.
    The tablet will gradually dissolve.
    Administration of subsequent tablets should be made to alternate sides of the mouth.
    Before applying the next tablet, clear away any remaining tablet material.
    Do not crush, chew or swallow.
    Food and drink can be taken normally.
    Avoid chewing gum.
    If tablet does not adhere or falls off within the first 6 hours, the same tablet should be repositioned immediately. If the tablet still does not adhere, a new tablet should be placed.
    If the tablet falls off or is swallowed after it was in place for 6 hours or more, a new tablet should not be applied until the next regularly scheduled dose.

    Injectable Administration

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

    Intravenous Administration

    Infusion:
    Dilute appropriate dose of solution in at least 200 ml of NS. Do not exceed a concentration of 6 mg/ml.
    Infuse over 30—60 minutes.

    Intrathecal Administration

    To be administered by a qualified health care professional experienced in drug administration into the CNS.
    Use the parenteral miconazole injection, it is preservative-free.
    No dilution necessary.

    Other Injectable Administration

    Intraventricular Administration
    To be administered by a qualified health care professional experienced in drug administration into the CNS.
    Use the parenteral miconazole injection, it is preservative-free.
    No dilution necessary.
     
    Intravesical Administration
    Dilute 200 mg of miconazole injection in at least 200 ml of NS.
    Instill intermittently or as a continuous irrigation into the bladder.

    Topical Administration

    Wash hands before and after use. Use universal precautions (i.e., gloves) for application if needed.
    Cleanse the affected area and dry thoroughly prior to application.
    In the treatment of cutaneous Candida infections, occlusive dressings should be avoided since these dressings provide favorable conditions for yeast growth.

    Cream/Ointment/Lotion Formulations

    Cream: Apply a thin layer to the affected area. Gently rub into the skin. Do not use creams labeled for dermatologic use intravaginally.

    Other Topical Formulations

    Shake powder: Sprinkle powder in a thin layer over the affected area.
    Spray powder or liquid: Shake aerosol can well before use. Hold spray 4—6 inches from the affected area. Spray product in a thin layer over the affected area. Do not inhale the spray or accidentally spray eyes or mucous membranes.

    Intravaginal Administration

    Apply intravaginally only those miconazole products labeled for intravaginal use. Other products may cause irritation to sensitive vaginal tissues.
    Wash hands before and after use. Use universal precautions (i.e., gloves) for application if needed.
    Some products supply both intravaginal suppositories and vulvar cream in a combination package; the cream may be applied to the externally to the affected area (vulva) to relieve itching and discomfort.
    Use special applicator supplied by the manufacturer.
    Instruct patient on proper administration and treatment course (see Patient Information).
    Instruct patient not to use tampons, douches, or spermicides during the treatment course; the patient should also be instructed to abstain from sexual activity during treatment. Vaginal miconazole products may damage condoms, diaphragms, and cervical caps and cause them to fail.

    STORAGE

    Generic:
    - Store at room temperature (between 59 to 86 degrees F)
    - Store below 86 degrees F
    Aloe Vesta:
    - Store at room temperature
    Antifungal:
    - Store at room temperature
    AZOLEN TINCTURE:
    - Protect from freezing
    - Store between 68 to 77 degrees F, excursions permitted 59 to 86 degrees F
    Baza:
    - Store at room temperature (between 59 to 86 degrees F)
    Cruex:
    - Store between 68 to 77 degrees F
    Desenex:
    - Exposure to temperatures above 120 degrees F may cause bursting
    - Store between 68 to 86 degrees F
    Desenex Jock Itch:
    - Store between 68 to 77 degrees F
    Fungoid:
    - Protect from freezing
    - Store between 68 to 77 degrees F, excursions permitted 59 to 86 degrees F
    Lotrimin AF:
    - Store between 68 to 77 degrees F
    Lotrimin AF Antifungal Liquid:
    - Exposure to temperatures above 120 degrees F may cause bursting
    - Store between 68 to 86 degrees F
    Lotrimin AF Deodorant:
    - Store between 68 to 77 degrees F
    Lotrimin AF Powder:
    - Store between 68 to 77 degrees F
    Lotrimin AF Spray:
    - Exposure to temperatures above 120 degrees F may cause bursting
    - Store between 68 to 86 degrees F
    Micaderm :
    - Store at room temperature
    Micatin:
    - Store at room temperature
    Miconazole 7:
    - Store between 68 to 77 degrees F, excursions permitted 59 to 86 degrees F
    Micotrin AP:
    - Avoid excessive heat (above 104 degrees F)
    - Protect from freezing
    Micro-Guard :
    - Store at room temperature (between 59 to 86 degrees F)
    Mitrazol:
    - Store at room temperature (between 59 to 86 degrees F)
    Monistat 1 Day or Night Combination Pack:
    - Store between 68 to 77 degrees F
    Monistat 1 Triple Action:
    - Store between 68 to 77 degrees F
    Monistat 1 Vaginal Ovule Combination Pack:
    - Store at controlled room temperature (between 68 and 77 degrees F)
    Monistat 1 Vaginal Ovule Combination Pack (Prefilled):
    - Store at controlled room temperature (between 68 and 77 degrees F)
    Monistat 3:
    - Store at controlled room temperature (between 68 and 77 degrees F)
    Monistat 3 Triple Action System Combination Pack:
    - Store between 68 to 77 degrees F, excursions permitted 59 to 86 degrees F
    Monistat 3 Vaginal Cream (Prefilled):
    - Store between 68 to 77 degrees F
    Monistat 3 Vaginal Cream Combination Pack:
    - Store between 68 to 77 degrees F
    Monistat 3 Vaginal Cream Combination Pack (Prefilled):
    - Store between 68 to 77 degrees F
    Monistat 3 Vaginal Ovule Combination Pack:
    - Store between 68 to 77 degrees F, excursions permitted 59 to 86 degrees F
    Monistat 3 Vaginal Suppositories Combination Pack:
    - Store between 68 to 77 degrees F, excursions permitted 59 to 86 degrees F
    Monistat 7:
    - Store between 68 to 77 degrees F, excursions permitted 59 to 86 degrees F
    Monistat 7 Vaginal Cream Combination Pack:
    - Store at controlled room temperature (between 68 and 77 degrees F)
    Monistat-Derm:
    - Store at room temperature
    Mycozyl AP:
    - Store at room temperature
    Neosporin AF:
    - Store at room temperature
    Novana Anti-Fungal:
    - Store at room temperature
    Oravig:
    - Protect from moisture
    - Store between 68 to 77 degrees F, excursions permitted 59 to 86 degrees F
    - Store in a dry place
    Remedy:
    - Store at room temperature
    Soothe & Cool INZO:
    - Store at room temperature
    Ting Antifungal:
    - Store between 68 to 77 degrees F
    Triple Paste AF :
    - Storage information not listed
    Vagistat-3:
    - Store between 68 to 77 degrees F, excursions permitted 59 to 86 degrees F
    Zeasorb Athlete's Foot:
    - Store below 77 degrees F
    Zeasorb Jock Itch:
    - Store at room temperature (between 59 to 86 degrees F)

    CONTRAINDICATIONS / PRECAUTIONS

    Azole antifungals hypersensitivity, milk protein hypersensitivity

    Miconazole is contraindicated in patients with known miconazole hypersensitivity. Miconazole buccal tablets are contraindicated in patients with milk protein hypersensitivity. There is no information regarding cross-hypersensitivity between miconazole and other azole antifungal agents. Monitor patients with a history of azole antifungals hypersensitivity. Discontinue miconazole immediately at the first sign of hypersensitivity.[40140]

    Hepatic disease

    Miconazole is metabolized by the liver. While miconazole systemic exposure is minimal after buccal application, use miconazole buccal tablets with caution in patients with hepatic disease.[40140]

    Children, infants, neonates

    The safety and efficacy of miconazole buccal tablets have not been established in neonates, infants, children, and adolescents younger than 16 years. The ability of pediatric patients to comply with the application instructions has not been evaluated. Use of the miconazole buccal tablets in younger children is not recommended due to the potential risk of choking.

    Ocular exposure

    Avoid ocular exposure with topical miconazole administration.[49548]

    Abdominal pain, fever, nausea/vomiting, vaginal discharge

    Vaginal miconazole use in patients with lower abdominal pain, back or shoulder pain, fever, chills, nausea/vomiting, first episode of vaginal itching and discomfort, foul-smelling vaginal discharge, or frequent vaginal yeast infections (e.g., once a month or 3 in 6 months) is only recommended under the supervision of a health care professional. The patient may have a more serious condition or underlying medical cause for the symptoms, such as diabetes or a weakened immune system, including due to human immunodeficiency virus (HIV).[30216]

    Tobacco smoking

    Topical miconazole sprays are flammable. Advise patients not to use miconazole sprays while tobacco smoking or near heat or flame.

    Pregnancy

    There are no available data on the use of miconazole buccal tablets in human pregnancy to evaluate for a drug-associated risk of major birth defects, miscarriage, or adverse maternal or fetal outcomes. Based on animal data, miconazole buccal tablet use may cause fetal harm when administered to pregnant women; advise pregnant women of the potential risk to the fetus. In animal reproduction studies, prolonged gestation, dystocia, and/or increased number of resorptions were observed after oral administration of miconazole during organogenesis.[40140] Vaginal miconazole use in pregnancy is only recommended under the supervision of a health care professional.[30216]

    Breast-feeding

    There is no data on the presence of miconazole in human milk, or the effects on the breast-fed child, or the effects on milk production after use of miconazole buccal tablets. Consider the developmental and health benefits of breast-feeding along with the mother's clinical need for miconazole buccal tablets and any potential adverse effects on the breast-fed infant from miconazole buccal tablets or the underlying maternal condition.[40140] Vaginal miconazole use in breast-feeding is only recommended under the supervision of a health care professional.[30216]

    Contraceptive devices, menstruation

    Advise patients who are using vaginal miconazole to avoid vaginal intercourse, tampons during menstruation, douches, spermicides, or other vaginal products. Contraceptive devices, including condoms and diaphragms, may be damaged and fail to prevent pregnancy or sexually transmitted diseases.[30216]

    ADVERSE REACTIONS

    Severe

    anaphylactoid reactions / Rapid / Incidence not known

    Moderate

    anemia / Delayed / 2.8-2.8
    lymphopenia / Delayed / 1.7-1.7
    elevated hepatic enzymes / Delayed / 1.0-1.0
    neutropenia / Delayed / Incidence not known
    oral ulceration / Delayed / Incidence not known

    Mild

    infection / Delayed / 11.9-15.9
    diarrhea / Early / 6.0-9.0
    headache / Early / 5.0-7.6
    nausea / Early / 0.7-6.6
    dysgeusia / Early / 2.9-4.1
    vomiting / Early / 0.7-3.8
    xerostomia / Early / 2.8-2.8
    cough / Delayed / 2.8-2.8
    fatigue / Early / 2.8-2.8
    pruritus / Rapid / 2.0-2.0
    rash / Early / Incidence not known
    vaginal discharge / Delayed / Incidence not known
    skin irritation / Early / Incidence not known
    abdominal pain / Early / Incidence not known
    fever / Early / Incidence not known

    DRUG INTERACTIONS

    Acetohexamide: (Moderate) Hypoglycemia, sometimes severe, has been reported when systemic azole antifungals are coadministered with sulfonylureas. No formal drug interaction studies have been performed with buccal miconazole. Miconazole is a known inhibitor of CYP2C9. Although the systemic absorption of miconazole following buccal administration is minimal and plasma concentrations are substantially lower than when miconazole is given intravenously, the potential for interaction with drugs metabolized through CYP2C9 (such as the sulfonylureas) cannot be ruled out.
    Belladonna Alkaloids; Ergotamine; Phenobarbital: (Moderate) No formal drug interaction studies have been performed with buccal miconazole. Miconazole is a known inhibitor of CYP3A4. Although the systemic absorption of miconazole following buccal miconazole administration is minimal and plasma concentrations of miconazole are substantially lower than when given intravenously, the potential for interaction with drugs metabolized through CYP3A4 (such as the ergot alkaloids) cannot be ruled out. Be alert for symptoms of a potential interaction, such as ischemia, cyanosis, and numbness of the extremities or other serious ergot-related effects.
    Chlorpropamide: (Moderate) Hypoglycemia, sometimes severe, has been reported when systemic azole antifungals are coadministered with sulfonylureas. No formal drug interaction studies have been performed with buccal miconazole. Miconazole is a known inhibitor of CYP2C9. Although the systemic absorption of miconazole following buccal administration is minimal and plasma concentrations are substantially lower than when miconazole is given intravenously, the potential for interaction with drugs metabolized through CYP2C9 (such as the sulfonylureas) cannot be ruled out.
    Desogestrel; Ethinyl Estradiol: (Minor) Miconazole vaginal products may be administered with most hormonal contraceptives containing ethinyl estradiol, as most of the time any increase in ethinyl estradiol AUC is minimal and unlikely to cause significant side effects, though some patients may notice breast tenderness or nausea. In patients using contraceptive vaginal rings, water-based miconazole products are preferred. Oil-based miconazole vaginal products appear to increase ethinyl estradiol exposure from the contraceptive vaginal rings. Water-based miconazole vaginal products or an alternative oral therapy may be used concurrently with vaginal rings containing ethinyl estradiol. In drug interaction studies with ethinyl estradiol-containing vaginal rings, single-dose vaginal administration of a 1,200 mg miconazole suppository increased the systemic exposure of ethinyl estradiol by 16% to 67%, depending on the contraceptive vaginal ring in use. When 200 mg miconazole vaginal suppositories were administered, the ethinyl estradiol systemic exposures were also increased, with a maximal reported increase of 42% on day 3 of miconazole vaginal suppository use. Multiple doses of a 200 mg miconazole nitrate vaginal cream with the etonogestrel; ethinyl estradiol ring increased the mean serum concentration of ethinyl estradiol by up to 40%. Water-based vaginal miconazole cream did not affect the pharmacokinetics of the segesterone acetate; ethinyl estradiol vaginal ring.
    Dihydroergotamine: (Moderate) No formal drug interaction studies have been performed with buccal miconazole. Miconazole is a known inhibitor of CYP3A4. Although the systemic absorption of miconazole following buccal miconazole administration is minimal and plasma concentrations of miconazole are substantially lower than when given intravenously, the potential for interaction with drugs metabolized through CYP3A4 (such as the ergot alkaloids) cannot be ruled out. Be alert for symptoms of a potential interaction, such as ischemia, cyanosis, and numbness of the extremities or other serious ergot-related effects.
    Drospirenone; Ethinyl Estradiol: (Minor) Miconazole vaginal products may be administered with most hormonal contraceptives containing ethinyl estradiol, as most of the time any increase in ethinyl estradiol AUC is minimal and unlikely to cause significant side effects, though some patients may notice breast tenderness or nausea. In patients using contraceptive vaginal rings, water-based miconazole products are preferred. Oil-based miconazole vaginal products appear to increase ethinyl estradiol exposure from the contraceptive vaginal rings. Water-based miconazole vaginal products or an alternative oral therapy may be used concurrently with vaginal rings containing ethinyl estradiol. In drug interaction studies with ethinyl estradiol-containing vaginal rings, single-dose vaginal administration of a 1,200 mg miconazole suppository increased the systemic exposure of ethinyl estradiol by 16% to 67%, depending on the contraceptive vaginal ring in use. When 200 mg miconazole vaginal suppositories were administered, the ethinyl estradiol systemic exposures were also increased, with a maximal reported increase of 42% on day 3 of miconazole vaginal suppository use. Multiple doses of a 200 mg miconazole nitrate vaginal cream with the etonogestrel; ethinyl estradiol ring increased the mean serum concentration of ethinyl estradiol by up to 40%. Water-based vaginal miconazole cream did not affect the pharmacokinetics of the segesterone acetate; ethinyl estradiol vaginal ring.
    Drospirenone; Ethinyl Estradiol; Levomefolate: (Minor) Miconazole vaginal products may be administered with most hormonal contraceptives containing ethinyl estradiol, as most of the time any increase in ethinyl estradiol AUC is minimal and unlikely to cause significant side effects, though some patients may notice breast tenderness or nausea. In patients using contraceptive vaginal rings, water-based miconazole products are preferred. Oil-based miconazole vaginal products appear to increase ethinyl estradiol exposure from the contraceptive vaginal rings. Water-based miconazole vaginal products or an alternative oral therapy may be used concurrently with vaginal rings containing ethinyl estradiol. In drug interaction studies with ethinyl estradiol-containing vaginal rings, single-dose vaginal administration of a 1,200 mg miconazole suppository increased the systemic exposure of ethinyl estradiol by 16% to 67%, depending on the contraceptive vaginal ring in use. When 200 mg miconazole vaginal suppositories were administered, the ethinyl estradiol systemic exposures were also increased, with a maximal reported increase of 42% on day 3 of miconazole vaginal suppository use. Multiple doses of a 200 mg miconazole nitrate vaginal cream with the etonogestrel; ethinyl estradiol ring increased the mean serum concentration of ethinyl estradiol by up to 40%. Water-based vaginal miconazole cream did not affect the pharmacokinetics of the segesterone acetate; ethinyl estradiol vaginal ring.
    Ergoloid Mesylates: (Moderate) No formal drug interaction studies have been performed with buccal miconazole. Miconazole is a known inhibitor of CYP3A4. Although the systemic absorption of miconazole following buccal miconazole administration is minimal and plasma concentrations of miconazole are substantially lower than when given intravenously, the potential for interaction with drugs metabolized through CYP3A4 (such as the ergot alkaloids) cannot be ruled out. Be alert for symptoms of a potential interaction, such as ischemia, cyanosis, and numbness of the extremities or other serious ergot-related effects.
    Ergonovine: (Moderate) No formal drug interaction studies have been performed with buccal miconazole. Miconazole is a known inhibitor of CYP3A4. Although the systemic absorption of miconazole following buccal miconazole administration is minimal and plasma concentrations of miconazole are substantially lower than when given intravenously, the potential for interaction with drugs metabolized through CYP3A4 (such as the ergot alkaloids) cannot be ruled out. Be alert for symptoms of a potential interaction, such as ischemia, cyanosis, and numbness of the extremities or other serious ergot-related effects.
    Ergot alkaloids: (Moderate) No formal drug interaction studies have been performed with buccal miconazole. Miconazole is a known inhibitor of CYP3A4. Although the systemic absorption of miconazole following buccal miconazole administration is minimal and plasma concentrations of miconazole are substantially lower than when given intravenously, the potential for interaction with drugs metabolized through CYP3A4 (such as the ergot alkaloids) cannot be ruled out. Be alert for symptoms of a potential interaction, such as ischemia, cyanosis, and numbness of the extremities or other serious ergot-related effects.
    Ergotamine: (Moderate) No formal drug interaction studies have been performed with buccal miconazole. Miconazole is a known inhibitor of CYP3A4. Although the systemic absorption of miconazole following buccal miconazole administration is minimal and plasma concentrations of miconazole are substantially lower than when given intravenously, the potential for interaction with drugs metabolized through CYP3A4 (such as the ergot alkaloids) cannot be ruled out. Be alert for symptoms of a potential interaction, such as ischemia, cyanosis, and numbness of the extremities or other serious ergot-related effects.
    Ergotamine; Caffeine: (Moderate) No formal drug interaction studies have been performed with buccal miconazole. Miconazole is a known inhibitor of CYP3A4. Although the systemic absorption of miconazole following buccal miconazole administration is minimal and plasma concentrations of miconazole are substantially lower than when given intravenously, the potential for interaction with drugs metabolized through CYP3A4 (such as the ergot alkaloids) cannot be ruled out. Be alert for symptoms of a potential interaction, such as ischemia, cyanosis, and numbness of the extremities or other serious ergot-related effects.
    Ethinyl Estradiol: (Minor) Miconazole vaginal products may be administered with most hormonal contraceptives containing ethinyl estradiol, as most of the time any increase in ethinyl estradiol AUC is minimal and unlikely to cause significant side effects, though some patients may notice breast tenderness or nausea. In patients using contraceptive vaginal rings, water-based miconazole products are preferred. Oil-based miconazole vaginal products appear to increase ethinyl estradiol exposure from the contraceptive vaginal rings. Water-based miconazole vaginal products or an alternative oral therapy may be used concurrently with vaginal rings containing ethinyl estradiol. In drug interaction studies with ethinyl estradiol-containing vaginal rings, single-dose vaginal administration of a 1,200 mg miconazole suppository increased the systemic exposure of ethinyl estradiol by 16% to 67%, depending on the contraceptive vaginal ring in use. When 200 mg miconazole vaginal suppositories were administered, the ethinyl estradiol systemic exposures were also increased, with a maximal reported increase of 42% on day 3 of miconazole vaginal suppository use. Multiple doses of a 200 mg miconazole nitrate vaginal cream with the etonogestrel; ethinyl estradiol ring increased the mean serum concentration of ethinyl estradiol by up to 40%. Water-based vaginal miconazole cream did not affect the pharmacokinetics of the segesterone acetate; ethinyl estradiol vaginal ring.
    Ethinyl Estradiol; Levonorgestrel; Folic Acid; Levomefolate: (Minor) Miconazole vaginal products may be administered with most hormonal contraceptives containing ethinyl estradiol, as most of the time any increase in ethinyl estradiol AUC is minimal and unlikely to cause significant side effects, though some patients may notice breast tenderness or nausea. In patients using contraceptive vaginal rings, water-based miconazole products are preferred. Oil-based miconazole vaginal products appear to increase ethinyl estradiol exposure from the contraceptive vaginal rings. Water-based miconazole vaginal products or an alternative oral therapy may be used concurrently with vaginal rings containing ethinyl estradiol. In drug interaction studies with ethinyl estradiol-containing vaginal rings, single-dose vaginal administration of a 1,200 mg miconazole suppository increased the systemic exposure of ethinyl estradiol by 16% to 67%, depending on the contraceptive vaginal ring in use. When 200 mg miconazole vaginal suppositories were administered, the ethinyl estradiol systemic exposures were also increased, with a maximal reported increase of 42% on day 3 of miconazole vaginal suppository use. Multiple doses of a 200 mg miconazole nitrate vaginal cream with the etonogestrel; ethinyl estradiol ring increased the mean serum concentration of ethinyl estradiol by up to 40%. Water-based vaginal miconazole cream did not affect the pharmacokinetics of the segesterone acetate; ethinyl estradiol vaginal ring.
    Ethinyl Estradiol; Norelgestromin: (Minor) Miconazole vaginal products may be administered with most hormonal contraceptives containing ethinyl estradiol, as most of the time any increase in ethinyl estradiol AUC is minimal and unlikely to cause significant side effects, though some patients may notice breast tenderness or nausea. In patients using contraceptive vaginal rings, water-based miconazole products are preferred. Oil-based miconazole vaginal products appear to increase ethinyl estradiol exposure from the contraceptive vaginal rings. Water-based miconazole vaginal products or an alternative oral therapy may be used concurrently with vaginal rings containing ethinyl estradiol. In drug interaction studies with ethinyl estradiol-containing vaginal rings, single-dose vaginal administration of a 1,200 mg miconazole suppository increased the systemic exposure of ethinyl estradiol by 16% to 67%, depending on the contraceptive vaginal ring in use. When 200 mg miconazole vaginal suppositories were administered, the ethinyl estradiol systemic exposures were also increased, with a maximal reported increase of 42% on day 3 of miconazole vaginal suppository use. Multiple doses of a 200 mg miconazole nitrate vaginal cream with the etonogestrel; ethinyl estradiol ring increased the mean serum concentration of ethinyl estradiol by up to 40%. Water-based vaginal miconazole cream did not affect the pharmacokinetics of the segesterone acetate; ethinyl estradiol vaginal ring.
    Ethinyl Estradiol; Norethindrone Acetate: (Minor) Miconazole vaginal products may be administered with most hormonal contraceptives containing ethinyl estradiol, as most of the time any increase in ethinyl estradiol AUC is minimal and unlikely to cause significant side effects, though some patients may notice breast tenderness or nausea. In patients using contraceptive vaginal rings, water-based miconazole products are preferred. Oil-based miconazole vaginal products appear to increase ethinyl estradiol exposure from the contraceptive vaginal rings. Water-based miconazole vaginal products or an alternative oral therapy may be used concurrently with vaginal rings containing ethinyl estradiol. In drug interaction studies with ethinyl estradiol-containing vaginal rings, single-dose vaginal administration of a 1,200 mg miconazole suppository increased the systemic exposure of ethinyl estradiol by 16% to 67%, depending on the contraceptive vaginal ring in use. When 200 mg miconazole vaginal suppositories were administered, the ethinyl estradiol systemic exposures were also increased, with a maximal reported increase of 42% on day 3 of miconazole vaginal suppository use. Multiple doses of a 200 mg miconazole nitrate vaginal cream with the etonogestrel; ethinyl estradiol ring increased the mean serum concentration of ethinyl estradiol by up to 40%. Water-based vaginal miconazole cream did not affect the pharmacokinetics of the segesterone acetate; ethinyl estradiol vaginal ring.
    Ethinyl Estradiol; Norgestrel: (Minor) Miconazole vaginal products may be administered with most hormonal contraceptives containing ethinyl estradiol, as most of the time any increase in ethinyl estradiol AUC is minimal and unlikely to cause significant side effects, though some patients may notice breast tenderness or nausea. In patients using contraceptive vaginal rings, water-based miconazole products are preferred. Oil-based miconazole vaginal products appear to increase ethinyl estradiol exposure from the contraceptive vaginal rings. Water-based miconazole vaginal products or an alternative oral therapy may be used concurrently with vaginal rings containing ethinyl estradiol. In drug interaction studies with ethinyl estradiol-containing vaginal rings, single-dose vaginal administration of a 1,200 mg miconazole suppository increased the systemic exposure of ethinyl estradiol by 16% to 67%, depending on the contraceptive vaginal ring in use. When 200 mg miconazole vaginal suppositories were administered, the ethinyl estradiol systemic exposures were also increased, with a maximal reported increase of 42% on day 3 of miconazole vaginal suppository use. Multiple doses of a 200 mg miconazole nitrate vaginal cream with the etonogestrel; ethinyl estradiol ring increased the mean serum concentration of ethinyl estradiol by up to 40%. Water-based vaginal miconazole cream did not affect the pharmacokinetics of the segesterone acetate; ethinyl estradiol vaginal ring.
    Ethynodiol Diacetate; Ethinyl Estradiol: (Minor) Miconazole vaginal products may be administered with most hormonal contraceptives containing ethinyl estradiol, as most of the time any increase in ethinyl estradiol AUC is minimal and unlikely to cause significant side effects, though some patients may notice breast tenderness or nausea. In patients using contraceptive vaginal rings, water-based miconazole products are preferred. Oil-based miconazole vaginal products appear to increase ethinyl estradiol exposure from the contraceptive vaginal rings. Water-based miconazole vaginal products or an alternative oral therapy may be used concurrently with vaginal rings containing ethinyl estradiol. In drug interaction studies with ethinyl estradiol-containing vaginal rings, single-dose vaginal administration of a 1,200 mg miconazole suppository increased the systemic exposure of ethinyl estradiol by 16% to 67%, depending on the contraceptive vaginal ring in use. When 200 mg miconazole vaginal suppositories were administered, the ethinyl estradiol systemic exposures were also increased, with a maximal reported increase of 42% on day 3 of miconazole vaginal suppository use. Multiple doses of a 200 mg miconazole nitrate vaginal cream with the etonogestrel; ethinyl estradiol ring increased the mean serum concentration of ethinyl estradiol by up to 40%. Water-based vaginal miconazole cream did not affect the pharmacokinetics of the segesterone acetate; ethinyl estradiol vaginal ring.
    Etonogestrel; Ethinyl Estradiol: (Minor) Miconazole vaginal products may be administered with most hormonal contraceptives containing ethinyl estradiol, as most of the time any increase in ethinyl estradiol AUC is minimal and unlikely to cause significant side effects, though some patients may notice breast tenderness or nausea. In patients using contraceptive vaginal rings, water-based miconazole products are preferred. Oil-based miconazole vaginal products appear to increase ethinyl estradiol exposure from the contraceptive vaginal rings. Water-based miconazole vaginal products or an alternative oral therapy may be used concurrently with vaginal rings containing ethinyl estradiol. In drug interaction studies with ethinyl estradiol-containing vaginal rings, single-dose vaginal administration of a 1,200 mg miconazole suppository increased the systemic exposure of ethinyl estradiol by 16% to 67%, depending on the contraceptive vaginal ring in use. When 200 mg miconazole vaginal suppositories were administered, the ethinyl estradiol systemic exposures were also increased, with a maximal reported increase of 42% on day 3 of miconazole vaginal suppository use. Multiple doses of a 200 mg miconazole nitrate vaginal cream with the etonogestrel; ethinyl estradiol ring increased the mean serum concentration of ethinyl estradiol by up to 40%. Water-based vaginal miconazole cream did not affect the pharmacokinetics of the segesterone acetate; ethinyl estradiol vaginal ring.
    Fosphenytoin: (Moderate) No formal drug interaction studies have been performed with buccal miconazole. Miconazole is a known inhibitor of CYP2C9. Although the systemic absorption of miconazole following buccal miconazole administration is minimal and plasma concentrations of miconazole are substantially lower than when given intravenously, the potential for interaction with drugs metabolized through CYP2C9 (such as phenytoin or fosphenytoin) cannot be ruled out.
    Glimepiride: (Moderate) Hypoglycemia, sometimes severe, has been reported when systemic azole antifungals are coadministered with sulfonylureas. No formal drug interaction studies have been performed with buccal miconazole. Miconazole is a known inhibitor of CYP2C9. Although the systemic absorption of miconazole following buccal administration is minimal and plasma concentrations are substantially lower than when miconazole is given intravenously, the potential for interaction with drugs metabolized through CYP2C9 (such as the sulfonylureas) cannot be ruled out.
    Glimepiride; Rosiglitazone: (Moderate) Hypoglycemia, sometimes severe, has been reported when systemic azole antifungals are coadministered with sulfonylureas. No formal drug interaction studies have been performed with buccal miconazole. Miconazole is a known inhibitor of CYP2C9. Although the systemic absorption of miconazole following buccal administration is minimal and plasma concentrations are substantially lower than when miconazole is given intravenously, the potential for interaction with drugs metabolized through CYP2C9 (such as the sulfonylureas) cannot be ruled out.
    Glipizide: (Moderate) Hypoglycemia, sometimes severe, has been reported when systemic azole antifungals are coadministered with sulfonylureas. No formal drug interaction studies have been performed with buccal miconazole. Miconazole is a known inhibitor of CYP2C9. Although the systemic absorption of miconazole following buccal administration is minimal and plasma concentrations are substantially lower than when miconazole is given intravenously, the potential for interaction with drugs metabolized through CYP2C9 (such as the sulfonylureas) cannot be ruled out.
    Glipizide; Metformin: (Moderate) Hypoglycemia, sometimes severe, has been reported when systemic azole antifungals are coadministered with sulfonylureas. No formal drug interaction studies have been performed with buccal miconazole. Miconazole is a known inhibitor of CYP2C9. Although the systemic absorption of miconazole following buccal administration is minimal and plasma concentrations are substantially lower than when miconazole is given intravenously, the potential for interaction with drugs metabolized through CYP2C9 (such as the sulfonylureas) cannot be ruled out.
    Glyburide: (Moderate) Hypoglycemia, sometimes severe, has been reported when systemic azole antifungals are coadministered with sulfonylureas. No formal drug interaction studies have been performed with buccal miconazole. Miconazole is a known inhibitor of CYP2C9. Although the systemic absorption of miconazole following buccal administration is minimal and plasma concentrations are substantially lower than when miconazole is given intravenously, the potential for interaction with drugs metabolized through CYP2C9 (such as the sulfonylureas) cannot be ruled out.
    Glyburide; Metformin: (Moderate) Hypoglycemia, sometimes severe, has been reported when systemic azole antifungals are coadministered with sulfonylureas. No formal drug interaction studies have been performed with buccal miconazole. Miconazole is a known inhibitor of CYP2C9. Although the systemic absorption of miconazole following buccal administration is minimal and plasma concentrations are substantially lower than when miconazole is given intravenously, the potential for interaction with drugs metabolized through CYP2C9 (such as the sulfonylureas) cannot be ruled out.
    Levonorgestrel; Ethinyl Estradiol: (Minor) Miconazole vaginal products may be administered with most hormonal contraceptives containing ethinyl estradiol, as most of the time any increase in ethinyl estradiol AUC is minimal and unlikely to cause significant side effects, though some patients may notice breast tenderness or nausea. In patients using contraceptive vaginal rings, water-based miconazole products are preferred. Oil-based miconazole vaginal products appear to increase ethinyl estradiol exposure from the contraceptive vaginal rings. Water-based miconazole vaginal products or an alternative oral therapy may be used concurrently with vaginal rings containing ethinyl estradiol. In drug interaction studies with ethinyl estradiol-containing vaginal rings, single-dose vaginal administration of a 1,200 mg miconazole suppository increased the systemic exposure of ethinyl estradiol by 16% to 67%, depending on the contraceptive vaginal ring in use. When 200 mg miconazole vaginal suppositories were administered, the ethinyl estradiol systemic exposures were also increased, with a maximal reported increase of 42% on day 3 of miconazole vaginal suppository use. Multiple doses of a 200 mg miconazole nitrate vaginal cream with the etonogestrel; ethinyl estradiol ring increased the mean serum concentration of ethinyl estradiol by up to 40%. Water-based vaginal miconazole cream did not affect the pharmacokinetics of the segesterone acetate; ethinyl estradiol vaginal ring.
    Levonorgestrel; Ethinyl Estradiol; Ferrous Bisglycinate: (Minor) Miconazole vaginal products may be administered with most hormonal contraceptives containing ethinyl estradiol, as most of the time any increase in ethinyl estradiol AUC is minimal and unlikely to cause significant side effects, though some patients may notice breast tenderness or nausea. In patients using contraceptive vaginal rings, water-based miconazole products are preferred. Oil-based miconazole vaginal products appear to increase ethinyl estradiol exposure from the contraceptive vaginal rings. Water-based miconazole vaginal products or an alternative oral therapy may be used concurrently with vaginal rings containing ethinyl estradiol. In drug interaction studies with ethinyl estradiol-containing vaginal rings, single-dose vaginal administration of a 1,200 mg miconazole suppository increased the systemic exposure of ethinyl estradiol by 16% to 67%, depending on the contraceptive vaginal ring in use. When 200 mg miconazole vaginal suppositories were administered, the ethinyl estradiol systemic exposures were also increased, with a maximal reported increase of 42% on day 3 of miconazole vaginal suppository use. Multiple doses of a 200 mg miconazole nitrate vaginal cream with the etonogestrel; ethinyl estradiol ring increased the mean serum concentration of ethinyl estradiol by up to 40%. Water-based vaginal miconazole cream did not affect the pharmacokinetics of the segesterone acetate; ethinyl estradiol vaginal ring.
    Methylergonovine: (Moderate) No formal drug interaction studies have been performed with buccal miconazole. Miconazole is a known inhibitor of CYP3A4. Although the systemic absorption of miconazole following buccal miconazole administration is minimal and plasma concentrations of miconazole are substantially lower than when given intravenously, the potential for interaction with drugs metabolized through CYP3A4 (such as the ergot alkaloids) cannot be ruled out. Be alert for symptoms of a potential interaction, such as ischemia, cyanosis, and numbness of the extremities or other serious ergot-related effects.
    Methysergide: (Moderate) No formal drug interaction studies have been performed with buccal miconazole. Miconazole is a known inhibitor of CYP3A4. Although the systemic absorption of miconazole following buccal miconazole administration is minimal and plasma concentrations of miconazole are substantially lower than when given intravenously, the potential for interaction with drugs metabolized through CYP3A4 (such as the ergot alkaloids) cannot be ruled out. Be alert for symptoms of a potential interaction, such as ischemia, cyanosis, and numbness of the extremities or other serious ergot-related effects.
    Norethindrone Acetate; Ethinyl Estradiol; Ferrous fumarate: (Minor) Miconazole vaginal products may be administered with most hormonal contraceptives containing ethinyl estradiol, as most of the time any increase in ethinyl estradiol AUC is minimal and unlikely to cause significant side effects, though some patients may notice breast tenderness or nausea. In patients using contraceptive vaginal rings, water-based miconazole products are preferred. Oil-based miconazole vaginal products appear to increase ethinyl estradiol exposure from the contraceptive vaginal rings. Water-based miconazole vaginal products or an alternative oral therapy may be used concurrently with vaginal rings containing ethinyl estradiol. In drug interaction studies with ethinyl estradiol-containing vaginal rings, single-dose vaginal administration of a 1,200 mg miconazole suppository increased the systemic exposure of ethinyl estradiol by 16% to 67%, depending on the contraceptive vaginal ring in use. When 200 mg miconazole vaginal suppositories were administered, the ethinyl estradiol systemic exposures were also increased, with a maximal reported increase of 42% on day 3 of miconazole vaginal suppository use. Multiple doses of a 200 mg miconazole nitrate vaginal cream with the etonogestrel; ethinyl estradiol ring increased the mean serum concentration of ethinyl estradiol by up to 40%. Water-based vaginal miconazole cream did not affect the pharmacokinetics of the segesterone acetate; ethinyl estradiol vaginal ring.
    Norethindrone; Ethinyl Estradiol: (Minor) Miconazole vaginal products may be administered with most hormonal contraceptives containing ethinyl estradiol, as most of the time any increase in ethinyl estradiol AUC is minimal and unlikely to cause significant side effects, though some patients may notice breast tenderness or nausea. In patients using contraceptive vaginal rings, water-based miconazole products are preferred. Oil-based miconazole vaginal products appear to increase ethinyl estradiol exposure from the contraceptive vaginal rings. Water-based miconazole vaginal products or an alternative oral therapy may be used concurrently with vaginal rings containing ethinyl estradiol. In drug interaction studies with ethinyl estradiol-containing vaginal rings, single-dose vaginal administration of a 1,200 mg miconazole suppository increased the systemic exposure of ethinyl estradiol by 16% to 67%, depending on the contraceptive vaginal ring in use. When 200 mg miconazole vaginal suppositories were administered, the ethinyl estradiol systemic exposures were also increased, with a maximal reported increase of 42% on day 3 of miconazole vaginal suppository use. Multiple doses of a 200 mg miconazole nitrate vaginal cream with the etonogestrel; ethinyl estradiol ring increased the mean serum concentration of ethinyl estradiol by up to 40%. Water-based vaginal miconazole cream did not affect the pharmacokinetics of the segesterone acetate; ethinyl estradiol vaginal ring.
    Norethindrone; Ethinyl Estradiol; Ferrous fumarate: (Minor) Miconazole vaginal products may be administered with most hormonal contraceptives containing ethinyl estradiol, as most of the time any increase in ethinyl estradiol AUC is minimal and unlikely to cause significant side effects, though some patients may notice breast tenderness or nausea. In patients using contraceptive vaginal rings, water-based miconazole products are preferred. Oil-based miconazole vaginal products appear to increase ethinyl estradiol exposure from the contraceptive vaginal rings. Water-based miconazole vaginal products or an alternative oral therapy may be used concurrently with vaginal rings containing ethinyl estradiol. In drug interaction studies with ethinyl estradiol-containing vaginal rings, single-dose vaginal administration of a 1,200 mg miconazole suppository increased the systemic exposure of ethinyl estradiol by 16% to 67%, depending on the contraceptive vaginal ring in use. When 200 mg miconazole vaginal suppositories were administered, the ethinyl estradiol systemic exposures were also increased, with a maximal reported increase of 42% on day 3 of miconazole vaginal suppository use. Multiple doses of a 200 mg miconazole nitrate vaginal cream with the etonogestrel; ethinyl estradiol ring increased the mean serum concentration of ethinyl estradiol by up to 40%. Water-based vaginal miconazole cream did not affect the pharmacokinetics of the segesterone acetate; ethinyl estradiol vaginal ring.
    Norgestimate; Ethinyl Estradiol: (Minor) Miconazole vaginal products may be administered with most hormonal contraceptives containing ethinyl estradiol, as most of the time any increase in ethinyl estradiol AUC is minimal and unlikely to cause significant side effects, though some patients may notice breast tenderness or nausea. In patients using contraceptive vaginal rings, water-based miconazole products are preferred. Oil-based miconazole vaginal products appear to increase ethinyl estradiol exposure from the contraceptive vaginal rings. Water-based miconazole vaginal products or an alternative oral therapy may be used concurrently with vaginal rings containing ethinyl estradiol. In drug interaction studies with ethinyl estradiol-containing vaginal rings, single-dose vaginal administration of a 1,200 mg miconazole suppository increased the systemic exposure of ethinyl estradiol by 16% to 67%, depending on the contraceptive vaginal ring in use. When 200 mg miconazole vaginal suppositories were administered, the ethinyl estradiol systemic exposures were also increased, with a maximal reported increase of 42% on day 3 of miconazole vaginal suppository use. Multiple doses of a 200 mg miconazole nitrate vaginal cream with the etonogestrel; ethinyl estradiol ring increased the mean serum concentration of ethinyl estradiol by up to 40%. Water-based vaginal miconazole cream did not affect the pharmacokinetics of the segesterone acetate; ethinyl estradiol vaginal ring.
    Nystatin: (Moderate) The combination of miconazole and nystatin represents duplication of therapy whenever the drugs are used by similar routes and are usually avoided.
    Pergolide: (Moderate) No formal drug interaction studies have been performed with buccal miconazole. Miconazole is a known inhibitor of CYP3A4. Although the systemic absorption of miconazole following buccal miconazole administration is minimal and plasma concentrations of miconazole are substantially lower than when given intravenously, the potential for interaction with drugs metabolized through CYP3A4 (such as the ergot alkaloids) cannot be ruled out. Be alert for symptoms of a potential interaction, such as ischemia, cyanosis, and numbness of the extremities or other serious ergot-related effects.
    Phenytoin: (Moderate) No formal drug interaction studies have been performed with buccal miconazole. Miconazole is a known inhibitor of CYP2C9. Although the systemic absorption of miconazole following buccal miconazole administration is minimal and plasma concentrations of miconazole are substantially lower than when given intravenously, the potential for interaction with drugs metabolized through CYP2C9 (such as phenytoin or fosphenytoin) cannot be ruled out.
    Pioglitazone; Glimepiride: (Moderate) Hypoglycemia, sometimes severe, has been reported when systemic azole antifungals are coadministered with sulfonylureas. No formal drug interaction studies have been performed with buccal miconazole. Miconazole is a known inhibitor of CYP2C9. Although the systemic absorption of miconazole following buccal administration is minimal and plasma concentrations are substantially lower than when miconazole is given intravenously, the potential for interaction with drugs metabolized through CYP2C9 (such as the sulfonylureas) cannot be ruled out.
    Progesterone: (Moderate) Vaginal preparations of progesterone (e.g., Crinone, Endometrin, and Prochieve) should not be used with other intravaginal products (e.g., vaginal antifungals, such as clotrimazole, miconazole nitrate, terconazole, or tioconazole vaginal) as concurrent use may alter progesterone release and absorption from the vagina. Separate the times of administration to avoid the interaction. The manufacturers of Crinone and Prochieve indicate that other intravaginal products can be used as long as 6 hours has lapsed either before or after vaginal administration of progesterone. Endometrin is generally not recommended for use with other vaginal products (e.g., antifungal products) as this may alter progesterone release and absorption from the vaginal insert and the potential for interaction has not been formally assessed; use other vaginal products if medically necessary, but be aware that the response to Endometrin may be altered.
    Segesterone Acetate; Ethinyl Estradiol: (Minor) Miconazole vaginal products may be administered with most hormonal contraceptives containing ethinyl estradiol, as most of the time any increase in ethinyl estradiol AUC is minimal and unlikely to cause significant side effects, though some patients may notice breast tenderness or nausea. In patients using contraceptive vaginal rings, water-based miconazole products are preferred. Oil-based miconazole vaginal products appear to increase ethinyl estradiol exposure from the contraceptive vaginal rings. Water-based miconazole vaginal products or an alternative oral therapy may be used concurrently with vaginal rings containing ethinyl estradiol. In drug interaction studies with ethinyl estradiol-containing vaginal rings, single-dose vaginal administration of a 1,200 mg miconazole suppository increased the systemic exposure of ethinyl estradiol by 16% to 67%, depending on the contraceptive vaginal ring in use. When 200 mg miconazole vaginal suppositories were administered, the ethinyl estradiol systemic exposures were also increased, with a maximal reported increase of 42% on day 3 of miconazole vaginal suppository use. Multiple doses of a 200 mg miconazole nitrate vaginal cream with the etonogestrel; ethinyl estradiol ring increased the mean serum concentration of ethinyl estradiol by up to 40%. Water-based vaginal miconazole cream did not affect the pharmacokinetics of the segesterone acetate; ethinyl estradiol vaginal ring.
    Sulfonylureas: (Moderate) Hypoglycemia, sometimes severe, has been reported when systemic azole antifungals are coadministered with sulfonylureas. No formal drug interaction studies have been performed with buccal miconazole. Miconazole is a known inhibitor of CYP2C9. Although the systemic absorption of miconazole following buccal administration is minimal and plasma concentrations are substantially lower than when miconazole is given intravenously, the potential for interaction with drugs metabolized through CYP2C9 (such as the sulfonylureas) cannot be ruled out.
    Tolazamide: (Moderate) Hypoglycemia, sometimes severe, has been reported when systemic azole antifungals are coadministered with sulfonylureas. No formal drug interaction studies have been performed with buccal miconazole. Miconazole is a known inhibitor of CYP2C9. Although the systemic absorption of miconazole following buccal administration is minimal and plasma concentrations are substantially lower than when miconazole is given intravenously, the potential for interaction with drugs metabolized through CYP2C9 (such as the sulfonylureas) cannot be ruled out.
    Tolbutamide: (Moderate) Hypoglycemia, sometimes severe, has been reported when systemic azole antifungals are coadministered with sulfonylureas. No formal drug interaction studies have been performed with buccal miconazole. Miconazole is a known inhibitor of CYP2C9. Although the systemic absorption of miconazole following buccal administration is minimal and plasma concentrations are substantially lower than when miconazole is given intravenously, the potential for interaction with drugs metabolized through CYP2C9 (such as the sulfonylureas) cannot be ruled out.
    Torsemide: (Minor) No formal drug interaction studies have been performed with buccal miconazole. Systemic absorption of miconazole following buccal administration is minimal. Vaginal and topical preparations are not likely to interact. However, the diuretic effect and blood pressure response may be affected if torsemide is administered with a CYP2C9 inhibitor. Torsemide is a substrate of CYP2C9; miconazole inhibits CYP2C9. Concomitant use of torsemide and miconazole can theoretically decrease torsemide clearance and increase torsemide plasma concentrations.
    Warfarin: (Moderate) Concomitant administration of miconazole and warfarin has resulted in enhancement of anticoagulant effect. Closely monitor prothrombin time, International Normalized Ratio (INR), or other suitable anticoagulation tests if miconazole is administered concomitantly with warfarin. Also monitor for evidence of bleeding. Miconazole is a known inhibitor of CYP2C9 and CYP3A4. The systemic absorption of buccal miconazole is minimal and plasma concentrations of miconazole are substantially lower than when given intravenously. However, there have been reported cases of bleeding and bruising with orally administered miconazole. (Moderate) Concomitant administration of miconazole and warfarin has resulted in enhancement of anticoagulant effect. Closely monitor prothrombin time, International Normalized Ratio (INR), or other suitable anticoagulation tests if topical or vaginal miconazole is administered concomitantly with warfarin. Also monitor for evidence of bleeding. Miconazole is a known inhibitor of CYP2C9 and CYP3A4. The systemic absorption of miconazole following vaginal or topical administration is minimal and plasma concentrations of miconazole are substantially lower than when given intravenously. However, there have been reported cases of bleeding and bruising following the concomitant use of warfarin and topical or intravaginal miconazole.

    PREGNANCY AND LACTATION

    Pregnancy

    There are no available data on the use of miconazole buccal tablets in human pregnancy to evaluate for a drug-associated risk of major birth defects, miscarriage, or adverse maternal or fetal outcomes. Based on animal data, miconazole buccal tablet use may cause fetal harm when administered to pregnant women; advise pregnant women of the potential risk to the fetus. In animal reproduction studies, prolonged gestation, dystocia, and/or increased number of resorptions were observed after oral administration of miconazole during organogenesis.[40140] Vaginal miconazole use in pregnancy is only recommended under the supervision of a health care professional.[30216]

    There is no data on the presence of miconazole in human milk, or the effects on the breast-fed child, or the effects on milk production after use of miconazole buccal tablets. Consider the developmental and health benefits of breast-feeding along with the mother's clinical need for miconazole buccal tablets and any potential adverse effects on the breast-fed infant from miconazole buccal tablets or the underlying maternal condition.[40140] Vaginal miconazole use in breast-feeding is only recommended under the supervision of a health care professional.[30216]

    MECHANISM OF ACTION

    Like other azole antifungals, miconazole exerts its effect by altering the fungal cell membrane. Miconazole inhibits ergosterol synthesis by interacting with 14-alpha demethylase, a cytochrome P-450 enzyme that is necessary for the conversion of lanosterol to ergosterol, an essential component of the membrane. Miconazole also affects the synthesis of triglycerides and fatty acids and inhibits oxidative and peroxidative enzymes, increasing the amount of reactive oxygen species within the cell. Azole antifungals are considered fungistatic. In contrast, amphotericin B binds to ergosterol after it is synthesized. Inhibition of ergosterol synthesis results in increased cellular permeability, causing leakage of cellular contents. Miconazole does not appear to have the same effect on human cholesterol synthesis. Other antifungal effects of azole compounds have been proposed and include: inhibition of endogenous respiration; interaction with membrane phospholipids; inhibition of yeast transformation to mycelial forms; and accumulation of ergosterol precursors and toxic peroxides resulting in cytolysis of the cell. Other mechanisms may involve inhibition of purine uptake and impairment of triglyceride and/or phospholipid biosynthesis.

    PHARMACOKINETICS

    Miconazole has been administered by the intravenous, intraventricular, intravesicular, topical, adhesive buccal tablet, and intravaginal routes. Parenteral formulations are no longer marketed in the US and, thus, it is primarily administered intravaginally, via adhesive buccal tablet, or topically.
     
    Most of the absorbed miconazole is metabolized by the liver, with less than 1% of the administered dose found in the urine. There are no active metabolites. Terminal half-life in healthy volunteers is 24 hours after systemic administration.
     
    Affected Cytochrome P450 (CYP450) isoenzymes and drug transporters: CYP2C9, CYP2C19, CYP3A4
    Miconazole is a potent inhibitor of the CYP2C9 isoenzyme. In vitro, it is a potent inhibitor of the CYP2C19 isoenzyme and a moderate inhibitor of the CYP3A4 isoenzyme.

    Oral Route

    Transmucosal Route
    The miconazole adhesive buccal tablet is used for local treatment. A single, 50 mg buccal tablet provided mean maximum salivary concentrations of 15.1 mcg/ml at 7 hours after application in 18 healthy volunteers. The average saliva exposure, estimated as an AUC, was 55.23 mcg x h/ml. The median Tmax was 7 hours. In healthy volunteers, the average duration of buccal adhesion was 15 hours after a single application. Plasma concentrations evaluated after 7 days of treatment in 40 HIV-positive patients were all below the limit of quantification. A  formal food effect study has not been conducted; however, patients were allowed to eat and drink normally during clinical trials.

    Intravenous Route

    When administered over 1 hour, IV infusions of 9 mg/kg or 350 mg/m2 or above are needed to achieve plasma miconazole concentrations of at least 1 mcg/ml. (The usual MIC for most susceptible fungi is 0.5-2 mcg/ml.) Miconazole is widely distributed into most bodily tissues and fluids including inflamed joints, the vitreous humor of the eye, and the peritoneal cavity. Poor penetration is achieved in the sputum and saliva. Protein binding is over 90%. The elimination of miconazole occurs in a triphasic manner, with biological half-lives of each phase being 0.4, 2.1, and 24.1 hours, respectively. Metabolism of miconazole is mainly in the liver. Roughly 14—22% of a dose of IV miconazole is excreted in the urine as inactive metabolites.

    Topical Route

    There have been no reports indicating that miconazole nitrate is absorbed following application to intact skin. Average peak serum concentrations of 4.2 ng/ml have been reported after six daily applications of the 14-day regimen for vulvovaginal candidiasis. About 1% of this dose was recovered in urine and feces. Distribution, metabolism, and elimination of topical miconazole are the same as after intravenous administration.

    Other Route(s)

    Intravaginal Route
    Only small amounts of intravaginal miconazole are absorbed systemically. Average peak serum concentrations of 4.2 ng/ml have been reported after six daily applications of the 14-day regimen for vulvovaginal candidiasis. About 1% of this dose was recovered in urine and feces. Distribution, metabolism, and elimination of topical miconazole are the same as after intravenous administration.
     
    Intrathecal and Intraventricular Route
    Because IV miconazole does not distribute well into the CSF, the drug must be administered intraventricularly or intrathecally to achieve fungistatic CSF concentrations. Intrathecal administration of 20 mg miconazole has produced CSF concentrations of 1.1—2.4 mcg/ml at 24 hours, which decline to less than 0.24 mcg/ml at 72 hours.