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 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%
Oravig Buccal Tablet, SL: 50mg
Triple Paste AF Topical Ointment: 2%

DOSAGE & INDICATIONS

MAXIMUM DOSAGE

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.

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.

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.

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.

Safety and efficacy have not been established.

Safety and efficacy have not been established.

DOSING CONSIDERATIONS

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.

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.

STORAGE

Generic:
- Store at room temperature (between 59 to 86 degrees F)
- Store below 86 degrees F
Aloe Vesta:
- Store at room temperature (between 59 to 86 degrees F)
Antifungal:
- Store at room temperature (between 59 to 86 degrees F)
AZOLEN TINCTURE:
- Brief exposure up to 104 degrees F does not adversely affect product
- Protect from freezing
- See package insert for detailed storage information
- 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:
- Store at room temperature (between 59 to 86 degrees F)
Desenex Jock Itch:
- Store between 68 to 77 degrees F
Fungoid:
- Brief exposure up to 104 degrees F does not adversely affect product
- Protect from freezing
- See package insert for detailed storage information
- 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 at room temperature (between 59 to 86 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 (between 59 to 86 degrees F)
Micatin:
- Store at room temperature (between 59 to 86 degrees F)
Miconazole 7:
- Store between 68 to 77 degrees F, excursions permitted 59 to 86 degrees F
Micotrin AP:
- Store at room temperature (between 59 to 86 degrees F)
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 at controlled room temperature (between 68 and 77 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 (between 59 to 86 degrees F)
Mycozyl AP:
- Store at room temperature (between 59 to 86 degrees F)
Neosporin AF:
- Store at room temperature (between 59 to 86 degrees F)
Novana Anti-Fungal:
- Store at room temperature (between 59 to 86 degrees F)
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 (between 59 to 86 degrees F)
Soothe & Cool INZO:
- Store at room temperature (between 59 to 86 degrees F)
Ting Antifungal:
- Do Not Store at Temperatures Above 120 degrees F (49 degrees C)
- Flammable, keep away from heat and flame
- Store between 59 to 77 degrees F
Triple Paste AF :
- Store between 15 to 30 degrees C (59 - 86 degrees F)
Vagistat-3:
- Store between 68 to 77 degrees F, excursions permitted 59 to 86 degrees F
Zeasorb Athlete's Foot:
- Store at room temperature (between 59 to 86 degrees F)
Zeasorb Jock Itch:
- Store at room temperature (between 59 to 86 degrees F)

CONTRAINDICATIONS / PRECAUTIONS

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]

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]

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.

Avoid ocular exposure with topical miconazole administration.[49548]

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]

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

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]

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

anaphylactoid reactions / Rapid / Incidence not known

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

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.
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.
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.
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.
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.
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

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.