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  • CLASSES

    Systemic Dermatological Antifungals

    DEA CLASS

    Rx

    DESCRIPTION

    Oral antifungal antibiotic produced by certain species of Penicillium. Marketed in several formulations to increase bioavailability and decrease GI intolerance. Used for tinea and other fungal infections, including onychomycosis.NOTE: On April 10, 2007, Ortho-McNeil and the FDA informed of a nationwide recall of griseofulvin oral suspension, due to 2 reports of glass fragments found in bottles of this liquid. The recall is limited to this liquid formulation (roughly 100 lots) from this manufacturer and does not include any other dosage form. The voluntary recall is being conducted by Ortho Dermatological, Division of Ortho-McNeil Pharmaceutical, Inc., manufacturer of GRIFULVIN V® and also of griseofulvin oral suspension under the Patriot Pharmaceuticals, L.L.C., label. Consumers should contact their pharmacy to see if they have the product that has been recalled. It is not clear that the recall will cause any shortages.

    COMMON BRAND NAMES

    Fulvicin P/G, Fulvicin U/F, Grifulvin V, Gris-Peg, Grisactin

    HOW SUPPLIED

    Fulvicin P/G/Fulvicin U/F/Grifulvin V/Grisactin/Griseofulvin, Microcrystalline/Griseofulvin, Ultramicrocrystalline/Gris-Peg Oral Tab: 125mg, 250mg, 500mg
    Grifulvin V/Griseofulvin, Microcrystalline Oral Susp: 5mL, 125mg

    DOSAGE & INDICATIONS

    For the treatment of tinea corporis, tinea cruris, tinea capitis, tinea barbae, caused by susceptible strains of Trichophyton sp., Microsporum sp., or Epidermophyton sp..
    Oral dosage
    Adults

    Dosage varies with formulation. FOR ULTRAMICROSIZE: 300 to 375 mg PO given either once daily or in 2 to 4 divided doses per day. FOR MICROSIZE: 500 mg PO given either once daily or in 2 to 4 divided doses per day. Duration of therapy is variable and should continue until organism is completely eradicated. Suggested periods of therapy are 2 to 4 weeks for tinea corporis and 4 to 6 weeks for tinea capitis. For tinea capitis caused by Microspoium canis or Microsporum audouinii, 3000 to 4000 mg PO of microsize griseofulvin as a single dose or in divided doses over 24 hours has been used, with a repeat dose in 3 to 4 weeks if necessary.

    Adolescents and Children greater than 2 years

     Dosage varies with formulation. FOR ULTRAMICROSIZE: 5 to 15 mg/kg/dose PO once daily (Max: 750 mg) is recommended by the American Academy of Pediatrics (AAP). The FDA-approved product label states that 7.3 mg/kg/day PO is usually an effective dose. The manufacturer suggests that children weighing 16 kg to 27 kg receive 125 to 187.5 mg/day PO and that children weighing more than 27 kg receive 187.5 to 375 mg/day PO. FOR MICROSIZE: 10 to 20 mg/kg/day PO in 2 divided doses (Max: 1 g/day) is recommended by AAP. The FDA-approved product label states that 10 mg/kg/day PO is usually an effective dose. The manufacturer suggests that children weighing 14 kg to 23 kg receive 125 to 250 mg/day PO and that children weighing more than 23 kg receive 250 to 500 mg/day PO in divided doses. Duration of therapy is variable and should continue until organism is completely eradicated. Suggested periods of therapy are as follows: tinea corporis, 2 to 4 weeks; tinea capitis, 4 to 6 weeks. For tinea capitis, some experts recommend 6 to 8 weeks (or longer) and use of doses at the upper end of the dosage range. For children, griseofulvin therapy can be difficult to adhere to.

    For the treatment of tinea pedis or tinea unguium (onychomycosis).
    Oral dosage
    Adults

    Dosage varies based on formulation. FOR ULTRAMICROSIZE: 660 to 750 mg PO given either once daily or in 2 to 4 divided doses. FOR MICROSIZE:  750 to 1000 mg PO given either once daily or in 2 to 4 divided doses. Duration of therapy is variable and should continue until organism is completely eradicated. Suggested periods of therapy are as follows: tinea pedis, 4 to 8 weeks; tinea unguium (onychomycosis), of fingernails at least 4 months, of toenails at least 6 months, depending on growth rate.

    Adolescents and Children greater than 2 years

    Dosage varies based on formulation. FOR ULTRAMICROSIZE: 5 to 15 mg/kg/dose PO once daily (Max: 750 mg) is recommended by the American Academy of Pediatrics (AAP). The FDA-approved product label states that 7.3 mg/kg/day PO is usually an effective dose. The manufacturer suggests that children weighing 16 to 27 kg receive 125 to 187.5 mg/day PO and that children weighing more than 27 kg receive 187.5 to 375 mg/day PO. FOR MICROSIZE: 10 to 20 mg/kg/day PO in 2 divided doses (Max: 1 g/day) is recommended by AAP. The FDA-approved product label states that 10 mg/kg/day PO is usually an effective dose. The manufacturer suggests that children weighing 14 to 23 kg receive 125 to 250 mg/day PO and that children weighing more than 23 kg receive 250 to 500 mg/day PO in divided doses. Duration of therapy is variable and should continue until organism is completely eradicated. Suggested periods of therapy are as follows: tinea pedis, 4 to 8 weeks; tinea unguium (onychomycosis), of fingernails at least 4 months, of toenails at least 6 months, depending on growth rate. For children, griseofulvin therapy can be difficult to adhere to.

    MAXIMUM DOSAGE

    Adults

    750 mg daily ultramicrosize griseofulvin PO, or 1 g daily microsize griseofulvin PO is recommended by the manufacturer.

    Geriatric

    750 mg daily ultramicrosize griseofulvin PO, or 1 g daily microsize griseofulvin PO is recommended by the manufacturer.

    Adolescents

    750 mg daily ultramicrosize griseofulvin PO, or 1 g daily microsize griseofulvin PO is recommended by the manufacturer.

    Children

    > 2 years: 15 mg/kg/day PO (Max: 750 mg/day) ultramicrosize griseofulvin or 20 mg/kg/day PO (Max: 1 g/day) microsize griseofulvin.
    <= 2 years: Safety and efficacy have not been established.

    DOSING CONSIDERATIONS

    Hepatic Impairment

    Specific dosage adjustments in hepatic impairment are not available. Griseofulvin does undergo hepatic metabolism; therefore, use with caution in patients with hepatic impairment. Griseofulvin is contraindicated in hepatocellular failure.

    Renal Impairment

    No dosage adjustment needed.

    ADMINISTRATION

    Oral Administration

    Bioavailability varies between microsize and ultramicrosize formulations as well as manufacturers (see Pharmacokinetics).

    Oral Solid Formulations

    Ultramicrosize griseofulvin tablets:
    Administer orally with a fatty meal to increase absorption.
    Tablets can be swallowed whole or crushed and sprinkled onto 1 tablespoonful of applesauce and swallowed immediately without chewing.
    Microsize griseofulvin tablets:
    Administer orally with a fatty meal to increase absorption.

    Oral Liquid Formulations

    Microsize griseofulvin suspension:
    Administer orally with a fatty meal to increase absorption.
    Shake the suspension well prior to administration.

    STORAGE

    Fulvicin P/G:
    - Store at controlled room temperature (between 68 and 77 degrees F)
    Fulvicin U/F:
    - Store at controlled room temperature (between 68 and 77 degrees F)
    Grifulvin V:
    - Store at controlled room temperature (between 68 and 77 degrees F)
    Grisactin:
    - Store at controlled room temperature (between 68 and 77 degrees F)
    Gris-Peg:
    - Store at controlled room temperature (between 68 and 77 degrees F)

    CONTRAINDICATIONS / PRECAUTIONS

    Hepatic disease

    Griseofulvin is contraindicated in patients with hepatocellular failure and should be used cautiously in patients with other hepatic disease. Griseofulvin is hepatically metabolized, and cases of hepatotoxicity (i.e., jaundice, elevated hepatic enzymes, and hyperbilirubinemia) have been associated with its use. Periodically assess both hepatic and renal function during griseofulvin therapy.

    Carbapenem hypersensitivity, cephalosporin hypersensitivity, penicillin hypersensitivity

    Griseofulvin is contraindicated in patients with a previous hypersensitivity to the drug. This hypersensitivity is manifested by urticaria, other rashes, and, rarely, angioedema and a reaction resembling serum sickness. Because griseofulvin is produced by a species of Penicillium, patients with penicillin hypersensitivity theoretically could exhibit a cross-sensitivity to griseofulvin. However, patients with penicillin hypersensitivity have been treated with griseofulvin without adverse affects. Similar warnings may apply to patients with cephalosporin hypersensitivity or carbapenem hypersensitivity because of the structural similarity of cephalosporins and carbapenems to penicillin.

    Systemic lupus erythematosus (SLE)

    Patients with systemic lupus erythematosus (SLE) or lupus-like syndromes should weigh the benefits to risks before taking griseofulvin because it has been known to exacerbate lupus.

    Sunlight (UV) exposure

    Photosensitivity reactions have been reported during griseofulvin therapy. Patients should avoid sunlight (UV) exposure via intense natural or artificial sunlight. Protective clothing and sunscreens should be used.

    Porphyria

    Griseofulvin is contraindicated in patients with porphyria. The drug interferes with porphyrin metabolism, and chronic administration of griseofulvin can result in elevated concentrations of porphyrins in both feces and erythrocytes. This may precipitate an attack of acute intermittent porphyria in susceptible patients.

    Pregnancy

    Due to possible teratogenic and abortifacient effects, use of griseofulvin during pregnancy is contraindicated. Since 1977, 2 cases of conjoined twins have been reported following first trimester use of griseofulvin. In both cases, surveillance by the FDA found griseofulvin use to be the only maternal drug exposure. In addition to congenital abnormalities, some women who received the drug during pregnancy have experienced spontaneous abortions. An analysis of data from 4,264 spontaneous abortions between 1980 and 1983 revealed 7 women exposed to griseofulvin within the preceding 3 months (RR = 2.5, 95% CI 1.01, 6.1). Pregnant women and women of childbearing age who may become pregnant should be notified of the potential risk to the fetus. Instruct women to use appropriate contraception both during and for 1 month after completing of griseofulvin therapy. Men are advised to wait 6 month after completing griseofulvin therapy before fathering a child. Of note, concurrent use has resulted in reduced oral contraceptive efficacy.  

    Breast-feeding

    Data are limited regarding the use of griseofulvin during breast-feeding and it is not known if it is excreted in human breast milk. Due to the potential for adverse effects in a nursing infant, use in a breast-feeding mother is not recommended. Consider the benefits of breast-feeding, the risk of potential infant drug exposure, and the risk of an untreated or inadequately treated condition. If a breast-feeding infant experiences an adverse effect related to a maternally ingested drug, healthcare providers are encouraged to report the adverse effect to the FDA.

    Serious rash

    Treatment with griseofulvin has been associated with the development of severe dermatologic adverse reactions, including Stevens-Johnson syndrome, toxic epidermal necrolysis, and erythema multiforme. Some of these adverse events may result in hospitalization or death. If a serious rash develops, discontinue use of the drug.

    New primary malignancy

    Griseofulvin has been associated with new primary malignancy (hepatic and thyroid tumors) in mice receiving chronic oral administration of this drug. Studies in other animal species are inadequate to assess the risk for tumorigenicity.

    ADVERSE REACTIONS

    Severe

    Stevens-Johnson syndrome / Delayed / Incidence not known
    lupus-like symptoms / Delayed / Incidence not known
    toxic epidermal necrolysis / Delayed / Incidence not known
    angioedema / Rapid / Incidence not known
    erythema multiforme / Delayed / Incidence not known
    GI bleeding / Delayed / Incidence not known
    coagulopathy / Delayed / Incidence not known
    proteinuria / Delayed / Incidence not known
    teratogenesis / Delayed / Incidence not known

    Moderate

    peripheral neuropathy / Delayed / Incidence not known
    confusion / Early / Incidence not known
    candidiasis / Delayed / Incidence not known
    elevated hepatic enzymes / Delayed / Incidence not known
    hepatitis / Delayed / Incidence not known
    hyperbilirubinemia / Delayed / Incidence not known
    jaundice / Delayed / Incidence not known
    leukopenia / Delayed / Incidence not known
    neutropenia / Delayed / Incidence not known

    Mild

    dizziness / Early / Incidence not known
    headache / Early / Incidence not known
    insomnia / Early / Incidence not known
    fatigue / Early / Incidence not known
    paresthesias / Delayed / Incidence not known
    diarrhea / Early / Incidence not known
    abdominal pain / Early / Incidence not known
    vomiting / Early / Incidence not known
    nausea / Early / Incidence not known
    rash / Early / Incidence not known
    photosensitivity / Delayed / Incidence not known
    urticaria / Rapid / Incidence not known

    DRUG INTERACTIONS

    Acetaminophen; Aspirin, ASA; Caffeine: (Moderate) Concurrent administration of griseofulvin with salicylates may result in decreased salicylate serum concentrations. Caution and close monitoring for changes in the effectiveness of the salicylate are recommended.
    Acetaminophen; Caffeine; Magnesium Salicylate; Phenyltoloxamine: (Moderate) Concurrent administration of griseofulvin with salicylates may result in decreased salicylate serum concentrations. Caution and close monitoring for changes in the effectiveness of the salicylate are recommended.
    Acetaminophen; Caffeine; Phenyltoloxamine; Salicylamide: (Moderate) Concurrent administration of griseofulvin with salicylates may result in decreased salicylate serum concentrations. Caution and close monitoring for changes in the effectiveness of the salicylate are recommended.
    Aminosalicylate sodium, Aminosalicylic acid: (Moderate) Concurrent administration of griseofulvin with salicylates may result in decreased salicylate serum concentrations. Caution and close monitoring for changes in the effectiveness of the salicylate are recommended.
    Aspirin, ASA: (Moderate) Concurrent administration of griseofulvin with salicylates may result in decreased salicylate serum concentrations. Caution and close monitoring for changes in the effectiveness of the salicylate are recommended.
    Aspirin, ASA; Butalbital; Caffeine: (Moderate) Concurrent administration of griseofulvin with salicylates may result in decreased salicylate serum concentrations. Caution and close monitoring for changes in the effectiveness of the salicylate are recommended.
    Aspirin, ASA; Butalbital; Caffeine; Codeine: (Moderate) Concurrent administration of griseofulvin with salicylates may result in decreased salicylate serum concentrations. Caution and close monitoring for changes in the effectiveness of the salicylate are recommended.
    Aspirin, ASA; Caffeine; Dihydrocodeine: (Moderate) Concurrent administration of griseofulvin with salicylates may result in decreased salicylate serum concentrations. Caution and close monitoring for changes in the effectiveness of the salicylate are recommended.
    Aspirin, ASA; Carisoprodol: (Moderate) Concurrent administration of griseofulvin with salicylates may result in decreased salicylate serum concentrations. Caution and close monitoring for changes in the effectiveness of the salicylate are recommended.
    Aspirin, ASA; Carisoprodol; Codeine: (Moderate) Concurrent administration of griseofulvin with salicylates may result in decreased salicylate serum concentrations. Caution and close monitoring for changes in the effectiveness of the salicylate are recommended.
    Aspirin, ASA; Dipyridamole: (Moderate) Concurrent administration of griseofulvin with salicylates may result in decreased salicylate serum concentrations. Caution and close monitoring for changes in the effectiveness of the salicylate are recommended.
    Aspirin, ASA; Omeprazole: (Moderate) Concurrent administration of griseofulvin with salicylates may result in decreased salicylate serum concentrations. Caution and close monitoring for changes in the effectiveness of the salicylate are recommended.
    Aspirin, ASA; Oxycodone: (Moderate) Concurrent administration of griseofulvin with salicylates may result in decreased salicylate serum concentrations. Caution and close monitoring for changes in the effectiveness of the salicylate are recommended.
    Aspirin, ASA; Pravastatin: (Moderate) Concurrent administration of griseofulvin with salicylates may result in decreased salicylate serum concentrations. Caution and close monitoring for changes in the effectiveness of the salicylate are recommended.
    Atropine; Benzoic Acid; Hyoscyamine; Methenamine; Methylene Blue; Phenyl Salicylate: (Moderate) Concurrent administration of griseofulvin with salicylates may result in decreased salicylate serum concentrations. Caution and close monitoring for changes in the effectiveness of the salicylate are recommended.
    Barbiturates: (Minor) Barbiturates can impair the oral absorption of griseofulvin, resulting in decreased serum concentrations and, potentially, decreased antifungal efficacy. The clinical significance of this interaction is uncertain, but the manufacturer recommends that these drugs not be co-administered.
    Benzoic Acid; Hyoscyamine; Methenamine; Methylene Blue; Phenyl Salicylate: (Moderate) Concurrent administration of griseofulvin with salicylates may result in decreased salicylate serum concentrations. Caution and close monitoring for changes in the effectiveness of the salicylate are recommended.
    Bismuth Subsalicylate: (Moderate) Concurrent administration of griseofulvin with salicylates may result in decreased salicylate serum concentrations. Caution and close monitoring for changes in the effectiveness of the salicylate are recommended.
    Bismuth Subsalicylate; Metronidazole; Tetracycline: (Moderate) Concurrent administration of griseofulvin with salicylates may result in decreased salicylate serum concentrations. Caution and close monitoring for changes in the effectiveness of the salicylate are recommended.
    Budesonide: (Moderate) Theoretically, induction of the cytochrome P450 3A4 isoenzyme by griseofulvin may result in a lowering of budesonide plasma concentrations, reducing the clinical effect.
    Budesonide; Formoterol: (Moderate) Theoretically, induction of the cytochrome P450 3A4 isoenzyme by griseofulvin may result in a lowering of budesonide plasma concentrations, reducing the clinical effect.
    Choline Salicylate; Magnesium Salicylate: (Moderate) Concurrent administration of griseofulvin with salicylates may result in decreased salicylate serum concentrations. Caution and close monitoring for changes in the effectiveness of the salicylate are recommended.
    Conjugated Estrogens: (Moderate) Concomitant use of griseofulvin and oral contraceptives has been reported to reduce the efficacy of the oral contraceptive and cause breakthrough bleeding. Patients who experience breakthrough bleeding while receiving these drugs together should notify their prescribers. An alternate or additional form of contraception should be used during concomitant treatment and should be continued for 1 month after griseofulvin discontinuation. Additionally, patients taking non-oral combination contraceptives, estrogens, or progestins for hormone replacement therapy may also experience reduced clinical efficacy; dosage adjustments may be necessary.
    Conjugated Estrogens; Bazedoxifene: (Moderate) Concomitant use of griseofulvin and oral contraceptives has been reported to reduce the efficacy of the oral contraceptive and cause breakthrough bleeding. Patients who experience breakthrough bleeding while receiving these drugs together should notify their prescribers. An alternate or additional form of contraception should be used during concomitant treatment and should be continued for 1 month after griseofulvin discontinuation. Additionally, patients taking non-oral combination contraceptives, estrogens, or progestins for hormone replacement therapy may also experience reduced clinical efficacy; dosage adjustments may be necessary.
    Conjugated Estrogens; Medroxyprogesterone: (Moderate) Concomitant use of griseofulvin and oral contraceptives has been reported to reduce the efficacy of the oral contraceptive and cause breakthrough bleeding. Patients who experience breakthrough bleeding while receiving these drugs together should notify their prescribers. An alternate or additional form of contraception should be used during concomitant treatment and should be continued for 1 month after griseofulvin discontinuation. Additionally, patients taking non-oral combination contraceptives, estrogens, or progestins for hormone replacement therapy may also experience reduced clinical efficacy; dosage adjustments may be necessary.
    Cyclosporine: (Moderate) Griseofulvin has been reported to reduce cyclosporine serum concentrations. Although very few reports of this interaction are known, the sequelae from this combination are significant. Closely monitor cyclosporine levels during concurrent treatment with griseofulvin. An increase in cyclosporine dose may be necessary if griseofulvin is added. The cyclosporine dosage may need to decreased if griseofulvin is discontinued.
    Dichlorphenamide: (Moderate) Use dichlorphenamide and griseofulvin together with caution. Dichlorphenamide increases potassium excretion and can cause hypokalemia and should be used cautiously with other drugs that may cause hypokalemia including antifungals. Measure potassium concentrations at baseline and periodically during dichlorphenamide treatment. If hypokalemia occurs or persists, consider reducing the dichlorphenamide dose or discontinuing dichlorphenamide therapy.
    Dienogest; Estradiol valerate: (Moderate) Concomitant use of griseofulvin and oral contraceptives has been reported to reduce the efficacy of the oral contraceptive and cause breakthrough bleeding. Patients who experience breakthrough bleeding while receiving these drugs together should notify their prescribers. An alternate or additional form of contraception should be used during concomitant treatment and should be continued for 1 month after griseofulvin discontinuation. Additionally, patients taking non-oral combination contraceptives, estrogens, or progestins for hormone replacement therapy may also experience reduced clinical efficacy; dosage adjustments may be necessary.
    Diethylstilbestrol, DES: (Moderate) Concomitant use of griseofulvin and oral contraceptives has been reported to reduce the efficacy of the oral contraceptive and cause breakthrough bleeding. Patients who experience breakthrough bleeding while receiving these drugs together should notify their prescribers. An alternate or additional form of contraception should be used during concomitant treatment and should be continued for 1 month after griseofulvin discontinuation. Additionally, patients taking non-oral combination contraceptives, estrogens, or progestins for hormone replacement therapy may also experience reduced clinical efficacy; dosage adjustments may be necessary.
    Drospirenone; Estradiol: (Moderate) Concomitant use of griseofulvin and oral contraceptives has been reported to reduce the efficacy of the oral contraceptive and cause breakthrough bleeding. Patients who experience breakthrough bleeding while receiving these drugs together should notify their prescribers. An alternate or additional form of contraception should be used during concomitant treatment and should be continued for 1 month after griseofulvin discontinuation. Additionally, patients taking non-oral combination contraceptives, estrogens, or progestins for hormone replacement therapy may also experience reduced clinical efficacy; dosage adjustments may be necessary.
    Drospirenone; Ethinyl Estradiol: (Moderate) Concomitant use of griseofulvin and oral contraceptives has been reported to reduce the efficacy of the oral contraceptive and cause breakthrough bleeding. Patients who experience breakthrough bleeding while receiving these drugs together should notify their prescribers. An alternate or additional form of contraception should be used during concomitant treatment and should be continued for 1 month after griseofulvin discontinuation. Additionally, patients taking non-oral combination contraceptives, estrogens, or progestins for hormone replacement therapy may also experience reduced clinical efficacy; dosage adjustments may be necessary.
    Drospirenone; Ethinyl Estradiol; Levomefolate: (Moderate) Concomitant use of griseofulvin and oral contraceptives has been reported to reduce the efficacy of the oral contraceptive and cause breakthrough bleeding. Patients who experience breakthrough bleeding while receiving these drugs together should notify their prescribers. An alternate or additional form of contraception should be used during concomitant treatment and should be continued for 1 month after griseofulvin discontinuation. Additionally, patients taking non-oral combination contraceptives, estrogens, or progestins for hormone replacement therapy may also experience reduced clinical efficacy; dosage adjustments may be necessary.
    Esterified Estrogens: (Moderate) Concomitant use of griseofulvin and oral contraceptives has been reported to reduce the efficacy of the oral contraceptive and cause breakthrough bleeding. Patients who experience breakthrough bleeding while receiving these drugs together should notify their prescribers. An alternate or additional form of contraception should be used during concomitant treatment and should be continued for 1 month after griseofulvin discontinuation. Additionally, patients taking non-oral combination contraceptives, estrogens, or progestins for hormone replacement therapy may also experience reduced clinical efficacy; dosage adjustments may be necessary.
    Esterified Estrogens; Methyltestosterone: (Moderate) Concomitant use of griseofulvin and oral contraceptives has been reported to reduce the efficacy of the oral contraceptive and cause breakthrough bleeding. Patients who experience breakthrough bleeding while receiving these drugs together should notify their prescribers. An alternate or additional form of contraception should be used during concomitant treatment and should be continued for 1 month after griseofulvin discontinuation. Additionally, patients taking non-oral combination contraceptives, estrogens, or progestins for hormone replacement therapy may also experience reduced clinical efficacy; dosage adjustments may be necessary.
    Estradiol Cypionate; Medroxyprogesterone: (Moderate) Concomitant use of griseofulvin and oral contraceptives has been reported to reduce the efficacy of the oral contraceptive and cause breakthrough bleeding. Patients who experience breakthrough bleeding while receiving these drugs together should notify their prescribers. An alternate or additional form of contraception should be used during concomitant treatment and should be continued for 1 month after griseofulvin discontinuation. Additionally, patients taking non-oral combination contraceptives, estrogens, or progestins for hormone replacement therapy may also experience reduced clinical efficacy; dosage adjustments may be necessary.
    Estradiol: (Moderate) Concomitant use of griseofulvin and oral contraceptives has been reported to reduce the efficacy of the oral contraceptive and cause breakthrough bleeding. Patients who experience breakthrough bleeding while receiving these drugs together should notify their prescribers. An alternate or additional form of contraception should be used during concomitant treatment and should be continued for 1 month after griseofulvin discontinuation. Additionally, patients taking non-oral combination contraceptives, estrogens, or progestins for hormone replacement therapy may also experience reduced clinical efficacy; dosage adjustments may be necessary.
    Estradiol; Levonorgestrel: (Moderate) Concomitant use of griseofulvin and oral contraceptives has been reported to reduce the efficacy of the oral contraceptive and cause breakthrough bleeding. Patients who experience breakthrough bleeding while receiving these drugs together should notify their prescribers. An alternate or additional form of contraception should be used during concomitant treatment and should be continued for 1 month after griseofulvin discontinuation. Additionally, patients taking non-oral combination contraceptives, estrogens, or progestins for hormone replacement therapy may also experience reduced clinical efficacy; dosage adjustments may be necessary.
    Estradiol; Norethindrone: (Moderate) Concomitant use of griseofulvin and oral contraceptives has been reported to reduce the efficacy of the oral contraceptive and cause breakthrough bleeding. Patients who experience breakthrough bleeding while receiving these drugs together should notify their prescribers. An alternate or additional form of contraception should be used during concomitant treatment and should be continued for 1 month after griseofulvin discontinuation. Additionally, patients taking non-oral combination contraceptives, estrogens, or progestins for hormone replacement therapy may also experience reduced clinical efficacy; dosage adjustments may be necessary.
    Estradiol; Norgestimate: (Moderate) Concomitant use of griseofulvin and oral contraceptives has been reported to reduce the efficacy of the oral contraceptive and cause breakthrough bleeding. Patients who experience breakthrough bleeding while receiving these drugs together should notify their prescribers. An alternate or additional form of contraception should be used during concomitant treatment and should be continued for 1 month after griseofulvin discontinuation. Additionally, patients taking non-oral combination contraceptives, estrogens, or progestins for hormone replacement therapy may also experience reduced clinical efficacy; dosage adjustments may be necessary.
    Estrogens: (Moderate) Concomitant use of griseofulvin and oral contraceptives has been reported to reduce the efficacy of the oral contraceptive and cause breakthrough bleeding. Patients who experience breakthrough bleeding while receiving these drugs together should notify their prescribers. An alternate or additional form of contraception should be used during concomitant treatment and should be continued for 1 month after griseofulvin discontinuation. Additionally, patients taking non-oral combination contraceptives, estrogens, or progestins for hormone replacement therapy may also experience reduced clinical efficacy; dosage adjustments may be necessary.
    Estropipate: (Moderate) Concomitant use of griseofulvin and oral contraceptives has been reported to reduce the efficacy of the oral contraceptive and cause breakthrough bleeding. Patients who experience breakthrough bleeding while receiving these drugs together should notify their prescribers. An alternate or additional form of contraception should be used during concomitant treatment and should be continued for 1 month after griseofulvin discontinuation. Additionally, patients taking non-oral combination contraceptives, estrogens, or progestins for hormone replacement therapy may also experience reduced clinical efficacy; dosage adjustments may be necessary.
    Ethanol: (Moderate) Some of ethanol's effects can be increased by griseofulvin. Patients can experience tachycardia, diaphoresis, and flushing. (Moderate) Some of ethanol's effects can be increased by griseofulvin. Patients can experience tachycardia, diaphoresis, and flushing.
    Ethinyl Estradiol: (Moderate) Concomitant use of griseofulvin and oral contraceptives has been reported to reduce the efficacy of the oral contraceptive and cause breakthrough bleeding. Patients who experience breakthrough bleeding while receiving these drugs together should notify their prescribers. An alternate or additional form of contraception should be used during concomitant treatment and should be continued for 1 month after griseofulvin discontinuation. Additionally, patients taking non-oral combination contraceptives, estrogens, or progestins for hormone replacement therapy may also experience reduced clinical efficacy; dosage adjustments may be necessary.
    Ethinyl Estradiol; Desogestrel: (Moderate) Concomitant use of griseofulvin and oral contraceptives has been reported to reduce the efficacy of the oral contraceptive and cause breakthrough bleeding. Patients who experience breakthrough bleeding while receiving these drugs together should notify their prescribers. An alternate or additional form of contraception should be used during concomitant treatment and should be continued for 1 month after griseofulvin discontinuation. Additionally, patients taking non-oral combination contraceptives, estrogens, or progestins for hormone replacement therapy may also experience reduced clinical efficacy; dosage adjustments may be necessary.
    Ethinyl Estradiol; Ethynodiol Diacetate: (Moderate) Concomitant use of griseofulvin and oral contraceptives has been reported to reduce the efficacy of the oral contraceptive and cause breakthrough bleeding. Patients who experience breakthrough bleeding while receiving these drugs together should notify their prescribers. An alternate or additional form of contraception should be used during concomitant treatment and should be continued for 1 month after griseofulvin discontinuation. Additionally, patients taking non-oral combination contraceptives, estrogens, or progestins for hormone replacement therapy may also experience reduced clinical efficacy; dosage adjustments may be necessary.
    Ethinyl Estradiol; Etonogestrel: (Moderate) Concomitant use of griseofulvin and oral contraceptives has been reported to reduce the efficacy of the oral contraceptive and cause breakthrough bleeding. Patients who experience breakthrough bleeding while receiving these drugs together should notify their prescribers. An alternate or additional form of contraception should be used during concomitant treatment and should be continued for 1 month after griseofulvin discontinuation. Additionally, patients taking non-oral combination contraceptives, estrogens, or progestins for hormone replacement therapy may also experience reduced clinical efficacy; dosage adjustments may be necessary.
    Ethinyl Estradiol; Levonorgestrel: (Moderate) Concomitant use of griseofulvin and oral contraceptives has been reported to reduce the efficacy of the oral contraceptive and cause breakthrough bleeding. Patients who experience breakthrough bleeding while receiving these drugs together should notify their prescribers. An alternate or additional form of contraception should be used during concomitant treatment and should be continued for 1 month after griseofulvin discontinuation. Additionally, patients taking non-oral combination contraceptives, estrogens, or progestins for hormone replacement therapy may also experience reduced clinical efficacy; dosage adjustments may be necessary.
    Ethinyl Estradiol; Levonorgestrel; Ferrous bisglycinate: (Moderate) Concomitant use of griseofulvin and oral contraceptives has been reported to reduce the efficacy of the oral contraceptive and cause breakthrough bleeding. Patients who experience breakthrough bleeding while receiving these drugs together should notify their prescribers. An alternate or additional form of contraception should be used during concomitant treatment and should be continued for 1 month after griseofulvin discontinuation. Additionally, patients taking non-oral combination contraceptives, estrogens, or progestins for hormone replacement therapy may also experience reduced clinical efficacy; dosage adjustments may be necessary.
    Ethinyl Estradiol; Levonorgestrel; Folic Acid; Levomefolate: (Moderate) Concomitant use of griseofulvin and oral contraceptives has been reported to reduce the efficacy of the oral contraceptive and cause breakthrough bleeding. Patients who experience breakthrough bleeding while receiving these drugs together should notify their prescribers. An alternate or additional form of contraception should be used during concomitant treatment and should be continued for 1 month after griseofulvin discontinuation. Additionally, patients taking non-oral combination contraceptives, estrogens, or progestins for hormone replacement therapy may also experience reduced clinical efficacy; dosage adjustments may be necessary.
    Ethinyl Estradiol; Norelgestromin: (Moderate) Concomitant use of griseofulvin and oral contraceptives has been reported to reduce the efficacy of the oral contraceptive and cause breakthrough bleeding. Patients who experience breakthrough bleeding while receiving these drugs together should notify their prescribers. An alternate or additional form of contraception should be used during concomitant treatment and should be continued for 1 month after griseofulvin discontinuation. Additionally, patients taking non-oral combination contraceptives, estrogens, or progestins for hormone replacement therapy may also experience reduced clinical efficacy; dosage adjustments may be necessary.
    Ethinyl Estradiol; Norethindrone Acetate: (Moderate) Concomitant use of griseofulvin and oral contraceptives has been reported to reduce the efficacy of the oral contraceptive and cause breakthrough bleeding. Patients who experience breakthrough bleeding while receiving these drugs together should notify their prescribers. An alternate or additional form of contraception should be used during concomitant treatment and should be continued for 1 month after griseofulvin discontinuation. Additionally, patients taking non-oral combination contraceptives, estrogens, or progestins for hormone replacement therapy may also experience reduced clinical efficacy; dosage adjustments may be necessary.
    Ethinyl Estradiol; Norethindrone Acetate; Ferrous fumarate: (Moderate) Concomitant use of griseofulvin and oral contraceptives has been reported to reduce the efficacy of the oral contraceptive and cause breakthrough bleeding. Patients who experience breakthrough bleeding while receiving these drugs together should notify their prescribers. An alternate or additional form of contraception should be used during concomitant treatment and should be continued for 1 month after griseofulvin discontinuation. Additionally, patients taking non-oral combination contraceptives, estrogens, or progestins for hormone replacement therapy may also experience reduced clinical efficacy; dosage adjustments may be necessary.
    Ethinyl Estradiol; Norethindrone: (Moderate) Concomitant use of griseofulvin and oral contraceptives has been reported to reduce the efficacy of the oral contraceptive and cause breakthrough bleeding. Patients who experience breakthrough bleeding while receiving these drugs together should notify their prescribers. An alternate or additional form of contraception should be used during concomitant treatment and should be continued for 1 month after griseofulvin discontinuation. Additionally, patients taking non-oral combination contraceptives, estrogens, or progestins for hormone replacement therapy may also experience reduced clinical efficacy; dosage adjustments may be necessary.
    Ethinyl Estradiol; Norethindrone; Ferrous fumarate: (Moderate) Concomitant use of griseofulvin and oral contraceptives has been reported to reduce the efficacy of the oral contraceptive and cause breakthrough bleeding. Patients who experience breakthrough bleeding while receiving these drugs together should notify their prescribers. An alternate or additional form of contraception should be used during concomitant treatment and should be continued for 1 month after griseofulvin discontinuation. Additionally, patients taking non-oral combination contraceptives, estrogens, or progestins for hormone replacement therapy may also experience reduced clinical efficacy; dosage adjustments may be necessary.
    Ethinyl Estradiol; Norgestimate: (Moderate) Concomitant use of griseofulvin and oral contraceptives has been reported to reduce the efficacy of the oral contraceptive and cause breakthrough bleeding. Patients who experience breakthrough bleeding while receiving these drugs together should notify their prescribers. An alternate or additional form of contraception should be used during concomitant treatment and should be continued for 1 month after griseofulvin discontinuation. Additionally, patients taking non-oral combination contraceptives, estrogens, or progestins for hormone replacement therapy may also experience reduced clinical efficacy; dosage adjustments may be necessary.
    Ethinyl Estradiol; Norgestrel: (Moderate) Concomitant use of griseofulvin and oral contraceptives has been reported to reduce the efficacy of the oral contraceptive and cause breakthrough bleeding. Patients who experience breakthrough bleeding while receiving these drugs together should notify their prescribers. An alternate or additional form of contraception should be used during concomitant treatment and should be continued for 1 month after griseofulvin discontinuation. Additionally, patients taking non-oral combination contraceptives, estrogens, or progestins for hormone replacement therapy may also experience reduced clinical efficacy; dosage adjustments may be necessary.
    Food: (Moderate) Food can affect the oral bioavailability of griseofulvin. Microsize griseofulvin absorption may be enhanced by concomitant intake of a high-fat meal, but results have been variable.
    Hyoscyamine; Methenamine; Methylene Blue; Phenyl Salicylate; Sodium Biphosphate: (Moderate) Concurrent administration of griseofulvin with salicylates may result in decreased salicylate serum concentrations. Caution and close monitoring for changes in the effectiveness of the salicylate are recommended.
    Magnesium Salicylate: (Moderate) Concurrent administration of griseofulvin with salicylates may result in decreased salicylate serum concentrations. Caution and close monitoring for changes in the effectiveness of the salicylate are recommended.
    Mestranol; Norethindrone: (Moderate) Concomitant use of griseofulvin and oral contraceptives has been reported to reduce the efficacy of the oral contraceptive and cause breakthrough bleeding. Patients who experience breakthrough bleeding while receiving these drugs together should notify their prescribers. An alternate or additional form of contraception should be used during concomitant treatment and should be continued for 1 month after griseofulvin discontinuation. Additionally, patients taking non-oral combination contraceptives, estrogens, or progestins for hormone replacement therapy may also experience reduced clinical efficacy; dosage adjustments may be necessary.
    Methoxsalen: (Moderate) Use methoxsalen and griseofulvin together with caution; the risk of severe burns/photosensitivity may be additive. If concurrent use is necessary, closely monitor patients for signs or symptoms of skin toxicity.
    Perampanel: (Major) Start perampanel at a higher initial dose of 4 mg once daily at bedtime when using concurrently with griseofulvin due to a potential reduction in perampanel plasma concentration. If introduction or withdrawal of griseofulvin occurs during perampanel therapy, closely monitor patient response; a dosage adjustment may be necessary. Griseofulvin is a CYP3A4 inducer, and perampanel is a CYP3A4 substrate.
    Photosensitizing agents: (Moderate) Use photosenitizing agents and griseofulvin together with caution; the risk of severe burns/photosensitivity may be additive. If concurrent use is necessary, closely monitor patients for signs or symptoms of skin toxicity.
    Progestins: (Major) The concurrent use of griseofulvin and oral contraceptives can reduce contraceptive efficacy and result in an unintended pregnancy and/or breakthrough bleeding. This risk is particularly serious because griseofulvin is contraindicated during pregnancy due to the risk of teratogenic and abortifacient effects. An alternate or additional form of contraception should be used during concomitant treatment and continued for 1 month after griseofulvin discontinuation. If these drugs are used together, counsel the patient about the risk of pregnancy and teratogenic effects, and instruct the patient to notify the prescriber if they experience breakthrough bleeding while receiving these drugs together. Additionally, patients taking non-oral combination contraceptives or progestins for hormone replacement therapy may also experience reduced clinical efficacy.
    Rivaroxaban: (Minor) Coadministration of rivaroxaban and griseofulvin may result in decreased rivaroxaban exposure and may decrease the efficacy of rivaroxaban. Griseofulvin is an inducer of CYP3A4, and rivaroxaban is a substrate of CYP3A4. If these drugs are administered concurrently, monitor the patient for signs of lack of efficacy of rivaroxaban.
    Saccharomyces boulardii: (Major) Because Saccharomyces boulardii is an active yeast, it would be expected to be inactivated by any antifungals. The manufacturer does not recommend taking in conjunction with any antifungal agents. Patients should avoid use of this probiotic yeast until the fungal or yeast infection is completely treated.
    Salicylates: (Moderate) Concurrent administration of griseofulvin with salicylates may result in decreased salicylate serum concentrations. Caution and close monitoring for changes in the effectiveness of the salicylate are recommended.
    Salsalate: (Moderate) Concurrent administration of griseofulvin with salicylates may result in decreased salicylate serum concentrations. Caution and close monitoring for changes in the effectiveness of the salicylate are recommended.
    Sulfonylureas: (Moderate) Additive photosensitization may be seen with concurrent administration of sulfonylureas and other photosensitizing agents including griseofulvin. Prevention of photosensitivity includes adequate protection from sources of UV radiation (e.g., avoiding sun exposure and tanning booths) and the use of protective clothing and sunscreens on exposed skin.
    Tazarotene: (Moderate) The manufacturer states that tazarotene should be administered with caution in patients who are also taking drugs known to be photosensitizers, such as griseofulvin, as concomitant use may augment phototoxicity. Patients should take care and use proper techniques to limit sunlight and UV exposure of treated areas.
    Tretinoin, ATRA: (Moderate) Griseofulvin may increase the CYP450 metabolism of tretinoin, ATRA, potentially resulting in decreased plasma concentrations of tretinoin, ATRA. No specific studies have been done with oral tretinoin and griseofulvin, however, patients should be closely monitored for decreased clinical effects of tretinoin, ATRA while receiving concomitant therapy. Additionally, a manufacturer of topical tretinoin states that tretinoin, ATRA should be administered with caution in patients who are also taking drugs known to be photosensitizers, such as griseofulvin, as concomitant use may augment phototoxicity. Patients should take care and use proper techniques to limit sunlight and UV exposure of treated areas.
    Ulipristal: (Major) Avoid administration of ulipristal with drugs that induce CYP3A4. Ulipristal is a substrate of CYP3A4 and griseofulvin is a CYP3A4 inducer. Concomitant use may decrease the plasma concentration and effectiveness of ulipristal.
    Warfarin: (Major) The anticoagulant effect of warfarin can be decreased if griseofulvin is used concurrently. The griseofulvin-warfarin drug interaction is one of the most well-documented warfarin drug interactions. The mechanism of this interaction is unclear. It is commonly believed that griseofulvin enhances the hepatic metabolism of warfarin. The interaction between warfarin and griseofulvin may require up to 12 weeks to fully manifest and may be more significant with the ultramicrocrystalline formulation of griseofulvin. The international normalized ratio (INR) should be monitored closely if griseofulvin is either added to or discontinued from warfarin therapy.

    PREGNANCY AND LACTATION

    Pregnancy

    Due to possible teratogenic and abortifacient effects, use of griseofulvin during pregnancy is contraindicated. Since 1977, 2 cases of conjoined twins have been reported following first trimester use of griseofulvin. In both cases, surveillance by the FDA found griseofulvin use to be the only maternal drug exposure. In addition to congenital abnormalities, some women who received the drug during pregnancy have experienced spontaneous abortions. An analysis of data from 4,264 spontaneous abortions between 1980 and 1983 revealed 7 women exposed to griseofulvin within the preceding 3 months (RR = 2.5, 95% CI 1.01, 6.1). Pregnant women and women of childbearing age who may become pregnant should be notified of the potential risk to the fetus. Instruct women to use appropriate contraception both during and for 1 month after completing of griseofulvin therapy. Men are advised to wait 6 month after completing griseofulvin therapy before fathering a child. Of note, concurrent use has resulted in reduced oral contraceptive efficacy.  

    Data are limited regarding the use of griseofulvin during breast-feeding and it is not known if it is excreted in human breast milk. Due to the potential for adverse effects in a nursing infant, use in a breast-feeding mother is not recommended. Consider the benefits of breast-feeding, the risk of potential infant drug exposure, and the risk of an untreated or inadequately treated condition. If a breast-feeding infant experiences an adverse effect related to a maternally ingested drug, healthcare providers are encouraged to report the adverse effect to the FDA.

    MECHANISM OF ACTION

    Griseofulvin exerts its fungistatic activity primarily by disrupting the mitotic spindle structure of the fungal cell, which causes an arrest of metaphase of cell division. The result is similar to the effect colchicine has on mitosis, albeit by a different mechanism of action. Griseofulvin also may produce defective DNA that is unable to replicate. Griseofulvin is effective in the treatment of superficial dermatophyte infections because it is deposited in keratin precursor cells, creating an unfavorable environment for fungal infection. Infected skin, cells, and hair are then slowly replaced by tissue that is not infected by the dermatophyte. Griseofulvin also possesses a direct vasodilatory effect.

    PHARMACOKINETICS

    Griseofulvin is administered orally. Griseofulvin concentrates in the skin, hair, nails, fat, and skeletal muscles. It deposits in keratin precursor cells and is tightly bound to new keratin. Concentrations increase rapidly after the first dose and rapidly decrease to undetectable levels after discontinuation. Griseofulvin undergoes hepatic metabolism, mainly through oxidative demethylation and conjugation with glucuronic acid. The major metabolite, 6-desmethylgriseofulvin, is inactive. The half-life is 9—24 hours. Griseofulvin is excreted through the urine, feces, and perspiration.
     
    Affected cytochrome P450 isoenzymes: CYP3A4
    In vitro data suggest that griseofulvin may induce the CYP3A4 isoenzyme.

    Oral Route

    Oral griseofulvin is absorbed mainly from the duodenum. Griseofulvin is marketed in several oral formulations in an attempt to increase bioavailability and decrease GI intolerance. Ultramicrosize griseofulvin has almost complete absorption, while microsize griseofulvin has a variable (25—70%) and unpredictable oral absorption. Peak serum concentrations of 0.4—2 mcg/ml are attained 4—8 hours after administration of 500 mg of microsize griseofulvin or 250 mg of ultramicrosize griseofulvin in fasting patients. Microsize griseofulvin absorption may be enhanced by concomitant intake of a high-fat meal, but results have been variable.

    Topical Route

    Griseofulvin does not penetrate the skin well enough to be administered topically.