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Griseofulvin

Pronunciation

Class: Antifungals, Miscellaneous
VA Class: AM700
CAS Number: 126-07-8
Brands: Grifulvin V, Gris-PEG

Introduction

Antifungal antibiotic produced by Penicillium.104 125

Uses for Griseofulvin

Dermatophytoses

Treatment of dermatophytoses of the skin, scalp, and nails, including tinea barbae (ringworm of bearded areas of face and neck), tinea capitis (scalp ringworm), tinea corporis (ringworm of the body), tinea cruris (jock itch; groin ringworm), tinea pedis (athlete’s foot, foot ringworm), and tinea unguium (onychomycosis; nail ringworm) caused by Trichophyton, Microsporum, or Epidermophyton floccosum.104 125

A drug of choice for treatment of tinea capitis;124 131 132 133 135 140 141 prolonged therapy usually is necessary to cure the infection and poor compliance may affect response to the drug.131 135 138 140 141 Tinea barbae and tinea capitis generally require treatment with an oral antifungal.124 131 135 137 140

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Tinea corporis and tinea cruris generally can be effectively treated using a topical antifungal; an oral antifungal may be necessary if the disease is extensive, dermatophyte folliculitis is present, the infection does not respond to topical therapy, or the patient is immunocompromised or has coexisting disease (e.g., diabetes mellitus).124 130 131 132 133 134 136 140

While topical antifungals usually are effective for treatment of acute, uncomplicated tinea manuum and tinea pedis,124 131 132 134 136 140 an oral antifungal usually is necessary for treatment of severe, chronic, or recalcitrant tinea pedis,124 chronic moccasin-type (dry-type) tinea pedis, and for treatment of tinea unguium (onychomycosis).131 134 136 140

Griseofulvin Dosage and Administration

Administration

Oral Administration

Administer orally.104 125

When microsize griseofulvin (Grifulvin V) tablets are used, absorption may be improved if given after a high-fat meal.125

Dosage

Dosage varies depending on whether the drug is administered as griseofulvin microsize (Grifulvin V) or griseofulvin ultramicrosize (Gris-PEG).104 124 125

Dosage and duration of treatment should be individualized according to the requirements and response of the patient.104 104 Griseofulvin generally should be continued for ≥4–12 weeks for treatment of tinea capitis;104 124 125 132 133 135 140 141 ≥2–4 weeks for treatment of tinea corporis;104 124 125 ≥4–8 weeks for tinea pedis; and from 4–6 months to a year or longer for tinea unguium.104 124 125

Pediatric Patients

Dermatophytoses
Microsize (Grifulvin V)
Oral

10–11 mg/kg daily, although dosages up to 20–25 mg/kg daily have been used.124 125 140

Manufacturer suggests that those weighing approximately 14–23 kg may receive 125–250 mg daily and that those weighing >23 kg may receive 250–500 mg daily.125

AAP recommends 10–20 mg/kg (maximum 1 g) daily in 1 or 2 doses.124 For tinea capitis, AAP recommends 15–20 mg/kg once daily.124

Ultramicrosize (Gris-PEG)
Oral

Children >2 years of age: Usually 7.3 mg/kg daily,104 although dosages up to 10–15 mg/kg daily have been used.140

Manufacturer suggests that those weighing approximately 16–27 kg may receive 125–187.5 mg daily and those weighing >27 kg may receive 187.5–375 mg daily.104

AAP recommends 5–10 mg/kg (maximum 750 mg) once daily.124

Adults

Dermatophytoses
Microsize (Grifulvin V)
Oral

500 mg daily for treatment of tinea capitis, tinea corporis, or tinea cruris.125 For more difficult infections (e.g., tinea pedis, tinea unguium), 1 g daily.125

Ultramicrosize (Gris-PEG)
Oral

375 mg once daily or in divided doses for treatment of tinea capitis, tinea corporis, or tinea cruris.104 For more difficult infections (e.g., tinea pedis, tinea unguium), 750 mg daily given in divided doses.104

Cautions for Griseofulvin

Contraindications

  • Hypersensitivity to griseofulvin.104 125

  • Porphyria or hepatocellular failure.104 125

  • Pregnant women.104 125 (See Fetal/Neonatal Morbidity and Mortality under Cautions.)

Warnings/Precautions

Warnings

Fetal/Neonatal Morbidity and Mortality

May cause fetal toxicity when administered to pregnant women.101 104 111 117 118 125

Some animal studies indicate that griseofulvin may be embryotoxic and teratogenic.101 104 106 113 114 115 116 125 There have been 2 cases of conjoined twins born to women who received griseofulvin during the first trimester of pregnancy; some women who received the drug during pregnancy reportedly have had spontaneous abortions or delivered infants with other congenital malformations.101 104 111 117 118 104 125

Griseofulvin should not be used in women who are pregnant104 125 or intend to become pregnant within 1 month after treatment.125

Women should use additional contraceptive precautions during griseofulvin treatment and for 1 month after the drug is discontinued.125 One manufacturer recommends that men wait at least 6 months after completing griseofulvin treatment before fathering a child.125

If a patient becomes pregnant while receiving griseofulvin, they should be advised of the potential hazard to the fetus.104

Sensitivity Reactions

Hypersensitivity Reactions

Hypersensitivity reactions (e.g., rash, urticaria, erythema multiforme-like reactions, angioneurotic edema) have been reported.104

Because griseofulvin is derived from Penicillium, there is a possibility of cross-sensitivity with penicillin.104 125 Patients with known penicillin hypersensitivity have received griseofulvin without such reactions.104 125

If hypersensitivity reaction occurs, discontinue griseofulvin and initiate appropriate therapy.104

Photosensitivity Reactions

Photosensitivity reactions have been reported.104 125 Lupus erythematosus may be aggravated if a photosensitivity reaction occurs.125

Avoid exposure to intense natural or artificial sunlight during griseofulvin treatment.104

General Precautions

Selection and Use of Antifungals

Prior to administration of griseofulvin for dermatophytoses, diagnosis should be confirmed either by direct microscopic examination of scrapings from infected tissue mounted in potassium hydrochloride (KOH) or by culture.104 125

Should not be used for treatment of minor or trivial dermatophytoses that may respond to topical antifungals alone.104 125

General hygiene measures should be observed to control sources of infection or reinfection.104 125 Concomitant use of topical antifungals or antibacterials may be required, particularly for treatment of tinea pedis (athlete’s foot, foot ringworm).104 125 In some forms of tinea pedis, yeasts and bacteria may also be involved and griseofulvin is ineffective against these organisms.104 125

Not effective and should not be used for treatment of pityriasis (tinea) versicolor or cutaneous Candida infections.104 125 a

Not effective and should not be used for treatment of systemic fungal infections, including blastomycosis, candidiasis, chromoblastomycosis, coccidioidomycosis, cryptococcosis, histoplasmosis, or sporotrichosis.104 125 a Safety and efficacy not established for prevention of fungal infections.104 125

Not effective and should not be used for treatment of bacterial infections, including actinomycosis or nocardiosis.104 125

Laboratory Monitoring

Periodically assess organ system functions, including renal, hepatic, and hematopoietic, during prolonged therapy.104 125

Specific Populations

Pregnancy

Category C.b (See Fetal/Neonatal Morbidity and Mortality under Cautions.)

Pediatric Use

Safety and efficacy of ultramicrosize griseofulvin not established in children ≤2 years of age.104 Microsize griseofulvin has been used in children as young as 3 months of age.138

Hepatic Impairment

Contraindicated in patients with hepatocellular failure.104

Common Adverse Effects

Hypersensitivity reactions (rash, urticaria); GI effects (oral thrush, nausea, vomiting, epigastric distress, diarrhea); CNS effects (headache, fatigue, dizziness, insomnia, mental confusion, impaired performance of routine activities).104 125

Interactions for Griseofulvin

Specific Drugs

Drug

Interaction

Comments

Alcohol

Tachycardia, flushing, and potentiation of alcohol effects has been reported in patients receiving griseofulvin104 a

Although clinical importance is unclear, some clinicians suggest that patients be warned of a possible reaction and to avoid alcohol during griseofulvin therapya

Anticoagulants, oral (warfarin)

Decreased PT reported104 125 a

Use concomitantly with caution; adjust anticoagulant dosage if needed during and after griseofulvin treatment104 125 a

Aspirin

Possible decreased plasma salicylate concentrations127

Barbiturates

Possible decreased antifungal activity104 125

Phenobarbital: Possible decreased griseofulvin concentrationsa

Dosage adjustment of griseofulvin may be necessary104 125

Phenobarbital: Avoid concomitant use;a if concomitant use is necessary, administer griseofulvin in 3 divided doses daily to maximize absorption, monitor griseofulvin concentrations, and adjust dosage of the antifungal if necessarya

Cyclosporine

Possible decreased concentrations of cyclosporine128

Hormonal contraceptives (oral contraceptives)

Amenorrhea, increased breakthrough bleeding, and possibility of decreased contraceptive efficacy reported with concomitant use100 104 105 125

The possibility of decreased contraceptive efficacy should be considered if griseofulvin is used concomitantly100 105 129

Theophylline

Increased clearance and decreased theophylline half-life reported in some patients; extent of this interaction appears to vary and increased clearance of theophylline is not evident in all individuals who receive the drugs concomitantly126

Griseofulvin Pharmacokinetics

Absorption

Bioavailability

Absorption of microsize griseofulvin is variable125 and unpredictable and ranges from 25–70% of an oral dose;a peak serum concentrations attained 4 hours after a dose.125

Ultramicrosize griseofulvin is almost completely absorbed following oral administration.a

Food

Absorption of microsize griseofulvin may be enhanced by administration after a high-fat meal.125 a

Distribution

Extent

Following oral absorption, griseofulvin is concentrated in skin, hair, nails, liver, fat, and skeletal muscles.a The drug can be detected in the outer layers of the stratum corneum soon after ingestion.a

Griseofulvin is deposited in keratin precursor cells and has greater affinity for diseased tissue.104 The drug is tightly bound to new keratin.104

Griseofulvin concentrations in skin are higher in warm climates than in cold, possibly because the drug is dissolved in perspiration and deposited in the horny layer of skin when perspiration evaporates.a This explanation has also been used to account for the reversed concentration gradient of the drug in skin; highest concentrations are found in the outermost horny layer, while concentrations are much lower in deeper layers.a

Elimination

Metabolism

Oxidatively demethylated and conjugated with glucuronic acid, principally in the liver.a The major metabolite, 6-desmethylgriseofulvin, is microbiologically inactive.a

Elimination Route

About 30% of a single oral dose of microsize griseofulvin is excreted in urine within 24 hours as 6-desmethylgriseofulvin and its glucuronide conjugate; 50% of the dose is excreted in urine within 5 days.a Unchanged griseofulvin in the urine accounts for <1% of the administered drug.a Approximately one-third of a single dose of microsize griseofulvin is excreted in feces within 5 days.a Griseofulvin also is excreted in perspiration.a

Half-life

9–24 hours.a

Stability

Storage

Oral

Tablets

Microsize or ultramicrosize: 15–30°C in tight, light-resistant container.104 125

Suspension

Microsize: Room temperature in tight, light-resistant container.125

Actions and Spectrum

  • Structurally unrelated to other antifungals (e.g., allylamines, azoles, echinocandins, polyenes, pyrimidines).a

  • Usually fungistatic in action.104 125 a

  • Antifungal activity principally involves disruption of the fungal cell’s mitotic spindle structure.a Although the effect on mitosis is similar to that caused by colchicine, a different mechanism is probably involved.a Griseofulvin may cause production of defective DNA which is unable to replicate.a

  • Griseofulvin is deposited in keratin precursor cells and is tightly bound to new keratin, resulting in an environment unfavorable for fungal invasion.104 125 a Infected skin, hair, or nails are then replaced with tissue not infected with the dermatophyte.125 a

  • Limited spectrum of antifungal activity.104 125 a Active against most dermatophytes, but not active against yeasts or other fungi, including Aspergillus, Blastomyces, Candida, Cryptococcus, Coccidioides, Histoplasma, Saccharomyces, Sporotrichum, or Malassezia furfur (Pityrosporum orbiculare).104 125 a

  • Dermatophytes: Active against Epidermophyton floccosum, Microsporum audouini, M. canis, M. gypseum, Trichophyton crateriform, T. gallinae, T. interdigitalis, T. megnini, T. mentagrophytes, T. rubrum, T. schoenleinii, T. sulphureum, T. tonsurans, and T. verrucosum.104 125

Advice to Patients

  • Importance of using griseofulvin for the full, prescribed treatment period, even if symptoms improve; importance of consulting with clinician if the condition does not improve after a full course of therapy.

  • Advise patients to avoid exposure to intense natural or artificial sunlight during griseofulvin treatment since photosensitivity reactions can occur.104 125

  • Importance of discontinuing use and contacting clinician if signs or symptoms of sensitization occur (e.g., rash, urticaria).104 125

  • Importance of informing clinicians of existing or contemplated therapy, including prescription and OTC drugs, as well as any concomitant illnesses.

  • Importance of women informing clinicians if they are or plan to become pregnant or to breast-feed. (See Fetal/Neonatal Morbidity and Mortality under Cautions.)

  • Importance of informing patients of other important precautionary information. (See Cautions.)

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Griseofulvin Microsize

Routes

Dosage Forms

Strengths

Brand Names

Manufacturer

Oral

Suspension

125 mg/5 mL

Grifulvin V (with alcohol 0.2% parabens and propylene glycol)

Ortho-Neutrogena

Tablets

500 mg

Grifulvin V (scored)

Ortho-Neutrogena

Griseofulvin Ultramicrosize

Routes

Dosage Forms

Strengths

Brand Names

Manufacturer

Oral

Tablets, film-coated

125 mg

Gris-PEG (with methylparaben; scored)

Pedinol

250 mg

Gris-PEG (with methylparaben and povidone; scored)

Pedinol

Comparative Pricing

This pricing information is subject to change at the sole discretion of DS Pharmacy. This pricing information was updated 02/2014. Actual costs to patients will vary depending on the use of specific retail or mail-order locations and health insurance copays.

Grifulvin V 500MG Tablets (VALEANT): 30/$192.30 or 90/$544.00

Gris-PEG 125MG Tablets (PEDINOL): 90/$206.37 or 270/$585.39

Griseofulvin Microsize 125MG/5ML Suspension (PATRIOT PHARMACEUTICALS LLC): 120/$42.99 or 360/$115.98

AHFS DI Essentials. © Copyright, 2004-2014, Selected Revisions July 1, 2006. American Society of Health-System Pharmacists, Inc., 7272 Wisconsin Avenue, Bethesda, Maryland 20814.

References

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104. Pedinol Pharmacal. Gris-PEG (griseofulvin ultramicrosize) tablets prescribing information. In: Physician’s desk reference. 56th ed. Montvale, NJ: Medical Economics Company Inc; 2002:2661-2.

105. Catalano PM, Blank H. Griseofulvin–oral contraceptive interaction. Arch Dermatol. 1985; 121:1381. [IDIS 209312] [PubMed 4051524]

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a. AHFS Drug Information 2004. McEvoy GK, ed. Griseofulvin. Bethesda, MD: American Society of Health-System Pharmacists; 2004:532-4.

b. Briggs GG, Freeman RK, Yaffe SJ. Drugs in pregnancy and lactation. 6th ed. Philadelphia; PA: Lippincott Wiliams & Wilkins; 2002:.

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