Gris-PEG®Tablets contain ultramicrosize crystals of griseofulvin, an antibiotic derived froma species of Penicillium.

Each Gris-PEG tablet contains:

Active Ingredient: griseofulvin ultramicrosize .... 125 mg

Inactive Ingredients: colloidal silicon dioxide, lactose, magnesiumstearate, methylcellulose, methylparaben, polyethylene glycol 400 and 8000, polyvinylpyrrolidone, and titaniumdioxide.

OR

Active Ingredient: griseofulvin ultramicrosize .... 250 mg

Inactive Ingredients: colloidal silicon dioxide, magnesiumstearate, methylcellulose, methylparaben, polyethylene glycol 400 and 8000, povidone, sodiumlauryl sulfate, and titaniumdioxide.

Gris-PEG (griseofulvin ultramicrosize) is indicated for the treatment of the following ringworminfections; tinea corporis (ringwormof the body), tinea pedis (athlete's foot), tinea cruris (ringwormof the groin and thigh), tinea barbae (barber's itch), tinea capitis (ringwormof the scalp), and tinea unguium(onychomycosis, ringwormof the nails), when caused by one or more of the following genera of fungi: Trichophyton rubrum, Trichophyton tonsurans, Trichophyton mentagrophytes, Trichophyton interdigitalis,Trichophyton verrucosum, Trichophyton megnini, Trichophyton gallinae, Trichophyton crateriform, Trichophyton sulphureum, Trichophyton schoenleini, Microsporumaudouini, Microsporumcanis, Microsporumgypseumand Epidermophyton floccosum. NOTE: Prior to therapy, the type of fungi responsible for the infection should be identified. The use of the drug is not justified in minor or trivial infections which will respond to topical agents alone. Griseofulvin is not effective in the following: bacterial infections, candidiasis (moniliasis), histoplasmosis, actinomycosis, sporotrichosis, chromoblastomycosis, coccidioidomycosis, North American blastomycosis, cryptococcosis (torulosis), tinea versicolor and nocardiosis.

Accurate diagnosis of infecting organismis essential. Identification should be made either by direct microscopic examination of a mounting of infected tissue in a solution of potassiumhydroxide or by culture on an appropriate medium. Medication must be continued until the infecting organismis completely eradicated as indicated by appropriate clinical or laboratory examination. Representative treatment periods are tinea capitis, 4 to 6 weeks; tinea corporis, 2 to 4 weeks; tinea pedis, 4 to 8 weeks; tinea unguium-depending on rate of growth-fingernails, at least 4 months; toenails, at least 6 months.

General measures in regard to hygiene should be observed to control sources of infection or reinfection. Concomitant use of appropriate topical agents is usually required, particularly in treatment of tinea pedis. In some forms of athlete's foot, yeasts and bacteria may be involved as well as fungi. Griseofulvin will not eradicate the bacterial or monilial infection.

GRIS-PEG® tablets may be swallowed whole or crushed and sprinkled onto 1 tablespoonful of applesauce and swallowed immediately without chewing.

Adults: Daily administration of 375 mg (as a single dose or in divided doses) will give a satisfactory response in most patients with tinea corporis, tinea cruris, and tinea capitis. For those fungal infections more difficult to eradicate, such as tinea pedis and tinea unguium, a divided dose of 750 mg is recommended.

Pediatric Use: Approximately 3.3 mg per pound of body weight per day of ultramicrosize griseofulvin is an effective dose for most pediatric patients. On this basis, the following dosage schedule is suggested: Children weighing 35-60 pounds - 125 mg to 187.5 mg daily. Pediatric patients weighing over 60 pounds - 187.5 mg to 375 mg daily. Children and infants 2 years of age and younger-dosage has not been established.

Clinical experience with griseofulvin in children with tinea capitis indicates that a single daily dose is effective. Clinical relapse will occur if the medication is not continued until the infecting organismis eradicated.

Gris-PEG®(griseofulvin ultramicrosize) Tablets, 125 mg, white scored, elliptical-shaped, embossed “Gris-PEG” on one side and “125” on the other. Gris-PEG (griseofulvin ultramicrosize) Tablets, 250 mg, white scored, capsule-shaped, embossed “Gris-PEG” on one side and “250” on the other. The 125 mg strength is available in bottles of 100 (NDC 0884-0763-04). The 250 mg strength is available in bottles of 100 and 500 (NDC 0884-0773-04 and NDC 0884-0773-50 respectively). Both strengths are film-coated.

Storage

Store Gris-PEG tablets at controlled roomtemperature 15° -30° C (59° -86° F) in tight, light-resistant containers.

Manufactured for: PEDINOL PHARMACAL INC. Farmingdale, NY 11735 U.S.A. By: NOVARTIS CONSUMER HEALTH INC. Lincoln, NE 68501, REV 01/07. FDA revision date: 1/24/2007

When adverse reactions occur, they are most commonly of the hypersensitivity type such as skin rashes, urticaria, erythema multiform-like drug reactions, and rarely, angioneurotic edema, and may necessitate withdrawal of therapy and appropriate countermeasures. Paresthesias of the hands and feet have been reported rarely after extended therapy. Other side effects reported occasionally are oral thrush, nausea, vomiting, epigastric distress, diarrhea, headache, fatigue, dizziness, insomnia, mental confusion, and impairment of performance of routine activities. Proteinuria and leukopenia have been reported rarely. Administration of the drug should be discontinued if granulocytopenia occurs. When rare, serious reactions occur with griseofulvin, they are usually associated with high dosages, long periods of therapy, or both.

No information provided.

Prophylactic Usage - Safety and efficacy of griseofulvin for prophylaxis of fungal infections have not been established.

Usage in Pregnancy - see CONTRAINDICATIONS section.

Animal Reproduction Studies - It has been reported in the literature that griseofulvin was found to be embryotoxic and teratogenic on oral administration to pregnant rats. Pups with abnormalities have been reported in the litters of a few bitches treated with griseofulvin. Suppression of spermatogenesis has been reported to occur in rats, but investigation in man failed to confirmthis.

Patients on prolonged therapy with any potent medication should be under close observation. Periodic monitoring of organ systemfunction, including renal, hepatic and hematopoietic, should be done. Since griseofulvin is derived fromspecies of Penicillium, the possibility of cross-sensitivity with penicillin exists; however, known penicillin-sensitive patients have been treated without difficulty. Since a photosensitivity reaction is occasionally associated with griseofulvin therapy, patients should be warned to avoid exposure to intense natural or artificial sunlight. Lupus erythematosus or lupus-like syndromes have been reported in patients receiving griseofulvin. Griseofulvin decreases the activity of warfarin-type anticoagulants so that patients receiving these drugs concomitantly may require dosage adjustment of the anticoagulant during and after griseofulvin therapy. Barbiturates usually depress griseofulvin activity and concomitant administration may require a dosage adjustment of the antifungal agent. There have been reports in the literature of possible interactions between griseofulvin and oral contraceptives. The effect of alcohol may be potentiated by griseofulvin, producing such effects as tachycardia and flush.

No information provided.

Two cases of conjoined twins have been reported since 1977 in patients taking griseofulvin during the first trimester of pregnancy. Griseofulvin should not be prescribed to pregnant patients. If the patient becomes pregnant while taking this drug, the patient should be apprised of the potential hazard to the fetus.

This drug is contraindicated in patients with porphyria or hepatocellular failure and in individuals with a history of hypersensitivity to griseofulvin.

Action

Microbiology - Griseofulvin is fungistatic with in vitro activity against various species of Microsporum, Epidermophyton and Trichophyton. It has no effect on bacteria or other genera of fungi.

Pharmacokinetics - Following oral administration, griseofulvin is deposited in the keratin precursor cells and has a greater affinity for diseased tissue. The drug is tightly bound to the new keratin which becomes highly resistant to fungal invasions.

The efficiency of gastrointestinal absorption of ultramicrocrystalline griseofulvin is approximately one and one-half times that of the conventional microsize griseofulvin. This factor permits the oral intake of two-thirds as much ultramicrocrystalline griseofulvin as the microsize form. However, there is currently no evidence that this lower dose confers any significant clinical differences with regard to safety and/or efficacy.

In a bioequivalence study conducted in healthy volunteers (N=24) in the fasted state, 250 mg ultramicrocrystalline griseofulvin tablets were compared with 250 mg ultramicrocrystalline griseofulvin tablets that were physically altered (crushed) and administered with applesauce. The 250 mg ultramicrocrystalline griseofulvin tablets were found to be bioequivalent to the physically altered (crushed) 250 mg ultramicrocrystalline griseofulvin tablets (See Table 1).

Table 1: Mean (± SD) of the Pharmacokinetic Parameters for Griseofulvin administered in applesauce as a Single Dose of GRIS-PEG® 250-mg Tablets Uncrushed and Crushed to fasted
Healthy Volunteers (N=24)

Animal Toxicology - Chronic feeding of griseofulvin, at levels ranging from0.5%-2.5% of the diet resulted in the development of liver tumors in several strains of mice, particularly in males. Smaller particle sizes result in an enhanced effect. Lower oral dosage levels have not been tested. Subcutaneous administration of relatively small doses of griseofulvin once a week during the first three weeks of life has also been reported to induce hepatomata in mice. Thyroid tumors, mostly adenomas but some carcinomas, have been reported in male rats receiving griseofulvin at levels of 2.0%, 1.0% and 0.2% of the diet, and in female rats receiving the two higher dose levels. Although studies in other animal species have not yielded evidence of tumorigenicity, these studies were not of adequate design to forma basis for conclusion in this regard. In subacute toxicity studies, orally administered griseofulvin produced hepatocellular necrosis in mice, but this has not been seen in other species. Disturbances in porphyrin metabolismhave been reported in griseofulvin-treated laboratory animals. Griseofulvin has been reported to have a colchicine-like effect on mitosis and cocarcinogenicity with methylcholanthrene in cutaneous tumor induction in laboratory animals.

No information provided. Please refer to the WARNINGS and PRECAUTIONS sections.

IMPORTANT NOTE: This is a summary and does not contain all possible information about this product. For complete information about this product or your specific health needs, ask your health care professional. Always seek the advice of your health care professional if you have any questions about this product or your medical condition. This information is not intended as individual medical advice and does not substitute for the knowledge and judgment of your health care professional. This information does not contain any assurances that this product is safe, effective, or appropriate for you.

GRISEOFULVIN - ORAL TABLET

(GRISS-ee-oh-FULL-vin)

COMMON BRAND NAME(S): Fulvicin, Grifulvin V, Gris-Peg, Grisactin

USES: This medication is used to treat fungal infections of the skin, hair, and nails that do not respond to creams/lotions. Clearing such infections will get rid of symptoms such as itching, red/peeling/scaly skin, and discolored nails. This medication works by stopping the growth of fungi. It does not treat infections due to bacteria or yeast.

HOW TO USE: Take this medication by mouth as directed by your doctor. For the best absorption, it is best taken with or after a meal containing a moderate amount of fat. Talk to your doctor or pharmacist about specific dietary instructions, especially if you are on a low-fat diet.

The dosage is based on your medical condition and response to therapy. In children, dosage is also based on weight. The length of treatment depends on the type of infection you have. It may take several weeks to months to complete treatment for infections of the scalp, feet, and body. Nail infections may require several months to a year or longer to treat.

Antifungal medications work best when the amount of medicine in your body is kept at a constant level. Therefore, take this drug at evenly spaced intervals.

Continue to take this medication for the full prescribed length of treatment even if symptoms improve after a few days. Stopping the medication too early may allow the fungus to continue to grow, which may result in a relapse of the infection.

Inform your doctor if your condition persists or worsens.

SIDE EFFECTS: Headache, nausea, vomiting, diarrhea, stomach upset, tiredness, dizziness, or trouble sleeping may occur. If any of these effects persist or worsen, notify your doctor or pharmacist promptly.

Remember that your doctor has prescribed this medication because he or she has judged that the benefit to you is greater than the risk of side effects. Many people using this medication do not have serious side effects.

Tell your doctor immediately if any of these unlikely but serious side effects occur: numbness/tingling of the hands/feet, mental/mood changes (e.g., confusion, trouble doing normal activities), sunburn-like rash, hearing changes, butterfly-shaped facial rash (around the nose and cheeks), joint/muscle pain.

Tell your doctor immediately if any of these rare but very serious side effects occur: yellowing eyes/skin, stomach/abdominal pain, persistent nausea/vomiting, dark/frothy urine, change in the amount of urine, signs of infection (e.g., fever, persistent sore throat).

Use of this medication for prolonged or repeated periods may result in oral thrush or a new vaginal yeast infection (oral or vaginal fungal infection). Contact your doctor if you notice white patches in your mouth, a change in vaginal discharge, or other new symptoms.

A very serious allergic reaction to this drug is unlikely, but seek immediate medical attention if it occurs. Symptoms of a serious allergic reaction may include: rash, itching, swelling, severe dizziness, trouble breathing.

This is not a complete list of possible side effects. If you notice other effects not listed above, contact your doctor or pharmacist.

Contact your doctor for medical advice about side effects. The following numbers do not provide medical advice, but in the US you may report side effects to the Food and Drug Administration (FDA) at 1-800-FDA-1088. In Canada, you may call Health Canada at 1-866-234-2345.

PRECAUTIONS: Before taking griseofulvin, tell your doctor or pharmacist if you are allergic to it; or if you have any other allergies.

This medication should not be used if you have certain medical conditions. Before using this medicine, consult your doctor or pharmacist if you have: a certain blood disorder (porphyria), severe liver disease (liver failure).

Before using this medication, tell your doctor or pharmacist your medical history, especially of: lupus.

This drug may make you dizzy or less alert. Do not engage in activities requiring alertness such as driving or using machinery until you know how this drug affects you and that you can safely perform these activities.

Avoid alcoholic beverages while you are taking this drug unless your doctor gives permission. Drinking alcohol during treatment with this drug could result in a fast heartbeat and flushing of the skin.

This medication may make you more sensitive to the sun. Avoid prolonged sun exposure, tanning booths, and sunlamps. Use a sunscreen and wear protective clothing when outdoors.

This medication is not recommended for use during pregnancy. It may harm an unborn baby. Consult your doctor for more details and to discuss delaying griseofulvin treatment. Use of reliable form(s) of birth control is recommended during treatment and for 1 month after the drug is stopped. If you are planning to become pregnant within 1 month after treatment, the manufacturer recommends avoiding this drug. (See also Drug Interactions.)

The effects of this drug on human sperm are unknown. However, based on animal cell studies, the manufacturer recommends waiting for a period of time after completing griseofulvin treatment before trying to father a child. Discuss the risks and benefits with your doctor, and ask how long to wait after your last dose before trying to father a child.

It is not known if this drug passes into breast milk. Due to the possible risk to the infant, breast-feeding while using this drug is not recommended. Consult your doctor before breast-feeding.

DRUG INTERACTIONS: Your healthcare professionals (e.g., doctor or pharmacist) may already be aware of any possible drug interactions and may be monitoring you for it. Do not start, stop or change the dosage of any medicine before checking with them first.

Before using this medication, tell your doctor or pharmacist of all prescription and nonprescription/herbal products you may use, especially of: barbiturates (e.g., phenobarbital), warfarin.

This medication may decrease the effectiveness of birth control pills. This can result in pregnancy. You may need to use an additional form of reliable birth control while using this medication. Consult your doctor or pharmacist for details.

This document does not contain all possible interactions. Therefore, before using this product, tell your doctor or pharmacist of all the products you use. Keep a list of all your medications with you, and share the list with your doctor and pharmacist.

OVERDOSE: If overdose is suspected, contact your local poison control center or emergency room immediately. US residents can call the US national poison hotline at 1-800-222-1222. Canadian residents should call their local poison control center directly.

NOTES: Do not share this medication with others.

This medication has been prescribed for your current condition only. Do not use it later for another infection unless told to do so by your doctor. A different medication may be necessary in those cases.

Laboratory and/or medical tests (e.g., kidney and liver function, complete blood count) should be performed periodically to check for side effects with prolonged treatment. Consult your doctor for more details.

Ask your doctor or pharmacist about ways to control the infection and to prevent re-infection. Fungus spreads easily in warm, moist areas. Follow good hygiene (e.g., wash and dry the infected area completely, and do not share articles of clothing or objects that come in contact with the infected area).

MISSED DOSE: If you miss a dose, take it as soon as you remember. If it is near the time of the next dose, skip the missed dose and resume your usual dosing schedule. Do not double the dose to catch up.

STORAGE: Store at room temperature between 59-86 degrees F (15-30 degrees C) away from light and moisture. Do not store in the bathroom. Keep all medicines away from children and pets.

Do not flush medications down the toilet or pour them into a drain unless instructed to do so. Properly discard this product when it is expired or no longer needed. Consult your pharmacist or local waste disposal company for more details about how to safely discard your product.

Information last revised July 2008 Copyright(c) 2008 First DataBank, Inc.