Label: ULTRAMICROSIZE GRISEOFULVIN tablet, coated

  • NDC Code(s): 0781-5827-01, 0781-5827-05, 0781-5828-01, 0781-5828-05
  • Packager: Sandoz Inc
  • Category: HUMAN PRESCRIPTION DRUG LABEL
  • DEA Schedule: None
  • Marketing Status: Abbreviated New Drug Application

Drug Label Information

Updated May 15, 2018

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  • DESCRIPTION

    Ultramicrosize griseofulvin tablets, USP contain ultramicrosize crystals of griseofulvin, an antibiotic derived from a species of Penicillium.

    The chemical name of griseofulvin, USP is 7-Chloro-2’,4,6-trimethoxy-6’β-methylspiro[benzofuran-2(3H),1’-[2]cyclohexene]-3,4’-dione. Its structural formula is:

    Structure.jpg

    Griseofulvin, USP occurs as a white to creamy white, odorless powder which is very slightly soluble in water, soluble in acetone, dimethylformamide, and chloroform and sparingly soluble in alcohol.

    Each ultramicrosize griseofulvin tablets, USP contains ultramicrosize griseofulvin 125 mg or 250 mg and the following inactive ingredients: calcium stearate, colloidal silicon dioxide, crospovidone, hypromellose, lactose anhydrous, polyethylene glycol, sodium lauryl sulfate, talc and titanium dioxide.

    In addition, the 125 mg tablet contains iron oxide yellow.

  • CLINICAL PHARMACOLOGY

  • 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 ultramicro-crystalline griseofulvin tablets (See Table 1).

    Table 1: Mean (± SD) of the Pharmacokinetic Parameters for Griseofulvin Administered in Applesauce as a Single Dose of Ultramicrosize Griseofulvin Tablets 250 mg Uncrushed and Crushed to Fasted Healthy Volunteers (N=24)

    250 mg Ultramicrocrystalline Griseofulvin Tablets Unaltered

    250 mg Ultramicrocrystalline Griseofulvin Tablets Physically Altered (Crushed and in Applesauce)

    Cmax (ng/mL)

    600.61 (± 167.6)

    672.61 (± 146.2)

    Tmax (hr)

    4.04 (± 2.2)

    3.08 (± 1.02)

    AUC (ng·hr/mL)

    8618.89 (± 1907.2)

    9023.71 (± 1911.5)

  • INDICATIONS AND USAGE

    Ultramicrosize griseofulvin tablets are indicated for the treatment of the following ringworm infections; tinea corporis (ringworm of the body), tinea pedis (athlete’s foot), tinea cruris (ringworm of the groin and thigh), tinea barbae (barber’s itch), tinea capitis (ringworm of the scalp), and tinea unguium (onychomycosis, ringworm of 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, Microsporum  audouini, Microsporum  canis, Microsporum  gypseum and 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.

  • CONTRAINDICATIONS

    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.

  • WARNINGS

    Prophylactic Usage

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

    Serious Skin Reactions

    Severe skin reactions (e.g. Stevens-Johnson syndrome, toxic epidermal necrolysis) and erythema multiforme have been reported with griseofulvin use. These reactions may be serious and may result in hospitalization or death. If severe skin reactions occur, griseofulvin should be discontinued (see ADVERSE REACTIONS section).

    Hepatotoxicity

    Elevations in AST, ALT, bilirubin, and jaundice have been reported with griseofulvin use. These reactions may be serious and may result in hospitalization or death. Patients should be monitored for hepatic adverse events and discontinuation of griseofulvin considered if warranted (see ADVERSE REACTIONS section).

    Animal Toxicology

    Chronic feeding of griseofulvin, at levels ranging from 0.5% to 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%, 1% 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 form a 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 metabolism have 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.

    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 confirm this.

  • PRECAUTIONS

    Patients on prolonged therapy with any potent medication should be under close observation. Periodic monitoring of organ system function, including renal, hepatic and hematopoietic, should be done. Since griseofulvin is derived from species 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.

  • ADVERSE REACTIONS

    There have been post-marketing reports of severe skin and hepatic adverse events associated with griseofulvin use (see WARNINGS section).

    When adverse reactions occur, they are most commonly of the hypersensitivity type such as skin rashes, urticaria, erythema multiforme-like drug reactions, and rarely, angioneurotic edema, and may necessitate withdrawal of therapy and appropriate countermeasures. Paresthesia of the hands and feet have been reported 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.

    To report SUSPECTED ADVERSE REACTIONS, contact Sandoz Inc., at 1-800-525-8747 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

  • DOSAGE AND ADMINISTRATION

    Accurate diagnosis of infecting organism is essential. Identification should be made either by direct microscopic examination of a mounting of infected tissue in a solution of potassium hydroxide or by culture on an appropriate medium. Medication must be continued until the infecting organism is 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.

    Ultramicrosize griseofulvin 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 7.3 mg per kg 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:

    16 to 27 kg: 125 mg to 187.5 mg daily.

    Over 27 kg: 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 organism is eradicated.

  • HOW SUPPLIED

    Ultramicrosize griseofulvin tablets, USP are available as follows:

    125 mg, are yellow colored, oval shaped, film coated biconvex tablets debossed with ‘I127’ on one side and scored on other side.

     
    NDC 0781-5827-01, bottle of 100 tablets
     
    NDC 0781-5827-05, bottle of 500 tablets

    250 mg, are white to off white colored, capsule shaped, film coated biconvex tablets debossed with ‘I126’ on one side and scored on other side.

     
    NDC 0781-5828-01, bottle of 100 tablets
     
    NDC 0781-5828-05, bottle of 500 tablets

    STORAGE

    Store at 20° to 25° C (68° to 77° F) [see USP Controlled Room Temperature]. Dispense in a tight, light-resistant container.

    Manufactured by: USV Private Limited

    OIDC, Mahatma Gandhi Udyog Nagar, Dabhel, Daman 396 210, India

    for:

    Sandoz Inc., Princeton, NJ 08540.

    Rev. May 2018.

  • Principal Display Panel

    NDC 0781-5827-01

    Ultramicrosize Griseofulvin Tablets, USP

    125 mg

    Rx only

    100 Tablets

    125 mg label
  • Principal Display Panel

    NDC 0781-5828-01

    Ultramicrosize Griseofulvin Tablets, USP

    250 mg

    Rx only

    100 Tablets

    250-mg
  • INGREDIENTS AND APPEARANCE
    ULTRAMICROSIZE GRISEOFULVIN 
    ultramicrosize griseofulvin tablet, coated
    Product Information
    Product TypeHUMAN PRESCRIPTION DRUGItem Code (Source)NDC:0781-5828
    Route of AdministrationORAL
    Active Ingredient/Active Moiety
    Ingredient NameBasis of StrengthStrength
    GRISEOFULVIN (UNII: 32HRV3E3D5) (GRISEOFULVIN - UNII:32HRV3E3D5) GRISEOFULVIN250 mg
    Inactive Ingredients
    Ingredient NameStrength
    POLYETHYLENE GLYCOL 6000 (UNII: 30IQX730WE)  
    SODIUM LAURYL SULFATE (UNII: 368GB5141J)  
    CROSPOVIDONE, UNSPECIFIED (UNII: 2S7830E561)  
    ANHYDROUS LACTOSE (UNII: 3SY5LH9PMK)  
    SILICON DIOXIDE (UNII: ETJ7Z6XBU4)  
    CALCIUM STEARATE (UNII: 776XM7047L)  
    HYPROMELLOSE 2910 (6 MPA.S) (UNII: 0WZ8WG20P6)  
    TALC (UNII: 7SEV7J4R1U)  
    POLYETHYLENE GLYCOL 8000 (UNII: Q662QK8M3B)  
    TITANIUM DIOXIDE (UNII: 15FIX9V2JP)  
    Product Characteristics
    ColorWHITEScore2 pieces
    ShapeCAPSULESize15mm
    FlavorImprint Code I126
    Contains    
    Packaging
    #Item CodePackage DescriptionMarketing Start DateMarketing End Date
    1NDC:0781-5828-01100 in 1 BOTTLE; Type 0: Not a Combination Product04/01/2020
    2NDC:0781-5828-05500 in 1 BOTTLE; Type 0: Not a Combination Product04/01/2020
    Marketing Information
    Marketing CategoryApplication Number or Monograph CitationMarketing Start DateMarketing End Date
    ANDAANDA20280504/01/2020
    ULTRAMICROSIZE GRISEOFULVIN 
    ultramicrosize griseofulvin tablet, coated
    Product Information
    Product TypeHUMAN PRESCRIPTION DRUGItem Code (Source)NDC:0781-5827
    Route of AdministrationORAL
    Active Ingredient/Active Moiety
    Ingredient NameBasis of StrengthStrength
    GRISEOFULVIN (UNII: 32HRV3E3D5) (GRISEOFULVIN - UNII:32HRV3E3D5) GRISEOFULVIN125 mg
    Inactive Ingredients
    Ingredient NameStrength
    POLYETHYLENE GLYCOL 6000 (UNII: 30IQX730WE)  
    SODIUM LAURYL SULFATE (UNII: 368GB5141J)  
    CROSPOVIDONE, UNSPECIFIED (UNII: 2S7830E561)  
    ANHYDROUS LACTOSE (UNII: 3SY5LH9PMK)  
    SILICON DIOXIDE (UNII: ETJ7Z6XBU4)  
    CALCIUM STEARATE (UNII: 776XM7047L)  
    TALC (UNII: 7SEV7J4R1U)  
    POLYETHYLENE GLYCOL 8000 (UNII: Q662QK8M3B)  
    TITANIUM DIOXIDE (UNII: 15FIX9V2JP)  
    FERRIC OXIDE YELLOW (UNII: EX438O2MRT)  
    HYPROMELLOSE 2910 (6 MPA.S) (UNII: 0WZ8WG20P6)  
    Product Characteristics
    ColorYELLOWScore2 pieces
    ShapeOVALSize15mm
    FlavorImprint Code I127
    Contains    
    Packaging
    #Item CodePackage DescriptionMarketing Start DateMarketing End Date
    1NDC:0781-5827-01100 in 1 BOTTLE; Type 0: Not a Combination Product04/01/2020
    2NDC:0781-5827-05500 in 1 BOTTLE; Type 0: Not a Combination Product04/01/2020
    Marketing Information
    Marketing CategoryApplication Number or Monograph CitationMarketing Start DateMarketing End Date
    ANDAANDA20280504/01/2020
    Labeler - Sandoz Inc (005387188)