CLOTRIMAZOLE: 2,597 Adverse Event Reports & Safety Profile

DESCRIPTION Clotrimazole cream USP, 1% contains clotrimazole, a synthetic antifungal agent having the chemical name {1-(o-Chloro-α, α-diphenylbenzyl)imidazole}; the molecular formula C 22 H 17 ClN 2 ; a molecular weight of 344.84; and the structural formula: Clotrimazole USP is an odorless, white crystalline substance. It is practically insoluble in water, sparingly soluble in ether and very soluble in polyethylene glycol 400, ethanol and chloroform. Each gram of clotrimazole cream USP contains 10 mg clotrimazole USP, dispersed in a vanishing cream base of sorbitan monostearate, polysorbate 60, cetyl esters wax, cetostearyl alcohol, octyldodecanol, purified water, and benzyl alcohol (1%) as preservative. structural formula

INDICATIONS AND USAGE Clotrimazole Lozenges are indicated for the local treatment of oropharyngeal candidiasis. The diagnosis should be confirmed by a KOH smear and/or culture prior to treatment.

Clotrimazole

Lozenges are also indicated prophylactically to reduce the incidence of oropharyngeal candidiasis in patients immunocompromised by conditions that include chemotherapy, radiotherapy, or steroid therapy utilized in the treatment of leukemia, solid tumors, or renal transplantation. There are no data from adequate and well-controlled trials to establish the safety and efficacy of this product for prophylactic use in patients immunocompromised by etiologies other than those listed in the previous sentence. (See DOSAGE AND ADMINISTRATION .)

Directions Read all package directions and warnings before use. Use only as directed. Clean the affected area with soap and warm water and dry thoroughly. Spray a thin layer of FUNGICURE over the affected area twice daily (morning and night) or as directed by a doctor. This product is not effective on the scalp or nails. Avoid applying to severely cracked or irritated areas. For ringworm and athlete's foot, use daily for 4 weeks; for jock itch, use daily for 2 weeks. If condition persists longer, consult a doctor. For athlete's foot, pay special attention to spaces between toes; wear well fitting, ventilated shoes, and change shoes and socks at least once daily. Supervise children in the use of this product. Intended for use by normally healthy adults only. Persons under 18 years of age or those with highly sensitive or allergic skin should use only as directed by a doctor.

CONTRAINDICATIONS Topical antifungal agents are contraindicated in those patients with a history of hypersensitivity to any of the components of the preparation.

ADVERSE REACTIONS Abnormal liver function tests have been reported in patients treated with clotrimazole lozenges; elevated SGOT levels were reported in about 15% of patients in the clinical trials (See PRECAUTIONS ). Nausea, vomiting, unpleasant mouth sensations and pruritus have also been reported with the use of the lozenge. To report SUSPECTED ADVERSE REACTIONS, contact Rising Pharma Holdings, Inc. at 1-844-874-7464 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch

Warnings For vaginal use only. Do not use if you have never had a vaginal yeast infection diagnosed by a doctor; if you have a fever (higher than 100° F), pain in the lower abdomen, back, either shoulder, or a foul-smelling vaginal discharge.You should see a doctor for treatment of these symptoms. Ask a doctor before use if you have

• Vaginal itching and discomfort for the first time, lower abdominal, back or shoulder pain, fever, chills, nausea, vomiting or foul-smelling vaginal discharge. You may have a more serious condition.
• Vaginal yeast infections often (such as once a month or 3 in 6 months). You could be pregnant or have a serious underlying medical cause for your symptoms, including diabetes or a weakened immune system.
• Been exposed to the human immunodeficiency virus (HIV) that causes AIDS. When using this product
• Do not use tampons, douches, spermicides, or other vaginal products. Condoms or diaphragms may be damaged and fail to prevent sexually transmitted disease or pregnancy.
• Do not have vaginal intercourse.
• Mild increase in vaginal burning, itching, or irritation may occur. Stop use and ask a doctor if symptoms do not improve in 3 days; symptoms last more than 7 days; you get a rash or hives, abdominal pain, fever, chills, nausea, vomiting or a foul-smelling vaginal discharge. If pregnant or breastfeeding , ask a health professional before use. Keep out of reach of children. If swallowed, call poison control or seek medical help.

PRECAUTIONS General If irritation or sensitivity develops with the use of clotrimazole, treatment should be discontinued and appropriate therapy instituted. Information for Patient This information is intended to aid in the safe and effective use of this medication. It is not a disclosure of all possible adverse or intended effects. The patient should be advised to: Use the medication for the full treatment time even though the symptoms may have improved. Notify the physician if there is no improvement after 4 weeks of treatment. Inform the physician if the area of application shows signs of increased irritation (redness, itching, burning, blistering, swelling, oozing) indicative of possible sensitization. Avoid sources of infection or reinfection.

Laboratory

Tests If there is lack of response to clotrimazole, appropriate microbiological studies should be repeated to confirm the diagnosis and rule out other pathogens before instituting another course of antimycotic therapy.

Drug Interactions

Synergism or antagonism between clotrimazole and nystatin, or amphotericin B, or flucytosine against strains of C. albicans has not been reported. Carcinogenesis, Mutagenesis, Impairment of Fertility An 18-month oral dosing study with clotrimazole in rats has not revealed any carcinogenic effect. In tests for mutagenesis, chromosomes of the spermatophores of Chinese hamsters which had been exposed to clotrimazole were examined for structural changes during the metaphase. Prior to testing, the hamsters had received five oral clotrimazole doses of 100 mg/kg body weight. The results of this study showed that clotrimazole had no mutagenic effect. Usage in Pregnancy Teratogenic Effects Pregnancy Category B The disposition of 14 C-clotrimazole has been studied in humans and animals. Clotrimazole is very poorly absorbed following dermal application or intravaginal administration to humans. (See CLINICAL PHARMACOLOGY ) In clinical trials, use of vaginally applied clotrimazole in pregnant women in their second and third trimesters has not been associated with ill effects. There are, however, no adequate and well-controlled studies in pregnant women during the first trimester of pregnancy. Studies in pregnant rats with intravaginal doses up to 100 mg/kg have revealed no evidence of harm to the fetus due to clotrimazole. High oral doses of clotrimazole in rats and mice ranging from 50 to 120 mg/kg resulted in embryotoxicity (possibly secondary to maternal toxicity), impairment of mating, decreased litter size and number of viable young and decreased pup survival to weaning. However, clotrimazole was not teratogenic in mice, rabbits and rats at oral doses up to 200, 180 and 100 mg/kg, respectively. Oral absorption in the rat amounts to approximately 90% of the administered dose. Because animal reproduction studies are not always predictive of human response, this drug should be used only if clearly indicated during the first trimester of pregnancy.

Nursing

Mothers It is not known whether this drug is excreted in human milk. Because many drugs are excreted in human milk, caution should be exercised when clotrimazole is used by a nursing woman.

Pediatric Use

Safety and effectiveness in pediatric patients have been established for clotrimazole when used as indicated and in the recommended dosage.

Drug Interactions Synergism or antagonism between clotrimazole and nystatin, or amphotericin B, or flucytosine against strains of C. albicans has not been reported.

Active ingredients Purpose Clotrimazole USP, 1% (50 mg in each applicatorful) Vaginal antifungal Clotrimazole USP, 1% (external cream) Vaginal antifungal

Inactive ingredients Ointment: beeswax, coconut oil (organic), cottonseed oil*, jojoba oil, magnesium oxide, MCT oil, peppermint oil, sage oil, silver stearate, tea tree oil, vegetable stearic acid (naturally sourced)* witch hazel, zinc oxide Soap Bar: beeswax, citric acid, glycerin, jojoba oil, lavender oil, magnesium oxide, MCT oil, peppermint oil, propylene glycol, silver stearate, sodium chloride, sodium citrate, sodium laurate, sodium laureth sulfate, sodium lauryl sulfate, sodium myristate, sodium oleate, sodium olivate, sodium shea butterate, sodium stearate, sorbitol, tea tree oil, tetrasodium etidronate, tetrasodium iminodisuccinate, titanium dioxide, water, zinc oxide *may contain this ingredient