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Nonteratogenic Effects

Ketoconazole has also been found to be embryotoxic in the rat when given in the diet at doses higher than 80 mg/kg during the first trimester of gestation.

In addition, dystocia (difficult labor) was noted in rats administered oral ketoconazole during the third trimester of gestation. This occurred when ketoconazole was administered at doses higher than 10 mg/kg (higher than 1.25 times the maximum human dose).

It is likely that both the malformations and the embryotoxicity resulting from the administration of oral ketoconazole during gestation are a reflection of the particular sensitivity of the female rat to this drug. For example, the oral LD₅₀ of ketoconazole given by gavage to the female rat is 166 mg/kg whereas in the male rat the oral LD₅₀ is 287 mg/kg.

Nursing Mothers

Since ketoconazole is probably excreted in the milk, mothers who are under treatment should not breast feed.

Pediatric Use

Ketoconazole tablets have not been systematically studied in children of any age, and essentially no information is available on children under 2 years. Ketoconazole should not be used in pediatric patients unless the potential benefit outweighs the risks.

ADVERSE REACTIONS

In rare cases, anaphylaxis has been reported after the first dose. Several cases of hypersensitivity reactions including urticaria have also been reported. However, the most frequent adverse reactions were nausea and/or vomiting in approximately 3%, abdominal pain in 1.2%, pruritus in 1.5%, and the following in less than 1% of the patients: headache, dizziness, somnolence, fever and chills, photophobia, diarrhea, gynecomastia, impotence, thrombocytopenia, leukopenia, hemolytic anemia, and bulging fontanelles. Oligospermia has been reported in investigational studies with the drug at dosages above those currently approved. Oligospermia has not been reported at dosages up to 400 mg daily, however sperm counts have been obtained infrequently in patients treated with these dosages. Most of these reactions were mild and transient and rarely required discontinuation of ketoconazole tablets. In contrast, the rare occurrences of hepatic dysfunction require special attention (see WARNINGS section).

In worldwide postmarketing experience with ketoconazole tablets there have been rare reports of alopecia, paresthesia, and signs of increased intracranial pressure including bulging fontanelles and papilledema. Hypertriglyceridemia has also been reported but a causal association with ketoconazole is uncertain.

Neuropsychiatric disturbances, including suicidal tendencies and severe depression, have occurred rarely in patients using ketoconazole tablets.

Ventricular dysrhythmias (prolonged QT intervals) have occurred with the concomitant use of terfenadine with ketoconazole tablets. (See BOX WARNING, CONTRAINDICATIONS, and WARNINGS sections.) Data suggest that coadministration of ketoconazole tablets and cisapride can result in prolongation of the QT interval and has rarely been associated with ventricular arrhythmias. (See CONTRAINDICATIONS, WARNINGS, and PRECAUTIONS sections.)

OVERDOSAGE

In the event of accidental overdosage, supportive measures, including gastric lavage with sodium bicarbonate, should be employed.

DOSAGE AND ADMINISTRATION

Adults

The recommended starting dose of ketoconazole tablets is a single daily administration of 200 mg (one tablet). In very serious infections or if clinical responsiveness is insufficient within the expected time, the dose of ketoconazole may be increased to 400 mg (two tablets) once daily.

Children

In small numbers of children over 2 years of age, a single daily dose of 3.3 to 6.6 mg/kg has been used. Ketoconazole tablets have not been studied in children under 2 years of age.

There should be laboratory as well as clinical documentation of infection prior to starting ketoconazole therapy. Treatment should be continued until tests indicate that active fungal infection has subsided. Inadequate periods of treatment may yield poor response and lead to early recurrence of clinical symptoms. Minimum treatment for candidiasis is one or two weeks. Patients with chronic mucocutaneous candidiasis usually require maintenance therapy. Minimum treatment for the other indicated systemic mycoses is six months.

Minimum treatment for recalcitrant dermatophyte infections is four weeks in cases involving glabrous skin. Palmar and plantar infections may respond more slowly. Apparent cures may subsequently recur after discontinuation of therapy in some cases.

HOW SUPPLIED

Ketoconazole Tablets, USP are available containing 200 mg of ketoconazole. The 200 mg tablets are white to off-white, round, flat-faced, beveled edge tablets debossed with M above the score and 261 below the score on one side of the tablet and blank on the other side. They are available as follows:

Unit does packages of 30 (3×10) NDC 68084-552-21

STORE AT ROOM TEMPERATURE

15° TO 30°C (59° TO 86°F).

PROTECT FROM MOISTURE.

PACKAGING INFORMATION

American Health Packaging unit dose blisters (see How Supplied section) contain drug product from Mylan Pharmaceuticals, Inc. as follows:

(200 mg / 30 UD) NDC 68084-552-21 packaged from NDC 0378-0261

Packaged and Distributed by:

American Health Packaging

Columbus, OH 43217

8255221/1111

Principal Display Panel

(click image for full-size original)

Revised: 01/2012 American Health Packaging