KETOCONAZOLE

Drug Interactions Coadministration of a number of CYP3A4 substrates such as dofetilide, quinidine cisapride and pimozide is contraindicated with ketoconazole tablets. Coadministration with ketoconazole can cause elevated plasma concentrations of these drugs and may increase or prolong both therapeutic and adverse effects to such an extent that a potentially serious adverse reaction may occur. For example, increased plasma concentrations of some of these drugs can lead to QT prolongation and sometimes resulting in life-threatening ventricular tachyarrhythmias including occurrences of torsades de pointes, a potentially fatal arrhythmia. (See PRECAUTIONS: DRUG INTERACTIONS .) Coadministration of ketoconazole tablets with lurasidone is contraindicated since it may result in an increase in lurasidone exposure and the potential for serious adverse reactions (see PRECAUTIONS: DRUG INTERACTIONS ). Additionally, the following other drugs are contraindicated with ketoconazole tablets: methadone, disopyramide, dronedarone, ergot alkaloids such as dihydroergotamine, ergometrine, ergotamine, methylergometrine, irinotecan, lurasidone, oral midazolam, alprazolam, triazolam, felodipine, nisoldipine, ranolazine, tolvaptan, eplerenone, lovastatin, simvastatin and colchicine. (See PRECAUTIONS: DRUG INTERACTIONS .) Enhanced Sedation Coadministration of ketoconazole tablets with oral midazolam, oral triazolam or alprazolam has resulted in elevated plasma concentrations of these drugs. This may potentiate and prolong hypnotic and sedative effects, especially with repeated dosing or chronic administration of these agents. Concomitant administration of ketoconazole tablets with oral triazolam, oral midazolam or alprazolam is contraindicated. (See PRECAUTIONS: DRUG INTERACTIONS .) Myopathy Coadministration of CYP3A4 metabolized HMG-CoA reductase inhibitors such as simvastatin, and lovastatin is contraindicated with ketoconazole tablets. (See PRECAUTIONS: DRUG INTERACTIONS .) Ergotism Concomitant administration of ergot alkaloids such as dihydroergotamine and ergotamine with ketoconazole tablets is contraindicated. (See PRECAUTIONS: DRUG INTERACTIONS .) Liver Disease The use of ketoconazole tablets is contraindicated in patients with acute or chronic liver disease. Hypersensitivity Ketoconazole tablets USP, 200 mg is contraindicated in patients who have shown hypersensitivity to the drug.

Controls flaking, scaling and itching associated with dandruff

DOSAGE AND ADMINISTRATION There should be laboratory as well as clinical documentation of infection prior to starting ketoconazole therapy. The usual duration of therapy for systemic infection is 6 months. Treatment should be continued until active fungal infection has subsided. Adults The recommended starting dose of ketoconazole tablets is a single daily administration of 200 mg (one tablet). If clinical responsiveness is insufficient within the expected time, the dose of ketoconazole tablets 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.

ADVERSE REACTIONS Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. The following adverse reactions were reported in clinical trials: Immune System Disorders: anaphylactoid reaction Endocrine Disorders: gynecomastia Metabolism and Nutrition Disorders: alcohol intolerance, anorexia, hyperlipidemia, increased appetite Psychiatric Disorders: insomnia, nervousness Nervous System Disorders: headache, dizziness, paresthesia, somnolence Eye Disorders: photophobia Vascular Disorders: orthostatic hypotension Respiratory, Thoracic and Mediastinal Disorders: epistaxis Gastrointestinal Disorders: vomiting, diarrhea, nausea, constipation, abdominal pain, abdominal pain upper, dry mouth, dysgeusia, dyspepsia, flatulence, tongue discoloration Hepatobiliary Disorders: hepatitis, jaundice, hepatic function abnormal Skin and Subcutaneous Tissues Disorders: erythema multiforme, rash, dermatitis, erythema, urticaria, pruritus, alopecia, xeroderma Musculoskeletal and Connective Tissue Disorders: myalgia Reproductive System and Breast Disorders: menstrual disorder General Disorders and Administration Site Conditions: asthenia, fatigue, hot flush, malaise, edema peripheral, pyrexia, chills Investigations: platelet count decreased. Post-Marketing Experience The following adverse reactions have been identified during postapproval use of ketoconazole tablets. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure. The following adverse reactions were reported during post-marketing experience: Blood and Lymphatic System Disorders: thrombocytopenia Immune System Disorders: allergic conditions including anaphylactic shock, anaphylactic reaction, angioneurotic edema Endocrine Disorders: adrenocortical insufficiency Nervous System Disorders: reversible intracranial pressure increased (e.g. papilloedema, fontanelle bulging in infants) Hepatobiliary Disorders: serious hepatotoxicity including hepatitis cholestatic, biopsy-confirmed hepatic necrosis, cirrhosis, hepatic failure including cases resulting in transplantation or death Skin and Subcutaneous Tissue Disorders: acute generalized exanthematous pustulosis, photosensitivity Musculoskeletal and Connective Tissue Disorders: arthralgia Reproductive System and Breast Disorders: erectile dysfunction; with doses higher than the recommended therapeutic dose of 200 or 400mg daily, azoospermia.