Alcohol or Hepatotoxic medications, other (concurrent use with Ketoconazole may result in an increased incidence of hepatotoxicity; patients, especially those on prolonged administration or those with history of liver disease, should be monitored carefully and should be advised to avoid alcoholic beverages and other hepatotoxins) (concurrent ingestion of alcohol with Ketoconazole has been reported to result disulfiram-like reaction, characterized by facial flushing; other symptoms may include difficult breathing, slight fever, and tightness of the chest; these effects subsided spontaneously within 24 hours with no lasting ill effects).
Alprazolam; Diazepam; Midazolam; Triazolam (concurrent use with Ketoconazole elevates the plasma concentration of oral Midazolam or Triazolam, which may potentiate and prolong their hypnotic and sedative effects; oral Midazolam and Triazolam should not be used in patients treated with Ketoconazole).
Antacids or Anticholinergics/antispasmodic; Histamine H2-receptor antagonists or Omeprazole and Sucralfate (these medications increase gastrointestinal pH; this may result in a marked reduction in absorption of Ketoconazole; Ketoconazole depends on stomach acid for dissolution and subsequent absorption; patients should be advised to take these medications at least 2 hours after taking Ketoconazole).
Astemizole and Terfenadine (concurrent use of these medications with Ketoconazole is contraindicated; concurrent use of these antihistamines with Ketoconazole may result in elevated plasma concentrations of Astemizole or Terfenadine by inhibiting the cytochrome P450 enzyme metabolic pathways; this has led to cardiac arrhythmias, including QT prolongation, ventricular tachycardia, torsades de pointes, and death).
Cisapride (concurrent use of Cisapride with oral Ketoconazole is contraindicated; concurrent use of Cisapride with these antifungals may inhibit the cytochrome P450 enzyme metabolic pathways, resulting in elevated plasma concentrations of Cisapride; this has led to ventricular arrhythmias, including torsades de pointes and QT prolongation, in patients taking Cisapride and oral Ketoconazole).
Cyclosporin and Tacrolimus (Ketoconazole has been reported to inhibit the metabolism of Cyclosporin and Tacrolimus; this may increase the plasma concentration of Cyclosporin or Tacrolimus to potentially toxic levels; plasma concentrations should be monitored carefully in patients receiving any of the azole antifungals; the dose of Cyclosporin may need to be reduced).
Didanosine (ddl) (Didanosine contains a buffer that increases gastrointestinal pH in order to increase its absorption; Ketoconazole require an acidic environment for their optimal absorption; concurrent administration may result in a marked reduction in absorption of any of these medications; Ketoconazole should be administered at least 2 hours before or 2 hours after Didanosine is given).
Digoxin (Ketoconazole may increase serum Digoxin concentrations, leading to toxicity; Digoxin concentrations should be monitored).
Indinavir; Ritonavir; Saquinavir (concurrent use of Ketoconazole with Indinavir increases the AUC for Indinavir by 68 + 48%; a dose reduction of Indinavir to 600 mg every 8 hours is recommended).
Isoniazid or Rifampin (concurrent use of Rifampin may increase metabolism of Ketoconazole, lowering their plasma concentrations; this may lead to clinical failure or relapse; concurrent use of Isoniazid with Ketoconazole has also been reported to decrease serum concentrations of Ketoconazole; Isoniazid or Rifampin is not recommended to be given concurrently with azole antifungals).
Warfarin (anticoagulant effects may be increased when Warfarin is used concurrently with any azole antifungal, resulting in an increase in prothrombin time [PT]; PT must be monitored carefully in patients receiving Warfarin and azole antifungals.