Itraconazole warnings and precautions

# Warnings
SPORANOX (itraconazole) Capsules and SPORANOX Oral Solution should not be used interchangeably. This is because drug exposure is greater with the Oral Solution than with the Capsules when the same dose of drug is given. In addition, the topical effects of mucosal exposure may be different between the two formulations. Only the Oral Solution has been demonstrated effective for oral and/or esophageal candidiasis.
Hepatic Effects
SPORANOX has been associated with rare cases of serious hepatotoxicity, including liver failure and death. Some of these cases had neither pre-existing liver disease nor a serious underlying medical condition, and some of these cases developed within the first week of treatment. If clinical signs or symptoms develop that are consistent with liver disease, treatment should be discontinued and liver function testing performed. Continued SPORANOX use or reinstitution of treatment with SPORANOX is strongly discouraged unless there is a serious or life-threatening situation where the expected benefit exceeds the risk. (See PRECAUTIONS: Information for Patients and ADVERSE REACTIONS.)
Cardiac Dysrhythmias
Life-threatening cardiac dysrhythmias and/or sudden death have occurred in patients using cisapride, pimozide, methadone, levacetylmethadol (levomethadyl), or quinidine concomitantly with SPORANOX and/or other CYP3A4 inhibitors. Concomitant administration of these drugs with SPORANOX is contraindicated. (See BOX WARNING, CONTRAINDICATIONS, and PRECAUTIONS: Drug Interactions.)
Cardiac Disease
SPORANOX Capsules should not be administered for the treatment of onychomycosis in patients with evidence of ventricular dysfunction such as congestive heart failure (CHF) or a history of CHF. SPORANOX Capsules should not be used for other indications in patients with evidence of ventricular dysfunction unless the benefit clearly outweighs the risk.
For patients with risk factors for congestive heart failure, physicians should carefully review the risks and benefits of SPORANOX therapy. These risk factors include cardiac disease such as ischemic and valvular disease; significant pulmonary disease such as chronic obstructive pulmonary disease; and renal failure and other edematous disorders. Such patients should be informed of the signs and symptoms of CHF, should be treated with caution, and should be monitored for signs and symptoms of CHF during treatment. If signs or symptoms of CHF appear during administration of SPORANOXCapsules, discontinue administration.
Itraconazole has been shown to have a negative inotropic effect. When itraconazole was administered intravenously to anesthetized dogs, a dose-related negative inotropic effect was documented. In a healthy volunteer study of itraconazole intravenous infusion, transient, asymptomatic decreases in left ventricular ejection fraction were observed using gated SPECT imaging; these resolved before the next infusion, 12 hours later.
SPORANOX has been associated with reports of congestive heart failure. In post-marketing experience, heart failure was more frequently reported in patients receiving a total daily dose of 400 mg although there were also cases reported among those receiving lower total daily doses.
Calcium channel blockers can have negative inotropic effects which may be additive to those of itraconazole. In addition, itraconazole can inhibit the metabolism of calcium channel blockers. Therefore, caution should be used when co-administering itraconazole and calcium channel blockers due to an increased risk of CHF. Concomitant administration of SPORANOX and nisoldipine is contraindicated.
Cases of CHF, peripheral edema, and pulmonary edema have been reported in the post-marketing period among patients being treated for onychomycosis and/or systemic fungal infections. (See CLINICAL PHARMACOLOGY: Special Populations, CONTRAINDICATIONS, PRECAUTIONS: Drug Interactions, and ADVERSE REACTIONS: Post-marketing Experience for more information.)
PRECAUTIONS
General
SPORANOX (itraconazole) Capsules should be administered after a full meal. (See CLINICAL PHARMACOLOGY: Pharmacokinetics and Metabolism.)
Under fasted conditions, itraconazole absorption was decreased in the presence of decreased gastric acidity. The absorption of itraconazole may be decreased with the concomitant administration of antacids or gastric acid secretion suppressors. Studies conducted under fasted conditions demonstrated that administration with 8 ounces of a cola beverage resulted in increased absorption of itraconazole in AIDS patients with relative or absolute achlorhydria. This increase relative to the effects of a full meal is unknown. (See CLINICAL PHARMACOLOGY: Pharmacokinetics and Metabolism.)
Hepatotoxicity
Rare cases of serious hepatotoxicity have been observed with SPORANOX treatment, including some cases within the first week. In patients with elevated or abnormal liver enzymes or active liver disease, or who have experienced liver toxicity with other drugs, treatment with SPORANOX is strongly discouraged unless there is a serious or life threatening situation where the expected benefit exceeds the risk. Liver function monitoring should be done in patients with pre-existing hepatic function abnormalities or those who have experienced liver toxicity with other medications and should be considered in all patients receiving SPORANOX. Treatment should be stopped immediately and liver function testing should be conducted in patients who develop signs and symptoms suggestive of liver dysfunction.
Neuropathy
If neuropathy occurs that may be attributable to SPORANOX Capsules, the treatment should be discontinued.
Hearing Loss
Transient or permanent hearing loss has been reported in patients receiving treatment with itraconazole. Several of these reports included concurrent administration of quinidine which is contraindicated (see BOX WARNING: Drug Interactions; CONTRAINDICATIONS: Drug Interactions andPRECAUTIONS: Drug Interactions). The hearing loss usually resolves when treatment is stopped, but can persist in some patients.