Laboratory

•  Hepatic enzymes at baseline and every 1-2 weeks after
• Therapeutic drug monitoring at steady state (~ 5 days)

Clinical

• GI effects
• Prolongation of QT interval with risk factors
• Hypersensitivity
• Photosensitivity
• Drug-drug interactions

• GI upset 
• Headaches
• Elevation in hepatic enzymes
• Hypersensitivity
• Rare but serious effects include QTc prolongation

Posaconazole is an inhibitor and is metabolized by cytochrome P4503A4; therefore, coadministration with other agents that are cytochrome P450 substrates, inducers, or inhibitors will result in significant drug interactions.

You must check for potential drug interactions when initiating posaconazole therapy or starting a new medication in patients already receiving posaconazole therapy.

Administration of the following agents with posaconazole is contraindicated:

• Terfenadine, Astemizole, Pimozide, Cisapride, Quinidine, Sirolimus, Halofantrine and ergot alkaloids

Posaconazole inhibits metabolism of the following agents. Dose reductions and close monitoring are recommended when Posaconazole is used with agents concomitantly:

• Tacrolimus – reduce tacrolimus dose to ⅓ and monitor levels
• Cyclosporine – reduce cyclosporine dose to ¾ and monitor drug level
• Midazolam – consider dose reducing
• Cimetidine, rifabutin, efavirenz and phenytoin – unless the benefit outweighs the risk, AVOID concomitant use. If used together, monitor effect of the drugs and consider decreasing dose when posaconazole is added
• Statins (avoid lovastatin and simvastatin), vinca alkaloids, calcium channel blockers, digoxin, atazanavir, ritanovir, QTc prolonging drugs (e.g. amiodarone and erythromycin) – monitor effect of the drugs and consider decreasing dose when posaconazole is added
• Cimetidine, rifabutin, phenytoin, efavirenz, esomeprazole, metoclopramide may decrease posaconazole blood levels.