Posaconazole

Restricted
Restricted

C. diff Risk

Low

Oral Bioavailability

Excellent

Approximate Cost

$$$$

Dosing

Adult

Suspension
200 - 400 mg 2-3 times daily, based on indication and pathogen.
Consult guidelines.

Delayed Release
300 mg q12 h x 2 doses, then 300 mg daily.

Restricted Use

  • For prophylaxis of invasive Aspergillus and Candida infections in severely immunocompromised patients

  • For Pediatric patients: restricted to use by Pediatric Infectious Diseases Service approval.

General Information

Acceptable Uses

  • Treatment of invasive zygomycosis in combination with Amphotericin B

  • Monotherapy for zygomycosis after 7 days of combination therapy with Amphotericin B

  • Note: posaconazole requires up to 7 days to achieve steady state concentrations. ID consult is advised.

Unacceptable Uses

  • Candidiasis/neutropenic fever

  • Primary treatment of aspergillosis

Common Usage

Prophylaxis of invasive fungal infection in immunocompromised patients such as stem cell transplant recipients

Treatment of invasive fungal infections such as candidiasis if conventional therapy has failed

Drug Monitoring

Laboratory

  • Hepatic enzymes at baseline and every 1-2 weeks after

  • Therapeutic drug monitoring at steady state (5-7 days). Target >1.25 mcg/mL for invasive fungal disease or >0.7 mcg/mL for prophylaxis

Clinical

  • GI effects

  • Prolongation of QT interval with risk factors

  • Hypersensitivity

  • Photosensitivity

  • Drug-drug interactions

Adverse Effects

  • GI upset (~40%),

  • Headaches

  • Elevation in hepatic enzymes

  • Hypersensitivity

  • Rare but serious effects include QTc prolongation

Major Interactions

  • 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.

Additional Information

High pharmacokinetic variability, dependent on fatty food administration (for solution).

The two oral formulations of posaconazole (delayed-release tablets and an oral suspension) are not interchangeable, and cannot be directly substituted without a change in dosage.

All orders for posaconazole must specify the dosage form, strength, and frequency

Pharmacology

Antimicrobial class: azole

Pregnancy category: C