The FDA has approved isavuconazonium sulfate (Cresemba – Astellas) for intravenous and oral treatment of invasive aspergillosis and invasive mucormycosis in adults. Isavuconazonium sulfate is a prodrug of isavuconazole, a broad-spectrum triazole antifungal.

The FDA has approved an IV formulation of the antifungal drug posaconazole (Noxafil - Merck) for prophylaxis of Aspergillus and Candida infections in adults at high risk for these infections, such as those with prolonged neutropenia. Posaconazole is also available as delayed-release tablets and an oral suspension.

With activity against Aspergillus and Candida, posaconazole has an antifungal spectrum similar to that of voriconazole (Vfend, and generics), but unlike voriconazole it is also active against many species of Mucorales (formerly called Zygomycetes), such as Mucor and Rhizopus. Posaconazole has variable activity against Fusarium spp. and Scedosporium spp.1

Fever, diarrhea, nausea, vomiting, rash, headache, fatigue, hypokalemia, QT interval prolongation, and abnormal liver function have been reported with posaconazole. Arrhythmias, toxic epidermal necrolysis, angioedema, and anaphylaxis have occurred rarely.

Posaconazole is primarily metabolized via UDP glucuronidation; it is also a substrate of P-glycoprotein (P-gp). Drugs that inhibit or induce these clearance pathways may alter serum concentrations of posaconazole. Posaconazole is a strong inhibitor of CYP3A4 and may increase serum concentrations of drugs that are primarily metabolized by this pathway.2 Taking posaconazole with other drugs that prolong the QT interval (www.crediblemeds.org), especially those metabolized by CYP3A4, may increase the risk of QT interval prolongation.

The new formulation of posaconazole is available in 300 mg/16.7 mL vials. The recommended dosage is 300 mg administered intravenously over 90 minutes twice on day 1 and once daily thereafter. To avoid accumulation of the vehicle, patients with moderate or severe renal impairment should not receive IV posaconazole. One vial of Noxafil costs $530.50.3

1. Antifungal drugs. Treat Guidel Med Lett 2012; 10:61.
2. Inhibitors and inducers of CYP enzymes and P-glycoprotein. Med Lett Drugs Ther 2013; 55:e44.
3. Approximate WAC. WAC = wholesaler acquisition cost or manufacturer’s published price to wholesalers; WAC represents a published catalogue or list price and may not represent an actual transactional price. Source: AnalySource® Monthly. January 5, 2015. Reprinted with permission by First Databank, Inc. All rights reserved. ©2015. www.fdbhealth.com/policies/drug-pricing-policy.

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The drugs of choice for treatment of fungal infections are listed in the table that begins on page 62. Some of the indications and dosages recommended here have not been approved by the FDA. More detailed guidelines for some of these infections are available online from the Infectious Diseases Society of America (www.idsociety.org).

The FDA has announced changes in the labeling of simvastatin to reduce the risk of myopathy. These changes include limiting the use of the 80-mg maximum dose to patients who have been taking it for 12 months or more without evidence of myopathy and new recommendations for use of simvastatin with other drugs. Simvastatin is available alone (Zocor, and others) and in combination with ezetimibe (Vytorin) and with niacin (Simcor).

The drugs of choice for treatment of some fungal infections are listed. Some of the indications and dosages recommended here have not been approved by the FDA. More detailed guidelines are available online from the Infectious Diseases Society of America (www.idsociety.org).

A recent letter to the editor of the Annals of Internal Medicine documented a single case of myopathy apparently due to an interaction between simvastatin (Zocor, and others) and green tea. Since it became available generically, simvastatin has surpassed atorvastatin (Lipitor) as the best selling statin. As such, it is probably the most common cause of statin-induced myopathy, which is often a result of drug interactions.

The drugs of choice for treatment of some fungal infections are listed in the tables. Some of the indications and dosages recommended here have not been approved by the FDA. Other guidelines are available from the Infectious Diseases Society of America (www.idsociety.org).

Posaconazole (Noxafil - Schering-Plough), an oral azole antifungal with a chemical structure similar to that of itraconazole (Sporanox), has been approved by the FDA to prevent Candida and Aspergillus infections in severely immunocompromised patients and for treatment of oropharyngeal candidiasis. It is likely also to be used off-label for treatment of other fungal infections, including those caused by Mucor and other Zygomycetes.