FDA Clears IV Formulation of Antifungal Posaconazole

Megan Brooks

Disclosures

March 18, 2014

The US Food and Drug Administration (FDA) has approved an intravenous (IV) formulation of the triazole antifungal posaconazole (Noxafil, Merck), according to the company.

Posaconazole is also available in 100-mg delayed-release tablets and 40 mg/mL oral suspension. Posaconazole injection is indicated in patients at least 18 years of age, whereas the delayed-release tablets and oral suspension are indicated in patients aged 13 years and older.

The availability of an IV formulation of posaconazole is "particularly important for those patients who may benefit from or require intravenous therapy, or who, for a variety of reasons, might not be able to take an oral formulation. In addition, patients have the possibility to start on Noxafil injection and transition to oral Noxafil," Nicholas Kartsonis, executive director, Infectious Disease, Merck Research Laboratories, said in a statement.

Posaconazole is indicated for prophylaxis of invasive Aspergillus and Candida infections in patients who are at high risk of developing these infections because of being severely immunocompromised, such as hematopoietic stem cell transplant recipients with graft-vs-host disease or those with hematologic malignancies with prolonged neutropenia from chemotherapy.

Posaconazole injection is given as a loading dose of 300 mg (one 300-mg vial) twice on the first day of treatment, followed by 300 mg (one 300-mg vial) once daily thereafter.

Once combined with a mixture of IV solution (150 mL of 5% dextrose in water or sodium chloride 0.9%), posaconazole injection should be administered immediately via a central venous line by slow IV infusion over approximately 90 minutes. If not used immediately, the solution can be stored up to 24 hours refrigerated at 2°C to 8°C (36°F - 46°F), the company said.

They note in the release that coadministering drugs that can decrease the plasma concentration of posaconazole should "generally be avoided unless the benefit outweighs the risk. If such drugs are necessary, patients should be monitored closely for breakthrough fungal infections."

In clinical trials, adverse reactions reported for posaconazole IV injection were generally similar to those reported in trials of posaconazole oral suspension. The most frequently reported adverse reactions with an onset during once-daily dosing were diarrhea (32%), hypokalemia (22%), fever (21%), and nausea (19%).

The company reminds clinicians that posaconazole is contraindicated in persons allergic to posaconazole or other azole antifungal agents. The administration of posaconazole with sirolimus, pimozide, quinidine, atorvastatin, lovastatin, simvastatin, and ergot alkaloids "must be avoided."

When administered with posaconazole, some drugs such as cyclosporine and tacrolimus required dosage adjustments and frequent monitoring of their levels in the blood, as serious adverse effects, including nephrotoxicity or leukoencephalopathy, and deaths have been reported in patients with increased cyclosporine or tacrolimus blood levels, the company notes.

Caution is needed when administering posaconazole to patients who may develop an irregular heart rhythm, as the antifungal has been shown to prolong the QT interval, and cases of potentially fatal torsades de pointes have been reported in patients taking the antifungal, the company adds.

Posaconazole injection is expected to be available at wholesalers in mid-April.

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