JAMP POSACONAZOLE

1 Dosing Considerations  The prescriber should follow the specific dosing instructions for oral suspension.  The tablet, oral suspension and intravenous solution are not to be used interchangeably due to the differences in the dosing of each formulation.

 Each dose of JAMP Posaconazole oral suspension should be administered with a meal, or with a nutritional supplement in patients who cannot tolerate food to enhance the oral absorption. For patients who cannot eat a full meal or tolerate an oral nutritional supplement, an alternative antifungal therapy should be considered or patients should be monitored closely for breakthrough fungal infections.

 Patients who have severe diarrhea or vomiting should be monitored closely for breakthrough fungal infections.  Co-administration of drugs that can decrease the plasma concentrations of JAMP 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 (see 9 DRUG INTERACTIONS). Product Monograph JAMP Posaconazole (posaconzole oral suspension) Page 7 of 57  Pharmacokinetic modeling suggests that patients weighing greater than 120 kg may have lower posaconazole plasma drug exposure.

It is, therefore, suggested to closely monitor for breakthrough fungal infections. 2 Recommended Dose and Dosage Adjustment Recommended Dose Table 1 – Recommended Dosing for JAMP Posaconazole oral suspension Indication Dose and Duration of therapy Prophylaxis of Invasive Fungal Infections (IFIs) 200 mg (5 mL) three times a day.

The duration of therapy is based on recovery from neutropenia or immunosuppression. For patients with acute myelogenous leukemia (AML) or myelodysplastic syndromes (MDS), prophylaxis with JAMP Posaconazole should start several days before the anticipated onset of neutropenia and continue for 7 days after the neutrophil count rises above 500 cells per mm3.

Treatment of Refractory IFIs / Intolerant Patients with IFIs 400 mg (10 mL) twice a daya In patients who cannot tolerate a meal or a nutritional supplement, JAMP Posaconazole should be administered at a dose of 200 mg (5 mL) four times a day.

Duration of therapy should be based on the severity of the underlying disease, recovery from immunosuppression, and clinical response. 5 mL) once a day for 13 days. a: Increasing the total daily dose of oral suspension above 800 mg does not further enhance the exposure to JAMP Posaconazole.

, Less Common Clinical Trial Adverse Drug Reactions (< 2%)). Dependence/Tolerance There is no known abuse potential for posaconazole. Hematologic Rare cases of hemolytic uremic syndrome and thrombotic thrombocytopenic purpura have been reported primarily among patients who had been receiving concomitant cyclosporine or tacrolimus for management of transplant rejection or graft vs.

host disease (GVHD). , mild to moderate elevations in ALT (Alanine aminotransferase), AST (Aspartate aminotransferase), alkaline phosphatase, total bilirubin, and/or clinical hepatitis) during treatment with posaconazole. The elevations in liver function tests were generally reversible on discontinuation of therapy, and in some instances these tests normalized without drug interruption and rarely required drug discontinuation.

, hematologic malignancy) during treatment with posaconazole.

Monitoring of hepatic function:

Liver function tests should be evaluated at the start of and during the course of JAMP Posaconazole therapy. Patients who develop abnormal liver function tests during JAMP Posaconazole therapy should be monitored for the development of more severe hepatic injury.

Patient management should include laboratory evaluation of hepatic function (particularly liver function tests and bilirubin). Discontinuation of JAMP Posaconazole should be considered if clinical signs and symptoms are consistent with development of worsening liver disease.

Hepatic Impairment:

JAMP Posaconazole should be used with caution in patients with severe hepatic impairment. Prolonged elimination half-life may lead to increased exposure.

Immune Patients Taking Immunosuppressant:

1 Dosing Considerations  The prescriber should follow the specific dosing instructions for oral suspension.  The tablet, oral suspension and intravenous solution are not to be used interchangeably due to the differences in the dosing of each formulation.

 Each dose of JAMP Posaconazole oral suspension should be administered with a meal, or with a nutritional supplement in patients who cannot tolerate food to enhance the oral absorption. For patients who cannot eat a full meal or tolerate an oral nutritional supplement, an alternative antifungal therapy should be considered or patients should be monitored closely for breakthrough fungal infections.

 Patients who have severe diarrhea or vomiting should be monitored closely for breakthrough fungal infections.  Co-administration of drugs that can decrease the plasma concentrations of JAMP 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 (see 9 DRUG INTERACTIONS). Product Monograph JAMP Posaconazole (posaconzole oral suspension) Page 7 of 57  Pharmacokinetic modeling suggests that patients weighing greater than 120 kg may have lower posaconazole plasma drug exposure.

It is, therefore, suggested to closely monitor for breakthrough fungal infections. 2 Recommended Dose and Dosage Adjustment Recommended Dose Table 1 – Recommended Dosing for JAMP Posaconazole oral suspension Indication Dose and Duration of therapy Prophylaxis of Invasive Fungal Infections (IFIs) 200 mg (5 mL) three times a day.

The duration of therapy is based on recovery from neutropenia or immunosuppression. For patients with acute myelogenous leukemia (AML) or myelodysplastic syndromes (MDS), prophylaxis with JAMP Posaconazole should start several days before the anticipated onset of neutropenia and continue for 7 days after the neutrophil count rises above 500 cells per mm3.

 Patients who are hypersensitive to this drug or to any ingredient in the formulation or component of the container. For a complete listing, see the Dosage Forms, Composition and Packaging section of the product monograph. There is no information regarding cross- sensitivity between posaconazole and other azole antifungal agents.

Caution should be used when prescribing JAMP Posaconazole to patients with hypersensitivity to other azoles.  Co-administration of JAMP Posaconazole and ergot alkaloids. Posaconazole may increase the plasma concentrations of ergot alkaloids, which may lead to ergotism (see 9 DRUG INTERACTIONS).

Product Monograph JAMP Posaconazole (posaconzole oral suspension) Page 6 of 57  Co-administration of JAMP Posaconazole and certain medicinal products metabolized through the CYP3A4 system: terfenadine, astemizole, cisapride, pimozide and quinidine.

Although not studied in vitro or in vivo, co-administration of these CYP3A4 substrates may result in increased plasma concentrations of those medicinal products, leading to potentially serious and/or life- threatening adverse events, such as QT prolongation and rare occurrences of torsade de pointes (see 9 DRUG INTERACTIONS).

 Co-administration of JAMP Posaconazole and HMG-CoA reductase inhibitors (statins) that are primarily metabolized through CYP3A4, since increased plasma concentration of these drugs can lead to rhabdomyolysis.  Co-administration of JAMP Posaconazole and sirolimus.

Concomitant administration of posaconazole with sirolimus increases the sirolimus blood concentrations by approximately 9- fold and can result in sirolimus toxicity.