• PO, IV: Treatment of invasive aspergillosis (tablets and injection).
• PO, IV: Prevention of invasive Aspergillus and Candida infections in patients who are severely immunocompromised, such as hematopoietic stem cell transplant recipients with graft-versus-host disease or those with hematologic malignancies with prolonged neutropenia from chemotherapy (tablets, oral suspension, delayed-release oral suspension, and injection).
• PO: Treatment of oropharyngeal candidiasis (including candidiasis unresponsive to itraconazole or fluconazole) (oral suspension).

Contraindicated in:

• Hypersensitivity to posaconazole or other azole antifungals
• Concurrent use of atorvastatin, ergot alkaloids, lovastatin, pimozide, quinidine, simvastatin, or sirolimus
• Concurrent use of venetoclax at initiation and during the ramp-up phase
• Hereditary fructose intolerance (for delayed-release oral suspension only).

Use Cautiously in:

• History of/predisposition to QTc prolongation including congenital QTc prolongation, concurrent medications that prolong QTc, or electrolyte abnormalities (hypokalemia, hypomagnesemia); correct pre-existing abnormalities prior to administration
• Moderate-severe renal impairment (CCr <50 mL/min); use only if justified by risk/benefit assessment (IV form should be avoided, use oral form only)
• Severe diarrhea, vomiting, or renal impairment (monitor for breakthrough fungal infections)
• OB: Use during pregnancy only if potential maternal benefit justifies potential fetal risk
• Lactation: Use while breastfeeding only if potential maternal benefit justifies potential risk to infant
• Pedi: Children <18 yr (IV) or <13 yr (oral) (safety and effectiveness not established).

CV: QT interval prolongation, TORSADES DE POINTES.

Endo: adrenal insufficiency.

F and E: hypokalemia, hypomagnesemia, hypocalcemia.

GI: diarrhea, nausea, vomiting, HEPATOCELLULAR DAMAGE, PANCREATITIS.

Neuro: headache.

Resp: cough.
Misc: fever, HYPERSENSITIVITY REACTIONS.

Drug-Drug:

• May ↑ cyclosporine, sirolimus, and tacrolimus levels and risk of toxicity; use with sirolimus contraindicated; for cyclosporine and tacrolimus, ↓ dose initially and monitor levels frequently.
• May ↑ quinidine and pimozide levels and the risk for arrhythmias; concurrent use contraindicated.
• May ↑ levels and risk of toxicity from ergot alkaloids, including ergotamine and dihydroergotamine; concurrent use contraindicated.
• May ↑ levels of simvastatin, atorvastatin, or lovastatin and the risk for rhabdomyolysis; concurrent use contraindicated.
• May ↑ risk of tumor lysis syndrome, neutropenia, and serious infection during initiation or the ramp-up phase of venetoclax in patients with chronic lymphocytic leukemia or small lymphocytic leukemia; concurrent use contraindicated.
• Rifabutin, phenytoin, cimetidine, and efavirenz may ↓ levels and may ↓ effectiveness; avoid concurrent use.
• Esomeprazole and metoclopramide may ↓ levels and effectiveness.
• May ↑ rifabutin levels and risk of toxicity; avoid concurrent use.
• QT interval prolonging drugs may ↑ risk for QT interval prolongation and torsades de pointes; avoid concurrent use.
• May ↑ digoxin levels and risk of toxicity; monitor levels frequently.
• May ↑ phenytoin, midazolam, ritonavir, and atazanavir levels and risk of toxicity; monitor for excess clinical effect.
• May ↑ levels of and risk of neurotoxicity, syndrome of inappropriate antidiuretic hormone, and paralytic ileus with concurrent use of vinca alkaloids, including vincristine and vinblastine; consider using an alternative non-azole antifungal.
• May ↑ levels and risk of adverse cardiovascular reactions to calcium channel blockers; consider dosage reduction.

(Generic available)

• Delayed-release tablets: 100 mg;
• Oral suspension (cherry-flavor): 40 mg/mL;
• Solution for injection: 18 mg/mL;

Treatment of Invasive Aspergillosis

• PO (Adults and Children 13 yr): Delayed-release tablets: 300 mg twice daily on Day 1, then 300 mg once daily starting on Day 2 for a total of 6–12 wk.
• IV (Adults and Children 13 yr): 300 mg twice daily on Day 1, then 300 mg once daily starting on Day 2 for a total of 6–12 wk.

Prophylaxis of Invasive Aspergillus and Candida Infections

• PO (Adults and Children 13 yr): Oral suspension: 200 mg 3 times daily. Duration of therapy is based on recovery from neutropenia or immunosuppression.
• PO (Adults and Children 2 yr and >40 kg): Delayed-release tablets: 300 mg twice daily on Day 1, then 300 mg once daily starting on Day 2. Duration of therapy is based on recovery from neutropenia or immunosuppression.
• IV (Adults): 300 mg twice daily on Day 1, then 300 mg once daily starting on Day 2. Duration of therapy is based on recovery from neutropenia or immunosuppression.
• IV (Children 2 yr): 6 mg/kg (max = 300 mg) twice daily on Day 1, then 6 mg/kg (max = 300 mg) once daily starting on Day 2. Duration of therapy is based on recovery from neutropenia or immunosuppression.

Treatment of Oropharyngeal Candidiasis

• PO (Adults and Children 13 yr): Oral suspension: 100 mg twice daily on Day 1, then 100 mg once daily for the next 13 days. For refractory oropharyngeal candidiasis, give 400 mg twice daily; duration of therapy is based on the severity of the patient’s underlying disease and clinical response.

Noxafil

• Blocks ergosterol synthesis, a major component of fungal plasma membrane.

• Fungistatic/fungicidal action against susceptible fungi.

Spectrum:

• Aspergillus spp.
• Candida spp.

Therapeutic Classification: antifungals

Pharmacologic Classification: triazoles

Absorption: Well absorbed following oral administration; absorption is optimized by food; IV administration results in complete bioavailability.

Distribution: Extensive extravascular distribution and penetration into body tissues.

Protein Binding: >98%.

Metabolism/Excretion: Some metabolism via UDP glucuronidation; 66% eliminated unchanged in feces, 13% in urine (mostly as metabolites).

Half-life: 35 hr.

Posanol

(plasma concentrations)

• Instruct patient to take posaconazole during or immediately (within 20 min) following a full meal or liquid nutritional supplement in order to enhance absorption. Take missed doses as soon as remembered. Advise patient to read the Patient Information before taking posaconazole and with each Rx refill in case of changes.
• Advise patient to notify health care professional if severe diarrhea or vomiting occurs; may decrease posaconazole blood levels and allow breakthrough fungal infections or if signs and symptoms of liver injury (itching, yellow eyes or skin, fatigue, flu-like symptoms) or change in heart rate or rhythm occur.
• Instruct patient to notify health care professional of all Rx or OTC medications, vitamins, or herbal products being taken and consult health care professional before taking any new medications.
• May cause fetal harm. Advise females of reproductive potential to notify health care professional if pregnancy is planned or suspected and to avoid breastfeeding during therapy.

po-sa-KON-a-zole