Trade Names:Noxafil- Suspension, oral 40 mg/mLSpriafil (Canada)
Blocks the synthesis of ergosterol, a key component of fungal cell membranes.
T max is approximately 3 to 5 h. Steady-state plasma concentrations are reached in 7 to 10 days.
Vd is 1,774 L, suggesting extensive extravascular distribution and penetration into body tissues. Posaconazole is over 98% protein bound, primarily to albumin.
Metabolism mainly involves glucuronide conjugation via uridine diphosphate glucuronidation.
Elimination is approximately 71% in feces and 13% in urine in up to 120 h. The mean t ½ is 35 h.
Prophylaxis of invasive Aspergillus and Candida infections in patients who are at high risk of developing these infections because of severe immunocompromise; treatment of oropharyngeal candidiasis refractory to itraconazole and/or fluconazole.
Coadministration of ergot derivatives; coadministration with CYP3A4 substrates, including cisapride, halofantrine, pimozide, or quinidine; hypersensitivity to any component of the product.
PO 200 mg tid. The duration is based on recovery from neutropenia or immunosuppression.Oropharyngeal CandidiasisAdults and children 13 yr of age and older
PO Start with a loading dose of 100 mg bid on the first day, then 100 mg once daily for 13 days.Oropharyngeal Candidiasis Refractory to Itraconazole and/or FluconazoleAdults and children 13 yr of age and older
PO 400 mg bid. Duration based on severity of the underlying disease and clinical response.
Store at 59° to 86°F. Do not freeze.
Posaconazole may elevate plasma levels of these agents, increasing the risk of toxicity.Cimetidine, phenytoin, rifabutin
Posaconazole plasma levels may be decreased; if possible, avoid coadministration.Cyclosporine, sirolimus, tacrolimus
Plasma levels of these drugs may be elevated by posaconazole, increasing the risk of serious adverse reactions, including nephrotoxicity.CYP3A4 substrates astemizole, cisapride, halofantrine, pimozide, quinidine, or terfenadine
Plasma levels of these agents may be elevated by posaconazole, leading to QTc prolongation and increasing the risk of life-threatening cardiac arrhythmias, including torsades de pointes. Coadministration with posaconazole is contraindicated.Ergot derivatives
Plasma levels may be elevated by posaconazole, increasing the risk of ergotism. Coadministration with posaconazole is contraindicated.HMG-CoA reductase inhibitors (statins) metabolized through CYP3A4
Posaconazole may elevate plasma levels of these agents, increasing the risk of adverse reactions (eg, rhabdomyolysis). Statin dose reduction is recommended.Midazolam, phenytoin, rifabutin
Plasma concentrations of these drugs may be elevated by posaconazole.Vinca alkaloids
Plasma concentrations may be elevated by posaconazole, increasing the risk of neurotoxicity.
None well documented.
Hypertension (18%); hypotension (14%); tachycardia (12%); QT/QTc prolongation (4%).
Headache (28%); fatigue, insomnia (17%); dizziness (11%); anxiety (9%); weakness (8%); asthenia (2%); somnolence, tremor (1%).
Rash (19%); pruritus (11%); increased sweating (2%).
Pharyngitis (12%); blurred vision, taste perversion (1%).
Diarrhea (42%); nausea (38%); vomiting (29%); abdominal pain (27%); constipation (21%); mucositis (17%); anorexia (15%); dyspepsia (10%); dry mouth, flatulence (1%).
Vaginal hemorrhage (10%); increased blood creatinine (2%).
Bilirubinemia (10%); increased ALT, AST, or gamma-glutamyl transferase (3%); hepatitis (1%).
Thrombocytopenia (29%); anemia (25%); neutropenia (23%); febrile neutropenia (20%); petechiae (11%).
Hypokalemia (30%); hypomagnesemia (18%); hyperglycemia (11%); increased alkaline phosphatase (2%); decreased weight, dehydration (1%).
Rigors (20%); musculoskeletal pain (16%); arthralgia (11%); back pain (10%).
Coughing (24%); dyspnea (20%); epistaxis (14%); upper respiratory tract infection (7%); pneumonia (3%).
Fever (45%); bacteremia (18%); herpes simplex, leg edema (15%); cytomegalovirus infection (14%); edema (9%); oral candidiasis (1%).
Monitor patients who have severe renal function impairment, severe diarrhea, or vomiting for breakthrough fungal infections. Monitor patients who develop abnormal LFTs during therapy for development of more severe hepatic injury.
Category C .
Safety and efficacy not established in children younger than 13 yr of age.
Because there is no information regarding cross-sensitivity with other azole antifungal agents, use with caution in patients with hypersensitivity to other azoles.
No adverse reactions were noted with doses up to 1,600 mg/day.
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