Noxafil

Posaconazole

Prophylaxis of invasive Aspergillus & Candida infections including both yeasts & molds in patients ≥13 yr who are at high risk of developing these infections (eg, w/ prolonged neutropenia or hematopoietic stem cell transplant recipients). Patients ≥13 yr w/ refractory invasive fungal infections (IFI) or intolerant patients w/ IFI. Oral susp: Oropharyngeal candidiasis in patients ≥13 yr who have severe disease or who are immunocompromised including those w/ disease that is refractory to itraconazole & fluconazole.

DR tab Patient ≥13 yr Prophylaxis of IFI Loading dose: 300 mg bd on the 1st day then 300 mg once daily thereafter. Patient w/ acute myelogenous leukemia or myelodysplastic syndromes Start for several days before anticipated neutropenia onset & continue for 7 days after the neutrophil count is >500 cells/mm³. Refractory IFI or IFI intolerant to 1st line therapy Loading dose: 300 mg bd on the 1st day then 300 mg once daily thereafter. Oral susp Patient ≥13 yr Prophylaxis of IFI 5 mL tds. Refractory IFI or intolerant patient w/ IFI 10 mL bd. Patient who cannot tolerate a meal/nutritional supplement 5 mL qds. Oropharyngeal candidiasis Loading dose: 5 mL once daily on the 1st day then 2.5 mL once daily for 13 days. Refractory oropharyngeal candidiasis 10 mL bd.

DR tab: May be taken with or without food: Swallow whole, do not divide/crush/chew. Oral susp: Should be taken with food: Take w/ a full meal or w/ 240 mL of liqd nutritional supplement in patients who cannot eat a full meal.

Hypersensitivity. Co-administration w/ terfenadine, astemizole, cisapride, pimozide, quinidine; HMG-CoA reductase inhibitors primarily metabolized through CYP3A4; ergot alkaloids.

Hypersensitivity to other azoles. Patients w/ potentially proarrhythmic conditions; not to be administered w/ known QTc interval-prolonging medicines & are metabolized through CYP3A4. Possible electrolyte disturbances; monitor K, Mg & Ca levels & correct as necessary before & during therapy. Concomitant administration w/ vincristine & venetoclax. Patient w/ severe GI dysfunction (eg, severe diarrhoea); closely monitor for breakthrough fungal infections in patients who have severe diarrhoea or vomiting. Posaconazole plasma conc following administration of DR tab is generally higher than w/ oral susp. Closely monitor patients w/ severe renal impairment for potential breakthrough fungal infections. Patient w/ severe hepatic impairment. Evaluate LFTs at the start & during the course of therapy. Consider discontinuation of treatment if clinical signs & symptoms consistent w/ liver disease develop. Advise women of childbearing potential to always use effective contraceptive measure during treatment & for at least 2 wk after completing therapy. Pregnancy & lactation. Childn <13 yr.

Nausea & diarrhea. Neutropenia; anorexia, electrolyte imbalance; dizziness, headache, paresthesia, somnolence; abdominal pain, dyspepsia, flatulence, dry mouth, vomiting; elevated LFTs (including AST, ALT, alkaline phosphatase, GGT, bilirubin); asterixis, cholestasis, hepatic failure, cholestatic hepatitis, hepatosplenomegaly, liver tenderness, splenomegaly, rash; asthenia, fatigue, fever.

Plasma conc may be affected by inhibitors or inducers of UDP glucuronidation (phase 2 enzymes) & P-gp efflux. Decreased C_max & AUC w/ rifabutin, efavirenz & phenytoin. May increase plasma levels of cytochrome P450 metabolized drugs. May increase plasma conc of ergot & vinca alkaloids; digoxin. Increased C_max & AUC of tacrolimus; rifabutin. Frequently monitor for adverse effects & toxicity related to Ca channel blockers. Increased C_max & AUC_0-INF of venetoclax. Decreased glucose conc w/ sulfonylureas (eg, glipizide). Oral susp: Decreased C_max & AUC w/ cimetidine, esomeprazole; avoid co-administration w/ H₂ receptor antagonists & PPIs if possible. Decreased plasma conc w/ metoclopramide. May decrease plasma conc w/ fosamprenavir. May increase plasma conc of terfenadine, astemizole, cisapride, pimozide & quinidine. Increased cyclosporine conc in heart transplant patients on stable doses of cyclosporine. Increased C_max & AUC of sirolimus; midazolam IV; atazanavir; simvastatin.

Antifungals

J02AC04 - posaconazole ; Belongs to the class of triazole and tetrazole derivatives. Used in the systemic treatment of mycotic infections.

POM