Noxafil

Posaconazole

Treatment of invasive aspergillosis in patients w/ disease that is refractory to amphotericin B or itraconazole or in patients who are intolerant of these medicinal products; fusariosis in patients w/ disease that is refractory to amphotericin B or in patients who are intolerant of amphotericin B; chromoblastomycosis & mycetoma in patients w/ disease that is refractory to itraconazole or in patients who are intolerant of itraconazole; coccidioidomycosis in patients w/ disease that is refractory to amphotericin B, itraconazole or fluconazole or in patients who are intolerant of these medicinal products; zygomycosis, in patients intolerant of, or w/ disease that is refractory to, alternative therapy; oropharyngeal candidiasis, as 1st-line therapy in patients who have severe disease or are immunocompromised, in whom response to topical therapy is expected to be poor. Prophylaxis of invasive fungal infections in patients receiving remission-induction chemotherapy for AML or myelodysplastic syndromes expected to result in prolonged neutropenia & who are at high risk of developing invasive fungal infections; hematopoietic stem cell transplant recipients undergoing high-dose immunosuppressive therapy for graft versus host disease & who are at high risk of developing invasive fungal infections.

Adult Refractory invasive fungal infections (IFI)/patients w/ IFI intolerant to 1st line therapy 200 mg (5 mL) qds. Alternatively, 400 mg (10 mL) bd in patients who can tolerate food or nutritional supplement. Oropharyngeal candidiasis Loading dose: 200 mg (5 mL) once daily on the 1st day, then 100 mg (2.5 mL) once daily for 13 days. Prophylaxis of invasive fungal infections 200 mg (5 mL) tds.

Should be taken with food: Administer during or immediately after a meal or a nutritional supplement in patients who cannot tolerate food.

Hypersensitivity. Co-administration w/ ergot alkaloids; CYP3A4 substrates (terfenadine, astemizole, cisapride, pimozide, halofantrine or quinidine); HMG-CoA reductase inhibitors (simvastatin, lovastatin & atorvastatin). Co-administration during the initiation & dose-titration phase of venetoclax in chronic lymphocytic leukaemia patients.

Reports of hepatic reactions (eg, mild to moderate elevations in ALT, AST, alkaline phosphatase, total bilirubin &/or clinical hepatitis). Evaluate liver function tests at treatment initiation & during therapy. Consider discontinuation in case of signs & symptoms consistent w/ liver disease. Some azoles have been associated w/ QTc interval prolongation. Monitor & correct electrolyte disturbances (eg, K, Mg or Ca levels) prior to & during therapy. Caution in patients w/ hypersensitivity to other azoles; pro-arrhythmic condition; severe GI dysfunction (eg, severe diarrhoea or vomiting); hepatic impairment. Concomitant use w/ CYP3A4 substrates; any benzodiazepines metabolised by CYP3A4 (eg, midazolam, triazolam, alprazolam); vincristine; rifamycin antibacterials (rifampicin, rifabutin), certain anticonvulsants (phenytoin, carbamazepine, phenobarb, primidone), efavirenz & cimetidine. Patients w/ rare glucose-galactose malabsorption should not take this medicine. Contains Na benzoate, benzyl alcohol, propylene glycol. May potentially affect driving or operating machinery. Women of childbearing potential must use effective contraception during treatment. Must not be used during pregnancy unless benefit to the mother clearly outweighs potential risk to the foetus. Stop breast-feeding on treatment initiation. Safety & efficacy have not been established in childn & adolescents <18 yr.

Nausea. Neutropenia; electrolyte imbalance, anorexia, decreased appetite, hypokalaemia, hypomagnesaemia; paresthesia, dizziness, somnolence, headache, dysgeusia; HTN; vomiting, abdominal pain, diarrhoea, dyspepsia, dry mouth, flatulence, constipation, anorectal discomfort; raised liver function tests (increased ALT, AST, bilirubin, alkaline phosphatase, GGT); rash, pruritus; pyrexia, asthenia, fatigue.

Decreased plasma conc w/ rifabutin, rifampicin; efavirenz; fosamprenavir; phenytoin, carbamazepine, phenobarb, primidone; cimetidine & other H₂ receptor antagonists; esomeprazole & other proton pump inhibitors. Increased absorption w/ food. Increased plasma conc of CYP3A4 substrates eg, terfenadine, astemizole, cisapride, pimozide, halofantrine, quinidine; ergot alkaloids; HMG-CoA reductase inhibitors metabolised through CYP3A4 (eg, simvastatin, lovastatin, atorvastatin); vinca alkaloids (eg, vincristine, vinblastine); rifabutin; sirolimus; ciclosporin; tacrolimus; HIV PIs; midazolam, triazolam, alprazolam; Ca channel blockers metabolised through CYP3A4 (eg, diltiazem, verapamil, nifedipine, nisoldipine); tretinioin; venetoclax. Potential increase in plasma conc of digoxin. Decreased glucose conc when co-administered w/ glipizide.

Antifungals

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

P₁S₁S₃