Vfend

Voriconazole

Invasive aspergillosis; fluconazole-resistant serious invasive Candida infections eg, C. krusei; serious Candida infections eg, esophageal candidiasis; candidemia in non-neutropenic patients & the following Candida infections: disseminated skin, abdomen, kidney, bladder wall & wound infections; serious fungal infections caused by Scedosporium & Fusarium spp. Prevention of breakthrough fungal infections in febrile high-risk neutropenic patients; prophylaxis in patients ≥12 yr at high risk of developing invasive fungal infections.

Oral All indications Patient ≥40 kg 200 mg (5 mL) every 12 hr, <40 kg 100 mg (2.5 mL) every 12 hr. IV Adult All indications Loading dose: 6 mg/kg every 12 hr for 1st 24 hr. Maintenance: Prevention of breakthrough infection 3 mg/kg every 12 hr after 1st 24 hr. Fluconazole-resistant serious invasive Candida/aspergillosis/Scedosporium & Fusarium infection/prophylaxis of invasive fungal infection 4 mg/kg every 12 hr after 1st 24 hr. Candidemia in non-neutropenic patient & other deep tissue Candida infection 3-4 mg/kg every 12 hr after 1st 24 hr. Childn 2 to <12 yr & young adolescent 12-14 yr, <50 kg Loading dose: 9 mg/kg every 12 hr for 1st 24 hr. Maintenance: 8 mg/kg IV bd or 9 mg/kg PO bd after 1st 24 hr, max: 350 mg PO bd. Adolescent 12-14 yr, ≥50 kg; 15-16 yr regardless of body wt Adult dose. Prophylaxis in adult & childn Initiated on day of transplant for up to 100 days. Continuing immunosuppression or graft versus host disease May continue up to 180 days after transplant.

Should be taken on an empty stomach: Take at least 1 hr before or after meals.

Hypersensitivity. Co-administration of CYP3A4 substrates, terfenadine, astemizole, cisapride, pimozide, quinidine, ivabradine, sirolimus, rifabutin, rifampicin, carbamazepine, long-acting barbiturates, St. John's wort, efavirenz (≥400 mg once daily), high-dose ritonavir (≥400 mg bd), ergot alkaloids, naloxegol, tolvaptan, venetoclax, lurasidone.

Hypersensitivity to azoles. Infusion-related reactions. Discontinue use if LFTs become markedly elevated; severe cutaneous AR, skeletal pain & radiologic findings compatible w/ periostitis or skin lesion consistent w/ premalignant skin lesions develops. Patients w/ potentially proarrhythmic conditions eg, congenital or acquired QT prolongation, cardiomyopathy, sinus bradycardia, existing symptomatic arrhythmias. Visual adverse events eg, optic neuritis, papilledema; SJS, TEN, DRESS; adrenal insufficiency, Cushing's syndrome; squamous cell skin carcinoma, melanoma. Correct electrolyte disturbances prior to & during therapy. Monitor hepatic, renal & pancreatic function; ECG regularly. Avoid exposure to direct sunlight. Long-term use. Not recommended in concomitant use w/ everolimus. Avoid concomitant use w/ phenytoin, ritonavir. Concomitant use w/ medicinal products prolonging QT interval; nephrotoxic medications; fluconazole, efavirenz, glasdegib, tyrosine kinase inhibitors, methadone, short- & long-acting opiates. May affect ability to drive & use machines. Hepatic cirrhosis & toxicity; severe hepatic impairment. Renal adverse events. Women of childbearing potential should use effective contraception during treatment. Not to be used during pregnancy & lactation. Not recommended in childn <2 yr. Powd for infusion: Not recommended for bolus inj. Not to be infused concomitantly w/ any blood product or short-term infusion of concentrated electrolytes. Moderate to severe renal dysfunction (CrCl <50 mL/min).

Peripheral oedema; headache; visual impairment; diarrhoea, vomiting, abdominal pain, nausea; abnormal LFT; rash; pyrexia. Sinusitis; agranulocytosis, pancytopenia, thrombocytopenia, leukopenia, anaemia; hypoglycaemia, hypokalaemia, hyponatraemia; depression, hallucination, anxiety, insomnia, agitation, confusional state; syncope, tremor, hypertonia, paraesthesia, somnolence, dizziness; retinal haemorrhage; supraventricular arrhythmia, tachycardia, bradycardia; hypotension, phlebitis; acute resp distress syndrome, pulmonary oedema; cheilitis, dyspepsia, constipation, gingivitis; jaundice, cholestatic jaundice, hepatitis; exfoliative dermatitis, alopecia, maculopapular rash, pruritus; back pain; acute renal failure, haematuria; chest pain, face oedema, asthenia, chills; increased blood creatinine.

QTc prolongation due to increased plasma conc of astemizole, cisapride, pimozide, quinidine, terfenadine, ivabradine, glasdegib. Decreased plasma conc by carbamazepine, long-acting barbiturates. Decreased C_max & AUC w/ efavirenz, rifampicin, ritonavir, letermovir. Increased plasma conc of ergot alkaloids, lurasidone, naloxegol, tolvaptan, venetoclax, lemborexant, tyrosine kinase inhibitors, coumarins, ivacaftor, midazolam, other benzodiazepines, sirolimus, everolimus, ciclosporin, tacrolimus, long-acting opiates, methadone, NSAIDs, omeprazole, other PPIs, OCs, alfentanil, fentanyl, statins, sulphonylureas, vinca alkaloids, prednisolone. Decreased AUC w/ St. John's wort. Increased C_max & AUC w/ fluconazole, cimetidine. Increased/decreased C_max & AUC w/ rifabutin, phenytoin. Increase plasma conc & sedative effect w/ eszopiclone. Inhibited metabolism of HIV PIs, NNRTIs. Increased conc & risk of AR w/ tretinoin.

Antifungals

J02AC03 - voriconazole ; Belongs to the class of triazole and tetrazole derivatives. Used in the systemic treatment of mycotic infections.

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