Voriconazole Kabi

Voriconazole

Invasive aspergillosis; candidaemia in non-neutropenic patients; fluconazole-resistant serious invasive Candida infections (including C. krusei); serious fungal infections caused by Scedosporium spp. & Fusarium spp. Prophylaxis of invasive fungal infections in high risk allogeneic hematopoietic stem cell transplant (HSCT) recipients.

IV Max infusion rate: 3 mg/kg per hr over 1-3 hr. Treatment Adults, adolescents 15-17 yr regardless of body wt, 12-14 yr & ≥50 kg Loading dose: 6 mg/kg every 12 hr for 1st 24 hr. Maintenance dose: 4 mg/kg bid after 1st 24 hr. Duration of treatment: As short as possible depending on patient's clinical & mycological response. Careful assessment of benefit-risk balance is required for long term exposure >180 days (6 mth). Patient unable to tolerate 4 mg/kg bid Reduce dose to 3 mg/kg bid. Prophylaxis Initiate on the day of transplant for up to 100 days. Prophylaxis should be as short as possible depending on risk for developing invasive fungal infection. Young adolescents w/ low body wt (12-14 yr & <50 kg), childn 2 to <12 yr Loading dose: 9 mg/kg every 12 hr for 1st 24 hr. Maintenance dose: 8 mg/kg bid after 1st 24 hr. May increase by 1 mg/kg steps if treatment response is inadequate. Reduce dose by 1 mg/kg steps if unable to tolerate treatment. Coadministration w/ rifabutin or phenytoin May be coadministered if the maintenance dose is increased to 5 mg/kg bid. Coadministration w/ efavirenz May be coadministered if the maintenance dose is increased to 400 mg every 12 hr & reduce efavirenz dose by 50% ie, 300 mg once daily. Restore initial efavirenz dosage when treatment w/ voriconazole is stopped.

Hypersensitivity. Coadministration w/ CYP3A4 substrates, terfenadine, astemizole, cisapride, pimozide, quinidine; rifampicin, carbamazepine & phenobarb; efavirenz; high-dose ritonavir (≥400 mg bid); ergot alkaloids (ergotamine, dihydroergotamine); sirolimus; St. John's Wort.

Not for bolus inj. Not to be used >6 mth. Hypersensitivity to other azoles. Discontinue use if LFTs become markedly elevated. Consider treatment discontinuation if severity of infusion-related reactions (eg, flushing & nausea) persist. Discontinue use if premalignant skin lesions or squamous cell carcinoma are identified; if patient develops skeletal pain & radiologic findings compatible w/ periostitis. Closely monitor if patient develops rash & discontinue if lesions progress. Consider use of alternative antifungals & treatment discontinuation if hepatotoxicity, severe skin reactions including phototoxicity & squamous cell carcinoma, severe or prolonged visual disorders & periostitis occur. Prolonged QTc interval. Serious (including clinical hepatitis, cholestasis & fulminant hepatic failure) & transient (including hepatitis & jaundice) hepatic reactions. Phototoxicity including ephelides, lentigo, actinic keratosis & pseudoporphyria. Blurred vision, optic neuritis & papilloedema. Reversible liver dysfunction on discontinuation of therapy. Non-infectious periostitis w/ elevated fluoride & alkaline phosphatase levels in transplant patients. History of cardiotoxic chemotherapy, cardiomyopathy, hypokalaemia. Patients w/ potentially proarrhythmic conditions eg, congenital or acquired QT prolongation, cardiomyopathy particularly w/ heart failure, sinus bradycardia, existing symptomatic arrhythmias & concomitant use of QTc prolonging medications; serious underlying medical conditions (predominantly haematological malignancy). Monitor & correct electrolyte disturbances eg, hypokalaemia, hypomagnesaemia & hypocalcaemia if necessary, prior to initiation or during therapy. Lab evaluation of hepatic function (specifically AST & ALT) at the treatment initiation & at least wkly for 1st of treatment. Monitor for serum creatinine, amylase or lipase; hepatic function. Long term exposure >180 days. Avoid exposure to direct sunlight during treatment & use protective clothing sunscreen w/ high sun protection factor. Perform systematic & regular dermatologic evaluation to allow early detection & management of premalignant lesions if treatment is continued. Decrease efavirenz dose to 300 mg every 24 hr. Avoid coadministration w/ phenytoin, rifabutin, low-dose ritonavir. Not recommended w/ everolimus. Concomitant use w/ QT prolonging & nephrotoxic medications, methadone, fentanyl, short- & long-acting opiates, fluconazole. May affect ability to drive & use machines. Moderate to severe renal dysfunction (CrCl <50 mL/min); acute renal failure in severely ill patients undergoing treatment. Hepatic cirrhosis & toxicity; severe hepatic impairment. Women of childbearing potential should use effective contraception during treatment. Not to be used during pregnancy. Discontinue lactation on treatment initiation. Not recommended in childn <2 yr. Avoid sun exposure in childn experiencing photoaging injuries eg, lentigines or ephelides & recommend dermatologic follow-up even after treatment discontinuation.

Peripheral oedema; headache; visual impairment; resp distress; 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; convulsion, 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, maculo-papular rash, pruritus, erythema; 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. Decreased plasma conc w/ carbamazepine; long-acting barbiturates (eg, phenobarb, mephobarbital). Decreased C_max & AUC w/ rifampicin; ritonavir. Increased plasma conc of ergot alkaloids (eg, ergotamine & dihydroergotamine); everolimus; statins (eg, lovastatin); sulfonylureas (eg, tolbutamide, glipizide, glyburide); vinca alkaloids (eg, vincristine & vinblastine). Increased/decreased C_max & AUC w/ efavirenz; rifabutin; phenytoin. Decreased AUC w/ St. John's wort. Increased C_max & AUC w/ fluconazole; omeprazole; ethinylestradiol, norethisterone; cimetidine. May increase prothrombin time of warfarin & oral coumarins (eg, phenprocoumon, acenocoumarol). Increased plasma conc & prolonged sedative effect of benzodiazepines (eg, midazolam, triazolam, alprazolam). Increased C_max & AUC of sirolimus, ciclosporin, tacrolimus; oxycodone, methadone; ibuprofen, diclofenac; prednisolone. Increased AUC of alfentanil, fentanyl. May inhibit metabolism of HIV PIs (eg, saquinavir, amprenavir and nelfinavir); NNRTIs (eg, delavirdine, nevirapine).

Antifungals

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

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