Vortimal

Voriconazole

Invasive aspergillosis; fluconazole-resistant serious invasive Candida infections eg, C. krusei; serious Candida infections eg, esophageal candidiasis; candidemia in non non-neutropenic patients & Candida infections eg, 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.

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/invasive 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 bd after 1st 24 hr. 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.

Hypersensitivity. Co-administration of CYP3A4 substrates, terfenadine, astemizole, cisapride, pimozide, quinidine, rifampicin, carbamazepine, phenobarb, efavirenz (≥400 mg once daily), high-dose ritonavir (≥400 mg bd), ergot alkaloids (eg, ergotamine, dihydroergotamine), sirolimus, St. John's wort.

Hypersensitivity to azoles. Not recommended for bolus inj. Infusion-related reactions. Discontinue use if LFTs become markedly elevated; if premalignant skin lesions or squamous cell carcinoma are identified; skeletal pain & radiological findings compatible w/ periostitis develops. History of cardiotoxic chemotherapy, cardiomyopathy, hypokalaemia; patients w/ potentially proarrhythmic conditions eg, congenital or acquired QTc prolongation, cardiomyopathy, sinus bradycardia, existing symptomatic arrhythmias. Visual reactions eg, blurred vision, optic neuritis, papilloedema; exfoliative cutaneous reactions eg, SJS, phototoxicity, pseudoporphyria. Patients on controlled Na diet. Correct electrolyte disturbances prior to & during therapy. Monitor hepatic, renal & pancreatic function. Avoid exposure to direct sunlight. Long-term use. Not to be infused concomitantly w/ any blood product or short-term infusion of concentrated electrolytes. Avoid concomitant use w/ phenytoin, rifabutin, ritonavir. Not recommended in co-administration w/ everolimus. Concomitant use w/ medicinal products prolonging QT interval; nephrotoxic medications; efavirenz, methadone, short- & long-acting opiates, fluconazole. May affect ability to drive & use machines. Hepatic cirrhosis & toxicity; severe hepatic impairment. Renal ARs; moderate to severe renal dysfunction (CrCl <50 mL/min). Women of childbearing potential should use effective contraception during treatment. Not to be used during pregnancy & lactation. Not recommended in childn <2 yr.

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

QTc prolongation due to increased plasma conc of astemizole, cisapride, pimozide, quinidine, terfenadine. Increased plasma conc of ergot alkaloids (eg, ergotamine, dihydroergotamine); everolimus; other oral coumarins (eg, phenprocoumon, acenocoumarol); benzodiazepines (eg, midazolam, triazolam, alprazolam); other CYP2C19 substrate PPIs; statins (eg, lovastatin); sulphonylureas (eg, tolbutamide, glipizide, glyburide); vinka alkaloids (eg, vincristine, vinblastine). Decreased plasma conc w/ carbamazepine & long-acting barbiturates (eg, phenobarb, mephobarbital). Decreased C_max & AUC w/ efavirenz; rifampicin; ritonavir. Increased C_max & AUC w/ fluconazole, omeprazole, cimetidine. Decreased AUC w/ St. John's wort. Max increased prothrombin time w/ warfarin. Increased C_max & AUC of sirolimus, ciclosporin, tacrolimus, oxycodone, methadone, NSAIDS (eg, ibuprofen, diclofenac), OCs (eg, norethisterone/ethinylestradiol), prednisolone. Increased AUC of short-acting opiates (eg, alfentanil, fentanyl). Increased/decreased C_max & AUC w/ rifabutin, phenytoin. Inhibited metabolism of HIV PIs (eg, saquinavir, amprenavir, nelfinavir), NNRTIs.

Antifungals

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

B