VFEND

Voriconazole

Invasive aspergillosis; candidemia in non-neutropenic patients; serious invasive Candida infections (including Candida krusei); esophageal candidiasis; serious fungal infections caused by Scedosporium apiospermum (asexual form of Pseudallescheria boydii) & Fusarium spp, including Fusarium solani in patients intolerant of, or refractory to, other therapy. Prevention of breakthrough of fungal infections in febrile high-risk patients (allogeneic bone marrow transplants, relapsed leukemia patients). Prophylaxis in patients at high risk of developing invasive fungal infections eg, haematopoietic stem cell transplant (HSCT) recipients.

Tab Adult Maintenance dose (after 1st 24 hr): Prophylaxis of invasive fungal infections/prevention of breakthrough infections, invasive aspergillosis/Scedosporium & Fusarium infections/other serious mould infections, candidemia in non-neutropenic patients, esophageal candidiasis Patient weighing ≥40 kg 200 mg every 12 hr. If response is inadequate, dose may be increased to 300 mg every 12 hr. If patients are unable to tolerate high dose treatment, reduce dose by 50 mg steps to min maintenance dose of 200 mg every 12 hr; <40 kg 100 mg every 12 hr. If response is inadequate, dose may be increased to 150 mg every 12 hr. If patients are unable to tolerate high dose treatment, dose may be reduced by 50 mg steps to min maintenance dose of 100 mg every 12 hr. Concomitant use w/ phenytoin Increase dose to 400 mg every 12 hr in patients weighing ≥40 kg or 200 mg every 12 hr in patients weighing <40 kg. Concomitant use w/ efavirenz Increase dose to 400 mg every 12 hr. Adolescent (12-14 yr weighing ≥50 kg; 15-16 yr regardless of body wt) Adult dose. Young adolescent 12-14 yr weighing <50 kg & childn 2 to <12 yr Maintenance dose (after 1st 24 hr): 9 mg/kg bid. Max dose: 350 mg bid. Dose adjustment: Dose may be increased by 1 mg/kg steps (or by 50 mg steps if max oral dose of 350 mg was used initially). If patients are unable to tolerate treatment, reduce dose by 1 mg/kg steps (or by 50 mg steps if max oral dose of 350 mg was used initially). IV Infuse at max rate of 3 mg/kg/hr over 1-3 hr. Dose may be increased to 4 mg/kg every 12 hr if patient response at 3 mg/kg every 12 hr dose is inadequate. Dose may be reduced to min 3 mg/kg every 12 hr if patient is unable to tolerate 4 mg/kg every 12 hr. Adult Loading dose for all indications (1st 24 hr): 6 mg/kg every 12 hr. Maintenance dose (after 1st 24 hr): Prophylaxis of invasive fungal infections/prevention of breakthrough infections, candidemia in non-neutropenic patients 3-4 mg/kg every 12 hr. Invasive aspergillosis/Scedosporium & Fusarium infections/other serious mould infections 4 mg/kg every 12 hr. Concomitant use w/ phenytoin Increase maintenance dose to 5 mg/kg every 12 hr. Adolescent (12-14 yr weighing ≥50 kg; 15-16 yr regardless of body wt) Adult dose. Young adolescent 12-14 yr weighing <50 kg & childn 2 to <12 yr Loading dose (1st 24 hr): 9 mg/kg every 12 hr. Maintenance dose (after 1st 24 hr): 8 mg/kg bid.

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

Hypersensitivity. Concomitant use w/ CYP3A4 substrates, terfenadine, astemizole, cisapride, pimozide, quinidine or ivabradine; sirolimus; rifabutin, rifampicin, carbamazepine, long-acting barbiturates (eg, phenobarb), St. John's wort; efavirenz (doses of ≥400 mg once daily); high-dose ritonavir (≥400 mg bid); ergot alkaloids (eg, ergotamine, dihydroergotamine); naloxegol; tolvaptan; venetoclax; lurasidone.

Hypersensitivity to other azoles. Discontinue treatment if patient develops severe cutaneous adverse reaction eg, SJS, TEN & DRESS; skin lesion consistent w/ pre-malignant skin lesions, squamous cell carcinoma (SCC) or melanoma; skeletal pain & radiologic findings compatible w/ periostitis; LFTs become markedly elevated. Consider stopping treatment if infusion-related reactions eg, flushing & nausea; phototoxic reactions occur. QT interval prolongation on ECG. Serious (clinical hepatitis, cholestasis & fulminant hepatic failure, including fatalities) & transient (hepatitis & jaundice) hepatic reactions. Prolonged visual adverse events eg, optic neuritis & papilledema. Acute renal failure in severely ill patients. Acute renal failure in severely ill patients. Adrenal insufficiency; Cushing's syndrome. SCC of skin (including cutaneous SCC in situ or Bowen's disease) & melanoma w/ long-term therapy. Patients w/ potentially proarrhythmic conditions eg, congenital or acquired QT-prolongation, cardiomyopathy in particular when heart failure is present, sinus bradycardia, existing symptomatic arrhythmias, concomitant use w/ medicinal product known to prolong QT interval. Monitor & correct electrolyte disturbances eg, hypokalemia, hypomagnesemia & hypocalcemia prior to initiation & during therapy. Carefully monitor for hepatic toxicity & evaluate hepatic function eg, AST & ALT at treatment initiation, & at least wkly for the 1st mth of treatment; adrenal cortex dysfunction during treatment & upon discontinuation in patients on long-term treatment w/ concomitant corticosteroids (including inhaled corticosteroids eg, budenoside). Monitor for development of abnormal renal function including lab evaluation of serum creatinine; pancreatitis in patients w/ risk factors for acute pancreatitis eg, recent chemotherapy & HSCT. Avoid direct sunlight exposure during treatment; use protective clothing & sunscreen w/ high sun protection factor. Perform dermatologic evaluation on systematic & regular basis to allow early detection & management of pre-malignant lesions. Not recommended in concomitant use w/ everolimus. Concomitant use w/ fluconazole, efavirenz, glasdegib, tyrosine kinase inhibitors, phenytoin, ritonavir, methadone, short- & long-acting opiates. May impair ability to drive & use machines. Severe hepatic impairment. Women of childbearing potential must always use effective contraception during treatment. Pregnancy. Stop breastfeeding upon initiation of treatment. Childn <2 yr. IV: Not recommended for bolus inj. Not to be infused concomitantly w/ any blood product or short-term conc electrolytes.

Peripheral edema; headache; visual impairment; diarrhea, vomiting, abdominal pain, nausea; abnormal LFT; rash; pyrexia. Sinusitis; agranulocytosis, pancytopenia, thrombocytopenia, leukopenia, anemia; hypoglycemia, hypokalemia, hyponatremia; depression, hallucination, anxiety, insomnia, agitation, confusional state; syncope, tremor, hypertonia, paresthesia, somnolence, dizziness; retinal hemorrhage; supraventricular arrhythmia, tachycardia, bradycardia; hypotension, phlebitis; acute resp distress syndrome, pulmonary edema; cheilitis, dyspepsia, constipation, gingivitis; jaundice, cholestatic jaundice, hepatitis; exfoliative dermatitis, alopecia, maculo-papular rash, pruritus; back pain; acute renal failure, hematuria; chest pain, face edema, asthenia, chills; increased blood creatinine. SJS, TEN, erythema multiforme. DRESS.

Increased plasma conc of astemizole, cisapride, pimozide, quinidine, terfenadine & ivabradine; ergot alkaloids (eg, ergotamine & dihydroergotamine); lurasidone; naloxegol; tolvaptan; venetoclax; lemborexant; tyrosine kinase inhibitors (eg, axitinib, bosutinib, cabozantinib, ceritinib, cobimetinib, dabrafenib, dasatinib, nilotinib, sunitinib, ibrutinib, ribociclib); other oral coumarins (eg, phenprocoumon, acenocoumarol); ivacaftor; benzodiazepines (eg, midazolam, triazolam, alprazolam); everolimus; omeprazole; statins (eg, lovastatin); sulphonylureas (eg, tolbutamide, glipizide, glyburide); vinca alkaloids (eg, vincristine & vinblastine); tretinoin. Decreased plasma conc w/ carbamazepine & long-acting barbiturates (eg, phenobarb & mephobarbital), flucloxacillin. Decreased AUC & C_max w/ efavirenz; rifabutin; rifampicin; ritonavir; phenytoin; letermovir. Increased AUC & C_max w/ fluconazole; cimetidine; prednisolone. Max increase in prothrombin time w/ warfarin. Decreased AUC w/ St. John's wort. Increased plasma conc & QTc prolongation of glasdegib. Increased plasma conc & sedative effect of eszopiclone. Increased AUC & C_max of of efavirenz, rifabutin, phenytoin, midazolam, sirolimus; ciclosporin; tacrolimus; oxycodone; methadone; NSAIDs (eg, ibuprofen, diclofenac); OCs (eg, norethisterone/ethinylestradiol). Increased AUC of short-acting opiates (eg, alfentanil, fentanyl). May inhibit the metabolism of HIV PIs (eg, saquinavir, amprenavir & nelfinavir); NNRTIs. Metabolism may be inhibited w/ other 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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