VFEND

Voriconazole

Invasive aspergillosis; candidemia in non-neutropenic patients; serious invasive Candida infections (including C. krusei); esophageal candidiasis; serious fungal infections caused by Scedosporium spp & Fusarium spp; other serious fungal infections 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 who are at high risk of developing invasive fungal infections eg, hematopoietic stem cell transplant (HSCT) recipients.

Adult Oral Maintenance dose (after 1st 24 hr): Prophylaxis of invasive fungal infections, prevention of breakthrough infections; invasive aspergillosis, Scedosporium & Fusarium infections, other serious mold infections; Candidemia in non-neutropenic patient; esophageal candidiasis Patient weighing ≥40 kg 200 mg every 12 hr. May increase to 300 mg every 12 hr if response is inadequate or may reduce by 50 mg steps to min of 200 mg every 12 hr if patient is unable to tolerate higher doses; <40 kg 100 mg every 12 hr. May increase to 150 mg every 12 hr if response is inadequate or may reduce by 50 mg steps to min of 100 mg every 12 hr if patient is unable to tolerate higher doses. Concomitant use w/ phenytoin Patient weighing ≥40 kg Increase maintenance dose to 400 mg every 12 hr; <40 kg Increase maintenance dose to 200 mg every 12 hr. Concomitant use w/ efavirenz Increase maintenance dose to 400 mg every 12 hr. IV 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 patient 3-4 mg/kg every 12 hr. Invasive aspergillosis, Scedosporium & Fusarium infections, other serious mold infections 4 mg/kg every 12 hr. Dose adjustment: May increase to 4 mg/kg every 12 hr if response to 3 mg/kg every 12 hr is inadequate or may reduce to min of 3 mg/kg every 12 hr if patient is unable to tolerate 4 mg/kg every 12 hr. Concomitant use w/ phenytoin Increase maintenance dose to 5 mg/kg IV every 12 hr. Adolescent (12-14 yr & ≥50 kg; 15-16 yr regardless of wt) Adult dose. Young adolescent (12-14 yr & <50 kg) & childn (2-<12 yr) Oral Maintenance dose (after 1st 24 hr): 9 mg/kg bid. Max: 350 mg bid. IV Loading dose regimen (1st 24 hr): 9 mg/kg every 12 hr. Maintenance dose (after 1st 24 hr): 8 mg/kg bid. Dose adjustment: May increase by 1 mg/kg steps if response is inadequate or reduce by 1 mg/kg steps if patient is unable to tolerate treatment (or by 50 mg steps if max oral dose of 350 mg was used initially). Prophylaxis in adult & childn Initiate on the day of transplant & administered for up to 100 days. May only be continued up to 180 days after transplantation in case of continuing immunosuppression or graft versus host disease.

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

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

Hypersensitivity to other azoles. Infusion-related reactions. Patients w/ potentially proarrhythmic conditions eg, congenital or acquired QT prolongation, cardiomyopathy (particularly when heart failure is present), sinus bradycardia, existing symptomatic arrhythmias, concomitant use w/ drugs known to prolong QT interval. Transient hepatic reactions including hepatitis & jaundice. Monitor & correct electrolyte disturbances (hypokalemia, hypomagnesemia & hypocalcemia) prior to initiation & during therapy. Evaluate hepatic function (AST/ALT) at the initiation & at least wkly for the 1st mth of treatment; discontinue if LFT become markedly elevated. Monitor for the development of abnormal renal function; pancreatitis in adults & childn w/ risk factors for acute pancreatitis (eg, recent chemotherapy, hematopoietic stem cell transplantation). Acute renal failure & prolonged visual adverse events (including optic neuritis & papilledema) in severely ill patients w/ underlying conditions &/or concomitant medications. Discontinue if severe cutaneous adverse reactions eg, SJS, TENs, drug reaction w/ eosinophilia & systemic symptoms develops. Avoid exposure to direct sunlight during treatment. Carefully monitor patients on long-term treatment for adrenal cortex dysfunction during treatment & discontinuation. Perform dermatologic evaluation on a systemic & regular basis to allow early detection & management of premalignant lesions; discontinue if patient develops a skin lesion consistent w/ premalignant skin lesions, squamous cell carcinoma or melanoma. Discontinue if patient develops skeletal pain & radiologic findings compatible w/ periostitis. Concomitant use w/ everolimus, fluconazole, phenytoin, methadone, short & long acting opiates. Avoid potentially hazardous tasks eg, driving or operating machinery. Effective contraception during treatment in women of child-bearing potential. Pregnancy. Stop initiation of treatment during lactation. Not recommended in childn <2 yr.

Pseudomembranous colitis, sinusitis; squamous cell carcinoma; disseminated intravascular coagulation, bone marrow failure, agranulocytosis, pancytopenia, thrombocytopenia, leukopenia, anemia, lymphadenopathy, eosinophilia; anaphylactoid reaction, hypersensitivity; adrenal insufficiency, hypothyroidism, hyperthyroidism; hypoglycemia, hypokalemia, hyponatremia, peripheral edema; depression, hallucination, anxiety, insomnia, agitation, confusional state; hepatic encephalopathy, brain edema, encephalopathy, syncope, extrapyramidal disorder, tremor, hypertonia, Guillain-Barré syndrome, peripheral neuropathy, ataxia, paresthesia, hypoesthesia, nystagmus, dysgeusia, somnolence, dizziness, headache; optic atrophy, optic nerve disorder, papilledema, retinal hemorrhage, oculogyric crisis, corneal opacity, visual impairment, diplopia, scleritis, blepharitis; hypoacusis, vertigo, tinnitus; torsades de pointes, ventricular fibrillation, extrasystoles, tachycardia, prolonged ECG QT, complete AV block, bundle branch block, nodal rhythm, supraventricular arrhythmia/tachycardia, bradycardia; thrombophlebitis, hypotension, phlebitis, lymphangitis; acute resp distress syndrome, pulmonary edema; peritonitis, pancreatitis, swollen tongue, diarrhea, vomiting, duodenitis, cheilitis, gastroenteritis, dyspepsia, abdominal pain, glossitis, constipation, gingivitis, nausea; hepatic failure, jaundice, cholestatic jaundice, hepatitis, hepatomegaly, cholecystitis, cholelithiasis, abnormal LFT; TEN, SJS, DRESS, angioedema, pseudoporphyria, erythema multiforme, exfoliative dermatitis, psoriasis, cutaneous lupus erythematosus, drug eruption, alopecia, photosensitivity reaction, purpura, maculo-papular rash, urticaria, rash, eczema, pruritus; back pain, arthritis; acute renal failure, renal tubular necrosis, proteinuria, nephritis, hematuria; chest pain, face edema, infusion site reaction, flu-like illness, asthenia, chills, pyrexia; increased blood creatinine, blood urea & blood cholesterol.

Increased plasma conc of astemizole, cisapride, pimozide, quinidine, terfenadine & ivabradine; ergot alkaloids (eg, ergotamine & dihydroergotamine); everolimus; naloxegol; other oral coumarins (eg, phenprocoumon, acenocoumarol); ivacaftor; benzodiazepines (eg, midazolam, triazolam, alprazolam); tolvaptan; lemborexant; tyrosine kinase inhibitors; omeprazole; statins (eg, lovastatin), sulphonylureas (eg, tolbutamide, glipizide, glyburide); vinca alkaloids (eg, vincristine & vinblastine). Increased risk of prolonged QTc & may increase plasma conc of glasdegib. May increase sedative effect & plasma conc of eszopiclone. Increased risk of adverse reactions (pseudomotor cerebri, hypercalcemia) & plasma conc of tretinoin. Decreased plasma conc w/ carbamazepine & long-acting barbiturates (eg, phenobarb, mephobarbital). Max increase in prothrombin time w/ warfarin. Increased levels of ciclosporin & tacrolimus. May inhibit metabolism w/ HIV-PIs (eg, saquinavir, amprenavir & nelfinavir) & NNRTIs (eg, delavirdine, nevirapine). Efavirenz, lurasidone, rifabutin, rifampicin, ritonavir, St. John's wort, venetoclax, fluconazole, phenytoin, letermovir, fluconazole, phenytoin, sirolumus, long acting opiates (oxycodone), methadone, NSAIDs (ibuprofen, diclofenac), OCs (norethisterone/ethinylestradiol), short acting opiates (alfentanil, fentanyl), cimetidine, digoxin, indinavir, macrolides (erythromycin, azithromycin), mycophenolic acid, prednisolone, ranitidine.

Antifungals

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

Rx