Voraiz

Voraiz

voriconazole

Manufacturer:

Siam Bheasach

Distributor:

Siam Pharmaceutical

Marketer:

Siam Pharmaceutical
Full Prescribing Info
Contents
Voriconazole.
Description
Each tablet contains Voriconazole 200 mg.
Action
Pharmacology: Pharmacodynamics: Voriconazole is a triazole antifungal agent. The primary mode of action of Voriconazole is the inhibition of fungal cytochrome P450 (CYP-450)-mediated 14 alpha-lanosterol demethylation, an essential step in fungal ergosterol biosynthesis. The accumulation of 14 alpha-methyl sterols correlates with subsequent loss of ergosterol in the fungal cell wall and may be responsible for the antifungal activity of Voriconazole. Voriconazole has a broad spectrum of activity against all Candida species, including fluconazole-resistant strains, as well as Aspergillus spp., Scedosporium spp., and Fusarium spp.
Pharmacokinetics: Absorption of Voriconazole is rapid and almost complete (oral bioavailability of 96% in adults and 45%-80% in children 2 to younger than 12 years) when given in the fasting state. Peak plasma Voriconazole concentrations are achieved 1-2 hours following a dose. In adults, steady state concentrations are achieved within 24 hours if a loading dose is administered or after 5-7 days if a loading dose is not administered. When Voriconazole are administered with high fat meals, the mean Cmax and AUC are reduced.
In pediatric patients < 12 years, the full pharmacokinetic profile for Voriconazole is not completely defined and for patients < 2 years, the data is sparse. In children 2 to younger than 12 years, current data suggest Voriconazole undergoes a high degree of variability in exposure with linear elimination at lower doses and nonlinear elimination in higher dose. Therefore, to achieve similar AUC as adults, increased dosage is necessary in children.
The volume of distribution at steady state for Voriconazole is estimated to be 4.6 L/kg. Plasma protein binding is estimated to be 58%. Voriconazole diffuses into CSF about 50% of plasma concentration.
Voriconazole is metabolized by hepatic cytochrome P450 isoenzyme, CYP2C19, CYP2C9 and CYP3A4. The major metabolite of Voriconazole is N-oxide which has minimal antifungal activity.
Voriconazole is eliminated via the hepatic metabolism, with less than 2% of the dose excreted unchanged in the urine. As a result of nonlinear pharmacokinetics, the terminal half-life of Voriconazole is dose dependent.
Indications/Uses
Voriconazole is a broad spectrum, triazole antifungal agent and is indicated as follows: Treatment of invasive aspergillosis.
Treatment of candidemia in non-neutropenic patients.
Treatment of serious invasive Candida infections (including C. krusei).
Treatment of esophageal candidiasis.
Treatment of serious fungal infections caused by Scedosporium spp. and Fusarium spp.
Treatment of other serious fungal infections in patients intolerant of, or refractory to, other therapy.
Prevention of break through 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, such as haematopoietic stem cell transplant (HSCT) recipients.
Dosage/Direction for Use
Recommended dose: Voriconazole is administered orally. Voriconazole film-coated tablets should be given at least 1 hour before or 1 hour after meals.
In adults, an oral Voriconazole dosage of 200 mg every 12 hours results in an area under the plasmaconcentration time curve (AUC) similar to that achieved with an intravenous dosage of 3 mg/kg every 12 hours; an oral Voriconazole dosage of 300 mg every 12 hours results in an AUC similar to that reported with an intravenous dosage of 4 mg/kg every 12 hours.
Adoption of Voriconazole as first-line treatment for invasive aspergillosis has been associated with improved survival versus other treatments. (See table.)

Click on icon to see table/diagram/image

Dosage adjustment: For patients 40 kg and above: If patient response is inadequate, the maintenance dosage may be increased from 200 mg every 12 hours to 300 mg every 12 hours, depending on condition.
If patients are unable to tolerate 300 mg every 12 hours, reduce the maintenance dosage by 50 mg steps to a minimum of 200 mg every 12 hours, depending on condition.
For patients less than 40 kg: If the patient response is inadequate, the maintenance dosage may be increased from 100 mg every 12 hours to 150 mg every 12 hours, depending on condition.
If patients are unable to tolerate 150 mg every 12 hours, reduce the maintenance dosage by 50 mg steps to a minimum of 100 mg every 12 hours, depending on condition.
Children 2 to less than 12 years: A loading dose of 9 mg/kg twice daily for the first 24 hours followed by 8 mg/kg twice daily is recommended for intravenous regimen. For oral maintenance dosage, 9 mg/kg every 12 hours of oral suspension with a maximum dose of 350 mg every 12 hours is recommended.
Patients with hepatic impairment: In adults with mild to moderate hepatic cirrhosis (Child-Pugh class A or B), usual oral loading dosage of Voriconazole should be used, but oral maintenance dosages should be decreased by 50%.
Patients with renal impairment: Adjustment of oral Voriconazole dosage is not necessary in patients with mild to severe renal impairment.
Geriatric patients: Dosage adjustment based on age is not necessary on geriatric adults.
Overdosage
There is no specific antidote for Voriconazole overdose; therefore, management of the patient should consist of symptomatic and supportive therapy.
Enhanced elimination is not likely to be effective for Voriconazole because it has a large volume of distribution.
Contraindications
Known hypersensitivity to Voriconazole or any ingredient in the formulation.
Concomitant use of carbamazepine, CYP3A4 substrate (terfenadine, astemizole, cisapride, pimozide, quinidine), efavirenz (400 mg/day or more), ergot alkaloids (ergotamine, dihydroergotamine), long acting barbiturates (phenobarbital, mephobarbital), rifabutin, rifampin, sirolimus, St John's Wort.
Concomitant use with high dose ritonavir (800 mg/day); also avoid low dose ritonavir (200 mg/day), unless potential benefits outweigh risks.
Special Precautions
Hypersensitivity: Voriconazole should be used with caution in patients hypersensitive to other azoles.
Hepatic effects: Serious hepatic effects, including hepatitis, cholestasis, and fulminant hepatic failure, have been reported rarely in clinical trials. Hepatic effects (including hepatitis and jaundice) have occurred in patients with no identifiable risk factors. Hepatic effects usually are reversible when Voriconazole is discontinued; however, fatalities have occurred. If abnormal liver function test results occur during Voriconazole therapy, the patient should be monitored for the development of more severe hepatic injury using appropriate laboratory evaluations (particularly liver function tests and bilirubin). Discontinuance of Voriconazole must be considered if signs and symptoms consistent with liver disease develop.
Ocular effects: Visual disturbances (e.g. abnormal vision, blurred vision, color vision change, photophobia) have been reported and may be related to high dosage and high plasma Voriconazole concentrations. There have been postmarketing reports of prolonged visual disturbances, including optic neuritis and papilledema, in patients receiving Voriconazole. Effect of Voriconazole on visual function is unknown if duration of therapy exceeds 28 days. Monitor visual function (visual acuity, visual field, and color perception) if duration of therapy exceeds 28 days.
Cardiovascular effects: Voriconazole has been associated with prolongation of QT interval. Arrhythmias (e.g. torsades de pointes), cardiac arrest, and sudden death have occurred rarely on patients receiving Voriconazole. Voriconazole should be used with caution in patients with potentially proarrhythmic conditions. Rigorous attempts should be made to correct electrolyte imbalances (i.e. potassium, magnesium, calcium) before initiating Voriconazole therapy.
Dermatologic effects: Serious exfoliative cutaneous reactions (e.g. Stevens-Johnson syndrome, erythema multiforme, toxic epidermal necrolysis) have occurred rarely in patients receiving Voriconazole. If an exfoliative cutaneous reaction occurs, Voriconazole should be discontinued. Photosensitivity skin reactions have been reported in patients receiving Voriconazole. Patients receiving the drug should avoid intense or prolonged exposure to direct sunlight. Squamous cell carcinoma of the skin and melanoma have been reported during long-term Voriconazole therapy in patients with photosensitivity reactions. If a skin lesion consistent with squamous cell carcinoma or melanoma develops, Voriconazole should be discontinued.
Renal effects: Acute renal failure has been reported in severely ill patients with other factors predisposing to impaired renal function (e.g. underlying conditions, concomitant nephrotoxic drugs).
Skeletal effects: Fluorosis and periostitis have been reported during long-term Voriconazole therapy. If a patient develops skeletal pain and radiologic findings compatible with fluorosis or periostitis, Voriconazole should be discontinued.
Effects on Ability to Drive and Use Machines: Voriconazole may cause transient and reversible changes to vision, including blurring, altered/enhanced visual perception and/or photophobia. Patients must avoid potentially hazardous tasks, such as driving or operating machinery while experiencing these symptoms. Patients should not drive at night while taking voriconazole.
Use In Pregnancy & Lactation
Pregnancy: Pregnancy category D.
Voriconazole can cause fetal harm when administered to a pregnant woman, Voriconazole was teratogenic and embryotoxic in animal studies. Woman of childbearing potential should use effective contraceptive during treatment. Should be used in pregnant woman only if benefit to mother justifies potential risk to the fetus.
Lactation: It is not known if Voriconazole is excreted in breast milk. Due to the potential for serious adverse reactions in the nursing infant, a decision should be made whether to discontinue nursing or to discontinue the drug, taking into account the importance of treatment to the mother.
Adverse Reactions
Cardiovascular: tachycardia, peripheral oedema.
Central nervous system: chills, hallucinations, headache.
Dermatologic: skin rash.
Endocrine & metabolic: hypokalemia.
Gastrointestinal: nausea, vomiting, diarrhea, abdominal pain.
Hepatic: cholestatic jaundice, increased serum alkaline phosphatase, increased serum ALT, increased serum AST, abnormalities in liver function test results.
Ophthalmic: visual disturbances, photophobia.
Renal: increased serum creatinine, acute renal failure.
Miscellaneous: fever.
Rare but important or life-threatening: Adrenocortical insufficiency, agranulocytosis, alopecia, anaphylactoid reaction, anemia (aplastic, hematolytic, macrocytic, megaloblastic, or microcytic), angioedema, arthritis, ataxia, atrial arrhythmia, atrioventricular block, bone marrow depression, bradycardia, bundle branch block, cerebral edema, chest pain, cholecystitis, cholelithiasis, color blindness, confusion, corneal opacity, depression, discoid lupus erythematosus, disseminated intravascular coagulation, duodenitis, eczema, eosinophilia, erythema multiforme, exfoliative dermatitis, extrapyramidal reaction, fixed drug eruption, Guillain-Barre syndrome, hepatic coma, hepatic failure, hepatomegaly, hyperbilirubinemia, hypercholesterolemia, hyper- /hypoglycemia, hyper-/hyponatremia, hyper-/hypotension, hyper-/hypothyroidism, hypersensitivity reaction, jaundice, leukopenia, lymphadenopathy, lymphangitis, maculopapular rash, nephritis, neuropathy, nodal arrhythmia, nystagmus, oculogyric crisis, optic atrophy, optic neuritis, pancreatitis, pancytopenia, papilledema, paresthesia, peripheral edema, peritonitis, prolonged QT interval on ECG, pruritus, pseudomembranous colitis, pseudoporphyria, psoriasis, pulmonary edema, purpura, renal tubular necrosis, respiratory distress syndrome, retinal hemorrhage, skin photosensitivity, Stevens-Johnson syndrome, supraventricular tachycardia, syncope, thrombocytopenia, thrombophlebitis, tongue edema, torsades de pointes, toxic epidermal necrolysis, urticaria, ventricular arrhythmia, ventricular fibrillation, ventricular tachycardia.
Drug Interactions
Metabolism/transport effects: substrate of CYP2C19 (major), CYP2C9 (major), CYP3A4 (minor).
Avoid concomitant use of Voriconazole with any of the following: Voriconazole may increase the levels/effects of: ado-trastuzumab emtansine, alfuzosin, aprepitant, astemizole, asunaprevir, avanafil, axitinib, barnidipine, bionanserin, bosutinib, bromocriptine, budesonide (systemic), ceritinib, cisapride, cobimetinib, conivaptan, crizotinib, dabrafenib, dapoxetin, domperidone, dronedarone, eletriptan, eplerenone, ergoloid mesylate, ergonovine, ergotamine, everolimus, flibanserin, halofantrine, ibrutinib, irinotecan product, isavuconazonium sulfate, ivabradine, lapatinib, lercanidipine, lomitapide, lovastatin, lurasidone, macitentan, methylergonovine, naloxegol, nilotinib, nimodipine, nisoldipine, olaparib, albociclib, pimozide, quinidine, ranolazine, red yeast rice, regorafenib, rifamycin derivatives, salmeterol, silodosin, simeprevir, simvastatin, sirolimus, sonidegib, suvorexant, tamsulosin, terfenadine, ticagrelor, tolvaptan, toremifene, ulipristal, vemurafenib, vincristine (liposomal), vorapaxar, trabectedin.
The levels/effects of Voriconazole may be increased by: atazanavir, fluconazole.
Voriconazole may decrease the levels/effects of: atazanavir, ticagrelor.
The levels/effects of Voriconazole may be decreased by: atazanavir, barbiturates, carbamazepine, lopinavir, lumacaftor, rifamycin derivatives, ritonavir, St John's Wort.
Storage
Store below 30°C.
MIMS Class
ATC Classification
J02AC03 - voriconazole ; Belongs to the class of triazole derivatives. Used in the systemic treatment of mycotic infections.
Presentation/Packing
Tab 200 mg (white, oval, biconvex, film-coated engraved with "
Click on icon to see table/diagram/image
" logo on one side and "V200" on the other side) x 3 x 10's.
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