Voriconazole

Indications
 Oral
Scedosporiosis and Fusariosis
Adult: ≥40 kg: 400 mg every 12 hr for the 1st 24 hr. Maintenance: 200 mg every 12 hr, increased if necessay to 300 mg every 12 hr. <40 kg: 200 mg every 12 hr for the 1st 24 hr. Maintenance: 100 mg every 12 hr, increased if necessary to 150 mg every 12 hr. For oesophageal candidiases: Loading dose is not necessary and treatment should be given for at least 14 days and continued for 7 days after symptoms resolved.
Child: 2-<12 yr: 200 mg every 12 hr.
Hepatic impairment: Child-Pugh category A and B: Standard loading doses but halved the maintenance doses. Child-Pugh category C: no studies done.
Oral
Invasive aspergillosis
Adult: ≥40 kg: 400 mg every 12 hr for the 1st 24 hr. Maintenance: 200 mg every 12 hr, increased if necessay to 300 mg every 12 hr. <40 kg: 200 mg every 12 hr for the 1st 24 hr. Maintenance: 100 mg every 12 hr, increased if necessary to 150 mg every 12 hr. For oesophageal candidiases: Loading dose is not necessary and treatment should be given for at least 14 days and continued for 7 days after symptoms resolved.
Child: 2-<12 yr: 200 mg every 12 hr.
Hepatic impairment: Child-Pugh category A and B: Standard loading doses but halved the maintenance doses. Child-Pugh category C: no studies done.
Oral
Deep tissue Candida infections
Adult: ≥40 kg: 400 mg every 12 hr for the 1st 24 hr. Maintenance: 200 mg every 12 hr, increased if necessay to 300 mg every 12 hr. <40 kg: 200 mg every 12 hr for the 1st 24 hr. Maintenance: 100 mg every 12 hr, increased if necessary to 150 mg every 12 hr. For oesophageal candidiases: Loading dose is not necessary and treatment should be given for at least 14 days and continued for 7 days after symptoms resolved.
Child: 2-<12 yr: 200 mg every 12 hr.
Hepatic impairment: Child-Pugh category A and B: Standard loading doses but halved the maintenance doses. Child-Pugh category C: no studies done.
Oral
Candidaemia
Adult: ≥40 kg: 400 mg every 12 hr for the 1st 24 hr. Maintenance: 200 mg every 12 hr, increased if necessay to 300 mg every 12 hr. <40 kg: 200 mg every 12 hr for the 1st 24 hr. Maintenance: 100 mg every 12 hr, increased if necessary to 150 mg every 12 hr. For oesophageal candidiases: Loading dose is not necessary and treatment should be given for at least 14 days and continued for 7 days after symptoms resolved.
Child: 2-<12 yr: 200 mg every 12 hr.
Hepatic impairment: Child-Pugh category A and B: Standard loading doses but halved the maintenance doses. Child-Pugh category C: no studies done.
Intravenous
Scedosporiosis and Fusariosis
Adult: Loading dose: 6 mg/kg every 12 hr for the 1st 24 hr. Maintenance: 4 mg/kg every 12 hr (3-4 mg/kg every 12 hr for candidaemia in non-neutropenic patients or patients intolerant of high doses). Max duration: 6 mth. Max infusion rate: 3 mg/kg/hr over 1-2 hr. May switch to oral therapy once patient is able to tolerate oral admin.
Child: 2-<12 yr: 7mg/kg every 12 hr (4mg/kg every 12 hr if intolerant of high doses).
CrCl (ml/min)Dosage Recommendation
<50Use oral voriconazole and avoid IV.
Hepatic impairment: Child-Pugh category A and B: Standard loading doses but halved the maintenance doses. Child-Pugh category C: no studies done.
Intravenous
Invasive aspergillosis
Adult: Loading dose: 6 mg/kg every 12 hr for the 1st 24 hr. Maintenance: 4 mg/kg every 12 hr (3-4 mg/kg every 12 hr for candidaemia in non-neutropenic patients or patients intolerant of high doses). Max duration: 6 mth. Max infusion rate: 3 mg/kg/hr over 1-2 hr. May switch to oral therapy once patient is able to tolerate oral admin.
Child: 2-<12 yr: 7mg/kg every 12 hr (4mg/kg every 12 hr if intolerant of high doses).
CrCl (ml/min)Dosage Recommendation
<50Use oral voriconazole and avoid IV.
Hepatic impairment: Child-Pugh category A and B: Standard loading doses but halved the maintenance doses. Child-Pugh category C: no studies done.
Intravenous
Deep tissue Candida infections
Adult: Loading dose: 6 mg/kg every 12 hr for the 1st 24 hr. Maintenance: 4 mg/kg every 12 hr (3-4 mg/kg every 12 hr for candidaemia in non-neutropenic patients or patients intolerant of high doses). Max duration: 6 mth. Max infusion rate: 3 mg/kg/hr over 1-2 hr. May switch to oral therapy once patient is able to tolerate oral admin.
Child: 2-<12 yr: 7mg/kg every 12 hr (4mg/kg every 12 hr if intolerant of high doses).
CrCl (ml/min)Dosage Recommendation
<50Use oral voriconazole and avoid IV.
Hepatic impairment: Child-Pugh category A and B: Standard loading doses but halved the maintenance doses. Child-Pugh category C: no studies done.
Intravenous
Candidaemia
Adult: Loading dose: 6 mg/kg every 12 hr for the 1st 24 hr. Maintenance: 4 mg/kg every 12 hr (3-4 mg/kg every 12 hr for candidaemia in non-neutropenic patients or patients intolerant of high doses). Max duration: 6 mth. Max infusion rate: 3 mg/kg/hr over 1-2 hr. May switch to oral therapy once patient is able to tolerate oral admin.
Child: 2-<12 yr: 7mg/kg every 12 hr (4mg/kg every 12 hr if intolerant of high doses).
CrCl (ml/min)Dosage Recommendation
<50Use oral voriconazole and avoid IV.
Hepatic impairment: Child-Pugh category A and B: Standard loading doses but halved the maintenance doses. Child-Pugh category C: no studies done.

Reconstitution: IV: Reconstitute the vial with 19 ml of Water For Inj in order to get a concentration of 10 mg/ml of voriconazole. The required volume is then further diluted with a suitable diluent (e.g. 5% dextrose; 0.9% sodium chloride).
Incompatibility: Do not infuse into the same line or cannula concomitantly with other drug infusions and parenteral nutrition. Do not infuse blood products simultaneously. Incompatible with 4.2% sodium bicarbonate infusion.
Contraindications
 Hypersensitivity. Lactation.
Warnings / Precautions
 Monitor renal and hepatic function before and during treatment. Monitor visual function if used >28 days. Monitor pancreatic function in patients at risk of acute pancreatitis. Haematological malignancy; patients with proarrhythmic conditions; hepatic and renal impairment. Use in pregnancy not recommended, ensure effective contraception during treatment. Avoid exposure to sunlight. Correct electrolyte abnormalities before treatment initiation. May affect ability to drive or operate machinery and do not drive at nght.
Adverse Reactions
 Transient and reversible visual disturbances; fever; headache; abdominal pain; chills; asthenia; back pains; chest pain; face oedema; flu-like syndrome; hypotension; thrombophloebitis; phloebitis; GI disturbances (eg, nausea, vomiting, diarrhoea); jaundice; cheilitis; cholestatic jaundice; gastroenteritis; blood dyscrasias; purpura; peripheral oedema; facial oedema; hypokalaemia; hypoglycaemia; dizziness; hallucinations; confusion; depression; anxiety; tremor; agitation; paraesthesia; respiratory distress syndrome; sinusitis; rash; pruritus; photosensitivity; alopecia; exfoliative dermatitis; acute kidney failure; haematuria; infusion-related reactions. Increased LFT and serum creatinine; prolongation of QT interval.
Potentially Fatal: Stevens-Johnson Syndrome, toxic epidermal necrolysis.
Drug Interactions
 Increased INR with acenocoumarol and warfarin. Increased alfentanil, erlotinib, bosentan, sulphonylureas, ciclosporin, tacrolimus, benzodiazepines, and omeprazole levels. Increased risk of rhabdomyolysis with statins. Increased both delavirdine and voriconazole levels with concurrent use. Increased both HIV protease inhibitors and voriconazole levels with concurrent use. Decreased voriconazole levels and increased efavirenz levels with concurrent use. Increased risk of methadone toxicity with voriconazole. Reduced both phenytoin and voriconazole levels with concurrent use. Increased risk of neurotoxicity with vinca alkaloids. Decreased voriconazole and increased rifabutin levels with concurrent use. Avoid concurrent use with clopidogrel.
Potentially Fatal: Increased risk of torsade de pointes with cisapride, astemizole, pimozide, quinidine and terfenadine. Reduced voriconazole levels with carbamazepine, rifampicin, ritonavir and phenobarbital. Increased risk of ergotism with ergot alkaloids. Increased sirolimus levels with voriconazole.
See Below for More voriconazole Drug Interactions
Food Interactions
 Decreased voriconazole levels with St John's Wort.
Mechanism of Actions
 Voriconazole is a triazole antifungal agent which inhibits cytochrome P450-dependent enzymes thereby inhibiting ergosterol synthesis in fungal cell membranes. It has a broad spectrum of activity against all Candida species (including strains resistant to fluconazole) ,Aspergillus spp., Scedosporium spp., and Fusarium spp.
Absorption: Rapidly and completely absorbed from GI tract. Bioavailability: 96% (oral). Peak plasma concentration: 1-2 hr. Food decreases oral absorption.
Distribution: Protein binding: 58%; diffuses into CSF.
Metabolism: Saturable metabolism. Metabolised by P450 isoenzyme CYP2C19, CYP2C9 and CYP3A4 to inactive metabolites.
Excretion: Excreted in urine (80%).
Administration
 Tab: Should be taken on an empty stomach. (Take at least 1 hr before or after meals.)
Susp: Should be taken on an empty stomach. (Take at least 1 hr before or 2 hr after meals.)
Storage Conditions
 Intravenous: Unreconstituted vials: Store at 15- 30°C (59-86°F); reconstituted concentrate: Store at 2-8°C for up to 24 hr (in a refrigerator). Oral: Tablets: Store at 15-30°C (59-86°F). Powder for oral suspension: Store at 2-8°C (in a refrigerator) before constitution; constituted suspension: Store at 15-30°C (do not refrigerate or freeze) for up to 14 days.
ATC Classification
 J02AC03 - voriconazole ; Belongs to the class of triazole derivatives. Used in the systemic treatment of mycotic infections.
Storage
 Intravenous: Unreconstituted vials: Store at 15- 30°C (59-86°F); reconstituted concentrate: Store at 2-8°C for up to 24 hr (in a refrigerator). Oral: Tablets: Store at 15-30°C (59-86°F). Powder for oral suspension: Store at 2-8°C (in a refrigerator) before constitution; constituted suspension: Store at 15-30°C (do not refrigerate or freeze) for up to 14 days.
Available As
  • Voriconazole 200 mg
  • Voriconazole 50 mg

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