Intravenous Candidaemia, Deep tissue candida infections, Invasive aspergillosis, Oesophageal candidiasis, Scedosporiosis and fusariosis
Adult: Loading dose: 6 mg/kg 12 hourly for the 1st 24 hours. Maintenance: 4 mg/kg 12 hourly, may reduce dose to 3 mg/kg 12 hourly, if necessary. Max rate: 3 mg/kg/hour. Duration of treatment is based on clinical response. Dosage and treatment recommendations may vary between countries and individual products (refer to specific product guidelines). Child: 2-14 years weighing <50 kg: Loading dose: 9 mg/kg 12 hourly for the 1st 24 hours. Maintenance: 8 mg/kg 12 hourly. Dose may be increased in increments of 1 mg/kg, if necessary, if higher doses are not tolerated, may reduce by 1 mg/kg steps. Max rate: 3 mg/kg/hour. 12-14 years weighing ≥50 kg and ≥15 years regardless of weight: Same as adult dose. Duration of treatment is based on clinical response. Treatment recommendations may vary between countries and individual products (refer to specific product guidelines).
Oral Candidaemia, Deep tissue candida infections, Invasive aspergillosis, Oesophageal candidiasis, Scedosporiosis and fusariosis
Adult: Patients weighing <40 kg: Loading dose: 200 mg 12 hourly for the 1st 24 hours. Maintenance: 100 mg bid, may be increased to 150 mg bid, if necessary. May decrease in steps of 50 mg to a minimum of 100 mg bid, if higher doses are not tolerated. Patients weighing ≥40 kg: Loading dose: 400 mg 12 hourly for the 1st 24 hours. Maintenance: 200 mg bid, may be increased to 300 mg bid, if necessary. May decrease in steps of 50 mg to a minimum of 200 mg bid, if higher doses are not tolerated. Duration of treatment is based on clinical response. Dosage and treatment recommendations may vary between countries and individual products (refer to specific product guidelines). Child: 2-14 years weighing <50 kg: Initiate with IV regimen for the 1st 24 hours, followed by oral dose of 9 mg/kg bid. Max: 350 mg bid. Dose may be increased by 1 mg/kg increments or by 50 mg steps, according to response. Max: 350 mg bid. May reduce dose by 1 mg/kg or by 50 mg steps, if patients are unable to tolerate. 12-14 years weighing ≥50 kg and ≥15 years regardless of weight: Same as adult dose. Duration of treatment is based on clinical response. Dosage and treatment recommendations may vary between countries and individual products (refer to specific product guidelines).
What are the brands available for Voriconazole in Hong Kong?
Voriconazole is mainly metabolized by CYP2C19 enzyme. CYP2C19 gene polymorphisms are associated with wide interpatient variability in serum concentrations, decreased clinical response and increased risk of adverse effects. Available data show that approx 15-20% of Asians, 3-5% Caucasians and Black are poor metabolisers. Genetic testing may be beneficial to avoid toxicity and to assess drug effectiveness.
Clinical Pharmacogenetics Implementation Consortium (CPIC) Guideline as of December 2016:
Higher dose-adjusted trough concentrations and increased risk of adverse events.
Consider using an alternative agent that is not primarily metabolised by CYP2C19 (e.g. isavuconazole, liposomal amphotericin B, and posaconazole). In cases where voriconazole is the most appropriate treatment, use at a lower dose with careful therapeutic drug monitoring.
Royal Dutch Pharmacists Association - Pharmacogenetics Working Group (DPWG) Guideline as of November 2018:
Phenotype
Implications
Recommendations
CYP2C19 ultrarapid metaboliser
Reduced therapeutic effect.
Use 1.5x higher initial dose and monitor plasma concentration.
CYP2C19 intermediate metaboliser
Increased plasma concentration that may result in improved therapeutic effect or increased risk of side effects.
Monitoring of plasma levels.
CYP2C19 poor metaboliser
Increased plasma concentration that may result in improved therapeutic effect or increased risk of side effects.
Use 50% of standard dose and monitoring of plasma levels.
Dosage or treatment recommendations may vary among countries. Refer to specific country guidelines for the appropriate clinical recommendations.
Renal Impairment
Intravenous:
CrCl (mL/min)
Dosage
<50
Use oral voriconazole when possible.
Hepatic Impairment
Mild to moderate (Child-Pugh class A and B): Initiate with usual adult loading dose. Maintenance dose must be reduced by 50%.
Administration
Voriconazole Should be taken on an empty stomach.
Reconstitution
Oral susp: Reconstitute with 46 mL of water to provide a suspension containing 40 mg/mL. Shake vigorously for about 1 minute. IV infusion: Reconstitute a vial labelled as containing 200 mg with 19 mL sterile water for inj to provide a concentration of 10 mg/mL and an extractable volume of 20 mL. Further dilute the required volume to a compatible IV infusion solution to a final concentration of 0.5-5 mg/mL.
Incompatibility
IV: Incompatible with 4.2% Na bicarbonate infusion. Do not infuse concomitantly with any blood products or short-term concentrated electrolytes even in separate IV line or cannula.
Contraindications
Hypersensitivity. Concomitant use with CYP3A4 substrates (e.g. terfenadine, astemizole, cisapride, pimozide, quinidine, ivabradine, naloxegol, ergot alkaloids such as ergotamine, dihydroergotamine); long-acting barbiturates (e.g. phenobarbital, mephobarbital), carbamazepine, efavirenz (≥400 mg/day), lurasidone, rifampicin, rifabutin, high-dose ritonavir (≥800 mg/day), sirolimus, tolvaptan, venetoclax (particularly during initiation and dose titration phase), St. John's wort.
Special Precautions
Patient with proarrhythmic condition (e.g. congenital long QT syndrome, sinus bradycardia, existing symptomatic arrhythmias, cardiomyopathy [particularly in the presence of HF], structural heart disease, electrolyte disturbances [e.g. hypocalcaemia, hypokalaemia, hypomagnesaemia]); porphyria; risk factors for acute pancreatitis (e.g. recent chemotherapy, haematopoietic stem cell transplantation). Electrolyte disturbances (e.g. hypokalaemia, hypomagnesaemia, hypocalcemia). Concomitant use of low-dose ritonavir (200 mg/day). Renal and hepatic impairment. Children and elderly. Pregnancy and lactation.
Women of childbearing potential must use effective contraception during treatment. This drug may cause blurred vision or other visual disturbances, if affected, do not drive or operate machinery. Avoid exposure to sunlight; wear protective clothing and use sunscreen.
Monitoring Parameters
Perform culture and susceptibility tests prior to treatment initiation. Consult local recommendations before treatment due to antimicrobial resistance risks. Monitor serum electrolytes (e.g. Ca, Mg, K) prior to and during therapy; LFTs (e.g. AST, ALT, bilirubin) at initiation, weekly during the 1st month and then monthly during treatment if no abnormalities noted; serum creatinine (particularly with IV therapy in individuals with CrCl <50 mL/min) at baseline and periodically thereafter; visual function (e.g. visual acuity, visual field, color perception) if treatment course is >28 days; pancreatic function (particularly in patients at risk for acute pancreatitis); total body skin examination (yearly or more frequently if lesions are noted). Observe for phototoxic reactions (particularly in children). Assess for signs and symptoms of fluorosis or periostitis (e.g. skeletal pain, radiologic findings).
Overdosage
Symptoms: Photophobia. Management: Symptomatic and supportive treatment. Haemodialysis may assist in removing the drug from the body.
Drug Interactions
Potentially Fatal: May increase the plasma levels of terfenadine, astemizole, cisapride, pimozide, quinidine, and ivabradine, thus increasing the risk of cardiac effects (e.g. QT interval prolongation, torsades de pointes). Significantly decreased plasma concentration with carbamazepine, long-acting barbiturates (e.g. phenobarbital), rifampicin, high-dose ritonavir (≥800 mg/day). May increase the plasma levels of ergot alkaloids (e.g. ergotamine, dihydroergotamine) resulting in ergotism; venetoclax (particularly during initiation and dose titration phase) which may increase risk of tumour lysis syndrome; efavirenz (≥400 mg/day); rifabutin naloxegol, lurasidone, sirolimus, tolvaptan.
Food Interaction
Decreased serum concentration with St. John's wort.
Action
Description: Mechanism of Action: Voriconazole, a synthetic fluconazole derivate, is a triazole antifungal agent. It inhibits fungal CYP450-mediated activity, 14α-lanosterol demethylation thereby decreasing ergosterol synthesis and inhibiting fungal cell membrane formation. Pharmacokinetics: Absorption: Rapidly and almost completely absorbed from the gastrointestinal tract. Food may decrease absorption. Bioavailability: 96% (oral). Time to peak plasma concentration: Approx 1-2 hours (oral). Distribution: Extensively distributed into tissues. Diffuses into the CSF. Plasma protein binding: Approx 58%. Metabolism: Metabolised in the liver by CYP2C19 into N-oxide (major metabolite, with minimal antifungal effect), and also by CYP2C9 and CYP3A4 isoenzymes. Excretion: Via urine (<2%, as unchanged drug).
Chemical Structure
Voriconazole Source: National Center for Biotechnology Information. PubChem Compound Summary for CID 71616, Voriconazole. https://pubchem.ncbi.nlm.nih.gov/compound/Voriconazole. Accessed Jan. 28, 2025.
Storage
Tab: Store below 30°C. Powder for oral suspension: Store between 2-8°C. Reconstituted suspension: Store between 15-30°C. Do not refrigerate or freeze. Stable for 14 days after reconstitution. Powder for infusion: Intact vial: Store between 15-30°C. Reconstituted solution: Stable between 2-8°C for 24 hours. Do not freeze.
J02AC03 - voriconazole ; Belongs to the class of triazole and tetrazole derivatives. Used in the systemic treatment of mycotic infections.
References
Moriyama B, Obeng Owusu A, Barbarino J et al. The Clinical Pharmacogenetics Implementation Consortium Guideline for CYP2C19 and Voriconazole Therapy. Clinical Pharmacology and Therapeutics. 2017 Jul;102(1):45-51. doi: 10.1002/cpt.583. Accessed 10/07/2024Annotation of AusNZ Guideline for Voriconazole and CYP2C19. Pharmacogenomics Knowledgebase (PharmGKB). https://www.pharmgkb.org. Accessed 10/07/2024.Annotation of CPIC Guideline for Voriconazole and CYP2C19. Pharmacogenomics Knowledgebase (PharmGKB). https://www.pharmgkb.org. Accessed 10/07/2024.Annotation of DWPG Guideline for Voriconazole and CYP2C19. Pharmacogenomics Knowledgebase (PharmGKB). https://www.pharmgkb.org. Accessed 10/07/2024.Annotation of FDA Label for Voriconazole and CYP2C19. Pharmacogenomics Knowledgebase (PharmGKB). https://www.pharmgkb.org. Accessed 10/07/2024.Anon. Voriconazole. AHFS Clinical Drug Information [online]. Bethesda, MD. American Society of Health-System Pharmacists, Inc. https://www.ahfscdi.com. Accessed 09/07/2024.Brayfield A, Cadart C (eds). Voriconazole. Martindale: The Complete Drug Reference [online]. London. Pharmaceutical Press. https://www.medicinescomplete.com. Accessed 09/07/2024.CYP2C19 - Voriconazole. UpToDate Lexidrug, Pharmacogenomics Online. Waltham, MA. UpToDate, Inc. https://online.lexi.com. Accessed 10/07/2024.Joint Formulary Committee. Voriconazole. British National Formulary [online]. London. BMJ Group and Pharmaceutical Press. https://www.medicinescomplete.com. Accessed 09/07/2024.Pfizer New Zealand Limited. Vfend 50 mg, 200 mg Film-coated Tablets; 40 mg/mL Powder for Oral Suspension; 200 mg Powder for Infusion data sheet 02 November 2023. Medsafe. http://www.medsafe.govt.nz. Accessed 09/07/2024.Vfend (Pfizer [Malaysia] Sdn. Bhd.). National Pharmaceutical Regulatory Agency - Ministry of Health Malaysia. https://www.npra.gov.my. Accessed 09/07/2024.Voriconazole 200 mg Powder for Solution for Infusion (Fresenius Kabi Limited). MHRA. https://products.mhra.gov.uk. Accessed 09/07/2024.Voriconazole Glenmark 50 mg Film-coated Tablets (Glenmark Pharmaceuticals Europe Limited). MHRA. https://products.mhra.gov.uk. Accessed 09/07/2024.Voriconazole Injection, Powder, Lyophilized, for Solution (Camber Pharmaceuticals, Inc.). DailyMed. Source: U.S. National Library of Medicine. https://dailymed.nlm.nih.gov/dailymed. Accessed 09/07/2024.Voriconazole Pfizer 40 mg/mL Powder for Oral Suspension (Pfizer Limited). MHRA. https://products.mhra.gov.uk. Accessed 09/07/2024.Voriconazole Powder, for Suspension (Slate Run Pharmaceuticals, LLC). DailyMed. Source: U.S. National Library of Medicine. https://dailymed.nlm.nih.gov/dailymed. Accessed 09/07/2024.Voriconazole Tablet, Film Coated (Aurobindo Pharma Limited). DailyMed. Source: U.S. National Library of Medicine. https://dailymed.nlm.nih.gov/dailymed. Accessed 09/07/2024.Voriconazole. UpToDate Lexidrug, Lexi-Drugs Multinational Online. Waltham, MA. UpToDate, Inc. https://online.lexi.com. Accessed 09/07/2024.
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