Formulary
Voriconazole: Indications, Dosing, Side Effects and Interactions
Voriconazole clinical drug profile including indications, dosing, side effects, cautions and interactions.
MedNext Academy | 6 min read
Voriconazole: Indications, Dosing, Side Effects and Interactions
Voriconazole clinical drug profile including indications, dosing, side effects, cautions and interactions.
Indications and dose
**Invasive aspergillosis,Serious infections caused byScedosporiumspp.,Fusariumspp., or invasive fluconazole-resistantCandidaspp. (includingC. krusei)**
- **Adult** (By Mouth): (body-weight 40 kg and above) Initially 400 mg every 12 hours for 2 doses, then 200 mg every 12 hours, increased if necessary to 300 mg every 12 hours.
- **Adult** (By Intravenous Infusion): Initially 6 mg/kg every 12 hours for 2 doses, then 4 mg/kg every 12 hours; reduced if not tolerated to 3 mg/kg every 12 hours ; for max. 6 months.
**Invasive aspergillosis, Serious infections caused by Scedosporium spp., Fusarium spp., or invasive fluconazole-resistant Candida spp. (including C. krusei) for voriconazole**
- **Child 2-11 years** (By mouth): Treatment should be initiated with intravenous regimen, and oral regimen should be considered only after there is a significant clinical improvement; maintenance 9 mg/kg every 12 hours, adjusted in steps of 1 mg/kg and increased if necessary up to 350 mg every 12 hours, then adjusted in steps of 50 mg as required.
- **Child 12-14 years (body-weight up to 50 kg)** (By mouth): Treatment should be initiated with intravenous regimen, and oral regimen should be considered only after there is a significant clinical improvement; maintenance 9 mg/kg every 12 hours, adjusted in steps of 1 mg/kg and increased if necessary up to 350 mg every 12 hours, then adjusted in steps of 50 mg as required.
- **Child 12-14 years (body-weight 50 kg and above)** (By mouth): Initially 400 mg every 12 hours for 2 doses, then 200 mg every 12 hours, increased if necessary to 300 mg every 12 hours.
- **Child 15-17 years (body-weight up to 40 kg)** (By mouth): Initially 200 mg every 12 hours for 2 doses, then 100 mg every 12 hours, increased if necessary to 150 mg every 12 hours.
- **Child 15-17 years (body-weight 40 kg and above)** (By mouth): Initially 400 mg every 12 hours for 2 doses, then 200 mg every 12 hours, increased if necessary to 300 mg every 12 hours.
- **Child 2-11 years** (By intravenous infusion): Initially 9 mg/kg every 12 hours for 2 doses, then 8 mg/kg every 12 hours; adjusted in steps of 1 mg/kg as required ; for max. 6 months.
- **Child 12-14 years (body-weight up to 50 kg)** (By intravenous infusion): Initially 9 mg/kg every 12 hours for 2 doses, then 8 mg/kg every 12 hours; adjusted in steps of 1 mg/kg as required ; for max. 6 months.
- **Child 12-14 years (body-weight 50 kg and above)** (By intravenous infusion): Initially 6 mg/kg every 12 hours for 2 doses, then 4 mg/kg every 12 hours; reduced if not tolerated to 3 mg/kg every 12 hours ; for max. 6 months.
- **Child 15-17 years** (By intravenous infusion): Initially 6 mg/kg every 12 hours for 2 doses, then 4 mg/kg every 12 hours; reduced if not tolerated to 3 mg/kg every 12 hours ; for max. 6 months.
Cautions
Avoid exposure to sunlight; bradycardia; cardiomyopathy; electrolyte disturbances; history of QT interval prolongation; patients at risk of pancreatitis; symptomatic arrhythmias
Contraindications
Acute porphyrias
Side effects
General side-effects: Common or very common Acute kidney injury; agranulocytosis; alopecia; anaemia; anxiety; arrhythmias; asthenia; bone marrow disorders; chest pain; chills; confusion; constipation; depression; diarrhoea; dizziness; drowsiness; dyspnoea; electrolyte imbalance; eye disorders; eye inflammation; fever; gastrointestinal discomfort; haemorrhage; hallucination; headache; hepatic disorders; hypoglycaemia; hypotension; increased risk of infection; insomnia; leucopenia; muscle tone increased; nausea; neutropenia; oedema; oral disorders; pain; pulmonary oedema; respiratory disorders; seizure; sensation abnormal; skin reactions; syncope; tetany; thrombocytopenia; tremor; vision disorders; vomiting Uncommon Adrenal insufficiency; arthritis; brain oedema; duodenitis; encephalopathy; eosinophilia; gallbladder disorders; hearing impairment; hypothyroidism; influenza like illness; lymphadenopathy; lymphangitis; movement disorders; nephritis; nerve disorders; pancreatitis; parkinsonism; phototoxicity; proteinuria; pseudomembranous enterocolitis; QT interval prolongation; renal tubular necrosis; severe cutaneous adverse reactions (SCARs); taste altered; thrombophlebitis; tinnitus; vertigo Rare or very rare Angioedema; cardiac conduction disorders; disseminated intravascular coagulation; hyperthyroidism Frequency not known Cutaneous lupus erythematosus; periostitis (more common in transplant patients); squamous cell carcinoma (more common in presence of phototoxicity) Specific side-effects: Frequency not known With intravenous use Infusion related reaction Side-effects, further information Hepatotoxicity Hepatitis, cholestasis, and acute hepatic failure have been reported; risk of hepatotoxicity increased in patients with haematological malignancy. Consider treatment discontinuation if severe abnormalities in liver function tests. Phototoxicity Phototoxicity occurs uncommonly. If phototoxicity occurs, consider treatment discontinuation; if treatment is continued, monitor for pre-malignant skin lesions and squamous cell carcinoma, and discontinue treatment if they occur.
Interactions
**Severe interactions:**
- Venetoclax [CYP3A substrate] Although not studied, voriconazole is likely to significantly increase the plasma concentrations of venetoclax.
- Anticonvulsants Carbamazepine and longacting barbiturates (including but not limited to: phenobarbital, mephobarbital) [potent CYP450 inducers] Although not studied, carbamazepine and long-acting...
- Antipsychotics Lurasidone [CYP3A4 substrate] Although not studied, voriconazole is likely to significantly increase the plasma concentrations of lurasidone.
- Coadministration of voriconazole and everolimus is not recommended because voriconazole is expected to significantly increase everolimus concentrations (see section 4.4).
- Non-steroidal selective mineralocorticoid receptor (MR) antagonists Finerenone [CYP3A4 substrate] Although not studied, voriconazole is likely to significantly increase the plasma concentrations of...
- Opioid receptor antagonists Naloxegol [CYP3A4 substrate] Although not studied, voriconazole is likely to significantly increase the plasma concentrations of naloxegol.
- Vasopressin receptor antagonists Tolvaptan [CYP3A substrate] Although not studied, voriconazole is likely to significantly increase the plasma concentrations of tolvaptan.
**Other interactions (52):**
- Voriconazole is metabolised by, and inhibits the activity of, cytochrome P450 isoenzymes, CYP2C19, CYP2C9, and CYP3A4.
- Inhibitors or inducers of these isoenzymes may increase or decrease voriconazole plasma concentrations, respectively, and there is potential for voriconazole to increase the plasma concentrations of...
- Unless otherwise specified, drug interaction studies have been performed in healthy adult male subjects using multiple dosing to steady state with oral voriconazole at 200 mg twice daily (BID).
- Voriconazole should be administered with caution in patients with concomitant medication that is known to prolong QTc interval.
- Interaction table Interactions between voriconazole and other medicinal products are listed in the table below (once daily as "QD", twice daily as "BID", three times daily as "TID" and not...
- Medicinal product Interaction geometric mean changes (%) Recommendations concerning coadministration Antacids Cimetidine (400 mg BID) [non-specific CYP450 inhibitor and increases gastric pH]...
Pregnancy
Toxicity in animal studies-manufacturer advises avoid unless potential benefit outweighs risk.
Breast feeding
Manufacturer advises avoid-no information available.
Hepatic impairment
Manufacturer advises caution, particularly in severe impairment (no information available). Dose adjustments Manufacturer advises use usual initial loading dose then halve maintenance dose in mild to moderate cirrhosis.
Renal impairment
Intravenous vehicle may accumulate if creatinine clearance less than 50 mL/minute-use intravenous infusion only if potential benefit outweighs risk, and monitor renal function; alternatively, use tablets or oral suspension (no dose adjustment required). M See Prescribing in renal impairment .
Medicinal forms
Tablet,Suspension,Solution
Clinical governance
**Author:** MedNext Clinical Team. **Clinical reviewer:** Dr Shameer Deen, MBBS, MS, MRCS. **Sources:** BNF, Indian Pharmacopoeia, CIMS India. **Correction:** Report errors at support@mednext.academy.
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