Oral voriconazole

Adult OPAT good practice prescribing guide for complex oral antibiotics

Voriconazole is a triazole antifungal drug which exhibits broad fungicidal activity against Candida species (including fluconazole resistant strains), Aspergillus infections and rare fungal pathogens Scedosporium species and Fusarium species. It is licensed for the treatment of invasive aspergillosis and the treatment of deep seated, disseminated Candida and specific mould infections.

This guide shares practical experience of the use of voriconazole in an OPAT setting. We took an evidence-based approach to create the guidance. We also used expert consensus and practical experience from across NHS Scotland.

This drug summary does not provide specific treatment guidance. Individual patient treatment should take into account the core principles of antimicrobial stewardship. This includes selection of the appropriate antimicrobial for the shortest duration with oral therapy being preferred, whenever possible.

For information on route and method of administration, contraindications, cautions and adverse effects and drug interactions please refer to the following approved resources:

These resources also have more information on licensed indication, use in pregnancy and use in breast feeding. When using an unlicensed medicine or a medicine off-label, follow local health board governance processes.   

It is strongly recommended that OPAT services in Scotland adhere to the Key performance indicators for the management of patients in an outpatient parenteral antimicrobial therapy (OPAT) setting.

Voriconazole

1. Indication and dose

Licensed indication(s) in the OPAT setting Dose

Treatment of invasive aspergillosis

OR

Treatment of serious invasive fungal infections including fluconazole resistant Candida species and fungal infections caused by Scedosporium species and Fusarium species

 

 

 

Patients 40kg and over
Loading dose (Day 1)
400mg 12 hourly

Maintenance dose (Day 2 onwards)
200mg 12 hourly

Patients less than 40kg
Loading dose (Day 1)
200mg 12 hourly

Maintenance dose (Day 2 onwards)
100mg 12 hourly

 

2. Dose adjustments 

Patient characteristics Dosage advice
Renal impairment No dose adjustment necessary.

Hepatic impairment

 

 

 

 

 

 

 

 

 
Hepatic impairment Voriconazole dose

Severe hepatic impairment.

(Defined as either liver function tests more than five times the normal upper limit or signs of liver damage, or both.)

Voriconazole is not recommended.

 

 

Mild to moderate chronic hepatic cirrhosis (Child Pugh score A and B).

 

 

Refer to indication and dosing table above:

  • give the usual loading dose (day 1)
  • give half the usual maintenance dose (day 2 onwards)
Severe, chronic hepatic cirrhosis (Child Pugh score C). Voriconazole is not recommenced.
Obesity No dose adjustment necessary.

 

3. Monitoring requirements

Frequency Recommended monitoring

Baseline

 

 

 

Urea and Electrolytes (U&Es), liver function tests (LFTs), C-reactive protein (CRP) and full blood count (FBC).

Perform Electrocardiography (ECG) particularly if known QTc prolongation, non-modifiable risk factors for prolonged QTc interval or on other drugs that can prolong the QTc interval.

Further monitoring

 

 

 

 

 

 

 

 

Weekly U&Es, LFTs and FBC for at least two weeks after starting voriconazole.

Weekly LFTs for first month of therapy then monthly until treatment complete and whilst patient remains with OPAT service.

CRP can be measured to monitor patient’s clinical progress.

If concerns of QTc prolongation, repeat ECG 48 to 72 hours after starting voriconazole. Perform or repeat ECG if new concerns of QTc prolongation, or when adding any new medication that is known to prolong the QTc interval.

Further monitoring once discharged from OPAT service is dependent upon patient and other clinical factors.

Therapeutic drug monitoring

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

Voriconazole therapeutic drug monitoring is required for all patients at the start of therapy. Subsequent concentration measurements should be considered if:

  • Significant drug interactions which may increase or decrease voriconazole plasma concentrations
  • Concern of poor compliance.
  • Poor clinical response.

Voriconazole exhibits non-linear kinetics. This means that a change in dose is not proportional to the change in the plasma concentration. If necessary, adjust the dose by increasing or decreasing the dose by 50mg at a time.

  • Voriconazole trough concentration measurements are required.
    • These should be taken after at least 48 hours of regular oral administration.
    • Ensure the patient is counselled on taking voriconazole at specific times and is taking voriconazole at equal administration intervals eg every 12 hours, 10 am and 10 pm.
    • Record the time of the previous voriconazole dose (eg previous night at 10 pm).
    • Take a voriconazole trough at the end of the dosage interval before the next dose is given (eg next morning at 10 am).
  • Blood samples may be sent to an off-site laboratory for analysis, therefore may take three to five working days to be reported.
  • Please note gel tubes may bind the analyte resulting in false low voriconazole concentrations. If sending to North Bristol Antimicrobial Reference Laboratory, please send 1 – 2ml separated serum in a plain clotted blood tube (red top). The Bristol reference laboratory provides further information.
Follow up Ensure follow up is arranged with referring specialty, infection specialist or both as necessary.

 

Target therapeutic voriconazole concentrations

PKPD parameter
(pharmacokinetic /pharmacodynamic)		 Recommended target

Trough concentration (pre-dose)

 

 

 

 

1.0 – 5.5mg/L

  • Plasma concentrations less than 1mg/L may be associated with reduced efficacy.
  • Plasma concentrations greater than 4mg/L may be associated with greater risk of toxicity.
  • Plasma concentrations over 2mg/L are recommended for severe disseminated, multifocal or central nervous system (CNS) fungal infections.

 

4. Serious Drug/ Drug and Drug/ Food Interactions

Please note that this is not an exhaustive list. Refer to the BNF or SPC for more information. 

Drug/ Food Recommendations

Voriconazole is primarily metabolised via cytochrome P450 2C19 (CYP2C19) to an inactive metabolite and to a lesser extent via CYP2C9 and CYP3A4 isoenzymes. Genetic polymorphism of CYP2C19 may be observed which can affect drug metabolism in some patients by up to 20%.
Voriconazole itself may also inhibit the activity of cytochrome P450 CYP2C19, CYP2C9 and CYP3A4 isoenzymes.

Anticonvulsants

 

 

 

 

 

 

 

Carbamazepine is a potent CYP3A4 isoenzyme inducer which can increase voriconazole metabolism resulting in markedly reduced maximum concentrations and total exposure. Co-administration is contraindicated by the manufacturers.

Phenytoin is a CYP2C9 substrate and a potent CYP3A4 isoenzyme inducer. Co-administration results in reduced concentrations and exposure of voriconazole and increased concentration and exposure of phenytoin. The manufacturers recommend avoiding this combination unless close monitoring of both phenytoin and voriconazole plasma concentrations is possible.

Antiretrovirals

 

 

 

 

 

 

 

 

Ritonavir has a high affinity for several cytochrome P450 isoenzymes. It is a potent inhibitor of CYP3A4 and inducer of CYP2C9 and CYP2C19. The combined effect results in reduced concentrations and exposure of both drugs. Other protease inhibitors may have a similar effect.

Efavirenz is both an inducer and inhibitor of CYP3A4 and an inducer of both CYP2C9 and CYP2C19 isoenzymes. Dose adjustments of both voriconazole and efavirenz are recommended when administered together. Other Non-Nucleoside Reverse Transcriptase Inhibitors may have a similar effect.

The Liverpool HIV Drug Interactions provides further information.

Analgesia (including non-steroidal anti-inflammatory drugs (NSAIDs) and opioids)

 

 

Voriconazole will increase the exposure of NSAIDs, codeine, tramadol, buprenorphine, morphine, oxycodone, alfentanil, fentanyl (including transdermal formulations) and methadone. Close monitoring for adverse drug reactions and analgesic dose reductions may be required to minimise the risk of toxicity.

Immunosuppressants

 

 

Several immunosuppressant drugs including ciclosporin and tacrolimus are metabolised via CYP3A4 isoenzyme. Close monitoring of the immunosuppressant drug concentrations and possible dose adjustments is recommended during co-administration and after stopping voriconazole.

Other drugs known to prolong QT interval

 

 

 

 

 

 

 

 

 

 

Voriconazole may prolong the QTc interval. Incidence may be increased in presence of the following additional risk factors:

  • Co-administration with other drugs also known to cause QT prolongation. These include anti-arrhythmic drugs (eg amiodarone, beta-blockers), tricyclic antidepressants (eg amitriptyline, nortriptyline), selective serotonin reuptake inhibitors (eg citalopram, sertraline, fluoxetine), antipsychotics (eg risperidone, quetiapine, olanzapine, clozapine), loperamide etc.
  • Patients with congenital or pre-existing prolonged QT interval.
  • Electrolyte disturbance (eg hypokalaemia, hypomagnesaemia).
  • Known underlying cardiac disease (eg heart failure, myocardial infarction, bradycardia).

Avoid co-administration of two or more drugs known to prolong the QT interval where possible. If this is not possible, perform baseline and steady state ECGs to assess for any change in the QT interval.

Proton pump inhibitors

 

 

 

 

Voriconazole concentrations may be increased by omeprazole and the effect augmented by poor metabolisers of CYP2C19 isoenzyme.
Voriconazole may markedly increase omeprazole and esomeprazole exposure via inhibition of CYP2C19 and CYP3A4 isoenzyme activity and may require initial dose reduction. Evidence of an effect is lacking but may be expected for other proton pump inhibitors.

Rifampicin

 

 

Rifampicin is a potent CYP3A4 isoenzyme inducer which can increase voriconazole metabolism resulting in markedly reduced maximum concentrations and total exposure. Co-administration is contraindicated by the manufacturers.

Warfarin

 

 

Voriconazole may enhance anticoagulant effect. Ensure follow up with Anticoagulant Service for International Normalised Ratio (INR) monitoring and any necessary dosage adjustments. Patients should also be counselled on signs of over anticoagulation (eg bruising, bleeding).

Drug/ Food interactions

 

Take on an empty stomach, one hour before or after food. Taken alongside a high fat meal can reduce absorption by up to one third.

 

5. Rare or Serious Adverse Effects

In May 2014, the Medicines and Healthcare products Regulatory Agency (MHRA) provided voriconazole safety advice.

Where possible, patients should be advised to carry a Voriconazole Alert Card (available for Pfizer® brand only).

Please note that this is not an exhaustive list. Refer to the BNF or SPC and advice below.

Adverse effects  Recommendations 

Hepatic impairment

 

 

 

 

Voriconazole may cause serious hepatotoxicity including raised LFTs, particularly the transaminases, cholestatic jaundice and liver failure. Patients require regular hepatic monitoring and they should be advised to report any signs of hepatic impairment (eg fever, malaise, vomiting or jaundice) promptly. Voriconazole therapy should be discontinued if LFTs (transaminases, alkaline phosphate and bilirubin) are greater than five times the upper limit of normal.

Phototoxicity/ skin cancer

 

 

 

 

 

 

 

Voriconazole may cause drug-induced photosensitivity. It is characterised as a severe sunburn affecting sun-exposed skin within minutes to hours of drug administration. Patients should be reminded to practice effective sun protection including avoidance of prolonged exposure to direct sunlight, to encourage the use of sunscreen and to wear sun-protective clothing.

Complications of drug-induced phototoxicity include squamous cell carcinoma. Patients should be advised to check their skin frequently and report any new or changes to skin lesions to the OPAT team, referring clinical team or both.

Psychiatric disorders

 

 

Voriconazole may cause hallucinations, insomnia and depression and may also trigger anxiety and panic attacks. These symptoms may be associated with high voriconazole concentrations. Patients should be advised to report any of these symptoms to the OPAT team, referring clinical team or both.

Visual disturbances

 

 

 

 

Visual disturbances including blurred vision, sensitivity to light, halo vision, seeing stationary objects moving, presence of vitreous floaters, night blindness and yellow tinged vision. These symptoms are usually acute, associated with high voriconazole concentrations and subside within 60 minutes of administration. Patients should be advised to report any new or continuing visual symptoms to the OPAT team, referring clinical team or both.

Scottish Antimicrobial Prescribing Group (SAPG)
Approved May 2026 for review May 2029
Content updated: July 2026