NHS Greater Glasgow & Clyde Area Drug and Therapeutics Committee
Greater Glasgow and Clyde Medicines
Medicines Update

Voriconazole: prescribing safely (PostScript 80)

Voriconazole is a broad spectrum, triazole antifungal agent indicated primarily in immunocompromised patients with progressive, possibly life-threatening infections, eg invasive aspergillosis. Treatment of candidaemia in non-neutropenic patients is restricted to those who cannot tolerate or are at increased risk of side effects of amphotericin B. The NHSGGC Formulary restricts its use to specialist prescribers only.

 

Voriconazole interacts with a variety of drugs due to inhibition of cytochrome P450 enzyme system. Prescribers will be aware of the importance of considering the potential for interactions when they prescribing new treatments. For more information on drug interactions and cytochrome P450, please refer to PostScript Acute 11 (June 2013) and 2 (January 2011).

 

Examples of Significant Interactions

Voriconazole has several associated interactions, many of which are clinically significant. Always check with the SPC, BNF or other information source and if the combination is contraindicated do not co-prescribe.

 

Examples of drugs that should be avoided with voriconazole include carbamazepine, efavirenz, ergotamine, everolimus, pimozide, quinidine, rifampicin, ritonavir, sirolimus and St John’s Wort.

 

Examples of drugs that require additional monitoring with voriconazole include immunosuppressants (ciclosporin, tacrolimus), warfarin and coumarins, opioid analgesics, benzodiazepines, NSAIDS, statins, omeprazole, sulphonylureas. Check the SPC for details of monitoring required.

 

QT interval prolongation

As well as being an enzyme inhibitor, voriconazole has been associated with QT interval prolongation. There have been rare cases of torsades de pointes in patients on voriconazole who had risk factors. More information on drug induced QT interval prolongation can be found here.

 

Voriconazole should be administered with caution to patients with potentially proarrhythmic conditions, such as

  • congenital or acquired QT-prolongation 
  • cardiomyopathy, in particular when heart failure is present
  • sinus bradycardia (<50 bpm)
  • existing symptomatic arrhythmias
  • concomitant medicinal product that is known to prolong QT interval
  • history of cardiotoxic chemotherapy
  • uncorrected hypokalaemia, hypocalcaemia or hypomagnesaemia

 

Hepatic toxicity

In clinical trials, there have been rare cases of serious hepatic reactions including clinical hepatitis, cholestasis and fulminant hepatic failure, including fatalities. Hepatic reactions occurred primarily in patients with serious underlying medical conditions; predominantly haematological malignancy. Transient hepatic reactions, including hepatitis and jaundice, have occurred among patients with no other identifiable risk factors. Liver dysfunction has usually been reversible on discontinuation of therapy.

 

Monitoring of hepatic function

Patients receiving voriconazole must be carefully monitored for hepatic toxicity. Clinical management should include laboratory evaluation of hepatic function (specifically ALT and AST) at the initiation of treatment with voriconazole and at least weekly for the first month of treatment. If the liver function tests become markedly elevated, voriconazole should be discontinued, unless the medical judgment of the risk-benefit of the treatment for the patient justifies continued use. Monitoring will be carried out by the specialist who recommended treatment. There is no shared care protocol in place.

 

Key points

  • It is essential that healthcare professionals who prescribe take responsibility for identifying and acting on drug interactions to minimise the risk to patients. Ensure effective medicines reconciliation.
  • Prescribers must take responsibility to ensure the medication can be prescribed safely. The dispensing pharmacist cannot always check interactions as they may not have information on the patient’s full medical history or other prescribed drugs. Drugs prescribed in hospital are unlikely to be on ECS. Interaction checks are not automatic via electronic systems.
  • Voriconazole is restricted to specialist use and should only be prescribed for indications listed in the NHSGGC Formulary.
  • Always check for interactions with all existing therapy before voriconazole is started. If the combination is contraindicated, do not co-prescribe.
  • If there is an interaction, decide on a management plan and document the details of the interaction in the patient’s medical notes. Consider what options exist for changing one or other of the drugs to allow safe prescribing. Consultation with the relevant specialists may be required.
  • Ensure the plan is documented, followed and communicated to other members of the multidisciplinary healthcare team including hospital and community pharmacies and the patient’s GP.
  • Interactions must be considered when prescribing any new medication
  • If unsure how to manage an interaction or of the potential significance of an interaction, contact pharmacy for advice.
  • GPs should consider adding voriconazole as an “outside” medication on repeat prescribing lists given the potential for interactions.

 

Sources to Check for Drug Interactions

 

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