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CP-029 How to deal with a new drug interaction? example of the contraindication alfuzosin–strong CYP3A4 inhibitors
  1. N Bensalah,
  2. I Carpentier,
  3. F Locher,
  4. S Garcia
  1. Pharmacie Centrale, Drug Information Center, Saint-Genis Laval, France

Abstract

Background Since 2014, the French Medicine Agency contraindicates alfuzosin with strong cytochrome P450 3A4 (CYP 3A4) inhibitors, but gives no information on how to manage it. We dispense drugs to haematological outpatients whose treatments can combine alfuzosin (for lower urinary tract symptoms, LUTS) with anti-infective drugs that may be strong CYP 3A4 inhibitors. We conducted a pharmaceutical intervention (PI) but lacked a clear and consensual management for physicians. However, to be efficient and accepted by prescribers, the PI must propose a clear, synthetic and argued way to proceed, adapted to the patient.

Purpose The objective of this work was to determine the incidence and clinical importance of this drug interaction (DI), how to manage it and what are the non-interacting alternatives.

Material and methods A review was conducted of the scientific literature, drug databases and regulatory documents, on the mechanism, clinical evidence and incidence of this DI. Then, the most recent French recommendations on the management of LUTS were used to identify non or less interacting alternatives. Finally, a clinical decision tool was redacted to help the pharmacist manage this DI, depending on patient condition.

Results The mechanism of this DI is established, but no clinical evidence has been found, except for two studies in healthy volunteers that mainly showed an increase in the area under the curve of alfuzosin when associated with ketoconazole. The contraindication was extrapolated from the DI between alfuzosin and telaprevir. Expected side effects are mainly an increased risk of postural hypotension, depending on risk factors that can be managed. In haematological patients, the CYP 3A4 inhibitor generally cannot be stopped because of the infectious risk. Stopping alfuzosin can put the patient at risk of urinary retention (as seen for one patient), but less or non-interacting alternatives exist for each type of LUTS. A guide was developed to offer an argued management of clinical situations when making a PI. Extensive work should be conducted on the positive impact of this guide on acceptance of a PI.

Conclusion Regulatory information may not be sufficient to manage a new DI but appropriate information searches to produce clinical decision tools can provide argued PI.

References and/or Acknowledgements M Boucquin (documentary search)

No conflict of interest.

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