Quinine: reminder of dose-dependent QT-prolonging effects; updated medicine interactions

Quinine has dose-dependent QT-interval-prolonging effects and should be used with caution in patients with risk factors for QT prolongation or in those with atrioventricular block.

• From: Medicines and Healthcare products Regulatory Agency
• Published: 24 November 2017

• Therapeutic area: Cardiovascular disease and lipidology, Infectious disease, Neurology, Pain management and palliation

Advice for healthcare professionals:

• be aware of dose-dependent effects on the QT interval and use caution if prescribing quinine in patients:
  • with conditions that predispose to QT prolongation such as pre-existing cardiac disease or electrolyte disturbance
  • taking other medicines that could prolong the QT interval
  • with atrioventricular block
• monitor patients closely if administration of quinine with phenobarbital or carbamazepine is necessary; serum levels of these anticonvulsant medicines could become raised and cause anticonvulsant toxicity
• consult the Summary of Product Characteristics for a full list of interacting medicines and potential adverse reactions
• report suspected adverse drug reactions with quinine on a Yellow Card

Cardiac effects

Quinine is well known to have effects on the QT interval. A 2017 routine EU review recommended that warnings for dose-dependent QT-prolonging effects should be present in the product information for all quinine-containing medicines.

Use caution if prescribing quinine medicines in patients with conditions that predispose to QT prolongation, such as pre-existing cardiac disease or electrolyte disturbances, or in patients taking other medicines that prolong the QT interval (see table from Stockley’s Drug Interactions for examples). Use caution when prescribing quinine to patients with atrioventricular block since quinine could aggravate conduction deficits.

CYP3A4-mediated interactions with other drugs

Quinine is metabolised via hepatic oxidative cytochrome P450 pathways, predominantly by CYP3A4. The 2017 review identified a pharmacokinetic study^{[footnote 1]} reporting that serum levels of phenobarbital or carbamazepine could become raised when these anticonvulsant drugs are used concomitantly with quinine. Although data appear to be limited to this study, it is advisable to monitor for evidence of toxicity if quinine is used concomitantly.

Since CYP3A4 is involved in the metabolism of many other drugs, consult the section 4.5 of the Summary of Product Characteristics (SPC) for a list of interacting medicines before prescribing quinine.

Reminder of other important adverse reactions associated with quinine

Quinine has been used in the UK for the treatment of nocturnal leg cramps for many years; however, you should be aware of important events that can occur in patients taking this medicine. Consult the SPC for important recommendations about the proper use of quinine. Report suspected adverse drug reactions with quinine on a Yellow Card.

Further information

Scientific conclusions and grounds for the variation to the terms of the Marketing Authorisation(s) for quinine medicines.

Quinine: not to be used routinely for nocturnal leg cramps. Drug Safety Update, June 2010.

BNF Quinine interactions.

Article citation: Drug Safety Update volume 11, issue 4; November 2017: 2.

1. Amabeoku GJ, et al. Pharmacokinetic interaction of single doses of quinine and carbamazepine, phenobarbitone and phenytoin in healthy volunteers. East Afr Med J 1993; 70: 90-93. ↩

Published 24 November 2017