Plaquenil® (hydroxycholoroquine): Risk of QT prolongation and other drug-drug interactions in the context of COVID-19 management

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Description:

In Malaysia, Plaquenil® is approved for the treatment of rheumatoid arthritis, juvenile chronic arthritis, discoid and systemic lupus erythematosus, and dermatological conditions caused or aggravated by sunlight. Due to limited clinical evidence to support the efficacy and safety of hydroxychloroquine in the management of COVID-19, Plaquenil® is not approved for COVID-19 management either alone or in combination. Any prescription issued for this purpose is considered as off-label use.

 

(i) Risk of QT-prolongation

Hydroxychloroquine has been documented to cause QT interval prolongation in some patients and it is dose-dependent. The risk of cardiac events depends on several factors and is increased by the association of hydroxychloroquine with other QT-prolongation drugs, such as class IA and III antiarrhythmics, tricyclic antidepressants, antipsychotics, and certain anti-infectives. Patient’s existing medical conditions such as cardiac disease, heart failure, myocardial infarction, bradycardia (< 50 bpm), history of ventricular dysrhythmias and uncorrected hypocalcemia, hypokalemia and/or hypomagnesemia may also potentiate the risk of QT prolongation.

Recently, an increasing number of serious and life-threatening cases of QT prolongation, torsades de pointes, syncope, cardiac arrest, and sudden death have been observed following the use of hydroxychloroquine in the context of COVID-19 management. In most of these cases, the drug was used in combination with another drug known to prolong the QT interval, such as azithromycin. Upon hydroxychloroquine discontinuation, most patients were reported to recover from the adverse event.

 

(ii) Other drug-drug interactions

There are also a number of known drug-drug interactions associated with hydroxychloroquine, such as:

Drugs affecting the absorption, concentration or efficacy of hydroxychloroquine;

  • Antacids (magnesium-containing antacids or kaolin)
  • CYP2C8 and CYP3A4 inhibitors (such as cimetidine, gemfibrozil, clopidogrel, ritonavir, itraconazole, clarithromycin and grapefruit juice)
  • CYP2C8 and CYP3A4 inducers (such as rifampicin, St John’s Wort, carbamazepine and phenobarbital).

 Inhibitory potential of hydroxychloroquine on other drugs;

  • P-glycoprotein substrates (some of these substrates include digoxin, dabigatran and ciclosporin).

 Please refer to the approved Plaquenil® product information for detailed information on these interactions.

 

NPRA has approved a Direct Healthcare Professional Communication (DHPC) letter issued by by Sanofi-aventis (Malaysia) Sdn. Bhd. to highlight this safety issue on 15th June 2020. For further information, please contact your local sales person for a copy of the DHPC.

  

DISCLAIMER:

This publication is aimed at health professionals. The information is meant to provide updates on medication safety issues, and not as a substitute for clinical judgement. While reasonable care has been taken to verify the accuracy of the information at the time of publication, NPRA shall not be held liable for any loss whatsoever arising from the use of or reliance on this publication.

 

 

 

National Pharmaceutical Regulatory Agency (NPRA)
Lot 36, Jalan Universiti, 46200 Petaling Jaya, Selangor, Malaysia.
  • Email: npra@npra.gov.my
  • Phone: +603-7883 5400
  • Fax: +603-7956 2924, +603-7956 7075

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The Government of Malaysia and the National Pharmaceutical Regulatory Agency are not responsible for any loss or damage caused by the usage of any information obtained from this website.

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  • Last Modified: Tuesday 20 October 2020, 15:46:44.
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