Is there evidence that quinine reduces muscle cramps?

Fråga: Is there evidence that quinine reduces muscle cramps? Have arrhythmias been reported as side effects of quinine?

Sammanfattning: It is not recommended to treat muscle cramps with quinine due to lack of approved indication and due to an increased risk of serious and life threatening side effects. A Cochrane report concludes that low quality evidence shows that quinine (200-500 mg daily) significantly reduces cramp number and cramp days. A number of case reports in the literature describe an association between quinine and cardiac side effects such as arrhythmias, ventricular fibrillation, ventricular arrhythmias, QT prolongation, and Torsade de pointes.

Svar: Question 1:

In Sweden, quinine is approved for treatment of the muscle diseases myotonia congenita and myotonia atrophica, and severe malaria. In some countries, such as the United Kingdom, quinine is approved treatment and prevention of nocturnal leg cramps in adults and the elderly, when cramps cause regular disruption of sleep (14). Quinine is not approved for treatment of muscle cramps in Sweden (1).

A Cochrane report from 2015 (2) reviewed the evidence about the effect of quinine on muscle cramps. The review included 23 trials, with 1586 patients. Low quality evidence shows that quinine (200-500 mg daily) significantly reduces cramp number and cramp days, and there is moderate quality evidence that quinine reduces cramp intensity.

The US Food and Drug Administration (FDA) does not recommend quinine for the treatment of leg cramps due to lack of approved indication and increased risk of serious and life threatening adverse effects such as hematologic and cardiovascular adverse effects (including thrombocytopenia, hypersensitivity reactions, and QT prolongation), hearing loss, rash, electrolyte imbalance, and drug interactions (3-4).

Question 2:

According to the Summary of Product Characteristics (1), quinine overdose may lead to widening of the QRS complex, arrhythmias, T wave flattening, and Torsade de pointes. QT prolongation is a rare side effect (<1/1000) of quinine.

A number of case reports in the literature describe an association between quinine and cardiac side effects such as arrhythmias (5-6), ventricular fibrillation (7-8), ventricular arrhythmias, QT prolongation (9), and Torsade de pointes (10-11).

In the Swedish adverse drug reaction database (12), there are a total of 121 reports on quinine. One case report from 1979 describes bradycardia, ventricular extrasystoles, and drug interaction associated with the use of quinine in one patient. In the WHO adverse drug reaction database (13), there are a total of 5150 reports on quinine. There are 189 reports of cardiac arrhythmias of which 80 concerned ventricular arrhythmias. Note that not all reports in the WHO database have been assessed for association. Produktresumé Kinin Recip. Meda. Datum för Översyn av Produktresumén 2016-05-11. Via Läkemedelsverkets webbplats (https://lakemedelsverket.se/LMF/Lakemedelsinformation/?nplid=19751203000011&type=product) Cochrane Library. El-Tawil S, Al Musa T, Valli H, Lunn MPT, Brassington R, El-Tawil T, Weber M. Quinine for muscle cramps. Cochrane Database of Systematic Reviews 2015, Issue 4. Art. No.: CD005044 (http://onlinelibrary.wiley.com/doi/10.1002/14651858. CD005044.pub3/epdf) U. S. Food and Drug Administration (FDA). Serious risks associated with using Quinine to prevent or treat nocturnal leg cramps. 2012 (http://www.fda.gov/downloads/ForHealthProfessionals/LearningActivities/UCM317816.pdf) FDA Drug Safety Communication: New risk management plan and patient Medication Guide for Qualaquin (quinine sulfate) 07-08-2010 (http://www.fda.gov/Drugs/DrugSafety/PostmarketDrugSafetyInformationforPatientsandProviders/ucm218202.htm#aihp) Gunawan CA, Harijanto PN, Nugroho A. Quinine-induced arrhythmia in a patient with severe malaria. Acta medica Indonesiana. 2007;39(1):27-32. Tigga FV, Satpathy SK, Das BS. Cardiac arrhythmia following intravenous quinine therapy. The Journal of the Association of Physicians of India. 2001;49:946-947. Busari O, Busari O. Ventricular fibrillation in a 5-year-old child on therapeutic dose of quinine dihydrochloride infusion for acute malaria. Journal of the National Medical Association. 2008;100(9):1063-1065. Kochar Shubhakaran DK, Kumawat B, Kochar SK. A patient with falciparum malaria and bilateral gangrene of the feet who developed arrhythmia/ventricular fibrillation after quinine therapy. QJM : monthly journal of the Association of Physicians. 1998;91(3):246. Bonington A, Davidson RN, Winstanley PA, Pasvol G. Fatal quinine cardiotoxicity in the treatment of falciparum malaria. Transactions of the Royal Society of Tropical Medicine and Hygiene. 1996;90(3):305-307. Martin ES, Rogalski K, Black JN. Quinine may trigger torsades de pointes during astemizole therapy. Pacing and clinical electrophysiology : PACE. 1997;20(8 Pt 1):2024-2025. Bodenhamer JE, Smilkstein MJ. Delayed cardiotoxicity following quinine overdose: a case report. The Journal of emergency medicine. 1993;11(3):279-285. Läkemedelsverkets biverkningsdatabas BiSi WHOs biverkningsdatabas VigiBase SPC Quinine Sulfate Tablets BP 200mg Actavis UK Limited, https://www.medicines.org.uk/emc/medicine/24105, cited 161130