Drug products: Sotacor®, Sotalol 2care4, Sotalol Ebb, Sotalol Mylan, Sotalol Orifarm, Sotalol ratiopharm, Sotalol-Carinopharm
ATC code: C07AA07
Substances: sotalol, sotalol hydrochloride
Many anti-arrhythmic drugs prolong the repolarization time which is visualized in the ECG as a prolongation of the QT-interval. This increases the risk of serious ventricular tachycardias of the type Torsade de pointes. Women have an overall higher risk of developing Torsade de pointes when treated with anti-arrhythmic drugs that do not seem to be related to serum concentration.
When treated with sotalol the increased risk of ventricular tachycardia in women should be considered.
Pharmacokinetics and dosing
An open-label randomized parallel study (12 men, 12 women) investigated the pharmacokinetics of intravenous doses of d-sotalol up to 3.0 mg/kg. Volume of distribution at steady-state (Vdss) was found to be 16% lower in women than men . The authors suggest this small difference to not be clinically important. For other pharmacokinetic parameters, there were no differences observed between men and women . Contrary to this, a single dose of 160 mg racemic sotalol to healthy volunteers (28 men, 11 women) resulted in higher mean peak plasma concentrations in women and a larger mean change in QT-interval in women .
Despite the small pharmacokinetic differences of sotalol, the clinical studies have shown effect with similar doses in men and women and no sex differentiation in dosing has been suggested .
In a randomized double-blind trial (234 men, 66 women), the efficacy of oral low-dose sotalol was compared with placebo in the prophylactic treatment of supraventricular tachyarrhythmia (SVT) shortly after coronary artery bypass grafting. Men had a less protection by sotalol and therefore developed more postoperative SVTs than women (RR 1.7) .
The mortality risk of sotalol in patients after myocardial infarction with left ventricular dysfunction was investigated in the SWORD trial (2679 men, 442 women). Men and women were at a similar risk of death in the overall SWORD population .
Sex differences in the proarrhythmic potential of QT-prolonging drugs are well documented. Women have a greater risk than men of developing dangerous ventricular tachycardias, Torsade de pointes (TdP), when given drugs prolonging repolarization . A meta-analysis of cardiovascular medications report that female sex is a risk factor for drug-induced TdP for many of the analyzed medications, including sotalol. Of the 332 cases of TdP in this meta-analysis, 70% were women . Thus, the occurrence of TdP was independent of dosage and does not appear to be related to any critical serum drug level. It is suggested that this finding could be explained by a female predisposition to prolonged cardiac repolarization. In general, women have a longer average QT-interval than men [7, 8]. Also in further analysis of a database including more than 3000 patients given sotalol for treatment of atrial or ventricular arrhythmias, women were found to be at increased risk of developing TdP when taking the drug; 4.1% of the women vs. 1.0% of the men had TdP .
Reproductive health issues
Regarding teratogenic aspects, please consult Janusmed Drugs and Birth Defects (in Swedish, Janusmed fosterpåverkan).
Date of litterature search: 2019-05-16
- Salazar DE, Much DR, Nichola PS, Seibold JR, Shindler D, Slugg PH. A pharmacokinetic-pharmacodynamic model of d-sotalol Q-Tc prolongation during intravenous administration to healthy subjects. J Clin Pharmacol. 1997;37:799-809. PubMed
- Darpo B, Karnad DR, Badilini F, Florian J, Garnett CE, Kothari S et al. Are women more susceptible than men to drug-induced QT prolongation? Concentration-QTc modelling in a phase 1 study with oral rac-sotalol. Br J Clin Pharmacol. 2014;77(3):522-31. PubMed
- Sotacor (sotalol). Summary of Product Charateristics. Swedish Medical Products Agency [updated 2018-09-30, cited 2019-05-16].
- Suttorp MJ, Kingma JH, Peels HO, Koomen EM, Tijssen JG, van Hemel NM et al. Effectiveness of sotalol in preventing supraventricular tachyarrhythmias shortly after coronary artery bypass grafting. Am J Cardiol. 1991;68:1163-9. PubMed
- Pratt CM, Camm AJ, Cooper W, Friedman PL, MacNeil DJ, Moulton KM et al. Mortality in the Survival With ORal D-sotalol (SWORD) trial: why did patients die?. Am J Cardiol. 1998;81:869-76. PubMed
- Wolbrette DL. Risk of proarrhythmia with class III antiarrhythmic agents: sex-based differences and other issues. Am J Cardiol. 2003;91:39D-44D. PubMed
- Makkar RR, Fromm BS, Steinman RT, Meissner MD, Lehmann MH. Female gender as a risk factor for torsades de pointes associated with cardiovascular drugs. JAMA. 1993;270:2590-7. PubMed
- Yarnoz MJ, Curtis AB. More reasons why men and women are not the same (gender differences in electrophysiology and arrhythmias). Am J Cardiol. 2008;101:1291-6. PubMed
- Lehmann MH, Hardy S, Archibald D, quart B, MacNeil DJ. Sex difference in risk of torsade de pointes with d,l-sotalol. Circulation. 1996;94:2535-41. PubMed
- Läkemedelsstatistik. Stockholm: Socialstyrelsen. 2018 [cited 2019-03-08.] länk
Reviewed by: Mia von Euler
Approved by: Karin Schenck-Gustafsson