Male/Female Differences in Pharmacology: Safety Issues with QT-Prolonging Drugs

For many reasons, information on differences in pharmacokinetics and pharmacodynamics between women and men is limited or lacking altogether. Although women have been included in clinical trials during the past 5-10 years, analyses of the data to address questions in women, men, and various racial/ethnic groups are lacking. Compounding factors are small numbers of women, women not included in early phase clinical trials, and weight or body mass index (BMI) not being considered. Although not much is documented about drug differences between women and men, data from drug adverse events have shown that women more often experience torsades de pointes, a potentially fatal arrhythmia. QT prolongation is considered to be surrogate for torsades because torsades is always preceded by QT prolongation. Drug-induced QT prolongation and accompanying torsades are challenging and urgent safety issues because it is not possible to predict which drugs will induce torsades and which patients are susceptible.