The full, clinically endorsed dose recommendation should be obtained from Lareb.

Rationale for drug selection  

Sotalol is used during pregnancy for the treatment of foetal indications, including supraventricular tachycardia and atrial flutter. Foetal tachycardia lacks a standardized pharmacological treatment guideline. To support more evidence-based dosing, we assessed foetal efficacy targets, whether current maternal dosing achieves adequate foetal exposure, and how to optimize sotalol dosing during pregnancy.

Pharmacokinetics of sotalol in pregnancy 

Sotalol is mainly eliminated by the kidneys. Due to increase of GFR during pregnancy, the  drug concentrations in both the mother and the foetus can decrease. Sotalol extensively crosses the placenta, with foetal plasma levels similar to maternal concentrations.  To optimize dosing during pregnancy, maternal-foetal PBPK model was used to simulate the effects of different dosing strategies. This model aimed to identify a dosing regimen that would achieve foetal therapeutic concentrations while avoiding excessive maternal exposure, thereby reducing the likelihood of maternal adverse effects. The simulations indicated that the maximum daily dose can be safely reduced without compromising foetal efficacy, thus minimizing the risks associated with maternal overexposure.

Benefits and risks with proposed dose adjustments 

The expected benefits and associated risk of lowering the maximal daily dose during pregnancy.

In short  

Sotalol is used to treat foetal arrythmias. During pregnancy, the mother clears sotalol faster, which can lower the amount that reaches the foetus. PBPK model simulations indicated that the maximum daily dose can be safely reduced without compromising foetal efficacy, thus minimizing the risks associated with maternal overexposure. Based on the weighing of benefits and risks, the working committee derived an appropriate dose adjustment. Consult Lareb for the model-informed dosing recommendation.