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

Rationale for drug selection  

Labetalol is used to manage hypertension in pregnancy. Pregnancy can alter the pharmacokinetics of drugs. Therefore, dose adjustments might be needed to sustain blood pressure control while minimising maternal and foetal risks.

Pharmacokinetics of labetalol in pregnancy 

Pregnancy alters the activity drug-metabolising enzymes and thereby elimination of labetalol. Specifically, CYP2C19 activity is reduced, while UGT1A1 and UGT2B7 activities are increased. The renal clearance of labetalol is also enhanced during pregnancy. These changes taken together lead to lower plasma concentrations and faster overall clearance during the second and third trimester of pregnancy. As a result, pregnant patients may need both a higher dose and a more frequent dosing schedule to maintain stable labetalol levels. Labetalol crosses the placenta, reaching cord concentrations that are typically about 50-60% of maternal levels. The alterations in plasma concentrations have been confirmed by a population-pharmacokinetic model. The model provided strong evidence on the influence of gestational age on the pharmacokinetics changes of labetalol in pregnancy, informing alternative dosing strategies and supporting decision-making.

Benefits and risks with the proposed dose adjustments 

The expected benefits and associated risk of a higher and more frequent dosing regimen of labetalol during pregnancy.

In short 

Labetalol is prescribed for hypertension during pregnancy. Maternal plasma concentrations of labetalol are reduced during pregnancy, especially in the second and third trimesters. Consequently, some patients may require a higher starting dose and more frequent dosing compared to non-pregnant individuals to maintain stable levels. Based on the weighing of benefits and risks, the working committee derived an appropriate dose adjustments. Consult Lareb for the model-informed dosing recommendations.