Clinical Pharmacokinetics and Pharmacodynamics of Anti-Tubercular Drugs in Pregnancy

The objectives of this qualitative review were to critically evaluate and summarize the currently available data on the use of anti-tuberculosis (TB) drugs during pregnancy, with a focus on treatment outcomes, safety, and pharmacokinetics. This qualitative, narrative review was based on literature searches in Medline, Pubmed, Embase, and Google Scholar (from their inception to 13 August 2020). Our search identified 22 papers related to treatment outcomes and 14 papers related to pharmacokinetic exposures and fetal distributions. While it is challenging to study this patient population, current evidence supports treatment of drug-susceptible TB, multidrug-resistant TB and latent TB infections. However, decisions regarding initiating, continuing, or discontinuing anti-tubercular medications while pregnant should be individualized and discussed with a specialist. Similarly, the pharmacokinetic data of anti-TB agents were mainly derived from small scale, observational studies many of which lacked high quality controls. Based on these data, it does not appear that pregnancy has an extensive impact on the pharmacokinetics of the majority of first-line and second-line agents, although caution (discussed in the review) should be exercised in data interpretation. Fetal drug exposure can also be significant and should be considered when selecting an anti-TB agent for longer term treatment. Overall, it is generally difficult to predict pregnancy-associated pharmacokinetic changes based only on drug’s physiochemical characteristics.