USE OF RIBAVIRIN IN PREGNANCY

Ribavirin is a synthetic nucleoside antiviral agent available in oral and aerosolised formulations. It is currently licensed to treat chronic hepatitis C in combination with interferon alfa-2b or peginterferon alfa-2b (oral), and for the treatment of respiratory syncytial virus (RSV) bronchiolitis in infants and children (aerosol). Unlicensed indications for ribavirin include influenza, severe acute respiratory syndrome (SARS), and adenoviral pneumonia.

Ribavirin is known to accumulate within cells, and is eliminated slowly from non-plasma compartments. As it has been shown to be teratogenic, embryotoxic, and mutagenic in various animal species at doses within the human therapeutic range, the advice from the manufacturers is that conception should be delayed for four months following discontinuation of therapy. Its intentional use during pregnancy has also generally been restricted or reserved for cases of severe maternal illness. As a result the available data are both highly limited and heavily confounded.

The available data currently consist of uncontrolled case reports/series which document the outcomes of approximately 165 direct maternal exposures, only 18 of which occurred in the first trimester. In addition, there are data from approximately 146 cases of indirect maternal exposure.  Although cases of congenital malformation, miscarriage, stillbirth, preterm delivery and low birth weight have been reported following ribavirin exposure in pregnancy, the data are too limited and not in a format to permit an evidence-based assessment of any increased risk of adverse effects on the developing fetus.

No published studies have investigated maternal or fetal outcomes of pregnant women occupationally exposed to ribavirin. Exposure estimation data suggest that only a small amount of ribavirin would ever reach the maternal systemic circulation, and therefore the fetus, following occupational exposure. However, due to a lack of adequately controlled data, it is currently not possible to state conclusively that there is no increased risk of adverse pregnancy outcomes. If occupational exposure is unavoidable, then adequate precautions should be taken to minimise exposure.

Ribavirin exposure at any stage in pregnancy would not usually be regarded as medical grounds for termination of pregnancy. However, other risk factors may be present in individual cases which may independently increase the risk of adverse pregnancy outcome. Clinicians are reminded of the importance of consideration of such factors when performing case-specific risk assessments. For cases of severe maternal illness, where ribavirin is considered to be the most effective treatment option, ribavirin should not be withheld on the account of pregnancy. Given the limited data, the possibility of an increased risk of adverse pregnancy outcomes following maternal ribavirin exposure cannot be excluded, and the need for additional fetal monitoring should be considered on a case-by-case basis.