The Medicines and Healthcare Products Regulatory Agency (MHRA) has issued a drug safety alert following reports of persistent pulmonary hypertension of the newborn (PPHN) after in-utero exposure to sildenafil.
The independent Dutch STRIDER (Sildenafil TheRapy in Dismal prognosis Early-onset fetal growth Restriction) study has been prematurely discontinued due to a higher incidence of PPHN and neonatal mortality with in utero sildenafil exposure.
The group assigned to sildenafil had an incidence of 17 cases of PPHN in 64 babies (27%), including 11 deaths before discharge. In the placebo group, 3 of 58 babies (5%) had PPHN, with no reported deaths before discharge. These findings occurred in the absence of any benefit shown on the primary endpoint of neonatal survival until term age.
The Dutch STRIDER study was 1 of 5 independent studies being conducted by the STRIDER Consortium in the United Kingdom, Ireland, The Netherlands, New Zealand/Australia and Canada.
The UK arm of the trial, with a sample of 135 women and a primary outcome of prolongation of pregnancy by 1 week, has completed and the results have been published.
The results of the UK arm of the trial found no difference in the median randomisation to delivery interval between women assigned to sildenafil (17 days) and women assigned to placebo (18 days). Although no significant difference in PPHN or neonatal mortality was identified, the sample comprised 135 women only.
Based on the emerging data, the MHRA advises that sildenafil (Revatio and Viagra) is not authorised for the treatment of intrauterine growth restriction. Revatio is not recommended for the treatment of pulmonary arterial hypertension unless strictly necessary and Viagra is not authorised for use in women.