Can sildenafil be used during pregnancy?

Sildenafil Use During Pregnancy

Sildenafil should generally be avoided during pregnancy due to insufficient safety data, though it may be considered in life-threatening maternal conditions (such as pulmonary arterial hypertension) when no safer alternatives exist, with careful risk-benefit assessment.

FDA Classification and Drug Label Information

• Sildenafil is classified as FDA Pregnancy Category B, meaning animal studies showed no fetal harm at doses 32-68 times the human dose, but adequate controlled studies in pregnant women are lacking 1
• The FDA label explicitly states: "sildenafil citrate should be used during pregnancy only if clearly needed" 1
• Animal studies in rats and rabbits at 200 mg/kg/day showed no teratogenicity, embryotoxicity, or fetotoxicity during organogenesis 1

Guideline Recommendations

Rheumatology Guidelines (Most Recent, 2025)

• The EULAR 2025 guidelines state that drugs with insufficient safety data in pregnancy should be avoided until further evidence is available, and sildenafil falls into this category for pregnant women 2
• However, these same guidelines note sildenafil can be continued in male patients trying to conceive, as it has not demonstrated clinically relevant impact on offspring outcomes 2, 3

Maternal-Fetal Medicine Evidence

• The Society for Maternal-Fetal Medicine provides a Grade 1B recommendation AGAINST sildenafil for in utero treatment of fetal growth restriction, stating no evidence exists that it improves placental perfusion or outcomes 3
• This is a critical point: despite theoretical benefits for placental blood flow, high-quality evidence does not support its use for fetal indications

Cardiovascular Guidelines

• The 2011 ESC guidelines classify sildenafil under FDA Category B but emphasize that in emergency situations, drugs not routinely recommended during pregnancy should not be withheld if maternal benefit outweighs potential fetal risk 2

Clinical Context: When Sildenafil Might Be Considered

Acceptable Maternal Indications (Life-Threatening Only)

• Pulmonary arterial hypertension (PAH) in the mother is the primary scenario where sildenafil use may be justified during pregnancy 2, 4
• In Scandinavian registry data, only 3 of 77 pregnant women using PDE5 inhibitors had documented PAH diagnosis, suggesting most use is off-label 4

Contraindicated or Unproven Fetal Indications

• Fetal growth restriction: No evidence of benefit and explicitly not recommended 3
• Preeclampsia, oligohydramnios, congenital diaphragmatic hernia: Limited, equivocal data with no established efficacy 5
• Intrapartum fetal compromise: One phase 2 trial showed reduced operative births, but the authors explicitly state "much larger phase 3 trials are needed before it can be routinely recommended" 6

Safety Profile During Pregnancy

Maternal Safety

• Clinical studies report mild maternal side effects with good tolerance depending on underlying pathology 5
• No significant differences in maternal adverse events were observed in randomized trials 6

Fetal and Neonatal Outcomes

• Only 3.6% of maternal sildenafil levels were detected in cord blood, suggesting limited placental transfer 6
• Scandinavian registry data (77 pregnancies) showed concerning outcomes: 9 preterm births, 6 small-for-gestational-age infants, 18 NICU admissions, and 8 with respiratory/cardiovascular conditions 4
• However, these outcomes may reflect underlying maternal disease severity rather than drug effects 4
• Systematic reviews note "good fetal tolerance and safety depending on the underlying pathology" but acknowledge limited data 5, 7

Breastfeeding Considerations

• The EULAR 2025 guidelines state sildenafil may be considered during breastfeeding if no alternative compatible drug can be used, given very low amounts excreted into breast milk and absence of reported harm in breastfed infants 2
• The FDA label notes it is unknown if sildenafil is excreted in human breast milk, recommending caution 1

Clinical Decision Algorithm

1. First: Assess maternal indication

   • Life-threatening maternal condition (PAH)? → Consider use with informed consent 2
   • Fetal indication (growth restriction, etc.)? → Do not use 3

2. Second: Evaluate alternatives

   • Are there safer, pregnancy-compatible alternatives for the maternal condition? If yes, use those instead 2

3. Third: If sildenafil is necessary

   • Obtain informed consent discussing Category B classification and limited human data 1
   • Use lowest effective dose 8
   • Implement therapeutic drug monitoring if available 8
   • Avoid concurrent nitrate use (absolute contraindication) 3

Critical Pitfalls to Avoid

• Do not use sildenafil for fetal indications despite theoretical vasodilatory benefits—evidence does not support efficacy and may cause harm 3
• Do not assume Category B means "safe"—it only means animal studies were reassuring, not that human pregnancy data are adequate 1
• Do not prescribe without documenting that maternal benefit clearly outweighs unknown fetal risks 2
• Most pregnancy exposure occurs in women over age 35, often for off-label indications—ensure appropriate indication before prescribing 4