Is Toradol (Ketorolac) safe to use during the 2nd trimester of pregnancy?

Safety of Toradol (Ketorolac) in 2nd Trimester Pregnancy

Toradol (ketorolac) should be avoided during the 2nd trimester of pregnancy unless the potential benefit clearly justifies the potential risk to the fetus.

FDA Classification and Evidence

Ketorolac is classified as Pregnancy Category C by the FDA, which means:

• Animal reproduction studies have shown adverse effects on the fetus
• There are no adequate well-controlled studies in humans
• The drug should only be used if potential benefits justify the potential risks 1

Risks Associated with Ketorolac Use in 2nd Trimester

Cardiovascular Risks

• NSAIDs like ketorolac can cause premature closure or constriction of the ductus arteriosus, even in the 2nd trimester
• While this effect is more commonly associated with 3rd trimester use, cases of ductus arteriosus constriction have been documented in the late 2nd trimester 2
• In one study, ductus arteriosus constriction was diagnosed in 0.5% of pregnancies with 2nd/3rd trimester NSAID exposure compared to 0% in those with only 1st trimester exposure 2

Renal Effects and Oligohydramnios

• Ketorolac can cause oligohydramnios (reduced amniotic fluid) due to decreased fetal renal function
• Risk of oligohydramnios in 2nd trimester exposure was 0.9% versus 0.2% in 1st trimester only exposure (RR 5.1,95% CI 1.1-24.0) 2
• This effect appears to be dose and duration dependent, with longer exposures posing greater risk

Duration of Exposure Considerations

The risk of adverse effects appears to depend on the duration of exposure:

• Short-term use (few days) in the 2nd trimester may not pose a substantial risk 3
• Long-term use in the late 2nd trimester has been associated with similar adverse effects as 3rd trimester use 2, 3
• Prolonged exposure (several weeks) in the 2nd trimester has been documented to cause oligohydramnios and ductus arteriosus constriction 2

Recommendations

1. First-line alternatives should be considered:

   • Acetaminophen (paracetamol) is generally considered safer for pain management during pregnancy

2. If ketorolac must be used:

   • Limit to shortest possible duration (ideally less than 48-72 hours)
   • Use lowest effective dose
   • Avoid use in late 2nd trimester when possible
   • Consider fetal monitoring if used for more than a few days

3. Absolute contraindications for ketorolac:

   • Labor and delivery (may adversely affect fetal circulation and inhibit uterine contractions) 1
   • History of oligohydramnios or fetal renal issues
   • Known fetal cardiac abnormalities

Clinical Monitoring

If ketorolac must be used in the 2nd trimester:

• Monitor amniotic fluid volume if treatment extends beyond a few days
• Consider fetal echocardiography to assess ductus arteriosus if prolonged use is necessary
• Discontinue immediately if any signs of oligohydramnios or ductus arteriosus constriction are detected

Conclusion

While short-term use of ketorolac in the early 2nd trimester may carry minimal risk, the potential for serious adverse fetal effects increases with duration of use and advancing gestational age. The risk-benefit ratio should be carefully evaluated, with preference given to safer alternatives whenever possible.