Which uterotonic agent is contraindicated with Human Immunodeficiency Virus (HIV) protease inhibitor medications?

Methylergonovine is Contraindicated with HIV Protease Inhibitors

Methylergonovine is absolutely contraindicated with HIV protease inhibitor medications due to potentially life-threatening vasospasm that can lead to cerebral ischemia and/or ischemia of the extremities. 1

Mechanism of Interaction

The contraindication between methylergonovine and HIV protease inhibitors is based on a serious drug-drug interaction:

• Methylergonovine is metabolized by the CYP3A4 enzyme system
• HIV protease inhibitors are potent inhibitors of CYP3A4
• When used together, protease inhibitors can:
  • Dramatically increase methylergonovine blood levels
  • Prolong methylergonovine's half-life
  • Lead to dangerous vasoconstrictive effects

Clinical Implications

The FDA drug label for methylergonovine explicitly states that potent CYP3A4 inhibitors, including HIV protease inhibitors, should not be coadministered with methylergonovine 1. This interaction can result in:

• Severe vasospasm
• Cerebral ischemia
• Peripheral ischemia
• Potentially fatal outcomes

Alternative Uterotonics for Patients on Protease Inhibitors

For patients taking HIV protease inhibitors who require uterotonic medications:

1. Oxytocin is the preferred first-line agent

   • No known interactions with antiretroviral medications
   • Safe to use with protease inhibitors

2. Misoprostol (prostaglandin E1 analog) can be considered as an alternative

   • No significant drug interactions with protease inhibitors

3. Carboprost (prostaglandin F2α) may be used if necessary

   • No documented interactions with protease inhibitors

Common Pitfalls to Avoid

1. Mistaking different ergot derivatives: All ergot alkaloids (including methylergonovine) are contraindicated with protease inhibitors

2. Overlooking the interaction: The interaction between methylergonovine and protease inhibitors is potentially life-threatening but may be overlooked in emergency situations

3. Assuming all uterotonics have similar interactions: Unlike methylergonovine, oxytocin does not have significant interactions with antiretroviral medications and remains safe to use in HIV-infected patients on protease inhibitors

Evidence Quality Assessment

The contraindication between methylergonovine and HIV protease inhibitors is well-established in drug labeling and guidelines. The FDA drug label provides the strongest and most direct evidence for this contraindication 1, which is supported by our understanding of the pharmacokinetic interactions between protease inhibitors and drugs metabolized by CYP3A4.

This recommendation prioritizes patient safety by preventing potentially fatal vasospastic events that could significantly impact morbidity and mortality.