Can cyclobenzaprine (Flexeril) be administered to a patient with preeclampsia?

Cyclobenzaprine (Flexeril) Should Not Be Given for Preeclampsia

Cyclobenzaprine has no role in the treatment or management of preeclampsia and should be avoided during pregnancy, particularly in the periconceptional period, due to emerging evidence of teratogenic risk.

Why Cyclobenzaprine Is Not Indicated

Wrong Drug Class for Preeclampsia

• Cyclobenzaprine is a skeletal muscle relaxant indicated only for acute musculoskeletal pain, not for any aspect of preeclampsia management 1
• Preeclampsia requires specific antihypertensive agents and anticonvulsants—muscle relaxants play no therapeutic role 2

Emerging Safety Concerns in Pregnancy

• A large multi-site case-control study (33,615 cases, 13,110 controls) found significantly elevated risks of multiple birth defects with periconceptional cyclobenzaprine exposure 1
• Specific defects with increased odds ratios included:
  • Cleft palate (OR = 4.79,95% CI 1.71-13.44) 1
  • d-Transposition of the great arteries (OR = 6.97,95% CI 2.17-22.36) 1
  • Anorectal atresia/stenosis (OR = 6.91,95% CI 1.67-28.65) 1
  • Coarctation of the aorta (OR = 5.58,95% CI 1.88-16.58) 1
  • Pulmonary valve stenosis (OR = 4.55,95% CI 1.10-18.87) 1
• While these findings are hypothesis-generating and require confirmation, the magnitude of risk elevations warrants extreme caution 1

Correct Management of Preeclampsia

For Seizure Prevention and Control

• Magnesium sulfate is the only appropriate anticonvulsant for preeclampsia and eclampsia 2, 3, 4
• Loading dose: 4-6 g IV over 20-30 minutes, followed by 1-2 g/hour continuous infusion 2
• Continue for at least 24 hours postpartum, as eclamptic seizures may first occur in the early postpartum period 2

For Blood Pressure Control in Severe Preeclampsia

When systolic BP ≥160 mmHg or diastolic BP ≥110 mmHg:

First-line agents:

• Intravenous labetalol (10-20 mg bolus, then 20-80 mg every 10 minutes; maximum 300 mg) 2, 5, 6
• Oral immediate-release nifedipine (10-30 mg sublingually, then 40-120 mg/day orally) 5, 6
• Nifedipine achieves effective BP control in 95.8% of cases versus 68% with hydralazine 6

Second-line agent:

• Intravenous hydralazine (5-10 mg initially, then 5 mg at 20-minute intervals) 2, 5, 3, 4
• Hydralazine is now considered inferior due to more unpredictable hypotension and increased perinatal adverse effects 2

Critical Drug Interaction to Avoid

• Never combine magnesium sulfate with calcium channel blockers (especially IV or sublingual nifedipine), as this causes severe myocardial depression and precipitous hypotension 2
• If both agents are needed, they must be given sequentially with careful monitoring, never simultaneously 2

Common Pitfalls

Misunderstanding the Question

• If a patient with preeclampsia has musculoskeletal pain requiring treatment, the risk-benefit analysis strongly favors avoiding cyclobenzaprine given the emerging teratogenic signals 1
• Alternative analgesics (acetaminophen, limited opioids if necessary) should be considered instead 2

NSAIDs in Preeclampsia

• Avoid NSAIDs for analgesia in women with preeclampsia unless other analgesics fail, especially if renal disease, placental abruption, or acute kidney injury is present 2

Postpartum Monitoring

• Women with preeclampsia remain at high risk for complications for at least 3 days postpartum and require BP monitoring every 4 hours while awake 2
• All women should be reviewed at 3 months postpartum to ensure BP, urinalysis, and laboratory abnormalities have normalized 2