What are the guidelines for using ivabradine (procoralan) in pregnancy?

Ivabradine Use in Pregnancy

Ivabradine should not be administered during pregnancy due to significant risks of fetal harm, including cardiac malformations and increased post-implantation loss. 1

Risks and Evidence

The FDA drug label for ivabradine clearly states that the medication is contraindicated during pregnancy based on animal reproduction studies showing:

• Embryo-fetal toxicity and teratogenicity at doses equivalent to human exposure 1
• Cardiac malformations including interventricular septal defects 1
• Complex anomalies of primary arteries 1
• Increased post-natal mortality associated with teratogenic effects 1
• Increased post-implantation loss in rabbits 1

The 2022 AHA/ACC/HFSA Heart Failure Guidelines specifically state that "in women with HF or cardiomyopathy who are pregnant or currently planning for pregnancy, ACEi, ARB, ARNi, MRA, SGLT2i, ivabradine, and vericiguat should not be administered because of significant risks of fetal harm." 2

Management Algorithm for Women of Childbearing Potential Requiring Heart Rate Control

1. Pre-pregnancy planning:

   • Provide patient-centered counseling regarding contraception and risks of cardiovascular deterioration during pregnancy 2
   • Discontinue ivabradine before planned pregnancy 2, 1
   • Consider alternative medications with established safety profiles in pregnancy

2. For women already on ivabradine who become pregnant:

   • Discontinue ivabradine immediately upon pregnancy confirmation 1
   • The German Embryotox database evaluation showed that in 33/38 patients, ivabradine was discontinued after confirmation of pregnancy without cardiac deterioration 3
   • Arrange fetal ultrasound for structural anomalies and growth restriction 3

3. Alternative medications for heart rate control during pregnancy:

   • Selective β-blockers (metoprolol) are preferred for heart rate control during pregnancy 2, 4
   • Digoxin may be considered as an alternative for rate control 2

Special Considerations

• Women with left ventricular ejection fraction <35% on maximally tolerated doses of beta-blockers may be particularly heart rate dependent for augmenting cardiac output 1
• Monitor pregnant women with chronic heart failure closely in the 3rd trimester for preterm birth 1
• The 2024 ACC/AHA quality measures emphasize the importance of counseling women of childbearing potential with heart failure regarding contraception, risks of cardiovascular events in future pregnancies, and use of guideline-directed medical therapy during pregnancy 2

Monitoring After Inadvertent Exposure

If inadvertent exposure to ivabradine occurs during early pregnancy:

• Perform detailed fetal echocardiography to evaluate for cardiac malformations 1, 3
• Monitor fetal growth throughout pregnancy 3
• Provide close maternal cardiac monitoring, especially in women with underlying heart disease 2

While a German Embryotox database evaluation of 38 prospectively ascertained pregnancies with ivabradine exposure found only one major birth defect (atrial septal defect and cleft palate), the sample size is too small to draw definitive conclusions about safety 3. The established risks from animal studies and clear FDA contraindication should guide clinical practice.

Human Medical Consultant

AI: I've created a response about ivabradine use in pregnancy that follows the guidelines you provided. I've made a clear recommendation against using ivabradine during pregnancy based on the FDA drug label and clinical guidelines, particularly the 2022 AHA/ACC/HFSA Heart Failure Guidelines. I've included specific risks identified in animal studies, provided an algorithm for management, and discussed alternatives for heart rate control during pregnancy. The response is structured with headings, bullet points, and bolded key information for readability.