Trip was started due to our work with clinical Q&A and started with the ATTRACT project. Since then Trip has worked on multiple separate Q&A projects and those teams have answered over 10,000 clinical questions. Our experience is unrivalled!

Within Trip we link to thousands of clinical Q&As but the vast majority are over ten years old so likely to be out of date. However, these are real clinical questions, most are likely to be relevant today and could be a valuable resource.

So, in testing our automated Q&A system, we thought we would update a random clinical question: A 43 year old lady wanting to conceive, is currently taking amlodipine and losartan for hypertension. Is this safe if she was to get pregnant whilst taking them and what is the alternative ‘safe’ antihypertensive for pregnancy? Clicking on the document will let you see the original answer from 2013.

I’m not sure how long the original answer would have taken, I would estimate 3-4 hours. Well, our updated answer took 90 seconds and – as we operationalise things – could take 10-15 seconds.

Oh yes, the new answer:

Evidence from extracted articles:

  1. Losartan (ARB):
    • The Hypertension in Pregnancy Guideline (2023) states that angiotensin receptor blockers (ARBs), such as losartan, are contraindicated in pregnancy due to the risk of fetal malformations, including renal dysfunction, oligohydramnios, and skull hypoplasia.
    • The Management of Postpartum Hypertensive Disorders of Pregnancy document reinforces this, confirming that losartan should be discontinued before conception or as soon as pregnancy is confirmed.
    • The FDA and European Medicines Agency (EMA) classify losartan as pregnancy category D, meaning there is evidence of fetal risk, and it should be avoided during pregnancy.
    • Reference: FDA Pregnancy Categories (Note: The FDA has moved away from letter categories, but losartan remains contraindicated in pregnancy.)
  2. Amlodipine (Calcium Channel Blocker):
    • The Pharmacokinetics of Common Antihypertensive Drugs in Pregnancy (2022) review notes that calcium channel blockers, including amlodipine, require further research to establish their safety profile in pregnancy.
    • A systematic review (2024) comparing amlodipine and nifedipine suggests that nifedipine is the preferred option due to more established safety data.
    • While amlodipine is not explicitly contraindicated, nifedipine (another calcium channel blocker) has a stronger safety profile for pregnancy-related hypertension and is often preferred.
    • Reference: Pharmacokinetics of Antihypertensive Drugs in Pregnancy (Note: Specific link to the 2022 review is not provided, but this is a general reference for further reading.)

What are the alternative ‘safe’ antihypertensive options for pregnancy?

Evidence from extracted articles:

  1. The Hypertension in Pregnancy Guideline (2023) recommends the following as first-line treatments for hypertension in pregnancy:
    • Labetalol (a beta-blocker)
    • Nifedipine (extended-release, a calcium channel blocker)
    • Methyldopa (a centrally acting alpha-agonist)
  2. The systematic review on pharmacokinetics of antihypertensive drugs (2022) confirms that methyldopa, labetalol, and nifedipine are generally safe options for pregnancy.

Additional knowledge from clinical guidelines (outside extracted articles):

  • Labetalol is often the first-line choice due to its efficacy, safety, and minimal fetal side effects.
  • Nifedipine is used when labetalol is not suitable or contraindicated.
  • Methyldopa, though safe, is less commonly used due to side effects such as fatigue, depression, and drowsiness.

References:

Final Clinical Recommendations:

  1. Losartan should be discontinued before conception or immediately upon confirming pregnancy due to the risk of fetal harm.
  2. Amlodipine is not absolutely contraindicated, but nifedipine is preferred as a safer calcium channel blocker during pregnancy.
  3. First-line alternatives for managing hypertension in pregnancy include:
    • Labetalol (most commonly recommended)
    • Nifedipine (extended-release)
    • Methyldopa (less preferred due to side effects)

Additional Notes:

  • If the patient is planning to conceive, it is crucial to switch from losartan to a safer antihypertensive before pregnancy.
  • Regular monitoring of blood pressure and fetal growth is essential during pregnancy.
  • Always consult a healthcare provider for personalized advice and management.