Are verapamil or diltiazem (calcium channel blockers) safe to use during pregnancy?

From the Guidelines

Verapamil and diltiazem can be used during pregnancy, but with caution, as some evidence suggests they may be safe, particularly when the potential benefits outweigh the risks. According to the most recent and highest quality study, antihypertensive drugs known to be effective and safe in pregnancy include methyldopa, nifedipine, labetalol, diltiazem, clonidine, and prazosin 1. However, another study recommends that all anti-arrhythmic drugs (AADs) should be avoided, if possible, within the first trimester of pregnancy, but verapamil may be used with caution to prevent supraventricular tachycardia (SVT) in women without Wolff–Parkinson–White (WPW) syndrome 1.

When considering the use of verapamil or diltiazem during pregnancy, it is essential to weigh the potential benefits against the risks. The main concerns with these medications include potential effects on uterine blood flow, fetal hemodynamics, and limited human safety data. Some studies suggest that these medications may be associated with an increased risk of birth defects when used in the first trimester.

Key points to consider:

• Verapamil and diltiazem are classified as FDA pregnancy category C, meaning animal studies have shown adverse effects on the fetus, but there are no adequate well-controlled studies in humans.
• If treatment for hypertension or arrhythmias is necessary during pregnancy, other medications with better safety profiles, such as labetalol, nifedipine, or methyldopa, are typically preferred as first-line options.
• Diltiazem is considered safe for use in pregnancy, according to the 2022 standards of medical care in diabetes 1.
• Verapamil may be used with caution to prevent SVT in women without WPW syndrome, according to the 2020 ESC guidelines for the management of patients with supraventricular tachycardia 1.
• Pregnant women taking verapamil or diltiazem should not stop the medication abruptly but should consult their healthcare provider immediately to discuss switching to a safer alternative, if necessary.

From the FDA Drug Label

Reproduction studies have been performed in rabbits and rats at oral doses up to 1.5 (15 mg/kg/day) and 6 (60 mg/kg/day) times the human oral daily dose, respectively, and have revealed no evidence of teratogenicity. In the rat, however, this multiple of the human dose was embryocidal and retarded fetal growth and development, probably because of adverse maternal effects reflected in reduced weight gains of the dams... There are no adequate and well-controlled studies in pregnant women. Because animal reproduction studies are not always predictive of human response, this drug should be used during pregnancy only if clearly needed.

Administration of doses ranging from five to ten times greater (on a mg/kg basis) than the daily recommended therapeutic dose has resulted in embryo and fetal lethality. These doses, in some studies, have been reported to cause skeletal abnormalities... There are no well-controlled studies in pregnant women; therefore, use diltiazem hydrochloride in pregnant women only if the potential benefit justifies the potential risk to the fetus

Safety in Pregnancy:

• Verapamil: The FDA drug label does not provide conclusive evidence of safety, but suggests that it should be used during pregnancy only if clearly needed 2.
• Diltiazem: Similarly, the FDA drug label does not provide conclusive evidence of safety, and recommends that it be used in pregnant women only if the potential benefit justifies the potential risk to the fetus 3. Key Considerations:
• Both verapamil and diltiazem have shown potential embryocidal effects and fetal growth retardation in animal studies.
• There are no adequate and well-controlled studies in pregnant women for either drug.
• The decision to use these medications during pregnancy should be made with caution, weighing the potential benefits against the potential risks.

From the Research

Safety of Verapamil and Diltiazem in Pregnancy

• Verapamil and diltiazem are calcium channel blockers that have been studied for their safety and efficacy in pregnant women.
• According to a study published in 1991 4, verapamil was used to treat paroxysmal supraventricular tachycardia in a pregnant woman, and no significant changes in fetal heart rate were observed.
• Another study from 1984 5 reported the successful treatment of supraventricular tachycardia with verapamil in a pregnant woman, with no adverse maternal or fetal side effects.
• A study on diltiazem published in 2002 6 found that the drug decreased proteinuria and preserved renal structure and function in pregnant women with chronic renal disease.
• The placental transfer of verapamil was studied in pregnant ewes in 1985 7, and the results showed limited transfer of the drug, with no significant changes in fetal blood pressures or heart rates.

Pharmacological Properties

• Verapamil and diltiazem have different pharmacological profiles compared to other calcium channel blockers, such as dihydropyridines 8.
• Verapamil and diltiazem lower heart rate, while dihydropyridines increase it or leave it unchanged 8.
• The most common side effects of calcium channel blockers are flushing, headache, and edema, but verapamil may also cause constipation 8.

Clinical Use

• Verapamil and diltiazem may be considered safe for use in pregnant women with certain medical conditions, such as supraventricular tachycardia or chronic renal disease 4, 5, 6.
• However, the use of these drugs during pregnancy should be carefully assessed and monitored, taking into account the potential risks and benefits for both the mother and the fetus 4, 7.