[Adverse effects of calcium channels blockers used as tocolytic treatment]

Abstract

Objective: Tocolysis with calcium channel blockers is widespread in France. However, these molecules are off label use for this indication. The objective of this work is to give an update on all the side effects of calcium channel blockers published or reported to the National Bank of Pharmacovigilance.

Materials and methods: We conducted a literature review incorporating the animal experimental data on calcium channel blockers, retrospective and prospective studies (randomized or not) comparing different tocolytics, and the published clinical case reports. Finally we inquired the National Bank of Pharmacovigilance for reported cases of adverse effects after use of calcium channel blockers as tocolytics.

Results: Adverse effects are found in 2% to 6% of patients after use of nifedipine, of which 0.9% to 1.9% are severe. These are mainly headache, flushes and arterial hypotension. Data on Nicardipine are more limited. For the latter, adverse effects specifically related to the route of administration (induced phlebitis) are described but it seems that other adverse effects reported are not more frequent. Several meta-analyses have demonstrated a decrease in maternal side effects when using calcium channel blockers compared to β-agonists. Comparison of calcium channel blockers to Atosiban is less documented. More rare serious side effects are reported as clinical cases, consisting almost exclusively of cardiovascular complications (dyspnea, pulmonary edema, myocardial infarction, arterial hypotension). They are more common with Nicardipine than Nifedipine. Similar observations are found by querying the National Bank of Pharmacovigilance.

Conclusion: The prescription of calcium channel blockers as tocolysis exposes patients to maternal side effects, which are not serious most of the time, and less frequent than with the β-agonist. Severe maternal complications were nonetheless reported more frequently with Nicardipine than Nifedipine, which justifies avoiding Nicardipine in tocolysis. Nifedipine is the most studied molecule. It is not possible to define a maximum posology from literature data. It seems unreasonable to associate different tocolytics and necessary to closely monitor maternal blood pressure, the occurrence of a skin reaction or hypersensitivity, dyspnea or chest pain during treatment.

Keywords: Adverse effects; Calcium channel blockers; Effets indésirables; Effets secondaires; Inhibiteurs calciques; Pulmonary edema; Side effects; Tocolyse; Tocolysis; Œdème aigu du poumon.