Can the use of verapamil in early pregnancy lead to fetal malformations?/nA woman in her thirties w

Fråga: Can the use of verapamil in early pregnancy lead to fetal malformations?

A woman in her thirties was treated with verapamil for supraventricular tachycardia during the first 18 weeks of pregnancy. Amniocentesis performed at 18-19 weeks´ gestation was suggestive of a neural tube defect and a post-abortion analysis showed anencephaly as well as adrenal hypoplasia and horseshoe kidneys.

Sammanfattning: No data linking the use of verapamil during early pregnancy with fetal defects could be located in the literature. However, the documentation is rather limited and caution is warranted. A single case report suggests an association between congenital hypertrophic cardiomyopathy and the use of verapamil during late pregnancy; and until more data become available this possibility should not be overlooked. In the present case, it seems unlikely that verapamil was the cause of the malformations observed.

Svar: Verapamil was re-classified in the Swedish catalogue of approved medical products in 1993 when the drug was moved from category A to category C. This was mainly based on the observation that calcium blockers of the dihydropyridine type (nifedipine, felodipine, isradipine, amlodipine) can cause skeletal malformations in animal studies (1,2). It should, however, be underscored that verapamil, albeit a calcium channel blocker, is a phenylalkylamine and not structurally related to the other members of the group.

In a surveillance study involving 229101 completed pregnancies conducted in Michigan between 1985 and 1992, 76 newborns had been exposed to verapamil during the first trimester (3). Only one major birth defect was observed (three expected), a cardiovascular defect. Of 78 women on calcium channel blockers seen in one clinic, (40 percent were on verapamil), there was a 3 percent malformation rate; all of these were on other medications, or had underlying medical conditions that could be responsible (4).

The use of verapamil during late pregnancy poses a potential risk of hypotension in the pregnant woman which might lead to reduced uterine blood flow with fetal hypoxia (2,3). This is especially important in patients receiving the drug intravenously (3). It should, however, be noted that verapamil-induced vasodilatory effects are moderate, as opposed to those of nifedipine (3). Indeed, verapamil has been successfully used in utero for the treatment of supraventricular tachycardia and in a number of reports; no adverse fetal or newborn effects attributable to verapamil were observed (3). However, a recent case report suggests an association between the use of verapamil during late pregnancy (30 weeks gestation) and the development of congenital hypertrophic cardiomyopathy (5). A similar association has previously been shown in rats, although the doses used were much higher (30 times greater blood levels) (6). 1 Drugline nr 10659 (year 1993)

2 FASS 1997 (The Swedish catalogue of approved medical products)
3 Briggs, Drugs in pregnancy and lactation. 1994; 4th ed: 878-880
4 The Motherisk program at the Hospital for sick children, Toronto, Canada

5 Shen O, Entebi E, Yagel S: Congenital hypertrophic cardiomyopathy associated with in utero verapamil exposure. Prenat Diagn 1995; 15:1088-1089 6 Pearc:e PC, Hawkey C, Symons C, Olsen EG: Role of calcium in the introduction of cardiac hypertrophy and myofibrillar disarray. Experimental studies of a possible cause of hypertrophic cardiomyopathy. Br Heart J 1985; 54: 420-427