A 46-year-old woman in week 5-6 of pregnancy has been taking the following drugs regularly: Loratad

Fråga: A 46-year-old woman in week 5-6 of pregnancy has been taking the following drugs regularly: Loratadine (Clarityn) 10 mg daily and paroxetine (Seroxat) 20 mg daily. In addition, she has taken norethindrone (Primolut-Nor) 10 mg daily for 10 days and a few tablets (exact number unknown) of sucralfate (Andapsin), famotidine (Pepcidin), flunitrazepam (Rohypnol), zopiclone (Imovane), and a combination preparation of ergotamine, meprobamate and caffeine (Anervan). Risk of teratogenic effects?

Sammanfattning: Your patient has been exposed to several drugs which are not recommended during pregnancy. None of them is considered as especially teratogenic but norethindrone can induce masculinization of a female fetus. The risk in the present case is, however, minimal.

Svar: The use of the above mentioned drugs during pregnancy has been subject to previous Drugline queries (1-7), some of which are enclosed. Briefly, norethindrone (category D), a progestin, can cause masculinization of a female fetus. The risk is considered to be greatest during weeks 8-12 of pregnancy (1). In addition, the total dose in this case (100 mg) is relatively low. Sucralfate (category A) do no absorb from the gastrointestinal tract and has therefore been considered as a safe drug during pregnancy (8). Ergotamine can induce uterine contractions and it should not be used during pregnancy (2). Malformations of the heart have been described after meprobamate exposure but epidemiological studies have failed to demonstrate an increased risk (9).

There are no reports linking the use of flunitrazepam with congenital defects (4). Use of zopiclone (category C) during pregnancy has not been previously dealt with. It is a novel hypnotic which is not known to have teratogenic effects (10). Textbooks on drug therapy during pregnancy do not mention zopiclone but we found one reference describing 15 women who had used the drug during the first trimester (11). There were no congenital abnormalities among the 7 births in this material, but one baby was born with mild talipes (clubfoot). The manufacturer was aware of 11 additional cases without negative effects on the fetus (12). Because of limited experience the use of zopiclone is, however, not recommended during pregnancy (5).

Famotidine (category B-1), loratadine (category B-3) and paroxetine (category B-3) are not known to possess teratogenic effects but because of limited experience their use is not recommended during pregnancy. A tricyclic antidepressant could be used instead of paroxetine if continuous antidepressive treatment is considered necessary for your patient (7). 1 Drugline nr 04618 (year 1985) (enclosed)

2 Drugline nr 07684 (year 1990) (enclosed)
3 Drugline nr 10185 (year 1994)
4 Drugline nr 06063 (year 1988)
5 Drugline nr 10957 (year 1993) (enclosed)
6 Drugline nr 09764 (year 1993)
7 Drugline nr 11529 (year 1994) (enclosed)
8 FASS 1994
9 Briggs, Drugs in pregnancy. 1990; page 398-399
10 Shepard TH. Catalog of teratogenic agents. 1992; 7th ed: 421-422
11 Inman W et al: Pharmacoepidemiol & Drug Safety 1993; 2: 499-521

12 Björn Rubin, Rhone-Poulenc Rorer, personal communication