A 31-year-old woman, in week 10 of pregnancy, is using amitriptyline (Tryptizol) 25 mg per day beca

Fråga: A 31-year-old woman, in week 10 of pregnancy, is using amitriptyline (Tryptizol) 25 mg per day because of a neurological complication with pain after a trauma a couple of years ago. The woman was also treated with diclofenac/misoprostol (Arthrotec) until weeks 4 to 6 of pregnancy. Risk of teratogenicity?

Sammanfattning: There is no documentation of teratogenicity in treatment with amitriptyline (Tryptizol). However, prenatal exposure during late pregnancy increases the risk of withdrawal symptoms. Concerning the exposure diclofenac, in this case the risk of premature closure of the ductus arteriosus should be small. Misoprostol is contraindicated in pregnant women as it has been found to increase uterine tone and may induce miscarriage. Congenital malformations of the frontotemporal region of the skull has also been reported. The risk in this case is hard to judge. However, in general exposure during the first four weeks after conception can be expected to lead an all-or-none effect, with an early miscarriage if the fetus has been harmed. If the pregnancy proceeds normally, the risk of malformation caused by the drug is probably not significant. One could recommend that ultrasound investigation of the fetus be made.

Svar: Questions concerning teratogenicity in treatment with amitriptyline/diclofenac has been dealt with previously (1,2,3,4).

Misoprostol is a prostaglandin E1 analogue developed for treatment of peptic ulcers which is used in the treatment and prevention of nonsteroidal antiinflammatory drug-induced gastrointestinal damage. Misoprostol has also been used improperly as an abortifacient by women in Brazil (5,6). In a German study on 56 women pregnant in the first trimester attempting to terminate a pregnancy with vaginal misoprostol (400-800 ug) about 50 per cent of the pregnancies were not terminated. Hydrocephalus and abnormal digits were reported in a baby born to one of these women (7). Five cases of an unusual congenital malformation of the frontotemporal region of the skull with an assymetrical, well-circumscribed defect of the cranium and overlying scalp, exposing dura mater through which the cerebrum can be seen, is described by Fonseca et al (8) in children whose mothers had taken misoprostol (400-600 ug) orally and/or vaginally without success during the first trimester of pregnancy. In two handbooks (8,10) it is pointed out that misoprostol should not be used in pregnancy as it has been found to increase uterine tone and contractions, increasing the risks of uterine bleeding and miscarriage (9). In contrast to this, 29 pregnant women unsuccessfully used misoprostol (200-11200 ug, mean 4000 ug) as an abortifacient during the first trimester of gestation. Three of these 29 pregnancies ended in second-trimester spontaneous abortions, three were still pregnant during the study and six cases could not be followed up. Of the remaining 17 live births no major malformation was found, though one of them had a preauricular tag.