Is pantoprazole (Pantoloc), tinidazole (Fasigyn) or clarithromycin (Klacid) harmful for the fetus?/
Fråga: Is pantoprazole (Pantoloc), tinidazole (Fasigyn) or clarithromycin (Klacid) harmful for the fetus? A woman now pregnant on week 7 was treated with pantoprazole, tinidazole and clarithromycin (unknown dosage) due to ulcus ventriculi during the first 5 weeks of pregnancy.
Sammanfattning: Neither pantoprazole, tinidazole or clarithromycin treatment during early pregnancy are an indication for elective abortion. A thorough ultrasound check-up is, however, recommended.
Svar: No study on the effect on the fetus of the combination pantoprazole, tinidazole and clarithromycin was found.
Pantoprozole is a proton pump blocker. A search in the literature, Medline and Drugline gave no documentation of the effects of pantoprozole on the fetus. Whether omeprazole, the most commonly used proton pump blocker, is safe to use during pregnancy has been discussed in previous Drugline answers (1). It was concluded that published data of a substantial number of pregnant women have not indicated any significantly increased risk for the fetus. It is however, not known if this relative safety of omeprazole can be generalised to pantoprozole.
Whether clarithromycin is harmful for the fetus has also been discussed in previous Drugline documents (2) and it was concluded that clarithromycin in very high doses increased the rate of spontaneous abortions in animal studies. An updated literature search found that no gross teratogenic effects were observed in a series of animal studies on rats, mice, rabbits and monkeys. However, in some of these studies, moderately increased rates of some anomalies were observed. The relevance of these results for humans is not known. In 29 pregnant women exposed to clarithromycin no indication that clarithromycin could be harmful for the fetus was found. The FDA´s register of congenital anomalies and clarithromycin through 1996 gave six diverse birth defects which indicates that these were not associated with clarithromycin (3). A prospective controlled study of 157 women exposed to clarithromycin has been published (4). Of these 122 were exposed to the drug in the first trimester. No significant differences were found between the two groups in the rates of major and minor malformations. Spontaneous abortions were significantly higher in the clarithromycin group (14 per cent versus 7 per cent in the control group), which the authors suggest may warrant further study.
Tinidazole treatment during pregnancy is also discussed in previous Drugline answers (5) and it was concluded that no case reports concerning teratogenic effects caused by tinidazole were found, but also that the clinical experience is very limited. In FASS (6) it is stated that in animal studies high doses of tinidazole gave a higher rate of stillborn fetuses, a higher frequency of spontaneous abortions and fetus resorptions. It is concluded that these toxic effects are probably due to the effect on the mother by the high dose. Tinidazole should thus be given to pregnant women only after special considerations. A new search in Medline, SWEDIS (Swedish Drug Information System) and of the literature gave no studies or case reports.
Metronidazole and tinidazole belong to the same group of nitro-imidazole and tinidazole is expected to have the same adverse effects as metronidazole. In previous Drugline documents (6) it is stated that low dose metronidazole treatment may be considered safe during the second and third trimester. Treatment during the first trimester is considered more controversial as available reports give conflicting conclusions concerning the possibility of teratogenic effects. In one meta-analysis, which consisted of one unpublished case-control and four published cohort studies, no increased teratogenic risk was found (8). No evaluation of especially first trimester exposure was made. In another meta-analysis of six prospective studies and one retrospective study, 253 and 1083 women exposed during first trimester, respectively, were identified (9). No association of increased teratogenic risk was found. In a retrospective cohort study of 1387 women exposed to metronidazole between 30 days before and 120 days after the onset of their last menstrual period, no evidence that periconceptional use of metronidazole increases the risk of overall birth defect occurrence was found (10). Of the 1387 women 718 filled a prescription during first trimester and also in this group no increased risk for birth defects was found. In a retrospective cohort study including 328846 children (8.1 per cent exposed and 91.9 per cent not exposed to metronidazole during pregnancy) an increased, but not significant, risk for neuroblastomas was found which requires further evaluation (11). (No specific evaluation of first trimester exposure was made).
Professor Källen states that he does not, in this case, find any indications for an elective abortion, although an extra thorough ultrasound check may be warranted (12).