A woman used Sporanox (itraconazole) 200 mg x2 for one day during her sixth week of pregnancy. No o

Fråga: A woman used Sporanox (itraconazole) 200 mg x2 for one day during her sixth week of pregnancy. No other concomitant medication was used. Does this treatment pose a sufficiently high risk to the fetus to consider an abortion?

Sammanfattning: Due to the limited data available, an adequate risk assessment is not possible at present. Both normal infants and those with malformations were born to women treated with itraconazole. Itraconazole is a relatively new drug and the experience of its use in pregnancy is limited. Therefore its use cannot be recommended during pregnancy. There is, however, no reason to assume that the normal risk for malformations should be considerably increased due to the drug intake. If the woman chooses to continue the pregnancy an ultrasound examination, after a few weeks looking for skeletal and neural tube malformations could be considered.

Svar: Itraconazole is a triazolderivate that inhibits the fungal ergosterol synthesis. This negatively affects the cell membrane and results in a fungicide effect. The treatment indications are candida vaginitis and invasive aspergillosis (1).

Very high doses of itraconazole given to rodents resulted in skeletal and neural tube defects in the embryo as well as macroglossia (2).

According to the manufacturer (3), there are at present 352 reports on itraconazole exposure during pregnancy (no information of doses, time of exposure or indication is known) with the following outcomes:

One hundred and fifty-three normal infants were born. Among these, 97 were exposed during the first trimester, and in 53 the time of treatment is not stated. No information is available on the remaining three.

Forty-two abortions were induced. One fetus had gastroschisis while in 37 there was no information available about the fetus morphology.

Thirty-nine spontaneous abortions, one of which triploidism was diagnosed, one with an unspecified malformation and one is still blinded in a clinical trial (3).

Fifteen cases of congenital malformations have been reported. Among these four cases are related to the skeleton.

Three cases of neonatal complications, two of these with intracranial bleedings and respiratory difficulties and one lacking data concerning the complication.

Another 99 pregnancies are still being followed after exposure to itraconazole (3).

As shown above the number of cases are too small to draw any conclusions with regard to teratogenic effects of itraconazole exposure during pregnancy. The present case was discussed with an expert (4) and there is no reason to assume that the normal risk for malformations should be considerably increased due to the drug intake. It should be noted that spontaneous reporting often results in biased data with an under-representation of reports of normally proceeding pregnancies.

No further information on pregnancy and itraconazole has been found on Medline or files of the Swedish Adverse Drug Reactions Advisory Committee (SADRAC).