Pregnancy & Lactation : הריון/הנקה

4.6     Fertility, pregnancy and lactation

Women of childbearing potential
Before initiating treatment, the patient should be informed of the potential risk to the foetus.
After single dose treatment, a washout period of 1 week (corresponding to 5-6 half- lives) is recommended before becoming pregnant (see section 5.2).
For longer courses of treatment, contraception may be considered, as appropriate, in women of childbearing potential throughout the treatment period and for 1 week after the final dose.

Pregnancy
Observational studies suggest an increased risk of spontaneous abortion in women treated with fluconazole during the first and/or second trimester compared to women not treated with fluconazole or treated with topical azoles during the same period.

Data from several thousand pregnant women treated with a cumulative dose of ≤ 150 mg of fluconazole, administered in the first trimester, show no increase in the overall risk of malformations in the foetus. In one large observational cohort study, first trimester exposure to oral fluconazole was associated with a small increased risk of musculoskeletal malformations, corresponding to approximately 1 additional case per 1000 women treated with cumulative doses ≤ 450 mg compared with women treated with topical azoles and to approximately 4 additional cases per 1000 women treated with cumulative doses over 450 mg. The adjusted relative risk was 1.29 (95% CI 1.05 to 1.58) for 150 mg oral fluconazole and 1.98 (95% CI 1.23 to 3.17) for doses over 450 mg fluconazole.

Available epidemiological studies on cardiac malformations with use of fluconazole during pregnancy provide inconsistent results. However, a meta-analysis of 5 observational studies including several thousand pregnant women exposed to fluconazole during the first trimester finds a 1.8-2 fold increased risk of cardiac malformations when compared to no fluconazole use and/or topical azoles use.

Case reports describe a pattern of birth defects among infants whose mothers received high-dose (400 to 800 mg/day) fluconazole during pregnancy for 3 months or more in the treatment of coccidioidomycosis. The birth defects seen in these infants include brachycephaly, ears dysplasia, giant anterior fontanelles, femoral bowing and radio- humeral synostosis. A causal relationship between fluconazole use and these birth defects is uncertain.


Fluconazole in standard doses and short-term treatments should not be used in pregnancy unless clearly necessary.

Fluconazole in high-dose and/or in prolonged regimens should not be used during pregnancy except for potentially life-threatening infections.

Breast-feeding
Fluconazole passes into breast milk to reach concentrations similar to those in plasma (see section 5.2). Breast-feeding may be maintained after a single-dose of 150 mg fluconazole.
Breast-feeding is not recommended after repeated use or after high-dose fluconazole. The developmental and health benefits of breast-feeding should be considered along with the mother’s clinical need for fluconazole and any potential adverse effects on the breast-fed child from fluconazole or from the underlying maternal condition.

Fertility
Fluconazole did not affect the fertility of male or female rats (see section 5.3).