This drug should not be used during pregnancy unless there are no alternatives and the benefit outweighs the risk to the fetus; use is not recommended unless clearly needed.

AU TGA pregnancy category: B3
US FDA pregnancy category: C

Comments: If pregnancy occurs during therapy, the patient should be apprised of the potential harm to the fetus.

Animal studies have revealed evidence of adverse effects on pregnancy outcome and/or embryofetal development (low incidence of cardiovascular anomalies, variable incidence of cleft palate, delayed fetal growth, spontaneous abortions) at doses producing plasma levels 2 to 17 times the human serum levels achieved using the maximum recommended human dose. There are limited controlled data in human pregnancy.

A prospective, controlled, multicenter study of 157 pregnant women found this drug to be safe when taken at the usual prescribed dosage during pregnancy. In the study, 122 of the women had first-trimester exposure. The incidence of major and minor congenital malformations did not differ from the background incidence of 1% to 3% and 10% to 15%, respectively, in first-trimester exposure to this drug. The rate of spontaneous abortion in the clarithromycin group was statistically higher than in the control group (14% versus 7%); the authors suggested that the difference could be due to confounding factors not controlled by their study.

Data showed no clear evidence of teratogenic effects or harmful effects on the health of the neonate when this drug was used during the first trimester in more than 200 pregnancies. Data from a limited number of pregnant women with first-trimester exposure showed a possible increased risk of abortions.

AU TGA pregnancy category B3: Drugs which have been taken by only a limited number of pregnant women and women of childbearing age, without an increase in the frequency of malformation or other direct or indirect harmful effects on the human fetus having been observed. Studies in animals have shown evidence of an increased occurrence of fetal damage, the significance of which is considered uncertain in humans.

US FDA pregnancy category C: Animal reproduction studies have shown an adverse effect on the fetus and there are no adequate and well-controlled studies in humans, but potential benefits may warrant use of the drug in pregnant women despite potential risks.

See references

This drug and its active metabolite (14-hydroxyclarithromycin) are excreted into human milk. In 1 study, steady-state serum and milk samples were collected from 12 lactating women after 3 days of therapy (250 mg orally twice a day). Peak milk levels were 0.85 mg/L for clarithromycin and 0.63 mg/L for 14-hydroxyclarithromycin at 2.2 and 2.8 hours after the dose, respectively; the drug half-life was 4.3 hours and the metabolite half-life was 9 hours. Based on limited data from this study (and assuming milk consumption of 150 mL/kg/day), a child exclusively fed human milk would receive 136 mcg/kg/day (estimated average) of this drug and its active metabolite with this maternal regimen. This is less than 2% of the maternal weight-adjusted dose and less than 1% of the pediatric dose (15 mg/kg/day) for children older than 6 months.

The low levels in milk are unlikely to cause harmful effects in the nursing infant. The infant should be monitored for possible effects on the gastrointestinal flora, such as diarrhea, candidiasis (thrush, diaper rash). According to unconfirmed epidemiologic evidence, maternal macrolide use during breastfeeding may increase the risk of hypertrophic pyloric stenosis in infants.

A prospective observational study compared 55 infants breastfed by mothers taking macrolide antibiotics (6 clarithromycin) to 36 infants breastfed by mothers taking amoxicillin. Side effects were reported in 12.7% of infants exposed to macrolides (similar to rate in amoxicillin-exposed infants) and included rash, diarrhea, loss of appetite, and somnolence.

LactMed: Use is considered acceptable.
-AU: Safety has not been established.
-UK: Safety has not been established; benefit to mother should outweigh risk to the infant.
-US: Caution is recommended.

Excreted into human milk: Yes

Comments:
The following should be considered:
-The development and health benefits of human milk feeding
-The mother's clinical need for this drug
-Potential side effects in the human milk fed child due to the drug or the mother's underlying condition
-Diarrhea and mucous membrane fungal infection could occur in the breastfed infant; nursing may need to be discontinued.

See references