The findings of a new study examined the link between Diflucan and birth defects, indicating that side effects of the anti-fungal drug may increase the risk of certain malformations when taking during pregnancy.
In a report published this month in the medical journal The BMJ, researchers from Brigham and Women’s Hospital in Boston found that while side effects of Diflucan were not associated with a number of types of birth defects, such as oral clefts or conotruncal malformations, it was linked to an increased risk of musculoskeletal malformations.
Diflucan (fluconazole) is a prescription drug by Pfizer used to treat yeast infections of the vagina, mouth, esophagus and other organs. It is also used to treat some kinds of meningitis and used as a yeast infection preventative in patients being treated with chemotherapy or radiation therapy before receiving a bone marrow transplant.
In recent years, case reports have suggested side effects of Diflucan may cause a pattern of birth defects when high-doses of the medication are used to treat severe fungal infections during pregnancy.
Researchers in this latest report conducted a cohort study involving nearly two million pregnancies in the U.S. from 2000 to 2014. The study looked at data on 37,650 pregnancies where the mother was exposed to Diflucan during the first trimester and compared them to 82,090 pregnancies where the mother was exposed to topical azoles during the first trimester instead.
While researchers found no statistically significant difference in oral cleft or conotruncal malformations, 52.1 out of every 10,000 pregnancies involving Diflucan use during the first trimester resulted in musculoskeletal malformations, compared to only 37.3 per 10,000 among those given topical azoles.
In addition, the researchers suspect the musculoskeletal malformation rate may be dose-dependent, which means that the higher the dose, the higher the risk of a certain outcome. This is usually considered a strong indicator of a causal relationship.
In 2011, the FDA issued a warning that high doses of Diflucan had been associated with birth defects and congenital anomalies. However, the data at the time indicated the risk was only associated with high doses involving at least 400-800 mgs.
“The increased risk of musculoskeletal malformations, that we observed, associated with exposure to fluconazole at common therapeutic doses during the first trimester, aligns with the patterns of malformations reported in previous case reports at high doses, summarized by the FDA,” the researchers in this latest study determined. “Previous studies might have been unable to detect this increased risk, probably because of an insufficient sample size. We also observed an almost twofold increased risk in the higher dose group (>450 mg of fluconazole), consistent with the dose-response relation in animal models.”
According to the FDA, Diflucan birth defects seen in infants exposed to long-term, high-doses during the first trimester included abnormal head, skull and face defects, cleft palate, cleft lip, bowing of the thigh bones, thin ribs, long bones, muscle weakness, joint deformities and congenital heart disease at birth.