Fluconazole

Use of Oral Fluconazole during Pregnancy and the Risk of Birth Defects.

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BACKGROUND

Case reports suggest that long-term, high-dose fluconazole treatment for severe fungal infections during pregnancy causes a pattern of birth defects. It is unclear whether commonly used lower doses increase the risk of specific birth defects.

METHODS

In a registry-based cohort of liveborn infants in Denmark, we evaluated first-trimester oral fluconazole exposure and the risk of birth defects overall and of birth defects previously linked to azole antifungal agents.

RESULTS

The majority of fluconazole-exposed pregnancies were in women who received common therapeutic doses of 150 mg (56% of pregnancies) or 300 mg (31%). Oral fluconazole exposure was not associated with an increased risk of birth defects overall (210 birth defects among 7352 fluconazole-exposed pregnancies [prevalence, 2.86%] and 25,159 birth defects among 968,236 unexposed pregnancies [prevalence, 2.60%]; adjusted prevalence odds ratio, 1.06; 95% confidence interval [CI], 0.92 to 1.21). In addition, oral fluconazole exposure was not associated with a significantly increased risk of 14 of 15 types of birth defects previously linked to azole antifungal agents: craniosynostosis, other craniofacial defects, middle-ear defects, cleft palate, cleft lip, limb defects, limb-reduction defects, polydactyly, syndactyly, diaphragmatic hernia, heart defects overall, pulmonary-artery hypoplasia, ventricular septal defects, and hypoplastic left heart. A significantly increased risk of tetralogy of Fallot was observed (7 cases in fluconazole-exposed pregnancies [prevalence, 0.10%] as compared with 287 cases in unexposed pregnancies [prevalence, 0.03%]; adjusted prevalence odds ratio, 3.16; 95% CI, 1.49 to 6.71).

CONCLUSIONS

Oral fluconazole was not associated with a significantly increased risk of birth defects overall or of 14 of the 15 specific birth defects of previous concern. Fluconazole exposure may confer an increased risk of tetralogy of Fallot.

Source: NEJM

 

 

 

 

 

Anti-Fungal Drug Not Tied to Most Birth Defects.

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Although some reports have shown that high doses of the anti-fungal drugfluconazole (Diflucan) may raise the risk of birth defects, a new Danish review finds that more commonly prescribed lower doses of the medicine do not carry the same dangers.

Yet, in spite of this reassurance, experts may remain reluctant to prescribe the drug for expectant mothers who have yeast infections, since it is still linked to an increased risk of a rare congenital heart problem called tetralogy of Fallot.

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“Many pregnant women suffer from a yeast infection called vaginal candidiasis, or vaginal thrush, which is the most common clinical indication for use of oral fluconazole,” explained lead researcher Ditte Molgaard-Nielsen, an epidemiologist at the Statens Serum Institute in Copenhagen.

First-line treatment for vaginal candidiasis during pregnancy is vaginal preparations of topical anti-fungal drugs, she noted.

“However, in cases when topical treatment is ineffective this study provides comprehensive safety information, and may help inform clinical decisions when treatment with oral fluconazole is considered in pregnancy,” Molgaard-Nielsen said.

Specifically, the researchers looked at 15 birth defects linked to fluconazole and found it was not associated with an increased risk for 14 of them, she said.

“However, we did see an increase in the risk of tetralogy of Fallot, an uncommon congenital heart defect, but the number of exposed cases were few and this association should be confirmed in other studies before anything can be concluded with any certainty,” Molgaard-Nielsen added.

The report was published Aug. 29 in the New England Journal of Medicine.

Dr. Scott Berns, senior vice president and deputy medical officer for the March of Dimes, said that “when pregnant it is important to avoid taking any medicines unnecessarily.”

“I would chose the topical drug to treat a yeast infection. That is my first line,” he said. “If I had to use oral fluconazole, this study is reassuring that most of the time the baby is going to be fine. But, there is that small chance of tetralogy of Fallot. So, why take that chance?”

Another expert doesn’t think these findings will change clinical practice.

“Ob/Gyns are still going to be reluctant to prescribe this drug,” said Dr. Kecia Gaither, director of maternal fetal medicine at Brookdale University Hospital and Medical Center in Brooklyn, N.Y.

Gaither prefers to use natural methods for treating yeast infections. “One of them is increasing the use of yogurt intake,” she said. “There is certain bacteria in yogurt that prevents yeast infections. I have not run into a person who continues to have recurrent yeast infections after that is done.”

For the study, Molgaard-Nielsen’s team collected data on more than 7,300 women who took fluconazole during their pregnancy, among whom 210 infants were born with birth defects, and compared them to a control group of more than 968,000 unexposed women, among whom more than 25,000 babies were born with birth defects.

In both groups, the risk for having an infant with a birth defect was 0.6 percent, the researchers found.

Moreover, fluconazole wasn’t linked to a significantly increased risk for 14 of 15 birth defects to which the drug had been previously linked, they added.

These include craniosynostosis (a defect in the baby’s skull), middle ear defects, cleft palate, cleft lip, limb defects, an abnormal number of finger or toes, fused fingers or toes, diaphragmatic hernia, heart defects and shifting of a lung.

There was, however, a significantly increased risk of tetralogy of Fallot, with seven cases (0.10 percent) among women who took fluconazole, compared with 287 cases (0.03 percent) in unexposed women, the researchers found.

According to the U.S. National Institutes of Health, tetralogy of Fallot is a rare, complex birth defect where four different areas of the heart are malformed and the heart cannot pump enough blood or oxygen to the rest of the body. Surgery is usually required shortly after birth, although the long-term outlook for these patients has improved greatly in recent years.

Source: Drugs.com

Cryptococcal meningitis: improving access to essential antifungal medicines in resource-poor countries.

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Cryptococcal meningitis is the leading cause of adult meningitis in sub-Saharan Africa, and contributes up to 20% of AIDS-related mortality in low-income and middle-income countries every year. Antifungal treatment for cryptococcal meningitis relies on three old, off-patent antifungal drugs: amphotericin B deoxycholate, flucytosine, and fluconazole. Widely accepted treatment guidelines recommend amphotericin B and flucytosine as first-line induction treatment for cryptococcal meningitis. However, flucytosine is unavailable in Africa and most of Asia, and safe amphotericin B administration requires patient hospitalisation and careful laboratory monitoring to identify and treat common side-effects. Therefore, fluconazole monotherapy is widely used in low-income and middle-income countries for induction therapy, but treatment is associated with significantly increased rates of mortality. We review the antifungal drugs used to treat cryptococcal meningitis with respect to clinical effectiveness and access issues specific to low-income and middle-income countries. Each drug poses unique access challenges: amphotericin B through cost, toxic effects, and insufficiently coordinated distribution; flucytosine through cost and scarcity of registration; and fluconazole through challenges in maintenance of local stocks—eg, sustainability of donations or insufficient generic supplies. We advocate ten steps that need to be taken to improve access to safe and effective antifungal therapy for cryptococcal meningitis.

Source: Lancet