There are three general classes of antifungal agents (number of agents): azole antifungals (9), echinocandins (3), and polyenes (5). The azole antifungals contain an azole ring and inhibit a wide range of fungi. Echinocandins target the fungal cell wall and the polyenes increase the fungal membrane permeability and lead to cell death.
Gerald G. Briggs
Pregnancy
Azole antifungals inhibit the growth of fungi. Their trade names and molecular weights:
- Clotrimazole (Mycelex), an over-the-counter product, is available as a topical cream. Several studies have found no association between the drug and birth defects.
- Fluconazole (Diflucan) is a teratogen when doses of ≥400 mg/day are used during the first trimester. Smaller doses do not appear to cause embryo/fetal harm.
- Isavuconazonium (Cresemba) if used in pregnancy, exposure of the embryo/fetus would probably be low based on the >99% plasma protein binding, but the plasma half-life is 130 hours. Moreover, the drug is a potent animal teratogen and is best avoided in pregnancy.
- Itraconazole (Onmel, Sporanox, Tolsura), has a low risk, if any, of structural defects, according to what reported human experience suggests.
- Ketoconazole (Xolegel, Extina, Nizoral; 531) does not appear to adversely effect embryos and fetuses, but the human data are very limited. As with any drug, avoiding organogenesis is the best recommendation.
- Miconazole (Oravig) is usually used topically. Small amounts are absorbed from the vagina. The available evidence suggests that the drug does not increase the risk of congenital malformations.
- Posaconazole (Noxafil) does not have reported use in human pregnancy. The animal reproduction data suggest risk. Based on its molecular weight (about 701), the drug will most likely cross the placenta to the embryo/fetus. Thus, the best course is to avoid the drug during pregnancy, especially in the first trimester.
- Voriconazole (Vfend) has one human report of the drug use in pregnancy. The drug was started at about 19 weeks and continued until the woman gave birth at 35 weeks to a healthy male baby. At 6 months of age, the baby remained normal.
Echinocandin antifungals target the fungal cell wall by inhibiting its synthesis. Their trade names and molecular weights:
- Anidulafungin (Eraxis; 1,140) has no published human data. It is indicated for the treatment of candidemia and other forms of Candida infections. The animal data suggest low risk.
- Caspofungin (Cancidas; 1,213) has no published human data. It is indicated for presumed fungal infections in febrile, neutropenic patients. The animal data are suggestive of human risk, especially if exposure occurs in the first trimester. If possible, maternal treatment should be avoided in the first trimester.
- Micafungin (Mycamine; 1,292) has no published human data. It is indicated for the treatment of patients with esophageal candidiasis and for the prophylaxis of Candida infections in patients undergoing hematopoietic stem cell transplantation. The animal data in one species suggest high risk. If possible, maternal treatment should be avoided in the first trimester.