However, there are no reports in the literature about negative effects to the fetus when used in pregnancy. It has a lactation category of L1 and is safe to use while breastfeeding. Clotrimazole is another antifungal commonly used to treat vulvovaginal yeast infection. It has been commonly used to treat these infections in pregnancy and is considered generally safe.
A single case was published about its potential association with spontaneous abortion in a patient. However, it was never confirmed to be the cause and there have been no reports since then of negative effects on the fetus when used in pregnant women.
It is labeled as pregnancy category C. It has an L2 lactation rating and is most likely safe to use during breastfeeding. It is assigned pregnancy category B as animal studies with the use of this agent have not demonstrated any adverse effects to the fetus. Also, topical terbinafine is not greatly absorbed through the skin. It is generally regarded as safe to prescribe during pregnancy. Ciclopirox is a medication used to treat many of the above-listed conditions.
It is usually only used topically and is pregnancy category B. In animal studies, this medication has not been shown to harm the growing fetus when administered either topically or orally to rats, mice, monkeys, and rabbits. Therefore, it can be used topically safely during pregnancy but is not often chosen as a first-line agent. Its effects on breastfeeding are less well known, and it is labeled L3.
Selenium sulfide is commonly found in shampoos and is used to treat conditions like seborrheic dermatitis itchy, flaky scalp, aka. We would like to focus on this agent since it is so common in over the counter products. It is important to note that it has been labeled pregnancy category C. The cream and pessary are often prescribed together. Clotrimazole is generally considered safe for pregnant women to use. If you are using the pessary to treat vaginal thrush during pregnancy it is recommended that you insert it with your fingers rather than with the applicator provided.
It is very common for pregnant women to suffer from thrush. If you think you have thrush it is best to consult your doctor or midwife who will advise you as to whether treatment is recommended.
It is mainly during this time that some medicines are known to cause birth defects. There is no scientific proof that using clotrimazole during early pregnancy increases the risk of having a baby with a birth defect. Two studies of miscarriage have been carried out, and while one showed no increased risk with clotrimazole use, the other showed a slightly increased risk.
However, women using clotrimazole in pregnancy may be more likely to be obese or to have diabetes, because these factors make women more prone to thrush. It is therefore possible that these factors, and not the clotrimazole treatment, explain the slightly increased risk of miscarriage seen in the one study.
More research is needed before firm conclusions can be drawn. The manufacturer therefore recommends that effective contraception should be continued throughout treatment and for 2 months thereafter. Voriconazole is an azole displaying fungistatic activity against Candida spp. Like other azoles, voriconazole has been shown to be teratogenic in rodents at high but also low doses equivalent of 0. It was also shown to be embryo—fetotoxic in rabbits, and classified as category D by the FDA due to the lack of human data.
The drug is therefore contraindicated during pregnancy. Since its approval by the FDA and the EMA in , only one report of voriconazole exposure during pregnancy has been reported.
Indeed, our group recently reported the observation of a neutropenic pregnant woman with life-threatening refractory invasive aspergillosis who received voriconazole during the second and third trimesters of pregnancy. Data on pregnancy exposure are limited to a single observation with good materno-fetal outcome.
It should not be considered in pregnancy, except in life-threatening maternal disease without a therapeutic alternative. Posaconazole is the most recently available triazole. It has expanded antifungal spectrum including Mucorales and has otherwise broad spectrum against most of the common yeasts and moulds.
The manufacturer has reported teratogenic effects in rats at 1. It was also shown to be embryotoxic and teratogenic in rabbits, at 2. The FDA labels posaconazole category C. It is embryotoxic and teratogenic in rodents and rabbits. No human data are available so far and it should not be considered in pregnancy, except in life-threatening maternal disease without a therapeutic alternative. Isavuconazole is a new investigational azole with broad-spectrum and large coverage of both yeasts and moulds, including Mucorales.
It is currently in Phase III of clinical development. To our knowledge, no data regarding isavuconazole and pregnancy have been reported. They display an excellent tolerance profile, and a broad fungal spectrum, including yeasts such as Candida spp.
It crosses the placenta of rats and rabbits and was shown to be embryotoxic and teratogenic in both at the recommended human dose reduction of litter size, ossification and rib malformations.
Its molecular weight and extensive plasma binding could limit the amount of crossing, but this could be counterbalanced by the long half-life of the molecule 9—11 h.
Micafungin crosses the placenta and was shown to be embryotoxic and teratogenic in rabbits visceral abnormalities and abortions at the equivalent of 4 times the recommended human dose. Anidulafungin crosses the placenta of pregnant rats and was shown to be possibly teratogenic in rodents skeletal abnormalities reported at the equivalent of 2 times the recommended human dose, but in the range of a historical control database.
It was associated with reduced fetal weight in pregnant rabbits at the equivalent of 4 times the recommended human dose. Whether either drug transfers across the human placenta remains unknown. High molecular weight around and extensive plasma binding could limit the amount of crossing, but this could be counterbalanced by the long half-life 16—50 h. All echinocandins are classified as pregnancy category C agents; embryotoxic and teratogenic effects have been reported in rodents and rabbits.
Human data are still non-existent in , and these drugs are not considered safe during pregnancy. Flucytosine was originally developed as an antimetabolite. It is also converted in fungal cells into fluorouracil, which interferes with both DNA and protein synthesis. Its antifungal spectrum is limited to yeasts Candida spp. Flucytosine has been shown to be teratogenic in rats at the equivalent of 0. It has been shown to be teratogenic and embryotoxic in rodents given the equivalent of human doses, but not in monkeys.
Flucytosine is classified as category C by the FDA. To our knowledge, no new report of pregnancy exposure has been published over the last 10 years. International recommendations, however, have been published suggesting the use of flucytosine in selected situations, detailed below. Limited case reports did not evidence adverse outcome after flucytosine exposure during the second and third trimesters. Data are lacking to study further its fetal toxicity and it should not be considered in pregnancy, except after the first trimester in life-threatening maternal infections where the benefits of adding flucytosine may justify the risk.
Polyenes are among the oldest antifungal drugs. They bind to ergosterol, forming transmembrane pores leading to ionic leakage and fungal death. Amphotericin B displays the broadest antifungal spectrum, including most yeasts, moulds including Mucorales and dimorphic fungi. Lipid formulations were later developed to limit amphotericin B nephrotoxicity: liposomal, colloidal dispersion and lipid complex forms.
A liposomal colloidal dispersion form was approved by the FDA in Amphotericin B is the safest systemic antifungal drug in pregnancy. Maternal nephrotoxicity is reported to be similar to that of non-pregnant patients. Case reports and series have provided further insight into the safety and efficacy of liposomal amphotericin B in pregnancy. Mueller et al. No fetal malformations were reported. Pagliano et al. It is considered as the safest antifungal drug in pregnancy and is a major tool in the fungal armamentarium in this setting.
Liposomal amphotericin B should also be considered safe in pregnancy. Data regarding other lipidic derivatives remain scarce and they should be used only in case of unavailability of other polyenes. Terbinafine is an allyamine available as topical and oral preparations. It acts by selectively inhibiting the fungal squalene epoxidase, which increases squalene to toxic levels, thus killing fungal cells.
It is indicated for the treatment of dermatophytic skin infections, onychomycosis and other cutaneous dermatophytoses, including chromomycosis and mycetoma, which are usually not therapeutic emergencies during pregnancy. Oral reproduction studies did not evidence any embryo—fetotoxicity in rabbits and rats administered up to 23 times the maximum recommended human dose.
Although it is classified as pregnancy category B, oral prescription should be postponed until after delivery. Breastfeeding should also be avoided, given terbinafine's active excretion in milk. Terbinafine is classified as category B by the FDA. It was not shown to be toxic in animal pregnancies, but human data are not available, hence hampering its systemic use in pregnancy.
In contrast, topical terbinafine, which has limited absorption ability, can be prescribed. Griseofulvin is an orally administered fungistatic drug that acts by altering DNA replication thereby blocking fungal mitosis. It is indicated in dermatophytoses and classified as category C by the FDA. Griseofulvin crosses the placenta 61 and was shown to be tumorigenic, embryotoxic and teratogenic in rodents at 3—45 times the recommended human dose.
An FDA report suggested a possible association between griseofulvin prescription and conjoined twins that was not confirmed later. Griseofulvin is classified as category C by the FDA. It is carcinogenic, embryotoxic and teratogenic in rodents. Human data are too limited to allow its use in pregnancy, especially in the first trimester. Topical azoles include bifonazole, clotrimazole, fenticonazole, isoconazole, ketoconazole, omoconazole, oxiconazole, sertaconazole, tioconazole, miconazole and econazole.
They are indicated for superficial fungal infections involving the skin Candida sp. Malassezia furfur , dermatophytes , and oral and vulvo-vaginal candidiasis. Topical azoles are not or are minimally absorbed and hence are allowed at any stage of pregnancy. The FDA has assigned miconazole, irrespective of its galenic formulation, to pregnancy category C. Like other topical azoles, animal studies did not evidence embryo—fetotoxicity or teratogenicity with topical miconazole.
No specific study has been performed in pregnancy, and miconazole should only be used in this setting in the absence of an alternative and if benefits outweigh risk.
Treatment with topical miconazole during the first trimester did not increase the risk of congenital abnormalities OR 0. Nystatin is poorly absorbed orally, if at all.
No animal data are available for this drug. Nystatin is classified as category A by the FDA in pregnancy. Czeizel et al. It was associated with a slightly increased risk of congenital abnormalities compared with unexposed women OR 1.
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