Which Antifungal Is Safe In Pregnancy?

Which Antifungal Is Safe In Pregnancy
Abstract – Medications should be employed with caution in women of childbearing age who are pregnant or considering pregnancy. Compared to oral or parenteral agents, topical medications have limited systemic absorption and are deemed safer. However, their safety profile must be assessed cautiously due to the limited available data.

  1. In this article, we aggregate human and animal studies to provide recommendations on utilizing topical antiviral and antifungal medications in pregnancy.
  2. For antiviral medications, acyclovir and trichloroacetic acid are safe to use in pregnancy.
  3. Docosanol, imiquimod and penciclovir are likely safe, but should be utilized as second-line agents.

Podofilox and podophyllin resin should be avoided. For antifungal medications, clotrimazole, miconazole and nystatin are considered first-line agents. Butenafine, ciclopirox, naftifine, oxiconazole and terbinafine may be utilized after the above agents.
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Contents

Which antifungal is safe during pregnancy?

Abstract – Careful consideration of the benefit to the mother and the risk to the fetus is required when prescribing antifungal therapy in pregnancy. Imidazoles are considered safe as topical therapy for fungal skin infections during pregnancy. Nystatin is minimally absorbed and is effective for vaginal therapy.

  1. Although vaginal use of the imidazoles is probably safe during the later stages of pregnancy, their systemic absorption is higher than when applied to the skin.
  2. The systemic antifungal drug with which there has been the most experience in pregnancy is amphotericin B.
  3. There have been no reports of teratogenesis attributed to this agent.

There is evidence to suggest that fluconazole exhibits dose-dependent teratogenic effects; however, it appears to be safe at lower doses (150 mg/day). Ketoconazole, flucytosine, and griseofulvin have been shown to be teratogenic and/or embryotoxic in animals.
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Which antifungal is not safe in pregnancy?

What’s the best way to treat a yeast infection during pregnancy? – Answer From Yvonne Butler Tobah, M.D. You can safely treat a yeast infection during pregnancy with various over-the-counter antifungal vaginal creams or suppositories. However, it’s best to confirm with your health care provider that your symptoms are actually due to a yeast infection before starting treatment.

  • Clotrimazole (Mycelex, Lotrimin AF)
  • Miconazole (Monistat 3)
  • Terconazole

These products can be used at any point during pregnancy and don’t pose a risk of birth defects or other pregnancy complications. For best results, choose a seven-day formula. Oral medication isn’t recommended if you’re pregnant. Some commonly prescribed antifungals — such as fluconazole (Diflucan) — should be avoided, especially during the first trimester.
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Is clotrimazole antifungal safe for pregnancy?

Is it safe to use clotrimazole in pregnancy? – 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,
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Is fluconazole safe in pregnancy?

Safety Announcement Additional Information for Patients Additional Information for Healthcare Professionals Data Summary References Safety Announcement The U.S. Food and Drug Administration (FDA) is informing the public that chronic, high doses (400-800 mg/day) of the antifungal drug Diflucan (fluconazole) may be associated with a rare and distinct set of birth defects in infants whose mothers were treated with the drug during the first trimester of pregnancy.

  • Used to treat yeast infections of the vagina, mouth, throat, esophagus, and other organs.
  • Used to treat meningitis caused by a certain type of fungus.
  • Used to prevent yeast infections in patients who are likely to become infected because they are being treated with chemotherapy or radiation therapy before a bone marrow transplant.
  • The dose of fluconazole for vaginal candidiasis is a single dose of 150 mg and is lower than for other indications.

There are several published case reports of birth defects in infants whose mothers were treated with high-dose fluconazole (400-800 mg/day) for serious and life-threatening fungal infections during most or all of the first trimester (see Data Summary below).1-4 The features seen in these infants are listed in Table 1,

  1. Based on this information, the pregnancy category for fluconazole indications (other than vaginal candidiasis) has been changed from category C to category D.
  2. The pregnancy category for a single dose of fluconazole 150 mg to treat vaginal candidiasis has not changed and remains category C.
  3. Pregnancy category D means there is positive evidence of human fetal risk based on human data but the potential benefits from use of the drug in pregnant women with serious or life-threatening conditions may be acceptable despite its risks.

Healthcare professionals should be aware of the potential risks with long-term, high-dose use of fluconazole and counsel patients if the drug is used during pregnancy or if a patient becomes pregnant while taking the drug. Additional Information for Patients

  • Use of long-term, high-dose (400-800 mg/day) fluconazole during the first three months of pregnancy (first trimester) may be associated with a rare and distinct set of birth defects in infants.
  • A single dose of fluconazole 150 mg to treat vaginal yeast infection during pregnancy does not appear to be associated with the birth defects.
  • Patients should notify their healthcare professional if they are pregnant or become pregnant while taking fluconazole.
  • Side effects from the use of fluconazole should be reported to the FDA MedWatch program, using the information in the “Contact Us” box at the bottom of the page.

Additional Information for Healthcare Professionals

  • The pregnancy category for a single 150 mg dose of fluconazole for vaginal candidiasis is category C based on data from animal studies that showed an adverse effect on the fetus. There are no adequate and well-controlled studies of fluconazole in pregnant women. Available human data do not suggest an increased risk of congenital anomalies following a single maternal dose of 150 mg.
  • The pregnancy category for fluconazole use for indications other than vaginal candidiasis is now category D. A few published case reports describe a rare pattern of distinct congenital anomalies in infants exposed in utero to high-dose maternal fluconazole (400-800 mg/day) during most or all of the first trimester.
  • The features seen in these infants include brachycephaly, abnormal facies, abnormal calvarial development, cleft palate, femoral bowing, thin ribs and long bones, arthrogryposis, and congenital heart disease. These effects are similar to those seen in animal studies.
  • If fluconazole is used during pregnancy, or if a patient becomes pregnant while taking fluconazole, the patient should be informed of the potential risk to the fetus.
  • Adverse events involving fluconazole should be reported to the FDA MedWatch program using the information in the “Contact Us” box at the bottom of this page.

Data Summary There are several case reports published in the medical literature that describe rare and distinct congenital anomalies in infants whose mothers were treated with chronic high-dose (400-800 mg/day) fluconazole for fungal infections in the first trimester of pregnancy.1-4 Four reports involved maternal use of chronic high-dose intravenous fluconazole for coccidioidal meningitis and one report involved a human immunodeficiency virus (HIV)-positive mother who received chronic high-dose oral fluconazole for vaginal candidiasis.

  1. Cases associated with high-dose fluconazole use all shared some characteristics with the autosomal recessive genetic disorder known as Antley-Bixler syndrome.
  2. This combination of congenital anomalies occurs rarely in the general population, and is similar to anomalies seen in animals following in utero fluconazole exposure.

Chronic high-dose fluconazole may be teratogenic in humans when used in the first trimester of pregnancy; however, the magnitude of this potential human teratogenic risk is unknown. The five reports of distinct and rare congenital anomalies following chronic, high-dose in utero exposure to fluconazole suggest a possible drug threshold effect for a fluconazole embryopathy.

The available data in the medical literature do not suggest an association between low-dose oral fluconazole use in the first trimester of pregnancy and congenital anomalies.5-11 The few published epidemiological studies of in utero exposure to low doses of fluconazole (most patients received a single oral dose of 150 mg) showed no consistent pattern of anomalies among affected infants; however, most of these studies were too small to accurately detect an increased risk for major birth defects overall.7, 9-11 In addition, none of these studies were large enough to accurately detect an increased risk for a rare or unique birth defect or syndrome.

Table 1.

Features Seen in Infants Exposed to long-term, high-dose Diflucan (fluconazole) in utero
short, broad head
abnormal looking face
abnormal development of the skullcap
oral cleft (opening in the lip or palate)
bowing of the thigh bones
thin ribs and long bones
muscle weakness and joint deformities
Congenital (present at birth) heart disease

References

  1. Lopez-Rangel E, Van Allen MI. Prenatal exposure to fluconazole: an identifiable dysmorphic phenotype. Birth Defects Res A Clin Mol Teratol,2005;73:919-23.
  2. Pursley TJ, Blomquist IK, Abraham J, Andersen HF, Bartley JA. Fluconazole-induced congenital anomalies in three infants. Clin Infect Dis,1996;22:336-40.
  3. Lee BE, Feinberg M, Abraham JJ, Murthy AR. Congenital malformations in an infant born to a woman treated with fluconazole. Pediatr Infect Dis J,1992;11:1062-4.
  4. Aleck KA, Bartley DL. Multiple malformation syndrome following fluconazole use in pregnancy: report of an additional patient. Am J Med Genet,1997;72:253-6.
  5. Rubin P, Wilton L, Inman W. Fluconazole and pregnancy: results of a prescription event monitoring study. Int J Gynecol Obstet,1992;37(Suppl):25-7.
  6. Inman W, Pearce G, Wilton L. Safety of fluconazole in the treatment of vaginal candidiasis. A prescription-event monitoring study, with special reference to the outcome of pregnancy. Eur J Clin Pharmacol,1994;46:115-8.
  7. Mastroiacovo P, Mazzone T, Botto LD, Serafini MA, Finardi A, Caramelli L, et al. Prospective assessment of pregnancy outcomes after first-trimester exposure to fluconazole. Am J Obstet Gynecol,1996;175:1645-50.
  8. Sanchez JM, Moya G. Fluconazole teratogenicity. Prenat Diagn,1998;18:862-3.
  9. Jick SS. Pregnancy outcomes after maternal exposure to fluconazole. Pharmacotherapy,1999;19:221-2.
  10. Sorensen HT, Nielsen GL, Olesen C, Larsen H, Steffensen FH, Schønheyder HC, et al. Risk of malformations and other outcomes in children exposed to fluconazole in utero. Br J Clin Pharmacol,1999;48:234-8.
  11. Nørgaard M, Pedersen L, Gislum M, Erichsen R, Søgaard KK, Schønheyder HC, et al. Maternal use of fluconazole and risk of congenital malformations: a Danish population-based cohort study. J Antimicrob Chemother,2008;62:172-6.

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Which antifungal is safest?

Introduction and background – Oral antifungals have been implicated in many case reports of hepatotoxicity and serious liver injuries in the last few decades, Antifungal-induced hepatic injury is often characterized as an acute, cholestatic, or mixed hepatocellular-cholestatic response,

The reaction generally resolves with discontinuation of treatment, but some liver damage can be chronic. Serious hepatic side effects of oral antifungal agents are considered rare, but reported incidence rates vary widely and depend on the agent, Fungal infections are a leading cause of ailment and death in immunocompromised and very ill patients,

Although antifungal drug options have increased in recent years, yet effective management significantly depends on the early and proper treatment that improves efficacy and safety, Existing liver disease can be a contraindication for antifungal administration due to safety concerns.

The liver is a major component of drug metabolism, and hepatic disease can dramatically alter the pharmacokinetics of antifungal drugs due to impaired clearance, liver blood flow, biliary excretion, and plasma protein binding. Such patients are less likely to tolerate drug-induced liver injury (DILI) than healthy people,

In addition, patients with cirrhosis are more prone to drug-related side effects, such as kidney failure, intestinal bleeding, and hepatic encephalopathy, A hepatic function can influence drug-drug interactions (DDI) due to reduced drug uptake and inhibition of metabolizing enzymes,

  • Hepatotoxicity is defined as chemical-induced liver damage,
  • There is a known link between ketoconazole and hepatotoxicity,
  • However, the early evidence suggested that ketoconazole-induced hepatotoxicity was mild, rarely fatal, and could be reversed upon drug discontinuation.
  • In the United Kingdom, hepatotoxicity was reported in one of 15,000 patients in the first decade after oral ketoconazole market approval,

DILI is one of the leading causes of acute and chronic liver diseases. To diagnose this condition, it is essential to distinguish detected biochemical abnormalities from actual hepatic dysfunction. DILI is typically characterized by increased levels of hepatic enzymes resulting from the effects of an active drug or its metabolites on the liver,

  • This biochemical imbalance is not necessarily associated with clinically significant liver dysfunction because the liver has significant healing properties,
  • However, DILI may cause hepatic dysfunction, which manifests as hyperbilirubinemia and coagulopathy, or severe liver failure, presenting with jaundice and hepatic encephalopathy,

Most drugs work by interfering with one or more cellular/molecular activities; they, therefore, have the potential to produce less desirable reactions, The antifungals fluconazole and itraconazole are considered relatively safe; they have been associated with only minor changes in liver function tests that usually do not require interruption of treatment.

Fluconazole is widely used in the treatment of various fungal infections. It is found in oral and parenteral forms and is different from other azoles as it is primarily metabolized by the kidneys rather than the liver, The mechanisms by which it causes temporary elevation of transaminases are unknown, although idiosyncratic reactions appear to be involved.

There have been two reported cases of marked liver toxicity due to fluconazole and itraconazole requiring the suspension of these azoles; in these cases, the symptoms resolved immediately after drug withdrawal, Ketoconazole has a higher incidence of hepatic damage than other systemic antifungals,

In a randomized clinical trial, patients with ketoconazole-treated onychomycosis were three times more likely to develop hepatitis than patients treated with griseofulvin, Cases of liver damage have also been reported in conjunction with griseofulvin, itraconazole, and terbinafine, and several fluconazole-related cases have occurred in severely immune-depressed patients,

In a recent post-marketing study of 25,884 patients treated with terbinafine, two cases of symptomatic hepatic injury related to antifungal treatment were identified, The risk of liver damage and hepatic dysfunction caused by an antifungal agent depends on several factors: the chemical characteristics of the agent, genetic predisposition, comorbidities including primary hepatic disease, associated hepatotoxic drugs and DDIs, and fungal infection severity and involvement of the liver,

Thus, the mechanisms of DILI can be multi-factorial. Chronic liver disease patients are at increased risk of developing diseases that lead to life-threatening conditions, such as sepsis and hepatic encephalopathy, for several reasons, including dysfunctional immune response, increased intestinal permeability resulting in changes in the quantity and quality of gut microorganisms, and genetic predisposition, which adds to the transmission of fungal infections from the gut to the circulatory system,

The onset of fungal infections has been linked to the emergence of many complications, such as severe kidney damage and multiple organ failure, all of which result in short- or long-term mortality, Fernandez et al. found that 2% of hospitalized patients with acute-on-chronic liver disease (ACLD) had fungal infections,

  • At any stage of liver disease, either compensated or non-compensated, and including severe or chronic liver failure, the added complication of fungal infection leads to an increased risk of death.
  • Overall, there is no clear consensus in the published literature about the use of antifungal agents in patients with pre-existing liver disease.

The understanding of liver damage caused by antifungal drugs in patients with hepatic impairment is not clear, and recommendations for dose adjustment in these cases are not straightforward. Most information about antifungal regimens dosing comes from clinical trials and pharmacokinetic studies which included only a few patients with varying degrees of liver disease.

The manufacturers of some antifungals recommend dose reduction in cases of hepatic dysfunction, while others do not, We aimed to summarize the current data on the pharmacokinetics of antifungals for these individuals and to increase clinical awareness of the proper use of various antifungal compounds in the case of liver injury.

Materials and methods This research was completed based on the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines to ensure transparency, completeness, and robustness of reporting. Inclusion and Exclusion Criteria Articles were selected for inclusion in this systematic review based on study type, participants, and interventions, as follows.

  1. Only randomized controlled trials, observational cohort studies, and case reports were included.
  2. For randomized trials, the researcher assessed the methodological approach to determine whether each study was based on a clearly described randomization method.
  3. The participants in the studies included in this review were patients with clinically diagnosed liver diseases or signs or symptoms of drug-induced liver damage who were undergoing antifungal therapy or had a recent history of oral antifungal administration.

We selected studies that evaluated pharmacological and non-pharmacological interventions to prevent and manage fungal infection in liver disease patients and included only studies that compared interventions with controls such as placebos, standard treatment, or no treatment were selected.

  1. We placed no publication date restrictions on the searches and included only peer-reviewed journal articles with full text and that were published in English.
  2. Articles were excluded if they did not meet the inclusion criteria, were not peer-reviewed, were published in websites ending with dot com, or described medications other than antifungals.

The primary outcomes were liver enzyme levels and the secondary outcomes were abdominal ultrasound and liver biopsy findings. Information Sources and Search Articles included in this review were obtained from searches in English-based databases with high quality and peer-reviewed articles, namely PubMed, CINAHL, and EMBASE.

  1. The searches were guided by the Cochrane Handbook for Systematic Reviews of Interventions, Version 5.1.0.
  2. We used keywords and Boolean search strategies, with terms such as OR, AND, and NOT used to identify relevant articles.
  3. The search carried in PubMed was based on the following combination of keywords: (“antifungal” OR “ketoconazole” OR “fluconazole” OR “griseofulvin” OR “terbinafine”) AND (“acute liver disease” OR “acute liver failure” OR “acute liver damage”).

Articles were filtered to include only full-text articles, articles published from the databases’ inception to 2021, articles published in English, and peer-reviewed articles. Study Selection The retrieved articles were manually screened to remove duplicates and to remove irrelevant articles.

The full texts of the remaining articles were then read to determine eligibility. We also assessed the bibliographies of the included articles for additional eligible studies not identified by the initial search, using the same eligibility criteria. The excluded studies were documented along with the reasons for exclusion.

The final list of selected studies is shown in Table 1,
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Can ketoconazole be used during pregnancy?

Abstract – The use of any medication in pregnant women requires careful consideration of benefit to the mother versus risk posed to the fetus. Fungal infections are not uncommon in pregnant women; in fact, the incidence of certain infections such as Candida vaginitis is increased in this patient population.

A variety of antimycotic agents are currently available to treat systemic or mucocutaneous fungal infections. Many of these agents are capable of penetrating the placental barrier and entering fetal cord blood, therefore adverse effects of these agents on the fetus are a valid concern. The use of topical azoles for the treatment of superficial fungal infections is safe and efficacious.

However, there are some data suggesting a dose-related increase in the risk of teratogenicity associated with the use of systemic azoles. Amphotericin B remains the drug of choice for the treatment of systemic fungal infections in pregnancy. There are serious risks of fetal malformations associated with the use of griseofulvin, ketoconazole, voriconazole, flucytosine and potassium iodide.
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Which antifungal drug causes birth defects?

Antifungal drug during pregnancy tied to miscarriage, birth defects

  • New findings from a large study of pregnant women in Quebec suggests that use of an oral antifungal treatment for vaginal yeast infections during pregnancy is associated with increased risk of miscarriage, researchers reported today in the Canadian Medical Association Journal.
  • The findings, from the Quebec Pregnancy Cohort, on ongoing population-based grouping that researchers use to study medication use in pregnant women, show that women who received a single dose of oral fluconazole during early pregnancy had a more than twofold increase in the risk of miscarriage compared with women who were not exposed to the drug.
  • In addition, exposure to a higher dose (150 milligrams or higher) of oral fluconazole during the first trimester was associated with an increased risk of having a newborn with a heart defect.

Vaginal yeast infections caused by Candida affect an estimated 10% of women during pregnancy, and topical antifungal creams are recommended as the first-line treatment for these infections. While a single dose of oral fluconazole (150 mg or less ) is also sometimes prescribed for more serious or persistent infections, concerns about potential links to miscarriage and birth defects have arisen in recent years.

In 2016, a Danish study published in the Journal of the American Medical Association ( JAMA ) reported an increased risk of miscarriage associated with low-dose oral fluconazole exposure compared with no exposure or with topical azole exposure. Case reports have also linked high doses of oral fluconazole taken during pregnancy to skeletal malformations in children.

The US Food and Drug Administration (FDA), which is reviewing the results of the Danish study, advises caution in prescribing oral fluconazole during pregnancy.
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Is miconazole safe in pregnancy?

This sheet is about exposure to miconazole or clotrimazole in pregnancy and while breastfeeding. This information should not take the place of medical care and advice from your healthcare providers. What is miconazole? Miconazole is a medication used to treat fungal infections. Miconazole is a cream used to treat skin and vaginal infections. Common trade names for miconazole include Monistat®, Micatin® and Mitrazole®. What is clotrimazole? Clotrimazole is also a medication used to treat fungal infections. Like miconazole, clotrimazole is available as a cream to treat skin and vaginal infections. Brand names of clotrimazole Femcare®, Lotrimin®, and Mycelex®. I just found out I am pregnant. Should I stop using miconazole or clotrimazole? Sometimes when people find out they are pregnant, they think about changing how they take their medication, or stopping their medication altogether. However, it is important to talk with your healthcare providers before making any changes to how you take this medication. Your healthcare providers can talk with you about the benefits of treating your condition and the risks of untreated illness during pregnancy. What should I do if I think I have a vaginal yeast infection while pregnant? People are more likely to get yeast infections during pregnancy than at other times. If you think you have a vaginal yeast infection, it is important to see your healthcare provider to be sure the infection is yeast before trying to treat it on your own. If you have another type of infection, you may need different treatment. I use miconazole or clotrimazole. Can it make it harder for me to become pregnant? Using miconazole or clotrimazole is not expected to make it harder to become pregnant. Does using miconazole or clotrimazole increase the chance for miscarriage? Miscarriage can occur in any pregnancy. One study found a small increased chance for miscarriage with miconazole and clotrimazole, but there were several problems with this study that could have affected the results. Other studies have not found that miconazole or clotrimazole increases the chance for miscarriage. Does taking miconazole or clotrimazole increase the chance of birth defects? Every pregnancy starts out with a 3-5% chance of having a birth defect. This is called the background risk. Topical (used on the skin) or vaginal medications enter the body in lower amounts than oral (pill) medications. This means less medication reaches the developing baby. Since topical and vaginal miconazole and clotrimazole are not well absorbed, they are unlikely to be a concern for the pregnancy. Most studies have shown that miconazole or clotrimazole at low doses (<400 mg/day) does not increase the chance of birth defects. Does using miconazole or clotrimazole increase the chance of other pregnancy related problems? Studies have not been done to see if miconazole or clotrimazole increases the chance for pregnancy-related problems such as preterm delivery (birth before week 37) or low birth weight (weighing less than 5 pounds, 8 ounces at birth). Does using miconazole or clotrimazole in pregnancy affect future behavior or learning for the child? Studies have not been done to see if miconazole or clotrimazole can cause behavior or learning issues for the child. Breastfeeding while using miconazole or clotrimazole: There are currently no studies looking at miconazole or clotrimazole use during breastfeeding. However, because only small amounts of the medication could pass into breastmilk when miconazole or clotrimazole is used topically, breastfeeding is not expected to be a concern. Miconazole and clotrimazole creams have been used directly on infants under the care of a healthcare provider to treat fungal infections. Talk to your healthcare provider about your breastfeeding questions. If a male uses miconazole or clotrimazole, could it affect fertility (ability to get partner pregnant) or increase the chance of birth defects? There are no studies looking at fertility or possible risks to a pregnancy when the father uses miconazole or clotrimazole. In general, exposures that fathers or sperm donors have are unlikely to increase the risks to a pregnancy. For more information, please see the MotherToBaby fact sheet Paternal Exposures at https://mothertobaby.org/fact-sheets/paternal-exposures-pregnancy/, View complete answer

Can clotrimazole cause birth defects?

This sheet is about exposure to miconazole or clotrimazole in pregnancy and while breastfeeding. This information should not take the place of medical care and advice from your healthcare providers. What is miconazole? Miconazole is a medication used to treat fungal infections. Miconazole is a cream used to treat skin and vaginal infections. Common trade names for miconazole include Monistat®, Micatin® and Mitrazole®. What is clotrimazole? Clotrimazole is also a medication used to treat fungal infections. Like miconazole, clotrimazole is available as a cream to treat skin and vaginal infections. Brand names of clotrimazole Femcare®, Lotrimin®, and Mycelex®. I just found out I am pregnant. Should I stop using miconazole or clotrimazole? Sometimes when people find out they are pregnant, they think about changing how they take their medication, or stopping their medication altogether. However, it is important to talk with your healthcare providers before making any changes to how you take this medication. Your healthcare providers can talk with you about the benefits of treating your condition and the risks of untreated illness during pregnancy. What should I do if I think I have a vaginal yeast infection while pregnant? People are more likely to get yeast infections during pregnancy than at other times. If you think you have a vaginal yeast infection, it is important to see your healthcare provider to be sure the infection is yeast before trying to treat it on your own. If you have another type of infection, you may need different treatment. I use miconazole or clotrimazole. Can it make it harder for me to become pregnant? Using miconazole or clotrimazole is not expected to make it harder to become pregnant. Does using miconazole or clotrimazole increase the chance for miscarriage? Miscarriage can occur in any pregnancy. One study found a small increased chance for miscarriage with miconazole and clotrimazole, but there were several problems with this study that could have affected the results. Other studies have not found that miconazole or clotrimazole increases the chance for miscarriage. Does taking miconazole or clotrimazole increase the chance of birth defects? Every pregnancy starts out with a 3-5% chance of having a birth defect. This is called the background risk. Topical (used on the skin) or vaginal medications enter the body in lower amounts than oral (pill) medications. This means less medication reaches the developing baby. Since topical and vaginal miconazole and clotrimazole are not well absorbed, they are unlikely to be a concern for the pregnancy. Most studies have shown that miconazole or clotrimazole at low doses (<400 mg/day) does not increase the chance of birth defects. Does using miconazole or clotrimazole increase the chance of other pregnancy related problems? Studies have not been done to see if miconazole or clotrimazole increases the chance for pregnancy-related problems such as preterm delivery (birth before week 37) or low birth weight (weighing less than 5 pounds, 8 ounces at birth). Does using miconazole or clotrimazole in pregnancy affect future behavior or learning for the child? Studies have not been done to see if miconazole or clotrimazole can cause behavior or learning issues for the child. Breastfeeding while using miconazole or clotrimazole: There are currently no studies looking at miconazole or clotrimazole use during breastfeeding. However, because only small amounts of the medication could pass into breastmilk when miconazole or clotrimazole is used topically, breastfeeding is not expected to be a concern. Miconazole and clotrimazole creams have been used directly on infants under the care of a healthcare provider to treat fungal infections. Talk to your healthcare provider about your breastfeeding questions. If a male uses miconazole or clotrimazole, could it affect fertility (ability to get partner pregnant) or increase the chance of birth defects? There are no studies looking at fertility or possible risks to a pregnancy when the father uses miconazole or clotrimazole. In general, exposures that fathers or sperm donors have are unlikely to increase the risks to a pregnancy. For more information, please see the MotherToBaby fact sheet Paternal Exposures at https://mothertobaby.org/fact-sheets/paternal-exposures-pregnancy/, Please click here for references. OTIS/MotherToBaby encourages inclusive and person-centered language. While our name still contains a reference to mothers, we are updating our resources with more inclusive terms. Use of the term mother or maternal refers to a person who is pregnant. Use of the term father or paternal refers to a person who contributes sperm. View PDF Fact Sheet View complete answer

Can you take fungal medication while pregnant?

Oral Antifungal Medications A common antifungal medication is Lamisil. This medication is safe to take during pregnancy. However, it is best to avoid using it while breastfeeding as it is distributed in breast milk.
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Can a pregnant woman take anti fungal drugs?

Since antifungals are needed for prolonged periods ranging from 6–12 weeks, all oral agents are best avoided in 1st trimester especially in mild to moderate skin infections. Topical azoles and terbinafine are preferred during pregnancy. In recalcitrant/recurrent dermatophytosis, oral terbinafine is the safest choice.
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Is terbinafine safe in pregnancy?

Key Points Question Is terbinafine use in pregnancy associated with an increased risk of major malformations and spontaneous abortion? Findings This Danish nationwide cohort study included all pregnancies with use of oral and topical terbinafine in pregnancy during the study period 1997-2016 (n = 4065) as well as 40 650 unexposed pregnancies.

In propensity score–matched comparisons, no significant differences in the risk of major malformations or spontaneous abortion between oral terbinafine-exposed, topical terbinafine-exposed, and unexposed pregnancies were identified. Meaning Oral or topical terbinafine use in pregnancy does not appear to be associated with an increased risk of major malformations or spontaneous abortion.

Importance Terbinafine is a commonly used antifungal agent, but safety data of its use in pregnancy are limited. Objective To examine the association between oral and topical terbinafine exposure in pregnancy and the risk of major malformations and spontaneous abortion.

Design, Setting, and Participants A nationwide, registry-based cohort study was conducted in Denmark from January 1, 1997, to December 31, 2016, in a cohort of 1 650 649 pregnancies. Data analysis was performed from July 11 to October 20, 2019. Pregnancies were matched on propensity scores comparing oral terbinafine exposed vs unexposed (1:10 ratio), topical terbinafine exposed vs unexposed (1:10), and oral vs topical terbinafine exposed (1:1).

Exposures Filled prescriptions for oral or topical terbinafine. Main Outcomes and Measures Logistic regression was used to compute prevalence odds ratios for the primary outcome of major malformations and Cox proportional hazards regression was used to compute hazard ratios for the secondary outcome of spontaneous abortion.

Results Based on a cohort of 1 650 649 pregnancies, oral terbinafine-exposed (n = 891 pregnancies; mean age, 30.4 years) and topical terbinafine-exposed (n = 3174; mean age, 29.5 years) pregnancies were identified; up to a total of 40 650 unexposed pregnancies were included for the matched outcome analyses.

In propensity-matched comparisons of the risk of major malformations, the prevalence odds ratios were 1.01 (95% CI, 0.63-1.62) for oral terbinafine-exposed vs unexposed pregnancies (absolute risk difference, 0.04%; 95% CI, −1.69% to 1.76%), 1.08 (95% CI, 0.81-1.44) for topical terbinafine-exposed vs unexposed pregnancies (ARD, 0.26%; 95% CI, −0.73% to 1.26%), and 1.18 (95% CI, 0.61-2.29) for oral vs topical terbinafine-exposed pregnancies (ARD, 0.59%; 95% CI, −1.71% to 2.88%).

For the risk of spontaneous abortion, the hazard ratios were 1.06 (95% CI, 0.86-1.32) for oral terbinafine-exposed vs unexposed pregnancies (ARD, 0.13%; 95% CI, −1.97% to 2.24%), 1.04 (95% CI, 0.88-1.21) for topical terbinafine-exposed vs unexposed pregnancies (ARD, 0.17%; 95% CI, −0.64% to 0.98%), and 1.19 (95% CI, 0.84-1.70) for oral vs topical terbinafine-exposed (ARD, 1.13%; 95% CI, −2.23% to 4.50%) pregnancies.

Conclusions and Relevance Among pregnancies exposed to oral or topical terbinafine, no increased risk of major malformations or spontaneous abortion was identified. Terbinafine is an allylamine antifungal agent, available in both topical and systemic formulations and indicated for treatment of common infections, such as dermatophytic skin infections, onychomycosis, and other cutaneous dermatophytosis; off-label use includes treatment of sporotrichosis.1 – 3 Terbinafine works primarily as a fungicidal agent, as opposed to the fungistatic azole agents, by interfering with fungal ergosterol biosynthesis by inhibiting squalene epoxidase in the fungal cell membrane.

This mechanism of action leads to a deficiency of ergosterol and an intracellular accumulation of squalene, thus disrupting fungal membrane functioning and cell wall synthesis, resulting in fungal cell death.4 – 6 While terbinafine is a commonly used effective antifungal agent and generally well tolerated in the nonpregnant population, limited data exist on the fetal safety of use in pregnancy.2, 7 – 9 Data from animal studies do not suggest a fetal risk of terbinafine exposure in pregnancy, 10 but findings may not be applicable to the human response.

To our knowledge, only 1 preliminary report has previously provided data concerning the fetal safety of terbinafine use in pregnancy.11 The study included 54 exposed pregnancies, of whom 26 received oral formulations, and, despite the lack of statistical testing, the data presented were not suggestive of a potential fetal risk.

Furthermore, terbinafine is selective for fungal enzymes and has only minimal effects on mammalian cholesterol synthesis 12 ; in addition, when terbinafine is applied topically, less than 5% has been reported to be absorbed systemically.6, 13, 14 The limited human data do not allow a sufficient evaluation of the potential fetal risk with terbinafine use in pregnant women.

Consequently, until more data become available, caution is advised and use of terbinafine preferably should be avoided during pregnancy.1, 8, 15 Given the wide use of terbinafine to treat common fungal infections, the lack of fetal safety data on terbinafine exposure in pregnancy emerges as an issue of considerable relevance for routine clinical care.

  1. In a nationwide, registry-based cohort study from 1997 to 2016, we investigated the associated risk of the primary outcome major malformations and the secondary outcome spontaneous abortion with oral and topical terbinafine exposure in pregnancy with use of a propensity score–matched design.
  2. Data Sources and Study Design We conducted a historical registry-based cohort study from January 1, 1997, until December 31, 2016.

Data analysis was performed from July 11 to October 20, 2019. With use of the unique personal identification number that is assigned to all inhabitants of Denmark, we linked individual-level data from different nationwide registries. The source population was established on the basis of all pregnancies (ie, both pregnancies ending in live birth and fetal death) registered in the Medical Birth Registry and the National Patient Registry during the study period.16, 17 The Medical Birth Registry contains information of all live births and stillbirths since 1978, including birth-related and maternal-related variables.

  • The National Patient Registry contains information on pregnancies ending in spontaneous or induced abortive outcomes, as well as hospital care use and diagnoses assigned by the treating physician according to the International Statistical Classification of Diseases, Tenth Revision ( ICD-10 ).
  • The gestational age registered at the date of birth or abortive outcome allowed us to follow up the cohort from pregnancy onset.

The gestational age is estimated based on maternal report of the first day of the last menstrual period and subsequently ultrasonographically confirmed at the antenatal screening. Multiple pregnancy records with overlapping dates and records with implausible or missing information on gestational age were excluded.

  • The study cohorts for the analyses of major malformation were derived from pregnancies resulting in live births, and the study cohorts for the analyses of spontaneous abortion were derived from all pregnancies.
  • Demographic and socioeconomic information were obtained from the Danish Civil Registration System and Statistics Denmark.18 With use of the Registry of Medicinal Product Statistics, we obtained information on all filled prescriptions, including Anatomical Therapeutic Chemical (ATC) code and date of filled prescriptions, for terbinafine as well as for other drugs from all pharmacies in Denmark.19 The study was approved by the Danish Data Protection Agency.

Ethical approval and informed consent are not required for registry-based research in Denmark. The study included 3 comparison groups for the analyses of the risk of major malformations and spontaneous abortion. These groups included oral terbinafine-exposed pregnancies, topical terbinafine-exposed pregnancies, and unexposed pregnancies.

With use of separate propensity score matching, we compared oral terbinafine-exposed vs unexposed pregnancies, topical terbinafine-exposed vs unexposed pregnancies, and oral terbinafine- vs topical terbinafine-exposed pregnancies in distinct cohorts. Exposure was defined as at least 1 filled prescription for oral terbinafine (ATC: D01BA02) or topical terbinafine (ATC: D01AE15) identified via the Registry of Medicinal Product Statistics.

The first day of exposure was defined by the date of first filled prescription (index date). We defined the exposure time windows according to the specific outcome analyses: the first trimester for the analyses of major malformations and before 22 completed gestational weeks for spontaneous abortion.

Women with a filled prescription for oral terbinafine during the 14 days prior to pregnancy onset were allowed inclusion in the oral terbinafine-exposed pregnancy group. For the topical terbinafine-exposed pregnancy group, we excluded pregnancies in case of filled prescriptions for oral terbinafine within 6 months prior to pregnancy onset.

The unexposed comparison group consisted of pregnant women with no filled prescriptions for oral or topical terbinafine or any other topical or systemic antifungal drugs (ATC: D01A, D01BA, J02AB, and J02AC) in pregnancy as well as in 1 year prior to pregnancy onset.

For a preplanned sensitivity analysis of the association between oral terbinafine and major malformations, we defined an additional comparative group of pregnant women with filled prescriptions for oral terbinafine in the time interval from 1 year until 3 months before conception but with no filled prescription in pregnancy or in the 3 months prior to pregnancy onset.

With use of the National Patient Registry, we identified outcome cases diagnosed via inpatient or outpatient care. The primary outcome was major malformations, defined as an infant who, within the first year of life, was diagnosed with a major malformation in accordance with the European Surveillance of Congenital Anomalies classification system of subgroups of major congenital anomalies.20 We excluded major malformations with known causes (eg, Down syndrome and fetal alcohol syndrome) and minor defects according to the European Surveillance of Congenital Anomalies exclusion list (eMethods in the Supplement ).20, 21 The secondary outcome was spontaneous abortion, defined as a pregnancy ending in fetal death before 22 completed gestational weeks ( ICD – 10 code O021 or O03).22 Spontaneous abortions occurring earlier than gestational week 6 were not included owing to the risk of misclassification of these very early abortions in the registry.

  • We used propensity score matching to take into account baseline characteristics that could be associated with the risk of the outcomes.
  • For each outcome analysis, individual propensity score estimations and matchings were performed.23 The propensity scores were estimated using a logistic regression model and included all variables reported in eTable 1 in the Supplement,

Based on the propensity scores, we created distinct matched cohorts of oral terbinafine-exposed vs unexposed pregnancies (matched in a 1:10 ratio), topical terbinafine-exposed vs unexposed pregnancies (1:10), and oral terbinafine-exposed vs topical terbinafine-exposed pregnancies (1:1).

  1. Matching was performed using the greedy nearest neighbor matching algorithm (caliper width 0.02 on the propensity-score scale).24, 25 Three comparative study cohorts were constructed for both the analyses of major malformations and spontaneous abortion.
  2. We imputed missing values (0%-4.1% missing; eTable 2 in the Supplement ) using the mode value.

The quality of matching was assessed by standardized differences. A covariate was considered well balanced between matched groups if the standardized difference was less than 10%. A logistic regression model was used to compute prevalence odds ratios (ORs) for the associated risk of major malformations.

A Cox proportional hazards regression model was used to compute hazard ratios (HRs) for the associated risk of spontaneous abortion, with gestational age (days) as the underlying time scale. We used a Wald test to assess the interaction between time scale and exposure. Pregnancies were censored if abortive outcome occurred on that date other than spontaneous abortion.

For the exposed vs unexposed pregnancies comparison analyses of spontaneous abortion, the gestational day on the first day of terbinafine exposure (index date) was added as an additional matching criterion, that is, unexposed pregnancies were eligible as matches if the pregnancy had lasted until the index date.

Follow-up for both the terbinafine-exposed and unexposed pregnancies started at the respective index date. For the oral vs topical terbinafine comparison analysis of spontaneous abortion, we added the gestational week of the first day of exposure as a matching criterion, and pregnancies were followed up from their respective index date.

Preplanned sensitivity analyses of the association between oral terbinafine exposure and major malformations included comparing pregnancies with previous oral terbinafine use before pregnancy onset (propensity score matched in a 1:2 ratio), a subgroup analysis of pregnancies with filled prescriptions in gestational weeks 4 to 10 (a time during which a teratogenic effect in general is considered to be most pronounced, if present), exposures occurring at any time in pregnancy, pregnancies exposed only in the second and third trimesters, subgroup analyses of singleton pregnancies, and exclusion of pregnancies with filled prescriptions in the 14 days prior to pregnancy onset.

Furthermore, we assessed the association between oral terbinafine use and risk of spontaneous abortion compared with unexposed by subgroup analyses of pregnancies with filled prescriptions later than gestational week 5 and excluding pregnancies in which the prescriptions were filled within the 14 days prior to pregnancy onset.

All measures of associations are reported with the corresponding 95% CIs. All statistical tests were 2-sided; we considered CIs not overlapping 1.0 to indicate statistical significance. SAS software, version 9.4 (SAS Institute Inc), was used for all analyses.

  • The Figure displays a flowchart of the cohort selection and construction of the study cohorts.
  • The source cohort consisted of a total of 1 650 649 pregnancies.
  • Subsequent to the application of the respective exclusion criteria and exposure definitions, 1 030 873 pregnancies were eligible for inclusion for the analyses of major malformations and 1 419 951 pregnancies were eligible for inclusion for the analyses of spontaneous abortion; eTable 3 and eTable 4 in the Supplement report the unmatched baseline characteristics.

Of these pregnancies, oral terbinafine- (n = 891 pregnancies; mean age, 30.4 years) and topical terbinafine- (n = 3174; mean age, 29.5 years) exposed pregnancies were identified. Up to a total of 40 650 unexposed pregnancies were included for the matched outcome analyses.

Following the propensity score estimation and matching, the cohorts used in the analyses of major malformations included 5742 pregnancies for the comparison of oral terbinafine exposed vs unexposed (matched in a 1:10 ratio), 16 236 pregnancies for topical terbinafine exposed vs unexposed (1:10 ratio), and 1020 pregnancies for oral vs topical terbinafine exposed (1:1 ratio).

The matched cohorts for the analyses of spontaneous abortion included 9801 pregnancies for oral terbinafine exposed vs unexposed, 34 914 pregnancies for topical terbinafine exposed vs unexposed, and 1234 pregnancies for oral vs topical terbinafine exposed Table 1 and eTable 5 in the Supplement report the baseline characteristics of the matched cohorts for the primary outcome major malformations and secondary outcome spontaneous abortion, respectively.

  • Across all matched cohorts, baseline characteristics were well balanced between groups with standardized differences less than 10% (eTable 6 and eTable 7 in the Supplement ).
  • Table 2 reports the matched analyses of the primary outcome major malformations for the 3 comparative study cohorts.
  • For the comparison of pregnancies exposed to oral terbinafine vs unexposed, infants diagnosed with a major malformation occurred in 20 pregnancies (3.8%) exposed to oral terbinafine compared with 198 unexposed pregnancies (3.8%) (prevalence OR, 1.01; 95% CI, 0.63-1.62), corresponding to an absolute risk difference (ARD) of 0.04% (95% CI, −1.69% to 1.76%).

For the topical terbinafine-exposed vs unexposed pregnancies comparison, a major malformation occurred in 53 pregnancies (3.6%) exposed to topical terbinafine compared with 419 unexposed pregnancies (3.3%) (prevalence OR, 1.08; 95% CI, 0.81-1.44), with an ARD of 0.26% (95% CI, −0.73% to 1.26%).

In the comparison of oral terbinafine- vs topical terbinafine-exposed pregnancies, a major malformation occurred in 20 pregnancies (3.9%) exposed to oral terbinafine vs 17 pregnancies (3.3%) exposed to topical terbinafine (prevalence OR, 1.18; 95% CI, 0.61-2.29), with an ARD of 0.59% (95% CI, −1.71% to 2.88%).

Table 3 reports the matched analyses of the secondary outcome spontaneous abortion for the 3 comparative study cohorts. The proportional hazards assumption was fulfilled for all analyses on spontaneous abortion. For the comparison of pregnancies exposed to oral terbinafine vs unexposed (median index date of gestational day 11; interquartile range, −2 to 28), spontaneous abortion occurred in 93 pregnancies (10.4%) exposed to oral terbinafine compared with 918 unexposed pregnancies (10.3%) (HR, 1.06; 95% CI, 0.86-1.32), corresponding to an ARD of 0.13% (95% CI, −1.97% to 2.24%).

For the topical terbinafine-exposed vs unexposed pregnancies comparison (median index date, day 66; IQR, 31-111), spontaneous abortion occurred in 166 pregnancies (5.2%) exposed to topical terbinafine compared with 1607 unexposed pregnancies (5.1%) (HR, 1.04; 95% CI, 0.88-1.21), with an ARD of 0.17% (95% CI, −0.64% to 0.98%).

In the comparison of oral terbinafine- vs topical terbinafine-exposed pregnancies (median index date, oral: day 20; IQR, 8-36; topical, day 20; IQR, 7-37), spontaneous abortion occurred in 66 pregnancies with oral terbinafine exposure (10.7%) vs 59 pregnancies (9.6%) with topical exposure (HR, 1.19; 95% CI, 0.84-1.70), with an ARD of 1.13% (95% CI −2.23% to 4.50%).

Table 4 reports the results of the sensitivity analyses of the association between oral terbinafine exposure in pregnancy and risk of major malformations. No statistically significant associations were identified in any of these sensitivity analyses. Sensitivity analyses of the association between oral terbinafine use and risk of spontaneous abortion did not provide any statistically significant results (eTable 8 in the Supplement ).

In this nationwide cohort study, we found no statistically significant differences in the risk of major malformations or spontaneous abortion comparing oral terbinafine-exposed, topical terbinafine-exposed, and unexposed pregnancies in propensity score–matched analyses.

  1. Previous data have not allowed for a proper assessment of the fetal risk of terbinafine use among pregnant women.
  2. Consequently, use of systemic terbinafine during pregnancy is currently not advised, and the US Food and Drug Administration recommends that terbinafine therapy should not be initiated during pregnancy.8, 15, 26 Among the 54 pregnant women exposed to terbinafine enrolled in 1 study, 1 major malformation and 3 spontaneous abortions were observed.11 Although no reports of statistical testing were presented in the published abstract, the authors concluded that the preliminary results were suggestive of no increased fetal risk.

As such, the results of our study support this notion as well as the preclinical safety data, while expanding the body of available epidemiologic fetal safety data. Oral terbinafine exposure in pregnancy was not associated with an increased risk of major malformations compared with unexposed pregnancies as well as compared with pregnancies exposed to topical terbinafine.

  • Several sensitivity analyses were carried out, none of which provided evidence of a significant association.
  • Given the relative rarity of the individual malformations, the power to address the risk of specific malformations in cohort studies is limited.21, 27 Although our results may provide reassurance for pregnancies exposed to oral terbinafine by reporting no overall increased risk of major malformations, we cannot exclude a potential increased risk of a specific malformation.

According to current guidelines, topical terbinafine can be safely used during pregnancy because of limited systemic absorption.1, 28 We are not aware of any previous studies investigating the specific fetal risk of topical terbinafine use in pregnant women.

  • Thus, to our knowledge, this study provides the first data from real-world routine clinical practice and reports no increased risk of major malformation and spontaneous abortion with topical terbinafine use in pregnancy compared with unexposed pregnancies.
  • Although this study may help inform clinicians, patients, and drug regulatory authorities regarding the fetal safety of terbinafine use in pregnancy when clinically indicated, the results should be confirmed in other populations.

Strengths and Limitations The study has several strengths and limitations. The data were derived from a cohort of all pregnancies in Denmark from 1997 through 2016 and included all filled prescriptions for terbinafine in this period, making the results generalizable to similar populations.

  1. The nationwide registries facilitated an independent and detailed assessment of exposures, outcomes, and covariates throughout the study period.
  2. The registrations of major malformations and spontaneous abortions in the National Patient Registry have high validity with positive predictive values of 88% and 97%, respectively.29, 30 Use of oral and topical terbinafine was based on filled prescriptions.

If the pregnant women did not adhere to the dispensed drug, the association with the outcome of the exposed pregnancies would be biased toward the unexposed pregnancies. In addition, although oral terbinafine is a prescription-only drug, topical terbinafine is available as an over-the-counter preparation (29.2% of the supply was personally identifiable during the study period 31 ); this availability could also introduce misclassification of exposure, which would bias the results toward the association with topical terbinafine exposure.

  1. To minimize the risk of this potential misclassification, we excluded pregnancies with use of any antifungal preparations in pregnancy as well as prior to pregnancy onset.
  2. To increase the probability of isolating any differential associations to the outcomes, we used propensity score matching to take into account a wide range of characteristics that might have influenced the associations.

Covariates were well balanced across all matched cohorts. However, residual confounding cannot be fully excluded, particularly to the extent that potential confounding factors not adjusted for (eg, other drug use or body mass index) were differently distributed between matched groups and not accounted for through adjustment for correlated variables (ie, proxies) included in the propensity score.

  1. Given the propensity-matched comparison design, results from the 3 study cohorts should primarily be interpreted separately.
  2. A main concern of observational cohort studies reporting null findings is inherited unadjusted factors that could mask a true association.
  3. Given our large study size, including all pregnancies in Denmark, and that such factors would need to be common or strongly associated with the exposure and inversely associated with the outcome, we expect such residual confounding to be limited or unlikely.

Another potential confounding issue would be if the indications for treatment with terbinafine were associated with the outcomes. The analyses of oral vs topical terbinafine-exposed pregnancies did not support this notion. Still, confounding by severity of the fungal infections cannot be ruled out, since oral terbinafine use may likely be associated with more-pronounced infections.

Information on the indication for a prescribed drug is unattainable in the Danish registries. Under the assumption that the fungal infections were present also during the first trimester, and thus potentially teratogenic in relation to the risk of congenital malformations, the sensitivity analysis of pregnancies exposed to oral terbinafine later in pregnancy was not suggestive of this type of confounding.

This nationwide cohort study found no increased risk of major malformations or spontaneous abortion among pregnancies exposed to oral or topical terbinafine. These results suggest that terbinafine can be used relatively safely in both oral and topical formulations during pregnancy.

  • Accepted for Publication: January 16, 2020.
  • Corresponding Author: Niklas Worm Andersson, MD, Department of Clinical Pharmacology, Copenhagen University Hospital Bispebjerg and Frederiksberg, Copenhagen NV, Denmark ( [email protected] ).
  • Published Online: March 4, 2020.
  • Doi: 10.1001/jamadermatol.2020.0142 Author Contributions: Drs Andersson and Andersen had full access to all of the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis.

Concept and design: All authors. Acquisition, analysis, or interpretation of data: All authors. Drafting of the manuscript: Andersson. Critical revision of the manuscript for important intellectual content: All authors. Statistical analysis: Andersson, Andersen.

  1. Administrative, technical, or material support: Thomsen.
  2. Supervision: Thomsen, Andersen.
  3. Conflict of Interest Disclosures: Dr Thomsen reports receiving grants and personal fees from Novartis outside the submitted work.
  4. No other disclosures were reported.2.
  5. Fuller LC, Barton RC, Mohd Mustapa MF, Proudfoot LE, Punjabi SP, Higgins EM.

British Association of Dermatologists’ guidelines for the management of tinea capitis 2014.  Br J Dermatol,2014;171(3):454-463. doi: 10.1111/bjd.13196  PubMed Google Scholar Crossref 3. Kauffman CA, Bustamante B, Chapman SW, Pappas PG; Infectious Diseases Society of America.

Clinical practice guidelines for the management of sporotrichosis: 2007 update by the Infectious Diseases Society of America.  Clin Infect Dis,2007;45(10):1255-1265. doi: 10.1086/522765  PubMed Google Scholar Crossref 10. Briggs GG, Freeman RK, Yaffe SJ. Drugs in Pregnancy and Lactation: A Reference Guide to Fetal and Neonatal Risk,

Philadelphia, PA: Lippincott Williams & Wilkins; 2012.13. Schaefer C, Peters PW, Miller RK. Drugs During Pregnancy and Lactation: Treatment Options and Risk Assessment, Cambridge, MA: Academic Press; 2014.16. Knudsen LB, Olsen J. The Danish Medical Birth Registry.

 Dan Med Bull,1998;45(3):320-323. PubMed Google Scholar 17. Lynge E, Sandegaard JL, Rebolj M. The Danish National Patient Register.  Scand J Public Health,2011;39(7 suppl):30-33. Google Scholar Crossref 19. Wallach Kildemoes H, Toft Sørensen H, Hallas J. The Danish National Prescription Registry.

 Scand J Public Health,2011;39(7 suppl):38-41. Google Scholar Crossref 21. Huybrechts KF, Bateman BT, Hernández-Díaz S. Use of real-world evidence from healthcare utilization data to evaluate drug safety during pregnancy.  Pharmacoepidemiol Drug Saf,2019;28(7):906-922.

doi: 10.1002/pds.4789  PubMed Google Scholar Crossref 27. Mitchell AA. Studies of drug-induced birth defects. In: Strom BL, Kimmel SE, Hennessy S, eds. Pharmacoepidemiology, Fifth Edition. Indianapolis: John Wiley & Sons, Ltd; 2012:487-504. doi: 10.1002/9781119959946.ch28  29. Larsen H, Nielsen GL, Bendsen J, Flint C, Olsen J, Sørensen HT.

Predictive value and completeness of the registration of congenital abnormalities in three Danish population-based registries.  Scand J Public Health,2003;31(1):12-16. doi: 10.1080/14034940210134194  PubMed Google Scholar Crossref 30. Schmidt M, Schmidt SAJ, Sandegaard JL, Ehrenstein V, Pedersen L, Sørensen HT.
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Can fluconazole lead to miscarriage?

Fluconazole Linked to Higher Rates of Miscarriage When Used During Pregnancy ​ ​By staff Montreal, Quebec— Pharmacists might want to caution expectant mothers about the risks of using fluconazole to treat vaginal yeast infections. in CMAJ (Canadian Medical Association Journal) linked the oral antifungal drug to higher rates of miscarriage.

Background information in the article adds that although topical treatments are first line for pregnant women with fungal infections, oral fluconazole is commonly used during pregnancy, as well.To reach their conclusions, University of Montreal–led researchers looked at data on 441,949 pregnancies from the Quebec Pregnancy Cohort between 1998 and 2015.

That information was linked to filled prescriptions listed in the Quebec Prescription Drug Insurance database. “Our study shows that taking any dose of oral fluconazole while pregnant may be associated with a higher chance of miscarriage,” explained Anick Bérard, PhD, of the Université de Montréal in Quebec.

“Taking higher doses of fluconazole over 150 mg in early pregnancy may be linked to a higher chance of a newborn with a heart defect.”Specifically, the study team sought to assess the effect of exposure to low and high doses of fluconazole during pregnancy on the occurrence of spontaneous abortions, major congenital malformations, and stillbirths.For purposes of the study, low-dose was defined as 150 mg or less, while high dose was defined as greater than 150 mg.

The researchers note that most, 69.5%, women exposed to fluconazole in pregnancy received the common single therapeutic dose of 150 mg.Results indicate that use of oral fluconazole during early pregnancy was associated with an increased risk of spontaneous abortion compared with no exposure (adjusted odds ratio for 345 cases exposed to low-dose treatment 2.23, 95% confidence interval, 1.96-2.54; adjusted OR for 249 cases exposed to high-dose treatment 3.20, 95% CI, 2.73-3.75).

Researchers report, however, that use of fluconazole during the first trimester did not increase the risk of overall major congenital malformations, although exposure to a high dose of the drug early in pregnancy was associated with an increased risk of cardiac septal closure anomalies (adjusted OR 1.81, 95% CI, 1.04-3.14; 13 exposed cases) versus no exposure.

The study found no association between exposure to fluconazole during pregnancy and the risk of stillbirth.”Any maternal exposure to fluconazole during pregnancy may increase risk of spontaneous abortion and doses higher than 150 mg during the first trimester may increase risk of cardiac septal closure anomalies,” study authors conclude, adding that their results are consistent with other research.
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Can fungal infection harm pregnancy?

A: No. A yeast infection won’t affect your developing baby – that’s why we don’t treat yeast infections that don’t have symptoms. However, most symptomatic yeast infections get worse when left untreated. This means more itching, redness, and inflammation.
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Is fungal infection common during pregnancy?

What’s a yeast infection? Vulvovaginal candidiasis, or moniliasis, is a yeast infection of the vulva and vagina. Yeast is a type of fungus. The yeast that most often causes these infections is Candida albicans, but other types of yeast — including Candida glabrata and Candida tropicalis — can also be responsible.

About three out of every four women will have at least one yeast infection in their lifetime, according to American Family Physician, Up to 45 percent will get two or more infections. During pregnancy, Candida (and the infections it causes) is even more common. According to one study, about 20 percent of women have Candida yeast in their vagina normally.

That number goes up to 30 percent during pregnancy. Yeast is more likely to cause infection during pregnancy due to hormone fluctuations. Because you can pass the yeast to your baby during delivery, it’s important to get treated.
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What is the most effective antifungal?

Butenafine may be more effective at treating fungal infections than other antifungals that prevent the fungus from growing (e.g., clotrimazole). That’s because it kills the fungus.
View complete answer

Is ketoconazole better than clotrimazole?

Abstract – The effects of two topical cream formulations containing clotrimazole 1% and ketoconazole 2%, respectively, were clinically compared in a double-blind, randomized manner for a 28-day therapy of interdigital tinea pedis in 106 treated patients.

  1. Etoconazole was to be used twice daily whereas clotrimazole was administered only once daily.
  2. The primary response criterion defined as the number of patients with cure or improvement after 28 treatment days was comparable with 62.0% vs.64.0% (clotrimazole vs.
  3. Ketoconazole) for the full analysis set of 100 (50 vs.50) patients.

The mycological response revealed a negative culture and microscopy in 53.1% vs.52.1% of the patients after 14, in 76.0% vs.79.2% after 28, and in 83.7% vs.76.9% after 56 days of observation, indicating a possibly better long-term efficacy of clotrimazole.

The development of the overall score of tinea-related signs and symptoms did not show relevant differences between the two drugs and continuously decreased from 11+/-5 in both groups at baseline to 2+/-2 vs.2+/-1 at day 56. As to the remission and improvement rates of single symptoms, better results were obtained under clotrimazole than under ketoconazole particularly for pruritus (97.8 vs.89.6%) and burning/stinging (97.5 vs.89.4%) which both are perceived as most bothersome by the patients.

Furthermore, both substances appeared as comparably safe and well tolerable (8 vs.7 adverse events with only 1 vs.3 drug related). In conclusion, a successful therapy of tinea pedis can be achieved with both clotrimazole and ketoconazole within 28 days of treatment and once-daily clotrimazole is equally effective as twice-daily ketoconazole with favourable influences on the most irritating symptoms of the disease.
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Which is safer itraconazole or fluconazole?

Efficacy of itraconazole versus fluconazole in vaginal candidiasis – PubMed Objective: To compare the efficacy of fluconazole 150mg single dose and itraconazole 200mg twice for one day in the treatment of acute vulvovaginal candidiasis. Methods: The study was carried out at the Department of Dermatology, PNS Shifa Hospital, Karachi, from March, 2008 to February 2009 and comprised 60 women with clinical and mycological diagnosis of vaginal candidiasis.

Diagnosis was based on history, clinical examination and relevant investigations. The women were divided into two equal groups. After initial assessment, Group 1 was treated with capsule fluconazole 150mg stat, and Group 2 with capsule itraconazole 200mg twice for one day. They were assessed clinically for cure and relapse on day 7 and 21 respectively.

All findings were recorded in the proforma. Data was analysed using SPSS 12. Results: The overall clinical evaluation showed 70% (n = 21) cure rate with itraconazole and 50% (n = 15) with fluconazole. In Group-1, 7 (23.33%) and in Group-2 8 (26.6%) showed some improvement, while 2 (6.66%) in Group 1, and 7 (23%) in Group 2 failed to respond.
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Can a pregnant woman take anti fungal drugs?

Since antifungals are needed for prolonged periods ranging from 6–12 weeks, all oral agents are best avoided in 1st trimester especially in mild to moderate skin infections. Topical azoles and terbinafine are preferred during pregnancy. In recalcitrant/recurrent dermatophytosis, oral terbinafine is the safest choice.
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Is it safe to use miconazole while pregnant?

This sheet is about exposure to miconazole or clotrimazole in pregnancy and while breastfeeding. This information should not take the place of medical care and advice from your healthcare providers. What is miconazole? Miconazole is a medication used to treat fungal infections. Miconazole is a cream used to treat skin and vaginal infections. Common trade names for miconazole include Monistat®, Micatin® and Mitrazole®. What is clotrimazole? Clotrimazole is also a medication used to treat fungal infections. Like miconazole, clotrimazole is available as a cream to treat skin and vaginal infections. Brand names of clotrimazole Femcare®, Lotrimin®, and Mycelex®. I just found out I am pregnant. Should I stop using miconazole or clotrimazole? Sometimes when people find out they are pregnant, they think about changing how they take their medication, or stopping their medication altogether. However, it is important to talk with your healthcare providers before making any changes to how you take this medication. Your healthcare providers can talk with you about the benefits of treating your condition and the risks of untreated illness during pregnancy. What should I do if I think I have a vaginal yeast infection while pregnant? People are more likely to get yeast infections during pregnancy than at other times. If you think you have a vaginal yeast infection, it is important to see your healthcare provider to be sure the infection is yeast before trying to treat it on your own. If you have another type of infection, you may need different treatment. I use miconazole or clotrimazole. Can it make it harder for me to become pregnant? Using miconazole or clotrimazole is not expected to make it harder to become pregnant. Does using miconazole or clotrimazole increase the chance for miscarriage? Miscarriage can occur in any pregnancy. One study found a small increased chance for miscarriage with miconazole and clotrimazole, but there were several problems with this study that could have affected the results. Other studies have not found that miconazole or clotrimazole increases the chance for miscarriage. Does taking miconazole or clotrimazole increase the chance of birth defects? Every pregnancy starts out with a 3-5% chance of having a birth defect. This is called the background risk. Topical (used on the skin) or vaginal medications enter the body in lower amounts than oral (pill) medications. This means less medication reaches the developing baby. Since topical and vaginal miconazole and clotrimazole are not well absorbed, they are unlikely to be a concern for the pregnancy. Most studies have shown that miconazole or clotrimazole at low doses (<400 mg/day) does not increase the chance of birth defects. Does using miconazole or clotrimazole increase the chance of other pregnancy related problems? Studies have not been done to see if miconazole or clotrimazole increases the chance for pregnancy-related problems such as preterm delivery (birth before week 37) or low birth weight (weighing less than 5 pounds, 8 ounces at birth). Does using miconazole or clotrimazole in pregnancy affect future behavior or learning for the child? Studies have not been done to see if miconazole or clotrimazole can cause behavior or learning issues for the child. Breastfeeding while using miconazole or clotrimazole: There are currently no studies looking at miconazole or clotrimazole use during breastfeeding. However, because only small amounts of the medication could pass into breastmilk when miconazole or clotrimazole is used topically, breastfeeding is not expected to be a concern. Miconazole and clotrimazole creams have been used directly on infants under the care of a healthcare provider to treat fungal infections. Talk to your healthcare provider about your breastfeeding questions. If a male uses miconazole or clotrimazole, could it affect fertility (ability to get partner pregnant) or increase the chance of birth defects? There are no studies looking at fertility or possible risks to a pregnancy when the father uses miconazole or clotrimazole. In general, exposures that fathers or sperm donors have are unlikely to increase the risks to a pregnancy. For more information, please see the MotherToBaby fact sheet Paternal Exposures at https://mothertobaby.org/fact-sheets/paternal-exposures-pregnancy/, Please click here for references. OTIS/MotherToBaby encourages inclusive and person-centered language. While our name still contains a reference to mothers, we are updating our resources with more inclusive terms. Use of the term mother or maternal refers to a person who is pregnant. Use of the term father or paternal refers to a person who contributes sperm. View PDF Fact Sheet View complete answer

Is itraconazole safe in pregnancy?

The capsule or tablet should not be used to treat onychomycosis in pregnant women or those who are planning to get pregnant.
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Are oral antifungals safe for pregnancy?

The data indicated that oral fluconazole exposure during pregnancy might slightly increase the risk of congenital heart defects and limb defects relative to the general population; oral itraconazole during pregnancy might increase the risk of eye defects.
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