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Drug Safety in Pregnancy


Ravindu Gunatilake

, MD, Valley Perinatal Services;

Avinash S. Patil

, MD, University of Arizona College of Medicine

Reviewed/Revised Oct 2023
Topic Resources

Medications may be required for various indications during pregnancy. The most commonly used medications include antiemetics, antacids, antihistamines, analgesics, antimicrobials, diuretics, antidepressants, and tranquilizers. Substance use and misuse is also common. Despite this trend, firm evidence-based guidelines for safe use of medications during pregnancy are still lacking.

Regulatory Information about Drug Safety During Pregnancy

Until the 2010s, the U.S. Food and Drug Administration (FDA) classified over-the-counter (OTC) and prescription drugs into 5 categories of safety for use during pregnancy (A, B, C, D, X). However, few well-controlled studies of therapeutic drugs have been done in pregnant women. Most information about drug safety during pregnancy is derived from animal studies, uncontrolled studies, and postmarketing surveillance. Consequently, the FDA classification system led to confusion and difficulty applying available information to clinical decisions. In December 2014, the FDA responded by requiring that the pregnancy categories A, B, C, D, and X be removed from the labeling of all drugs.

Instead of categories, the FDA now requires that drug labels provide information about the specific drug in a consistent format (called the final rule, or Pregnancy and Lactation Labeling (Drugs) Final Rule [PLLR]).

The information required by the FDA has 3 subsections:

  • Pregnancy: Information relevant to the use of the drug in pregnant women (eg, dosing, fetal risks) and information about whether there is a registry that collects and maintains data on how pregnant women are affected by the drug

  • Lactation: Information about using the drug while breastfeeding (eg, the amount of drug in breast milk, potential effects on the breastfed child)

  • Females and males of reproductive potential: Information about pregnancy testing, contraception, and infertility as it relates to the drug

The pregnancy and lactation subsections each include 3 subheadings (risk summary, clinical considerations, and data) that provide more detail. The final rule does not apply to nonprescription (over-the-counter) drugs.

Drug Transfer and Metabolism During Pregnancy

During pregnancy, medications are often required to treat certain disorders. In general, when potential benefit outweighs known risks, medications may be considered for treatment of disorders during pregnancy.

Not all medications or other substances in the maternal circulation cross the placenta (transfer) to the fetus. Some drugs that cross the placenta may have a direct toxic effect or a teratogenic effect. Drugs that do not cross the placenta may still harm the fetus by

  • Constricting placental vessels and thus impairing gas and nutrient exchange

  • Producing severe uterine hypertonia that results in anoxic injury

  • Altering maternal physiology (eg, causing hypotension)

For a list of some medications with adverse effects during pregnancy, see table .

Drugs diffuse across the placenta similarly to the way they cross other epithelial barriers (see Absorption Drug Absorption Drug absorption is determined by the drug’s physicochemical properties, formulation, and route of administration. Dosage forms (eg, tablets, capsules, solutions), consisting of the drug plus... read more ). Whether and how quickly a drug crosses the placenta depend on the drug’s molecular weight, extent of its binding to another substance (eg, carrier protein), area available for exchange across the placental villi, and amount of drug metabolized by the placenta. Most drugs with a molecular weight of < 500 daltons readily cross the placenta and enter the fetal circulation. Substances with a high molecular weight (eg, protein-bound drugs) usually do not cross the placenta. One exception is immune globulin G, which may be used to treat disorders such as fetal alloimmune thrombocytopenia or fetal hemachromatosis. Generally, equilibration between maternal blood and fetal tissues takes at least 30 to 60 minutes; however, some drugs do not reach similar concentrations in the maternal and fetal circulation.

A drug’s effect on the fetus is determined largely by fetal age at exposure, placental permeability, maternal factors, drug potency, and drug dosage.

Fetal age affects the type of drug effect:

The overall rate of major structural birth defects in the United States is approximately 3% (1 References Medications may be required for various indications during pregnancy. The most commonly used medications include antiemetics, antacids, antihistamines, analgesics, antimicrobials, diuretics... read more ); most malformations result from genetic, environmental, multifactorial, or unknown causes. It is difficult to determine the overall rate of congenital malformations caused by therapeutic drugs. As an example, in one study of 5504 cases of birth defects, only 20% had a definite cause and < 1% of cases with known causes were due to medications (2 References Medications may be required for various indications during pregnancy. The most commonly used medications include antiemetics, antacids, antihistamines, analgesics, antimicrobials, diuretics... read more ).


Vaccines During Pregnancy

The CDC recommends COVID-19 vaccination COVID-19 Vaccine COVID-19 vaccines provide protection against COVID-19, the disease caused by infection with the SARS-CoV-2 virus. Vaccination is the most effective strategy to prevent severe illness and death... read more for all people 5 years and older, including people who are pregnant, breastfeeding, trying to get pregnant, or might become pregnant in the future. Evidence about the safety and effectiveness of COVID-19 vaccination during pregnancy has been growing. These data suggest that the benefits of receiving a COVID-19 vaccine outweigh any known or potential risks of vaccination during pregnancy. (See also CDC: COVID-19 Vaccines While Pregnant or Breastfeeding.)

In August 2023, the US Food and Drug Administration approved use of a respiratory syncytial virus (RSV) Respiratory Syncytial Virus (RSV) and Human Metapneumovirus Infections Respiratory syncytial virus and human metapneumovirus infections cause seasonal lower respiratory tract disease, particularly in infants and young children. Disease may be asymptomatic, mild... read more vaccine in pregnant individuals between 32 to 36 weeks of gestation, with a warning to avoid use prior to 32 weeks. Clinical trials have found increased rates of preterm birth, preeclampsia in pregnant patients, and low birth weight and jaundice in infants following prenatal administration of RSV vaccine versus placebo; further study is needed to evaluate these potential risks (3 References Medications may be required for various indications during pregnancy. The most commonly used medications include antiemetics, antacids, antihistamines, analgesics, antimicrobials, diuretics... read more ).

Other vaccines should be reserved for situations in which the woman or fetus is at significant risk of exposure to a hazardous infection and risk of adverse effects from the vaccine is low. Vaccinations for cholera Prevention Cholera is an acute infection of the small bowel by the gram-negative bacterium Vibrio cholerae, which secretes a toxin that causes copious watery diarrhea, leading to dehydration, oliguria... read more , hepatitis A Hepatitis A (HepA) Vaccine There are two hepatitis A vaccines; both provide long-term protection against hepatitis A. For more information, see Hepatitis A Advisory Committee on Immunization Practices Vaccine Recommendations... read more , hepatitis B Hepatitis B (HepB) Vaccine The hepatitis B vaccine is 80 to 100% effective in preventing infection or clinical hepatitis B in people who complete the vaccine series. For more information, see Hepatitis B Advisory Committee... read more , measles, mumps Measles, Mumps, and Rubella (MMR) Vaccine The measles/mumps/rubella vaccines (MMR vaccines) effectively protect against all 3 infections ( measles, mumps, rubella). Historically, people who are given the MMR vaccine according to the... read more , plague, poliomyelitis Poliomyelitis Vaccine Extensive vaccination has almost eradicated polio worldwide. But cases still occur in areas with incomplete immunization, such as sub-Saharan Africa and southern Asia. There are 3 serotypes... read more , rabies Prevention , typhoid Vaccination Typhoid fever is a systemic disease caused by the gram-negative bacterium Salmonella enterica serotype Typhi (S. Typhi). Symptoms are high fever, prostration, abdominal pain, and... read more Vaccination , and yellow fever Prevention may be given during pregnancy if risk of infection is substantial.

Live-virus vaccines should not be given to women who are or may be pregnant. Rubella vaccine Measles, Mumps, and Rubella (MMR) Vaccine The measles/mumps/rubella vaccines (MMR vaccines) effectively protect against all 3 infections ( measles, mumps, rubella). Historically, people who are given the MMR vaccine according to the... read more , an attenuated live-virus vaccine, may cause subclinical placental and fetal infection. However, no defects in neonates have been attributed to rubella vaccine, and women vaccinated inadvertently during early pregnancy need not be advised to terminate pregnancy based solely on theoretical risk from the vaccine. Varicella vaccine Varicella Vaccine Varicella vaccination provides effective protection against varicella (chickenpox). It is not known how long protection against varicella lasts. But, live-virus vaccines, like the varicella... read more is another attenuated live-virus vaccine that can potentially infect the fetus; risk is highest between 13 weeks and 22 weeks gestation. This vaccine is contraindicated during pregnancy.

Antivirals During Pregnancy

Some antivirals (eg, zidovudine and ritonavir for HIV infection) have been safely used during pregnancy for many years. However, some antivirals may have significant risks for the fetus.

Antivirals for influenza Influenza Influenza is a viral respiratory infection causing fever, coryza, cough, headache, and malaise. Mortality is possible during seasonal epidemics, particularly among high-risk patients (eg, those... read more should be started as soon as possible, without waiting for test results to confirm the diagnosis, because treatment within 48 hours of illness onset is most effective. However, treatment at any point during the infection reduces risk of severe complications. Controlled clinical studies of zanamivir and oseltamivir have not been done in pregnant women; however, many observational studies indicate that their use during pregnancy does not increase risk of adverse effects. There are fewer data about the safety of peramivir during pregnancy and no data about baloxavir in pregnant women. Health care professionals should tell pregnant women what the symptoms and signs of influenza are and advise them to seek treatment as soon as symptoms begin.

Acyclovir (oral and topical) appears to be safe during pregnancy.

Antidepressants During Pregnancy

Antidepressants Medications for Treatment of Depression Several drug classes and drugs can be used to treat depression: Selective serotonin reuptake inhibitors (SSRIs) Serotonin modulators (5-HT2 blockers) Serotonin-norepinephrine reuptake inhibitors... read more , particularly selective serotonin reuptake inhibitors (SSRIs), are commonly used during pregnancy because the prevalence of clinical depression during pregnancy is high (7 to 12% in one review) (6 References Medications may be required for various indications during pregnancy. The most commonly used medications include antiemetics, antacids, antihistamines, analgesics, antimicrobials, diuretics... read more ). Physiologic and psychosocial changes during pregnancy can affect depression (possibly worsening it) and possibly reduce the response to antidepressants. Ideally, a multidisciplinary team that includes an obstetrician and a psychiatric specialist should manage depression during pregnancy.

Pregnant women who are taking antidepressants should be asked about depressive symptoms at each prenatal visit, and appropriate fetal testing should be done. It may include the following:

  • A detailed evaluation of fetal anatomy during the second trimester

  • If a pregnant woman takes paroxetine, echocardiography to evaluate the fetus's heart because in some studies, paroxetine appeared to increase the risk of congenital cardiac anomalies

To reduce the risk of withdrawal symptoms in the neonate, clinicians should consider tapering the dose of all antidepressants to the lowest effective dose during the third trimester. However, the benefits of tapering must be carefully balanced against the risk of symptom recurrence and postpartum depression. Postpartum depression Postpartum Depression Postpartum depression is depressive symptoms that last > 2 weeks after delivery and meet criteria for major depression. Postpartum depression occurs in 10 to 15% of women after delivery.... read more is common, often unrecognized, and should be treated promptly. Periodic visits with a psychiatrist and/or social workers may be helpful.


  • 1. Centers for Disease Control and Prevention (CDC): Update on overall prevalence of major birth defects--Atlanta, Georgia, 1978-2005. MMWR Morb Mortal Wkly Rep 57(1):1-5, 2008.

  • 2. Feldkamp ML, Carey JC, Byrne JLB, Krikov S, Botto LD: Etiology and clinical presentation of birth defects: population based study. BMJ 357:j2249, 2017. Published 2017 May 30. doi:10.1136/bmj.j2249

  • 3. U.S. Food and Drug Administration (FDA): FDA Approves First Vaccine for Pregnant Individuals to Prevent RSV in Infants. FDA News Release, August 21, 2023.

  • 4. Garneau WM, Jones-Beatty K, Ufua MO, et al: Analysis of clinical outcomes of pregnant patients treated with nirmatrelvir and ritonavir for acute SARS-CoV-2 infection. JAMA Netw Open 5(11):e2244141, 2022. Published 2022 Nov 1. doi:10.1001/jamanetworkopen.2022.44141

  • 5. Liggins GC, Howie RN: A controlled trial of antepartum glucocorticoid treatment for prevention of the respiratory distress syndrome in premature infants. Pediatrics 50(4):515-525, 1972.

  • 6. Bennett HA, Einarson A, Taddio A, et al: Prevalence of depression during pregnancy: systematic review [published correction appears in Obstet Gynecol 103(6):1344, 2004]. Obstet Gynecol 103(4):698-709, 2004. doi:10.1097/01.AOG.0000116689.75396.5f

More Information

  • The FDA's Content and Format of Labeling for Human Prescription Drug and Biological Products; Requirements for Pregnancy and Lactation Labeling: This document discusses the change in labeling for pregnancy, which eliminates the pregnancy categories (A, B, C, D, X) and replaces them with more helpful and detailed information. The new labeling requires a summary of the risks of drug use during pregnancy and lactation, data to support that summary, and relevant information to help health care professionals make prescribing decisions and advise women about drug use during pregnancy and lactation.

  • Teratogen Information System: This web site provides resources to help clinicians determine the risks of drugs (and of environmental exposures [eg, vaccines, infections]) during pregnancy. It provides expert information about > 1700 drugs (including 200 of the most frequently prescribed drugs). Clinical and experimental literature is summarized, and based on that information, teratogenic risk is assigned. A subscription is required.

Drugs Mentioned In This Article

Drug Name Select Trade
Sitavig, Zovirax, Zovirax Cream, Zovirax Ointment, Zovirax Powder, Zovirax Suspension
Brisdelle, Paxil, Paxil CR, Pexeva
NOTE: This is the Professional Version. CONSUMERS: View Consumer Version
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