Suggested prescribing approach
Before prescribing
- Confirm the indication and whether treatment is clinically necessary.
- Consider whether untreated maternal disease creates fetal or maternal risk.
- Review gestational age and timing of exposure.
- Use medication-specific data rather than relying on broad drug classes.
When selecting therapy
- Prefer medications with reassuring human pregnancy experience when clinically appropriate.
- Use a single effective agent when possible.
- Use the lowest effective dose, but avoid undertreatment of significant maternal disease.
- Check for interactions with prescription, over-the-counter, herbal, and supplement use.
Modified in part from: Norwitz ER, Greenberg JA. Antibiotics in pregnancy: are they safe? Rev Obstet Gynecol. 2009;2(3):135-136. PMID: 19826569
PLLR-era review framework
The older FDA pregnancy letter categories A, B, C, D, and X are obsolete. Current prescription labeling uses a narrative risk-benefit structure under the Pregnancy and Lactation Labeling Rule (PLLR), including pregnancy, lactation, and reproductive potential sections. For prescription drugs, review the current prescribing information, preferably through DailyMed or the manufacturer label. Under PLLR, focus on the clinical narrative rather than a single risk letter.
| Label section | What to review clinically |
|---|---|
| 8.1 Pregnancy | Risk summary, human data, animal data, disease-associated maternal/fetal risk, dose-response considerations, timing of exposure, and clinical management recommendations. |
| 8.2 Lactation | Presence of drug in human milk, infant exposure, reported infant effects, effect on milk production, and whether alternatives are preferred. |
| 8.3 Females and Males of Reproductive Potential | Pregnancy testing, contraception recommendations, infertility concerns, and reproductive counseling when relevant. |
How to counsel when information is limited
- Avoid stating that a medication is “safe” without qualification; use medication-specific wording such as “available human data have not shown an increased risk of major birth defects” when supported.
- Separate background pregnancy risks from medication-attributable risk.
- Document indication, dose, timing, and alternatives reviewed.
- For inadvertent exposure, avoid reflexive discontinuation; assess risk based on gestational timing and available human data.
Factors influencing placental transfer
- Molecular weight: Drugs with molecular weight below approximately 500 Da generally cross the placenta more readily. Transfer is often incomplete for larger molecules, and very large molecules such as insulin do not normally cross in clinically meaningful amounts.
- Lipid solubility and ionization: Lipophilic and nonionized drugs tend to cross more readily. Strongly dissociated acids may transfer incompletely, but prediction is not absolute.
- Placental physiology: Maternal and fetal blood flow, gestational age, placental surface area, and placental disease can alter transfer.
- Enzymes and transporters: Placental enzymes and transporters may reduce or modify fetal exposure. Examples include 11β-hydroxysteroid dehydrogenase type 2 metabolism of prednisolone and efflux transporters that may limit fetal exposure to selected medications.
- Protein binding: Protein binding can influence free drug concentration, but its effect on placental transfer is variable and medication-specific.
Breastfeeding medication review
Lactation decisions should weigh the benefit of breastfeeding, the need for maternal therapy, drug levels in milk, oral bioavailability to the infant, infant age and prematurity, and reported infant adverse effects.
Higher caution situations
- Premature or medically fragile infant
- Neonate younger than 1 month
- Long half-life medications
- High maternal doses or multidrug therapy
- Medications with sedation, respiratory depression, marrow suppression, or antineoplastic effects
Useful lactation data points
- Milk-to-plasma ratio
- Relative infant dose
- Infant serum levels
- Reported infant effects
- Preferred alternatives when available
Primary lactation resource: LactMed.
OBRx medication resources
- OBRx Index Perinatology.com medication reference index for obstetric prescribing.
- Prescription Drugs of Choice During Pregnancy First-line medication options during pregnancy by condition.
- Over-the-Counter Medications During Pregnancy Common nonprescription medication considerations.
- FDA Pregnancy Categories Archive Historical reference only; FDA letter categories are obsolete.
Recommended external resources
- DailyMed Current FDA labeling for prescription and nonprescription drug products.
- Drugs.com Pregnancy and Breastfeeding Warnings Drug-specific pregnancy and breastfeeding warning summaries, including links to consumer and professional monographs.
- FDA Pregnancy and Lactation Labeling Resources Official PLLR information and labeling resources.
- LactMed Drug and lactation database maintained by the National Library of Medicine.
- MotherToBaby Fact Sheets Patient-facing pregnancy and breastfeeding exposure information.
- BUMPS: Best Use of Medicines in Pregnancy UK patient-facing medication information in pregnancy.
- InfantRisk Center Lactation and pregnancy medication risk information.
- Australian Prescribing Medicines in Pregnancy Database Australian pregnancy medication categorization system.
- Reprotox Subscription teratology database.
- Drugs in Pregnancy and Lactation Briggs, Freeman, Towers, and Forinash reference text.
- RxList Pill Identifier Pill identification tool.
Clinician documentation template
Medication exposure counseling note
Medication exposure reviewed: [medication, dose, route, frequency]. Indication: [condition]. Gestational age/exposure timing: [GA/timing]. Counseling included review of maternal benefit of treatment, potential fetal/neonatal risks, limitations of available human data, and alternatives when appropriate. Current labeling and pregnancy/lactation resources were reviewed. Patient advised not to stop or change medication without coordination with the prescribing clinician. Plan: [continue/change/alternative/monitoring/referral].
Breastfeeding medication counseling note
Lactation medication review performed for [medication]. Counseling included maternal need for therapy, expected infant exposure through milk, infant age/clinical status, potential infant adverse effects, and available alternatives. LactMed and/or other lactation resources reviewed. Plan: [compatible/monitor infant/consider alternative/avoid breastfeeding temporarily/consult pediatrics or lactation specialist].
References
Expand/Close
- U.S. Food and Drug Administration. Pregnancy and Lactation Labeling Resources. FDA PLLR resources.
- U.S. Food and Drug Administration. Pregnancy, Lactation, and Reproductive Potential: Labeling for Human Prescription Drug and Biological Products — Content and Format. FDA guidance.
- National Library of Medicine. Drugs and Lactation Database (LactMed). LactMed.
- MotherToBaby. Fact Sheets: Pregnancy and Breastfeeding Exposures. MotherToBaby fact sheets.
- Pacifici GM, Nottoli R. Placental transfer of drugs. Clin Pharmacokinet. 1995;28(3):235-269. PMID: 7758253.
- Menon RK, Cohen RM, Sperling MA, Cutfield WS, Mimouni F, Khoury JC. Transplacental passage of insulin in pregnant women with insulin-dependent diabetes mellitus. N Engl J Med. 1990;323(5):309-315. PMID: 2195347.
- van Runnard Heimel PJ, Franx A, Schobben AFAM, Huisjes AJM, Derks JB, Bruinse HW. The transplacental passage of prednisolone in pregnancies complicated by early-onset HELLP syndrome. Placenta. 2005;26(10):842-845. PMID: 16226134.
- Neumanova Z, Cerveny L, Ceckova M, Staud F. Interactions of tenofovir and tenofovir disoproxil fumarate with drug efflux transporters ABCB1, ABCG2, and ABCC2. AIDS. 2014;28(1):9-17. PMID: 24413260.
- Hemauer SJ, Patrikeeva SL, Nanovskaya TN, Hankins GDV, Ahmed MS. Role of placental transporters in the efflux of glyburide, rosiglitazone, and metformin. Am J Obstet Gynecol. 2010;202(4):383.e1-383.e7. PMID: 20350646.
- Norwitz ER, Greenberg JA. Antibiotics in pregnancy: are they safe? Rev Obstet Gynecol. 2009;2(3):135-136. PMID: 19826569.
Last reviewed: . This page is for clinician education and should be interpreted in the context of individual patient circumstances and current prescribing information.