Disclaimer

The information provided in this article is for educational and informational purposes only. It is not intended to substitute professional medical advice, diagnosis, or treatment. Drug safety in pregnancy and lactation can vary depending on individual health conditions, trimester, dosage, and clinical history. Always consult a qualified doctor, obstetrician, or healthcare provider before starting, stopping, or changing any medication during pregnancy or breastfeeding. The author and publisher are not responsible for any adverse effects resulting from the use of the information presented here.

Pregnancy Drug Risk Categories – What Do They Mean?

Earlier, the US FDA used letter categories (A, B, C, D, X) to classify drug safety in pregnancy. Although this system has now been replaced by the Pregnancy and Lactation Labeling Rule (PLLR), these categories are still commonly referenced in textbooks and exams.
More information here https://www.fda.gov/drugs/labeling-information-drug-products/pregnancy-and-lactation-labeling-resources

Older categories explained

Category A -Safest

• Controlled human studies show no risk
• Safest category
• Very few drugs fall here

Category B

• Animal studies show no risk
  OR
• Animal studies show risk but human studies do not
• Generally considered relatively safe

Category C

• Animal studies show adverse effects
• No adequate human studies
• Use only if benefits outweigh risks

Category D

• Positive evidence of human fetal risk
• May be used in life-threatening situations

Category X – Most Unsafe

• Proven fetal abnormalities
• Contraindicated in pregnancy

PLLR (Pregnancy and Lactation Labeling Rule)

PLLR Includes 3 Main Sections:

Pregnancy

• Risk summary
• Human and animal data
• Clinical considerations

Lactation

• Whether the drug passes into breast milk
• Potential effects on the infant

Females and Males of Reproductive Potential

• Contraception recommendations
• Fertility considerations

General Risks of Antihistamines in Pregnancy & Lactation

Before discussing individual drugs, let’s understand possible risks of Antihistamines in Pregnancy.

Possible Risks During Pregnancy

• Fetal sedation
• Anticholinergic effects
• Possible association with congenital defects
• Uterine stimulation
• QT prolongation (effect on heart rate)

Risks During Lactation (Breastfeeding)

• Infant sedation
• Irritability
• Reduced milk supply (especially sedating antihistamines)
• Dry mouth & feeding difficulty in infant

Second-generation antihistamines are generally preferred in lactation because they cause less sedation.

Individual Drug Safety Overview for Antihistamines in Pregnancy

Levocetirizine

Risks:

• Limited human pregnancy data
• Possible mild sedation
• Minimal data in breastfeeding

Safe Aspects:

• Second-generation (less CNS penetration)
• No clear teratogenic evidence

Final Category:

• Similar to Category B/C (data limited)
• ⚠️ Use if clearly needed
• Not first-line but acceptable

Cetirizine

Risks:

• Mild drowsiness
• Limited but reassuring pregnancy data

Safe Aspects:

• Well-studied
• Commonly used in pregnancy
• Low breast milk transfer

Final Category:

• Category B (older classification)
• Generally safe in pregnancy
• Preferred non-sedating option

Chlorpheniramine (CPM)

Risks:

• Sedation
• Anticholinergic effects

Safe Aspects:

• Long history of use
• No proven teratogenic risk

Final Category:

• Category B
• Considered safe
• Often first-line in pregnancy

Hydroxyzine

Risks:

• Crosses placenta
• Fetal CNS depression
• Sedation
• Possible QT prolongation

Safe Aspects:

• Strong antihistaminic effect

Final Category:

• Category C
• Avoid especially in first trimester
• Not preferred in pregnancy

Fexofenadine

Risks:

• Limited pregnancy data
• Minimal sedation

Safe Aspects:

• Non-sedating
• Low CNS penetration

Final Category:

• Category C (data limited)
• ⚠️ Use only if necessary
• Not first-line

Loratadine

Risks:

• Minimal
• Rare sedation

Safe Aspects:

• Extensive safety data
• Widely recommended in pregnancy

Final Category:

• Category B
• ✅ Safe and preferred option

Diphenhydramine

Risks:

• Sedation
• Anticholinergic effects
• Avoid high doses near delivery

Safe Aspects:

• Long safety history
• Used for nausea and allergy

Final Category:

• Category B
• ⚠️ Generally safe but sedating
• Avoid near term if possible

Desloratadine

Risks:

• Limited human data

Safe Aspects:

• Active metabolite of loratadine
• Non-sedating

Final Category:

• Category C
• ⚠️ Use only if benefit outweighs risk

Dimenhydrinate

Risks:

• Sedation
• Anticholinergic
• Avoid high doses late pregnancy

Safe Aspects:

• Used for nausea and motion sickness
• Long clinical use

Final Category:

• Category B
• ✅ Generally safe when used appropriately

Final Clinical Summary Table

Antihistamines in Pregnancy

Drug	Preferred?	Avoid?
Loratadine	Yes	No
Cetirizine	Yes	No
Chlorpheniramine	Yes	No
Dimenhydrinate	Acceptable	Avoid high doses
Diphenhydramine	Acceptable	Avoid near term
Levocetirizine	Use if needed	Not first-line
Fexofenadine	Use if needed	Not first-line
Desloratadine	Limited data	Not preferred
Hydroxyzine	Avoid	Especially 1st trimester