Pharmacotherapy during pregnancy is an important aspect of a medical practice that requires an understanding of both maternal physiology and fetal development. While treating pregnant patients, clinicians must evaluate therapeutic benefit from the drug and potential risks to the developing fetus.
Pregnancy induces significant physiological changes that alter the pharmacokinetics (absorption, distribution, metabolism and elimination) of many drugs.
This short video lecture explains the unique Physiological Changes During Pregnancy and Breastfeeding:
Moreover, placental drug transfer plays a critical role in fetal drug exposure and teratogenicity. Drugs that are Lipophilic, low molecular weight, and non-ionized are more likely to cross the placenta more readily, on the other hand, hydrophilic, high molecular weight, ionized and highly protein bound drugs are less likely to cross placenta.
This Video about General Principles of Pharmacotherapy in Pregnancy – covers FDA pregnancy categories, teratogenicity, placental drug transfer, and lactation pharmacology.
Drug toxicity in pregnancy can be due to uterine effects (either decreasing uterine blood flow and/or causing uterine constriction) affecting placenta and/or affecting fetus directly.
Teratogen is a chemical that can alter the development of the fetus. Drug safety and teratogenic effect is also dependent on a timing of a drug exposure:
- Pre-implantation phase (0–2 weeks of embryonic development): Drug has “all or none” effect (death or no effect)
- Organogenesis (3–8 weeks of embryonic development): Highest risk for structural malformations
- Fetal period (after 8 weeks of embryonic development): Functional and growth-related abnormalities
This picture summarizes FDA drug classification, FDA classifies drugs from A to X class, A is safest and X is absolutely contraindicated.
Antibiotic Use in Pregnancy:
The selection of appropriate antimicrobial therapy during pregnancy can be challenging. To facilitate clinical decision-making, the following classification simplifies the categorization of antibiotics used in pregnancy based on safety profiles. This framework is not intended to replace academic guidelines but to aid recall in time-sensitive scenarios.
Antibiotics Generally Considered Safe During Pregnancy:
- β-Lactams: Penicillins (e.g., Ampicillin, Amoxicillin) and Cephalosporins
- Monobactams: Aztreonam
- Carbapenems: Imipenem, Meropenem
- Nitroimidazoles: Metronidazole
- Nitrofurans: Nitrofurantoin (except near term due to risk of hemolytic anemia in G6PD deficiency)
- Phosphonic acid derivatives: Fosfomycin
- Glycopeptides: Vancomycin
- Lincosamides: Clindamycin
These antibiotics are often first-line for urinary tract infections, intra-abdominal infections, and soft tissue infections in pregnant patients.
Antibiotics to Use With Caution: careful Risk–Benefit Assessment Required
These agents may pose potential risks based on animal data or limited human studies, but may still be justified when clinically indicated:
- Macrolides: Azithromycin and erythromycin (excluding erythromycin estolate, which is hepatotoxic)
- Oxazolidinones: Linezolid: Use reserved for resistant Gram-positive infections
- Lipopeptides: Daptomycin: Limited data, but may be used when alternatives are contraindicated
- Antimycobacterial agents: Isoniazid, Rifampin, Pyrazinamide, Ethambutol are used in Tuberculosis disease.
Note: Rifampin causes orange discoloration of body fluids, including breast milk. Patients should be counseled about this harmless side effect.
Contraindicated or High-Risk Antibiotics in Pregnancy
These drugs are associated with significant fetal toxicity or teratogenic effects and should generally be avoided unless no alternatives exist:
- Aminoglycosides (e.g., Gentamicin, Amikacin, Streptomycin): Risk of fetal nephrotoxicity and ototoxicity, including irreversible hearing loss.
- Fluoroquinolones (e.g., Ciprofloxacin, Levofloxacin, Moxifloxacin): Impair fetal cartilage and bone development
- Tetracyclines: Cause fetal tooth discoloration, impaired skeletal development, and hepatotoxicity in the mother
- Doxycycline may be an exception, but its use remains controversial.
- Sulfonamides (TMP-SMX)
- First trimester: Interferes with folate metabolism → neural tube defects
- Third trimester: Displaces bilirubin → can cause kernicterus in neonates
- Telavancin and Lefamulin: Associated with adverse developmental outcomes in animal studies
This picture summarizes Contraindicated antibiotics in pregnancy:
For a comprehensive review of antibiotic therapy refer to our Comprehensive Antibiotic Course on Udemy.
Author: Mamuka Asatiani