Pharmacotherapy during pregnancy

Last updated: August 4, 2022

Summary

Pharmacotherapy during pregnancy is an important concern for a medical professional because there are only a limited number of drugs that can be safely administered during this period. Many drugs can cause harm to the fetus in the form of defects in organogenesis, growth retardation, and functional deficits. The aim of drug selection in this period is to prescribe an agent that effectively alleviates the mother's medical complaints while ensuring the safety of the unborn fetus. This article provides a brief overview of drugs that can be used for common conditions in pregnant women. It also lists the substances that should be avoided during pregnancy.

Antibiotics during pregnancy

Overview of antibiotics to avoid during pregnancy ^[1]^[2]^[3]
	Harmful side effects	Drugs of choice
Tetracycline	Inhibition of bone growth Malformation and permanent yellow discoloration of the primary teeth	Penicillin group : ampicillin, amoxicillin, flucloxacillin, penicillin V, propicillin Cephalosporins Macrolides: erythromycin, azithromycin Nitrofurantoin
Aminoglycoside	Ototoxicity (CN VIII toxicity) and hearing loss
Trimethoprim/sulfonamide combinations	Cardiovascular birth defects Neonatal jaundice (risk of kernicterus)
Chloramphenicol	Gray baby syndrome: a syndrome associated with chloramphenicol accumulation in the body, leading to ashen gray color of the skin, cardiovascular collapse, and abdominal distention
Clarithromycin	Embryotoxic
Fluoroquinolones	Bone and cartilage damage
Metronidazole	Even though studies in humans show no increase in congenital defects, avoiding the drug during the first trimester and during breastfeeding is recommended, if possible. ^[4]

“Teethracycline:” teeth discoloration with tetracycline.
“A mean guy stepped on baby's ear:” Aminoglycoside can cause ototoxicity.

Other medical therapy during pregnancy

Antihypertensives

Overview of antihypertensives to avoid during pregnancy ^[5] ^[6]
	Harmful side effects	Recommended drugs
Diuretics	Reduction of placental perfusion, particularly in the third trimester.	Methyldopa in arterial hypertension and hypertensive crisis Beta blockers (particularly metoprolol and labetalol) Especially in the first and second trimesters Avoid during the third trimester Dihydralazine in uncontrolled hypertension Nifedipine
ACE inhibitors ^[7]	First trimester: cardiovascular and CNS malformations ^[8] Second and third trimesters Oligohydramnios Fetal renal hypoplasia Poor cranial ossification Fetal death
Angiotensin-receptor blockers	Severe renal malformation Oligohydramnios
Atenolol	Intrauterine growth retardation (IUGR) ↓ Placental growth

“Moms Love Healthy Newborns:” Methyldopa, Labetalol, Hydralazine, Nifedipine are safe to use during pregnancy.

Antifungals

Overview of antifungals to avoid during pregnancy ^[9]
	Harmful side effects	Recommended drugs
Ketoconazole, flucytosine, and griseofulvin	Teratogenic and/or embryotoxic	Topical: imidazoles Vaginal: nystatin Systemic: amphotericin B
Itraconazole, fluconazole (> 300 mg)	Teratogenic and/or embryotoxic
Iodides	Congenital goiter

Antivirals

Overview of antivirals to avoid during pregnancy ^[10]^[11]^[12]^[13]^[14]
	Harmful side effects	Recommended drugs
Efavirenz ^[15]	Fetal neural tube defects	Acyclovir and valacyclovir for herpes Oral oseltamivir and zanamivir for influenza Zidovudine PLUS lamivudine PLUS nevirapine PLUS atazanavir for HIV infection (see “HIV in Pregnancy”)
Ribavirin	Preterm birth Significant teratogenic and/or embryocidal effects
Interferon α
Ribavirin and interferon α combination
Didanosine and stavudine combination	Lactic acidosis and hepatic failure leading to death
Nevirapine	Potentially fatal hepatotoxicity

Nevirapine should not be used as first-line therapy if avoidable!

Anticoagulants

Overview of anticoagulants to avoid during pregnancy ^[16]^[17]
Drugs to avoid	Harmful side effects	Recommended drugs
Warfarin	Can pass through the placental barrier and may cause: Spontaneous abortion, stillbirth, or preterm death Cerebral hemorrhage leading to CNS abnormalities Atrophy of the optic nerve Bone deformities (e.g., stippled epiphyses, nasal hypoplasia)	Heparin: anticoagulant of choice (does not cross the placental barrier) Aspirin (ASA) Low doses may be prescribed for high-risk preeclampsia. High doses should be especially avoided in the third trimester .
Phenprocoumon
Non-vitamin K oral anticoagulants (apixaban, rivaroxaban, dabigatran)	The data available do not suggest a high risk of embryopathy, but, because of significant data gaps, they are to be avoided in pregnancy.

“Don't Warry, be Heppy:” warfarin should be replaced with heparin during pregnancy.

Analgesics

Overview of analgesics to avoid during pregnancy ^[18]
	Harmful side effects	Recommended drugs
NSAIDs (in the second and third trimesters)	Premature closure of the ductus arteriosus Persistent pulmonary hypertension Inhibits uterine contractility	Non-opioid analgesics Acetaminophen, especially in the third trimester NSAIDs in the first trimester only Opioid analgesics (e.g., fentanyl, codeine) for moderate to severe pain
Metamizole	In the first and second trimesters: increased occurrence of Wilms tumor in the embryo/fetus In the third trimester: causes premature closure of the ductus arteriosus.

Thyroid agents

Overview of thyroid agents to avoid during pregnancy ^[19]

Harmful side effects

Recommended drugs

Radioiodine therapy (absolutely contraindicated)

Ablation of fetal thyroid tissue leading to hypothyroidism

Antithyroid drugs
- First trimester: propylthiouracil
- Second and third trimester: methimazole
L-thyroxine

Methimazole (first trimester)

Carbimazole

Thiamazole

Aplasia cutis: a congenital dermatological condition characterized by the absence of a portion of skin in a localized or widespread area at birth
Craniofacial malformations (e.g., facial dysmorphism, choanal atresia)
Gastrointestinal malformations (e.g., esophageal atresia with or without tracheoesophageal fistula)

Antiepileptics

Overview of antiepileptics to avoid during pregnancy ^[2]^[20]^[21]

Harmful side effects

Recommended drugs

Phenytoin

Carbamazepine

Fetal hydantoin syndrome
- Characterized by cleft palate, phalanx/fingernail hypoplasia, excessive hair growth, and intrauterine growth restriction
- Due to impaired absorption of folate
Neural tube defects (carbamazepine only)

Individualized treatment based on seizure type and most tolerated drug

Valproate

Neural tube defects (e.g., spina bifida)
Craniofacial dysmorphism

Antiemetics during pregnancy ^[22]

See “Antiemetic therapy for nausea and vomiting of pregnancy.”

Other drug classes ^[2]^[20]^[21]

Overview of other drugs to avoid during pregnancy
Drugs to avoid		Harmful effects
Drugs to avoid		Harmful effects	Steroid therapy (especially as antiallergenics)	Reduced birth weight Increased risk of preeclampsia Increased risk of oral and lip clefts
Oral antidiabetic agents		Pre-eclampsia Neonatal jaundice Macrosomia Neonatal hypoglycemia: low blood sugars in a newborn Can be caused by several conditions, e.g., persistent hyperinsulinemic hypoglycemia (e.g., due to gestational diabetes), prematurity, sepsis May be asymptomatic or manifest with autonomic symptoms (e.g., tachycardia, sweating, tremors) and neurological symptoms (e.g., hypotonia, lethargy, seizures).
Methotrexate		Neural tube defects
Cholestyramine		Fetal and maternal hemorrhage
Lithium		Congenital heart defects (particularly Ebstein anomaly)
Antineoplastic drugs (specifically antifolate metabolites and alkylating agents)		Congenital malformation of digits Other malformations (e.g., neural tube defects)
Isotretinoin and excessive intake of vitamin A (> 8,000 IU vitamin A per day as retinol/retinyl esters)		High risk of miscarriage Multiple congenital malformations, including cardiac anomalies, facial cleft, and skeletal abnormalities
Misoprostol		Abortions Increased risk malformations ^[23] Möbius sequence (bilateral congenital paralysis of the abducens nerve and facial nerve) Hydrocephalus, encephalocele Terminal limb reduction defects (e.g., clubfoot, syndactyly)
5α-reductase inhibitor		Increased risk of male genital malformation (e.g., hypospadias) ^[24]
Antacids	Calcium carbonate	Increased risk of milk-alkali syndrome (hypercalcemia, metabolic alkalosis, and acute kidney injury) ^[25]
Antacids	Magnesium hydroxide	Inhibition of uterine contractions ^[26] Might delay the onset of lactation ^[27]

“IsoTERATinoin” is a TERrible TERATogen.”

First-generation antihistamines (e.g., chlorpheniramine) may be used as antiallergenics during pregnancy. Second-generation antihistamines (e.g., loratadine, fexofenadine, cetirizine) may be considered if chlorpheniramine is not tolerated. Loratadine is the best-studied second-generation antihistamine. ^[28]

Type 2 diabetes during pregnancy or gestational diabetes requires insulin therapy!

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