Pharmacotherapy during pregnancy

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 learning card 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.

Drugs to avoid	Effects	Drugs of choice
Tetracycline	Bone damage Malformation and permanent yellow discoloration of the primary teeth	Penicillin group : ampicillin, amoxicillin, flucloxacillin, penicillin V, propicillin Cephalosporins Macrolides: erythromycin, azithromycin Metronidazole Nitrofurantoin
Aminoglycoside	Ototoxicity (CN VIII toxicity) and hearing loss
Trimethoprim/sulfonamide combinations	Cardiovascular birth defects Neonatal jaundice
Chloramphenicol	Gray baby syndrome: 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

References:^{[1][2][3][4][5]}

Antihypertensives

Drugs to avoid	Harmful 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	First trimester: cardiovascular and central nervous system malformations Second and third trimesters: fetal kidney damage or death
Angiotensin-receptor blockers	Severe renal malformation Oligohydramnios
Atenolol	Intrauterine growth retardation (IUGR) ↓ Placental growth

Antifungals

Drugs to avoid	Harmful effects	Recommended drugs
Ketoconazole, flucytosine, and griseofulvin	Teratogenic and/or embryotoxic	Topical: imidazoles Vaginal: nystatin Systemic: amphotericin B
Itraconazole, fluconazole (> 300 mg)
Iodides	Congenital goiter

Antivirals

Drugs to avoid	Harmful effects	Recommended drugs
Efavirenz	Fetal neural tube defects	Acyclovir and valacyclovir for herpes Oral oseltamivir and zanamivir for influenza Zidovudine + lamivudine + nevirapine + atazanavir for HIV infection (see also 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

Drugs to avoid	Harmful 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 Bone deformities	Heparin: anticoagulant of choice 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 does not suggest a high risk of embryopathy, but, because of significant data gaps, they are to be avoided in pregnancy.

Analgesics

Drugs to avoid	Harmful 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 Paracetamol, 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

Drugs to avoid	Harmful 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 Craniofacial malformations (facial dysmorphism; choanal atresia), gastrointestinal malformations (esophageal atresia with or without tracheoesophageal fistula)

Antiepileptics

Drugs to avoid	Harmful 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)

Antiemetics during pregnancy

80% of pregnant women are affected by nausea and, potentially, vomiting, which may be treated with:

• Selected antihistamines :
  • Doxylamine-pyridoxine (vitamin B₆) combination
  • Meclizine
  • Dimenhydrinate: only in the first and second trimesters
• Metoclopramide, especially in the second trimester
• Ondansetron, promethazine, or prochlorperazine in patients with refractory nausea and vomiting despite other medical therapy

Other drug classes

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
Methotrexate	Neural tube defects
Cholestyramine	Fetal and maternal hemorrhage
Lithium	Congenital heart defects (particularly Ebstein's anomaly)
Antineoplastic drugs (specifically antifolate metabolites and alkylating agents)	Congenital malformation of digits; other malformations
Isotretinoin and excessive intake of vitamin A (> 8,000 IU vitamin A per day as retinol/retinyl esters)	Multiple congenital malformations, including facial cleft and skeletal abnormalities
Misoprostol	Abortions Frontotemporal congenital malformations

First-generation antihistamines (e.g., chlorpheniramine) may be used as antiallergenics during pregnancy!

Type 2 diabetes during pregnancy or gestational diabetes requires insulin therapy!
References:^{[6][7][8][9][10][11][12][13][14][15][16][17][18][19][20][21][22][23][24][4][4][4][4][25][26][27][28][29][30][31]}