Pharmacotherapy during pregnancy

Last updated: September 15, 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

Drugs of choice

Penicillin group : ampicillin, amoxicillin, flucloxacillin, penicillin V, propicillin
Cephalosporins
Macrolides: erythromycin, azithromycin
Metronidazole
Fosfomycin (see also: “UTI in pregnancy”)

Drugs to avoid

Overview of antibiotics to avoid during pregnancy ^[1]^[2]^[3]
	Harmful side effects
Tetracycline	Inhibition of bone growth Malformation and permanent yellow discoloration of the primary teeth
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

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

Other medical therapy during pregnancy

Antihypertensives

Drugs of choice

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
See also: “Treatment of hypertension in pregnancy”.

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

Drugs to avoid

Overview of antihypertensives to avoid during pregnancy ^[4]^[5]
	Harmful side effects
Diuretics	Reduction of placental perfusion, particularly in the third trimester.
ACE inhibitors ^[6]	First trimester: cardiovascular and CNS malformations ^[7] 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

Antifungals

Drugs of choice

Topical: imidazoles
Vaginal: nystatin
Systemic: amphotericin B

Drugs to avoid

Overview of antifungals to avoid during pregnancy ^[8]
	Harmful side effects
Ketoconazole, flucytosine, and griseofulvin	Teratogenic and/or embryotoxic
Itraconazole, fluconazole (> 300 mg)	Teratogenic and/or embryotoxic
Iodides	Congenital goiter

Antivirals

Drugs of choice

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”)

Drugs to avoid

Overview of antivirals to avoid during pregnancy ^[9]^[10]^[11]^[12]^[13]
	Harmful side effects
Efavirenz ^[14]	Fetal neural tube defects
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 of choice

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

Drugs to avoid

Overview of anticoagulants to avoid during pregnancy ^[15]^[16]
Drugs to avoid	Harmful side effects
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)
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

Drugs of choice

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

Drugs to avoid

Overview of analgesics to avoid during pregnancy ^[17]
	Harmful side effects
NSAIDs (in the second and third trimesters)	Premature closure of the ductus arteriosus Persistent pulmonary hypertension Inhibits uterine contractility
Metamizole	In the first and second trimesters: increased occurrence of nephroblastoma in the embryo/fetus In the third trimester: causes premature closure of the ductus arteriosus.

Thyroid agents

Drugs of choice

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

Drugs to avoid

Overview of thyroid agents to avoid during pregnancy ^[18]

Harmful side effects

Radioiodine therapy (absolutely contraindicated)

Ablation of fetal thyroid tissue leading to hypothyroidism

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

Drugs of choice

Individualized treatment based on seizure type and most tolerated drug

Drugs to avoid

Overview of antiepileptics to avoid during pregnancy ^[2]^[19]^[20]

Harmful side effects

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)

Valproate

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

Antiemetics during pregnancy ^[21]

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

Other drug classes to avoid during pregnancy ^[2]^[19]^[20]

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 ^[22] 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) ^[23]
Antacids	Calcium carbonate	Increased risk of milk-alkali syndrome (hypercalcemia, metabolic alkalosis, and acute kidney injury) ^[24]
Antacids	Magnesium hydroxide	Inhibition of uterine contractions ^[25] Might delay the onset of lactation ^[26]

“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. ^[27]

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

References

Podymow T, August P. Update on the use of antihypertensive drugs in pregnancy. Hypertension. 2008; 51 (4): p.960-969. doi: 10.1161/HYPERTENSIONAHA.106.075895 . | Open in Read by QxMD
Cauldwell M, Dos Santos F, Steer PJ, Swan L, Gatzoulis M, Johnson MR. Pregnancy in women with congenital heart disease. BMJ. 2018; 360 : p.k478. doi: 10.1136/bmj.k478 . | Open in Read by QxMD
Kubota-Sjogren Y, Nelson-Piercy C. Fulminant antenatal pulmonary oedema in a woman with hypertension and superimposed preeclampsia.. BMJ case reports. 2015; 2015 . doi: 10.1136/bcr-2015-212751 . | Open in Read by QxMD
Cooper WO, Hernandez-diaz S, Arbogast PG, et al. Major congenital malformations after first-trimester exposure to ACE inhibitors. N Engl J Med. 2006; 354 (23): p.2443-2451. doi: 10.1056/NEJMoa055202 . | Open in Read by QxMD
King CT, Rogers PD, Cleary JD, Chapman SW. Antifungal therapy during pregnancy. Clin Infect Dis. 1998; 27 (5): p.1151-1160.
Recommendations for Use of Antiretroviral Drugs in Pregnant HIV-1-Infected Women for Maternal Health and Interventions to Reduce Perinatal HIV Transmission in the United States. https://aidsinfo.nih.gov/guidelines/html/3/perinatal-guidelines/0. Updated: October 26, 2016. Accessed: February 22, 2017.
Kang SH, Chua-gocheco A, Bozzo P, Einarson A. Safety of antiviral medication for the treatment of herpes during pregnancy. Can Fam Physician. 2011; 57 (4): p.427-428.
Recommendations for Obstetric Health Care Providers Related to Use of Antiviral Medications in the Treatment and Prevention of Influenza. https://www.cdc.gov/flu/professionals/antivirals/avrec_ob.htm. Updated: November 3, 2016. Accessed: February 22, 2017.
Ribavirin. https://aidsinfo.nih.gov/drugs/28/ribavirin/138/professional. Updated: November 1, 2017. Accessed: October 24, 2018.
Peginterferon Alfa-2b (HCV). https://aidsinfo.nih.gov/drugs/487/peginterferon-alfa-2b--hcv-/0/professional. Updated: May 1, 2018. Accessed: October 24, 2018.
Chersich MF, Urban MF, Venter FW, et al. Efavirenz use during pregnancy and for women of child-bearing potential. AIDS Res Ther. 2006; 3 : p.11. doi: 10.1186/1742-6405-3-11 . | Open in Read by QxMD
Practice Advisory on Low-Dose Aspirin and Prevention of Preeclampsia: Updated Recommendations.
Beyer-Westendorf J, Marten S, Michalski F. Outcome of Noac Exposure during Pregnancy (and the problem of event reporting). Blood. 2015; 126 (23): p.1125.
Babb M, Koren G, Einarson A. Treating pain during pregnancy. Can Fam Physician. 2010; 56 (1): p.25, 27.
Azizi F, Amouzegar A. Management of hyperthyroidism during pregnancy and lactation. Eur J Endocrinol. 2011; 164 (6): p.871-876. doi: 10.1530/eje-10-1030 . | Open in Read by QxMD
Schellack G, Schellack N, Kriel M. Pharmacotherapy during pregnancy, childbirth and lactation: points and principles to consider (a 2015 update). S Afr Fam Pract. 2015; 57 (6).
Schaefer C, Peters PWJ, Miller RK. Drugs During Pregnancy and Lactation. Academic Press ; 2014
Hibbard J. Update on Medical Disorders in Pregnancy, An Issue of Obstetrics and Gynecology Clinics - E-Book. Elsevier Health Sciences ; 2010
Quinlan JD, Hill DA. Nausea and vomiting of pregnancy. Am Fam Physician. 2003; 68 (1): p.121-128.
Auffret M, Bernard-Phalippon N, Dekemp J, et al. Misoprostol exposure during the first trimester of pregnancy: Is the malformation risk varying depending on the indication?. Eur J Obstet Gynecol Reprod Biol. 2016; 207 : p.188-192. doi: 10.1016/j.ejogrb.2016.11.007 . | Open in Read by QxMD
Hirshburg JM, Kelsey PA, Therrien CA, Gavino AC, Reichenberg JS. Adverse Effects and Safety of 5-alpha Reductase Inhibitors (Finasteride, Dutasteride): A Systematic Review.. The Journal of clinical and aesthetic dermatology. 2016; 9 (7): p.56-62.
Kolnick L, Harris BD, Choma DP, Choma NN. Hypercalcemia in pregnancy: a case of milk-alkali syndrome.. Journal of general internal medicine. 2011; 26 (8): p.939-42. doi: 10.1007/s11606-011-1658-0 . | Open in Read by QxMD
Hillier K. Magnesium Sulfate. Elsevier ; 2007 : p. 1-5
Editors of LactMed. Magnesium Hydroxide. Drugs and Lactation Database (LactMed). 2006 .
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Pharmacotherapy during pregnancy

Summary

Antibiotics during pregnancy

Drugs of choice

Drugs to avoid

Other medical therapy during pregnancy

Antihypertensives

Drugs of choice

Drugs to avoid

Antifungals

Drugs of choice

Drugs to avoid

Antivirals

Drugs of choice

Drugs to avoid

Anticoagulants

Drugs of choice

Drugs to avoid

Analgesics

Drugs of choice

Drugs to avoid

Thyroid agents

Drugs of choice

Drugs to avoid

Antiepileptics

Drugs of choice

Drugs to avoid

Antiemetics during pregnancy [21]

Other drug classes to avoid during pregnancy [2][19][20]

References

3 free articles remaining

Antiemetics during pregnancy ^[21]

Other drug classes to avoid during pregnancy ^[2]^[19]^[20]