Drugs to avoid preconceptionally
Women of reproductive age can be taking medications for chronic diseases, may start new medications during pregnancy, or require over-the-counter medications during the preconception period or during pregnancy.
We will discuss medications taken commonly during pregnancy separately from those taken for chronic illness. For these chronic illnesses, most prescription drug regimens should be optimized in the preconception period, and medication changes avoided during pregnancy, unless indicated. For more detailed information regarding drugs used in the following chronic diseases, please see the appropriate section elsewhere in this chapter for the specific chronic disease category: diabetes mellitus, hypothyroidism, hypertension, heart disease, IBD, neurological disease, thrombophilic disorders, and HIV infection.Many medications require a period of clearance from the maternal circulation, prior to conception. The following commonly used medications should be optimized in the preconception period, with the optimal period of clearance prior to conception dependent on the medication, if indicated:
Pain and fever
• Non-steroidal anti-inflammatory drugs (NSAIDs): safety profile varies with gestational age, however NSAIDs should generally be avoided during pregnancy. Limit use in months of preconception.
• AcetaminophenZparacetamol: generally regarded as safe in pregnancy. Long-term use is not advised, but it is the antipyretic and analgesic of choice in pregnancy if short-term medication is needed.
• Opioids: although not recommended for use in pregnancy, the balance of maternal pain control with the potential effects on the fetus must be considered. Studies have shown evidence of neonatal withdrawal syndrome; however, this is uncommon (103). First-line treatment for non-cancer chronic pain in pregnancy is initiation of methadone, and should be considered in the preconception period.
Antibiotics
Antibiotics deemed safe in pregnancy include the following, and can thus be used in the preconception period: penicillins, cephalosporins, azithromycin, clindamycin, and erythromycin.
Gastroesophageal reflex disease
• Antacids: considered generally safe in pregnancy, and can be used in the preconception period.
• H2 receptor antagonists (e.g. ranitidine (104)): considered safe in pregnancy, and can be used in the preconception period. Caution should be used in breastfeeding.
• Proton pump inhibitors (e.g. pantoprazole) (105): considered generally safe in pregnancy, and can be used in the preconception period.
Headaches and migraine
Preferred agents include acetaminophen and metoclopramide, which are considered safe in pregnancy and thus recommended in the preconception period.
Vaccinations
For all women of reproductive age in the preconception period, immunization status should be checked annually and updated as indicated for the following: tetanus-diphtheria toxoid/ diphtheria-tetanus-pertussis; measles, mumps, and rubella; and varicella.
• Tetanus-diphtheria toxoid/diphtheria-tetanus-pertussis: preferred immunity in the preconception period, however can be given in pregnancy after 20 weeks' gestation, and ideally after 28 weeks' gestation.
• Measles, mumps, and rubella: contraindicated in pregnancy, and therefore should be given 3 or more months prior to conception. If preconception immunization is not possible, then the vaccine should be given immediately postpartum.
• Varicella: contraindicated in pregnancy, and therefore should be given prior to conception. If preconception immunization is not possible, then the vaccine should be given immediately postpartum.
• Influenza: one dose in preconception or conception period, given annually.
• Hepatitis B: preferred immunity in the preconception period, however can be given in pregnancy if unvaccinated or at high risk of exposure.
• HPV: routine screening, with recommended subgroups vaccination as per regional health authority recommendations.
Antidepressants
Antidepressants are commonly used in pregnancy, in approximately 3% of women in Europe, and 8% of women in the United States.
This class of medications crosses the placenta and the fetal blood-brain barrier, and should therefore be used with caution. In consideration of this class of drugs in the preconception period, a trial of taper can be tried 6 months in advance of conception, with the goal to have the medication regimen optimized 3 months prior to conception. When considering discontinuation of antidepressants, the balance between the maternal psychiatric condition and health of the fetus must be balanced, with an emphasis placed on maternal health in the preconception period. If multiple agents are used, then transition to a single agent in the preconception period is advised if possible.Antihypertensives
• ACE inhibitors are contraindicated in pregnancy, and should be discontinued with an appropriate antihypertensive regiment established 2-3 months preconceptionally (32). Preferred agents include labetalol, nifedipine, and methyldopa.
• Angiotensin II receptor blockers, similar to ACE inhibitors, are contraindicated in pregnancy and should be discontinued with an appropriate antihypertensive regiment established 2-3 months preconceptionally (32).
Antiepileptic drugs (AEDs)
(See ‘Epilepsy' for more detailed information.)
• Divalproex sodium and valproic acid are contraindicated in pregnancy, and should therefore be replaced with a different AED 6 months prior to conception. The benefits of switching AEDs should be balanced with the maternal seizure condition, with an emphasis placed on maternal health.
Immunosuppressive agents
(See ‘Preconceptional counselling of women with inflammatory bowel disease' for more detailed information.)
• Methotrexate is contraindicated in pregnancy due to the potent abortifacient effect and congenital malformations, and should be replaced with a different monotherapy of anti-inflammatory or immunosuppressive therapy in discussion with a gastroenterologist (60). Discontinuation at least 4 months prior to conception, and 6 months if possible is recommended (106).
Treatment of thromboembolic disorders
(See ‘Preconceptional management strategies in women with thrombophilic disorders' for more detailed information, including treatment course and timeline.)
• The recommended agent for treatment of VTE in pregnancy is low-molecular-weight heparin (e.g. dalteparin), and should therefore be considered as the first-line treatment in the preconception period.
• Warfarin (brand name: Coumadin) is contraindicated in pregnancy due to congenital malformations (37).
Antiretroviral therapy
• Considered safe in pregnancy, and should be continued throughout pregnancy. If not initiated prior to conception, and there is no urgent medical indication for ARV therapy, then initiation can be delayed until 14 weeks' gestation.
• Two ARV therapies, didanosine and efavirenz, are not recommended in pregnancy, and therefore should be avoided if alternatives are available, with transition to a different ARV. These have shown toxicity and an increased rate of fetal congenital malformations in human and/or animal studies, respectively.
In the United Kingdom, the British National Formulary provides an exhaustive reference guide for medications and their safety profile in pregnancy. Historically, the United States Food and Drug Administration (FDA) provided a five-letter categorization of drug safety profile in pregnancy (A, B, C, D, and X) that was commonly used to report the safety profile of medications (107). The FDA has recently published the Pregnancy and Lactation Labelling Rule, which changes the labelling system to provide more comprehensive information, and also provides an additional category of information for couples regarding contraception and infertility related to medications (108).