Medication safety during pregnancy - Clinicians need to be familiar with available data on the teratogenicity of newer medications to effectively counsel patients

Medication safety during pregnancy - Clinicians need to be familiar with available data on the teratogenicity of newer medications to effectively counsel patients - ModernMedicine

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Increased risk of birth defects has been linked to use of certain antidepressants during pregnancy.
Newer antidepressants have not been shown to increase the risk of fetal malformation.
Proton pump inhibitors are generally considered safe to use during pregnancy.
Use of disease-modifying antirheumatic drugs during pregnancy should be determined by the clinician on a patient-by-patient basis.
Placental transfer of glyburide is minimal.
Glargine use has been associated with reduced fetal femoral growth in mid- to late pregnancy.

Nearly half of women 18 to 44 years old use prescription drugs.¹ Therefore, clinicians must be prepared to counsel these patients regarding medication use during conception and pregnancy.

Table 1: FDA pregnancy categories for medication use during pregnancy

Since 1979, clinicians in the United States have derived information about the safety of medication use during pregnancy from the US Food and Drug Administration (FDA) classification system. This system classifies medications into 5 categories (A, B, C, D, and X) based on the level of available data and risk-benefit ratio (Table 1).² A variety of new drug therapies likely to be used by women of reproductive age have also been classified (Table 2).²

Table 2 FDA pregnancy classification for new drug therapies

FDA recently proposed revisions to the pregnancy classification system that would eliminate the letter categories but include a risk summary, clinical considerations for counseling, and a review of data in product labeling.³ FDA has proposed adding information about how the disease the respective drug is intended to treat affects the mother and fetus.³ This is important because discontinuing medications sometimes has adverse consequences that must be weighed against potential risks of the drug.

Antiepileptic drugs

A recent American Academy of Neurology guideline on the management of epilepsy during pregnancy recommends avoiding polypharmacy as well as monotherapy with valproate.⁴ Use of multiple antiepileptic drugs (AEDs) during pregnancy is associated with an increased risk of major congenital anomalies.⁵ Valproate, an older AED, has been linked to an increased risk of neural tube defects and facial clefts.^5,6 Teratogenicity data are becoming available for lamotrigine and levetiracetam, 2 commonly used newer AEDs.

Final data from the International Lamotrigine Pregnancy Registry covered 2,444 women and 2,492 pregnancy outcomes between September 1992 and June 3, 2009.⁷ The rate of major defects associated with first-trimester exposure to lamotrigine was 2.2% for monotherapy and 2.8% for polytherapy with AEDs other than valproate.⁷ (By comparison, the incidence of birth defects in the general population is about 3%.⁸ ) The highest rate of major birth defects (10.7%) was seen after first-trimester exposure to lamotrigine in polytherapy regimens that included valproate.⁷

Limitations of this registry should be noted. It was powered to detect only a large increase in specific birth defects. As with most registries, an internal control group of nonexposed patients was not available. Voluntary enrollment introduces the possibility of selection bias. Ascertainment bias also exists because data were collected from 43 countries with different methodologies.

Data from the North American AED registry suggested a possible link between first-trimester lamotrigine exposure and orofacial clefts.⁹ However, no such association was found in a large case-control study, and there were only 2 cases of cleft palate among 629 infants with first-trimester exposure to lamotrigine in the International Lamotrigine Pregnancy Registry.^7,10

A registry from the United Kingdom provided prospective data on 117 first-trimester exposures to levetiracetam, including 39 cases of monotherapy and 78 cases of polytherapy.¹¹ Major congenital malformations were noted in 3 (2.7%) patients, all of whom were also exposed to other AEDs.¹¹ A recent review of 147 cases of levetiracetam exposure during pregnancy found no significant increase in risk of major congenital malformations.¹² Levetiracetam levels should be monitored during pregnancy because of enhanced clearance, particularly in the third trimester.¹³

When use of AEDs is necessary to maintain seizure control during pregnancy, monotherapy with an AED other than valproate is preferred. The optimal time to make changes to AED regimens is before pregnancy; much of the risk accrues early in the first trimester, and it is best to ensure that seizures are controlled without complications on a new regimen before conception.⁴

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