From the FDA Drug Label
Use in Specific Populations 8. 1 Pregnancy Pregnancy Category C: There are no adequate and well-controlled studies in pregnant women. In nonclinical studies in mice, rats, and rabbits, gabapentin was developmentally toxic when administered to pregnant animals at doses similar to or lower than those used clinically. Gabapentin should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus When pregnant mice received oral doses of gabapentin (500 mg, 1000 mg, or 3000 mg/kg/day) during the period of organogenesis, embryo-fetal toxicity (increased incidences of skeletal variations) was observed at the two highest doses The no-effect dose for embryo-fetal developmental toxicity in mice was 500 mg/kg/day or approximately ½ of the maximum recommended human dose (MRHD) of 3600 mg/kg on a body surface area (mg/m2) basis In studies in which rats received oral doses of gabapentin (500 to 2000 mg/kg/day), during pregnancy, adverse effect on offspring development (increased incidences of hydroureter and/or hydronephrosis) were observed at all doses. The lowest effect dose for developmental toxicity in rats is approximately equal to the MRHD on a mg/m2 basis When pregnant rabbits were treated with gabapentin during the period of organogenesis, an increase in embryo-fetal mortality was observed at all doses tested (60 mg, 300 mg, or 1500 mg/kg). The lowest effect dose for embryo-fetal developmental toxicity in rabbits is less than the MRHD on a mg/m2 basis
The effects of Gabapentin on pregnancy are not well understood due to the lack of adequate and well-controlled studies in pregnant women. However, nonclinical studies in animals have shown that Gabapentin can be developmentally toxic at doses similar to or lower than those used clinically.
- Embryo-fetal toxicity was observed in mice at high doses.
- Adverse effects on offspring development were seen in rats at all tested doses.
- Increased embryo-fetal mortality was found in rabbits at all tested doses. Gabapentin should only be used during pregnancy if the potential benefit justifies the potential risk to the fetus 1.
From the Research
Gabapentin should be used during pregnancy only when the potential benefits outweigh the risks, as it has been associated with an increased risk of adverse neonatal and maternal outcomes, including preterm birth, small for gestational age, and neonatal intensive care unit admission, as shown in a recent study 2. The medication crosses the placenta and has been associated with a small increased risk of congenital malformations, particularly when used in the first trimester. Key points to consider when using gabapentin during pregnancy include:
- The potential for adverse effects on fetal development, as seen in animal studies at doses similar to human therapeutic doses
- The importance of consulting a healthcare provider before starting or continuing gabapentin during pregnancy
- The need for regular prenatal monitoring to assess fetal development and adjust treatment as needed
- The consideration of alternative medications with better safety profiles during pregnancy, depending on the condition being treated
- The risk of preterm birth, small for gestational age, and neonatal intensive care unit admission, particularly when gabapentin is used late in pregnancy, as reported in a study of 1,753,865 Medicaid-eligible pregnancies 2. For women with epilepsy who require gabapentin, sudden discontinuation could lead to breakthrough seizures that may pose greater risks to both mother and fetus than continuing the medication. If gabapentin is necessary during pregnancy, the lowest effective dose should be used, and women taking gabapentin who become pregnant should not stop the medication abruptly but should immediately discuss management options with their healthcare provider, as recommended by a study published in the European journal of obstetrics, gynecology, and reproductive biology 3. A systematic review of gabapentinoid use during pregnancy and its impact on pregnancy and childhood outcomes also highlights the need for careful evaluation of the benefit-risk balance for both mother and fetus/infant when using gabapentin during pregnancy 4.