Pregnant Women: Epilepsy: pms-TOPIRAMATE can cause fetal harm when administered to a pregnant woman. Data from pregnancy registries indicate that infants exposed to topiramate in utero have an increased risk for cleft lip and/or cleft palate (oral clefts). When multiple species of pregnant animals received topiramate at clinically relevant doses, structural malformations, including craniofacial defects, and reduced fetal weights occurred in offspring. pms-TOPIRAMATE should be used during pregnancy only if the potential benefit outweighs the potential risk. If this drug is used during pregnancy, or if the patient becomes pregnant while taking this drug, the patient should be apprised of the potential hazard to a fetus (see Fetal Toxicity under Precautions).
pms-TOPIRAMATE treatment can cause metabolic acidosis. The effect of topiramate-induced metabolic acidosis has not been studied in pregnancy; however, metabolic acidosis in pregnancy (due to other causes) can cause decreased fetal growth, decreased fetal oxygenation, and fetal death, and may affect the fetus' ability to tolerate labour. Pregnant patients should be monitored for metabolic acidosis and treated as in the non-pregnant state. Newborns of mothers treated with pms-TOPIRAMATE should be monitored for metabolic acidosis because of transfer of topiramate to the fetus and possible occurrence of transient metabolic acidosis following birth (see Endocrine and Metabolism: Metabolic Acidosis under Precautions).
Migraine Prophylaxis: Prophylactic treatment of migraine: In pregnancy, the occurrence of seizures presents a significant risk for the mother and child. Prescribing pms-TOPIRAMATE to prevent seizures therefore outweighs the risk of malformations to the fetus. However, taking pms-TOPIRAMATE to prevent migraine attacks does not outweigh this risk. Consequently, pms-TOPIRAMATE is contraindicated for the indication prophylaxis of migraine in pregnancy and in women of child-bearing potential who are not using an effective method of contraception (see Dosing Considerations under Dosage & Administration; Contraindications).
Women of Childbearing Potential: Data from pregnancy registries indicate that infants exposed to topiramate in utero have an increased risk for cleft lip and/or cleft palate (oral clefts) (see Pregnancy Registry Data as follows). Consider the benefits and the risks of pms-TOPIRAMATE when prescribing this drug to women of childbearing potential. Because of the risk of oral clefts to the fetus, which occur in the first trimester of pregnancy before many women know they are pregnant, all women of childbearing potential should be apprised of the potential hazard to the fetus from exposure to pms-TOPIRAMATE. If the decision is made to use pms-TOPIRAMATE, women who are not planning a pregnancy should use effective contraception (see Drug-Drug Interactions: Other Drug Interactions: Oral Contraceptives under Interactions). Women who are planning a pregnancy should be counselled regarding the relative risks and benefits of pms-TOPIRAMATE use during pregnancy, and alternative therapeutic options should be considered for these patients (see Information for Patients: Fetal Toxicity under Precautions).
Labour and Delivery: pms-TOPIRAMATE may cause fetal harm when administered to a pregnant woman. There is an increased risk of pre-term labor and premature delivery associated with the use of AEDs, including topiramate.
pms-TOPIRAMATE should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus. The development of topiramate-induced metabolic acidosis in the mother and/or in the fetus might affect the fetus' ability to tolerate labour (see Pregnant Women: Epilepsy as previously mentioned).
Pregnancy Registry Data: Data from the North American Antiepileptic Drug (NAAED) Pregnancy Registry indicate an increased risk of oral clefts in infants exposed to topiramate monotherapy during the first trimester of pregnancy. The prevalence of oral clefts was 1.2% compared to a prevalence of 0.39% to 0.46% in infants exposed to other AEDs, and a prevalence of 0.12% in infants of mothers without epilepsy or treatment with other AEDs. For comparison, the Centers for Disease Control and Prevention (CDC) reviewed available data on oral clefts in the United States and found a similar background rate of 0.17%. The relative risk of oral clefts in topiramate-exposed pregnancies in the NAAED Pregnancy Registry was 9.6 (95% Confidence Interval = CI 3.6 - 25.7) as compared to the risk in a background population of untreated women. The UK Epilepsy and Pregnancy Register reported a similarly increased prevalence of oral clefts of 3.2% among infants exposed to topiramate monotherapy. The observed rate of oral clefts was 16 times higher than the background rate in the UK, which is approximately 0.2%.
Nursing Women: Topiramate is excreted in the milk of lactating rats. The excretion of topiramate in human milk has not been evaluated in controlled studies. However, some observations in patients suggest that topiramate is extensively excreted into human breast milk. Diarrhea and somnolence have been reported in breastfed infants whose mothers receive topiramate treatment. Therefore, a decision should be made to either discontinue breast-feeding or to discontinue pms-TOPIRAMATE taking into account the benefit of breast-feeding for the child and the benefit of the drug to the mother. Caution should be exercised when administered to a nursing woman.