Also known as McN-4853, RWJ-17021, TPM, Tipiramate, Tipiramato, Topamax, Topiramato, Topiramatum

A sulfamate-substituted monosaccharide with anticonvulsant property. Although the mechanism of action has not been fully elucidated, topiramate antagonizes kainate/AMPA subtype of the glutamate receptors, which are ligand-activated cation channels that mediate the fast component of excitatory postsynaptic currents in neurons of the central nervous system. This antagonistic action results in stabilizing hyper-excited neural membranes, inhibiting repetitive neuronal firing, and decreasing propagation of synaptic impulses, thereby impedes seizure occurrences. In addition, this agent augments gamma-aminobenzoic acid (GABA) activity and thereby attenuating GABAnergic inhibitory transmission.

Originator: NCI Thesaurus | Source: The website of the National Cancer Institute (http://www.cancer.gov)

Can I take Topiramate while breastfeeding?

Limited information indicates that maternal doses of topiramate up to 200 mg daily produce relatively low levels in infant serum. Monitor the infant for diarrhea, drowsiness, irritability, adequate weight gain, and developmental milestones, especially in younger, exclusively breastfed infants and when using combinations of anticonvulsant or psychotropic drugs.

Drug levels

In published reports of anticonvulsant use during breastfeeding, most women were taking a combination of anticonvulsants. Some other anticonvulsants (e.g., phenytoin, carbamazepine) stimulate the metabolism of other drugs including anticonvulsants, whereas others (e.g., valproic acid) inhibit the metabolism of other drugs. Therefore, the relationship of the maternal dosage to the concentration in breastmilk can be quite variable, making calculation of the weight-adjusted percentage of maternal dosage less meaningful than for other drugs in this database.

Maternal Levels. Three women were taking oral topiramate daily. One taking 150 mg daily had an average milk level of 2.3 mg/L on day 24 postpartum. A mother taking 200 mg daily had average milk levels of 4.8 mg/L on day 20 postpartum and 4.6 mg/L on day 97 postpartum. The third woman who was taking 200 mg daily had average milk level 610 mcg/L on day 14 postpartum and 1.2 mg/L on day 27 postpartum. The authors estimated that the infants received doses between 0.1 and 0.7 mg/kg/day which was between 3 and 23% of the mother’s weight-adjusted dose.[1]

A woman was taking 175 mg of topiramate daily. On day 12 postpartum, her dose was reduced to 150 mg daily and 4 hours after the dose, her milk topiramate concentration was 3.1 mg/L.[2]

A nursing mother was taking 100 mg of topiramate daily. Topiramate was detected in breastmilk at a concentration of 5.3 mg/L at an unspecified time with respect to the dose. The authors estimated that the infant might have received 35% of the maternal weight-adjusted dosage, although their calculation method is unclear.[3] Using the milk level of 5.3 mg/L, the infant would have received 56% of the maternal weight-adjusted dosage.

Infant Levels. Three infants were breastfed from birth while their mothers were taking oral topiramate for epilepsy. Serum levels in a 24-day-old infant whose mother was taking 150 mg daily were about 475 mcg/L. Another infant whose mother was taking 200 mg daily had an average serum level of 594 mcg/L at 20 days of age and 713 mcg/L at 97 days of age. A third infant whose mother was taking 200 mg daily had undetectable (<305 mcg/L) serum levels at 14 and 27 days of age. Overall, their plasma levels were about 10 to 20% of maternal plasma levels.[1] In a preliminary report that added 3 new infants to the original 3 reported had consistent findings. Five of 6 infants had detectable (>305 mcg/L) serum concentrations, but none had quantifiable (>949 mcg/L) serum topiramate concentrations.[4]

A woman was taking 175 mg of topiramate daily. On day 26 postpartum, her breastfed infant had a serum level of 0.8 mg/L at 3 hours after a dose, which was 15% of the mother’s simultaneous serum level.[2]

Effects in breastfed infants

In published reports of anticonvulsant use during breastfeeding, most women were taking a combination of anticonvulsants. Some other anticonvulsants (e.g., phenytoin, carbamazepine) stimulate the metabolism of other drugs including anticonvulsants, whereas others (e.g., valproic acid) inhibit the metabolism of other drugs. Therefore, the relationship of the maternal dosage to the concentration in breastmilk can be quite variable, making calculation of the weight-adjusted percentage of maternal dosage less meaningful than for other drugs in this database.

Maternal Levels. Three women were taking oral topiramate daily. One taking 150 mg daily had an average milk level of 2.3 mg/L on day 24 postpartum. A mother taking 200 mg daily had average milk levels of 4.8 mg/L on day 20 postpartum and 4.6 mg/L on day 97 postpartum. The third woman who was taking 200 mg daily had average milk level 610 mcg/L on day 14 postpartum and 1.2 mg/L on day 27 postpartum. The authors estimated that the infants received doses between 0.1 and 0.7 mg/kg/day which was between 3 and 23% of the mother’s weight-adjusted dose.[1]

A woman was taking 175 mg of topiramate daily. On day 12 postpartum, her dose was reduced to 150 mg daily and 4 hours after the dose, her milk topiramate concentration was 3.1 mg/L.[2]

A nursing mother was taking 100 mg of topiramate daily. Topiramate was detected in breastmilk at a concentration of 5.3 mg/L at an unspecified time with respect to the dose. The authors estimated that the infant might have received 35% of the maternal weight-adjusted dosage, although their calculation method is unclear.[3] Using the milk level of 5.3 mg/L, the infant would have received 56% of the maternal weight-adjusted dosage.

Infant Levels. Three infants were breastfed from birth while their mothers were taking oral topiramate for epilepsy. Serum levels in a 24-day-old infant whose mother was taking 150 mg daily were about 475 mcg/L. Another infant whose mother was taking 200 mg daily had an average serum level of 594 mcg/L at 20 days of age and 713 mcg/L at 97 days of age. A third infant whose mother was taking 200 mg daily had undetectable (<305 mcg/L) serum levels at 14 and 27 days of age. Overall, their plasma levels were about 10 to 20% of maternal plasma levels.[1] In a preliminary report that added 3 new infants to the original 3 reported had consistent findings. Five of 6 infants had detectable (>305 mcg/L) serum concentrations, but none had quantifiable (>949 mcg/L) serum topiramate concentrations.[4]

A woman was taking 175 mg of topiramate daily. On day 26 postpartum, her breastfed infant had a serum level of 0.8 mg/L at 3 hours after a dose, which was 15% of the mother’s simultaneous serum level.[2]

Possible effects on lactation

Relevant published information was not found as of the revision date.

References

1. Ohman I, Vitols S, Luef G et al. Topiramate kinetics during delivery, lactation, and in the neonate: preliminary observations. Epilepsia. 2002;43:1157-60. PMID: 12366729

2. Froscher W, Jurges U. [Topiramate used during breast feeding]. Aktuel Neurol. 2006;33:215-7.

3. Westergren T, Hjelmeland K, Kristoffersen B et al. Probable topiramate-induced diarrhea in a 2-month-old breast-fed child – A case report. Epilepsy Behav Case Report. 2014;2:22-3. PMID: 25667861

4. Ohman I, Luef G, Tomson T. Topiramate kinetics during lactation. Epilepsia. 2007;48 (Suppl 7):156-7. Abstract p417.

5. Johannessen SI, Helde G, Brodtkorb E. Levetiracetam concentrations in serum and in breast milk at birth and during lactation. Epilepsia. 2005;46:775-7. PMID: 15857447

6. Gentile S. Topiramate in pregnancy and breastfeeding. Clin Drug Investig. 2009;29:139-41. PMID: 19133709

Last Revision Date

20150602

Disclaimer:Information presented in this database is not meant as a substitute for professional judgment. You should consult your healthcare provider for breastfeeding advice related to your particular situation. The U.S. government does not warrant or assume any liability or responsibility for the accuracy or completeness of the information on this Site.

Source: LactMed – National Library of Medicine (NLM)

3D Model of the Topiramate molecule

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