Also known as Keppra, Levetiracetame, Levetiracetamum, Levitiracetam
A pyrrolidine with antiepileptic activity. The exact mechanism through which levetiracetam exerts its effects is unknown but does not involve inhibitory and excitatory neurotransmitter activity. Stereoselective binding of levetiracetam was confined to synaptic plasma membranes in the central nervous system with no binding occurring in peripheral tissue. Levetiracetam inhibits burst firing without affecting normal neuronal excitability, which suggests that it may selectively prevent hyper-synchronization of epileptiform burst firing and propagation of seizure activity.
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Can I take Levetiracetam while breastfeeding?
Maternal doses of levetiracetam up to 3500 mg daily produce low levels in milk and would not be expected to cause any adverse effects in breastfed infants, especially if the infant is older than 2 months. If levetiracetam is required by the mother, it is not a reason to discontinue breastfeeding. However, the infant should be monitored for drowsiness, adequate weight gain, and developmental milestones, especially in younger, exclusively breastfed infants and when using combinations of anticonvulsants. Maternal serum level monitoring and dosage adjustment is advisable in the early postpartum period if the drug was taken throughout pregnancy and breastfeeding.[1] Some evidence suggests that levetiracetam might reduce the maternal breastmilk supply in some women.
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. A woman who was taking phenytoin, valproic acid and an unspecified dosage of levetiracetam had a milk levetiracetam level of 16.9 mg/L 3 hours after a dose, which was 3.1 times her simultaneous serum level.[2]
Breastmilk levels in 12 mothers who were monitored at 4 days and 2 to 3 months postpartum were “significantly lower” than maternal blood levels. Further details were not published in the abstract.[3]
Seven women taking an average of 2430 mg daily (range 1500 to 3500 mg daily) of levetiracetam plus various other anticonvulsants for epilepsy at the time of delivery had foremilk levels measured 3 to 5 days postpartum. Average milk levels were 12.5 mg/L (range 4.8 to 26 mg/L). Milk levels were again measured in 5 of the women plus another woman at one or more of the following times: 2, 4, 6 to 8 weeks and 4 or 10 months postpartum. Specific milk levels were not reported at those times, but the milk to plasma ratio was very similar at those times to the values at 3 to 5 days postpartum.[4]
Eleven mothers who were 4 to 23 days postpartum and taking levetiracetam provided milk samples before nursing. Three women taking 100 mg daily had an average milk levetiracetam concentration of 8.68 mg/L (range 5.79 to 10.55 mg/L); 2 women taking 2000 mg daily had milk levels of 11.7 and 35.7 mg/L; 4 women taking 2500 mg daily had an average milk levetiracetam concentration of 13.95 mg/L (range 10 to 20.4 mg/L); and 2 women taking 3000 mg daily had milk concentrations of 17.4 and 29.1 mg/L. The authors estimated that a fully breastfed infant would receive 7.9% of the maternal weight-adjusted dosage.[5]
A pregnant woman was treated with levetiracetam 1000 mg and lacosamide 100 mg twice daily as well as enoxaparin and labetalol for the rest of her pregnancy and postpartum. Levetiracetam was undetectable (<3 mg/L) in a milk sample on day 5 postpartum (exact time not specified).[6] Infant Levels. An infant (aged approximately 1 to 2 weeks) of a mother taking phenytoin, valproic acid and levetiracetam (dosage unspecified) had a serum levetiracetam level of 1 mg/L 96 hours after the mother discontinued breastfeeding.[2]
Seven breastfed infants whose mothers were taking an average dosage of 2430 mg daily (range 1500 to 3500 mg daily) of levetiracetam plus various other anticonvulsants during pregnancy and lactation had serum levetiracetam measured before the mother’s morning dose at 3 to 5 days of age. In 6 infants, levetiracetam was undetectable (<1.7 mg/L), although one of them had a serum level of 13 mg/L at the age of 1 day. A seventh infant who was fully breastfed had a serum level of 2.5 mg/L at 3 to 5 days of age. This infant and had serum levels ranging from 2.5 to 2.9 mg/L during the first 8 weeks of life and an undetectable serum level at 4 months of age.[4] Ten infants who were 4 to 23 days old were breastfed by mothers taking levetiracetam in dosages of 1000 to 3000 mg daily. Infant plasma levels were obtained 30 to 120 minutes after nursing and before their mother’s morning dose (10 to 15 hours after the last evening dose), except for one infant whose plasma was sampled before nursing. The average levetiracetam plasma concentration was 1.9 mg/L (range 0.7 to 3.4 mg/L). The infants’ plasma levels averaged 13.5% of the maternal plasma concentration taken before their morning dose. The authors found that 13 newborns’ levetiracetam elimination half-life averaged 18 hours, which is 2 to 3 times that of adults.[5] The 10-day-old breastfed (extent not stated) infant of a mother who was taking levetiracetam 3000 mg daily had a serum concentration of 2.1 mg/L, which was less than half of the low end of the therapeutic range. Timing of the sample was not stated.[7] A pregnant woman was treated with levetiracetam 1000 mg and lacosamide 100 mg twice daily as well as enoxaparin and labetalol for the rest of her pregnancy and postpartum. Her infant was delivered at 36 weeks gestation and about 50% breastfed for the first 15 days of life. The infant had a cord blood levetiracetam concentration of 23 mg/L at birth and an undetectable (<3 mg/L) levetiracetam blood level on day 8 of age.[6]
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. A woman who was taking phenytoin, valproic acid and an unspecified dosage of levetiracetam had a milk levetiracetam level of 16.9 mg/L 3 hours after a dose, which was 3.1 times her simultaneous serum level.[2]
Breastmilk levels in 12 mothers who were monitored at 4 days and 2 to 3 months postpartum were “significantly lower” than maternal blood levels. Further details were not published in the abstract.[3]
Seven women taking an average of 2430 mg daily (range 1500 to 3500 mg daily) of levetiracetam plus various other anticonvulsants for epilepsy at the time of delivery had foremilk levels measured 3 to 5 days postpartum. Average milk levels were 12.5 mg/L (range 4.8 to 26 mg/L). Milk levels were again measured in 5 of the women plus another woman at one or more of the following times: 2, 4, 6 to 8 weeks and 4 or 10 months postpartum. Specific milk levels were not reported at those times, but the milk to plasma ratio was very similar at those times to the values at 3 to 5 days postpartum.[4]
Eleven mothers who were 4 to 23 days postpartum and taking levetiracetam provided milk samples before nursing. Three women taking 100 mg daily had an average milk levetiracetam concentration of 8.68 mg/L (range 5.79 to 10.55 mg/L); 2 women taking 2000 mg daily had milk levels of 11.7 and 35.7 mg/L; 4 women taking 2500 mg daily had an average milk levetiracetam concentration of 13.95 mg/L (range 10 to 20.4 mg/L); and 2 women taking 3000 mg daily had milk concentrations of 17.4 and 29.1 mg/L. The authors estimated that a fully breastfed infant would receive 7.9% of the maternal weight-adjusted dosage.[5]
A pregnant woman was treated with levetiracetam 1000 mg and lacosamide 100 mg twice daily as well as enoxaparin and labetalol for the rest of her pregnancy and postpartum. Levetiracetam was undetectable (<3 mg/L) in a milk sample on day 5 postpartum (exact time not specified).[6] Infant Levels. An infant (aged approximately 1 to 2 weeks) of a mother taking phenytoin, valproic acid and levetiracetam (dosage unspecified) had a serum levetiracetam level of 1 mg/L 96 hours after the mother discontinued breastfeeding.[2]
Seven breastfed infants whose mothers were taking an average dosage of 2430 mg daily (range 1500 to 3500 mg daily) of levetiracetam plus various other anticonvulsants during pregnancy and lactation had serum levetiracetam measured before the mother’s morning dose at 3 to 5 days of age. In 6 infants, levetiracetam was undetectable (<1.7 mg/L), although one of them had a serum level of 13 mg/L at the age of 1 day. A seventh infant who was fully breastfed had a serum level of 2.5 mg/L at 3 to 5 days of age. This infant and had serum levels ranging from 2.5 to 2.9 mg/L during the first 8 weeks of life and an undetectable serum level at 4 months of age.[4] Ten infants who were 4 to 23 days old were breastfed by mothers taking levetiracetam in dosages of 1000 to 3000 mg daily. Infant plasma levels were obtained 30 to 120 minutes after nursing and before their mother’s morning dose (10 to 15 hours after the last evening dose), except for one infant whose plasma was sampled before nursing. The average levetiracetam plasma concentration was 1.9 mg/L (range 0.7 to 3.4 mg/L). The infants’ plasma levels averaged 13.5% of the maternal plasma concentration taken before their morning dose. The authors found that 13 newborns’ levetiracetam elimination half-life averaged 18 hours, which is 2 to 3 times that of adults.[5] The 10-day-old breastfed (extent not stated) infant of a mother who was taking levetiracetam 3000 mg daily had a serum concentration of 2.1 mg/L, which was less than half of the low end of the therapeutic range. Timing of the sample was not stated.[7] A pregnant woman was treated with levetiracetam 1000 mg and lacosamide 100 mg twice daily as well as enoxaparin and labetalol for the rest of her pregnancy and postpartum. Her infant was delivered at 36 weeks gestation and about 50% breastfed for the first 15 days of life. The infant had a cord blood levetiracetam concentration of 23 mg/L at birth and an undetectable (<3 mg/L) levetiracetam blood level on day 8 of age.[6]
Possible effects on lactation
In a study of mothers taking levetiracetam during breastfeeding, 7 of 18 mothers discontinued or reduced breastfeeding because of poor milk output. The infant of one mother taking 3000 mg of levetiracetam daily plus clobazam had poor weight gain at day 15 of life.[7]
References
1. Lopez-Fraile IP, Cid AO, Juste AO, Modrego PJ. Levetiracetam plasma level monitoring during pregnancy, delivery, and postpartum: clinical and outcome implications. Epilepsy Behav. 2009;15:372-5. PMID: 19362602
2. Kramer G, Hosli I, Glanzmann R et al. Levetiracetam accumulation in human breast milk. Epilepsia. 2002;43 (Suppl 7):105. Abstract.
3. Greenhill L, Betts T, Yarrow H et al. Breast milk levels of levetiracetam after delivery. Epilepsia. 2004;45 (suppl 7):230. Abstract.
4. 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
5. Tomson T, Palm R, Kallen K et al. Pharmacokinetics of levetiracetam during pregnancy, delivery, in the neonatal period, and lactation. Epilepsia. 2007. PMID: 17381438
6. Ylikotila P , Ketola RA, Timonen S et al. Early pregnancy cerebral venous thrombosis and status epilepticus treated with levetiracetam and lacosamide throughout pregnancy. Reprod Toxicol. 2015;57:204-6. PMID: 26187779
7. Paret N, Gouraud A, Bernard N et al. Long-term follow-up of infants exposed to levetiracetam during breastfeeding: Comparison to a control group. Birth Defects Res A Clin Mol Teratol. 2014 ;100:537-8. Abstract.
8. Rauchenzauner M, Kiechl-Kohlendorfer U, Rostasy K, Luef G. Old and new antiepileptic drugs during pregnancy and lactation – report of a case. Epilepsy Behav. 2011;20:719-20. PMID: 21444249
Last Revision Date
20150908
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Source: LactMed – National Library of Medicine (NLM)