Zonisamide

Drug Levels and Effects:




Summary of Use during Lactation:


Limited information indicates that maternal doses of zonisamide up to 400 mg daily produce relatively high levels in milk, but serum levels in neonates decrease during the first month of life while nursing. Monitor the infant for drowsiness, adequate weight gain, and developmental milestones, especially in younger, exclusively breastfed infants and when using combinations of anticonvulsant drugs. Measurement of an infant serum level might help rule out toxicity if there is a concern.


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 took zonisamide monotherapy (dosage and regimen not specified) during pregnancy and postpartum. Two serum concentration were measured: 13.6 mg/L at 3 hours before delivery and 23.2 mg/L on day 17 postpartum. Milk samples were collected postpartum and measured for zonisamide using untreated breastmilk in an enzyme immunoassay. Milk levels were 4.6 mg/L at 58 hours postpartum, 13.6 at 61 hours postpartum, and 19.2 mg/L at 77 hours postpartum.[1]

A mother was taking oral zonisamide 300 mg daily. Milk levels measured 1.5 hours after her dose on days 6 and 30 postpartum were 9.75 and 10.5 mg/L, respectively. Milk levels measured 2.5 hours after her dose on days 3 and 15 postpartum were 8.25 and 9.12 mg/L, respectively.[2] The same authors reported that "patients" (number and time postpartum unspecified) taking oral zonisamide 300 mg daily had an average (+/- SD) breastmilk level of 9.41 +/- 0.95 mg/L.[3] These values are exactly the same as the average and standard deviation of the former patient's 4 milk levels. It is likely that these results are merely a duplicate of the above results.

A mother who was taking oral zonisamide 400 mg,carbamazepine1 g, and clonazepam 1 mg daily had breastmilk whey levels of zonisamide measured 9 times from day 1 to day 10 postpartum. All of the levels were distributed (neither increasing nor decreasing) in the range of 8.9 to 10.9 mg/L.[4]

Using data from the 2 patients with relatively complete information on dosage and milk levels,[1][3] the average amounts in milk represent an infant dosage of about 23 to 28% of the maternal weight-adjusted dosage.

Infant Levels.

The serum zonisamide levels were measured in a breastfed infant whose mother was taking zonisamide 400 mg,carbamazepine1 g, and clonazepam 1 mg daily. In this infant and in another breastfed infant whose mother was taking zonisamide 400 mg andcarbamazepine800 mg daily, high transplacentally acquired plasma levels of about 14 and 11 mg/L, respectively, fell over a 6- to 7-day monitoring period despite intake via breastmilk. The first infant's plasma level on day 24 was 3.9 mg/L.[4]

An infant whose mother was taking zonisamide (dose not specified) during pregnancy and breastfeeding had a serum zonisamide concentration that was 3.6 mg/L or 17% of the maternal serum concentration at 9 days postpartum. The half-life of zonisamide in this infant and one other was estimated to be about 100 hours.[5]


Effects in Breastfed Infants:


A patient taking zonisamide 300 mg orally 3 times daily as well as other unspecified antipsychotics was followed at 0, 3, 14 and 30 days postpartum. Her infant exhibited no behavioral problems.[2]


Possible Effects on Lactation:


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


Alternate Drugs to Consider:


Dependent on the condition being treated.


References:


1. Kimura S. [Zonisamide: its placental transport, biological half-life in the newborn, and transport into mother's milk--a study of a case of an infant born of a mother who had been treated with zonisamide alone during pregnancy]. No To Hattatsu. 1998;30:350-1. PMID:9734979
2. Shimoyama R, Ohkubo T, Sugawara K. Monitoring of zonisamide in human breast milk and maternal plasma by solid-phase extraction HPLC method. Biomed Chromatogr. 1999;13:370-2. PMID:10425030
3. Sugawara K, Shimoyama R, Ohkubo T. Determinations of psychotropic drugs and antiepileptic drugs by high-performance liquid chromatography and its monitoring in human breast milk. Hirosaki Med J. 1999;51 (Suppl):S81-6.
4. Kawada K, Itoh S, Kusaka T et al. Pharmacokinetics of zonisamide in perinatal period. Brain Develop. 2002;24:95-7. PMID:11891100
5. Ohman I, Tomson T. Pharmacokinetics of zonizamide in neonatal period and during lactation. Basic Clin Pharmacol Toxicol. 2011;109:73. Abstract.



Substance Identification:




Substance Name:

Zonisamide

CAS Registry Number:

68291-97-4

Drug Class:


  • Anticonvulsants


  • Administrative Information:




    LactMed Record Number:


    397


    Last Revision Date:


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