Zonisamide

For an informed discussion with your doctor or pharmacist. This information collection is not a clinically validated interaction checker. Missing data do not establish safety. Do not change or stop prescribed medicines on the basis of this information. The findings apply to the specific conditions studied; laboratory and animal studies cannot be directly extrapolated to humans.

Active substance: Zonisamide

Examples of brand names: Zonegran [EU/DE]

ATC code: N03AX15

Main use (for orientation): Epilepsy

Documented research summary

The adult concentration increase in the early 2017 expanded-access analysis is not significant for zonisamide in the expanded same programme in 2023 (n=33; p=0.7598); not independent replication. A small paediatric study reports associations between zonisamide and CBD pharmacokinetics. A dog study with a CBD/CBDA mixture shows no difference in zonisamide concentrations; a paediatric liver case involving several medicines does not allow isolated zonisamide causality.

Uncertainties and limitations

Does not establish safety for less-studied cannabinoids or untested formulations/doses.

Do not infer clinical dosage from preclinical effects or enzyme hypotheses.

Separately recorded findings

5 separately recorded findings. Each statement applies to its documented study context.

CBD – clinical signals

Finding ID: B0074

Type of result: No / minor effect under the conditions studied

Observation: No concentration signal; p=0.7598.

Mechanism: PK observation

Study type: Observational study: no signal detected

Context studied: n=33.

Clinical interpretation: Not ruled out

Limitations and uncertainties: Context / limitations of CL20; a lack of statistical significance does not establish equivalence.

Original sources for this finding: Final analysis of potential drug-drug interactions between highly purified cannabidiol and anti-seizure medications in an open-label expanded access program [CL20]

CBD – clinical signals

Finding ID: B0077

Type of result: Positive finding / indication

Observation: Concentration increase associated with CBD dose.

Mechanism: Mechanism uncertain

Study type: Open-label observational study

Context studied: 81 in total; adults only.

Clinical interpretation: Unclear

Limitations and uncertainties: Consider CL20 as a later analysis; not an independent replication.

Original sources for this finding: Interactions between cannabidiol and commonly used antiepileptic drugs [CL21]

CBD/CBDA-containing hemp extract – laboratory and animal studies

Finding ID: B0353

Type of result: Preclinical evidence

Observation: Zonisamide serum concentrations did not differ significantly between extract and placebo (treatment p=0.83).

Mechanism: Veterinary pharmacokinetics: no detectable concentration difference

Study type: Veterinary study

Context studied: Randomised crossover dog study, 11 animals receiving zonisamide, combined CBD/CBDA approximately 2 mg/kg every 12 hours; other cannabinoids in the extract.

Clinical interpretation: Limited

Limitations and uncertainties: Not a human study; small sample, polytherapy, no washout phase; no isolated conclusion about CBDA.

Original sources for this finding: Safety and efficacy of cannabidiol-cannabidiolic acid rich hemp extract in the treatment of refractory epileptic seizures in dogs. [C_PR_35967998]

CBD-rich cannabis extract (CBD pharmacokinetics measured; not an isolate study) – clinical signals

Finding ID: B0354

Type of result: Clinical signals

Observation: Concomitant zonisamide was associated with CBD elimination constant and distribution parameter V1.

Mechanism: Observed association with CBD pharmacokinetics

Study type: Observational study

Context studied: Prospective paediatric observational study, 29 evaluable patients in total, CBD-rich extract.

Clinical interpretation: Limited

Limitations and uncertainties: Abstract does not quantify direction/magnitude of the zonisamide effect; degradation during storage and uncontrolled co-medication limit the conclusion.

Original sources for this finding: Disposition of Oral Cannabidiol-Rich Cannabis Extracts in Children with Epilepsy. [C_PR_32048179]

Hemp extract; composition unclear – clinical signals

Finding ID: B0355

Type of result: Clinical signals

Observation: Severe liver dysfunction in a two-year-old child receiving clobazam, zonisamide and non-prescribed hemp extract; improvement after extract discontinuation.

Mechanism: Hepatotoxicity case during polytherapy; mechanism unresolved

Study type: Case report

Context studied: Single case, abstract; additional respiratory disease.

Clinical interpretation: Limited

Limitations and uncertainties: Not an isolated zonisamide interaction or attribution to an individual cannabinoid; a probable product adverse reaction is not interaction evidence.

Original sources for this finding: Severe liver dysfunction in a toddler receiving nonprescription phytocannabinoid. [C_PR_35422394]

References and access status

[C_LABEL_D0052] ZONISAMIDE CAPSULE ZONISAMIDE (ZONISAMIDE) CAPSULE [SUN PHARMACEUTICAL INDUSTRIES, INC.]

Original source / bibliographic reference

Authors: SUN PHARMACEUTICAL INDUSTRIES, INC.

Year: 2026

Source type: US Structured Product Label

Source access – 23 October 2026: Source destination was accessible when checked.

Bibliographic attribution or source identity cross-checked.

[C_PR_35967998] Safety and efficacy of cannabidiol-cannabidiolic acid rich hemp extract in the treatment of refractory epileptic seizures in dogs.

Original source / bibliographic reference

Authors: Garcia GA, Kube S, Carrera-Justiz S, Tittle D, Wakshlag JJ.

Year: 2022

Source type: Primary source, full text read

DOI: 10.3389/fvets.2022.939966

PMID: 35967998

Source access – 23 October 2026: Automated direct retrieval was restricted; this does not establish that the link is broken.

Bibliographic attribution or source identity cross-checked.

PubMed – bibliographic reference / abstract

PubMed Central – archived text

DOI – publisher access (access restrictions may apply)

[C_PR_35422394] Severe liver dysfunction in a toddler receiving nonprescription phytocannabinoid.

Original source / bibliographic reference

Authors: Singh M, Sehgal M, Yacoub M, Greenberg J, Dugan M, Chen C, Simmont A, Jha P.

Year: 2022

Source type: Primary source, abstract read

DOI: 10.1016/j.japh.2022.03.013

PMID: 35422394

Source access – 23 October 2026: Automated direct retrieval was restricted; this does not establish that the link is broken.

Bibliographic attribution or source identity cross-checked.

DOI – publisher access (access restrictions may apply)

[CL21] Interactions between cannabidiol and commonly used antiepileptic drugs

Original source / bibliographic reference

Authors: Gaston TE; Bebin EM; Cutter GR; Liu Y; Szaflarski JP; UAB CBD Program

Year: 2017

Source type: Open-label observational study

DOI: 10.1111/epi.13852

PMID: 28782097

Source access – 23 October 2026: Source destination was accessible when checked.

Bibliographic attribution or source identity cross-checked.

DOI – publisher access (access restrictions may apply)

[C_PR_32048179] Disposition of Oral Cannabidiol-Rich Cannabis Extracts in Children with Epilepsy.

Original source / bibliographic reference

Authors: Wang GS, Bourne DWA, Klawitter J, Sempio C, Chapman K, Knupp K, Wempe MF, Borgelt L, Christians U, Leonard J, Heard K, Bajaj L.

Year: 2020

Source type: Primary source, abstract read

DOI: 10.1007/s40262-020-00869-z

PMID: 32048179

Source access – 23 October 2026: Direct retrieval could not be fully verified; availability remains unresolved.

Bibliographic attribution or source identity cross-checked.

DOI – publisher access (access restrictions may apply)

[CL20] Final analysis of potential drug-drug interactions between highly purified cannabidiol and anti-seizure medications in an open-label expanded access program

Original source / bibliographic reference

Authors: Gaston TE; Bebin EM; Cutter GR; Grayson L; Szaflarski JP

Year: 2023

Source type: Open-label longitudinal observational study

DOI: 10.1002/epi4.12815

PMID: 37593907

Source access – 23 October 2026: Automated direct retrieval was restricted; this does not establish that the link is broken.

Bibliographic attribution or source identity cross-checked.

PubMed – bibliographic reference / abstract

DOI – publisher access (access restrictions may apply)

Europe PMC – full-text access according to the literature database – Listed as freely available HTML full text in the official Europe PMC metadata. Direct retrieval was not fully verified here.

Research as of 23 October 2026. Not all original full texts could be reviewed in full. Source accessibility and the strength of scientific evidence must be assessed separately. An accessible link does not establish medical approval; a bibliographic record with an abstract does not replace the original full text.

Drug search and explanation of the evidence · Guide: cannabinoids and medicines · Author and responsibility