Pregabalin (Lyrica) and Zonisamide Drug Interaction
Pregabalin and zonisamide can be safely co-prescribed without clinically significant drug interactions, as both medications have minimal effects on drug metabolism pathways and do not interact with each other pharmacokinetically.
Pharmacokinetic Basis for Safety
Pregabalin's Non-Interactive Profile
- Pregabalin does not bind to plasma proteins and is excreted virtually unchanged (<2% metabolism) by the kidneys, making it unlikely to cause or be subject to pharmacokinetic drug-drug interactions 1
- Pregabalin is not subject to hepatic metabolism and does not induce or inhibit liver enzymes such as the cytochrome P450 system, which has been confirmed in clinical pharmacokinetic studies 1
- The lack of hepatic metabolism and lack of interaction with cytochrome P-450 isoenzymes explains the absence of drug interactions with pregabalin 2
Zonisamide's Favorable Interaction Profile
- Zonisamide has no effect on the steady-state pharmacokinetics of other antiepileptic drugs including carbamazepine, phenytoin, sodium valproate, or lamotrigine 3
- Zonisamide is essentially devoid of clinically significant interactions with other antiepileptic drugs, oral contraceptives, and all other classes of therapeutic agents investigated to date 3
- Zonisamide has a favorable pharmacokinetic profile that makes it an uncomplicated agent when employed as adjunctive therapy 3
Clinical Implications
No Dose Adjustments Required
- No dosage adjustments are necessary when combining pregabalin and zonisamide solely because they are being used together, as neither drug affects the metabolism or clearance of the other 1, 3
- Both medications demonstrate predictable pharmacokinetics that are not altered by co-administration 1, 4
Monitoring Considerations
- Monitor for potential additive central nervous system side effects including dizziness and somnolence, which are common adverse events with both medications 1, 2
- Patients with renal insufficiency require dose adjustment for pregabalin, as it is eliminated unchanged by the kidneys 1, 2
- Zonisamide clearance may be affected by enzyme-inducing antiepileptic drugs (carbamazepine, phenytoin, phenobarbital), but pregabalin does not fall into this category 3
Common Pitfalls to Avoid
- Do not assume that all antiepileptic drug combinations require dose modifications—pregabalin and zonisamide represent newer agents with superior interaction profiles compared to older-generation antiepileptic drugs 4
- Do not confuse the lack of pharmacokinetic interaction with the absence of additive pharmacodynamic effects on sedation and dizziness, which should still be monitored 1, 2