Azithromycin Safety with Levetiracetam (Keppra)
Yes, azithromycin is safe to use with levetiracetam (Keppra) in patients with seizures or epilepsy, as levetiracetam lacks cytochrome P450 enzyme-inducing potential and is not associated with clinically significant pharmacokinetic interactions with other drugs. 1
Pharmacokinetic Profile Supporting Safety
Levetiracetam has several characteristics that make it exceptionally safe for combination with other medications:
Levetiracetam undergoes minimal metabolism consisting only of hydrolysis of the acetamide group, with primarily renal elimination, avoiding hepatic drug interaction pathways. 1
The drug lacks cytochrome P450 isoenzyme-inducing potential, which is the primary mechanism by which most drug-drug interactions occur with antibiotics like azithromycin. 1
No clinically significant pharmacokinetic interactions have been documented between levetiracetam and other drugs, including other antiepileptic medications. 1
Clinical Implications for Seizure Management
When prescribing azithromycin to patients on levetiracetam:
Continue levetiracetam at the current dose without adjustment when starting azithromycin, as no dose modifications are required. 1
Monitor for seizure control as you normally would, but do not attribute any breakthrough seizures to drug interaction—instead investigate other precipitating factors such as infection, fever, sleep deprivation, or medication non-compliance. 2
Ensure the patient maintains therapeutic levetiracetam levels by verifying medication compliance, as non-compliance is a more common cause of breakthrough seizures than drug interactions. 2, 3
Advantages of Levetiracetam in Polypharmacy
The non-enzyme-inducing profile of levetiracetam makes it particularly advantageous:
European guidelines specifically recommend non-enzyme-inducing anticonvulsants like levetiracetam to avoid impacting metabolism of other medications including antibiotics and steroids. 4
Levetiracetam demonstrates enhanced protective activity when combined with other medications without exacerbation of side effects or pharmacokinetic interactions. 5
Common Pitfall to Avoid
Do not discontinue or reduce levetiracetam when starting azithromycin—this is unnecessary and may precipitate withdrawal seizures. 3
If breakthrough seizures occur during azithromycin treatment, investigate the underlying infection or fever as the seizure trigger rather than assuming a drug interaction. 2