What medications interact with Levetiracetam (Keppra)?

From the Guidelines

Keppra (levetiracetam) can interact with several medications, including other antiepileptic drugs like carbamazepine, phenytoin, and valproic acid, which may affect Keppra's effectiveness or increase side effects. According to the study published in the Annals of Emergency Medicine 1, medications such as carbamazepine, phenytoin, and valproate may have interactions with Keppra.

Key Interactions

• Other antiepileptic drugs like carbamazepine, phenytoin, and valproic acid may interact with Keppra, affecting its effectiveness or increasing side effects 1.
• Methotrexate may increase the risk of Keppra-related side effects.
• Sedatives, tranquilizers, and sleep medications like benzodiazepines (diazepam, lorazepam) may enhance the sedative effects of Keppra, causing increased drowsiness and impaired coordination.
• Alcohol should be avoided as it can worsen side effects like dizziness and drowsiness.
• Certain antibiotics and antifungals might alter Keppra levels in some cases.

Mechanism of Interactions

The mechanism behind these interactions often involves changes in how the body metabolizes these drugs, affecting their concentration in the bloodstream or their effects on the central nervous system 1.

Clinical Implications

Patients should always inform their healthcare provider about all medications they're taking, including over-the-counter drugs and supplements, before starting Keppra. If side effects like extreme drowsiness, confusion, or coordination problems develop, medical attention should be sought promptly.

From the FDA Drug Label

In vitro data on metabolic interactions indicate that levetiracetam is unlikely to produce, or be subject to, pharmacokinetic interactions Levetiracetam and its major metabolite, at concentrations well above Cmax levels achieved within the therapeutic dose range, are neither inhibitors of nor high affinity substrates for human liver cytochrome P450 isoforms, epoxide hydrolase or UDP glucuronidation enzymes. Potential pharmacokinetic interactions were assessed in clinical pharmacokinetic studies (phenytoin, valproate, oral contraceptive, digoxin, warfarin, probenecid) and through pharmacokinetic screening in the placebo-controlled clinical studies in epilepsy patients Drug-Drug Interactions Between Levetiracetam And Other Antiepileptic Drugs (AEDs) Phenytoin Levetiracetam (3000 mg daily) had no effect on the pharmacokinetic disposition of phenytoin in patients with refractory epilepsy. Valproate Levetiracetam (1500 mg twice daily) did not alter the pharmacokinetics of valproate in healthy volunteers. Potential drug interactions between levetiracetam and other AEDs (carbamazepine, gabapentin, lamotrigine, phenobarbital, phenytoin, primidone and valproate) were also assessed by evaluating the serum concentrations of levetiracetam and these AEDs during placebo-controlled clinical studies These data indicate that levetiracetam does not influence the plasma concentration of other AEDs and that these AEDs do not influence the pharmacokinetics of levetiracetam. Other Drug Interactions Oral Contraceptives Levetiracetam (500 mg twice daily) did not influence the pharmacokinetics of an oral contraceptive containing 0.03 mg ethinyl estradiol and 0. 15 mg levonorgestrel, or of the luteinizing hormone and progesterone levels, indicating that impairment of contraceptive efficacy is unlikely. Digoxin Levetiracetam (1000 mg twice daily) did not influence the pharmacokinetics and pharmacodynamics (ECG) of digoxin given as a 0. 25 mg dose every day. Warfarin Levetiracetam (1000 mg twice daily) did not influence the pharmacokinetics of R and S warfarin. Probenecid Probenecid, a renal tubular secretion blocking agent, administered at a dose of 500 mg four times a day, did not change the pharmacokinetics of levetiracetam 1000 mg twice daily.

Drugs that cause interactions with Keppra (levetiracetam) are not explicitly listed as causing interactions, but the following drugs have been studied for potential interactions:

• Phenytoin: No effect on the pharmacokinetic disposition of phenytoin
• Valproate: No alteration of the pharmacokinetics of valproate
• Carbamazepine: No influence on the plasma concentration of levetiracetam
• Gabapentin: No influence on the plasma concentration of levetiracetam
• Lamotrigine: No influence on the plasma concentration of levetiracetam
• Phenobarbital: No influence on the plasma concentration of levetiracetam
• Primidone: No influence on the plasma concentration of levetiracetam
• Oral Contraceptives: No influence on the pharmacokinetics of an oral contraceptive
• Digoxin: No influence on the pharmacokinetics and pharmacodynamics of digoxin
• Warfarin: No influence on the pharmacokinetics of R and S warfarin
• Probenecid: No change in the pharmacokinetics of levetiracetam, but may decrease renal clearance of the metabolite ucb L057 2

From the Research

Drug Interactions with Keppra (Levetiracetam)

• Keppra is known to interact with various drugs, including those used to treat cardiovascular conditions and psychiatric disorders 3, 4.
• Studies have shown that certain angiotensin-converting enzyme (ACE) inhibitors, such as perindopril arginine, may positively influence the anticonvulsant action of Keppra 3.
• However, other cardiovascular drugs like losartan potassium, candesartan cilexetil, captopril, hydrochlorothiazide, and ethacrynic acid do not appear to affect Keppra's anticonvulsant activity 3.
• Benzodiazepines, which are commonly used to treat anxiety and insomnia, may interact with Keppra, although the clinical significance of this interaction is unclear 5, 6.
• Selective serotonin reuptake inhibitors (SSRIs), which are used to treat depression and anxiety, may also interact with Keppra, particularly fluoxetine and fluvoxamine, which can inhibit the metabolism of certain drugs 5.

Mechanisms of Interaction

• The interactions between Keppra and other drugs can be pharmacodynamic or pharmacokinetic in nature 5.
• Pharmacokinetic interactions occur when one drug affects the metabolism or elimination of another drug, while pharmacodynamic interactions occur when two drugs have additive or synergistic effects on the same physiological system 5.
• The cytochrome P450 (CYP) enzyme system plays a crucial role in the metabolism of many drugs, including Keppra, and interactions can occur when two drugs compete for the same enzyme or when one drug inhibits or induces the activity of an enzyme 5.

Clinical Significance

• The clinical significance of drug interactions with Keppra depends on various factors, including the nature of the interaction, the potency of the interacting drugs, and the individual patient's characteristics 5.
• Healthcare providers should carefully monitor patients taking Keppra and other drugs for potential interactions and adjust the dosage or discontinue the interacting drug as needed 3, 4.
• Further research is needed to fully understand the interactions between Keppra and other drugs and to develop strategies for minimizing the risk of adverse interactions 5, 7.