Summary

The interaction between levetiracetam and methotrexate is generally considered minor to moderate, with potential for increased risk of central nervous system side effects. While both drugs can be used together with appropriate monitoring, healthcare providers should be aware of additive neurological effects and potential impacts on seizure control.

Introduction

Levetiracetam (brand name Keppra) is an antiepileptic drug (AED) commonly prescribed for the treatment of epilepsy and seizure disorders. It works by binding to synaptic vesicle protein SV2A and modulating neurotransmitter release. Methotrexate is an antimetabolite and antifolate drug used primarily as a chemotherapy agent for various cancers and as an immunosuppressive medication for autoimmune conditions such as rheumatoid arthritis and psoriasis. It works by inhibiting dihydrofolate reductase, thereby interfering with DNA synthesis and cell division.

Mechanism of Interaction

The interaction between levetiracetam and methotrexate primarily involves additive central nervous system effects rather than direct pharmacokinetic interactions. Methotrexate can cross the blood-brain barrier and may cause neurological side effects including confusion, seizures, and encephalopathy, particularly at high doses or with intrathecal administration. When combined with levetiracetam, there may be an increased risk of CNS depression, cognitive impairment, and paradoxically, breakthrough seizures in some patients. Additionally, methotrexate-induced folate deficiency may potentially affect neuronal function and seizure threshold.

Risks and Symptoms

The primary clinical risks of combining levetiracetam and methotrexate include increased central nervous system side effects such as drowsiness, confusion, dizziness, and cognitive impairment. Patients may experience enhanced sedation and reduced alertness, which can impact daily activities and increase fall risk. There is also a potential for breakthrough seizures in epileptic patients, as methotrexate may lower seizure threshold, particularly in cases of methotrexate-induced neurotoxicity. Patients receiving high-dose methotrexate or intrathecal administration face higher risks of neurological complications that could interfere with seizure control.

Management and Precautions

When prescribing levetiracetam and methotrexate together, healthcare providers should implement close monitoring for enhanced CNS effects and changes in seizure control. Patients should be counseled about potential increased drowsiness and advised to avoid driving or operating machinery until effects are established. Regular neurological assessments are recommended, particularly during methotrexate treatment initiation or dose changes. Seizure frequency should be monitored closely, and levetiracetam doses may need adjustment if breakthrough seizures occur. Folate supplementation, commonly prescribed with methotrexate, should be continued as it may help mitigate some neurological risks. Consider more frequent follow-up appointments during concurrent therapy, and educate patients to report any new or worsening neurological symptoms promptly.

Levetiracetam interactions with food and lifestyle

Levetiracetam can be taken with or without food as food does not significantly affect its absorption. However, alcohol should be avoided or used with extreme caution while taking levetiracetam, as alcohol can increase the risk of drowsiness, dizziness, and impaired coordination, potentially worsening the side effects of this antiepileptic medication. Patients should also be cautious when driving or operating machinery, especially when starting treatment or adjusting doses, as levetiracetam may cause drowsiness, fatigue, or behavioral changes that could impair cognitive function and reaction times.

Methotrexate interactions with food and lifestyle

Alcohol consumption should be avoided or strictly limited while taking methotrexate due to increased risk of liver toxicity and hepatotoxicity. Both methotrexate and alcohol can cause liver damage, and their combination significantly increases this risk. Patients should also maintain adequate hydration and avoid excessive sun exposure, as methotrexate can increase photosensitivity. Folic acid supplementation is commonly recommended to reduce certain side effects, though this should be discussed with a healthcare provider as timing and dosing are important.