Methylphenidate with Carbamazepine Interaction Details

Brand Names Associated with Methylphenidate

Brand Names Associated with Carbamazepine

Medical Content Editor Dr. Brian Staiger, PharmD
Last updated Nov 25, 2023

Interaction Effect

Loss of methylphenidate efficacy

Interaction Summary

Two case reports describe the loss of methylphenidate efficacy after carbamazepine therapy was introduced. Carbamazepine is an inducer of cytochrome P450 enzymes, a pathway involved in methylphenidate metabolism. Although methylphenidate plasma concentrations are not routinely measured, they may be helpful in patients receiving carbamazepine who are showing no benefits or side effects from methylphenidate.

Severity

Moderate

Onset

Delayed

Evidence

Probable

How To Manage Interaction

Clinicians should monitor patient response to methylphenidate therapy when carbamazepine is initiated. Monitoring of plasma methylphenidate levels may also be helpful. Doses of methylphenidate may need to be increased to maintain efficacy.

Mechanism Of Interaction

Induction by carbamazepine of cytochrome P450 3A4-mediated methylphenidate metabolism

Literature Reports

A) A 7-year-old male with severe mental retardation and attention deficit disorder was failing to respond to methylphenidate 20 mg every four hours and thiothixene 10 mg daily. Other drug therapy included carbamazepine 1000 mg daily to control grand mal epilepsy. After five days of confirmed medication compliance, plasma levels of methylphenidate were measured two hours after the morning dose. No trace of either psychotropic agent or of their metabolites could be found. Doses were increased to methylphenidate 30 mg every four hours and thiothixene 20 mg daily with no evidence of efficacy or side effects. Both agents were then discontinued .

B) Attention deficit/hyperactivity disorder (ADHD) was being treated with methylphenidate 20 mg three times daily in a 13-year-old female. Because of mood lability and significant impulsivity, carbamazepine was introduced at 200 mg daily. The strict two-hour peak methylphenidate and ritalinic acid serum level was 5.3 ng/mL (normal range 5 to 20 ng/mL) at this time. ADHD symptoms began to worsen as the carbamazepine dose was increased to 800 mg daily. Six weeks after the start of combination therapy, the patient's methylphenidate and ritalinic acid strict two-hour peak blood level had decreased to 4.2 ng/mL. A month later, the carbamazepine dose was increased to 1000 mg daily with a steady-state blood level of 11.2 mcg/mL. Despite an increase in her methylphenidate dose to 35 mg three times daily, her methylphenidate and ritalinic acid peak level had further decreased to 2.4 ng/mL. After another two months, her carbamazepine dose was 1200 mg daily with a steady-state blood level of 11.5 mcg/mL, and methylphenidate was increased to 60 mg three times daily to regain the benefit from the drug that she had experienced before the initiation of carbamazepine .

Methylphenidate Overview

• Methylphenidate is used as part of a treatment program to control symptoms of attention deficit hyperactivity disorder (ADHD; more difficulty focusing, controlling actions, and remaining still or quiet than other people who are the same age) in adults and children. Methylphenidate (Methylin) is also used to treat narcolepsy (a sleep disorder that causes excessive daytime sleepiness and sudden attacks of sleep). Methylphenidate is in a class of medications called central nervous system (CNS) stimulants. It works by changing the amounts of certain natural substances in the brain.

Carbamazepine Overview

• Carbamazepine is used alone or in combination with other medications to control certain types of seizures in people with epilepsy. It is also used to treat trigeminal neuralgia (a condition that causes facial nerve pain). Carbamazepine extended-release capsules (Equetro brand only) are also used to treat episodes of mania (frenzied, abnormally excited or irritated mood) or mixed episodes (symptoms of mania and depression that happen at the same time) in patients with bipolar I disorder (manic-depressive disorder; a disease that causes episodes of depression, episodes of mania, and other abnormal moods). Carbamazepine is in a class of medications called anticonvulsants. It works by reducing abnormal electrical activity in the brain.

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Definitions

Severity Categories

Contraindicated

These drugs, generally, should not be used together simultaneously due to the high risk of severe adverse effects. Combining these medications can lead to dangerous health outcomes and should be strictly avoided unless otherwise instructed by your provider.

Major

This interaction could result in very serious and potentially life-threatening consequences. If you are taking this drug combination, it is very important to be under close medical supervision to minimize severe side effects and ensure your safety. It may be necessary to change a medication or dosage to prevent harm.

Moderate

This interaction has the potential to worsen your medical condition or alter the effectiveness of your treatment. It's important that you are monitored closely and you potentially may need to make adjustments in your treatment plan or drug dosage to maintain optimal health.

Minor

While this interaction is unlikely to cause significant problems, it could intensify side effects or reduce the effectiveness of one or both medications. Monitoring for changes in symptoms and your condition is recommended, and adjustments may be made if needed to manage any increased or more pronounced side effects.

Onset

Rapid: Onset of drug interaction typically occurs within 24 hours of co-administration.

Delayed: Onset of drug interaction typically occurs more than 24 hours after co-administration.

Evidence

Level of documentation of the interaction.

Established: The interaction is documented and substantiated in peer-reviewed medical literature.

Theoretical: This interaction is not fully supported by current medical evidence or well-documented sources, but it is based on known drug mechanisms, drug effects, and other relevant information.

How To Manage The Interaction

Provides a detailed discussion on how patients and clinicians can approach the identified drug interaction as well as offers guidance on what to expect and strategies to potentially mitigate the effects of the interaction. This may include recommendations on adjusting medication dosages, altering the timing of drug administration, or closely monitoring for specific symptoms.

It's important to note that all medical situations are unique, and management approaches should be tailored to individual circumstances. Patients should always consult their healthcare provider for personalized advice and guidance on managing drug interactions effectively.

Mechanism Of Interaction

The theorized or clinically determined reason (i.e., mechanism) why the drug-drug interaction occurs.

Disclaimer: The information provided on this page is for informational purposes only and should not be considered medical advice. Always consult with a qualified healthcare professional regarding your specific circumstances and medical conditions.

Where Does Our Information Come From?

Information for our drug interactions is compiled from several drug compendia, including:

• Gold Standard Drug Database
• Micromedex
• Lexicomp
• DrugBank

The prescribing information for each drug, as published on DailyMED, is also used. 

Individual drug-drug interaction detail pages contain references specific to that interaction. You can click on the reference number within brackets '[]' to see what reference was utilized.

The information posted is fact-checked by HelloPharmacist clinicians and reviewed quarterly.