Lamotrigine with Ritonavir Interaction Details
Brand Names Associated with Lamotrigine
- Lamictal®
- Lamictal® CD
- Lamictal® ODT
- Lamictal® XR
- Lamotrigine
Brand Names Associated with Ritonavir
- Norvir®
- Ritonavir
- RTV
Medical Content Editor Dr. Brian Staiger, PharmD
Last updated
Nov 08, 2023
Interaction Effect
Decreased lamotrigine serum concentrations
Interaction Summary
Coadministration of ritonavir and lamotrigine may result in decreased serum concentrations of lamotrigine. Coadministration of lamotrigine and lopinavir/ritonavir in healthy subjects significantly decreased lamotrigine exposure and half-life, and increased lamotrigine clearance in an open-label, sequential, 3-period trial. The postulated mechanism of action is enhanced glucuronosyl transferase activity associated with drugs that are metabolized by direct glucuronidation . If lamotrigine and ritonavir are administered concomitantly, doses of lamotrigine may need to be increased . In one study, a doubling of the lamotrigine dose was required to overcome the interaction effect . Monitor patients for loss of lamotrigine efficacy.
Severity
Moderate
Onset
Delayed
Evidence
Established
How To Manage Interaction
Coadministration of lamotrigine and ritonavir may result in decreased lamotrigine serum concentrations. Doses of lamotrigine may need to be increased. In one study, a doubling of the lamotrigine dose was required to overcome the interaction effect . Monitor patients for loss of lamotrigine efficacy.
Mechanism Of Interaction
Increased lamotrigine metabolism
Literature Reports
A) In an open-label, sequential, 3-period trial, coadministration of lamotrigine and lopinavir/ritonavir in healthy subjects significantly decreased lamotrigine exposure and half-life, and increased lamotrigine clearance; a doubling of the lamotrigine dose is required to overcome the interaction effect. Subjects aged 18 to 65 years (n=24) received oral lamotrigine 50 mg once daily for days 1 and 2, followed by 100 mg twice daily on day 3 to day 23. Lopinavir 400 mg/ritonavir 100 mg twice daily was added on day 11. Lamotrigine trough levels (Cmin) were measured between days 10 and 20 and the dose was increased to 150 mg to 300 mg twice daily depending on the percentage of decrease. Among 18 patients who completed the study, lamotrigine Cmin decreased by 55.4% +/- 7.5% on day 20 (lamotrigine plus lopinavir/ritonavir) compared to day 10 (lamotrigine alone). The median AUC, Cmax, Cmin, and half-life values of lamotrigine on day 20 were not bioequivalent to those on day 10, with a geometric mean ratio (GMR) for lamotrigine AUC (day 20/day 10) of 0.5 (90% confidence interval (CI), 0.47 to 0.54). Consequently, the lamotrigine dose was increased to 200 mg twice daily from day 23 to day 31 in all 18 subjects. The median AUC on day 31 was bioequivalent to that on day 10, with a GMR (day 31/day 10) of 0.91 (90% CI, 0.82 to 1.02). The median AUC of lamotrigine's principal 2N-glucuronide metabolite to lamotrigine on day 20 was almost double to that on day 10 (0.57 on day 10 versus 1.12 on day 20). This interaction was believed to occur due to induction of glucuronidation of lamotrigine by ritonavir, and possibly also due to lopinavir. The pharmacokinetics of lopinavir/ritonavir were not significantly altered .
Lamotrigine Overview
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Lamotrigine extended-release (long-acting) tablets are used with other medications to treat certain types of seizures in patients who have epilepsy. All types of lamotrigine tablets (tablets, orally disintegrating tablets, and chewable tablets) other than the extended-release tablets are used alone or with other medications to treat seizures in people who have epilepsy or Lennox-Gastaut syndrome (a disorder that causes seizures and often causes developmental delays). All types of lamotrigine tablets other than the extended-release tablets are also used to increase the time between episodes of depression, mania (frenzied or abnormally excited mood), and other abnormal moods in patients with bipolar I disorder (manic-depressive disorder; a disease that causes episodes of depression, episodes of mania, and other abnormal moods). Lamotrigine has not been shown to be effective when people experience the actual episodes of depression or mania, so other medications must be used to help people recover from these episodes. Lamotrigine is in a class of medications called anticonvulsants. It works by decreasing abnormal electrical activity in the brain.
Ritonavir Overview
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Ritonavir is used along with other medications to treat human immunodeficiency virus (HIV) infection. Ritonavir is in a class of medications called protease inhibitors. It works by decreasing the amount of HIV in the blood. Although ritonavir does not cure HIV, it may decrease your chance of developing acquired immunodeficiency syndrome (AIDS) and HIV-related illnesses such as serious infections or cancer. Taking these medications along with practicing safer sex and making other lifestyle changes may decrease the risk of transmitting the HIV virus to other people.
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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:
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.