Lamotrigine with Norgestimate Interaction Details
Brand Names Associated with Lamotrigine
- Lamictal®
- Lamictal® CD
- Lamictal® ODT
- Lamictal® XR
- Lamotrigine
Medical Content Editor Dr. Brian Staiger, PharmD
Last updated
Nov 08, 2023
Interaction Effect
Decreased lamotrigine plasma concentrations
Interaction Summary
The concomitant use of combined hormonal contraceptives and lamotrigine has resulted in significant decreases in plasma lamotrigine levels. A sudden change in a patient's clinical condition and altered plasma levels of lamotrigine may occur with the use, or changes in the use, of oral contraceptives . There have been reports of decreased lamotrigine concentrations following introduction of oral contraceptives and reports of increased lamotrigine concentrations following withdrawal of oral contraceptives in women taking lamotrigine. Dosage adjustments may be necessary to maintain clinical response when starting or discontinuing oral contraceptives during lamotrigine therapy .
Severity
Moderate
Onset
Delayed
Evidence
Established
How To Manage Interaction
Estrogen-containing oral contraceptives have been shown to significantly decrease lamotrigine plasma concentrations during concomitant use. Carefully monitor and adjust lamotrigine doses in women who choose estrogen-containing hormonal contraception.
Mechanism Of Interaction
Induction of lamotrigine glucuronidation by combination contraceptive
Literature Reports
A) Evidence from a double-blind, placebo-controlled trial involving 7 women with epilepsy suggests that oral contraceptives induce the metabolism of lamotrigine. All patients were treated with lamotrigine monotherapy and taking combination oral contraceptives at study enrollment. They were then allocated in a crossover fashion to receive either placebo or contraceptive (ethinyl estradiol 35 mcg/norgestimate 250 mcg) over 4 periods (21 days of treatment followed by a 7-day pause). Steady-state blood samples were collected as trough levels (just prior to the next dose) and urine samples were collected between the evening and morning doses. Mean lamotrigine plasma concentrations increased by 84% (95% CI, 45% to 134%) after placebo for 21 days compared with oral contraceptive treatment for 21 days. Urine excretion of lamotrigine metabolites, measured as the N-2-glucuronide/lamotrigine ratio, was decreased by 31% (95% CI, -20% to 61%) when placebo was taken instead of oral contraceptive. Seizures occurred in 3 patients during oral contraceptive therapy while no seizures occurred during placebo therapy. The mechanism of the interaction is likely the induction of glucuronidation pathways involved in the metabolism of lamotrigine and ethinyl estradiol .
B) Several cases in which oral contraceptives changed the plasma levels of lamotrigine as well as the patient's clinical condition have been reported. Five patients who were seizure-free (1 with epilepsy, 2 with complex partial seizures, and 2 with absence epilepsy) had decreased lamotrigine serum concentrations after oral contraceptives were initiated. Two other patients, 1 with simple partial seizures and 1 with complex partial seizures, had discontinued their oral contraceptives. Plasma levels of lamotrigine in these 2 patients had increased significantly as well. Oral contraceptives reduce the plasma levels of lamotrigine 41% to 64% (mean, 49%). As a result, seizure control deteriorated when oral contraceptives were added, or side effects occurred when oral contraceptives were discontinued. These effects were independent of whether the oral contraceptives contained desogestrel, ethinyl estradiol, or norethindrone. The author concludes that there is a need for careful monitoring and adjustment of the lamotrigine doses in women with epilepsy who use combination contraceptives .
C) Lamotrigine plasma levels are reduced by greater than 50% during oral contraceptive coadministration. A retrospective study evaluated 52 women, 22 who used oral contraceptives and 30 who did not. The mean lamotrigine dose was 349 mg/day among women taking oral contraceptives and 327 mg/day among those who did not. Mean plasma level of lamotrigine was 13 mcmol/L in patients on oral contraceptives and 28 mcmol/L in patients without oral contraceptives (p less than 0.0001). Oral contraceptives markedly decrease plasma concentrations of lamotrigine .
D) In a study of 16 female volunteers, estrogen-containing oral contraceptive (ethinyl estradiol 30 mcg/levonorgestrel 150 mcg) increased the apparent clearance of lamotrigine 300 mg/day by approximately 2-fold with a mean decrease in AUC of 52% and in Cmax of 39%. Trough serum lamotrigine concentrations gradually increased and were approximately 2-fold higher at the end of the week of inactive treatment ("pill-free" week) compared with trough serum lamotrigine concentrations at the end of the active hormone cycle. This increase occurred in women not taking a drug that increased the clearance of lamotrigine (carbamazepine, phenytoin, phenobarbital, primidone, or rifampin). Dosage adjustment of lamotrigine will be necessary in women taking estrogen-containing oral contraceptives .
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.
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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.