Drug-Drug Interaction

LAMOTRIGINE/HORMONAL CONTRACEPTIVES

MECHANISM OF ACTION
Hormonal contraceptives increase the clearance of lamotrigine. Lamotrigine may induce the metabolism of contraceptives.(1,2)

DISCUSSION
In a study in 16 females, concurrent ethinylestradiol (30 mcg) and levonorgestrel (150 mcg) with lamotrigine (300 mg per day) increased lamotrigine clearance by 2-fold, with a mean decrease in lamotrigine area-under-curve (AUC) and maximum concentration (Cmax) by 52% and 39%, respectively. Serum trough lamotrigine levels were two-fold higher at the end of the week of inactive tablets when compared to lamotrigine levels at the end of the active hormonal cycle. This effect should be expected in women not taking carbamazepine, phenytoin, phenobarbital, primidone, or rifampin.(1)

CLINICAL EFFECTS
Concurrent use of lamotrigine and hormonal contraceptives may result in decreased levels and effectiveness of both agents.(1,2)

SEVERITY LEVEL
3-Moderate Interaction: Assess the risk to the patient and take action as needed.

PATIENT MANAGEMENT
No adjustments to the recommended lamotrigine dose escalation guidelines should be necessary in patients taking hormonal contraceptives.(1)

PREDISPOSING FACTORS
The interaction is more severe in patients not taking carbamazepine, phenytoin, phenobarbital, primidone, or rifampin.

REFERENCES

  1. Lamictal (lamotrigine) US prscribing information. GlaxoSmithKline April, .Lamictal (lamotrigine) US prscribing information. GlaxoSmithKline April, 2009.
  2. Dear Healthcare Professional, Subject: Important new safety information .Dear Healthcare Professional, Subject: Important new safety information concerning the antiepileptic, LAMICTAL (lamotrigine). GlaxoSmithKline Canada September, 2004.
  3. Sabers A, Ohman I, Christensen J, Tomson T. Oral contraceptives reduce .Sabers A, Ohman I, Christensen J, Tomson T. Oral contraceptives reduce lamotrigine plasma levels. Neurology 2003 Aug 26;61(4):570-1.
  4. Sabers A, Buchholt JM, Uldall P, Hansen EL. Lamotrigine plasma levels .Sabers A, Buchholt JM, Uldall P, Hansen EL. Lamotrigine plasma levels reduced by oral contraceptives. Epilepsy Res 2001 Nov;47(1-2):151-4.
  5. Reimers A, Helde G, Brodtkorb E. Ethinyl estradiol, not progestogens, .Reimers A, Helde G, Brodtkorb E. Ethinyl estradiol, not progestogens, reduces lamotrigine serum concentrations. Epilepsia 2005 Sep;46(9):1414-7.
  6. Christensen J, Petrenaite V, Atterman J, Sidenius P, Ohman I, Tomson T, .Christensen J, Petrenaite V, Atterman J, Sidenius P, Ohman I, Tomson T, Sabers A. Oral contraceptives induce lamotrigine metabolism: evidence from a double-blind, placebo-controlled trial. Epilepsia 2007 Mar;48(3):484-9.
  7. Contin M, Albani F, Ambrosetto G, Avoni P, Bisulli F, Riva R, Tinuper P, .Contin M, Albani F, Ambrosetto G, Avoni P, Bisulli F, Riva R, Tinuper P, Baruzzi A. Variation in lamotrigine plasma concentrations with hormonal contraceptive monthly cycles in patients with epilepsy. Epilepsia 2006 Sep;47(9):1573-5.
  8. Sidhu J, Job S, Singh S, Philipson R. The pharmacokinetic and .Sidhu J, Job S, Singh S, Philipson R. The pharmacokinetic and pharmacodynamic consequences of the co-administration of lamotrigine and a combined oral contraceptive in healthy female subjects. Br J Clin Pharmacol 2006 Feb;61(2):191-9.