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Is there a risk of interaction between lamotrigine and progestogen-only-pills?

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Does the plasma concentration of lamotrigine change during the oral contraceptives pill-free period and can the combination be used?

Is there a risk of interaction between lamotrigine and progestogen-only-pills?

Case description

An 18-year-old woman is treated with lamotrigine due to epilepsy. Now she wishes to receive oral contraceptives. The GP is aware of the risk of reducing the effect of lamotrigine when introducing combination oral contraceptives, and requests information on how the serum concentration acts during the pill-free period. She asks also, if progestogen-only-pills can be used instead. 

Background information

The issue on interaction between lamotrigine and oral contraceptives has previously been dealt with (1). Based on a case serie (2), it was concluded that a clinically relevant pharmacokinetic interaction should be anticipated as oral contraceptives reduce lamotrigine (LTG) plasma levels by greater than 50 %, and there is a need for carefully monitoring and adjustment of lamotrigine doses, if oral contraceptives are given concomitantly.


Since then, one retrospective study (3) and two prospective studies have confirmed the results (4,5).


In the retrospective study the mean plasma LTG concentration was approximately 60 % lower in 22 women taking LTG plus an oral contraceptive compared to the concentration in 30 women on LTG alone (3).


In one prospective study serum concentration of LTG decreased (by in average 39% in Cmax and 52% in AUC) during co-administration with the combined oral contraceptive. During the "pill-free" week LTG concentrations increased in a fairly rapid and liniar manner with concentration at the end of the week being approximately two-fold higher than during co-administration of the combined oral contraceptive. During co-administration, AUC of the progestogen component was decreased by 19%, but there was no corresponding hormonal evidence of ovulation (4).


The other prospective study was a three-armed open study where LTG serum concentration was analysed in female patients using no hormonal contraception (n = 18) a combination hormonal contraception (CC) (n = 11) or a progestogen (PG) only contraception (n = 16). The PG-group included different administration routes and different progestogens. The LTG serum concentration, to dose ratio (CDR), was reduced by more than 50 % in the CC-group compared to women in the control group and the group using PG-only. The CDR in PG-only group was not statistically different from the controls. and it was concluded that it was the ethinyl estradiol component of oral contraceptives that interacts with lamotrigine (5).


In contrast to this study two case reports indicate that PG-only contraception may reduce the lamotrigine concentration (2,6)


Finally, an abstract reported the opposite effect, that the oral PG compound desogestrel increased LTG serum concentration by 20-100 % in seven out of ten patients. The effect varied considerably (7). 


A clinical relevant interaction should be anticipated if hormonal combination contraceptives is added to lamotrigine therapy. Lamotrigine serum concentration decreases by 50-60 % during co-administration with combination contraceptives and during the pill-free period, a gradual transient two-fold increase in the serum concentration should be expected.


Although not consistently, the best evidence indicates that PG-only contraceptives do not interact with lamotrigine.


To avoid the fluctuation in lamotrigine serum concentration we recommend to avoid combination contraceptives, and use a PG-only contraceptive instead. The serum concentration should be monitored carefully and lamotrigine dosage adjusted if necessary. 


  1. Drugline no: 21227 (year 2003).
  2. Sabers A, Buchholt JM, Uldall P, Hansen EJ. Lamotrigene plasma levels reduced by oral contraceptives. Epilepsy Research 2001;47:151-4.
  3. Sabers A, Ohman I, Christensen J, Tomson T. Oral contraceptives reduce lamotrigine plasma levels. Neurology. 2003;61(4):570-1.
  4. 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;61(2):191-9.
  5. Reimers A, Helde G, Brodtkorb E. Ethinyl estradiol, not progestogens, reduces lamotrigine serum concentrations. Epilepsia. 2005;46(9):1414-7.
  6. P-piller paverker effekten av det antiepileptiske medlet Lamictal (lamotrigin). Medical Product Agency homepage. (Cited 2004-11-05) www.lakemedelsverket.se.
  7. Scwenkhagen AM, Stodieck SR. Interaction between lamotrigine and a progestin-only contraceptive pill containing desogestrel 75 ug (Cerazette). Epilepsia 2004;45 (suppl 7):144. Abstract. 

References Consulted

Institut for Rationel Farmakoterapi, 29. juni 2006


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