Major Finding: Half of healthy women taking the antiepileptic carbamazepine ovulated despite taking a low-dose oral contraceptive.
Data Source: A randomized, double-blind crossover study of 24 healthy women aged 18–35 years.
Disclosures: Dr. Davis has received personal compensation from Bayer Pharmaceuticals and Schering Plough for participating on their advisory boards.
TORONTO — A standard dose of the antiepileptic drug carbamazepine allowed ovulation and the potential for pregnancy in women using low-dose birth control in a small randomized, double-blind study of healthy women without epilepsy.
The key clinical implication of the findings is that women using antiepileptic drugs who wish to avoid pregnancy should take additional birth control measures, according to Dr. Anne Davis of Columbia University in New York.
“We were very surprised to see that half of the women who took the [carbamazepine] ovulated,” placing them at an obvious increased risk for pregnancy, she said in an interview.
Clinicians have suspected that oral contraceptives are not fully effective in women who take antiepileptic medications, Dr. Davis and colleagues said in a poster.
But case reports of breakthrough bleeding in epileptic patients were not enough to establish a causal relationship between the antiepileptic drug carbamazepine and the loss of effectiveness from low-dose oral contraceptives, the researchers said.
In this study, the researchers randomized 24 women, aged 18–35 years, with regular menstrual cycles to receive a low-dose birth control pill containing 20 mcg of ethinyl estradiol and 100 mcg of levonorgestrel for 4 months. In addition, the women took either 600 mg of carbamazepine or a matching placebo daily for 2 months.
Breakthrough bleeding was more frequent in the carbamazepine group, with a median of 7 bleeding days, compared with zero bleeding days in the placebo group. At least 3 days of breakthrough bleeding occurred in 8 of 10 carbamazepine cycles, compared with 2 of 10 placebo cycles.
In addition, progesterone levels greater than 3 ng/mL (suggestive of ovulation) occurred in five of the carbamazepine cycles, compared with one of the placebo cycles. Three women in the carbamazepine group showed increased levels of progesterone during week 1 of a cycle, immediately after the placebo pills in the oral contraceptive pack.
The differences between the groups fell short of statistical significance, in part because only 10 of the 24 women completed the entire study.
Of the women initially randomized, two in the carbamazepine group and one in the placebo group did not take the drug. Five women in the carbamazepine group discontinued due to reversible side effects, and three women in the placebo group discontinued for reasons unrelated to the medication. One patient in the placebo group discontinued due to an adverse event, and samples were lost for one patient in each group, leaving four carbamazepine patients and six placebo patients in the final analysis.
Despite the study's small size, the results show that the known pharmacokinetic effect of carbamazepine on contraceptive steroids has a clinically significant effect, Dr. Davis said.
“If a woman is taking carbamazepine, and she needs birth control, a low-dose pill is not going to be effective,” Dr. Davis noted. “I think the next question is to figure out what will be effective for women in that situation.”
Progesterone levels suggestive of ovulation occurred in five of the carbamazepine cycles, compared with one placebo cycle.
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