Pharmacotherapeutic Issues for Women of Childbearing Age with Epilepsy

Chang, Shu-Ing; McAuley, James W.

doi:10.1345/aph.17253

Cited by 28 publications

(19 citation statements)

References 43 publications

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“…In a recent article, Ragueneau et al (14) categorized AEDs into three groups on the basis of their potential to cause induction‐drug interactions. Old AEDs, such as PHT, PB, and CBZ may reduce steroid OC levels during concomitant administration because of induction by CYP3A and other metabolizing enzymes and increase in OC‐binding globulin levels (3,15). Both mechanisms may contribute to reduced OC levels during concomitant OC–AED administration (14).…”

Section: Discussionmentioning

confidence: 99%

Effect of Topiramate or Carbamazepine on the Pharmacokinetics of an Oral Contraceptive Containing Norethindrone and Ethinyl Estradiol in Healthy Obese and Nonobese Female Subjects

et al. 2003

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Summary:Purpose: To study the pharmacokinetics of a combination oral contraceptive (OC) containing norethindrone and ethinyl estradiol during OC monotherapy, concomitant OC and topiramate (TPM) therapy, and concomitant OC and carbamazepine (CBZ) therapy in order to comparatively evaluate the pharmacokinetic interaction, which may cause contraceptive failure.Methods: This randomized, open-label, five-group study included two 28-day cycles. Five groups of female subjects received oral doses of ORTHO-NOVUM 1/35 alone (cycle 1) and then concomitant with TPM or CBZ (cycle 2). The treatment groups were group 1, TPM, 50 mg/day; group 2, TPM, 100 mg/day; group 3, TPM, 200 mg/day; group 4, TPM, 200 mg/day (obese women); and group 5, CBZ, 600 mg/day. Group 4 comprised obese women whose body mass index (BMI) was between 30 and 35 kg/m 2 . The BMI of the remaining four groups was Յ27 kg/m 2 .Results: Coadministration of TPM at daily doses of 50, 100, and 200 mg (nonobese) and 200 mg (obese) nonsignificantly (p > 0.05) changed the mean area under the curve (AUC) of ethinyl estradiol by -12%, +5%, -11%, and -9%, respectively, compared with OC monotherapy. A similar nonsignificant difference was observed with the plasma levels and AUC values of norethindrone (p > 0.05). CBZ (600 mg/day) significantly (p < 0.05) decreased the AUC values of norethindrone and ethinyl estradiol by 58% and 42%, respectively, and increased their respective oral clearance by 69% and 127% (p < 0.05). Because CBZ induces CYP 3A-mediated and glucuronide conjugation metabolic pathways, the significant increase in the oral clearance of ethinyl estradiol and norethindrone was anticipated. Conclusions: TPM, at daily doses of 50-200 mg, does not interact with an OC containing norethindrone and ethinyl estradiol. The lack of the TPM-OC interaction is notable when it is compared with the CBZ-OC interaction.

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Section: Discussionmentioning

confidence: 99%

Effect of Topiramate or Carbamazepine on the Pharmacokinetics of an Oral Contraceptive Containing Norethindrone and Ethinyl Estradiol in Healthy Obese and Nonobese Female Subjects

et al. 2003

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“…Older AEDs, such as PHT, PB, and CBZ, potently induce CYP-drug metabolizing enzymes, and they also increase sex hormone-binding globulin levels (1,27,28). Both mechanisms may contribute to reduced steroid contraceptive levels during concomitant administration of these older AEDs and OCs, resulting in unplanned pregnancy (3)(4)(5)(6)(7).…”

Section: Discussionmentioning

confidence: 99%

Levetiracetam Does Not Alter the Pharmacokinetics of an Oral Contraceptive in Healthy Women

Ragueneau‐Majlessi

Levy

Janik³

2002

Epilepsia

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Summary:Purpose: This study was designed to evaluate whether levetiracetam, a novel antiepileptic drug (AED), influences the pharmacokinetics of steroid oral contraceptives.Methods: During a run-in phase, 18 healthy female patients received an oral contraceptive containing ethinyl estradiol, 0.03 mg, and levonorgestrel, 0.15 mg, for the first 21 days of two consecutive menstrual cycles. In a subsequent double-blind, randomized, two-way crossover treatment phase, subjects received either levetiracetam, 500 mg, or placebo twice daily concomitant with the oral contraceptive. Plasma concentrations of ethinyl estradiol and levonorgestrel were measured on days 14 and 15 of the two treatment periods for the evaluation of the 24-h kinetic parameters, and an additional sample was collected on day 21 to determine the trough plasma concentrations. Serum progesterone and luteinizing hormone (LH) levels were determined on days 13, 14, 15, and 21 of each cycle of the treatment phase.Results: The plasma concentration-time curves and pharmacokinetic parameters of ethinyl estradiol and levonorgestrel were not statistically different during concomitant treatment with either levetiracetam or placebo. The ratios of the logtransformed geometric mean areas under the plasma concentration-time curves (AUCs), maximal (C max ) and minimal (C min ) plasma concentrations, and trough concentrations on day 21 (C 21 ) ranged from 99.12 to 99.96% for ethinyl estradiol and from 97.13 to 99.41% for levonorgestrel. The 90% confidence intervals of these ratios were well within the 80 to 125% acceptance range for lack of interaction. Serum progesterone and LH concentrations were fairly constant during the run-in and treatment phases and remained markedly below their respective physiologic levels. Safety and menstrual-bleeding patterns were comparable during levetiracetam and placebo administration.Conclusions: Levetiracetam does not affect the pharmacokinetics of an oral contraceptive containing ethinyl estradiol and levonorgestrel, and on the basis of serum progesterone and LH levels, it does not affect the contraceptive efficacy.

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“…There are marked species differences and dosing issues in progression from rodents to humans. Reproductive studies have shown various effects with felbamate, gabapentin, topiramate, tiagabine, and zonisamide (37,38). Prospective studies and patient registries ( Figure 3) are important in evaluating AED fetal effects in humans as soon as possible.…”

Section: Congenital Malformations and Other Complicationsmentioning

confidence: 99%

The Effects of Epilepsy and Its Treatment on Sexual and Reproductive Function

Penovich

2000

Epilepsia

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Summary: Male and female sexuality and reproductive functions are complex systems with cortical, limbic system, hypothalamic, pituitary, and end organ interactions. Sexual steroids are produced in the sexual glands, the adrenals, and the brain. They undergo interconversion in the brain, bind to different brain areas, and have multiple effects behaviorally and neurophysiologically. Progesterone, estrogen and testosterone have neuroendocrine effects that alter epileptogenicity. Seizure frequency may change throughout the life cycle as a result of hormonal status. Changes in central control, peripheral hormone levels, and/or medication effects may all contribute to decreased libido, potency, and fertility. Antiepileptic drugs (AEDs) interact with hormone-binding metabolism, resulting in altered human reproductive function. AEDs alter contraceptive hormone treatments. Information on the effects of new AEDs is being gathered by the National Pregnancy Registry. Catamenial epilepsy and some sexual dysfunction in men may be treatable. Key Words: Epilepsy-Women-MenSexuality-Reproduction.The quality of human life is a summation of many factors. Male and female sexuality, relationships, and successful reproduction are paramount in the accomplishment of a meaningful life for most individuals. Evaluation of these measures for our patients with epilepsy has revealed a disparity between their experience and that of the general population. Human sexuality is a psychological and physiological experience. To understand the problems our patients encounter, we will briefly review the human hormonal sexual system and what is altered in the experience of the individual with epilepsy.Steroids are hormones that are released into the circulation. At target tissue membranes, they are taken into the cell and bind to an intracellular cytosolic receptor. This complex is then transported into the nucleus and binds to DNA, which results in increased RNA polymerase activity and eventual polypeptide formation. These are long latency effects. Steroids have short latency effects as well (1) ( Table 1). FEMALE SEXUAL FUNCTIONThe sexual steroids are 17p steroids. The primary female compounds are estrogen and progesterone (Figure

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Pharmacotherapeutic Issues for Women of Childbearing Age with Epilepsy

Cited by 28 publications

References 43 publications

Effect of Topiramate or Carbamazepine on the Pharmacokinetics of an Oral Contraceptive Containing Norethindrone and Ethinyl Estradiol in Healthy Obese and Nonobese Female Subjects

Effect of Topiramate or Carbamazepine on the Pharmacokinetics of an Oral Contraceptive Containing Norethindrone and Ethinyl Estradiol in Healthy Obese and Nonobese Female Subjects

Levetiracetam Does Not Alter the Pharmacokinetics of an Oral Contraceptive in Healthy Women

The Effects of Epilepsy and Its Treatment on Sexual and Reproductive Function

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