Serum Valproate Levels with Oral Contraceptive Use

  title={Serum Valproate Levels with Oral Contraceptive Use},
  author={Andrew G Herzog and Erin L. Farina and A S Blum},
It has long been recognized that the use of the older enzyme-inducing antiepileptic drugs (AEDs), such as barbiturates, phenytoin (PHT) and carbamazepine (CBZ), is associated with higher failure rates of oral contraceptive pills (OCPs), likely because of the induction of the catabolism and binding of reproductive steroids (1). A newer enzyme-inducing AED, topiramate (TPM), also has been shown to reduce serum OCP steroid levels at daily dosages of ≥200 mg (2). Clinically significant interactions… 
Pharmacokinetic interactions between contraceptives and antiepileptic drugs
It is recommended that change in OC use is assisted by AED monitoring whenever possible and the change in the elimination rate is often unpredictable and can be influenced by a number of co-variants such as co-medication of other drugs, as well as genetic and environmental factors.
Clinically relevant drug interactions with antiepileptic drugs.
  • E. Perucca
  • Medicine
    British journal of clinical pharmacology
  • 2006
Some patients with difficult-to-treat epilepsy benefit from combination therapy with two or more antiepileptic drugs (AEDs), and pharmacodynamic interactions involving AEDs have not been well characterized, but their understanding is important for a more rational approach to combination therapy.
Interactions between antiepileptic drugs, and between antiepileptic drugs and other drugs.
  • G. Zaccara, E. Perucca
  • Medicine
    Epileptic disorders : international epilepsy journal with videotape
  • 2014
These interactions can have potentially beneficial effects, such as the therapeutic synergism of valproic acid combined with lamotrigine, or adverse effects,such as the reciprocal potentiation of neurotoxicity observed in patients treated with a combination of sodium channel blocking antiepileptic drugs.
Reproductive endocrine side effects of antiepileptic drugs
The most prominent finding was a significant dose-dependent increase of the testosterone/estradiol ratio in cells exposed to valproate, which suggestsvalproate is capable of inhibiting conversion of testosterone to estradiol.
Antiepileptic drugs and other medications: What interactions may arise?
To identify potential drug interactions before they lead to toxicity or therapy failure, the treating clinician should combine knowledge of the patient’s overall history with a general knowledge of comorbid conditions in which significant interactions involving AEDs are most likely to occur.
Bipolar Disorders and Valproate: Pharmacokinetics, Pharmacodynamics, Therapeutic Effects and Indications of Valproate: Review of Articles
Valproate is a mood stabilizer which is approved for use in acute and maintenance mania. It is the first line drug for bipolar patients with presence rapid cycling, irritable mania, bipolar disorder
The use of hormonal contraception among women taking anticonvulsant therapy.
To avoid contraceptive failure or increased seizure activity, women with epilepsy should be offered contraceptive methods that do not interact with anticonvulsant medication.
Which contraception for women with epilepsy?
The use of intrauterine devices is an alternative method of contraception in the majority of women, with the advantage of no relevant drug-drug interactions.
Contraception for women taking antiepileptic drugs
Antiepileptic drugs (AEDs) that induce hepatic enzyme activity may alter the metabolism of most hormonal methods of contraception, and this may affect their contraceptive efficacy. There is also the
Variation in Lamotrigine Plasma Concentrations with Hormonal Contraceptive Monthly Cycles in Patients with Epilepsy
Summary:  Purpose: This is the first report comparing intrasubject lamotrigine (LTG) plasma concentrations between hormonal contraceptive (HC) intake and week‐off phases in epilepsy patients


Lamotrigine plasma levels reduced by oral contraceptives
The interaction was of clinical relevance in most of the patients who either experienced increased seizure frequency/recurrence of seizures after OC's had been added, or adverse effects following withdrawal of OC's.
Interactions Between Antiepileptic Drugs and Hormonal Contraception
There are no interactions between the combined oral contraceptive pill, progesterone-only pill, medroxyprogesterone injections or levonorgestrel implants or AEDs valproic acid (sodium valproate), vigabatrin, lamotrigine, gabapentin, tiagabine, levetiracetam, zonisamide, ethosuximide and the benzodiazepines.
Oral contraceptives reduce lamotrigine plasma levels
The mean steady-state plasma concentration of lamotrigine (LTG) was 13 μmol/L in 22 women taking LTG in combination oral contraceptives (OC) compared with 28 μmol-L among 30 women on LTG who did not take OC (p < 0.0001), indicating that LTG plasma levels are reduced by >50% during OC co-medication.
Effect of Topiramate or Carbamazepine on the Pharmacokinetics of an Oral Contraceptive Containing Norethindrone and Ethinyl Estradiol in Healthy Obese and Nonobese Female Subjects
To comparatively evaluate the pharmacokinetic interaction, which may cause contraceptive failure, a combination oral contraceptive containing norethindrone and ethinyl estradiol is studied during OC monotherapy, concomitant OC and topiramate therapy, and concomant OC and carbamazepine therapy.
Phenytoin pharmacokinetics in catamenial epilepsy
Seventeen women with seizures who were taking phenytoin (DPH) and whose seizures were more frequent perimenstrually were examined and mean serum DPH levels were lower during the menses.
Ovarian hormones, anticonvulsant drugs, and seizures during the menstrual cycle in women with epilepsy.
The effect of progesterone deficit on seizure susceptibility before menstrual bleeding is discussed, and the need of serum anticonvulsant level determination during the premenstrual phase in epileptic women is suggested.
Three Patterns of Catamenial Epilepsy
The existence of three hormonally based patterns of seizure exacerbation is proposed on the basis of the neuroactive properties of estradiol and progesterone and the menstrually related cyclic variations of their serum concentrations.
Pharmacokinetics and hormonal effects of lamotrigine-combined oral contraceptive co-administration
  • Epilepsia 2004;45(suppl 7):330. Epilepsia,
  • 2005
Ethinyl estradiol, but not gestagens, reduces lamotrigine serum concentrations
  • Epilepsia
  • 2004