The interaction of phenobarbital and other anticonvulsants with oral contraceptive steroid therapy

Back, DJ; Bates, Margaret W.; Bowden, Alexandra; Breckenridge, AM; Hall, Melanie; Jones, H Lewis; MacIver, M Bruce; Orme, M.; Perucca, Emilio; Richens, A.; Rowe, Philip H.; Smith, Eileen

doi:10.1016/0010-7824(80)90102-x

Cited by 117 publications

(34 citation statements)

References 13 publications

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“…The cytochrome P450 (CYP) enzyme system in the liver plays a significant role in drug metabolism, and drugs (possibly including the herbal medication, St John's Wort) that induce these enzymes can cause increased elimination of contraceptive steroids, resulting in reduced reliability and, consequently, unplanned pregnancy. 3 A variety of potent enzyme inducers known to have deleterious effects on hormonal contraceptives include some antiepileptics (carbamazepine, oxcarbazepine, phenytoin, phenobarbital, primidone, topiramate), [16][17][18][19] antibiotics (rifampicin, rifabutin), [20][21][22][23][24] antifungals (griseofulvin), 25 protease inhibitors (amprenavir, atazanavir, nelfinavir, lopinavir, saquinavir, ritonavir), 26 and non-nucleoside reverse transcriptase inhibitors (efavirenz, nevirapine). 27 There have been sporadic reports of Implanon failure due to suspected interaction with concomitantly administered drugs, resulting in intrauterine 10,11,28 or ectopic [29][30][31] pregnancies.…”

Section: Discussionmentioning

confidence: 99%

Failure of Implanon® on antituberculous therapy

Gbolade¹

2010

OAJC

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Implanon ® , a contraceptive implant, is increasingly being used because of its efficacy and nonuser-dependent nature. However, as for other steroid contraceptives, its efficacy can be reduced by enzyme-inducing drugs, such as antituberculous medication, resulting in unplanned pregnancy. We present the case of a 27-year-old para 1 + 0 referred to us for termination of a pregnancy that resulted from failure of Implanon during concomitant treatment with Rifinah ® (a rifampicin-isoniazid combination). All health care providers should be aware of the adverse effects of hepatic enzyme inducers on hormonal contraceptives, obtain details of current contraceptive methods from women of reproductive age, and refer them to contraceptive and reproductive health care professionals as appropriate for optimal management. This will ensure that such women do not experience the psychologic trauma of a termination of pregnancy.

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Section: Discussionmentioning

confidence: 99%

Failure of Implanon® on antituberculous therapy

Gbolade¹

2010

OAJC

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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). A second group of AEDs includes TPM, FBM, and OCBZ, which are less potent inducers of CYP but have been shown to alter plasma concentrations of the contraceptive steroids (12,29).…”

Section: Discussionmentioning

confidence: 99%

“…Contraceptive failure and unplanned pregnancy have been well documented in women with epilepsy treated concomitantly with CYP-inducing AEDs and OCs (3)(4)(5)(6)(7). Newer AEDs, including topiramate (TPM), felbamate (FBM), and oxcarbazepine (OCBZ), are less potent inducers of CYP, but they also may interfere with the metabolism of OCs, thereby altering plasma concentrations of the contraceptive steroids and potentially decreasing their efficacy (8)(9)(10)(11)(12).…”

mentioning

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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“…For example, the efficacious PXR activators rifampin and St. Johns wort increase clearance of the anti-rejection drug cyclosporine by inducing CYP3A4 and MDR1 expression, possibly leading to organ rejection in an allograft recipient [59]. Similarly, CAR and PXR activators increase metabolism of the estrogen component of combined oral contraceptives, potentially leading to unintended pregnancy [60][61][62].…”

Section: Overlapping Transcriptional Targets Of Vdr Pxr and Carmentioning

confidence: 99%

Evolution and Function of the NR1I Nuclear Hormone Receptor Subfamily (VDR, PXR, and CAR) with Respect to Metabolism of Xenobiotics and Endogenous Compounds

Reschly¹,

Krasowski²

2006

CDM

126

130

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The NR1I subfamily of nuclear hormone receptors includes the 1,25-(OH) 2 -vitamin D 3 receptor (VDR; NR1I1), pregnane X receptor (PXR; NR1I2), and constitutive androstane receptor (CAR; NR1I3). PXR and VDR are found in diverse vertebrates from fish to mammals while CAR is restricted to mammals. Current evidence suggests that the CAR gene arose from a duplication of an ancestral PXR gene, and that PXR and VDR arose from duplication of an ancestral gene, represented now by a single gene in the invertebrate Ciona intestinalis. Aside from the high-affinity effects of 1,25-(OH) 2 -vitamin D 3 on VDRs, the NR1I subfamily members are functionally united by the ability to bind potentially toxic endogenous compounds with low affinity and initiate changes in gene expression that lead to enhanced metabolism and elimination (e.g., induction of cytochrome P450 3A4 expression in humans). The detoxification role of VDR seems limited to sensing high concentrations of certain toxic bile salts, such as lithocholic acid, whereas PXR and CAR have the ability to recognize structurally diverse compounds. PXR and CAR show the highest degree of crossspecies variation in the ligand-binding domain of the entire vertebrate nuclear hormone receptor superfamily, suggesting adaptation to species-specific ligands. This review examines the insights that phylogenetic and experimental studies provide into the function of VDR, PXR, and CAR, and how the functions of these receptors have expanded to evolutionary advantage in humans and other animals.

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The interaction of phenobarbital and other anticonvulsants with oral contraceptive steroid therapy

Cited by 117 publications

References 13 publications

Failure of Implanon® on antituberculous therapy

Failure of Implanon® on antituberculous therapy

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

Evolution and Function of the NR1I Nuclear Hormone Receptor Subfamily (VDR, PXR, and CAR) with Respect to Metabolism of Xenobiotics and Endogenous Compounds

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The interaction of phenobarbital and other anticonvulsants with oral contraceptive steroid therapy

Cited by 117 publications

References 13 publications

Failure of Implanon&reg; on antituberculous therapy

Failure of Implanon&reg; on antituberculous therapy

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

Evolution and Function of the NR1I Nuclear Hormone Receptor Subfamily (VDR, PXR, and CAR) with Respect to Metabolism of Xenobiotics and Endogenous Compounds

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Failure of Implanon® on antituberculous therapy

Failure of Implanon® on antituberculous therapy