Ignite Creation Date:
2024-05-05 @ 12:10 PM
Last Modification Date:
2024-10-26 @ 9:21 AM
Study NCT ID:
NCT00266149
Status:
TERMINATED
Last Update Posted:
2008-04-24
First Post:
2005-12-14
Brief Title:
Lamotrigine and Oral Contraceptives
Sponsor:
University of Aarhus
Organization:
University of Aarhus
Study Overview
Official Title:
Phase 3 Metabolism of Lamotrigine During Treatment With Oral Contraceptives
Status:
TERMINATED
Status Verified Date:
2005-12
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
The present study evaluates the effect of oral contraceptives on lamotrigine plasma concentrations in a double blind placebo controlled cross-over study in patients with epilepsy
Detailed Description:
Lamotrigine is widely used as an antiepileptic drug in the treatment of newly onset as well as refractory epilepsy 12 Lamotrigine is unique among the antiepileptic drug since the major route 76 of elimination is conjugation with glucuronic acid glucuronidation 3 This conjugation reaction is catalyzed by the uridine 5-diphosphate UDP-glucuronosyltransferases UGTs of which the isoform UGT1A4 probably is the major route of metabolism in humans 3 The pathway is inhibited by valproate and induced by other anticonvulsants 3 and explains the effect of these drugs on lamotrgine metabolism 4 Other drugs that are metabolized via direct glucoronidation may interfere with the metabolism of lamotrigine eg acetaminophen 5 Estrogeneous substrates are metabolized via glucuronidation 6-8 and may potentially interact with the metabolism of lamotrigine In the development of lamotrigine for use in epilepsy patients the effect on the oral contraceptive pill was studied In contrast to other commonly used antiepileptic drugs eg carbamazepine and phenytoin9 lamotrigine did not significantly influence the constituents of the oral contraceptive pill 10-12 In addition it was initially assumed from population pharmacokinetic studies that oral contraceptives did not influence the metabolism of lamotrigine 13However recent retrospective studies indicate that oral contraceptives may increase the metabolism of lamotrigine resulting in a significant decrease in plasma concentration of lamotrigine when given with oral contraceptives 1415 This effect is probably related to the ethinyl estradiol content of the combined contracetive pill and no the progesterone content 16
To confirm and further extend these findings the present study evaluates the effect of oral contraceptives on lamotrigine plasma concentrations in a double blind placebo controlled cross-over study in patients with epilepsy
Reference List
1 French JA Kanner AM Bautista J Abou-Khalil B Browne T Harden CL et al Efficacy and Tolerability of the New Antiepileptic Drugs II Treatment of Refractory Epilepsy Report of the TTA and QSS Subcommittees of the American Academy of Neurology and the American Epilepsy Society Epilepsia 2004 455410-423
2 French JA Kanner AM Bautista J Abou-Khalil B Browne T Harden CL et al Efficacy and Tolerability of the New Antiepileptic Drugs I Treatment of New-Onset Epilepsy Report of the TTA and QSS Subcommittees of the American Academy of Neurology and the American Epilepsy Society Epilepsia 2004 455401-409
3 Dickins M Chen C Lamotrigine Chemistry Biotransformation and Pharmacokinetics In Levy RH Mattson RH Meldrum BS Perucca E editors Antiepileptic Drugs Philidelphia Lippincott Williams Wilkins 2002 370-379
4 Patsalos PN Perucca E Clinically important drug interactions in epilepsy general features and interactions between antiepileptic drugs Lancet Neurol 2003 26347-356
5 Depot M Powell JR Messenheimer JAJ Cloutier G Dalton MJ Kinetic effects of multiple oral doses of acetaminophen on a single oral dose of lamotrigine Clin Pharmacol Ther 1990 484346-355
6 Tephly TR Green MD UDP-Glucuronosyltransferases In Levy RH Thummel KE Trager W Hansten PD Eichelbaum M editors Metabolic Drug Interactions Philidelphia Lippincott Williams Wilkins 2000 161-174
7 Shipkova M Wieland E Glucuronidation in therapeutic drug monitoring Clin Chim Acta 2005 3581-22-23
8 Ebner T Remmel RP Burchell B Human bilirubin UDP-glucuronosyltransferase catalyzes the glucuronidation of ethinylestradiol Mol Pharmacol 1993 434649-654
9 Patsalos PN Perucca E Clinically important drug interactions in epilepsy interactions between antiepileptic drugs and other drugs Lancet Neurol 2003 28473-481
10 Crawford P Interactions between antiepileptic drugs and hormonal contraception CNS Drugs 2002 16 4 263 -72 2002 164263-272
11 Doose DR Wang SS Padmanabhan M Schwabe S Jacobs D Bialer M Effect of topiramate or carbamazepine on the pharmacokinetics of an oral contraceptive containing norethindrone and ethinyl estradiol in healthy obese and nonobese female subjects Epilepsia 2003 Apr 44 4 540 -9 444540-549
12 Holdish T Whiteman P Orme M Back D Ward S Effect of lamotrigine on the pharmacology of the combined oral contraceptive pill Epilepsia 32suppl 1 s96 1991
13 Hussein Z Posner J Population pharmacokinetics of lamotrigine monotherapy in patients with epilepsy retrospective analysis of routine monitoring data Br J Clin Pharmacol 1997 435457-465
14 Sabers A Ohman I Christensen J Tomson T Oral contraceptives reduce lamotrigine plasma levels Neurology 2003 Aug 26 61 4 570 -1 2003 614570-571
15 Sabers A Buchholt JM ULDALL P Hansen EL Lamotrigine plasma levels reduced by oral contraceptives Epilepsy Res 2001 Nov 47 1 -2 151 -4 471-2151-154
16 Reimers A Helde G Brodtkorb E Ethinyl estradiol not progestogens reduces lamotrigine serum concentrations Epilepsia 2005 4691414-1417
To confirm and further extend these findings the present study evaluates the effect of oral contraceptives on lamotrigine plasma concentrations in a double blind placebo controlled cross-over study in patients with epilepsy
Reference List
1 French JA Kanner AM Bautista J Abou-Khalil B Browne T Harden CL et al Efficacy and Tolerability of the New Antiepileptic Drugs II Treatment of Refractory Epilepsy Report of the TTA and QSS Subcommittees of the American Academy of Neurology and the American Epilepsy Society Epilepsia 2004 455410-423
2 French JA Kanner AM Bautista J Abou-Khalil B Browne T Harden CL et al Efficacy and Tolerability of the New Antiepileptic Drugs I Treatment of New-Onset Epilepsy Report of the TTA and QSS Subcommittees of the American Academy of Neurology and the American Epilepsy Society Epilepsia 2004 455401-409
3 Dickins M Chen C Lamotrigine Chemistry Biotransformation and Pharmacokinetics In Levy RH Mattson RH Meldrum BS Perucca E editors Antiepileptic Drugs Philidelphia Lippincott Williams Wilkins 2002 370-379
4 Patsalos PN Perucca E Clinically important drug interactions in epilepsy general features and interactions between antiepileptic drugs Lancet Neurol 2003 26347-356
5 Depot M Powell JR Messenheimer JAJ Cloutier G Dalton MJ Kinetic effects of multiple oral doses of acetaminophen on a single oral dose of lamotrigine Clin Pharmacol Ther 1990 484346-355
6 Tephly TR Green MD UDP-Glucuronosyltransferases In Levy RH Thummel KE Trager W Hansten PD Eichelbaum M editors Metabolic Drug Interactions Philidelphia Lippincott Williams Wilkins 2000 161-174
7 Shipkova M Wieland E Glucuronidation in therapeutic drug monitoring Clin Chim Acta 2005 3581-22-23
8 Ebner T Remmel RP Burchell B Human bilirubin UDP-glucuronosyltransferase catalyzes the glucuronidation of ethinylestradiol Mol Pharmacol 1993 434649-654
9 Patsalos PN Perucca E Clinically important drug interactions in epilepsy interactions between antiepileptic drugs and other drugs Lancet Neurol 2003 28473-481
10 Crawford P Interactions between antiepileptic drugs and hormonal contraception CNS Drugs 2002 16 4 263 -72 2002 164263-272
11 Doose DR Wang SS Padmanabhan M Schwabe S Jacobs D Bialer M Effect of topiramate or carbamazepine on the pharmacokinetics of an oral contraceptive containing norethindrone and ethinyl estradiol in healthy obese and nonobese female subjects Epilepsia 2003 Apr 44 4 540 -9 444540-549
12 Holdish T Whiteman P Orme M Back D Ward S Effect of lamotrigine on the pharmacology of the combined oral contraceptive pill Epilepsia 32suppl 1 s96 1991
13 Hussein Z Posner J Population pharmacokinetics of lamotrigine monotherapy in patients with epilepsy retrospective analysis of routine monitoring data Br J Clin Pharmacol 1997 435457-465
14 Sabers A Ohman I Christensen J Tomson T Oral contraceptives reduce lamotrigine plasma levels Neurology 2003 Aug 26 61 4 570 -1 2003 614570-571
15 Sabers A Buchholt JM ULDALL P Hansen EL Lamotrigine plasma levels reduced by oral contraceptives Epilepsy Res 2001 Nov 47 1 -2 151 -4 471-2151-154
16 Reimers A Helde G Brodtkorb E Ethinyl estradiol not progestogens reduces lamotrigine serum concentrations Epilepsia 2005 4691414-1417
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None
Secondary IDs
| Secondary ID | Type | Domain | Link |
|---|---|---|---|
| EKj nr 20030009 | None | None | None |