Contraception, Drug Interactions
Conditions
Keywords
etonogestrel implant, anti-epileptic drugs, pharmacokinetics
Brief summary
Data on the interaction between the etonogestrel (ENG) implant and antiepileptic drug (AED) regimen are scarce. We will evaluated the effect of 2 AED regimens (1 including carbamazepine and the other topiramate) on the pharmacokinetic (PK) parameters of an ENG-releasing implant in women with epilepsy.
Interventions
DRUGCarbamazepine-Implant
Women with epilepsy using carbamazepine for at least 3 months will have an etonogestrel-releasing implant inserted
DRUGTopiramate-Implant
Women with epilepsy using carbamazepine for at least 3 months will have an etonogestrel-releasing implant inserted
DRUGImplant
Women without epilepsy and not using an anti-epileptic drug will have an etonogestrel-releasing implant inserted
Sponsors
University of Sao Paulo
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
OTHER
Masking
SINGLE (Outcomes Assessor)
Intervention model description
It is a non-randomized clinical trial (controlled clinical trial)
Eligibility
Sex/Gender
FEMALE
Age
18 Years to 40 Years
Healthy volunteers
Yes
Inclusion criteria
* women 18- 45 years old; * with regular menstrual cycles; * with BMI between 18 and 29.9 (kg/m2); * who has selected the ENG implant as a contraceptive method; * Using a stable antiepileptic drug regimen including carbamazepine or topiramate for ate least 3 months (only for women with epilepsy).
Exclusion criteria
* use of short-acting hormonal contraceptives in the month prior to enrollment; * use of depomedroxyprogesterone acetate in the 6 months prior to enrollment; * women with conditions classified as category 3 and/or 4 for etonogestrel implant use according to the World Health Organization Medical Eligibility Criteria for contraceptive use; * drug or alcohol addiction; * use of other drugs metabolized by CYP3A4 30 days prior to enrollment; * non adherence to antiepileptic drug regimen (only for women with epilepsy); * illiteracy
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Plasma minimum concentration (Cmin) of ENG in women with epilepsy (WWE) using carbamazepine | Prior to etonogestrel implant insertion and each 15 days for 24 weeks after implant placement | Blood will be collected prior to ENG implant insertion and each 15 days for 24 weeks after implant placement for evaluation of plasma Cmin of ENG. The plasma ENG Cmin will be compared to that of women without epilepsy and without carbamazepine use prior to ENG implant insertion and each 15 days for 24 weeks after implant placement. |
| Time to maximum concentration (Tmax) of ENG in women with epilepsy (WWE) using carbamazepine | Prior to etonogestrel implant insertion and each 15 days for 24 weeks after implant placement | Blood will be collected prior to ENG implant insertion and each 15 days for 24 weeks after implant placement for evaluation of Tmax of ENG. The Tmax of ENG will be compared to that of women without epilepsy and without carbamazepine use prior to ENG implant insertion and each 15 days for 24 weeks after implant placement. |
| Area under the plasma concentration versus time curve (AUC) of ENG in women with epilepsy (WWE) using carbamazepine | Prior to etonogestrel implant insertion and each 15 days for 24 weeks after implant placement | Blood will be collected prior to ENG implant insertion and each 15 days for 24 weeks after implant placement for area under the curve evaluation of ENG (AUC, 0-24 weeks). The plasma ENG AUC will be compared to that of women without epilepsy and without carbamazepine use prior to ENG implant insertion and each 15 days for 24 weeks after implant placement. |
| Plasma maximum concentration (Cmax) of ENG in women with epilepsy (WWE) using carbamazepine | Prior to etonogestrel implant insertion and each 15 days for 24 weeks after implant placement | Blood will be collected prior to ENG implant insertion and each 15 days for 24 weeks after implant placement for evaluation of plasma Cmax of ENG. The plasma ENG Cmax will be compared to that of women without epilepsy and without carbamazepine use prior to ENG implant insertion and each 15 days for 24 weeks after implant placement. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Plasma minimum concentration (Cmin) of ENG in women with epilepsy (WWE) using topiramate | Prior to etonogestrel implant insertion and each 15 days for 24 weeks after implant placement | Blood will be collected prior to ENG implant insertion and each 15 days for 24 weeks after implant placement for evaluation of plasma Cmin of ENG. The plasma ENG Cmin will be compared to that of women without epilepsy and without topiramate use prior to ENG implant insertion and each 15 days for 24 weeks after implant placement. |
| Time to maximum concentration (Tmax) of ENG in women with epilepsy (WWE) using topiramate | Prior to etonogestrel implant insertion and each 15 days for 24 weeks after implant placement | Blood will be collected prior to ENG implant insertion and each 15 days for 24 weeks after implant placement for evaluation of Tmax of ENG. The Tmax of ENG will be compared to that of women without epilepsy and without topiramate use prior to ENG implant insertion and each 15 days for 24 weeks after implant placement. |
| Area under the plasma concentration versus time curve (AUC) of carbamazepine in women with epilepsy (WWE) before and after ENG implant placement | Prior to implant placement and at 24 weeks of implant use | Blood will be collected prior to etonogestrel implant use and at 24 weeks of its placement to evaluate AUC (0-8 hours) of carbamazepine |
| Plasma maximum concentration (Cmax) of carbamazepine in women with epilepsy (WWE) before and after ENG implant placement | Prior to implant placement and at 24 weeks of implant use | Blood will be collected prior to etonogestrel implant use and at 24 weeks of its placement to evaluate Cmax of carbamazepine |
| Time to maximum concentration (Tmax) of carbamazepine in women with epilepsy (WWE) before and after ENG implant placement | Prior to implant placement and at 24 weeks of implant use | Blood will be collected prior to etonogestrel implant use and at 24 weeks of its placement to evaluate Tmax of carbamazepine |
| Area under the plasma concentration versus time curve (AUC) of topiramate in women with epilepsy (WWE) before and after ENG implant placement | Prior to implant placement and at 24 weeks of implant use | Blood will be collected prior to etonogestrel implant use and at 24 weeks of its placement to evaluate AUC (0-8 hours) of topiramate |
| Plasma maximum concentration (Cmax) of topiramate in women with epilepsy (WWE) | Prior to implant placement and at 24 weeks of implant use | Blood will be collected prior to etonogestrel implant use and at 24 weeks of its placement to evaluate Cmax of topiramate |
| Plasma minimum concentration (Cmin) of topiramate in women with epilepsy (WWE) before and after ENG implant placement | Prior to implant placement and at 24 weeks of implant use | Blood will be collected prior to etonogestrel implant use and at 24 weeks of its placement to evaluate Cmin of topiramate |
| Time to maximum concentration (Tmax) of topiramate in women with epilepsy (WWE) before and after ENG implant placement | Prior to implant placement and at 24 weeks of implant use | Blood will be collected prior to etonogestrel implant use and at 24 weeks of its placement to evaluate Tmax of topiramate |
| Plasma minimum concentration (Cmin) of carbamazepine in women with epilepsy (WWE) before and after ENG implant placement | Prior to implant placement and at 24 weeks of implant use | Blood will be collected prior to etonogestrel implant use and at 24 weeks of its placement to evaluate Cmin of carbamazepine |
| Bleeding pattern associated with etonogestrel implant use | Daily for 24 weeks | Bleeding pattern (frequency, duration and number of bleeding/spotting days) associated with etonogestrel implant use will be evaluated in WWE using carbamazepine or topiramate and in women without epilepsy and without antiepileptic drug use |
| Area under the plasma concentration versus time curve (AUC) of ENG in women with epilepsy (WWE) using topiramate | Prior to etonogestrel implant insertion and each 15 days for 24 weeks after implant placement | Blood will be collected prior to ENG implant insertion and each 15 days for 24 weeks after implant placement for area under the curve evaluation of ENG (AUC, 0-24 weeks). The plasma ENG AUC will be compared to that of women without epilepsy and without topiramate use prior to ENG implant insertion and each 15 days for 24 weeks after implant placement. |
| Plasma maximum concentration (Cmax) of ENG in women with epilepsy (WWE) using topiramate | Prior to etonogestrel implant insertion and each 15 days for 24 weeks after implant placement | Blood will be collected prior to ENG implant insertion and each 15 days for 24 weeks after implant placement for evaluation of plasma Cmax of ENG. The plasma ENG Cmax will be compared to that of women without epilepsy and without topiramate use prior to ENG implant insertion and each 15 days for 24 weeks after implant placement. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Acceptability | At 24 weeks of implant placement | A questionnaire will be used to measure acceptability to etonogestrel implant by WWE |
| Satisfaction | At 24 weeks of implant placement | A questionnaire will be applied to measure satisfaction of WWE with etonogestrel implant |
Countries
Brazil
Outcome results
None listed