CONTRACEPTIVE IMPLANT WHAT YOU NEED TO KNOW ABOUT A NEW CLASS OF - PowerPoint PPT Presentation

NEXT UP- SUBDERMAL CONTRACEPTIVE IMPLANT WHAT YOU NEED TO KNOW ABOUT A NEW CLASS OF DRUG COMING SOON REGINA RENNER, MD, MPH, FRCSC, FACOG, CLINICAL ASSOCIATE PROFESS OR DEPARTMENT OF OBSTETRICS AND GYNAECOLOGY, UNIVERSITY OF BRITISH COLUMBIA REGINA.RENNER@UBC.CA NICOLE TODD, MD, FRCSC, CLINICAL ASSOCIATE PROFESSOR, DEPARTMENT OF OBSTETRICS AND GYNAECOLOGY, UNIVERSITY OF BRITISH COLUMBIA NTODD@CW.BC.CA

SPEAKER DISCLOSURES Regina Renner has no relationship with commercial interests Research / Project funders: CIHR Nicole Todd has received speaking honoraria from Bayer 2

MITIGATING POTENTIAL BIAS • All available contraceptive options available in Canada will be presented • We will not be speaking about off-label medication use • We will be speaking about the contraceptive progestin only implant • Not currently available in Canada • Slide decks provided by Merck are clearly indicated 3

LEARNING OBJECTIVES After this session, participants will be able to: • Summarize trends in Reproductive Health in Canada • Review the history of the subdermal implant • Discuss the subdermal implant as a contraceptive option • Identify contraindications for the subdermal implant • Effectively counsel patients on the process of insertion and removal of the subdermal implant • Integrate current best evidence on subdermal implant into contraceptive plans for our patients 4

TRENDS IN REPRODUCTIVE HEALTH • On average, Canadian women spend <3 years of their lives pregnant, attempting to conceive, or immediately post-partum • Average age of first birth is over 30 years • Women are spending at least half of their lives at risk for unintended pregnancy • 1/3 Canadian women have at least one induced abortion in their reproductive lifetime 5

CONTRACEPTION IN CANADA General population pregnancy outcomes: 77% birth 21% induced abortions 2% fetal loss 6 Black et al. Canadian Contraception Consensus (1 of 4). No. 329. October 2015.

CONTRACEPTIVE USE IN CANADA 2006 Canadian Contraception Survey (CCHS) • 14.9% of sexually active women were using no contraception while 20% were using contraception inconsistently Most commonly used methods of contraception: • oral contraceptives (44%) and condoms (54%) • third most commonly used was withdrawal (12%) Significant variations in use of effective contraception in Canada • low rates of use (“high unmet need”) among vulnerable populations such as youth, those living in rural and remote territories, recent immigrants and low socioeconomic status 7 Black et al. Canadian Contraception Consensus (1 of 4). No. 329. October 2015.

CONTRACEPTIVE METHODS 8 Innovating Education in Reproductive Health. UCSF. http://innovating-education.org

EVIDENCE-BASED CONTRACEPTION GUIDELINES Where to access contraceptive guidelines: • World Health Organization, 2016 • CDC Medical Eligibility for Contraceptive Use, 2016 • SOGC Contraceptive Guidelines, 2016 • United Kingdom Medical Eligibility for Contraceptive Use, 2016 9

MEDICAL ELIGIBILITY CRITERIA (MEC) Evidence-based guidelines for safety of methods with co-existing conditions 10 MEC 2016. https://www.cdc.gov/reproductivehealth/contraception/mmwr/mec/summary.html

CDC MEDICAL ELIGIBILITY FOR CONTRACEPTIVE USE (2016) Category Recommendation 1 A condition for which there is no restriction for the use of the contraceptive method 2 A condition for which the advantages of using the method generally outweigh the theoretical or proven risks 3 A condition for which the theoretical or proven risks usually outweigh the advantages of using the method 4 A condition that represents an unacceptable health risk if the contraceptive method is used. This method should not be used 11 MEC 2016. https://www.cdc.gov/reproductivehealth/contraception/mmwr/mec/summary.html

SUBDERMAL IMPLANTS – A BRIEF HISTORY • Subdermal implants are currently used in 85 countries!! • Norplant (6 rod subdermal implant) was discontinued in Canada in 2000 • Manufacturing inconsistencies affecting contraceptive efficacy • Bringing new contraceptives to Canada • Health Canada has different requirements for clinical trials, and had requested further trials from Merck (manufacturer of subdermal implant) Black A, 2019 12 Black et al, 2016

PROGESTIN ONLY SUBDERMAL IMPLANT • Single-rod, progestin-only (etonogestrel, 68mg) subdermal implant  Single use preloaded applicator  Placed at the inner side of the upper arm overlying the triceps just underneath skin  8-10 cm from the medial epicondyle of the humerus and 3-5 cm posterior to the sulcus between bicep and tricep muscles  Barium sulfate in the ethylene vinyl acetate core, allowing for visualization on X ray, and/or ultrasound • Effective for up to 3 years • Contraceptive effect achieved by suppression of ovulation, increased viscosity of the cervical mucus, and alterations in the endometrium 13 Black et al, 2016

Implant description Im 4 cm 4 cm 2 mm 2 mm Core: Core: 37% ethylene vinyl acetate (EVA) copolymer 37% ethylene vinyl acetate (EVA) copolymer 60% etonogestrel (68 mg) 60% etonogestrel (68 mg) 3% barium sulfate (15 mg) 3% barium sulfate (15 mg) Rate-controlling membrane (0.06 mm):100% EVA Rate-controlling membrane (0.06 mm):100% EVA *Please refer to the approved Canadian Product Monograph.

SUBDERMAL IMPLANT • Training video on insertion • Training video on removal 15

SUBDERMAL IMPLANT • Indications • Long-acting reversible contraception • Continued use at 12 months: 84% • Can be inserted: • Post-abortion • Post-partum – immediate, breastfeeding • Obesity Black et al, 2016; Hansen 2020 16

NON CONTRACEPTIVE BENEFITS • In women with baseline dysmenorrhea, 77% report a complete resolution of dysmenorrhea. • Pain associated with endometriosis is reduced with the use of the ENG implant. • A small, randomized, controlled trial demonstrated decreased pain in women with pelvic congestion syndrome. • Amenorrhea occurs in 22% to 29% of ENG implant users. • Improved anemia Black et al, 2016 17

CONTRAINDICATIONS • Known or suspected pregnancy • Active venous thromboembolic disorder • Known or suspected sex steroid sensitive malignancies • Presence or history of liver tumours (benign or malignant) • Presence or history of severe hepatic disease, as long as liver function values have not returned to normal • Undiagnosed abnormal vaginal bleeding • Hypersensitivity to the drug, any ingredients of the formulation or any of the components *Please refer to the approved Canadian Product Monograph. 18

MEDICATION INTERACTIONS • Women using NNRTIs containing either efavirenz or nevirapine or those using protease inhibitors (atazanavir, darunavir, lopinavir/ritonavir, ritonavir) generally can use ENG implants (category 2). • Reports of contraceptive failure with Efavirenz, nelfinavir • These medications may reduce its contraceptive effectiveness: anticonvulsants (barbiturates, carbamazepine, oxcarbazepine, phenytoin, primidone, topiramate), rifampicin, bosentan, St. John’s wort and ulipristal acetate • Counsel on barrier protection Black et al, 2016 19

NEXPLANON cli clinical tri trial EFFICACY & SAFETY 1 • No on-treatment pregnancies in NEXPLANON clinical trial* (n=301, 655 woman-years) 1  PI=0 (95% CI: 0, 0.56) • No drug or device-associated SAEs • Most commonly reported AEs:  vaginal bleeding (28%); headaches (19%); acne (13%); weight gain (12%; mean 1.3 kg) • Local AEs associated with insertion/ removal:  hematoma 3.3%; insertion site erythema 4%; pain 1% 4.4% removals encountered fibrosis • Additional efficacy & safety information obtained by an observational study performed in the U.S. (n=7364) 2 *Please refer to the approved Canadian Product Monograph. 1. Contraception. 2010;82:243-9; 2. Contraception. 2019;100:31-36.

IM IMPLANON cli clinical tria trials FFICACY & SAFETY 1 EFF • No on-treatment pregnancies occurred in Phase 3 IMPLANON trials (n=923 non-lactating women, ~24K cycles, 1832 woman-years).  PI= 0 pregnancies per 100 woman-years of use (95% CI: 0, 0.2)  Rapidly reversible: 6 pregnancies conceived within 14 days (range 7-13 days) of implant removal • Effectiveness of etonogestrel implant in overweight women not defined because women who weighed more than 130% of their ideal body weight were not studied in the clinical trials.  Serum level is largely inversely proportional to duration of use and bodyweight; earlier replacement should be considered • On-treatment pregnancies reported in post-marketing surveillance and observational studies. No contraceptive is 100% effective. *Please refer to the approved Canadian Product Monograph. PI: cumulative pearl index. 1. Contraception 2010; 82: 243-9.

PERFECT VERSUS TYPICAL USE Failure Rate Contraceptive Method Perfect Use Typical Use Progestin Pills < 1% 9 % Combined Pill/ Patch/ Ring < 1% 9 % < Combined 1-month injection < 1% 9 % 3-Month Injection < 1% 6% = Implants < 1% < 1% Copper IUD/ LNG IUD < 1% < 1% 22 Innovating Education in Reproductive Health. UCSF. http://innovating-education.org