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

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SPEAKER DISCLOSURES

Regina Renner has no relationship with commercial interests Research / Project funders: CIHR

Nicole Todd has received speaking honoraria from Bayer

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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

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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

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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

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CONTRACEPTION IN CANADA

Black et al. Canadian Contraception Consensus (1 of 4). No. 329. October 2015.

General population pregnancy outcomes: 77% birth 21% induced abortions 2% fetal loss

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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

Black et al. Canadian Contraception Consensus (1 of 4). No. 329. October 2015.

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CONTRACEPTIVE METHODS

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

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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

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MEDICAL ELIGIBILITY CRITERIA (MEC)

Evidence-based guidelines for safety of methods with co-existing conditions

MEC 2016. https://www.cdc.gov/reproductivehealth/contraception/mmwr/mec/summary.html

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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

• utweigh 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

CDC MEDICAL ELIGIBILITY FOR CONTRACEPTIVE USE (2016)

MEC 2016. https://www.cdc.gov/reproductivehealth/contraception/mmwr/mec/summary.html

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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 Black et al, 2016

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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
• n 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

Black et al, 2016

Im Implant description

Rate-controlling membrane (0.06 mm):100% EVA

4 cm 2 mm

Core: 37% ethylene vinyl acetate (EVA) copolymer 60% etonogestrel (68 mg) 3% barium sulfate (15 mg) Rate-controlling membrane (0.06 mm):100% EVA

4 cm 2 mm

Core: 37% ethylene vinyl acetate (EVA) copolymer 60% etonogestrel (68 mg) 3% barium sulfate (15 mg)

*Please refer to the approved Canadian Product Monograph.

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SUBDERMAL IMPLANT

• Training video on insertion
• Training video on removal

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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

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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

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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.

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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

NEXPLANON cli clinical tri trial EFFICACY & SAFETY1

• 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

• 1. Contraception. 2010;82:243-9; 2. Contraception. 2019;100:31-36.

*Please refer to the approved Canadian Product Monograph.

IM IMPLANON cli clinical tria trials EFF FFICACY & SAFETY1

• 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.
• 1. Contraception 2010; 82: 243-9.

*Please refer to the approved Canadian Product Monograph. PI: cumulative pearl index.

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PERFECT VERSUS TYPICAL USE

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

Contraceptive Method

Failure Rate 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%

<

=

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ADVERSE REACTIONS

(>5% IN PHASE 3 IMPLANON CLINICAL TRIALS)

Adverse reactions All studies (N=942) Adverse reactions All studies (N=942) Headache 24.9% Dysmenorrhea 7.2% Vaginitis 14.5% Back pain 6.8% Weight increase 13.7% Emotional lability 6.5% Acne 13.5% Nausea 6.4% Breast pain 12.8% Pain 5.6% Abdominal pain 10.9% Nervousness 5.6% Pharyngitis 10.5% Depression 5.5% Leukorrhea 9.6% Hypersensitivity 5.4% Influenza-like symptoms 7.6% Insertion site pain 5.2% Dizziness 7.2%

*Please refer to the approved Canadian Product Monograph

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• Change in menstrual bleeding pattern (irregular menses) was the most common adverse reaction

causing discontinuation of treatment

• Irregular bleeding (10.8%) was the single most common reason women stopped treatment, while

amenorrhea (0.3%) was cited less frequently.

Adverse reactions le leading to dis iscontinuation

(>1% of subjects in IMPLANON Phase 3 clinical trials) Adverse reactions

All studies (N=942)

Bleeding irregularitiesa 11.1% Emotional lability 2.3% Weight increase 2.3% Headache 1.6% Acne 1.3% Depression 1.0%

*Please refer to the approved Canadian Product Monograph.

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Ble leedin ing Patterns wit ith IM IMPLANON

90 90-day Reference Peri riod 2 – 6 (1 (1.5 .5 Years)

Mean prevalence, % Discontinuing users, % Overall 11.3% Amenorrhoea 22.2 0.8 Infrequent bleeding

1-2 episodes/90 days

33.6 ≈1-2 Normal bleeding

3-5 episodes

37.5 ≈1-2 Frequent bleeding

>5 episodes

6.7 4.2 Prolonged bleeding (>14days) 17.7 3.4

Mansour D, et al. Eur J Contracept Reprod Health Care. 2008;13:13-28.

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COMPLICATIONS AT INSERTION

• Should be inserted subdermally so it will be palpable after insertion
• In the NEXPLANON clinical trial, 300/301 implants were palpable immediately after insertion. The non-

palpable implant was not placed according to instructions.

• Deeply placed implants may be difficult or impossible to remove in the office setting and may require

additional procedures (e.g. ultrasound localization, fluoroscopy)

• Palpate immediately after insertion to confirm placement
• Undetected failure to insert the implant may lead to an unintended pregnancy
• If inserted deeply (intramuscular or adjacent to the deep fascia), neural or vascular injury may
• ccur at the time of insertion or during attempted removal
• Deep insertions have been associated with paresthesia (due to neural injury), migration of the

implant (due to intramuscular or fascial insertion), and intravascular insertion

• Migration of the implant to the pulmonary artery and lung has been reported. In some cases, the

patient is asymptomatic; in other cases, the patient presents with dyspnea, cough or hemoptysis

*Please refer to the approved Canadian Product Monograph.

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COMPLICATIONS OF INSERTION AND REMOVAL

May include:

• Pain,
• Paresthesia
• Bleeding
• Hematoma
• Scarring
• Infection
• Incomplete insertions or infections may lead to implant expulsion
• Implant removal may be difficult or impossible if the implant is inserted too

deeply, is not palpable, is encased in fibrotic tissue or has migrated

Black 2016, *Please refer to the approved Canadian Product Monograph.

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RETURN TO FERTILITY

• In clinical trials for IMPLANON, the etonogestrel levels in blood decreased

below sensitivity of the assay by 1 week after removal of the implant.

• In the IMPLANON clinical trials, pregnancies were conceived as early as 7-14

days after removal and usually within 3 weeks. Therefore, a woman should restart contraception immediately after removal of the implant if continued contraceptive protection is desired.

Black 2016,. Merck

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HOW DO WE HELP OUR PATIENTS DECIDE BETWEEN LARC METHODS?

• Success – you will be successful with IUD and subdermal implant insertions in

adolescents, nulliparous!

• IUD associated with more discomfort post-insertion, and may be reason for

removal

• Undetectable – both methods are undetectable
• Bleeding
• Most common reason for removal in both IUD and subdermal implant removals
• Ongoing use
• At 12 months, both methods associated with ~80% ongoing use
• Patient preference!
• CHOICE study indicated IUD preferred over implant
• Ask patients what motivates them for contraceptive choice

Peipert et al. Obstet Gynecol 2012

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SUMMARY

• Progestin implants have failure rates as low as permanent contraception. (II-2)
• The use of a progestin implant immediately postpartum and postabortion is an effective

way of decreasing repeat pregnancy in adolescents and repeat abortions. (II-2)

• The most common side effect of progestin-only contraceptive methods is menstrual

cycle disturbances. (II-2)

• Amenorrhea is very common with depot medroxyprogesterone acetate and progestin

implant use. (II-2)

• The use of progestins given at contraceptive doses does not appear to increase the

risk of venous thromboembolism, myocardial infarction, or stroke. (II-2)

• The efficacy of progestin implants or depot medroxyprogesterone acetate is not

decreased in overweight and obese women. (II-2)

Provider Resources

Resources:

• https://www.cdc.gov/reproductivehealth/contraception/mmwr/mec/summary.

html

• www.who.int – medical eligibility criteria
• www.reproductiveaccess.org – materials for provider and patients
• www.prch.org - Physicians for Reproductive Choice and Health
• www.aap.org - The American Academy of Pediatrics
• www.acog.org - The American College of Obstetricians and Gynecologists
• www.adolescenthealth.org - The Society for Adolescent Medicine
• http://www.aclu.org/reproductiverights/ - The Reproductive Freedom

Project of the American Civil Liberties Union

• www.advocatesforyouth.org – Advocates for Youth
• www.guttmacher.org – Guttmacher Institute
• www.cahl.org/ - Center for Adolescent Health and the Law
• www.gynob.emory.edu - The Jane Fonda Center of Emory University
• www.siecus.org - The Sexuality Information and Education Council of the

United States

• www.arhp.org - The Association of Reproductive Health Professionals
• https://bedsider.org - Bedsider

QUESTIONS

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