PRODUCT BRIEF Caucus on New and Underused Reproductive Health Technologies

Contraceptive implants

Description compared to women who do not use contraception,7 as the synthetic continuous-release hormones in Introduced 30 years ago, contraceptive implants are one implants have a short half-life. A new can of the most effective family planning methods available. be inserted at the time of removal if continued Implants are thin, flexible rods that are inserted just contraception is desired. under the skin of a woman’s upper arm and provide Contraceptive implants can be used by almost all sustained contraception, ranging from three to five women. Implants are best suited to women who desire years depending on the type of implant. a user-independent contraceptive method for birth The Population Council developed the first spacing and limiting. Implants should not be inserted contraceptive implant—Norplant®—which was in women during the first six weeks after if approved in 1983 in Finland, the country of they are exclusively or partially breastfeeding; in women manufacture. Norplant® consisted of six rods (2.4 mm with serious liver disease, problems with blood clots, or x 34 mm), each containing 36 mg of , unusual vaginal bleeding; or in women who have a synthetic progestin similar to the natural female or have had breast cancer. Contraceptive implants hormone progesterone. Production of Norplant® was do not provide protection from sexually transmitted discontinued in 2008 because the new generation of infections (STIs).7 products—the two-rod implants, Jadelle® and Sino- implant (II)®, and one-rod implants, Implanon® and Nexplanon®/Implanon NXT®—are easier to insert and Efficacy remove. Jadelle®, which was approved by the United Contraceptive implants are one of the most effective States Food and Drug Administration (USFDA) in 1996, contraceptive methods available. consists of two rods (2.5 mm x 43 mm), each containing 75 mg of levonorgestrel. In 1996, Sino-implant (II)®, Annual rates are less than 1 percent with a similar two-rod implant (2.4 mm x 44 mm) with all implants.2,8,9 Continuation rates are often better the same amount of active ingredient as Jadelle®, was for longer-acting methods, including implants, than introduced in China. This was followed by Implanon®, those for shorter-acting methods.10 No significant which was first introduced in 1998 and was approved by differences are found in contraceptive effectiveness USFDA in 2006. This single-rod contraceptive implant or continuation rates among users of the various (2 mm x 40 mm) contains 68 mg (also contraceptive implants.2,8,9 a progestin).1,2,3,4 A new one-rod implant, Implanon NXT®, has the same design as Implanon® but is also The major side effect associated with the use of radio-opaque, allowing x-ray detection if the rod is contraceptive implants is a change in bleeding patterns difficult to locate due to deep insertion. Implanon NXT® (frequency, duration, and amount). Other potential side also has an improved trocar, the surgical instrument effects include weight gain, headaches, abdominal pain, used to insert the rod.5 acne, dizziness, nausea, breast tenderness, and mood changes. Rarely, infection at the site of the implant can Implants provide long-lasting contraception by occur.7,11 Ovarian cysts may also occur but usually do suppressing , impeding sperm transit by not require treatment.3 thickening the cervical mucus, and altering the endometrial structure.6 The duration of contraceptive In 2012, the United Nations Commission on Life-Saving protection varies by brand: Jadelle® is registered to Commodities for Women and Children endorsed provide contraception for five years, Sino-implant (II)® contraceptive implants as one of its 13 Life-Saving for four years, and Implanon® and Nexplanon® for three Commodities, catalyzing inter-organizational efforts to years. Implant insertion and removal procedures are overcome several commodity-specific barriers currently generally short, uncomplicated, and must be conducted inhibiting women in the developing world from by a well-trained health care provider. After removal, benefiting from the drug. there is no delayed return to fertility for implant users CAUCUS ON NEW AND UNDERUSED REPRODUCTIVE HEALTH TECHNOLOGIES PRODUCT BRIEF at lower prices. becoming more widely available indeveloping countries availability of Sino-implant (II)®mean that implants are reductions of Jadelle® and Implanon® and increasing the contraceptiveacting methods. and more cost effective compared to other shorter- require frequent resupply, implants are more reliable years), are independent of users’ compliance, and donot arethey effective for a number of years (i.e.,three to five resource-constrained settings until recently. Because upfront commodity to access abarrier cost in has been in family planning programs. arethey popular and demand inhigh available when of implants’Because effectiveness and convenience, Current program/sector use by Pharm Access Ltd.; Africa, as Trust Implant® by DKT Ethiopia; as Femplant™ by Marie Stopes International; and as Simplant® by WomanCare Global. *In addition to manufacturer’s the name for product, the Sino-implant product (II)®,the is marketed under avariety of names by different distributors:Zarin® as Registration status/suppliers By 2012,procurement rose to 3.4million region. inthe 132,000 implants were procured insub-Saharan Africa. Health Interchange show that, in2005,approximately years.last several of contraceptive implants have reported over been the worldwide, significant global increases in procurement implants—as apercent of mix—remains method the low limited access to supplies and services. potential future has use) always constrained been by supply. True demand remains (and since uncertain use In past, the demand for implants has often exceeded Implanon NXT® Implanon® Sino-implant (II)®* Jadelle® PRODUCT 14 Data gathered by Reproductive the Merck/MSD Merck/MSD Co., Ltd. Pharmaceuticals Shanghai Dahua OY MANUFACTURER 12 13 However, high the In addition, recent price 12 Although of use sterile insertion device Preloaded, disposable, sterile insertion device Preloaded, disposable, trocar Disposable, sterile trocar Disposable, sterile PRESENTATION 15

the nextfew years replace Implanon®in allcountries in Implanon NXT® will progressively additional countries; Registrations pendingin11 Registered in38countries; countries Review underway in11additional Registered in60 countries; countries Registration pendingin11additional Registered in24 countries; private sector presentation for sales through Also registered insingle-pack additional countries; Registrations pendingineight package) in41 countries; Registered (in1X10standard REGISTRATION access to The and toolkit is quality ofavailable services. practices, andbest resources and tools to help improve and accurate information on training, guidance on toolkit on contraceptive implants provides up-to-date up is available for providers and managers. An online Guidance for effective implant introduction scale- and or community-basedmobile programs. services forespecially women receive who implants through removal, and establishing adequate referral systems— of providers, providing sufficient commodities for This includes ensuringservices. adequatetraining have access to same-day, affordable implant removal groupsdelivery work together to guarantee that women It that critical donors, is policymakers, also and service- or other STIs. and that implantsservices, donot protect against HIV how side effects to expect, to reliably access removal before that so insertion women know what potential of implant provision is ensuring excellent counseling only aminor surgical procedure. An essential element settings, and as insertion their in all removal require Contraceptive implants are for method apractical use increases inprocurements of implants are anticipated. With price new reductions below), additional (see at www.k4health.org/toolkits/implants. 1 No Yes under review prequalification application process(GMP) certified; manufacturing Organization good No; WorldHealth Yes WHO PREQUALIFICATION 16 2 CAUCUS ON NEW AND UNDERUSED REPRODUCTIVE HEALTH TECHNOLOGIES PRODUCT BRIEF partners thatpartners guarantee will funding for 27million units agreement negotiated with acoalition of international Jadelle® from unit US$18to US$8.50per as aresult of an Jadelle®: In January 2013,Bayer OY lowered price the of Public-sector price agreements Merck/MSD. Implanon® and Implanon NXT® are manufactured by Pharmaceuticals Co., Ltd. Sino-implant (II)®is manufactured by Shanghai Dahua Jadelle® is manufactured by Bayer OY. Manufacturer endorsement by theCoalition orits wider membership. For additional information, please contact health sectors. Responsibility for theselectionand contents of theproduct briefs rests solely with theCaucus and does not imply broaden thediscussion within theCoalition of reproductive health technologies that are not well integrated into thepublic orcommercial Technologies, athematic group established under theauspices of theReproductive Health Supplies Coalition. The Caucus’ aimis to This publication forms part of aseries of technical briefs, written by members of theCaucus onNewand Underused Reproductive Health http://www.rhsupplies.org/working-groups/caucus-on-newunderused-rh-technologies.html For more information ontheCaucus onNewand Underused RHTechnologies, please visit our web page at 2. 1. References over next the sixyears. for 13million units of Implanon® and Implanon NXT® international guarantee That partners. will deal funding a result of an agreement negotiated with acoalition of price of Implanon®—this unit to time US$8.50per as unit. pricethat reduction afurther triggered to US$16.50per procurement volumes under IAI the reached thresholds than 100,000live 100to 150per births. In late 2012, income countries with maternal mortality ratios greater of sub-Saharan and other Africa low- and middle- of Implanon® from US$20to US$18/unit countries inall The Coalition. yielded IAI an immediate drop in price Merck/MSD and Reproductive the Health Supplies launched inJune 2011—ajoint initiative between Implanon®: The Implanon® Access Initiative (IAI) was approximately unit. US$8per and nongovernmental organization sectors for Sino-implant (II)®is currently available public inthe agreements are established with distribution partners. Sino-implant (II)®:Public-sector price ceiling than 50countries globally. Initiative, product the is available at price this inmore over next the sixyears. Throughthe new Jadelle® Access 2007;(3):CD001326. TheCochrane Database of Systematic Reviews other implants as effective methods for preventing pregnancy. contraceptives versus other forms of reversible contraceptives or Power J, French Cowan F. R, Subdermal implantable Population Reports Ramchandran D, Upadhyay UD. Implants: next the generation. 18 Finally, inMay 2013,Merck again reduced the . October 2007;7:1–19. . October 19 17 . July 18, 12. 11. 10. 9. 8. 7. 6. 5. 4. 3. 19. 18. 17. 16. 15. 14. 13. Contraceptive implants inKenya: current status and future Hubacher D, Kimani J, Steiner MJ, Solomon M,Ndugga MB. 2003;26(5):303–335. levonorgestrel-releasing contraceptive implants. Sivin I.Risks and benefits, advantages and disadvantages of 2009;80(6):497–499. Grimes DA. Forgettable contraception. 201. randomizedthe controlled trials. levonorgestrel-releasing two-rod implant: systematic of review Steiner M,Grimes D, M,Lopez etal. Sino-implant (II)—a . discontinuation rates, return to fertility, and outcome of Glasier A.Implantable contraceptives for women: effectiveness, Baltimore and and CCP WHO; Geneva: 2011. Family(CCP). Planning: Handbook AGlobal for Providers. ofSchool Public Health/Center for Communication Programs and Research (WHO/RHR) and Johns Hopkins Bloomberg World Health Organization Department of Reproductive Health 27. of progestin implants for women. Croxatto HB. Mechanisms that explain contraceptive the action Family Planning and Reproductive Health Care Mansour D. Nexplanon®: what Implanon® didnext. Jun;37(3):361–368. of Obstetric, Gynecologic, &Neonatal Nursing Fischer MA.Implanon: contraceptive anew implant. and Gynecology Obstetrics Hohmann H,Creinin MD. The contraceptive implant. now-more-affordable-to-the-worlds-poorest-countries.html. rhsupplies.org/nc/news/newsview/article/single-rod-implant- Supplies May Coalition; 20,2013.Available at: http://www. countries [press release]. Reproductive Brussels, Belgium: Health Single-rod implant now more affordable the to world’spoorest initiative-triggers-more-than-15-million-in-savings.html. rhsupplies.org/nc/news/newsview/article/coalition-supported- Supplies November Coalition; 19,2012.Available at: http://www. savings [press release]. Reproductive Brussels, Belgium: Health Coalition-supported initiative more triggers than $15million in Cost-Of-Bayers-Reversible-Contraceptive-Implant. Media-Center/Press-Releases/2013/02/Partnership-Reduces- February 27,2013.Available at: http://www.gatesfoundation.org/ &Melinda Bill Leverkusen, Germany: Gates Foundation; contraceptive implant by more than 50percent [press release]. Partnership reduces cost of Bayer’s long-acting reversible 2012 May;85(5):432–433. provision of contraceptive subdermal implants. Hubacher D, Dorflinger L. Avoiding controversy ininternational Accessedrhi/index.do?locale=en_US. February 2013. RHInterchange website. Available at: http://rhi.rhsupplies.org/ possible inKenya? M, Bratt J. The promise of affordable implants: iscost recovery Tumlinson K,Steiner MJ, KH,Olawo Rademacher A,Solomon & Research Clinical Obstetrics &Gynaecology Mavranezouli I.Health economics of contraception. prospects. Contraception Contraception Contraception [email protected] . 2007;75(6):468–473. . 2007;50(4):907–917. . 2002;65(1):29–37. . 2011;83(1):88–93. Contraception Contraception This brief was last updated July 2013 Contraception . . 2008May– . 2009;23(2):187–98. . 2010;36(4):187. . 2010;81(3)197– Contraception . 2002;65(1):21– Drug Safety Drug . Journal of of Journal Best Practice Practice Best Journal Journal . Clinical Clinical

. . 3