PRODUCT BRIEF Caucus on New and Underused Technologies

Contraceptive Implants

Description for three years. insertion and removal procedures are generally short, uncomplicated, and Introduced almost 30 years ago, contraceptive implants must be conducted by a well-trained health care are one of the most effective methods provider. After removal, there is no delayed return available when used in accordance with approved to fertility for implant users compared to women prescribing information. Implants are thin, flexible rods who do not use contraception,7 as the synthetic that are inserted just under the skin of a woman’s upper continuous-release in implants have a short arm and provide sustained contraception, ranging from half-life. A new implant can be inserted at the time three to five years. of removal if continued contraception is desired. The Population Council developed the first contraceptive Contraceptive implants can be used by almost all implant—Norplant—which was approved in 1983 in women. Implants are best suited for women who desire Finland, the country of manufacture. Norplant consisted a user-independent contraceptive method for birth of six rods (2.4 mm x 34 mm), each containing 36 mg spacing and limiting. Implants should not be inserted of (a synthetic progestin similar to the in women during the first six weeks after if natural female ). Production they are exclusively or partially ; in women of Norplant was discontinued in 2008 because the with serious liver disease, problems with blood clots, new generation of products—the two-rod implants, or unusual vaginal bleeding; or in women who have or Jadelle and Sino-implant (II), and 1-rod implants, have had . Contraceptive implants do not Implanon and Nexplanon/Implanon NXT —are easier provide protection from sexually transmitted infections.7 to insert and remove. Jadelle, which was approved by the USFDA in 1996, consists of two rods (2.5 mm x 43 mm), each containing 75 mg of levonorgestrel. In Efficacy 1996, Sino-implant (II), a similar two-rod implant with Contraceptive implants are one of the most effective the same amount of active ingredient as Jadelle, was contraceptive methods available. introduced in China. This was followed by Implanon, which was first introduced in 1998 and was approved by Annual rates are less than 1 percent with USFDA in 2006. This single-rod all implants.2,8,9 Continuation rates are often better for (2 mm x 40 mm) contains 68 mg (also a longer-acting methods, including implants, than those progestin).1,2,3,4 A new one-rod implant, Nexplanon, has for shorter-acting methods.10 No significant differences the same design as Implanon but is also radio-opaque, are found in contraceptive effectiveness or continuation allowing x-ray detection if the rod is difficult to locate rates among users of the various contraceptive due to deep insertion. Nexplanon also has an improved implants.2,8,9 trocar, the surgical instrument used to insert the rod.5 The major side effect associated with the use of Implants provide long-lasting contraception by contraceptive implants is a change in bleeding patterns suppressing , impeding sperm transit by (frequency, duration, and amount). Other potential side thickening the cervical mucus, and altering the effects include weight gain, headaches, , endometrial structure.6 The duration of contraceptive acne, dizziness, , breast tenderness, and mood protection varies by brand: Jadelle is registered to changes. Rarely, infection at the site of the implant can provide contraception for five years, Sino-implant occur.7,11 Ovarian cysts may also occur, but usually do (II) for four years, and Implanon and Nexplanon not require treatment.3 CAUCUS ON NEW AND UNDERUSED REPRODUCTIVE HEALTH TECHNOLOGIES PRODUCT BRIEF different distributors: as Zarin by Pharm Access Africa, Ltd.; asTRUST by DKT Ethiopia; and as Femplant by Marie Stopes International. *In additionto themanufacturer’s name for theproduct (Sino-implant (II)),theproduct is marketed under a variety of names by over years. last the several contraceptive implants have reported worldwide been meet demand.meet there are not enough supplies available and to services demandthat true for the implants is unknown because waiting lists or another choose This method. suggests supply. In some settings, potential implant users go on mix—remains low worldwide, demand often exceeds Although of use implants—as apercent of method the family planning programs. arethey popular and demand inhigh available when in of implants’Because effectiveness and convenience, Current program/sector use 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 donations rose to more than 2.5million. implants were donated insub-Saharan By 2011, Africa. Interchange show that in2005,approximately 132,000 contraceptive methods. more cost-effective compared to other shorter-acting require frequent resupply, implants are more reliable and years), are independent of users’ compliance, and donot are effective for a number of years (i.e.,three to five in resource-constrained settings. Still, they because commodity to cost access, abarrier canespecially be Nexplanon Implanon Sino-implant (II)* Jadelle Product Registration status/suppliers 12 Significant increases in procurement of 13 Merck/MSD Merck/MSD Pharmaceuticals Co., Ltd. Shanghai Dahua HealthCare Manufacturer 14 12 Data gathered by RH the However, upfront high the 15

insertion deviceinsertion disposable, sterile Preloaded, deviceinsertion disposable, sterile Preloaded, trocar Disposable, sterile trocar Disposable, sterile Presentation Merck/MSD. Implanon and Nexplanon are manufactured by Pharmaceuticals Co., Ltd. Sino-implant (II)is manufactured by Shanghai Dahua Jadelle is manufactured by Bayer HealthCare. Manufacturers toolkits/implants. access to www.k4health.org/ and quality of 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-based programs.services for women receive who implants through mobile and establishing adequate referral systems—especially providers, providing sufficient commodities for removal, This includes ensuringservices. adequatetraining of 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 few years. countries inthenext Implanon inall progressively replace Implanon NXTwill countries. Nexplanon/ Registered in21 countries. approximately 80 Registered in countries. in ten additional Review underway countries. Registered in19 countries. in ten additional Review underway than 47countries. Registered inmore Registration 1 No Yes No Yes WHO Prequalification 16 CAUCUS ON NEW AND UNDERUSED REPRODUCTIVE HEALTH TECHNOLOGIES PRODUCT BRIEF or its wider membership. For additional information, please contact [email protected]. Responsibility for theselectionand contents of the product briefs rests solely with theCaucus and does not imply endorsement by theCoalition the discussion within theCoalition of reproductive health technologies that are not well-integrated into the public orcommercial health sectors. Technologies, athematic group established under theauspices of theReproductive Health Technologies Coalition. The Caucus’ aimis to broaden This publication forms partof aseries of technical briefs, written by members of the Caucus 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 [email protected]. membership. For additional information, contact please not imply endorsement by or Coalition the its wider briefstechnical rests solely with Caucus the and does Responsibility for and selection the contents of the integrated into public the or commercial sectors. of reproductive technologies health that are not well- aim is to broaden discussion the within Coalition the Reproductive Health SuppliesCaucus’ The Coalition. thematic group established under auspices the of the and Underused Reproductive Health Technologies, a briefs, written by members of Caucus the on New This publication forms part series of of a technical Guarantee for Health. financing mechanisms inconjunctionwiththe Pledge to enhance access through improved affordability and Access Initiative was launched inJune 2011,and aims Health, USAID, UNFPA, and NGOs. The Implanon made through contracts with individual Ministries of Implanon: Public-sector price agreements have been approximately US$8/unit. is currently available public inthe and NGO sectors at established with distribution Sino-implant partners. (II) Sino-implant (II):Public-sector price agreements are developing countries. Pharma lowered price the of Jadelle to US$18/unit in (NGOs) offering family planning. BayerIn 2012, Fund (UNFPA), and nongovernmental organizations Development United (USAID),the Nations Population organizations such as USAgency the for International Jadelle: Public-sector price agreements are inplace with Public-sector price agreements 2. 1. References

No.:CD001326. DOI:10.1002/14651858.CD001326.pub2. DatabaseCochrane of Systematic 2007,Issue Reviews 3.Art. 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 K:Injectables Series and Reports. Implants 2007;7:1–19. Ramchandran D, Upadhyay UD. Implants: The Generation.Next 12. 11. 10. 9. 8. 7. 6. 5. 4. 3. 16. 15. 14. 13.

prospects. Contraception 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. Safety Drug Sivin I.Risks and benefits, advantages and disadvantages of 2009;80(6):497–499. Grimes DA. Forgettable contraception. Contraception. 201. randomizedthe controlled Contraception trials. levonorgestrel-releasing two-rod implant: systematic of review Steiner M,Grimes D, M,Lopez etal. Sino-implant (II)—a . Contraception discontinuation rates, return to fertility, and outcome of Glasier A.Implantable contraceptives for women: effectiveness, Providers. Baltimore and and CCP WHO, Geneva: 2007. INFOProject.(CCP), Family Planning: Handbook AGlobal for ofSchool Public Health/Center for Communication Programs and Research (WHO/RHR) and Johns Hopkins Bloomberg World Health Organization Department of Reproductive Health of progestin implants for women. Contraception Croxatto HB. Mechanisms that explain contraceptive the action Family Planning and Reproductive Health Care Mansour D. Nexplanon®: what Implanon® of didnext. Journal Neonatal NursGynecol Fischer MA.Implanon: contraceptive anew implant. Obstet J and Gynecology Obstetrics Hohmann H,Creinin MD.Contraceptive The Implant. Clinical 2012—in press. provision of contraceptive subdermal implants. Contraception Hubacher D, Dorflinger L. Avoiding controversy ininternational rhi/index.do?locale=en_US RHInterchange. Accessed January 2012.http://rhi.rhsupplies.org/ possible inKenya? Contraception M, Bratt J. The promise of affordable implants: iscost recovery Tumlinson K,Steiner MJ, KH,Olawo Rademacher A,Solomon Gynaecol Obstet Clin Res Mavranezouli I.Health economics of contraception. Best Pract . 2008May–Jun;37(3):361–368. . 2009;23(2):187–98. . 2007;75(6):468–473. . 2007;50(4):907–917. . 2002;65(1):29–37. . 2011;83(1):88–93. This brief was last updated March 2012. . 2010;36(4):187. . 2002;65(1):21–27. . 2010;81(3)197–

. . PRODUCT BRIEF Caucus on New and Underused Reproductive Health Technologies

CycleBeads®

Description Current program/sector use

CycleBeads® are a color-coded string of beads that help To date, the Standard Days Method® and CycleBeads® a woman use the Standard Days Method®, a clinically have been used in more than 50 countries and have tested natural method of family planning that enables been successfully integrated into many existing women to manage their own fertility. CycleBeads® are family planning programs and community networks, appropriate for women with menstrual cycles 26 to 32 resulting in more than two million users worldwide.5 days long. Using CycleBeads®, a woman can track her The Standard Days Method® does not require special , identify the days when unprotected equipment, medical procedures, facilities, or costly intercourse is likely to result in pregnancy, and monitor commodities, and as a knowledge-based method, it is her cycle length. She either uses a barrier method or easy to teach and learn. Thus, it can be offered through a abstains on her potentially fertile days—identified as wide variety of programs and by a range of providers— days 8–19 of the menstrual cycle—to avoid pregnancy. including physicians, nurses, auxiliary nurses, community volunteers, public- and private-sector A woman can use CycleBeads® by placing the rubber reproductive health programs, faith-based organizations, ring on the RED bead on the first day of her period. and social marketing programs through pharmacies She moves the ring one bead each day. She abstains or and other retailers—without significant additional uses a when the ring is on any WHITE bead resources. This method also addresses the needs of if she does not want to become pregnant. She can have diverse populations with varied religious and ethical unprotected sex when the ring is on any BROWN bead, beliefs, educational backgrounds, and socioeconomic as she is not likely to get pregnant on those days. She status. It has no side effects and can be used by women needs to move the ring to the RED bead again when her who want a pregnancy, as well as by those who do not. next period starts, skipping over any remaining beads. Programs in several countries have found that including the Standard Days Method® and CycleBeads® among Efficacy the options they offer contributes to contraceptive prevalence, enhances the method mix, and brings first- Research has shown that the Standard Days Method® time users to family planning.3 Given the scientific and is more than 95 percent effective with correct use programmatic evidence, the Standard Days Method® ( or abstinence during days 8–19 of the and CycleBeads® are included in numerous documents menstrual cycle), and more than 88 percent effective in of the World Health Organization, the US Agency for typical use,1 similar to a number of other user-directed International Development (USAID), International methods.2 Similar levels of efficacy have been found Federation, and Contraceptive when the method is offered in regular service delivery.3 Technology.6,7,8,9 Further, studies of women who purchased CycleBeads® The primary impediment to expanded availability in the context of social marketing—and thus relied on and use of this method is ensuring sufficient supply of the CycleBeads® instructional insert and point-of-sale CycleBeads®. Because the Standard Days Method® is a materials for method use—showed that their ability to relatively new method, governments and implementing understand and use the method correctly was equal to partners often do not have data about current use on that of women who received instruction from a trained which to forecast future demand and base estimations provider.4 The Standard Days Method® provides 1.5 for CycleBeads® procurement. However, a toolkit couple-years of protection (CYPs). is available to aid countries interested in procuring CAUCUS ON NEW AND UNDERUSED REPRODUCTIVE HEALTH TECHNOLOGIES PRODUCT BRIEF or its wider membership. For additional information, please contact [email protected]. Responsibility for theselectionand contents of the product briefs rests solely with theCaucus and does not imply endorsement by theCoalition the discussion within theCoalition of reproductive health technologies that are not well-integrated into the public orcommercial health sectors. Technologies, athematic group established under theauspices of theReproductive Health Technologies Coalition. The Caucus’ aimis to broaden This publication forms partof aseries of technical briefs, written by members of the Caucus 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 Technologies, www.cyclebeads.com). directly (see CycleBeads® should contact manufacturer, the Cycle Non-USAID-funded groups interested inpurchasing should forwarded be to CSL the backstop. country Acquisition and Assistance Request Document. Orders project CCP the either as field support or as a Modified funding requests for procurement of CycleBeads® to other contraceptive Missions methods. can provide and ordered can be by USAIDprograms alongside and (CSL) Logistics DivisionSecurity at USAID, Procurement Project (CCP) of Commodities the mixavailablemethod through Contraceptive Central the CycleBeads® are now offered part as the contraceptiveof Public-sector price agreements social-marketing programs. organizations, faith-based organizations, and public 2003 and are now offeredthrough nongovernmental CycleBeads®. CycleBeads® have available been since Cycle Technologies manufacturer is licensed the of Manufacturer/supplier program managers, donors, researchers, and advocates. commodity management, analysis, and planning for RHInterchange, supports which pipeline monitoring, Reproductivethe Health Supplies Coalition’s online procurement by and country donor found can be on Additionally, up-to-date data on CycleBeads® product anthem ideal for low-resource settings. and are to environmental impervious conditions make storageno special facilities, have an indefinite shelf life, com and www.irh.org.that The fact CycleBeads® require edu. For additional information, www.cyclebeads. see com); individuals may contact also irhinfo@georgetown. USAID |DELIVER PROJECT (email: askdeliver@jsi. country.in their It is available electronically from the estimating supply initial the of CycleBeads® needed CycleBeads® by providing astep-by-step process for 8. 7. 6. 5. 4. 3. 2. 1. References 9.

C16571DD72F5/0/medservdelivery04.pdf. C16571DD72F5/0/medservdelivery04.pdf. http://www.ippf.org/NR/rdonlyres/DD4055C9-8125-474A-9EC9- Reproductive 3rd Ed. 2004.Available Health Services at: Guidelines Delivery and forIPPF Medical Sexual and Service SDM%20Technical%20Brief%202004.pdf 2004. Available at: http://irh.org/sites/default/files/USAID%20 Effective Natural USAID Global Method. Health Technical Briefs Jennings V, Lundgren Standard R. Days Method: ASimple reproductive-health/publications/mec/fab.html. World Health Organization, 2004.Available at: www.who.int/ Medical Eligibility Criteria for Contraceptive Use 3rd Ed. Geneva: and distributer of CycleBeads®. Data provided by Cycle Technologies, manufacturer licensed the Method. Article pending publication Marketingfor Social aKnowledge-Based Family Planning Kavle J, Foreit J, M,Lundgren Eber Jennings R, V. The Potential Standard Days Method®. Contraception about Contraceptive Introduction: the Experience Theof Gribble J, Lundgren Velasquez R, Strategic C,Anastasi E.Being Contraception algorithm of time cycle. menstrual to fertile the the identify Sinai I,Jennings V, Arevalo M.Thetwo-day algorithm: A new 2002;65(5):333–338. family planning: Standard the Days Method. Contraception Arevalo M,Jennings V, Sinainew ofamethod of I.Efficacy New York: Ardent Media Inc., 2007:343–349. F, Kowal D, Contraceptive eds. Technology Edition. Revised 19th Methods. In: Hatcher Trussell RA, J, Nelson AL,Cates W, Stewart Jennings V, Arevalo M.Chapter 15:-Based . 1999;60(2):65–70. This brief was last updated 2012. January , 2011. . 2008;77(3):147–154.

. PRODUCT BRIEF Caucus on New and Underused Reproductive Health Technologies

Diaphragm

The diaphragm is a barrier device that covers the Efficacy and part of the vaginal wall, preventing pregnancy by blocking sperm from entering the uterus. Traditionally, Contraceptive effectiveness depends on correct and diaphragms were made of latex, but now most are made consistent use. The diaphragm used with is of silicone. Diaphragms are made in different sizes 84–94 percent effective in preventing pregnancy during (generally four to seven sizes depending on the brand), the first year of use.4 Due to concern about its effect on and a woman must be fitted for the correct size by a the vaginal epithelium, use of spermicide containing clinician. Diaphragms are durable and reusable, making Nonoxynol-9 (N-9) is not recommended for women at them a low-cost contraceptive method. high risk of HIV infection or women who participate in multiple sex acts on a daily basis.5 Several prospective The diaphragm is held in place by a flexible rim. To use studies that looked at the efficacy of diaphragms without it, a woman inserts the diaphragm with contraceptive spermicide suggest that spermicide improves efficacy, gel before intercourse and leaves it in place for six hours but to a modest degree.6,7,8 While these prospective afterwards. The diaphragm can be inserted before sex, studies provide evidence that a cervical barrier without but should not be kept in place for more than 24 hours has contraceptive efficacy not dramatically without removing it to wash. Research evaluating different than that of cervical barriers plus spermicides, the safety and acceptability of continuous use of the definitive information on contraceptive efficacy without diaphragm (still removing once a day for cleaning) spermicides is not available. is ongoing.1,2 Clinical guidelines recommend adding additional contraceptive gel before further acts of intercourse. In addition, women who use the diaphragm Current program/sector use must be able to wash and store the device.3 Since it is worn internally, diaphragms offer more Challenges discreet protection than other barrier methods such as There are a number of obstacles to expanded use of female or male condoms. As a female-initiated method, traditional-sized diaphragms. One is the requirement for the diaphragm provides contraceptive protection a clinician fitting; another is the complexity of supplying without requiring male partner involvement. Although product in multiple sizes. A reanalysis of fitting data some men report not being aware of the diaphragm from previous barrier-method clinical trials suggests during sex, women may choose to discuss this method that many women could be correctly fitted with a one- with their partner depending on the communication size diaphragm.9 There are currently two single-sized and expectations in their relationship. Diaphragms are products under evaluation; at least one is expected to be appropriate for women who cannot or choose not to use available in some markets in 2012. hormonal or other long-term contraceptive methods, and for women who want protection only around the Effective use also is dependent upon a continued supply time they have sex. Diaphragms are also an appropriate of contraceptive gel. Given concern about increased back-up method in case a woman has missed taking oral risk of HIV, many family planning programs in contraceptive pills or her other method is out-of-stock regions with HIV prevalence have stopped supplying at the family planning clinic. There are no age or parity products containing N-9. Efforts are under way to restrictions on use, and a woman can use a diaphragm identify contraceptive gel alternatives that do not use throughout her reproductive life (although the size may N-9. Even when an alternative gel is identified and need to be checked). Return to fertility is immediate validated, supply and cost issues will remain, which after use. Diaphragms are best suited for a woman who is why reproductive health researchers are interested finds using a method near or at the time of intercourse in evaluating the efficacy and acceptability of the acceptable, can learn the insertion technique, and feels diaphragm without contraceptive gel. she has sufficient privacy for insertion and removal. CAUCUS ON NEW AND UNDERUSED REPRODUCTIVE HEALTH TECHNOLOGIES PRODUCT BRIEF and Madagascar who havewho no previous with method. the experience that diaphragms are well-accepted evenamong women Dominican Republic, and United the States—have found Britain. to 95mm).Reflexions is manufactured and marketed in more delicate. It is available innine sizes(from 55mm thata rim is similar to coil the spring but and thinner TheReflexions Flat diaphragm rubber Spring® isa with Spring® Flat Diaphragm Reflexions Commerce Ltd. The product is marketed in Brazil. 85 mm)and is manufactured by Industries Semina and with avisible coil spring. It comes insixsizes(60mmto Semina DiaphragmThe is a clear, silicone diaphragm Diaphragm Semina mm) and are made of silicone. are styles Both availableEast. ineight sizes(60mmto 95 Unitedthe States, Canada,Europe, Asia, and Middle the manufactured Surgical by and Cooper are distributed in Milex Wide-Seal® Arcing and Omniflexdiaphragms are Milex in four sizes(65mmto 80mm). Diaphragm is now made from silicone and is available and aflexiblewithrim an arcing spring. The ALL-FLEX® The ALL-FLEX® is adiaphragmwith a shallow dome Diaphragm ALL-FLEX® ORTHO Manufacturers/suppliers research and information (www.cbas.org). for as (CBAS) aportal diaphragmSociety serves my.ibpinitiative.org/. Barrier AdvancementCervical The Knowledge Gateway for Reproductive Health at http:// Methods” Barrier “Cervical the community at the programs worldwide by accessed can joining be A June 2008online discussion about diaphragm house.in the have access to private bathrooms or water running diaphragmsuse donot they successfully evenwhen One report from India emphasized that women can successfully by women inlow-resource settings. 13 countries have found diaphragms used can be planning. studies past clinical the decade, Over in acceptable andvery of as successful amethod family support from find diaphragms they partners, their When women receive information from providers and Opportunities discontinued inCanada. FLEX® is available globally, though as of 2008it has been market indiaphragm leader and sales distribution. ALL- Ortho-McNeil-Janssen Pharmaceuticals, Inc., world the ™ Wide-Seal Diaphragm Wide-Seal 10 Other studies Other inZimbabwe, Kenya, 11 —as well as Thailand,South Africa, 16 15 It is manufactured by 17 12,13,14 6. 5. 4. 3. 2. 1. References None. Public-sector price agreements 17. 16. 15. 14. 13. 12. 11. 10. 9. 8. 7.

spermicidal fit-free diaphragm.spermicidal Contraception Smith C,Farr G,Feldblum PJ, Spence A.Effectiveness the of non- http://whqlibdoc.who.int/hq/2003/WHO_RHR_03.08.pdf. Nonoxynol-9: Summary WHO. Report. Geneva: Available at: WHO. Technical (2002).WHO/CONRAD Consultation on table.html. Media, 2007.Available at: www.contraceptivetechnology.com/ Technology: Nineteenth Edition Revised . New York, NY: Ardent J, Nelson AL,Cates W, Stewart FH,Kowal D. Contraceptive Trussell J. Contraceptive efficacy. In Hatcher RA, Trussell htm. Accessed August 1,2008. website. Available at: www.rho.org/html/cont-female_barriers. Female Methods Barrier page. Reproductive Health Outlook Prevention diaphragmthe with candidate microbicide. AIDSEducation and continuous as astrategy for use achievingof adherence inatrial Penman-Aguilar A,Swezey T, Turner AN,etal. Promoting Madagascar. Sexually Transmitted Infections. 2005;81:472–476. feasibility of continuous diaphragm among use workers sex in F,Behets Turner A,Van Damme K,etal. Acceptability and Accessed January 31,2012. Contraceptive_Diaphragms/Reflexions_Flat_Spring_Diaphragm. Available at: http://www.wms.co.uk/Family_Planning/ Williams Medical. Reflexions Flat Spring Diaphragm webpage. Accessed January 31,2012. Milex%20Wide%20Seal%20Diaphragms%20Literature.pdf. Available at: http://www.coopersurgical.com/Documents/ Surgical. Milex™ Wide-SealCooper Diaphragms factsheet. information/diaphragms.cfm. Accessed January 31,2012. website. Available at: http://www.cervicalbarriers.org/ Diaphragms Advancement Barrier webpage. Cervical Society 237–244. single-size contraceptive Contraception device. Schwartz J, etal. SILCS diaphragm: postcoital testing of anew and Reproductive Health Care couples and inSouthThailand. Africa Journal of Family Planning Short-term acceptability of asingle-size diaphragm among PS, Coffey BeksinskaKilbourne-Brook M, M,Thongkrajai E. Contraception diaphragms among couples Dominican inthe Republic. Comparative acceptability of SILCS the and ALL-FLEX® Ortho PS, Coffey Kilbourne-Brook M, Brache Cochón L. V, January 6,2011. cervicalbarriers.org/information/recentResearch.cfm. Accessed Advancement Barrier website.Cervical Society Available at: www. publications/detail.php?i=693. Outlook PATH. Devices. Barrier Re-examining Role the of Cervical 2004;24(4):263–266. Is trials: clinical clinician fitting Contraception necessary? Mauck JJ, C,Lai Schwartz J, Weiner DH. Diaphragms in with and without Contraception spermicide. safety andnew barrier contraceptive ofavaginal efficacy used Mauck C,Glover E,etal. Lea’s LH,Miller Shield®: Astudy of the Medicine randomized, comparative Journaltrial. efficacy of Reproductive W,Bounds etal. The diaphragmwith andwithout A spermicide. . 2003;20(2).Available at: http://www.path.org/ . 1995;40:764–774. . 2009;21(6):512–525. . 2008;78(5):418–423. . 2008;34(4):233–236. . 1996;53(6):319–335. . 1995;51:289–291. . 2008;78(3): . CAUCUS ON NEW AND UNDERUSED REPRODUCTIVE HEALTH TECHNOLOGIES PRODUCT BRIEF or its wider membership. For additional information, please contact [email protected]. Responsibility for theselectionand contents of the product briefs rests solely with theCaucus and does not imply endorsement by theCoalition the discussion within theCoalition of reproductive health technologies that are not well-integrated into the public orcommercial health sectors. Technologies, athematic group established under theauspices of theReproductive Health Technologies Coalition. The Caucus’ aimis to broaden This publication forms partof aseries of technical briefs, written by members of the Caucus 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 This brief was last updated 2012. January

PRODUCT BRIEF Caucus on New and Underused Reproductive Health Technologies

Emergency contraceptive pills

Emergency oral contraceptive pills are a post-coital Efficacy contraceptive option, allowing women to prevent pregnancy after intercourse has occurred. Low Depending on the formulation used and timing of use, contraceptive-prevalence rates along with high levels ECPs can reduce a woman’s risk of becoming pregnant of unmet need for family planning in many developing from a single act of intercourse between 75 and 89 countries indicate a high frequency of unprotected percent. sexual relationships. As a result, many couples are at risk for an unplanned and/or unwanted pregnancy. (EC) is effective in preventing Current program/sector use a substantial proportion of pregnancies when it is ECPs are registered and available commercially in a used promptly after unprotected intercourse. It is an number of countries. They are regulated as an over-the- especially important option in cases of sexual coercion counter or non-prescription product in many developed or . and developing countries. Still, many women are not The most commonly available regimen is 1.5 mg aware of EC, and the pills often are not included in levonorgestrel in a single dose, packaged either as a public-sector programs. single pill or as two pills of 0.75 mg each. Although the ECPs can be provided by or pharmacy two-pill products usually include instructions to take personnel with minimal or no training. Women can self- one pill up to 72 hours after unprotected intercourse and diagnose the need for use and can administer the pills the second one 12 hours later, they can both be taken without supervision. ECPs can safely be provided over together without increasing side effects; this minimizes the counter and in a number of countries are regulated the chance of the second dose being missed.1 This for over-the-counter dispensing. They do not require product is on WHO’s Model List of Essential Medicines2 high training or start-up investments when being and is included in many countries’ national medicines added to family planning or social marketing programs. lists or formularies. However, programs may wish to work to raise women’s More recently, a regimen containing 30 mg of the awareness of this contraceptive option. compound has been made available and can also be taken up to 120 hours after unprotected intercourse.3 As of January 2012, this regimen is not Manufacturers/suppliers available in developing countries. There are many manufacturers of ECPs. The Emergency contraceptive pills (ECPs) work mainly by International Consortium for Emergency Contraception either preventing or delaying ovulation; this is likely lists manufacturers in its products database: http://www. the only mechanism of action, although there is some cecinfo.org/database/pill/pillData.php. evidence showing that they may prevent the sperm and Some (but not all) of these products are of assured egg from meeting by altering the cervical mucus.4 ECPs quality, either because they have been approved by a are more effective the sooner they are taken. Regular stringent regulatory authority* such as the US Food oral contraceptives taken in specific doses also can serve and Drug Administration or the European Medicines as EC. For a list of regular oral contraceptives that can Agency, prequalified by WHO, or undergone rigorous be used for EC purposes, visit: http://ec.princeton.edu/ quality evaluations as part of a procurement process. worldwide/default.asp#country.

* See www.theglobalfund.org/documents/psm/PSM_CountriesSRA_List_en/ for more information on stringent regulatory authorities. CAUCUS ON NEW AND UNDERUSED REPRODUCTIVE HEALTH TECHNOLOGIES PRODUCT BRIEF or its wider membership. For additional information, please contact [email protected]. Responsibility for theselectionand contents of the product briefs rests solely with theCaucus and does not imply endorsement by theCoalition the discussion within theCoalition of reproductive health technologies that are not well-integrated into the public orcommercial health sectors. Technologies, athematic group established under theauspices of theReproductive Health Technologies Coalition. The Caucus’ aimis to broaden This publication forms partof aseries of technical briefs, written by members of the Caucus 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 NGOs wishing to purchase products. their provide adiscounted price to public-sector agencies or and distributors have demonstrated to awillingness agencies) at apreferential price. manufacturers Other productthe available to public the (government sector Richter,Gedeon manufacturer the of Postinor-2, makes Public-sector price agreements htm. Contraception site at www.cecinfo.org/database/index. go to International the Consortium for Emergency 140 countries. For alist of registrations, country please Dedicated ECPformulations are registered inmore than status Registration 4. 3. 2. 1. References

MOA_ENG_2011.pdf. Accesssed January 4,2012. Available at: http://www.cecinfo.org/publications/PDFs/policy/ Contraceptive Pills (LNG ECPs) Prevent Pregnancy? March 2011. Mechanism of Action: How doLevonorgestrel-alone Emergency International Consortium for Emergency Contraception. International Federation of and Obstetrics Gynecology EllaOne Products for Human Use (CHMP).CHMPAssessment Report for European Medicines Agency (EMEA)/Committee for Medicinal index.html. Available at: http://www.who.int/selection_medicines/list/en/ WHO Model List of Medicines Essential list 17th (March 2011). PDFs/policy/Dosage_Timing_English.pdf. ICEC; 2003.Available at: http://www.cecinfo.org/publications/ (ICEC). Policy Statement: Regimen Update . Washington, DC: The InternationalConsortium forContraception Emergency . Doc.Ref.: EMEA/261787/2009.London:. Doc.Ref.: EMEA;2009. This brief was last updated 2012. January

PRODUCT BRIEF Caucus on New and Underused Reproductive Health Technologies

Female condom

Description with silicone, but can also be used with water-based lubricants. Oil-based lubricants cannot be used with The is a condom made of a soft, thin natural rubber latex condoms. The Phoenurse® female material that fits inside a woman’s vagina. Like the condom is made of polyurethane; comes pre-lubricated male condom, the female condom is a barrier method, with a silicone-based lubricant; and is packaged with an keeping the penis and sperm from contact with the insertion tool, sanitary towel, and disposable bag. The cervix and vagina. But unlike the male condom, it also Woman’s Condom is made of thin polyurethane film and covers parts of the external female genitalia. The female is packaged un-lubricated. Each Woman’s Condom is condom offers protection against both unintended supplied with a separate sachet of water-based lubricant pregnancy and sexually transmitted infections (STIs), to be applied at point of use.† including HIV. Current models on the market have a flexible ring, Efficacy sponge, or capsule containing foam shapes at the closed end of the condom, enabling insertion of the device and Data from the 2007 World Health Organization family helping to keep the condom in place during sex. A ring planning handbook indicates that about 21 pregnancies or frame at the open end of the condom stays outside occur per 100 women using female condoms over the the vagina, lying flat across the genital area and ensuring first year. When female condoms are used correctly that the condom stays in place, as well as protecting with every act of sex, about five pregnancies occur per from external STIs. The female condom can be inserted 100 women over the first year.1 The effectiveness studies into the vagina prior to , is not these data are based upon were undertaken with the dependent on a male erection, and can remain in place FC1® female condom (no longer on the market), and after ejaculation. It has no known side effects or risks while one cannot extrapolate this data to all female and can be used by women of all ages.* condoms, they do provide basis for discussion. The World Health Organization and the US Food and The first-generation female condom (FC1®), Drug Administration have determined that the FC2® is manufactured by the Female Health Company (FHC), equivalent to the FC1®. Estimates on the contraceptive was made from polyurethane—a thin, odorless material efficacy of the FC1® are within the range of other that is hypoallergenic, stronger than natural rubber barrier protective methods (e.g., male condoms). FC1® latex, and conducts heat. The FC1® was launched on the maintains lower failure rates than either the market in 1992, but is no longer manufactured and has or diaphragm. been replaced by a second-generation product, the FC2®. The FC2® is made of nitrile rubber—a synthetic type In vitro studies of the FC1® confirm that the product of latex—and can be used with any type of lubricant, provides an effective barrier against many common including oil-, silicone-, or water-based products. STIs, including HIV. Calculations based on correct and consistent use estimate a 97.1 percent reduction in the In addition to the FC2®, there are four other female risk of HIV infection for each act of intercourse.2 condom models on the market: the VA w.o.w®, Cupid™, Phoenurse®, and the Woman’s Condom. The Research conducted on the FC1® in Brazil, India, VA w.o.w.® and the Cupid™ female condoms are both Thailand, the , and Zambia indicates an made of natural rubber latex and come pre-lubricated increase of protected sexual acts and decrease in STI

* Women who are allergic to latex are recommended to not use latex female † See table below for additional information on currently available brands of condoms. female condoms. CAUCUS ON NEW AND UNDERUSED REPRODUCTIVE HEALTH TECHNOLOGIES PRODUCT BRIEF male andmale female condoms were available. prevalence from decreased 52to 40percent both when increased from acts 57to 88percent,sexual and STI 37 to 93 percent. from 40 countries show acceptability rates ranging from of HIVprevention that are safe and effective. Studies Female condoms are only the female-initiated methods condoms. prevalence FC1®is when available alongside male a Included below are five the condomfemale productsthat are the on market:

VA w.o.w. Health Company. Manufactured by theFemale lubricated. Nitrile (synthetic latex), pre- Care, and many others). such as Femidon, Protectiv, (also known under brand names FC2 Product Company, China. Dahua Medical Apparatus Manufacturedby Shanghai lubricant. packaged with water-based Condom is un-lubricated and polyvinyl alcohol. capsuleinsertion made of of polyurethane; dissolving ring, and foam shapes made the China market). Pouch, (also known as O’lavie Woman’s Condom Tianjin, China. Polyurethane Tech. Co. Ltd, Condombao Medical Manufacturedby Tianjin Polyurethane, pre-lubricated. Phoenurse® female condom Manufactured by Cupid. lubricated. Natural rubber latex, pre- Cupid™ Condom Products Ltd. Manufactured by Medtech lubricated. natural rubber latex, pre- Polyurethane sponge and V’Amour, L’amour). (also known as: Reddy, procurement conditions, including volume and contractual stipulations. Pricing information inthis table is based onthemost accurate information and/orestimates available. Prices may fluctuate dependingon various ® female condom 3,4,5,6,7 ® female condom In apilot study from Thailand, protected 9 ™ for USFDA approved, 2009. WHO prequalified,2007. CE marking. Regulatory status/availability approval. effectiveness study needed for USFDA Undergoing contraceptive prequalification. Under WHO review for Administration approval. Shanghai Food and Drug CE marking. prequalification. Under WHO review for agency (ANVISA). Registered within Brazilian regulatory approval. Tianjin Food and DrugAdministration prequalification. Under WHO review for agency (ANVISA). Registered within Brazilian regulatory CE marking. prequalification. Under WHO review for completed. USFDA Phase 1clinical trials agency (ANVISA). Registered with Brazilian regulatory India DrugControl Authority approval. CE marking. 8 units in2005to 50 million in2010. in developing countries, has increased from 14million countries. Availability of female condoms, particularly programssector are inmore underway than 90 have distributed been in120countries, and public- Since 1993,approximately 300million female condoms Current program/sector use on data Reproductive inthe Health Interchange, female Retail: US$2.00. discounts may apply. US$0.57/unit; volume General price estimates approximately US$2.35. Retail inChina: discounts may apply. US$0.87/unit, volume US$1.80-2.80. Retail: approximately million units. US$0.59/unit at 1 Retail: US $0.65. million units. US$0.35/unit at 1 Retail: US$1.00 million units. US $0.23/unit at 35 a countries. or distributed in120 Registered and/ Distribution distribution inChina. Limited private-sector Africa and Brazil. opportunitiesin South Currently seeking China. Limited distribution in from 2012onwards. large scale inMozambique Will be distributed at a and Mozambique. Africa,Netherlands, South Brazil, Indonesia, the scale distribution in India, plus small- United Kingdom. Swaziland, and the South Africa, Indonesia, Portugal, Germany, India, Argentina, Brazil, 10 However, based CAUCUS ON NEW AND UNDERUSED REPRODUCTIVE HEALTH TECHNOLOGIES PRODUCT BRIEF were commercially sold 2003and between 2007. approximately five million VA w.o.w.® condomsfemale planning, and HIVprevention programs. In addition, strong, comprehensive reproductive family health, work with stakeholders on apro-bono basis to build team consisting of professional program advisors that Female Health Company public-sector funds aglobal (UNFPA), and governmental The ministries. health Development, United the Nations Population Fund organizations such as USAgency the for International The FC2® is purchased for public-sector programs by condomglobal procurement. condoms only account for approximately 0.19percent of ‡ addition, VA the w.o.w.® and Cupid™ the condoms have and Woman’s CEmarking. In Condom carry all The VA w.o.w.® condom,female Cupid™ condom, and Administration Drug (USFDA). In March 2009,FC2®received approval by USFood the eligible for procurement by United Nations agencies. Committee on female condoms in2006,making it World Health Organization’s (WHO) Technical Review The FC2®completedevaluationthe process the of status Registration markets, and Woman’s the sells Condom. Apparatus Company of Shanghai, manufactures, China, Phoenurse® female condom, Dahua Medical while Tianjin, manufactures, China, markets, and the sells Condombao Medical Polyurethane Tech. Co. Ltd. of markets and Cupid™ the sells condom. Tianjin condom. Cupid Ltd., of also India, manufactures, manufactures, markets, and VA the sells w.o.w.® female and FC2®.Medtech the sells Products Ltd. of India The Female Company Health manufactures, markets, Manufacturer sector distributionsector channels. availablebeen since September 2011inlimited private- Condom, branded O’lavie ™ for market, China the has Brazilianthe and markets. South African The Woman’s and manufacturers are currently working on entering 2009. Phoenurse® has limited distribution inChina products. Phoenurse® entered market Chinese the in The Phoenurse® theand Woman’sCondom are newer Mozambique. Brazil, Indonesia, Netherlands, the and South Africa The Cupid condom has limited distribution in India, health, andhealth, environmental requirements. product has met European Union consumer safety, condom hasthat CEmarking, also certifies which a request. conformity. The document hasbe made to available to authorities on upset file, atechnical a and sign EuropeanCommunity declaration of CEmarking:can the bear must they complete aconformity assessment, manufacturers dohave obligatory to certain take steps before product the productthe European meets Economic Area regulations. However, the The manufacturer of a product affixes theCE marking to it, assuring 11 13 The FC2® female ‡ 12

determine suitability their for public-sector purchase. WHO/UNFPAthe Technical Committee to Review female condom designs, are currently by under review latter four female condoms, along with sixother Administration and inChina from ANVISA. received approval from Tianjin the Food and Drug female condom not does have CEmarking, but it has and Administration Drug The inChina. Phoenurse® Woman’s Condom has approval from Shanghai the Food Brazilianthe regulatory the agency (ANVISA),while approval from India the Control Drug Authority and date of publication. this have notto sold public-sector been purchasers as of the Phoenurse®, and Woman’s Condom female condoms Swaziland, and SouthIndonesia. Africa, The Cupid™, public-sector programs inBrazil, Finland, Portugal, although it supplied has been quantities insmall to VA w.o.w.® female condom is not currently available, organizations. Public-sector pricing information on the bilateral donors, governments, and nongovernmental and lower cost the of female condoms for UNagencies, toFC2® was designed replace FC1®female the condom Public-sector price agreements § 8. 7. 6. 5. 4. 3. 2. 1. References

and regulatory agencies inmany other countries.table above. See The FC2® also hasalso The FC2® approval the of Brazilian regulatory (ANVISA) agency Journal of STD &AIDS.2007;18:461–466. following introduction of workers. female the sex International transmittedin sexually infection prevalence and condom use Hoke TH,Feldblum PJ, Van Damme K,etal. Temporal trends Transmitted Diseases.1998;25(5):260–264. Zambia. infection in virus immunodeficiency Sexually of female the condom among couples at risk of high human Musaba E,Morrison CS,Sunkutu etal. Long-term use MR, 2000;27(8):431–437. hierarchy for STD prevention. Sexually Transmitted Diseases. condom among use women after counselingrisk-reduction ina M,GollubLatka E,French P, etal. Male-condom and female- randomized controlled AIDS.1998;12(14):1851–1859. trial. choicethe of using or male the female condom: results from a transmittedsexually by diseases granting workers sex inThailand Fontanet AL,Saba J, Chandelying V, etal. Protection against Research The Report. Female Company; Health 2004. Health Company. Female Condom: The Final IndianExperience: Hindustan Latex Family Planning Promotion Trust/The Female 2007. of Health,Ministry National STD/AIDS Coordinating Office; condom indifferent contexts:social Final research report. Brazil: RM,Berqu E,KalckmannBarbose S.Acceptability of female the Familymethods. Planning Perspectives contraceptive the of efficacy female condom and other barrier Trussell J, Sturgen K,StricklerJ, Comparative Dominik R. Baltimore and and CCP WHO; Geneva: 2007. Project. Family Planning: Handbook AGlobal for Providers. Health/Center for Communication Programs INFO (CCP), and Research and Johns Hopkins Bloomberg of School Public World Health Organization Department of Reproductive Health . 1994;26:66–72. § These These CAUCUS ON NEW AND UNDERUSED REPRODUCTIVE HEALTH TECHNOLOGIES PRODUCT BRIEF 13. 12. 11. 10. 9. or its wider membership. For additional information, please contact [email protected]. Responsibility for theselectionand contents of the product briefs rests solely with theCaucus and does not imply endorsement by theCoalition the discussion within theCoalition of reproductive health technologies that are not well-integrated into the public orcommercial health sectors. Technologies, athematic group established under theauspices of theReproductive Health Technologies Coalition. The Caucus’ aimis to broaden This publication forms partof aseries of technical briefs, written by members of the Caucus 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

latestCrisis/idUSN10547381. March 11,2009.Available at: http://www.reuters.com/ article/ Reuters. USFDA approves new, cheaper female condom. 2008. Personal communications. RinoMeyers, IDA Solutions. July 3, Accessed January 6,2011. Interchange web page. Available at: www.rhi.rhsupplies.org. Reproductive Health Supplies Reproductive Coalition. Health 2010. December prequalificationthe of condoms.female Bangkok, Thailand; Presentation of WHO the at WHO/UNFPA the workshop on FemCondom/acceptability.htm. Accessed March 1,2011. website. Available at: www.fhi.org/en/RH/Pubs/Briefs/ Female condom acceptability page. Family Health International This brief was last updated 2012. January

PRODUCT BRIEF Caucus on New and Underused Reproductive Health Technologies

HPV Vaccines

Description Efficacy, target groups for vaccination, and duration of protection Two vaccines against human papillomavirus (HPV)— a sexually transmitted virus that causes cervical In large, international clinical trials in young adult cancer—were approved in 2006 and 2007, respectively, females, both vaccines were shown to be at least 92 after more than ten years of intensive research and percent efficacious in preventing HPV infections and commercial development. Both vaccines—Gardasil®, precancerous lesions caused by vaccine types when the quadrivalent vaccine, and Cervarix®, the bivalent administered prior to HPV infection.6,7 While efficacy vaccine—prevent infection and precancerous cervical against infection and lesions was not demonstrated lesions caused by HPV types 16 and 18. Gardasil® also in young adolescents (because most were not yet prevents infection with types 6 and 11, which cause exposed to infection), bridging studies have shown genital warts and respiratory papillomatosis. HPV that antibody levels after vaccination are as high or types 16 and 18 account for approximately 70 percent higher in young adolescent females and males8-10 as in 1 of cervical cancer cases worldwide and a similar young adult females. According to the World Health 2 proportion of anal cancers. The USFDA recently also Organization, young adolescent girls aged 10 to 13 approved the quadrivalent vaccine for use in boys years are the primary target group for HPV vaccination and men 9 to 26 years of age for prevention of anal because the vaccines are most efficacious in people not precancerous lesions, cancer, and genital warts. The yet exposed to the viruses.11 Some countries have also vaccines also offer some degree of cross-protection targeted a secondary group for “catch-up” vaccinations, against a few non-vaccine cancer-causing types. Both often women aged 14 to 18 years. There is evidence vaccines are given in a series of three intramuscular that duration of protection is at least five years for injections over a six-month period. the quadrivalent12 and more than eight years for the 13 More than half of all sexually active people will contract bivalent vaccine (the length of follow-up studies an HPV infection at some point in their lives, although published to date), and longer-term efficacy is still being 14-16 only a relatively small percentage of women will evaluated. progress to cervical cancer.3,4 However, this translates to an estimated 530,000 women worldwide developing Global use cervical cancer every year and 275,000 dying from the 5 disease. The vast majority of these women—around 85 HPV vaccines are available through the private sector percent—live in developing countries, where life-saving in more than 100 countries and have been introduced services to screen for and treat precancerous lesions into public immunization programs in more than 30 are not available (e.g., Pap smears or other screening countries. While they are not yet widely available in the technologies, followed by treatment). By 2030, cervical developing world, several middle-income countries— cancer is expected to kill more than 474,000 women per including Mexico, Panama, Peru, and Malaysia—and year, with more than 95 percent of these deaths in low- some low-income countries—including Bhutan and and middle-income countries.5 CAUCUS ON NEW AND UNDERUSED REPRODUCTIVE HEALTH TECHNOLOGIES PRODUCT BRIEF 1. References vaccine within reach of world’s the poorest nations. nationaltheir programs. GAVI’s support put will HPV many low-resource countries addHPVvaccine to will projects Asia, and inAfrica, America—that Latin likely—based on recent with demonstration experience Now that GAVI subsidizing has begun vaccine, the it is vaccine itself, responsible andbe will for costs. delivery for aco-pay of about for dose US$0.20to 0.40per the requesting GAVI-supported responsible be vaccine will quoted price this to GAVI inJune 2011.Countries for quadrivalent the HPVvaccine. Merck &Co., Inc. lowest publically is documentedUS$5 dose price per price negotiations with two the manufacturers, and the began offering HPVvaccines as well. GAVI is continuing 70 countries developing inthe world. In 2012,GAVI private offers partners, vaccinessubsidized to morethan world’s top agencies, health global governments, and The GAVIAlliance, an immunization coalition the of Public-sector price agreements vaccines may not marketed yet be inagiven country. in114.However,countries and Cervarix® licensed As of April 2011,Gardasil® was approved in123 Registration status (PAHO) Revolving Fund for Vaccine Procurement. (UNICEF) and Pan the American Health Organization agencies such as United the Nations Children’s Fund HPVvaccinesboth for procurement by United Nations In World 2009,the Health Organization “prequalified” GlaxoSmithKline (www.gsk.com). (www.merck.com). is manufactured Cervarix® by Gardasil® is manufactured by Merck &Co., Inc. Manufacturers HPV-vaccine-implementation.htm. HPV vaccination programs, http://www.rho.org/ see informationpractical on planning for and implementing cervical_cancer_vaccine.php. For publications with in low-resource settings, visit www.path.org/projects/ acceptability, and cost of HPVvaccination programs For information on research into feasibility, the Rwanda—have national started vaccination programs.

2010;11(11):1048–1056. a retrospective cross-sectional worldwide study. Oncology Lancet papillomavirus genotype attribution ininvasive cancer: cervical de Sanjose S,Quint WGV, Alemany L, etal. Human . 8. 7. 6. 5. 4. 3. 2. 16. 15. 14. 13. 12. 11. 10. 9.

Pediatric Infectious Disease Journal Disease Infectious Pediatric preadolescents and adolescents -Arandomized controlled trial. papillomavirus vaccine in particle 6,11,16,18L1virus-like types and persistent immunogenicity of aquadrivalent human Reisinger KS,Block SL, Lazcano-Ponce E,etal. Safety Lancet situ: acombined analysis of four The randomised trials. clinical intraepithelial neoplasia 3,and 2,grade grade adenocarcinoma in papillomavirus vaccine on L1virus-like-particle risk of cervical Ault KA, FUTUREIIStudy Group. Effect of prophylactic human in young women.Lancet The (PATRICIA): final analysis of adouble-blind, randomised study infection and precancercervical caused by oncogenic HPVtypes papillomavirus AS04-adjuvanted (HPV)-16/18 vaccine against Paavonen J, Naud P, Salmeron J, of etal. Efficacy human globocan.iarc.fr/. Research on Cancer. Lyon, France; 2010.Available at: http:// IARC No. CancerBase 10[Internet]. International Agency for 2008V1.2,CancerGlobocan Incidence and Mortality Worldwide: Ferlay J, Bray Shin HR, F, Forman D, Mathers C,Parkin DM. 2005;32(Supplement 1):16–24. papillomavirus infections. Journal of Clinical Virology. JG,Baseman Koutsky The epidemiology LA. of human 2006;(Supplement):S5–S10. history, and sequelae. clinical OBG MANAGEMENT. Spitzer M.Human Papillomavirus: epidemiology, natural intraepithelial lesions. Int JCancer. 2009;124(10):2375–2383. papillomavirus distribution type inanal cancer and anal Hoots BE, Palefsky JM,Pimenta JM,Smith JS.Human 2010;19(4):916–922. Cancer Rica. studies inCosta Epidemiol Biomarkers Prev. operation of abiorepository for molecularepidemiologic B,Ortes M, Schiffman Herreroal.EstablishmentR, et and STD & AIDS.2006;17(4):237–246. human papillomavirus vaccine efficacy. International Journal of enrolmentbased of adolescents inalong-term follow-up of trial Lehtinen M,Idänpään-Heikkilä I,Lunnas T, etal. Population- 517–521. guessing. International Journal of STD &.2006;17(8): AIDS humanguarding papillomavirus against vaccine efficacy: adolescent women follow-up to cancer registry for long-term Lehtinen M,Apter D, Dubin G,etal. Enrollment of 22,000 (ESPID), Nice, France 2010. of European the for Paediatric Society Infectious Diseases vaccine: follow-up to 8.4years. Abstract at annual 28th meeting immunogenicity andthe HPV-16/18 of efficacy ASO4-adjuvanted Roteli-Martins CM,Naud P, P, Borba etal. Sustained follow-up. British Journal of Cancer . 2006;95(11):1459–1466. vaccine through particle 6/11/16/18 L1virus-like 5years of of aprophylactic quadrivalent human papillomavirus types Villa RL,Petta LL,Costa CA,etal. High sustained efficacy WHO position paper. Wkly Epidemiol Rec World Health Organization. Human papillomavirus vaccines. Adolescent Health vaccine containing particle virus-like AS04 adjuvant. of Journal adolescent females with human papillomavirus 16and type 18L1 Pedersen C,Petaja T, Strauss G,etal. Immunization of early young adult women. Pediatrics vaccine and inmale particle virus-like female adolescents and quadrivalent human papillomavirus 6,11,16,and (types 18)L1 immunogenicity and reactogenicity of aprophylactic Block SL, Nolan T, Sattler C, et al. Comparison of the . 2007;369(9576):1861–1868. . 2007;40(6):564–571. . 2009;374(9686):301–314. . 2006;118(5):2135–2145. . 2007;26(3):201–209. . 2009;84(15):118–131. CAUCUS ON NEW AND UNDERUSED REPRODUCTIVE HEALTH TECHNOLOGIES PRODUCT BRIEF or its wider membership. For additional information, please contact [email protected]. Responsibility for theselectionand contents of the product briefs rests solely with theCaucus and does not imply endorsement by theCoalition the discussion within theCoalition of reproductive health technologies that are not well-integrated into the public orcommercial health sectors. Technologies, athematic group established under theauspices of theReproductive Health Technologies Coalition. The Caucus’ aimis to broaden This publication forms partof aseries of technical briefs, written by members of the Caucus 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 This brief was last updated March 2012.

PRODUCT BRIEF Caucus on New and Underused Reproductive Health Technologies

Levonorgestrel intrauterine system

Description expulsion due to inappropriate device location, and pelvic inflammatory disease.6 Side effects associated with The levonorgestrel intrauterine system (LNG IUS) is use of the LNG IUS include possible change in bleeding a T-shaped, plastic, contraceptive intrauterine system patterns (in frequency, duration, and amount), absence (IUS) that releases the progestin hormone levonorgestrel of bleeding, and benign ovarian cysts. into the uterus at a dose of 20 μg per day for up to five In addition to the protection against pregnancy years. LNG IUS prevents pregnancy by thickening associated with the use of LNG IUS, there are a number cervical mucus, inhibiting sperm motility, and of significant health benefits related to the product’s suppressing the growth of the uterine wall.1,2,3 additional indication for the treatment of heavy The LNG IUS must be inserted and removed by a menstrual bleeding.7 These include the reduction of qualified medical or health care practitioner using iron-deficiency anaemia, reduced volume of menstrual aseptic techniques. A gynaecological examination is bleeding, and the lessening of menstrual cramps.8 The advised before device insertion (to screen for infections reduction of menstrual bleeding enabled by LNG IUS and exclude pregnancy) and again four to twelve is attributable to the product’s gradual reduction of the weeks after insertion. Thereafter, annual check-ups are thickness and vascularity of the over the recommended to ensure that the device remains in place first three to six months of use. As a result, women who and to ensure that the user’s needs are being met. There had previously experienced heavy menstrual bleeding are no age or parity restrictions on its use, and women noticed a significant reduction of blood loss, of between can use an LNG IUS throughout their reproductive life 79 and 98 percent.8 Practically speaking, women using if it is replaced at the recommended intervals. Removal LNG IUS gradually experience lighter menstrual of an LNG IUS can be done at any time by a qualified bleeding for fewer days. Because of this additional effect medical or health care practitioner. Upon removal, of LNG IUS, a provider may recommend it to women fertility will return rapidly. LNG IUS is best suited for with menorrhagia or who seek to lessen heavy periods.7 women who desire a long-term, reliable contraceptive For more information on LNG IUS, its health benefits, method for birth spacing or limiting, and also have and contraceptive dynamics, see the special issue of the access to a qualified medical or health care practitioner journal Contraception on IUS/intrauterine devices of for counselling, examination, insertion, and check-ups. contraception.9 The LNG IUS does not provide protection from sexually transmitted infections, including HIV. Current program/sector use Efficacy IUSs are now being introduced in both developed and developing countries and are gaining popularity in a The LNG IUS is one of the most effective and long- number of countries in South Asia, Africa, and Latin lasting contraceptive methods available. Over the first America.10 Mirena®, an IUS produced by Bayer Pharma, year of use, the pregnancy rate is 2 per 1,000 women is provided commercially through gynaecologists and using an LNG IUS—in other words, 0.2 percent. After other qualified providers in the countries where it is the first year, there is a lower risk of pregnancy— registered. During 2010, approximately 3.17 million cumulatively only 5 to 8 pregnancies per 1,000 women units were sold globally, with the largest sales reported in over five years of use.4,5 the United States and Europe. Since its introduction into the market, more than 18 million women have selected Complications from LNG IUS use are rare, but may Mirena® as their method of choice.11 The International include uterine perforations at the time of insertion, Contraceptive Access (ICA) Foundation, founded by CAUCUS ON NEW AND UNDERUSED REPRODUCTIVE HEALTH TECHNOLOGIES PRODUCT BRIEF or its wider membership. For additional information, please contact [email protected]. Responsibility for theselectionand contents of the product briefs rests solely with theCaucus and does not imply endorsement by theCoalition the discussion within theCoalition of reproductive health technologies that are not well-integrated into the public orcommercial health sectors. Technologies, athematic group established under theauspices of theReproductive Health Technologies Coalition. The Caucus’ aimis to broaden This publication forms partof aseries of technical briefs, written by members of the Caucus 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 Nigeria), but is available through public-sector registered inthree countries (Ghana, Kenya, and The LNG IUS provided the by ICA Foundation is Unitedthe States by Arch the Foundation. Pharma, and donated to public-sector organizations in countries worldwide, distributed commercially by Bayer The Mirena® IUS is registered in morethan 120 Registration status/suppliers Mirena® marketed is also by Bayer Pharma. Pharma. The LNG IUS availablethe in private market as LNG IUSsare manufactured inTurku, Finland by Bayer Manufacturer privatethe is sector high. term effectiveness, the cost initial yet the of product in expensive contraceptive of because methods its long- terms of costs over time, LNG the IUSis among least the upfront cost of product the private inthe sector. In are obstacles to several its expanded use, including the Despite increasing the popularity of LNG the IUS,there and South Africa. Ghana, Indonesia, Kenya, Nigeria, Paraguay, Saint Lucia, Dominican Republic, Ecuador, Salvador, El Ethiopia, providing LNG the IUSfor projects inBrazil, Curacao, donations. Specifically,the ICA Foundationcurrently is countries through public the and nonprofitsector via a bioequivalent LNG IUSthat is now available in13 Populationthe and Council Bayer Pharma, provides meeting patients’ needs. shown sufficient to be in treating complications and woman’s desire for removal. This guidance been has in response to negative signs and symptoms, or a important; thereafter, visitsclinic are only recommended to ensure proper placement and absence of infection is IUS. Requiring aclinic follow-up after soon insertion reduce costs and increase patient acceptability of the follow-upunnecessary visits may another be way to and cost-saving inanumber of settings. out procedure this carry shown has been effective to be IUDs/IUSs. Authorizing workers health trained allied to nurses and practitioners medical are permitted to insert countries are challenging also access, as only certified ICAthe Foundation. The prevailingpolicies in many not available indeveloping countries except through acurrentis also constraint; LNG the IUSis generally 14 12 Availability of product the 13 Eliminating 2. 1. References womenpoor and families. offer then who the LNG IUS at reduced or no cost to governmental(both and nongovernmental affiliates) development agencies and public-health organizations The ICA Foundation donates LNG IUSs to international Public-sector price agreements registration. forthan is used Mirena® and often requires adifferent Controller. The LNG adifferent IUS uses inserter ofsuch Health as Ministry the or National Drug donations with approval by national authorities medical 16. 15. 14. 13. 12. 11. 10. 9. 8. 7. 6. 5. 4. 3. by ICA the Foundation. approximately 40,000LNG IUSunits have donated been

website. Available at: www.arhp.org. Accessed January 6,2011. Association of Reproductive Health Professionals (ARHP) Baltimore and and CCP WHO, Geneva: 2007. Family(CCP). Planning: Global A Handbook for Providers ofSchool Public Health/Center for Communication Programs and Research (WHO/RHR) and Johns Hopkins Bloomberg World Health Organization Department of Reproductive Health com. Accessed January 6, 2011. The Arch Foundation website. Available www.archfoundation.at: ICA Foundation, 2010. Salem Planning Acceptance, and Programmatic Studies Effects. in Family Midwife Insertion of TinThailand: Copper the Performance, Wright NH,Sujpluem C,Rosenfield AG, Varakamin S. Nurse- 2006. Salem, Accessed January 20,2012. annualreport2010.bayer.com/en/bayer-annual-report-2010.pdfx. Bayer AG 2010annual report. Available at: http://www. 2006 Salem, Available at: www.contraceptionjournal.org. IssueSpecial on IUD/IUSof Contraception hormonal 2010;82:396–403. systems. Contraception. Fraser IA. Non-contraceptive benefits health to intrauterine what-does-mirena-mean-for-you.jsp. Accessed January 31,2012. website. Available at: http://www.mirena-us.com/what-it-does/ Mirena® SignificantlyReduced Heavy Bleeding Menstrual WHO, 2007. Accessed January 6,2011. 2006; B(7).Available at: www.populationreports.org/b7/. contraceptive options toPopulation needs. their meet Reports New R. AttentionSalem to IUD:Expanding the women’s WHO/JHU/CCP, 2007. Available at: www.ica-foundation.org. Accessed 28,2010. October International Contraceptive Access (ICA) Foundation website. , 2006. . September 1977;8(9)237-243. 16 15 As of 2011, December This brief was last updated 2012. January . 2007;75(6S).

. . PRODUCT BRIEF Caucus on New and Underused Reproductive Health Technologies

Magnesium sulfate

Description Efficacy, safety, and benefits

Magnesium sulfate is an drug A three-year study called “the Magpie Trials” was recommended by the World Health Organization launched in 2002 as a collaborative effort including the as the most effective, safe, and low-cost treatment World Health Organization, the UK Medical Research available for severe pre-eclampsia and eclampsia. Severe Council, and other partners to comprehensively study pre-eclampsia is a common cause of maternal death, the efficacy of magnesium sulfate to treat eclampsia. The leading to approximately 50,000 maternal deaths per study was conducted in 33 countries and included nearly year.1 Some early symptoms manifest as headaches, 10,000 pre-eclamptic pregnant women. The results of the epigastric or right hypochondrial pain, , and study were that the women who were given magnesium visual disturbances.2 If left untreated, the condition can sulfate had a 58 percent lower risk of eclampsia and a 45 lead to seizures and convulsions (known as eclampsia), percent lower risk of dying from eclampsia than women hypertension, kidney and liver damage, and death. who were administered a placebo.7,8 These results are Teenage mothers in developing countries are most consistent with other studies of the drug, notably the affected by eclampsia, which typically manifests during 1995 Collaborative Eclampsia Trial, in which the relative a woman’s first pregnancy and is more common in effectiveness of magnesium sulfate was compared with areas of general poverty and poor access to antenatal Diazepam and Phenytoin (two anticonvulsant drugs and intrapartum care. However, the efficacy and low- commonly used to treat eclampsia), validating the cost of magnesium sulfate make this condition a highly significantly higher efficacy rate of magnesium sulfate treatable one.3 in the treatment of eclampsia and in the prevention of recurring seizures. Women administered magnesium Although its exact mechanism of action is unclear, sulfate had a 52 and 67 percent lower rate of convulsions magnesium sulfate is thought to treat eclampsia through than those treated with Diazepam and Phenytoin, affecting a series of cardiovascular and neurological respectively.9,10,11 functions and by altering calcium metabolism.4 Some studies have suggested that magnesium sulfate could When magnesium sulfate is carefully administered act as a vasodilator, having actions which relieve and closely monitored, the toxicity of this treatment vasoconstriction, protect the blood-brain barrier, is minimal (<2 percent). Magnesium sulfate is nearly decrease cerebral edema formation, and act as a cerebral entirely broken down in the body, with 90 percent of the anticonvulsant.5 compound being released through the urine within 24 hours.12 Consequently, it does not act as a cure for pre- In terms of administering the drug, magnesium sulfate eclampsia, but rather as a treatment for eclampsia during is a solution that can be administered intramuscularly or individual births. It is currently being studied for use as intravenously, at a recommended concentration of 1.8 to a prophylactic. 3.0mmol/L. For intramuscular administration, an initial 4g dose is given intravenously, followed immediately by In multiple studies including the Magpie Trials, there a 10g intramuscular dose, and then 5g intramuscular were no attributable deaths found in women who were doses every four hours in alternating buttocks. For administered the drug. The risk that magnesium sulfate intravenous administration, an initial 4g dose is given poses to infants is likewise minimal.13,14 There are a few intravenously, followed by a 1-2g/h maintenance minor side effects for women. About a quarter of women infusion given by a controlled infusion pump.6 administered magnesium sulfate experienced headaches, nausea or vomiting, muscle weakness, or respiratory CAUCUS ON NEW AND UNDERUSED REPRODUCTIVE HEALTH TECHNOLOGIES PRODUCT BRIEF availability of magnesium sulfate areas. inthese lack of adequate training, service-provider and lack of This is due lackto of public awareness the drug, of achieved widespread usage indeveloping countries. is the drug ofis drug the choice to treat eclampsia. general international consensus that magnesium sulfate Phenytoin. However, since Magpie the Trials, there is multipurpose such as Diazepam and that it was undesirable compared with more common, less common inEurope due to ageneral perception women. comparison with enormous the benefit it has for at-risk side effects of using magnesium sulfate are in negligible century. and eclampsia United inthe States throughout 20th the Europe, having to treat used been severe pre-eclampsia is relativelyuse widespread United inthe States and doses ofdoses magnesium sulfate. government aprice has of set pack of US$5.76 per ten governments.their For example, South the African domesticbetween pharmaceutical companies and country,the however, price agreements may exist agreements for magnesium sulfate. on Depending There are no existingglobal public-sector price Public-sector price agreements pharmaceutical companies to produce it. itsbecause low cost leaves little profit-based incentive for Magnesium sulfate is rarely manufactured globally and 5g/10ml.) Plastic Syringe containers (2.5g/5ml at doses varying format) is encapsulated inHospira’s Ansyr® Single-Dose Hospira, Inc. (www.hospira.com). (liquid The drug manufacturerThe primary of magnesium sulfate is Manufacturers ampoule).per affordableis highly typical (a dosage costs US$0.35 Organization’s essential medicines list since 1996and Magnesium sulfate on has World the been Health Current program/sector use issues. for prequalification. Interest accept list for as requests adrug will they which It was, however, on placed 2010Expression their of yet prequalified manufacturers of magnesium sulfate. As of January 2012,WHO regulatory authorities had not for information on how to doso. pharmaceutical companieslocal (or comparable entities) it is advisable of Health to Ministry contact and local the providers or distributors to acquire magnesium sulfate, 15 However, there is ageneral consensus that the 18 Use of magnesium sulfate was for many years 16 However, magnesium sulfate has not 19 20 For service For service 10,17 Its 5. 4. 3. 2. 1. References 20. 19. 18. 17. 16. 15. 14. 13. 12. 11. 10. 9. 8. 7. 6.

28, 2011. early/2009/02/10/STROKEAHA.108.527788.short. Accessed July 1524-4628. Available at: http://stroke.ahajournals.org/content/ Association Heart Eclampsia. ABrief Review. Stroke; Journal of the American Euser A,Cipolla M.Magnesium Sulfate for Treatment the of . 1996;15(3):188–199. Experience Drug Safety:Drug An International Journal of Medical Toxicology & seizure prevention inpatients with pre-eclampsia &eclampsia. Anthony J, Johanson L.Role RB, of magnesium Duley sulfate in 2011. AdminMagSulfPreeclampsia.asp#/Details .Accessed July 26, 2008. Available at: http://www.popcouncil.org/projects/134_ State, Nigeria. Population Council,Project Online Page. Karlyn A.Expanding Access to Magnesium Sulfate inKano StudyMGSO Mexico.asp. Accessed July 26,2011. 2011. Available at: http://www.popcouncil.org/projects/238_ State, Mexico. Population Council,Project Online Page. 2009- Use to Manage Pre-eclampsia Severe and Eclampsia inOaxaca Contreras X,Garcia S,Van Dijk M.Studies on Magnesium Sulfate cd007388_sonibl_com/en/. Accessed July 26,2011. who.int/rhl/pregnancy_childbirth/medical/hypertension/ WorldGeneva: Health Organization. Available at: http://apps. Marchrevised: 1,2011).The WHOReproductive Library; Health with Pre-eclampsia and Eclampsia: RHLcommentary (last BL.Soni Alternative Magnesium Sulfate Regimens for Women Eclampsia-Report.pdf. Accessed July 26,2011. engenderhealth.org/files/pubs/maternal-health/EngenderHealth- in Developing Countries. 2007.Available at: http://www. Pregnant Women with Life-Threatening ConditionsHypertensive Engender Health. Expanding Treatment Balancing Scales: the for Green M,2003. Euser A,2009. Reproductive Health Matters. 2006;14(27):219. Maternal Nigeria, Mortality: Burkina Faso and Pakistan. Human Resources and for Reproductive Sexual Health Care. index.html. Accessed July 26,2011. www.who.int/alliance-hpsr/projects/mohpakistan_medicines/en/ ofResearch; Health, Ministry Pakistan. 2010.Available at: http:// A Study to Develop Informed Policy. Access to Medicines Policy Hafeez to Use A.Barriers the of Magnesium Sulphate inPakistan: 28(3):136–137. Eclampsia. International Family Planning Perspectives. 2002; Guttmacher Institute. Magnesium Sulfate Safely Prevents Altman D, 2002. Karlyn A,2008. Lu JF, 2000. Journal of Medicine. 2003;384(4):275–276. Green M.Magnesium Sulfate for Preeclampsia. The EnglandNew Eclampsia Trial. Studies inFamily Planning. 1995;26(6):373. for Women with Eclampsia? Evidence from Collaborative the EclampsiaThe Collaborative Trial Group. Which Anticonvulsant Karlyn A,2008. 2002;359(9321):1877–1890. The Magpie arandomizedTrial: placebo-controlled Lancet trial. eclampsia, and babies, their from benefit magnesium sulfate? Altman D, women L,etal. Do Carroli G,Duley with pre- releases/release44/en/. Accessed August 4,2011. 2002. Available at: http://www.who.int/mediacentre/news/ Convulsions inPregnant Women, Study Finds. Media Center. World Health Organization. Inexpensive Prevents Drug Fatal 2000;38(4):305–314. pre-eclampsia: pharmacokinetic principles. Pharmacokinet Clin Lu JF, Nightingale CH.Magnesium sulfate ineclampsia and . 2009;Print ISSN: ISSN: 0039-2499;Online . . CAUCUS ON NEW AND UNDERUSED REPRODUCTIVE HEALTH TECHNOLOGIES PRODUCT BRIEF or its wider membership. For additional information, please contact [email protected]. Responsibility for theselectionand contents of the product briefs rests solely with theCaucus and does not imply endorsement by theCoalition the discussion within theCoalition of reproductive health technologies that are not well-integrated into the public orcommercial health sectors. Technologies, athematic group established under theauspices of theReproductive Health Technologies Coalition. The Caucus’ aimis to broaden This publication forms partof aseries of technical briefs, written by members of the Caucus 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 This brief was last updated 2012. January

PRODUCT BRIEF Caucus on New and Underused Reproductive Health Technologies

Manual vacuum aspiration

Description accessible, and potentially less expensive way to offer high‑quality services to women.5 Manual vacuum aspiration (MVA) can be used to Studies demonstrate that the efficacy of MVA is manage a number of maternal health conditions—such comparable to EVA and is successful in approximately as incomplete and spontaneous or unsuccessful 99 percent of cases for early‑elective abortion and —and can be used to perform management of early pregnancy loss. Studies show first‑trimester induced and endometrial that 98 percent of vacuum aspiration procedures occur biopsies. MVA allows for evacuation of the uterus using without complications, much higher than the alternative a hand‑held plastic aspirator attached to a cannula (a D&C method, which may induce incidences of excessive thin tube). Unlike electric suction, the suction used for blood loss, pelvic infection, cervical injury, and uterine uterine evacuation is created manually by extending perforation.6 the plunger of the syringe‑like aspirator. MVA is similar to electric vacuum aspiration (EVA). The two methods share a mechanism of action—using suction as the force Current program/sector use to remove uterine contents via the cannula. However, for EVA, a large electric machine generates the suction, and Vacuum aspiration, both electric and manual, is used the aspiration is performed using a long tube connected for about 97 percent of first trimester surgical‑induced to the EVA machine. The need for electricity, the larger abortions in the United States. The United Kingdom, size, and the greater cost of the machine precludes the Canada, China, New Zealand, Singapore, and other use of EVA in many parts of the world, whereas MVA countries use vacuum aspiration for most of their can be used in any location where basic medical care is first trimester surgical‑induced abortions.7 In many provided. developing countries, such as Bangladesh and Vietnam, MVA has been used for several decades to provide MVA is safe, effective, easy to use, portable, and early‑induced abortion, including procedures referred to reusable. It is appropriate for use in many different as “menstrual regulation.” MVA is well‑suited for use in clinical settings (including developing‑country conjunction with medical abortion* if there is a concern outpatient centers), does not require lengthy training for that the uterus has not been completely evacuated. proper operation, and has yielded both high patient and provider satisfaction.1,2 Additionally, there is substantial evidence that mid‑level providers—for example, Manufacturer/supplier midwives, clinical officers, nurse practitioners, physician assistants—can perform MVA procedures safely and MVA is available in many countries. Many governments effectively in a range of health care settings.3,4 have identified MVA in clinical guidelines as the preferred method for uterine evacuation. Inclusion in clinical guidelines also helps to ensure adequate and Efficacy reliable supplies of MVA instruments in their public health systems. MVA has been demonstrated to be effective and very safe through clinical studies over the last 30 years. The The original MVA device was developed by Ipas—an World Health Organization (WHO) recommends MVA international organization that works to increase as a preferred method of uterine evacuation.2 When compared to sharp curettage (also known as dilation * For more information on medical abortion, please see the Caucus’ Medical and curettage or D&C), MVA is a safer, more readily Abortion brief. CAUCUS ON NEW AND UNDERUSED REPRODUCTIVE HEALTH TECHNOLOGIES PRODUCT BRIEF or its wider membership. For additional information, please contact [email protected]. Responsibility for theselectionand contents of theproduct briefs rests solely with theCaucus and does not imply endorsement by theCoalition the discussion within theCoalition of reproductive health technologies that are not well integrated into the public orcommercial health sectors. Technologies, athematic group established under theauspices of theReproductive Health Technologies Coalition. The Caucus’ aimis to broaden This publication forms partof aseries of technical briefs, written by members of the Caucus 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 registrations are not required. countriesthe where it operates, individual so country CE marking on MSI’s MVA products is sufficient for clinics, but are they available to procurers. external The MSI’s MVA products are currently mainly inMSI used proceduresclinical and approved devices. medical incountriesGlobal throughout world the as accepted Ipas MVA products are registered by WomanCare status Registration document relative their quality. variable. Some efforts have made been to assess and available from other manufacturers, but quality can be Currently, there are anumber of other MVA products developing and developed countries. of reproductive spectrum full the care health inboth mark. MSI non is aglobal single Malaysia,in China, and Taiwan manufacture who both Marie Stopes International (MSI) has manufacturers more than 100countries. productshealth public the inboth and private sectors in WomanCare provides Global access to reproductive has conducted verification testing for compliance. quality standards, audits manufacturers, their and manufactured inTaiwan. WCG adheres to ISO13485 double distributor of Ipas MVA instruments (single injuries. WomanCare (WCG) Global is exclusive the rights, and to reduce abortion‑related deaths and women’s ability to and exercise reproductive sexual their - and double - valve aspirators), are which CEmarked and - valve MVA. CE the possess Both - profit organization providing 8 - and 4. 3. 2. 1. References mariestopes.org) for MSI MVA instruments. instruments or Marie Stopes International (orders@ ([email protected]) for Ipas MVA Procurers are encouraged to contact WomanCare Global time.this There are knownno public Public-sector price agreements 8. 7. 6. 5.

1965–72. randomized controlled Lancet equivalence trial. doctors and mid‑level providers and inSouthVietnam: Africa a in first‑trimester manual vacuum aspiration abortion done by Warriner IK,Meirik O, HoffmanRatesal. M,et of complications Americanservices. Journal of Public Health, 2004;94(8). Physician assistants as providers of surgically induced abortion Goldman MB, Occhiuto JS,Peterson LE,Zapka JG, Palmer RH. Technical and policy guidance for health systems WHO.. Geneva: World Health Organization (WHO). abortion: 2003.Safe Accessed January 6,2011. Vacuum_Aspiration_‑_Frequently_Asked_Questions.aspx?ht. Ipas website. Available at: www.ipas.org/Library/FAQs/Manual_ Manual vacuum aspiration—frequently asked questions page. 2003;83(2):219–232. instruments. International Journal of Gynecology &Obstetrics. S,RuminjoGirvin J. An evaluation of manual vacuum aspiration Ipas; 2001. Women’s Access to Safe Abortion. Chapel Hill, Services N.C.: Baird TL,FlinnSK. Manual Vacuum Aspiration: Expanding Medical and social aspects. London: Academic Press; 1981. Unitedthe States. In: Hodgeson, JEed. Abortion and : Cates WJ, Grimes DA. Morbidity and mortality of abortion in preventable pandemic. Lancet Grimes DA, J, Benson Singh S,etal. Unsafe abortion: The - . 2006;368(9550):1908–1919. sector pricingsector agreements at This brief was last updated 2012. January . 2006;368:

PRODUCT BRIEF Caucus on New and Underused Reproductive Health Technologies

Medical Abortion

Description the rate of continuing pregnancy is less than 1 percent in gestations up to 63 days’ amenorrhea. Medical abortion (MA) is a nonsurgical procedure Even though the combined regimen of in which drugs are used to induce abortion. The followed by misoprostol is significantly more effective most effective and safest medical abortion regimen than use of misoprostol-alone for early medical requires the use of two medications: mifepristone abortion,4 misoprostol is generally more widely and misoprostol. Mifepristone blocks the action of available than mifepristone and has been used alone progesterone to enhance the contractility of the uterus safely and successfully for medical abortion around the and prompt the detachment of the implanted embryo. world.5 Complete abortion rates with misoprostol-only Misoprostol stimulates strong contractions of the uterus, regimens range from 76 to 96 percent, according to expelling the products of conception. This process existing research.4,6,7 is very similar to that of a spontaneous abortion or .1 Repeated administration of misoprostol The use of mifepristone and misoprostol is very safe; alone can also be used to induce abortion. Both drugs medical abortion has not been associated with long- also soften and dilate the cervix. term health impacts and is statistically less risky than continuation of pregnancy.8 Medical abortion may be Quality abortion care should include counseling, preferable to surgical abortion for some women and confirmation of intra-uterine pregnancy, and estimation their providers, as medical abortion is less invasive and of length of gestation by the patient’s history, bimanual can be perceived to be a more private procedure by exam, or with ultrasound—although the latter is not some women. required. Family planning and contraception counseling should be provided at the time of the abortion or afterwards. Medical abortion options have made Current program/sector use abortion more available to women in a variety of health care settings, and home administration of medical There are a number of political, logistical, cultural, abortion is also highly acceptable.2 religious, financial, and other barriers that limit universal access to medical abortion. Elective abortion is legally restricted in many countries, but almost Efficacy all countries have provisions under which abortion is legal, including to save the woman’s life, preserve The International Federation of Obstetrics and physical or mental health, when the pregnancy is a Gynaecology (FIGO) published revised guidelines for result of rape or incest, or on socioeconomic grounds. the use of mifepristone and misoprostol for MA up to Where abortion is legal, challenges may arise in terms nine weeks, 9-12 weeks, and after 12 weeks gestation of health-system restrictions on where the services can in December 2011.3 All the regimens use 200 mg be provided, procurement of the drugs, and provider of mifepristone followed by 800 μg of misoprostol training to properly inform and counsel patients about administered vaginally, bucally, or sublingually. The their options. However, medical abortion is being made misoprostol is taken 24–48 hours after mifepristone up available to women in numerous countries, including to 9 weeks gestational age or 36–48 hours from 9–12 some sub-Saharan African countries. The level of use in weeks and after 12 weeks gestational age. Additional developed countries such as the United States and those doses of 400 μg misoprostol may be be required in Europe suggests that women appreciate having an depending on gestational age. These combinations result alternative to surgical abortion; women in Europe have in complete abortion in more than 95 percent of cases; CAUCUS ON NEW AND UNDERUSED REPRODUCTIVE HEALTH TECHNOLOGIES PRODUCT BRIEF available inFrance. name misoprostol product, though it is currently only product. Pharma) Gymiso®(HRA is another brand- 80 countries, is most the widely available misprostol markets. Cytotec® (Pfizer), registered in morethan mifepristone, many only make products for local their to low- and middle-income countries, but, as with of manufacturers these are making products for export ‡ † * misoprostol. support applications from generic manufacturers of Medicines Programme, and efforts are to underway eligiblebecame for WHO’s the Prequalification of In May 2010,misoprostol and mifepristone packs as interest grows globally. manufacturers are planning also combination to export Sun Pharmaceuticals, is available for Other export.* Medabon®, acombination pack manufactured by are market for local inthe use only. However, productsthese are made inIndia and and China in low-and middle-income countries. Most of (200 μgeach)are currently only made by manufacturers mifepristone (200mg) and four tablets of misoprostol Combination packs containing one tablet of packs combination Mifepristone-misoprostol Mexico, United the States, France, and Russia. Peru, China, Egypt, South Korea, Argentina, Chile, income countries including India, Bangladesh, Brazil, pharmaceutical companies and middle-, inhigh-, low- versions of misoprostol are manufactured by More than 50branded and non-branded generic Misoprostol capacity export their is limited. middle-income countries such as India and but China, by numerous pharmaceutical companies inlow- and non-branded generic versions of mifepristone are made mostly high-income countries. Many more branded and a non-branded generic (Linepharma), are available in Laboratories) and (Laboratoire Mifegyne and Exelgyne), Two branded generics of mifepristone, Mifeprex (Danco Mifepristone (mifepristone, misoprostol, and combination packs). There are numerous manufacturersthree all of products and incombination for packs made specifically MA. manufacturers, as individually-packaged medicines Mifepristone and misoprostol are available from generic Manufacturer/supplier 20 years. using mifepristonebeen and misoprostol for more than

brief on Misoprostol. For more information on misoprostol for use obstetric indications inaddition Caucus’ the abortion, to see please medical brief New and Underused RHTechnologies The International Obstetrics 2007, Journal & of Gynecology Volume 99, Supplement 2,contains series of a articles on misoprostol for obstetric indications. For more information, Concept Foundation see website at www.conceptfoundation.org and www.medabon.info. 10

9 Some Some Misoprostol). Gymiso®) and Russia (registered by Pentcroft Pharma as termination inFrance (registered by Pharma HRA as forwithspecifically mifepristone use for pregnancy legal andlegal acceptable, up to 9weeks of gestation. Medicines for termination of pregnancy where Health Organization (WHO) Model List of Essential misoprostol for MAwas included on World the MA. for anumber of obstetric indications, including existing supporting evidence misoprostol’s effectiveness prevention of ulcers. This gastric is despite a breadth of (Cytotec®) is only registered for treatment the and countries most the commonly available product around world, the but inalarge number of those misoprostol products are registered inmost countries lack of awareness among makers. For policy example, in many countries, due to sensitivities political and a Registration for ofused drugs MA is the often difficult status Registration in developing countries. number the Overall, of price for public-sector procurement of Medabon® ConceptThe Foundation has negotiated a preferential Public-sector price agreements registered for MA,but are they not available for export. many brands of Indian-made combination packs are other countriesseveral in sub-Saharan In Africa. India, register combination packs from other manufacturers in India, Nepal, and Zambia. Efforts are to underway Ghana, abortion inBangladesh,medical Cambodia, Medabon® is only the product currently registered for packs combination Mifepristone-misoprostol Ethiopia and Ghana. approvedbeen for MAinafew countries, including is far from universal. Misoprostol products have only As noted above, registration of misoprostol for MA Misoprostol Nepal, Vietnam, and Zambia. registered are Ghana, Cambodia, India, Mozambique, low-income countries where mifepristone is currently abortion in50countriesin medical worldwide; the Mifepristone registered has been and approved for use Mifepristone status for and eachdrug combination the pack. information registration below global highlightsthe foruses are they which effective, including MA. The ensure are drugs both registered for breadth the of makers andwith policy care health officials to number of international organizations are working † In combination 2005,the of mifepristone and ‡,13 Misoprostol registered has been

12 11 A CAUCUS ON NEW AND UNDERUSED REPRODUCTIVE HEALTH TECHNOLOGIES PRODUCT BRIEF or its wider membership. For additional information, please contact [email protected]. Responsibility for theselectionand contents of the product briefs rests solely with theCaucus and does not imply endorsement by theCoalition the discussion within theCoalition of reproductive health technologies that are not well integrated into thepublic orcommercial health sectors. Technologies, athematic group established under theauspices of theReproductive Health Technologies Coalition. The Caucus’ aimis to broaden This publication forms partof aseries of technical briefs, written by members of the Caucus 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 demand. andcountry-specific, is often dependentupon product continuing to evolve. Pricing varies by manufacturer, is manufacturers for is large, drugs these and market the is 6. 5. 4. 3.

2011;Sep;118(3):601–8. misoprostol before and afterdays 42 gestation. Hum. Reprod KA,Zikopoulos etal. Early pregnancy termination with vaginal Gynecology &Obstetrics, 2007;99Suppl 2:S172–7. up to 12completed weeks of pregnancy. International Journal of Faundes A,etal. Misoprostol for termination the of pregnancy trimester abortion: arandomized Gynecol controlled Obstet trial. misoprostol compared with misoprostol alone for second- Ngoc NT, Shochet T, Raghavan S,etal. Mifepristone and terminationthe of pregnancy. Int Obstet. J, Gynecol Faundes A.The combination of mifepristone and misoprostol for 85(4):394–7. of misoprostol for abortion. Contraception medical significant factors affecting acceptability of home administration Kopp C,Gemzell-Danielsson Kallner K.Assessment H,Fiala of Trimester, Italy Bellagio, Consensus Conference on Medical Abortion in Early First Questions About Medical Abortion: Conclusions of an International World Health Organization (WHO). Frequently Asked Clinical 2002. 17(12):3079–3083. . Geneva: WHO;. Geneva: 2006. . 2011 Sep 28. . 2011Sep 2011;115;1–4. ., . 13. 12. 11. 10. 9. 8. 7.

resources.html. Accessed March 19,2012. Innovations Website. Available at: http://www.vsinnovations.org/ Map of Misoprostol Approval page. Venture Strategies mifepristone-approval/. Accessed February 7,2011. June 2011.Available at: http://gynuity.org/resources/info/list-of- List of Mifepristone approval page. Gynuity website. updated Last essentialmedicines/en/. Accessed 19,2011 December Available online at http://www.who.int/medicines/publications/ World Health Organization Model Lists of Medicines Essential 16,2011. December info_applicants/eoi/EOI_ReproductiveHealth-V5.pdf. Accessed Organization, Available Geneva. at http://apps.who.int/prequal/ to WHO the Prequalification Programme, World Health to submit an Expression of Interest (EOI) for product evaluation Invitation5th to manufacturers of reproductive products health 2009;105:180–186. InternationalMisoprostol. Journal of Gynecology and Obstetrics. Fernandez MM,etal. Assessing Availability Global the of Journal of Obstetrics and Gynecology. 2006;194(1):92–94. by pregnancy outcome, United States, 1991to 1999.American Grimes DA. Estimation of pregnancy-related mortality risk evacuation. Fertility and Sterility , 2009;91(1):28–31. by 800[mu]g single-dose misoprostol compared with surgical Prasad S,AKumar, Early ADivya. termination of pregnancy This brief was last updated March 2012.

PRODUCT BRIEF Caucus on New and Underused Reproductive Health Technologies

Misoprostol for maternal health

Description blood loss.2 In a study of women delivering at home in India, oral misoprostol was associated with a significant reduction in the rate of acute postpartum hemorrhage Misoprostol can be used for a number of obstetric compared to women not using a uterotonic.3 A indications that address maternal health concerns. significant reduction in PPH was also observed with Misoprostol acts as a uterotonic by stimulating oral misoprostol when administered by traditional birth strong contractions of the uterus and also softens attendants during home deliveries in Pakistan.4 and dilates the cervix, similar to the natural process In 2000, the World Health Organization (WHO) of labor. Its uses related to maternal health are recommended the prophylactic use of a uterotonic many and include the prevention and treatment of immediately after delivery for all women, as part of postpartum hemorrhage, labor induction, treatment the active management of the third stage of labor,5 of incomplete abortion and miscarriage, induced and oxytocin is recommended as the first line drug. In abortion, treatment of missed abortion, treatment March 2011, the WHO included the use of 600 mg oral of intrauterine fetal death, and cervical ripening. misoprostol for prevention of PPH in the 17th Model 6 Dosing regimens vary depending on the medical List of Essential Medicines. indication. For labor induction and cervical ripening, For the treatment of PPH: In women who were given the dose can be as low as 25 mg; however, the other prophylactic oxytocin as part of the active management indications require a dose of between 400–800 mg. of the third stage of labor, misoprostol and oxytocin Recommended routes of administration are oral, were found to be clinically equivalent when used to stop sublingual, rectal, or vaginal. Dosage guidelines for excessive post-partum bleeding.7 In women not exposed all indications listed above have been issued by the to prophylactic oxytocin, although oxytocin was found International Federation of Gynecology and Obstetrics to be more effective at controlling bleeding within 20 1 (FIGO). See also http://www.misoprostol.org. minutes, researchers concluded that 800 mg sublingual Misoprostol is available in tablet form, and marketed misoprostol might be a suitable first-line treatment in products typically have a shelf life of 18–36 months settings in which use of oxytocin is not feasible.8 when stored below 25–30°C (77–86°F) in a dry area. For the treatment of incomplete abortion and miscarriage: The efficacy of misoprostol to treat Efficacy incomplete abortion and miscarriage is between 91 to 99 percent, equivalent to the use of manual vacuum For the prevention of postpartum hemorrhage (PPH): aspiration.* Medical management of incomplete Misoprostol is an effective alternative uterotonic, where abortion and miscarriage with misoprostol provides use of oxytocin or other injectable uterotonics requiring a good opportunity to scale up post-abortion care refrigeration and administration by a skilled provider services.† Use of 600 mg oral misoprostol for this is not feasible. For these reasons, misoprostol can be indication was included in the WHO 16th Model List of especially useful in home deliveries. In a multi-center Essential Medicines in 2009 and in the WHO Priority study conducted in hospitals, oxytocin performed Medicines for Mothers and Children issued in 2011.7,9 marginally better than oral misoprostol in controlling

* For a complete list of references and discussion, please refer to the medial Post-abortion care (PAC) toolkit located at www.vsinnovations.org/resources.html or www.ipas.org/ma/mpactoolkit. † Further information on the treatment of incomplete abortion with misoprostol and service delivery guidelines for integrating misoprostol into PAC services can be found at http://vsinnovations.org/resources.html or http://www.ipas.org/ma/mpactoolkit and http://gynuity.org/resources/info/guidebook-on-misoprostol-for- treatment-of-incomplete-abortion/. CAUCUS ON NEW AND UNDERUSED REPRODUCTIVE HEALTH TECHNOLOGIES PRODUCT BRIEF hourly) misoprostol for induction the of labor. of oral both two-hourly) (25mg, or six- (25μg, vaginal abortion around world. the safelyand used has and been successfully for medical misoprostol is more widely available than mifepristone as combination the of mifepristone and misoprostol, from 76to 96percent. Even though it is not as effective alone regimens for early-term abortion range medical ‡ low-income countries including India, Bangladesh, by pharmaceutical companies and middle-, inhigh-, versions of 200mg misoprostol tablets are manufactured More than 50branded and non-branded generic Manufacturer/supplier as baby their soon is delivered. Studies inAfghanistan, to self-administer 600µgmisoprostol tablets orally as prevention of PPH, pregnant women have taught been obstetric indications are implemented. being For the misoprostol into system health the for avarietyof In developing countries, programs to introduce where permissible. legally combination with mifepristone for abortion, medical induction ripening, and of in labor and cervical off-label for many of indications,its clinical including In developed-world the setting, misoprostol is used Current program/sector use of labor not with doses exceeding 50mg; at least as effective dinoprostoneas vaginal for induction that oral misoprostol is more effectivethan placebo and For have labor Reviews induction: Cochrane concluded For abortion induced Programs inEthiopia, Kenya, Tanzania, workershealth to women planning to deliver at home. isdeliveries) distributed drug the when by community misoprostol consistently and safely (evenfor twin Nepal, post-abortion care programs. for treatment of incomplete abortion and in miscarriage programs and are including also of use the misoprostol up of use the misoprostol innational safe motherhood deliveries. Some countries are now steps taking to scale that misoprostol safely is used and correctly at home and through community workers health is effective and have shown that distribution at antenatal-care checks Zambia, Bangladesh, Uganda, Nigeria, and Senegal preferable. conventional low methods, oral misoprostol dose is misoprostol vaginal while is more effectivethan other

For more information on misoprostol for Caucus the on induced abortion, see New please medical and Underused RHTechnologies brief on Medical Abortion. 16 and Bangladesh 12 In WHO 2011,the recommended use the ‡ : Effectiveness of misoprostol- 17 14 show that women can use 10 18 11 Mozambique, similarly, 13 15

manufacturers of misoprostol. are to support underway applications from generic Prequalification of Medicines Programme,20 and efforts 2010, misoprostol eligible became for WHO’s the are few manufacturers of 25mg the tablet. As of May mostthe widely available misoprostol product. There markets.local Cytotec® (manufactured by Pfizer) is countries, but many only make products for their products for to low- export and middle-income Russia.19 Some of manufacturers these are making Argentina, Mexico, United the States, France, and Brazil, Peru, China, Egypt, South Korea, Chile, http://www.vsinnovations.org/resources.html. statusglobal of misoprostol registration found can be at safe motherhood programs. More information on the ofwillingness governments to integrate misoprostol into onusually depend level the of commitment and indications for is granted drug the which approval are registered for multiple obstetric indications. The PPH prevention and treatment, inothers while they in some countries, products are only registered for grows. The approved indications across countries; vary coming inthe yearsexpected as interest inmisoprostol Tanzania, Uganda, and Zambia. More registrations are Myanmar, Nepal, Pakistan, Sudan, Senegal, Somaliland, India, Ethiopia, Kenya, Malawi, Mali, Mozambique, more than 15countries, including Bangladesh, Bolivia, Products are registered for obstetric indications in there are likely others. to be Square Pharmaceuticals, and Zizhu Pharmaceutical, and Acme Formulations, Cipla, Sigma Pharmaceuticals, have registered products for obstetric indications include misoprostol for manufacturers Exporting export. that indications. Alimited number of manufacturers make Misoprostol is increasingly registered being for obstetric forused off-label indications. previously, inmany countries misoprostol may legally be countries but only for two indications. these As noted ulcers; Cytotec®,gastric is registered inmore than 80 commonly registered for prevention and treatment of indications at For all. example, misoprostol is most inmanywhile countries it is not registered for these registered for some of its many obstetric indications, registration status of misoprostol varies. It is often only indications for application the which was made. The bycountry apharmaceutical distributor for medical the from manufacturer aspecific be marketedto that in regulatorydrug agency, grants permission for aproduct Registration, or market approval of by adrug acountry’s status Registration CAUCUS ON NEW AND UNDERUSED REPRODUCTIVE HEALTH TECHNOLOGIES PRODUCT BRIEF or its wider membership. For additional information, please contact [email protected]. Responsibility for theselectionand contents of the product briefs rests solely with theCaucus and does not imply endorsement by theCoalition the discussion within theCoalition of reproductive health technologies that are not well integrated into thepublic orcommercial health sectors. Technologies, athematic group established under theauspices of theReproductive Health Technologies Coalition. The Caucus’ aimis to broaden This publication forms partof aseries of technical briefs, written by members of the Caucus 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 1. References market approval. negotiate price the with distributor the that holds the product that is registered and country intheir can misoprostol. Governments can purchase amisoprostol There are global public-sectorno agreementsprice for Public-sector price agreements 8. 7. 6. 5. 4. 3. 2.

217–23. randomised, non-inferiority Lancet. trial. in women receiving prophylactic oxytocin: adouble-blind, haemorrhage with sublingual misoprostol versus oxytocin Blum J, WinikoffRaghavan B, al. S,et Treatment post-partumof 16,2011. December http://whqlibdoc.who.int/hq/2011/a95053_eng.pdf. Accessed World Health Organization, 2000.Available Geneva. online at WHO Model List of Medicines Essential List (March 17th 2011). hq/2000/WHO_RHR_00.7.pdf. Accessed 16,2011. December 2000.AvailableGeneva. online at http://whqlibdoc.who.int/ and doctors, 2000reprinted in2007.World Health Organization, complications inpregnancy and childbirth: aguidefor midwives Integrated Management of Pregnancy and Managing Childbirth. randomised placebo-controlled BJOG trial. postpartum haemorrhage inhomebirths inPakistan: a misoprostol by trained traditional attendants birth to prevent Mobeen N,Durocher J, N,etal. Administration Zuberi of 2006;368:1248–53. communities:poor arandomised controlled Lancet. trial. in preventing postpartum haemorrhage inresource- Derman RJ, Kodkany BS,Goudar misoprostol SS,etal. Oral stage of labour. Lancet ofrandomised misoprostol trial management inthe of third the Gülmezoglu AM,Villar J, Ngoc NT, etal. WHO multicentre guidelines. Accessed 16,2011. December online at http://www.figo.org/news/misoprostol-safe-dosage- and (FIGO).Gynecology Obstetrics November 2009.Available Misoprostol Safe Dosage Guidelines. International Federation of 375(9710):210–6. double-blind, randomised, non-inferiority Lancet. trial. oxytocin inwomen to oxytocin not a during exposed labour: partum haemorrhage with sublingual misoprostol versus Winikoff DurocherR, Dabash B, al.D, et Treatment post- of , 2001;358(9283):689-95. 2010;375(9710): 2011;118(3):353–61. 2010;

17. 16. 15. 14. 13. 12. 11. 10. 9. 20. 19. 18.

Action 2011;4:7017. Bangladesh: howbirths inrural effective is it? Global Health misoprostol for preventing postpartum haemorrhage inhome Nasreen HE,Nahar S,Mamun M,Afsana K,Byass P. Oral 282–8. International Journal of Gynecology and Obstetrics. 2010;108: distribution of misoprostol: Operations research inNepal. protection following childbirth thought community-based Rajbhandari S,Hodgins S,Sanghvi H,etal. Expanding uterotonic 2010; 108:276–81. Afghanistan. International Journal of Gynecology and Obstetrics. J. Prevention of postpartum hemorrhage at home in birth Sanghvi H,Ansari N,Prata JVN,Gibson H,Ehsan A,Smith use. BJOG label drug Weeks AD, C,Safar Fiala P. Misoprostol and debate the over off- Accessed 16,2011. December whqlibdoc.who.int/publications/2011/9789241501156_eng.pdf. World Health Organization, 2000.Available Geneva. at http:// WHO Recommendations for Induction of Labour, 2011. Rev ripening and induction ofcervical labour. Cochrane Database Syst Hofmeyr GJ, Gülmezoglu C.Vaginal AM,Pileggi misoprostol for Cochrane Database Syst. 2006Apr Rev 19;(2):CD001338. Z, Alfirevic misoprostol A.Oral Weeks for induction labour.of Gynecology &Obstetrics, 2007;99Suppl 2:S172–7. up to 12completed weeks of pregnancy. International Journal of Faundes A,etal. Misoprostol for termination the of pregnancy prioritymedicines/en/. Accessed 19,2011. December Organization, Available Geneva. at www.who.int/childmedicines/ Priority Medicines for Mothers and Children. World Health Accessed 16,2011. December Programme managed by WHO. http://apps.who.int/prequal. Prequalification of Medicines Programme. A United Nations 2009;105,180–186. I Misoprostol. Fernandez MM,etal. Assessing Availability Global the of 2005; 90:51–5. Tanzania. International Journal of Gynecology &Obstetrics. Controlling postpartum hemorrhage after home in births Prata N,Mbaruku G,Campbell M,Potts M,Vahidnia F. . 2010 Oct 6;(10) . 2010Oct nternational Journal of Gynecology and Obstetrics. . 2005Mar;112(3):269–72. This brief was last updated March 2012.

PRODUCT BRIEF Caucus on New and Underused Reproductive Health Technologies

Oxytocin brief

Description can save mothers’ lives during difficult pregnancies and childbirth.9 Oxytocin is a peptide hormone best known for its roles The standard dose of oxytocin for preventing PPH is ten in childbirth and breastfeeding. It is released in large international units (IU) administered intramuscularly amounts from the body’s pituitary gland during labor, within a few minutes after birth. If a woman is causing contractions of the uterus to facilitate birth. experiencing heavy bleeding after delivery and the initial It also stimulates contractions during the third stage intramuscular dose of oxytocin, the WHO recommends of labor—separation of the placenta from the uterine an intravenous (IV) line be inserted and the woman wall and compression of maternal blood vessels after given 20- to 40-IU oxytocin in one liter of IV fluid at delivery of the placenta.1 When uterine contractions 60 drops per minute, and that oxytocin infusion be are not strong enough to compress blood vessels, continued at 20 IU in one liter of IV fluid at 40 drops postpartum hemorrhage (PPH) can threaten a woman’s per minute until hemorrhage stops.10 Oxytocin is life. In this situation, a woman will be given a uterotonic most commonly available in either 5- or 10-IU glass medicine, such as oxytocin or ergometrine, to stimulate ampoules. contractions and stop the bleeding.* Obstetric hemorrhage is estimated to cause 25 percent of all maternal deaths and is the leading direct cause Efficacy of maternal mortality worldwide.2 In Africa and Asia, WHO has determined that, as a package, AMTSL can nearly a third of pregnancy-related deaths are associated reduce PPH by as much as 60 percent.11 WHO also with PPH.3,4 The World Health Organization (WHO)5 reviewed the available evidence for using oxytocics and other international bodies6 recommend active for treatment of PPH, and while both oxytocin and management of the third stage of labor (AMTSL) to ergometrine were similarly effective, ergometrine is prevent severe bleeding after childbirth. This includes associated with more adverse effects, especially vomiting administration of a uterotonic soon after birth of and high blood pressure.11 the baby, delayed cord clamping, and delivery of the placenta by controlled cord traction and uterine massage.5 Current program/sector use According to the WHO, oxytocin is the preferred drug Oxytocin is used worldwide for several indications. As for prevention and initial treatment of PPH because it noted above, it is the WHO preferred uterotonic for is effective in two to three minutes after injection, can prevention and treatment of PPH and it is also used to be used in all women, and is more stable in storage induce and augment labor. In some developed countries than ergometrine.7 WHO, with the Partnership for it is used to initiate or increase breast milk production. Maternal, Newborn, and Child Health, lists oxytocin as a first-line drug for induction of labor, AMTSL, and In developing countries, oxytocin is commonly used in the prevention and management of PPH.8 The United clinical environments where a skilled birth attendant Nations Population Fund (UNFPA) and its partners have and refrigeration are available. However, utilization identified oxytocin as one of four priority medicines that of oxytocin for the indications noted previously is not universal and other drugs are also being used for

* If oxytocin or ergometrine are unavailable, or bleeding continues despite the administration of one of these drugs, the WHO recommends women be given a prostaglandin such as misprostol. Please see the Caucus product brief on Misoprostol for more information. CAUCUS ON NEW AND UNDERUSED REPRODUCTIVE HEALTH TECHNOLOGIES PRODUCT BRIEF facilities by providers used skilled has successfully been inhealth in Uniject), apre-filled, injection single-dose system, Oxytocin Uniject™** inthe injection system (oxytocin storage requirements for various the drugs. guidelines; and differencesthe in availability, cost, and corresponding differences incountry-level protocols and including changes inrecommendations over time; routes, powder suchinhalation. as dry make oxytocin to easier deliver through non-parenteral others. of Midwives, and pharmaceutical companies, among made up of WHO, the International the Confederation to heat the stability of oxytocin, including aconsortium organizations are investigating potential improvements attendants birth skilled and refrigeration. Anumber of for developing-country settings with limited access to making it more heat stable and to easier use, particularly Work to is increase underway access to oxytocin by Ghana, Vietnam, India, and Senegal, Mali. community-level deliveries is currently in underway Uniject for prevention the of PPH during home- and ** confusion about proper storage practices. oxytocin from various manufacturers, canto which lead inconsistency storage labeled inthe conditions for storage labeled the conditions. There widespreadis (2°–8°C) inorder to ensure quality and comply with room temperature (25°Cor less) or refrigerated storage oxytocin products should stored be at either controlled manufacturerthe and regulatory agency specification, Uniject™, is aheat-sensitive product. upon Depending ampoules or aprefilled injectionsuch device as As noted above, oxytocin, packaged whether in manufacturing oxytocin inUniject. (BIOL) (Argentina) and Gland Pharma (India), are Two manufacturers, Instituto Biologio Argentino Bangladesh,China, Argentina, Pakistan, and Indonesia. pharmaceutical manufacturing sector, including India, countriesalmost all that have an active sterileinjectables There are multiple generic manufacturers of in oxytocin some countries and other producers inother countries. Novartis; and Pitocin©, is which marketed by Pfizer in broadly Syntocinon©, recognized: is which marketed by around world. the Two oxytocin brand names are protection, and it is widely produced and distributed Oxytocin no is agenericlonger drug subject to patent Manufacturer/supplier or treatment of PPH. induction and augmentation of labor, and for prevention

Uniject is atrademark of BD. 18 Some of organizations these are to seeking also 13-17 and research on of use the oxytocin in 12 This is due to avariety of reasons, Guide for prices in2010, According to International the Price Indicator Drug Public-sector price agreements it is not actively marketing product the at time. this registered oxytocin inUniject for inIndia sale although product are under way inArgentina. Gland Pharma has Uruguay by BIOL. Modest commercial of sales the Guatemala, Honduras, Nicaragua, Paraguay, and commercial inArgentina, sale Ecuador, Bolivia, Oxytocin inUniject is currently registered for registered oxytocin product. brief; however, countries almost all have one or more registrationscountry is of beyond scope the this listing of manufacturers all and corresponding their manufacturers producing oxytocin globally, acomplete as well as induction of labor. to large Due the number of indications including prevention and treatment of PPH, Oxytocin is often registered for multiple obstetric status Registration 6. 5. 4. 3. 2. 1. References for oxytocin and oxytocin inUniject. Efforts aresecure WHO to underway prequalification holds market the approval. and can negotiate price the with distributor the that oxytocin products that are registered country intheir agreements for oxytocin. Governments can purchase There are knownno global public-sector price US$0.24, but cost the as canlow be as US$0.03. governments purchasing from agencies such is as these 10-IUampoule.is US$0.18per The median cost for for-profit organizationsthat sell to charitablegroups) of oxytocin nonprofits (both such as UNFPA and

Gynaecologists and Obstetricians; 2003. Confederation of Midwives &International Federation of of labour to prevent post-partum haemorrhage. International ICM and FIGO. Joint statement: Management of the third stage World Health Organization; 2007. prevention of postpartum haemorrhage Switzerland:. Geneva, World Health Organization. WHO recommendations for the WA: PATH; 2006. principles for their inclusion on national medicines lists . Seattle, Fund. Essential Medicines for Reproductive Health: Guiding PATH, World Health Organization, United Nations Population inferiority Lancet trial. controlled cord arandomised, traction: controlled, non- management of third the stage of labour with and without Gulmezoglu AM,Lumbiganon P, Landoulsi S,etal. Active Lancet WHO analysis of causes of maternal death: asystematic review. Khan KS,Wojdyla D, Say L,Gulmezoglu AM,Van PF. Look postpartum hemorrhage. Seattle, WA: PATH; 2008. POPPHI. Uterotonic drugs for the prevention and treatment of . 2006;367(9516):1066–1074. . 2012;In press. 19 the median the cost to procurers CAUCUS ON NEW AND UNDERUSED REPRODUCTIVE HEALTH TECHNOLOGIES PRODUCT BRIEF or its wider membership. For additional information, please contact [email protected]. Responsibility for theselectionand contents of the product briefs rests solely with theCaucus and does not imply endorsement by theCoalition the discussion within theCoalition of reproductive health technologies that are not well integrated into thepublic orcommercial health sectors. Technologies, athematic group established under theauspices of theReproductive Health Technologies Coalition. The Caucus’ aimis to broaden This publication forms partof aseries of technical briefs, written by members of the Caucus 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 11. 10. 9. 8. 7. 13. 12.

in Indonesia. Int Obstet Gynaecol J prefilled injectionUniject for devices managingthird-stage labor Tsu VD, Sutanto A,Vaidya K,Coffey P, Widjaya A. in Oxytocin Group Meeting, Presented at: The Oxytocin Initiative’s India Technical Advisory of DeliveriesObservation Study inKarnataka and Uttar Pradesh. Stanton C.The Oxytocin Initiative’s LandscapeReview India Organization; 2009. and retained haemorrhage placenta postpartum of World Health Organization. WHO guidelines for the management Switzerland: World Health Organization; 2006. and newborn care: aguide for essential practice . Geneva, World Health Organization. Pregnancy, childbirth, postpartum supplies/pid/3586. Accessed March 8,2012. Available at: http://www.unfpa.org/public/cache/offonce/home/ UNFPA. What are essential reproductive supplies? health 2012. PMNCH; 2011. Newborn and Child Health Switzerland: (RMNCH). Geneva, of theReview Key Interventions Related to Reproductive, Maternal, The Partnership for Maternal, Child & Global A Health. Newborn Health Organization; 2006. haemorrhage by active management of third stage of labour . World World Health Organization. Prevention of postpartum . 2003;83(1):103–111. . World Health 19. 18. 17. 16. 15. 14.

Cambridge, MA:Management for Sciences Health, Inc.; 2011. Indicator Guide JE,Editor.Frye Price Drug International March 14,2012. private-partnership-development-heat-stable-oxytocin. Accessed Available at: http://www.mdg5-meshwork.org/content/public- partnership for development the of heat-stable oxytocin. 2010. MeshworkMDG5 for Improving Maternal Health. Public private delivery technology inAMTSL Mali: evaluation of the safety and feasibility of anew PATH. POPPHI. Pilot of use oxytocin in aUnijectTM for device 2011;114(2):184–189. thirdthe stage of labor Int America. inLatin Obstet Gynaecol J ofincrease use the prophylactic oxytocin for management of Althabe F, Mazzoni A,Cafferataal. ML,et Using Uniject to Institutional Level in Guatemala. PATH; 2012. Active Management of theThird Stage Laborof (AMTSL) at the PATH. Pilot Introduction of Oxytocin in Uniject® During 2006;32(5):489–496. management of third-stage labor. Res Gynaecol Obstet J hemorrhage inVietnam: assessing effectiveness the of active Tsu VD, Mai TT, Nguyen YH,Luu HT. Reducing postpartum . Seattle, WA: PATH; 2008. This brief was last updated March 2012.

. . . PRODUCT BRIEF Caucus on New and Underused Reproductive Health Technologies

Progesterone

Description Efficacy

The progesterone vaginal ring Progering® is used to Clinical trials have shown a high contraceptive efficacy extend the contraceptive effectiveness of lactational (over 98.5 percent) and a good safety profile. There amenorrhea among breastfeeding women. Progesterone have been some sideeffect reports of vaginal discharge, vaginal rings are inserted in the vagina for continuous urinary discomfort, bleeding disturbances, and rare use for up to three months and replaced with a new ring reproductive tract infections. In a Chilean study, less if breastfeeding is continued and extended contraception than 5 percent of users experienced any one of these side is desired. Women can use these rings continuously for effects.3 up to one year. Although not recommended, the ring The effectiveness of the progesterone ring during the may be removed during sexual intercourse for a period recommended three months of use has been shown of up to two hours. If the ring is removed for a longer to be comparable to that of the Copper T-380A period of time, an additional contraceptive method . While progesterone rings are less should be used for the following seven days. Upon effective overall than rings containing both a progestin weaning of the breastfeeding infant, progesterone rings and an , they are highly effective among should be replaced with another effective method if breastfeeding women because exclusive breastfeeding continued contraception is desired.1 itself provides some protection from pregnancy. Also, The progesterone vaginal ring functions by diffusing a they are more appropriate for use by breastfeeding continuous flow of progesterone through the vaginal women because they do not contain estrogen, which walls—approximately 10mg per day—which then enters can reduce milk production. The most common reason the bloodstream and regulates the woman’s fertility by for discontinuation of progesterone rings is weaning, as suppressing ovulation. Progesterone also thickens the mothers choose more effective contraception after they cervical mucus, inhibiting sperm penetration into the reduce breastfeeding episodes. Bleeding disturbances, a uterus. common side effect of all progesterone-only methods, is another frequent reason for discontinuation.3 The Progesterone vaginal rings have a noteworthy progesterone ring does not provide protection from presence in today’s contraceptive method mix, sexually transmitted infections, including HIV. especially as a contraceptive choice for breastfeeding women. Acceptability studies conducted with other contraceptive rings in Australia, Canada, Chile, the Current program/sector use Dominican Republic, the United States, and Europe have demonstrated that women generally like the vaginal ring The product Progering® is sold commercially in six for many reasons, including its effectiveness; its ease of countries in Latin America through gynaecologists. use, including insertion and removal; the user control of There is limited data on commercial sales in these these actions; and the lack of need to check it regularly.2 countries and available information suggests that market penetration is weak. CAUCUS ON NEW AND UNDERUSED REPRODUCTIVE HEALTH TECHNOLOGIES PRODUCT BRIEF or its wider membership. For additional information, please contact [email protected]. Responsibility for theselectionand contents of the product briefs rests solely with theCaucus and does not imply endorsement by theCoalition the discussion within theCoalition of reproductive health technologies that are not well-integrated into the public orcommercial health sectors. Technologies, athematic group established under theauspices of theReproductive Health Technologies Coalition. The Caucus’ aimis to broaden This publication forms partof aseries of technical briefs, written by members of the Caucus 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 including Ecuador, Chile, Bolivia, Guatemala, Honduras, launched in2010other countries America inLatin for by use breastfeeding women. It was approved and Progering® was registered and inChile Peru in1998 Registration status Laboratorios Andromaco. Andromaco The SAinChile. product is supplied by contraceptive and use is manufactured by Laboratorios ringvaginal currently available for America inLatin Progering® is brand the name of progesterone the Manufacturer Saharan prior Africa to introduction markets. inthese conductedstudies be will inthree countries insub- by Controller Drug the of India. Further acceptability registration and commercialization there once approved conducted on product this inIndia, inanticipation of its research andFurther social are trials clinical being also 3. 2. 1. References None. Public-sector price agreements its development. private companies SAand Silesia Andromaco SAfunded and Peru. The PopulationCouncil,CONRAD, theand

1999;60(1):9–14. nursing ringvaginal inChilean women. Contraception safetythe and contraceptive ofa efficacy progesterone Massai Miranda R, P, Valdes P, etal. Preregistration study on www.infoforhealth.org/pr/m19/. ofSchool Public Health, INFOProject; April 2005.Available at: M,No.Series 19.Baltimore: The Johns Hopkins Bloomberg Upadhyay UD. New contraceptive choices. Population Reports, 428–434. contraceptive during use lactation. Contraception. Nath A,Sitruk-Ware Progesterone R. ring vaginal for This brief was last updated 2012. January 2010;82(5): ‑ . releasing