The Nation’s Best-Kept Secret: Strategies for Promoting Emergency Contraception

What if ?

A condom broke or slipped off, you had sex when you didn’t expect to, you didn’t use any birth control that weekend, you missed several pills, your diaphragm or cap slipped out of place, you were forced to have sex . . .

Emergency Contraceptives

Regular contraceptives used in a different way

Prevent pregnancy after intercourse

Inhibit ovulation, fertilization, or implantation

Do not cause abortion

Emergency Contraceptives (cont)

Will not interrupt or harm an established pregnancy

Are not the same as mifepristone

Do not protect against sexually transmitted infections (STIs)

Definition of Pregnancy

NIH/FDA

“Pregnancy encompasses the period of time from confirmation of implantation until expulsion or extraction of the fetus.”

ACOG

“Pregnancy is the state of a female after conception and until termination of the gestation.”

“Conception is the implantation of the blastocyst. It is not synonymous with fertilization; synonym: implantation.”

Emergency Contraception: History

1500 B.C.

Sneezing, hopping, jumping, and dancing

Douching with various herbs and roots

Late 1960s

Postcoital douching with Coca-ColaÔ

Emergency Contraception: History

1960s-70s: Diethylstilbesterol (DES)

No longer used because of teratogenicity

1974: Yuzpe [pilot study]

100 mg ethinyl estradiol (EE) with 1.0 mg dl-norgestrel; as effective as DES

1977: Yuzpe modified (original dose given twice, 12 hours apart)

1984: Yuzpe available in Europe

Emergency Contraception: History

1997: US FDA declares certain OCs safe and effective for EC

1998: FDA approves PREVENÔ (Yuzpe)

1998: Large WHO trial reports favorable safety/efficacy data for levonorgestrel EC

1999: FDA approves Plan BÔ (levonorgestrel)

2004: FDA rejects scientific panel recommendation to change Plan B status over-the-counter

Women Obtaining Abortions Who Reported Contraceptive Use, by Year

Emergency Contraception: Indications

Intercourse within past 72 hours without contraceptive protection (independent of time in the menstrual cycle)

Contraceptive mishap

Barrier method dislodgment/breakage

Expulsion of IUD

Missed oral contraceptive pills

Sexual assault

Exposure to teratogens (eg, cytotoxic drug)

Emergency Options in the
United States

Oral contraceptive pills containing estrogen and progestin

Oral contraceptive pills containing only progestin

Emergency Copper-T IUD insertion

Conflicting Contraindications: Combined ECPs

World Health Organization

Confirmed pregnancy

Faculty of FP and RH Care (United Kingdom)

Confirmed pregnancy

Migraine at presentation (if Hx of focal migraine)

Past Hx of thromboembolism (relative contraindication)

Planned Parenthood Federation of America

Suspicion or evidence of established pregnancy

Conflicting Contraindications: Combined ECPs

Preven^®

Known or suspected pregnancy

Pulmonary embolism (current or history)

Ischemic heart disease (current or history)

History of cerebrovascular accidents

Valvular heart disease with complications

Severe hypertension

Diabetes with vascular involvement

Headaches with focal neurological symptoms

Conflicting Contraindications: Combined ECPs

Preven (continued)

Major surgery with prolonged immobilization

Known or suspected carcinoma of the breast or personal history of breast cancer

Liver tumors (benign and malignant) active liver disease

Heavy smoking (>15 cigarettes per day) and over the age of 35

Known hypersensitivity to any component of this product.

Contraindications:
Progestin-only ECPs

Plan B®

Known or suspected pregnancy

Hypersensitivity to any component of the product

Undiagnosed abnormal genital bleeding

Emergency Contraceptive Pills: Combined

Ordinary birth control pills

Contain estrogen and progestin

2 doses of 2 Preven tablets or, for other

OCs 2, 4, or 5 pills, depending on brand

First dose within 72 hours after intercourse

Second dose 12 hours later

Side effects: nausea (50%) and vomiting (20%)

Emergency Contraceptive Pills: Progestin-only

Birth control pills containing only progestin

2 doses of 1 Plan B tablet or 20 Ovrette tablets

First dose within 72 hours after intercourse

Second dose 12 hours later

More effective than combined ECPs

Less nausea and vomiting than with combined ECPs

Copper IUD Insertion

Copper-T IUD (ParaGard)

Insertion within 5 days after ovulation (but most protocols state within 5 days after unprotected intercourse)

10 more years of highly effective contraception

Much more effective than ECPs

Not recommended for women at risk of sexually transmitted infections (STIs)

Effectiveness

How Long After the Morning After?
Meta-Analysis of 9 Yuzpe Trials

How Long After the Morning After?
WHO Pooled Data (Yuzpe and LNg)

How Long After the Morning After?
Quebec (Yuzpe)

How Long After the Morning After?
Population Council (Yuzpe)

How Long After the Morning After?
Latest WHO Trial (LNg)

Yuzpe Regimen: PREVENÔ

Yuzpe Regimen: OC Formulations

Yuzpe Regimen: Efficacy

1999 – Trussell J, et al, meta-analysis of 8 studies, including a large international WHO trial

Yuzpe results in an approximate 75% reduction (range 63%-79%) in the number of pregnancies estimated to occur without treatment

Yuzpe Regimen: Side Effects

Side effects

Nausea (50%)

Vomiting (20%)

Heavy menses/Breast tenderness

Use of antiemetic 1 hour before first dose decreases nausea and vomiting

Menses occurs within 3 weeks of therapy in up to 98% of women

No evidence of teratogenicity (based on combined OC data)

Yuzpe Regimen: Contraindications

FDA, WHO, ACOG – Known pregnancy

FDA – Relative (based on OC labeling, but no data available)

Clotting problems, venous thromboembolism, ischemic heart disease, stroke, migraine, liver tumors, breast cancer, breast biopsies

Plan B: Progestin-Only Emergency Contraception

First Dose: Take one tablet within 72 hours of unprotected intercourse

Second Dose: Take remaining tablet 12 hours after first dose

Plan B: Progestin-Only EC

Levonorgestrel 0.75 mg taken twice, 12 hours apart (traditional, two-dose administration)

Unlabeled equivalent

20 pills/dose of Ovrette taken 12 hours apart

More effective/fewer side effects than Yuzpe

Data indicate a single dose of 1.5 mg levonorgestrel is as effective and causes similar side effects as traditional two-dose levonorgestrel

Mechanism of action is inhibition of ovulation

Proportion of Pregnancies Prevented by Levonorgestrel vs. Yupze Regimen*

Proportion of Pregnancies Prevented by Levonorgestrel vs. Yupze, by Timing of Treatment

Levonorgestrel and Yuzpe Regimens: Delay of Treatment and Pregnancy Rates

Levonorgestrel vs. Yuzpe:
Side Effects

Single vs. Two-Dose Levonorgestrel vs. Mifepristone: Efficacy*

Single vs. Two-Dose Levonorgestrel: Side Effects

Copper IUD for EC

Second-line method

Estimated failure rate £0.1% (based on 8,400 postcoital insertions)

Mechanism(s) of action

Impairs fertilization

Alters sperm motility and integrity

Impairs implantation

Copper IUD for EC

Indications for emergency contraception

Unprotected intercourse

Need/desire for long-term contraception

Woman at low risk of STDs

May be inserted up to 5 days after the earliest estimated day of ovulation

Contraindications

Sexual assault, multiple sexual partners, uterine abnormality that prevents proper insertion

Mifepristone (RU 486)

Synthetic steroid that prevents progesterone from binding to progesterone and glucocorticoid receptors

Mechanism(s) of action

Disrupts follicular maturation and endocrine function of the granulosa cell

Disrupts midcycle LH surge

Interrupts hormonal support of the endometrium, making it asynchronous

Mifepristone: Efficacy

Glasier, et al, 1992

800 women and adolescents

Single 600 mg dose given within 72 hours of unprotected coitus was 100% effective

WHO 1999

1,700 women

10 mg and 50 mg mifepristone equal in efficacy to 600 mg dose (85% decrease in number of pregnancies estimated to occur without treatment)

Effective up to 5 days after unprotected sex

Mifepristone: Side Effects

Less nausea and vomiting than Yuzpe

Nausea: 40% vs. 60%

Vomiting: 3% vs. 17%

More delay of menses than Yuzpe

Delay menses >7 days: 42% vs. 13%

Nausea & vomiting similar to levonorgestrel

More delay menses >7 days: 9% vs. 0% [mifepristone vs. two-dose levonorgestrel]

Mifepristone vs. Yuzpe*: Side Effects

Delay of Menses* by Dose of Mifepristone for Emergency Contraception

Mifepristone: Prescribing for EC

FDA approved as abortifacient October 2000

Can legally be prescribed off label as EC

Only available in the 200 mg dose (50 mg and 10 mg just as effective as 600 mg for EC with fewer side effects)

Limited prescriber availability (FDA prescriber agreement required)

Emergency Contraception:
Rx by Telephone

3 questions to ask:

Have you had unprotected sex or a problem with your birth control (such as condom breakage) during the last 3 days (rule out sexual assault)?

Did your last menstrual period begin less than 4 weeks ago?

Was the timing and duration of your last menstrual period normal?

If the patient responds “yes” to all 3 questions, a clinician may prescribe emergency contraception over the telephone

Patient Counseling for EC

How to take medication (give written instructions when possible)

Use of antiemetic (Rx or OTC) 1 hour prior to first dose of Yuzpe

Expected side effects (nausea/vomiting/cramping)

When to expect menses (up to 98% bleed within 21 days of EC)

If no menses after 3 weeks, rule out pregnancy

May discuss contraceptive needs, STD protection, follow-up if EC fails

Emergency Contraception: Barriers

Rx or Pharmacist dispensing creates delay

Woman must:

Identify the need for EC

Locate a prescriber

Call/visit prescriber

Find a pharmacy that stocks the product (discuss EC with pharmacist in pharmacy-access states)

Plan BÔ: Rx Data

20,000 Rxs/month for Plan B

5 Pharmacy-access states

Washington, California, Alaska, New Mexico, Hawaii

Washington: only 26% of pharmacies and 23% of pharmacists participate in the access program

California: only 14% of pharmacies participate

Albuquerque, NM: 89% of pharmacies did not carry Plan B; only 47% could access within 24 h

Pennsylvania: only 35% of pharmacies could get Plan B or PREVEN within 24 h

Advance Provision of EC

Glasier and Baird 1998

553 given advance supply of EC pills

187 (47%) used at least once; 98% correctly

18 unintended pregnancies

522 told to obtain EC pills when needed by visiting a physician

87 (27%) used at least once

25 unintended pregnancies

Neither group experienced adverse events

No difference in use of other contraceptives

Advance Provision of EC: Teens

Gold, et al, 2004, prospective randomized trial at urban, hospital-based adolescent clinic

301 minority, low-income women age 15-20 years

Advance provision vs. instructions on how to get EC

At 1 month, the advance Rx group reported nearly twice as much EC use as control group (15% vs. 8%, p=0.05)

Advance EC group began EC significantly sooner (11.4 h vs. 21.8 h, p=0.005)

No detrimental effects on condom or hormonal contraceptive use/no increase in unprotected intercourse

FDA Rejects Plan B OTC

Reproductive Drugs and OTC Advisory Committees met Dec 16, 2003

Voted “Yes” to place Plan B OTC (23 to 4)

Plan B is safe, effective, and easy to use

FDA sent manufacturer a Non-Approvable Letter in May 2004

ACOG and other organizations express dismay at the FDA’s decision, suggesting political agenda

The Setting

3.0 million unintended pregnancies each year in the United States: half (48%) of all pregnancies

Half (48%) of women aged 15-44 have ever had an unintended pregnancy

Emergency contraception has the potential to reduce unintended pregnancy significantly

Emergency contraception is highly cost-effective

Potential Impact

Actual Impact

In 2000, 1.3% of women having abortions reported using ECPs to prevent that pregnancy.

35% of those using ECPs had used no method of contraception in the month they became pregnant; 65% used ECPs for backup contraception.

Up to 51,000 abortions were averted by use of ECPs in 2000

The Problem:
Why a 25-Year Delay ?

Companies did not market pills or IUDs for emergency contraception in the U.S.

Clinicians do not routinely counsel women (or men) about emergency contraception

Women (and men) do not know about emergency contraception

The Solution

Market EC

marketing promotes awareness

specifically packaged products are less confusing for users and providers, and may reduce chances of incorrect prescribing or use

Change provider practices

counsel women and men in advance

provide ECPs in advance

Educate women and men

Change from Rx to over/behind the counter

The Value of a Dedicated Product

Emergency Contraception in Europe

Slide 61

Slide 62

Slide 63

Slide 64

Slide 65

Slide 66

"OTC in Norway 10/00 and..."

OTC in Norway 10/00 and Sweden 11/01

Dispensed by school nurses in every junior and senior high school in France

And dispensed at no cost to minors by pharmacists

Emergency Contraception BTC

ECPs are available directly from pharmacists without having first to get a prescription from a clinician in:

Pharmacists Providing ECPs

Response to Enhanced Availability: Washington State

10,000 patient visits per year

42% of visits were during evenings, weekends, or holidays

95% of women had sufficient opportunity to ask questions

85% of women were satisfied with the on-going contraceptive counseling provided by pharmacists

Medicaid projects annual savings of up to $10 million

California Pharmacy Access Partnership

Effective January 1, 2002

Pharmacists can provide EC without a prescription

Collaborative agreements with local physicians

Minors can receive EC services in pharmacies

500+ pharmacies statewide by 12/31/2002

Based on Washington State Model (1998)

Planned Parenthood State Hotlines

Prescriptions are called in to the client’s pharmacy of choice

Connecticut: 1-800-230-PLAN

Georgia: 1-877-ECPills

Illinois: 1-866-222-EC4U

Maryland: 1-877-99-GO-4-EC

North Carolina: 1-866-942-7762

Planned Parenthood State Hotlines

Prescriptions are called in to the client’s pharmacy of choice

Georgia: www.ecconnection.org

Illinois: www.plannedparenthoodchicago.com

Indiana: www.ppin.org/ecaccess.com/ecinfo.html

Oregon: www.ppcw.org

Providing EC is Now the
Medico-Legal Standard of Care

ACOG Practice Pattern on ECPs (12/96) established the professional standard of care

FDA notice in Federal Register on ECPs (2/97) declared 6 (now 13) brands of regular OCs to be safe and effective for use for emergency contraception

FDA explicitly approved Preven and Plan B as dedicated products, but FDA still recognizes 13 brands of regular combined OCs to be safe and effective for use for emergency contraception

Provider Practice: Good News

Provider Practice: Bad News

The Clinical Bottleneck

Clinicians overwhelmingly think ECPs are safe and effective, and the majority have prescribed in the last year

Clinicians are waiting for women to ask for EC

The Clinical Bottleneck (cont)

But women do not know to ask

while 76% of women have heard of ECPs/morning-after pills

only 16% of women know 72-hour time frame

only 2% of women have ever used ECPs

Educate Women

Providers on the Hotline and Website

Public Education Campaign Messages

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Slide 86

Resources:
Emergency Contraception

Hotlines

1-888-NOT-2-Late or 800-584-9911

Web Sites

http://www.NOT-2-Late.org

(http://www.ec.princeton.edu/)

http://www.PREVEN.com

http://kaisernetwork.org

http://cecinfo/html/updates.htm (emergency contraception newsletters)

http://www.acog.org

Summary

Unintended pregnancy/induced abortion are major problems in the United States

Reliable and easy-to-use emergency contraceptive methods are available (Plan B, PREVEN)

The Alan Guttmacher Institute estimates that in 2000 EC prevented 50,000 induced abortions

Single dose levonorgestrel first-line method, followed by two-dose levonorgestrel, then Yuzpe

In May 2004, the FDA rejected its scientific advisory panel’s recommendation to switch Plan B to OTC

ACOG’s public education campaign, “Every Woman, Every Visit” will continue to urge Ob/Gyns to provide advance prescriptions for EC at every office visit

Sponsored by
Association of Reproductive Health Professionals

This presentation is made possible by an unrestricted educational grant from the

Open Society Institute

Medical Advisory Committee

Don Downing, RPh

Univ of Washington School of Pharmacy

Renton, WA

David A. Grimes, MD

Family Health International

Durham, NC

Edith Guilbert, MD

Family Planning Clinic and Public Health

Ste Foy, Quebec

Elizabeth Raymond, MD, MPH

Family Health International

Durham, NC

Sharon Schnare, FNP, CNM

Olalla, WA

Felicia Stewart, MD

Center for Reproductive Health Research & Policy, UCSF

San Francisco, CA

James Trussell, BPhil, PhD

Princeton University

Princeton, NJ


	A condom broke or slipped off, you had sex when you didn’t expect to, you didn’t use any birth control that weekend, you missed several pills, your diaphragm or cap slipped out of place, you were forced to have sex . . .


	Regular contraceptives used in a different way
	Prevent pregnancy after intercourse
	Inhibit ovulation, fertilization, or implantation
	Do not cause abortion


	Will not interrupt or harm an established pregnancy
	Are not the same as mifepristone
	Do not protect against sexually transmitted infections (STIs)


	NIH/FDA
		“Pregnancy encompasses the period of time from confirmation of implantation until expulsion or extraction of the fetus.”
	ACOG
		“Pregnancy is the state of a female after conception and until termination of the gestation.”
		“Conception is the implantation of the blastocyst. It is not synonymous with fertilization; synonym: implantation.”


	1500 B.C.
		Sneezing, hopping, jumping, and dancing
	Douching with various herbs and roots
	Late 1960s
		Postcoital douching with Coca-ColaÔ


	1960s-70s: Diethylstilbesterol (DES)
		No longer used because of teratogenicity
	1974: Yuzpe [pilot study]
		100 mg ethinyl estradiol (EE) with 1.0 mg dl-norgestrel; as effective as DES
	1977: Yuzpe modified (original dose given twice, 12 hours apart)
	1984: Yuzpe available in Europe


	1997: US FDA declares certain OCs safe and effective for EC
	1998: FDA approves PREVENÔ (Yuzpe)
	1998: Large WHO trial reports favorable safety/efficacy data for levonorgestrel EC
	1999: FDA approves Plan BÔ (levonorgestrel)
	2004: FDA rejects scientific panel recommendation to change Plan B status over-the-counter


	Intercourse within past 72 hours without contraceptive protection (independent of time in the menstrual cycle)
	Contraceptive mishap
		Barrier method dislodgment/breakage
		Expulsion of IUD
		Missed oral contraceptive pills
	Sexual assault
	Exposure to teratogens (eg, cytotoxic drug)


	Oral contraceptive pills containing estrogen and progestin
	Oral contraceptive pills containing only progestin
	Emergency Copper-T IUD insertion


	World Health Organization
		Confirmed pregnancy
	Faculty of FP and RH Care (United Kingdom)
		Confirmed pregnancy
		Migraine at presentation (if Hx of focal migraine)
		Past Hx of thromboembolism (relative contraindication)
	Planned Parenthood Federation of America
		Suspicion or evidence of established pregnancy


	Preven^®
		Known or suspected pregnancy
		Pulmonary embolism (current or history)
		Ischemic heart disease (current or history)
		History of cerebrovascular accidents
		Valvular heart disease with complications
		Severe hypertension
		Diabetes with vascular involvement
		Headaches with focal neurological symptoms


	Preven (continued)
		Major surgery with prolonged immobilization
		Known or suspected carcinoma of the breast or personal history of breast cancer
		Liver tumors (benign and malignant) active liver disease
		Heavy smoking (>15 cigarettes per day) and over the age of 35
		Known hypersensitivity to any component of this product.


	Plan B®
		Known or suspected pregnancy
		Hypersensitivity to any component of the product
		Undiagnosed abnormal genital bleeding


	Ordinary birth control pills
	Contain estrogen and progestin
	2 doses of 2 Preven tablets or, for other
	OCs 2, 4, or 5 pills, depending on brand
	First dose within 72 hours after intercourse
	Second dose 12 hours later
	Side effects: nausea (50%) and vomiting (20%)


	Birth control pills containing only progestin
	2 doses of 1 Plan B tablet or 20 Ovrette tablets
	First dose within 72 hours after intercourse
	Second dose 12 hours later
	More effective than combined ECPs
	Less nausea and vomiting than with combined ECPs


	Copper-T IUD (ParaGard)
	Insertion within 5 days after ovulation (but most protocols state within 5 days after unprotected intercourse)
	10 more years of highly effective contraception
	Much more effective than ECPs
	Not recommended for women at risk of sexually transmitted infections (STIs)


	1999 – Trussell J, et al, meta-analysis of 8 studies, including a large international WHO trial
	Yuzpe results in an approximate 75% reduction (range 63%-79%) in the number of pregnancies estimated to occur without treatment


	Side effects
		Nausea (50%)
		Vomiting (20%)
		Heavy menses/Breast tenderness
	Use of antiemetic 1 hour before first dose decreases nausea and vomiting
	Menses occurs within 3 weeks of therapy in up to 98% of women
	No evidence of teratogenicity (based on combined OC data)


	FDA, WHO, ACOG – Known pregnancy
	FDA – Relative (based on OC labeling, but no data available)
		Clotting problems, venous thromboembolism, ischemic heart disease, stroke, migraine, liver tumors, breast cancer, breast biopsies


	First Dose: Take one tablet within 72 hours of unprotected intercourse
	Second Dose: Take remaining tablet 12 hours after first dose


	Levonorgestrel 0.75 mg taken twice, 12 hours apart (traditional, two-dose administration)
	Unlabeled equivalent
		20 pills/dose of Ovrette taken 12 hours apart
	More effective/fewer side effects than Yuzpe
	Data indicate a single dose of 1.5 mg levonorgestrel is as effective and causes similar side effects as traditional two-dose levonorgestrel
	Mechanism of action is inhibition of ovulation


	Second-line method
	Estimated failure rate £0.1% (based on 8,400 postcoital insertions)
	Mechanism(s) of action
		Impairs fertilization
		Alters sperm motility and integrity
		Impairs implantation


	Indications for emergency contraception
		Unprotected intercourse
		Need/desire for long-term contraception
		Woman at low risk of STDs
		May be inserted up to 5 days after the earliest estimated day of ovulation
	Contraindications
		Sexual assault, multiple sexual partners, uterine abnormality that prevents proper insertion


	Synthetic steroid that prevents progesterone from binding to progesterone and glucocorticoid receptors
	Mechanism(s) of action
		Disrupts follicular maturation and endocrine function of the granulosa cell
		Disrupts midcycle LH surge
		Interrupts hormonal support of the endometrium, making it asynchronous


	Glasier, et al, 1992
		800 women and adolescents
		Single 600 mg dose given within 72 hours of unprotected coitus was 100% effective
	WHO 1999
		1,700 women
		10 mg and 50 mg mifepristone equal in efficacy to 600 mg dose (85% decrease in number of pregnancies estimated to occur without treatment)
		Effective up to 5 days after unprotected sex


	Less nausea and vomiting than Yuzpe
		Nausea: 40% vs. 60%
		Vomiting: 3% vs. 17%
	More delay of menses than Yuzpe
		Delay menses >7 days: 42% vs. 13%
	Nausea & vomiting similar to levonorgestrel
	More delay menses >7 days: 9% vs. 0% [mifepristone vs. two-dose levonorgestrel]


	FDA approved as abortifacient October 2000
	Can legally be prescribed off label as EC
	Only available in the 200 mg dose (50 mg and 10 mg just as effective as 600 mg for EC with fewer side effects)
	Limited prescriber availability (FDA prescriber agreement required)


	3 questions to ask:
		Have you had unprotected sex or a problem with your birth control (such as condom breakage) during the last 3 days (rule out sexual assault)?
		Did your last menstrual period begin less than 4 weeks ago?
		Was the timing and duration of your last menstrual period normal?
	If the patient responds “yes” to all 3 questions, a clinician may prescribe emergency contraception over the telephone


	How to take medication (give written instructions when possible)
	Use of antiemetic (Rx or OTC) 1 hour prior to first dose of Yuzpe
	Expected side effects (nausea/vomiting/cramping)
	When to expect menses (up to 98% bleed within 21 days of EC)
	If no menses after 3 weeks, rule out pregnancy
	May discuss contraceptive needs, STD protection, follow-up if EC fails


	Rx or Pharmacist dispensing creates delay
	Woman must:
		Identify the need for EC
		Locate a prescriber
		Call/visit prescriber
		Find a pharmacy that stocks the product (discuss EC with pharmacist in pharmacy-access states)