LABELING GUIDANCE TEXT FOR PROGESTIN-ONLY ORAL CONTRACEPTIVES*
PRESCRIBING INFORMATION
PROFESSIONAL LABELING
Revised May 1995
++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++
PROPRIETARY NAME (ESTABLISHED NAME)
Patients should be counseled that this product does not protect against
HIV infection (AIDS) and other sexually transmitted diseases.
DESCRIPTION [Supplied by manufacturer]
CLINICAL PHARMACOLOGY
1. MODE OF ACTION
[Brand Name] progestin-only oral contraceptives prevent conception by
suppressing ovulation in approximately half of users, thickening the
cervical mucus to inhibit sperm penetration, lowering the midcycle LH
and FSH peaks, slowing the movement of the ovum through the fallopian
tubes, and altering the endometrium.
2. PHARMACOKINETICS
Serum progestin levels peak about two hours after oral administration,
followed by rapid distribution and elimination. By 24 hours after drug
ingestion, serum levels are near baseline, making efficacy dependent
upon rigid adherence to the dosing schedule. There are large variations
in serum levels among individual users. Progestin-only administration
results in lower steady-state serum progestin levels and a shorter
elimination half-life than concomitant administration with estrogens.
INDICATIONS AND USAGE
1. Indications
Progestin-only oral contraceptives are indicated for the prevention of
pregnancy.
______________________________________________________________________
*This guidance is an informal communication representing the best judgment of the Division of Metabolism and Endocrine Drug
Products based on current information. It is not a formal issuance of the Center for Drug Evaluation and Research of the Food and
Drug Administration, and does not bind or otherwise obligate the Center to the views expressed.
1
2. Efficacy
If used perfectly, the first-year failure rate for progestin-only oral
contraceptives is O.5%. However, the typical failure rate is estimated
to be closer to 5%, due to late or omitted pills. The following table
lists the pregnancy rates for Users of all major methods of
contraception.
Comparison of reversible contraceptive methods: Percent of women
experiencing a contraceptive failure (pregnancy) during the first year
of use.
Percent of Women Experiencing a
Pregnancy within the
First Year of Use
Average Use Perfect Use
Method
No contraception 85 85
Spermicides 21 6
Periodic abstinence 20 1-91
Withdrawal 19 4
Cervical caps
Given birth 36 26
Never given birth 18 9
Diaphragms 18 6
Condoms
Female 21 5
Male 12 3
Pills
Progestin-only - 0.5
Combined - 0.1
IUDs
Progesterone 2 1.5
Copper T 380A 0.8 0.6
Injectables 0.3 0.3
Implant 0.09 0.09
____________________________________________________________________Adapted with permission2.
1. Depending on method (calendar, ovulation, sympto-thermal, post-ovulation).
2. Hatcher RA' Trussell J. Stewart F. Stewart OK, Kowal D, Guest F' Cates W. Policar M. Contraceptive
Technology
1594-1996.
New
York
NY:
Irvington
Publishers.
1994.
2
CONTRAINDICATIONS
Progestin-only oral contraceptives should not be used by women who
currently have the following conditions:
o Known or suspected pregnancy
o Known or suspected carcinoma of the breast
o Undiagnosed abnormal genital bleeding
WARNINGS
1. Ectopic Pregnancy
The incidence of ectopic pregnancies for progestin-only oral
contraceptive users is 5 per 1000 woman-years, which is higher than
for women using other contraceptive methods but similar to the
incidence for women not using any contraception. Up to 10% of
pregnancies reported in clinical studies of progestin-only oral
contraceptive users are extrauterine. Although symptoms of ectopic
pregnancy should be watched for, a history of ectopic pregnancy need
not be considered a contraindication to use of this contraceptive
method.
2. Delayed Follicular Atresia
If follicular development occurs, atresia of the follicle is
sometimes delayed, and the follicle may continue to grow beyond the
size it would attain in a normal cycle. Generally these enlarged
follicles disappear spontaneously. Often they are asymptomatic; in
some cases they are associated with mild abdominal pain. Rarely they
may twist or rupture, requiring surgical intervention.
3. Irregular Genital Bleeding
Irregular menstrual patterns are common among women using progestin-
only oral contraceptives. If genital bleeding is suggestive of
infection, malignancy or other abnormal conditions, such
nongharmacologic causes should be ruled out. If prolonged amenorrhea
occurs, the possibility of pregnancy should be evaluated.
4. Carcinoma of the Breast and Reproductive Organs
Several studies have demonstrated no elevated risk of breast cancer
among users of progestin-only oral contraceptives. However, women
with breast cancer should not use oral contraceptives because the
role of female hormones in breast cancer has not been fully
determined. Few data are available regarding any association of
progestin-only oral contraceptives with endometrial or ovarian
cancer but they do not indicate adverse effects.
3
PRECAUTIONS
1. General
Patients should be counseled that this product does not protect
against HIV infection (AIDS) and other sexually transmitted
diseases.
2. Physical Examination and Follow Up
It is considered good medical practice for sexually active women
using oral contraceptives to have annual history and physical
examinations. The physical examination may be deferred until after
initiation of oral contraceptives if requested by the woman and
judged appropriate by the clinician.
3. Carbohydrate and Lipid Metabolism
Some users may experience slight deterioration in glucose tolerance,
with increases in plasma insulin but women with diabetes mellitus
who use progestin-only oral contraceptives do not generally
experience changes in their insulin requirements.
Lipid metabolism is occasionally affected in that HDL, HDL2, and
apolipoprotein A-I and A-II may be decreased; hepatic lipase may be
increased. There is no effect on total cholesterol, HDL3, LDL, or
VLDL.
4. Drug Interactions
The effectiveness of progestin-only pills is reduced by hepatic
enzyme-inducing drugs such as the anticonvulsants phenytoin,
carbamazapine, and barbiturates, and the antituberculosis drug
rifampin. No significant interaction has been found with broad-
spectrum antibiotics.
5. Interactions with Laboratory Tests
The following endocrine tests may be affected by progestin-only oral
contraceptive use:
o Sex hormone-binding globulin (SHBG) concentrations may be decreased.
o Thyroxine concentrations may be decreased, due to a decrease in thyroid
binding globulin (TBG).
4
6. Carcinogenesis
See WARNINGS section.
7. Pregnancy
Many studies have found no effects on fetal development associated
with long-term use of contraceptive doses of oral progestins. The few
studies of infant growth and development that have been conducted
have not demonstrated significant adverse effects. It is nonetheless
prudent to rule out suspected pregnancy before initiating any
hormonal contraceptive use.
8. Nursing Mothers
No adverse effects have been found on breastfeeding performance or on
the health, growth or development of the infant. Small amounts of
progestin pass into the breast milk, resulting in steroid levels in
infant plasma of 1-6% of the levels of maternal plasma.
9. Fertility Following Discontinuation
The limited available data indicate a rapid return of normal
ovulation and no delay of return to fertility following
discontinuation of progestin-only oral contraceptives.
INFORMATION FOR THE PATIENT
1. See Patient Labeling for detailed information.
2. Counseling issues
The following points should be discussed with prospective users
before prescribing progestin-only oral contraceptives:
o The necessity of taking pills at the same time every day,
including throughout all bleeding episodes.
o The need to use a backup method such as condoms and
spermicides for the next 4a hours whenever a progestin-only
oral contraceptive is taken 3 or more hours late.
o The potential side effects of progestin-only oral
contraceptives, particularly menstrual irregularities.
o The need to inform the clinician of prolonged episodes of
bleeding, amenorrhea or severe abdominal pain.
o The importance of using a barrier method in addition to
progestin-only oral contraceptives if a woman is at risk of
contracting or transmitting STDs/HIV.
5
ADVERSE REACTIONS
o Menstrual irregularity is the most frequently reported side
effect.
o Frequent and irregular bleeding are common, while long
duration of bleeding episodes and amenorrhea are less
likely.
o Headache, breast tenderness, nausea, and dizziness are
increased among progestin-only oral contraceptive users in
some studies.
o Androgenic side effects such as acne, hirsutism, and weight
gain occur rarely.
OVERDOSAGE
There have been no reports of serious ill effects from overdosage,
including ingestion by children.
DOSAGE AND ADMINISTRATION
To achieve maximum contraceptive effectiveness, [BRAND NAME] must be
taken exactly as directed. One tablet is taken every day, at the same
time. Administration is continuous, with no interruption between pill
packs. See Patient Labeling for detailed instructions.
HOW SUPPLIED
[Manufacturer to supply information on available dosage forms, potency,
color, and packaging.]
STORAGE
[Manufacturer to supply information on pill storage.]
REFERENCE
McCann M, and Potter L. Progestin-Only Oral Contraceptives: A
Comprehensive Review. Contraception, 50:60 (Suppl. 1), December 1994.
DATE OF LATEST REVISION: May 1995
6
LABELING GUIDANCE TEXT FOR PROGESTIN-ONLY ORAL CONTRACEPTIVES
PATIENT PACKAGE INSERT
DETAILED INFORMATION FOR THE PATIENT
Revised May 1995
+++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++
PROPRIETARY NAME (ESTABLISHED NAME)
This product (like all oral contraceptives) is used to prevent
pregnancy. It does not protect against HIV infection (AIDS) or other
sexually transmitted diseases.
DESCRIPTION [Supplied by manufacturer]
INTRODUCTION
This leaflet is about birth control pills that contain one hormone, a
progestin. Please read this leaflet before you begin to take your
pills. It is meant to be used along with talking with your doctor or
clinic.
Progestin-only pills are often called "POPs" or "the minipill". POPs
have less progestin than the combined birth control pill (or "the
pill") which contains both an estrogen and a progestin.
HOW EFFECTIVE ARE POPS?
About 1 in 200 POPs users will get pregnant in the first year if they
all take POPs perfectly (that is, on time, every day). About 1 in 20
"typical" POPs users (including women who are late taking pills or miss
pills) gets pregnant in the first year of use. The following table will
help you compare the efficacy of different methods.
7
IUDs
Table
Comparison of reversible contraceptive methods:
Percent of women who become pregnant during the first year of use
Percent of Women Experiencing a
Pregnancy within the
First Year of Use
Method Average Use Perfect Use
No contraception 8s Us
Spermicides 21 6
Periodic abstinence 20 1-91
Withdrawal 19 4
Cervical caps
Given birth 36 26
Never given birth 18 9
Diaphragms 18 6
Condoms
Female 21 5
Male 12 3
Pills 3 -
POPs - 0.5
Combined pills - 0.1
IUDs
Progesterone 2 0.5
Copper T 380A 0.8 0.6
Injectables 0.3 0.3
Implants 0.09 0.09
_______________________________________________________________________
Adapted with permleslon2
1. Depending on method (calendar, ovulation, sympto-thermal, or post ovulation Method).
2. Hatcher RA, Trussell J. Stewart F. Stewart OK, Kowal D, Guest F. Cates W. Pollcar M. Contraceptive
Technology 1994-1996. New York NY: Irvington Publishers. 1994.
8
HOW DO POPS WORK?
o They make the cervical mucus at the entrance to the womb
the uterus)too thick for the sperm to get through to the
egg.
o They prevent ovulation (release of the egg from the ovary)
about half the time.
o They also affect other hormones, the fallopian tubes and the
lining of the uterus.
YOU SHOULD NOT TAKE POPS
o If there is any chance you may be pregnant.
o If you have breast cancer.
o If you have bleeding between your periods which has not
been diagnosed.
o If you are taking certain drugs for epilepsy (seizures) or
for TB. (See "Using POPs with Other Medicines" below)
SAFETY OF POPS
No studies have shown that POPs increase the risk of cancer or heart
disease.
RISKS OF TAKING POPS
WARNING
If you have sudden or severe pain in your lower abdomen or
stomach area, you may have an ectopic pregnancy or an ovarian
cyst. If this happens, you should contact your doctor or
clinic immediately.
Ectopic Pregnancy
An ectopic pregnancy is a pregnancy outside the womb. Because POPs
protect against pregnancy, the chance of having a pregnancy outside
the womb is very low. If you do get pregnant while taking POPs, you
have a slightly higher chance that the pregnancy will be ectopic than
do users of some other birth control methods.
Ovarian Cysts
These cysts are small sacs of fluid in the ovary. They are more
common among POP users than among users of most other birth control
methods. They usually disappear without treatment and rarely cause
problems.
9
SEXUALLY-TRANSMITTED DISEASES (STDS)
WARNING
POPs do not protect against getting or giving someone HIV
(AIDS)or any other STD, such as chlamydia, gonorrhea, genital
warts or herpes.
SIDE EFFECTS
Irregular Bleeding:
The most common side effect of POPS is a change in menstrual bleeding.
Your periods may be either early or late, and you may have some spotting
between periods. Taking pills late or missing pills can also result in
some spotting or bleeding.
Other Side Effects:
Less common side effects include headaches, tender breasts, nausea and
dizziness. Weight gain, acne and extra hair on your face and body have
been reported, but are rare.
If you are concerned about any of these side effects, check with your
doctor or clinic.
USING POPS WITH OTHER MEDICINES
If you are taking medicines for seizures (epilepsy) or tuberculosis
(TB), tell your doctor or clinic. These medicines can make POPs less
effective:
Medicines for seizures:
o Phenytoin (Dilantin)
o Carbamazopine (Tegretol)
o Phenobarbital
Medicine for TB:
o Rifampir1 (Rifampicin)
Before you begin taking any new medicines be sure your doctor or clinic
knows you are taking birth control pills that contain a progestin.
10
HOW TO TAKE POPS
---------------------------------------------------------------------
IMPORTANT POINTS TO REMEMBER
---------------------------------------------------------------------
o POPs must be taken at the same time every day, so choose a time
and then take the pill at that same time every day. Every time you
take a pill late, and especially if you miss a pill, you are more
likely to get pregnant.
o Start the next pack the day after the last pack is finished. There
is no break between packs. Always have your next pack of pills
ready.
o You may have some menstrual spotting between periods. Do not stop
taking your pills if this happens.
o If you vomit soon after taking a pill, use a backup method (such
as condom and/or spermicide) for 48 hours.
o If you want to stop taking POPs, you can do so at any time.
o If you are not sure about how to take POPs, ask your doctor or
clinic.
------------------------------------------------------------------------
STARTING POPS
------------------------------------------------------------------------
o It's best to take your first POP on the first day of your
menstrual period.
o If you decide to take your first POP on another day, use a backup
method (such as condom and/or spermicide) every time you have sex
during the next 48 hours.
o If you have had a miscarriage or an abortion, you can start POPs
the next day.
------------------------------------------------------------------------
IF YOU ARE LATE OR MISS TAKING YOUR POPS
------------------------------------------------------------------------
o If you are more than 3 hours late or you miss one or more POPs:
1) TAKE a missed pill as soon as you remember that you missed,
2) THEN go back to taking POPS at your regular time,
3) BUT be sure to use a back-up method (such as condom and/or
spermicide) every time you have sex for the next 48 hours.
o If you are not sure what to do about the pills you have missed,
keep taking POPs and use a back-up method until you can talk to
your doctor or clinic.
------------------------------------------------------------------------
IF YOU ARE BREASTFEEDING
------------------------------------------------------------------------
o If you are fully breastfeeding (not giving your baby any food or
formula), you may start your pills 6 weeks after delivery.
O If you are partially breastfeeding (giving your baby some food or
formula), you should start taking pills by 3 weeks after delivery.
11 ------------------------------------------------------------------------
IF YOU ARE SWITCHING PILLS
------------------------------------------------------------------------
o If you are switching from the combined pills to POPs, take the first
POP the day after you finish the last active combined pill. Do not
take any of the 7 inactive pills from the combined pill pack.
o If you are switching from POPs to the combined pills, take the first
active combined pill on the first day of your period, even if your
POPs pack is not finished.
o If you switch to another brand of POPs, start the new brand
anytime.
o If you are breastfeeding, you can switch to another method of
birth control at any time, except do not switch to the combined
pills until you stop breastfeeding or at least until 6 months
after delivery.
PREGNANCY WHILE ON THE PILL
If you become pregnant, or think you might be, stop taking POPs.
Even though research has shown that POPS do not cause harm to the unborn
baby, it is always best not to take any drugs or medicines that you
don't need when you are pregnant.
You should get a pregnancy test:
o If your period is late and you took one or more pills late or
missed taking them and had sex without a backup method.
o Anytime you miss 2 periods in a row.
WILL POPS AFFECT YOUR ABILITY TO GET PREGNANT LATER?
If you want to become pregnant, simply stop taking POPs. POPs will not
delay your ability to get pregnant.
BREASTFEEDING
If you are breastfeeding, POPs will not affect the quality or amount of
your breastmilk or the health of your nursing baby.
OVERDOSE
No serious problems have been reported when many pills were taken by
accident, even by a small child, so there is usually no reason to treat
an overdose.
12 OTHER QUESTIONS OR CONCERNS
If you have any questions or concerns, check with your doctor or
clinic. You can also ask for the more detailed "professional package
labeling" written for doctors and other health care providers.
1. Depending on method (calendar, ovulation, symptothermal,
post-ovulation)