Emergency contraceptive tablet. Each Plan B® tablet contains 0.75 mg of a single active steroid ingredient, levonorgestrel [18,19-Dinorpregn-4-en-20-yn-3-one-13-ethyl-17-hydroxy-, (17α)- (-)-], a totally synthetic progestogen. The inactive ingredients present are colloidal silicon dioxide, potato starch, gelatin, magnesium stearate, talc, corn starch, and lactose monohydrate. Levonorgestrel has a molecular weight of 312.45, and the following structural and molecular formulas:

For women age 17 and younger, Plan B® is a prescription-only emergency contraceptive that can be used to prevent pregnancy following unprotected intercourse or a known or suspected contraceptive failure. To obtain optimal efficacy, the first tablet should be taken as soon as possible within 72 hours of intercourse. The second tablet must be taken 12 hours later.

One tablet of Plan B® should be taken orally as soon as possible within 72 hours after unprotected intercourse. The second tablet should be taken 12 hours after the first dose. Efficacy is better if Plan B® is taken as directed as soon as possible after unprotected intercourse. Plan B® can be used at any time during the menstrual cycle.

The user should be instructed that if she vomits within one hour of taking either dose of medication she should contact her health care professional to discuss whether to repeat that dose.

Plan B® (levonorgestrel) tablets, 0.75 mg are available for a single course of treatment in PVC/aluminum foil blister packages of two tablets each. The tablet is white, round, and marked: INOR.

Available as:
Unit-of-use NDC 51285-038-93

Store Plan B® tablets at controlled room temperature, 20° to 25°C (68° to 77°F); excursions permitted between 15° to 30°C (59° to 86°F) [See USP].

Mfg. by Gedeon Richter, Ltd., Budapest, Hungary
for Duramed Pharmaceuticals, Inc.
Subsidiary of Barr Pharmaceuticals, Inc.
Pomona, NY 10970
Phone: 1-800-330-1271 Web site: www.go2planb.com
Revised August 2006
BR- 038 / 21000382503

The most common adverse events in the clinical trial for women receiving Plan B® included nausea (23%), abdominal pain (18%), fatigue (17%), headache (17%), and menstrual changes. The table below shows those adverse events that occurred in ≥5% of Plan B® users.

Table 3
Adverse Events in ≥ to 5% of Women, by % Frequency

Plan B® demonstrated a superior safety profile over the Yuzpe regimen for the following adverse events:

• Nausea: Occurred in 23% of women taking Plan B® (compared to 50% with Yuzpe)
• Vomiting: Occurred in 6% of women taking Plan B® (compared to 19% with Yuzpe)

DRUG ABUSE AND DEPENDENCE

There is no information about dependence associated with the use of Plan B®.

Theoretically, the effectiveness of low-dose progestin-only pills is reduced by hepatic enzyme-inducing drugs such as the anticonvulsants phenytoin, carbamazepine, and barbiturates, and the antituberculosis drug rifampin. No significant interaction has been found with broad-spectrum antibiotics. It is not known whether the efficacy of Plan B® would be affected by these or any other medications.

Plan B® is not recommended for routine use as a contraceptive.

Plan B® is not effective in terminating an existing pregnancy.

Effects on Menses

Menstrual bleeding patterns are often irregular among women using progestin-only oral contraceptives and in clinical studies of levonorgestrel for postcoital and emergency contraceptive use. Some women may experience spotting a few days after taking Plan B®. At the time of expected menses, approximately 75% of women using Plan B® had vaginal bleeding similar to their normal menses, 12-13% bled more than usual, and 12% bled less than usual. The majority of women (87%) had their next menstrual period at the expected time or within ± 7 days, while 13% had a delay of more than 7 days beyond the anticipated onset of menses. If there is a delay in the onset of menses beyond 1 week, the possibility of pregnancy should be considered.

Ectopic Pregnancy

Ectopic pregnancies account for approximately 2% of reported pregnancies (19.7 per 1,000 reported pregnancies). Up to 10% of pregnancies reported in clinical studies of routine use of progestin-only contraceptives are ectopic. A history of ectopic pregnancy need not be considered a contraindication to use of this emergency contraceptive method. Health providers, however, should be alert to the possibility of an ectopic pregnancy in women who become pregnant or complain of lower abdominal pain after taking Plan B®.

Pregnancy

Many studies have found no effects on fetal development associated with long-term use of contraceptive doses of oral progestins (POPs). The few studies of infant growth and development that have been conducted with POPs have not demonstrated significant adverse effects.

STD/HIV

Plan B®, like progestin-only contraceptives, does not protect against HIV infection (AIDS) and other sexually transmitted diseases.

Physical Examination and Follow-up

A physical examination is not required prior to prescribing Plan B®. A follow-up physical or pelvic examination, however, is recommended if there is any doubt concerning the general health or pregnancy status of any woman after taking Plan B®.

Carbohydrate Metabolism

The effects of Plan B® on carbohydrate metabolism are unknown. Some users of progestin-only oral contraceptives (POPs) may experience slight deterioration in glucose tolerance, with increases in plasma insulin; however, women with diabetes mellitus who use POPs do not generally experience changes in their insulin requirements. Nonetheless, diabetic women should be monitored while taking Plan B®.

Nursing Mothers

Small amounts of progestin pass into the breast milk in women taking progestin-only pills for long-term contraception resulting in steroid levels in infant plasma of 1-6% of the levels of maternal plasma. However, no adverse effects due to progestin-only pills have been found on breastfeeding performance, either in the quality or quantity of the milk, or on the health, growth or development of the infant.

Pediatric Use

Safety and efficacy of progestin-only pills have been established in women of reproductive age for long-term contraception. Safety and efficacy are expected to be the same for postpubertal adolescents under the age of 16 and for users 16 years and older. Use of Plan B® emergency contraception before menarche is not indicated.

Fertility Following Discontinuation

The limited available data indicate a rapid return of normal ovulation and fertility following discontinuation of progestin-only pills for emergency contraception and long-term contraception.

There are no data on overdosage of Plan B®, although the common adverse event of nausea and its associated vomiting may be anticipated.

Progestin-only contraceptive pills (POPs) are used as a routine method of birth control over longer periods of time, and are contraindicated in some conditions. It is not known whether these same conditions apply to the Plan B® regimen consisting of the emergency use of two progestin pills. POPs however, are not recommended for use in the following conditions:

• Known or suspected pregnancy
• Hypersensitivity to any component of the product

Emergency contraceptives are not effective if the woman is already pregnant. Plan B® is believed to act as an emergency contraceptive principally by preventing ovulation or fertilization (by altering tubal transport of sperm and/or ova). In addition, it may inhibit implantation (by altering the endometrium). It is not effective once the process of implantation has begun.

Pharmacokinetics

Absorption

No specific investigation of the absolute bioavailability of Plan B® in humans has been conducted. However, literature indicates that levonorgestrel is rapidly and completely absorbed after oral administration (bioavailability about 100%) and is not subject to first pass metabolism. After a single dose of Plan B® (0.75 mg) administered to 16 women under fasting conditions, maximum serum concentrations of levonorgestrel are 14.1 ± 7.7 ng/mL (mean ± SD) at an average of 1.6 ± 0.7 hours. No formal study of the effect of food on the absorption of levonorgestrel has been undertaken.

Table 1
Pharmacokinetic Parameter Values Following Single Dose Administration of Plan B (Levonorgestrel 0.75 mg) to Healthy Female Volunteers

Distribution

Levonorgestrel in serum is primarily protein bound. Approximately 50% is bound to albumin and 47.5% is bound to sex hormone binding globulin (SHBG).

Metabolism

Following a single oral dosage, levonorgestrel does not appear to be extensively metabolized by the liver. The primary metabolites are 3α,5β- and 3α,5β-tetrahydrolevonorgestrel with 16β-hydroxynorgestrel also identified. Together, these account for less than 10% of parent plasma levels. Urinary metabolites hydroxylated at the 2α and 16β positions have also been identified. Small amounts of the metabolites are present in plasma as sulfate and glucuronide conjugates.

Excretion

The elimination half-life of levonorgestrel following single dose administration as Plan B® (0.75 mg) is 24.4 ± 5.3 hours. Excretion following single dose administration as emergency contraception is unknown, but based on chronic, low-dose contraceptive use, levonorgestrel and its metabolites are primarily excreted in the urine, with smaller amounts recovered in the feces.

Special Populations

Geriatric: This product is not intended for use in geriatric (age 65 years or older) populations and pharmacokinetic data are not available for this population.

Pediatric: This product is not intended for use in pediatric (premenarchal) populations, and pharmacokinetic data are not available for this population.

Race: No formal studies have evaluated the effect of race. However, clinical trials demonstrated a higher pregnancy rate in the Chinese population with both Plan B® and the Yuzpe regimen (another form of emergency contraception consisting of two doses of ethinyl estradiol 0.1 mg + levonorgestrel 0.5 mg). The reason for this apparent increase in the pregnancy rate of emergency contraceptives in Chinese women is unknown.

Hepatic Insufficiency and Renal Insufficiency: No formal studies have evaluated the effect of hepatic insufficiency or renal insufficiency on the disposition of emergency contraceptive tablets.

Drug-Drug Interactions: No formal studies of drug-drug interactions were conducted.

CLINICAL STUDIES

A double-blind, controlled clinical trial in 1,955 evaluable women compared the efficacy and safety of Plan B® (one 0.75 mg tablet of levonorgestrel taken within 72 hours of intercourse, and one tablet taken 12 hours later) to the Yuzpe regimen (two tablets of 0.25 mg levonorgestrel and 0.05 mg ethinyl estradiol, taken within 72 hours of intercourse, and two tablets taken 12 hours later). Plan B® was at least as effective as the Yuzpe regimen in preventing pregnancy. After a single act of intercourse, the expected pregnancy rate of 8% (with no contraception) was reduced to approximately 1% with Plan B®.

Emergency contraceptives are not as effective as routine contraception since their failure rate, while low based on a single use, would accumulate over time with repeated use (see WARNINGS). See Table 2 below.

Table 2
Percentage of Women Experiencing an Unintended Pregnancy During the First Year of Typical Use and the First Year of Perfect Use of Contraception, and the Percentage Continuing Use at the End of the first Year- United States

Emergency Contraceptive Pills: Treatment initiated within 72 hours after unprotected intercourse reduces the risk of pregnancy by at least 75%.⁹

Lactational Amenorrhea Method: LAM is a highly effective temporary method of contraception.¹⁰

Source: Trussell J. Contraceptive efficacy. In Hatcher RA, Trussell J, Stewart F, Cates W, Stewart GK, Kowal D, Guest F, Contraceptive Technology; Seventeenth Revised Edition. New York, NY: Irvington Publishers, 1998.

1.  Among typical couples who initiate use of a method (not necessarily for the first time), the percentage who experience an unintended pregnancy during the first year if they do not stop use for any other reason.
2.  Among couples who initiate use of a method (not necessarily for the first time) and who use it perfectly (both consistently and correctly), the percentage who experience an unintended pregnancy during the first year if they do not stop use for any other reason.
3.  Among couples attempting to avoid pregnancy, the percentage who continue to use a method for one year.
4.  The percentages of women becoming pregnant in columns (2) and (3) are based on data from populations where contraception is not used and from women who cease using contraception in order to become pregnant. Among such populations, about 89% become pregnant within one year. This estimate was lowered slightly (to 85%) to represent the percentage who would become pregnant within one year among women now relying on reversible methods of contraception if they abandoned contraception altogether.
5.  Foams, creams, gels, vaginal suppositories, and vaginal film.
6.  Cervical mucus (ovulation) method supplemented by calendar in the pre-ovulatory and basal body temperature in the post-ovulatory phase.
7.  With spermicidal cream or jelly.
8.  Without spermicides.
9.  The treatment schedule is one dose within 72 hours after unprotected intercourse and a second dose 12 hours after the first dose. The Food and Drug Administration has declared the following brands of oral contraceptives to be safe and effective for emergency contraception: Ovral (1 dose is 2 white pills), Alesse (1 dose is 5 pink pills), Nordette or Levlen (1 dose is 2 light-orange pills), Lo/Ovral (1 dose is 4 white pills), Triphasil or Tri-Levlen (1 dose is 4 yellow pills).
10.  However, to maintain effective protection against pregnancy, another method of contraception must be used as soon as menstruation resumes, the frequency or duration of breastfeeds is reduced, bottle feeds are introduced or the baby reaches six months of age.

Plan B®
(levonorgestrel) Tablets 0.75 mg
Emergency Contraceptive

What is Plan B®?

Plan B® is emergency contraception. Emergency contraception is a backup method of preventing pregnancy and is not for routine use. Drugs used for emergency contraception are called emergency contraceptive pills, postcoital pills, or morning after pills. Plan B® can reduce your chance of pregnancy after unprotected sex (if your regular birth control method fails or if you have had sex without birth control). For example, if you were using a condom and it broke, or if you forgot to take 2 or more of your birth control pills this month, or if you did not use any birth control method, Plan B® may work for you.

How does Plan B® work?

Plan B® contains a dose of the hormone levonorgestrel that is higher than in a single birth control pill. Levonorgestrel has been used in birth control pills for over 35 years. Plan B® works like a birth control pill to prevent pregnancy mainly by stopping the release of an egg from the ovary. It is possible that Plan B® may also work by preventing fertilization of an egg (the uniting of sperm with the egg) or by preventing attachment (implantation) to the uterus (womb), which usually occurs beginning 7 days after release of an egg from the ovary. Plan B® will not do anything to a fertilized egg already attached to the uterus. The pregnancy will continue.

When is it appropriate to use Plan B®?

You can use Plan B® after you have had unprotected sex 1 or more times in the last 3 days (72 hours), and you don't want to become pregnant.

Plan B® can be used as a backup method to birth control if, for example,

• Your regular birth control failed (your partner's condom broke or slipped)
• You made a mistake with your regular method (you missed 2 or more birth control pills this month)
• You did not use any birth control method

When is it not appropriate to use Plan B®?

• Plan B® should not be used as a regular birth control method. It does not work as well as most other forms of birth control when they are used consistently and correctly. Plan B® is a backup or emergency method of contraception
• Plan B® should not be used if you are already pregnant because it will not work
• Plan B® should not be used if you are allergic to levonorgestrel
• Plan B® does not protect against HIV (the virus that causes AIDS) or other sexually transmitted diseases (STDs). The best ways to protect yourself against getting HIV or other STDs are to use a latex condom correctly with every sexual act or not to have sex at all

How can I get the best results from Plan B®?

You have only a few days to prevent pregnancy after unprotected sex. Plan B® works better the sooner you take it. Take the first Plan B® tablet as soon as possible but not later than 3 days (72 hours) after unprotected sex. Take the second tablet 12 hours later.

How effective is Plan B®?

Plan B® works best the sooner you use it. If it is taken within 72 hours (3 days) after sex, it will significantly decrease the chance that you will get pregnant. Seven out of every 8 women who would have gotten pregnant will not become pregnant. Plan B® works even better than this if taken within the first 24 hours after sex.

How will I know if Plan B® worked?

Most women will have their next menstrual period at the expected time or within a week of the expected time. If your menstrual period is delayed beyond 1 week, you may be pregnant and you should get a pregnancy test and follow up with your healthcare professional.

What if I am already pregnant and use Plan B®?

There is no medical evidence that Plan B® would harm a developing baby. If you take Plan B® accidentally after you are already pregnant, or it does not work and you become pregnant, it is not likely to cause any harm to you or your pregnancy. Plan B® should not have any effect on a pregnancy after implantation.

What should I do if my menstrual period is delayed beyond 1 week and I have severe lower stomach pain?

If you have severe lower stomach pain about 3 to 5 weeks after taking Plan B®, you may have a pregnancy outside the uterus (a tubal pregnancy). See a healthcare professional right away because a tubal pregnancy requires immediate medical treatment.

Can I use Plan B® for regular birth control?

Plan B® should not be used for regular birth control. Plan B® is not as effective as using a regular birth control method correctly and consistently. It is a backup method to be used if your regular birth control fails or if you have sex without birth control. You should not have unprotected sex following treatment because Plan B® will not protect you from getting pregnant.

How often can I use Plan B®?

Plan B® is meant for infrequent emergency protection. If you need to use emergency contraception often, you should consult with your healthcare professional for your best methods of birth control and STD prevention.

Will I experience any side effects from Plan B®?

When used as directed, Plan B® is safe for women. Plan B® has no serious or lasting medical side effects. Some women will experience non-serious side effects, such as nausea, stomach pain, headache, dizziness, or breast tenderness. These are similar to the side effects of regular birth control pills. Some women have menstrual changes such as spotting or bleeding before their next period. Some women may have a heavier or lighter next period, or a period that is early or late. If your period is more than a week late, you should get a pregnancy test.

See WARNINGS, PRECAUTIONS and CONTRAINDICATIONS.

IMPORTANT NOTE: This is a summary and does not contain all possible information about this product. For complete information about this product or your specific health needs, ask your health care professional. Always seek the advice of your health care professional if you have any questions about this product or your medical condition. This information is not intended as individual medical advice and does not substitute for the knowledge and judgment of your health care professional. This information does not contain any assurances that this product is safe, effective, or appropriate for you.

LEVONORGESTREL - ORAL

(lee-voh-nor-JEST-rell)

COMMON BRAND NAME(S): Plan B

USES: This medication is used in women to prevent pregnancy after birth control failure (e.g., broken condom) or unprotected sex. It is a progestin hormone that prevents pregnancy by preventing the release of an egg (ovulation) and changing the womb and cervical mucus to make it more difficult for an egg to meet sperm (fertilization) or attach to the wall of the womb (implantation).

Using this medication will not stop an existing pregnancy or protect you against sexually transmitted diseases (e.g., HIV, gonorrhea, chlamydia).

This medication should not be used as a regular form of birth control.

HOW TO USE: Take 1 tablet by mouth as soon as possible after unprotected sex. Take the second tablet by mouth 12 hours after taking the first dose. This medication may be taken with or without food. This medication works best when it is taken within 72 hours (3 days) after unprotected sex. In some cases, your doctor may instruct you to take both tablets at once. Take the medication exactly as prescribed by your doctor.

If you vomit within 1 hour of taking either dose of the medication, contact your doctor to discuss whether you need to repeat the dose.

The amount and timing of your period may be irregular after taking this medication. Notify your doctor immediately if your period is more than 7 days late. You may need to take a pregnancy test.

SIDE EFFECTS: Nausea/vomiting, abdominal pain, tiredness, dizziness, changes in vaginal bleeding, breast tenderness, diarrhea, or headache may occur. If any of these effects persist or worsen, tell your doctor or pharmacist promptly.

Remember that your doctor has prescribed this medication because he or she has judged that the benefit to you is greater than the risk of side effects. Many people using this medication do not have serious side effects.

Tell your doctor immediately if any of these rare but very serious side effects occur: lower abdominal pain.

A very serious allergic reaction to this drug is rare. However, seek immediate medical attention if you notice any of the following symptoms of a serious allergic reaction: rash, itching, swelling, severe dizziness, trouble breathing.

This is not a complete list of possible side effects. If you notice other effects not listed above, contact your doctor or pharmacist.

Contact your doctor for medical advice about side effects. The following numbers do not provide medical advice, but in the US you may report side effects to the Food and Drug Administration (FDA) at 1-800-FDA-1088. In Canada, you may call Health Canada at 1-866-234-2345.

PRECAUTIONS: Before using this medication, tell your doctor or pharmacist if you are allergic to it; or to other progestins (e.g., norethindrone); or if you have any other allergies.

This medication should not be used if you have certain medical conditions. Before using this product, consult your doctor or pharmacist if you have: unexplained vaginal bleeding, current or suspected pregnancy.

Before using this product, tell your doctor your medical history, especially of: diabetes, migraine headaches.

This drug may make you dizzy. Use caution while driving, using machinery, or doing any activity that requires alertness. Limit alcoholic beverages.

If you have diabetes, this medication may make it harder to control your blood sugar levels. Monitor your blood sugar regularly as directed by your doctor. Tell your doctor the results and any symptoms such as increased thirst/urination. Your anti-diabetic medication or diet may need to be adjusted.

This medication should not be used during pregnancy. If you become pregnant or think you may be pregnant, inform your doctor immediately.

This medication passes into breast milk. Though there have been no reports of harm to nursing infants, consult your doctor before breast-feeding.

DRUG INTERACTIONS: Your doctor or pharmacist may already be aware of any possible drug interactions and may be monitoring you for them. Do not start, stop, or change the dosage of any medicine before checking with them first.

This drug should not be used with the following medications because very serious interactions may occur: sodium tetradecyl sulfate.

If you are currently using the medication listed above, tell your doctor or pharmacist before starting this medication.

Before taking this medication, tell your doctor of all prescription and nonprescription medications you may use, especially of: amprenavir, drugs affecting liver enzymes that remove levonorgestrel from your body (such as bosentan, modafinil, nevirapine, HIV protease inhibitors including ritonavir, griseofulvin, rifamycins including rifabutin, St. John's wort, certain anti-seizure medicines including carbamazepine, phenytoin, phenobarbital), troleandomycin.

This document does not contain all possible interactions. Therefore, before using this product, tell your doctor or pharmacist of all the products you use. Keep a list of all your medications with you, and share the list with your doctor and pharmacist.

OVERDOSE: If overdose is suspected, contact your local poison control center or emergency room immediately. US residents should call the US National Poison Hotline at 1-800-222-1222. Canada residents should call their provincial poison control center directly. Symptoms of overdose may include: severe nausea/vomiting.

NOTES: Do not share this medication with others.

MISSED DOSE: If you miss a dose, contact your doctor immediately.

STORAGE: Store at room temperature between 68-77 degrees F (20-25 degrees C) away from light and moisture. Brief storage between 59-86 degrees F (15-30 degrees C) is permitted. Do not store in the bathroom. Keep all medicines away from children and pets.

Do not flush medications down the toilet or pour them into a drain unless instructed to do so. Properly discard this product when it is expired or no longer needed. Consult your pharmacist or local waste disposal company for more details about how to safely discard your product.

Information last revised July 2008 Copyright(c) 2008 First DataBank, Inc.