Levonorgestrel (levonorgestrel 1.5 mg) Dailymed

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Drugs or herbal products that induce enzymes, including CYP3A4, that metabolize progestins may decrease the plasma concentrations of progestins, and may decrease the effectiveness of progestin-only pills. Some drugs or herbal products that may decrease the effectiveness of progestin-only pills include:

• barbiturates
• bosentan
• carbamazepine
• felbamate
• griseofulvin
• oxcarbazepine
• phenytoin
• rifampin
• St. John’s wort
• topiramate

Significant changes (increase or decrease) in the plasma levels of the progestin have been noted in some cases of coadministration with HIV protease inhibitors or with non-nucleoside reverse transcriptase inhibitors.

Consult the labeling of all concurrently used drugs to obtain further information about interactions with progestin-only pills or the potential for enzyme alterations.


Drugs or herbal products that induce certain enzymes, such as CYP3A4, may decrease the effectiveness of progestin-only pills. (7)

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• Nursing Mothers: Small amounts of progestin pass into the breast milk of nursing women taking progestin-only pills for long-term contraception, resulting in detectable steroid levels in infant plasma. (8.3)
• Next Choice One Dose^TM tablet is not intended for use in premenarcheal (8.4) or postmenopausal females (8.5).

8.1 Pregnancy

Many studies have found no harmful 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 with progestin-only pills have not demonstrated significant adverse effects.

8.3 Nursing Mothers

In general, no adverse effects of progestin-only pills have been found on breastfeeding performance or on the health, growth, or development of the infant. However, isolated post-marketing cases of decreased milk production have been reported. Small amounts of progestins pass into the breast milk of nursing mothers taking progestin-only pills for long-term contraception, resulting in detectable steroid levels in infant plasma.

8.4 Pediatric Use

Safety and efficacy of progestin-only pills for long-term contraception have been established in women of reproductive age. Safety and efficacy are expected to be the same for postpubertal adolescents less than 17 years and for users 17 years and older. Use of Next Choice One Dose^TM emergency contraception before menarche is not indicated.

8.5 Geriatric Use

This product is not intended for use in postmenopausal women.

8.6 Race

No formal studies have evaluated the effect of race. However, clinical trials demonstrated a higher pregnancy rate in Chinese women with both levonorgestrel tablets (2 doses of 0.75 mg levonorgestrel taken 12 hours apart) and the Yuzpe regimen (another form of emergency contraception). There was a non-statistically significant increased rate of pregnancy among Chinese women in the levonorgestrel tablet trial. The reason for this apparent increase in the pregnancy rate with emergency contraceptives in Chinese women is unknown.

8.7 Hepatic Impairment

No formal studies were conducted to evaluate the effect of hepatic disease on the disposition of levonorgestrel tablet.

8.8 Renal Impairment

No formal studies were conducted to evaluate the effect of renal disease on the disposition of levonorgestrel tablet.

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Levonorgestrel is not a controlled substance. There is no information about dependence associated with the use of levonorgestrel.

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There are no data on overdosage of levonorgestrel tablet, although the common adverse event of nausea and associated vomiting may be anticipated.

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Next Choice One Dose^TM contains 1.5 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, corn starch, FD&C Yellow #6, lactose monohydrate,  magnesium stearate, povidone.

Levonorgestrel has a molecular weight of 312.45, and the following structural and molecular formulas:

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12.1 Mechanism of Action

Emergency contraceptive pills are not effective if a woman is already pregnant. Levonorgestrel 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.

12.3 Pharmacokinetics

Absorption Following a single dose administration of levonorgestrel 1.5 mg in 30 women under fasting conditions, maximum plasma concentrations of levonorgestrel of 19.1 ng/mL were reached at 1.7 hours. See Table 2.

Table 2: Pharmacokinetic Parameter Values Following Single Dose Administration of  Levonorgestrel Tablet 1.5 mg to 30 Healthy Female Volunteers under Fasting Conditions

Â	 Mean (± SD)
Â	 Cmax	 AUCt	 AUCinf	 Tmax	 t1/2
Â	 (ng/mL)	 (ng·hr/mL)*	 (ng·hr/mL)*	 (hr)**	 (hr)
     Levonorgestrel Â	 19.1(9.7)	 294.8 (208.8)	 307.5(218.5)	 1.7(1.0 to 4.0)	 27.5(5.6)

C_max = maximum concentrationAUC_t = area under the drug concentration curve from time 0 to time of last determinable concentrationAUC_inf = area under the drug concentration curve from time 0 to infinityT_max = time to maximum concentrationt_1/2 = elimination half life*N = 29**median (range)

Effect of Food: The effect of food on the rate and the extent of levonorgestrel absorption following single oral administration of levonorgestrel 1.5 mg has not been evaluated.

Distribution The apparent volume of distribution of levonorgestrel is reported to be approximately 1.8 L/kg. It is about 97.5 to 99% protein-bound, principally to sex hormone binding globulin (SHBG) and, to a lesser extent, serum albumin.

Metabolism Following absorption, levonorgestrel is conjugated at the 17β-OH position to form sulfate conjugates and, to a lesser extent, glucuronide conjugates in plasma. Significant amounts of conjugated and unconjugated 3α, 5β-tetrahydrolevonorgestrel are also present in plasma, along with much smaller amounts of 3α, 5α-tetrahydrolevonorgestrel and 16βhydroxylevonorgestrel. Levonorgestrel and its phase I metabolites are excreted primarily as glucuronide conjugates. Metabolic clearance rates may differ among individuals by several-fold, and this may account in part for the wide variation observed in levonorgestrel concentrations among users.

Excretion About 45% of levonorgestrel and its metabolites are excreted in the urine and about 32% are excreted in feces, mostly as glucuronide conjugates.

Pediatric This product is not intended for use in the premenarcheal population, and pharmacokinetic data are not available for this population.

Geriatric This product is not intended for use in postmenopausal women, 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 Chinese women with both levonorgestrel tablets and the Yuzpe regimen (another form of emergency contraception). There was a non-statistically significant increased rate of pregnancy among Chinese women in the levonorgestrel tablet trial. The reason for this apparent increase in the pregnancy rate with emergency contraceptives in Chinese women is unknown [see USE IN SPECIFIC POPULATIONS ( 8.6 )].

Hepatic Impairment No formal studies were conducted to evaluate the effect of hepatic disease on the disposition of levonorgestrel tablet.

Renal Impairment No formal studies were conducted to evaluate the effect of renal disease on the disposition of levonorgestrel tablet.

No formal drug-drug interaction studies were conducted with levonorgestrel tablet [see DRUG INTERACTIONS ( 7 )].

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13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility

Carcinogenicity: There is no evidence of increased risk of cancer with short-term use of progestins. There was no increase in tumorgenicity following administration of levonorgestrel to rats for 2 years at approximately 5 mcg/day, to dogs for 7 years at up to 0.125 mg/kg/day, or to rhesus monkeys for 10 years at up to 250 mcg/kg/day. In another 7 year dog study, administration of levonorgestrel at 0.5 mg/kg/day did increase the number of mammary adenomas in treated dogs compared to controls. There were no malignancies.

Genotoxicity: Levonorgestrel was not found to be mutagenic or genotoxic in the Ames Assay, in vitro mammalian culture assays utilizing mouse lymphoma cells and Chinese hamster ovary cells, and in an in vivo micronucleus assay in mice.

Fertility: There are no irreversible effects on fertility following cessation of exposures to levonorgestrel or progestins in general.

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A double-blind, randomized, multicenter, multinational study evaluated and compared the efficacy and safety of three different regimens for emergency contraception. Subjects were enrolled at 15 sites in 10 countries; the racial/ethnic characteristics of the study population overall were 54% Chinese, 34% Caucasian, and 12% Black or Asian (other than Chinese). 2,381 healthy women with a mean age of 27 years, who needed emergency contraception within 72 hours of unprotected intercourse were involved and randomly allocated into one of the two levonorgestrel groups. A single dose of 1.5 mg of levonorgestrel (levonorgestrel tablet) was administered to women allocated into group 1. Two doses of 0.75 mg levonorgestrel 12 hours apart (levonorgestrel tablets) were administered to women in group 2. In the levonorgestrel tablet group, 16 pregnancies occurred in 1,198 women and in the levonorgestrel tablets group, 20 pregnancies occurred in 1,183 women. The number of pregnancies expected in each group was calculated based on the timing of intercourse with regard to each woman’s menstrual cycle. Among women receiving levonorgestrel tablet, 84% of expected pregnancies were prevented and among those women taking levonorgestrel tablets, 79% of expected pregnancies were prevented. The expected pregnancy rate of 8% (with no contraceptive use) was reduced to approximately 1% with levonorgestrel tablet.

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 INDICATIONS AND USAGE ( 1 )].

In the clinical study, bleeding disturbances were the most common adverse event reported after taking the levonorgestrel-containing regimens. More than half of the women had menses within two days of the expected time; however, 31% of women experienced change in their bleeding pattern during the study period; 4.5% of women had menses more than 7 days after the expected time.

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Next Choice One Dose^TM (Levonorgestrel) tablet 1.5 mg is available in a PVC/aluminum foil buler package. The tablet is supplied as a peach, round tablet and is embossed with 287 on one side and WATSON on the other side.

NDC 52544-287-54 (1 tablet unit of use package)

Store Next Choice One Dose^TM at 20° to 25°C (68° to 77°F) [See USP Controlled Room Temperature].

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17.1Information for Patients

• Take Next Choice One Dose^TM as soon as possible and not more than 72 hours after unprotected intercourse or a known or suspected contraceptive failure.
• If you vomit within two hours of taking the tablet, immediately contact your healthcare provider to discuss whether to take another tablet.
• Seek medical attention if you experience severe lower abdominal pain 3 to 5 weeks after taking Next Choice One Dose^TM, in order to be evaluated for an ectopic pregnancy.
• After taking Next Choice One Dose^TM, consider the possibility of pregnancy if your period is delayed more than one week beyond the date you expected your period.
• Do not use Next Choice One Dose^TM as routine contraception.
• Next Choice One Dose^TM is not effective in terminating an existing pregnancy.
• Next Choice One Dose^TM does not protect against HIV-infection (AIDS) and other sexually transmitted diseases/infections.
• For women younger than age 17 years, Next Choice One Dose^TM is available only by prescription.
• Next Choice One Dose^TM tablets contain FD&C Yellow #6 as a color additive.

Manufactured by: Watson Laboratories, Inc. Corona, CA 92880 USA

Distributed by: Watson Pharma, Inc. Parsippany, NJ 07054 USA

Phone: 1-866-9WATSON (1-866-992-8766)www.mynextchoiceonedose.com

Revised: October 2012                                                      205050-1

PATIENT INFORMATION Next Choice One Dose ^TM (Levonorgestrel Tablet, 1.5 mg) Emergency Contraceptive Contains FD&C Y ellow #6 as a color additive.

Important Information About Next Choice One Dose^TM, Birth Control & Sexually Transmitted Diseases.

For additional information intended for healthcare professionals, please see enclosed Product Information for Next Choice One Dose^TM.

What is Next Choice One Dose ^TM ? Next Choice One Dose ^TM is emergency contraception that helps prevent pregnancy after birth control failure or unprotected sex. It is a backup method of preventing pregnancy and is not to be used routinely.

Next Choice One Dose^TM can reduce your chance of pregnancy after unprotected sex (if your regular birth control was used incorrectly or fails, or if you have had sex without birth control). For example, if you were using a condom and it broke or slipped, if you did not use your regular birth control as you should have, or if you did not use any birth control, Next Choice One Dose^TM may work for you.

What Next Choice One Dose ^TM is not. Next Choice One Dose^TM will not work if you are already pregnant and will not affect an existing pregnancy. Next Choice One Dose^TM should not be used as regular birth control. It is important to have another reliable source of birth control that is right for you. Next Choice One Dose^TM will not protect you from HIV infection (the virus that causes AIDS) and other sexually transmitted diseases.

When is the appropriate time to use Next Choice One Dose ^TM ? You can use Next Choice One Dose^TM after you have had unprotected sex in the last 72 hours (3 days), and you do not want to become pregnant.

Next Choice One Dose^TM can be used as a backup or emergency method to regular birth control if, for example,

• Your regular birth control method was used incorrectly or failed (your partner’s condom broke or slipped)
• You made a mistake with your regular method
• You did not use any birth control method

When is it not appropriate to use Next ChoiceOne Dose ^TM ?

• Next Choice One Dose^TM 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. Next Choice One Dose^TM is a backup or emergency method of contraception.
• Next Choice One Dose^TM should not be used if you are already pregnant because it will not work.
• Next Choice One Dose^TM should not be used if you are allergic to levonorgestrel or any other ingredients in Next Choice One Dose^TM.
• Next Choice One Dose^TM 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 does Next Choice One Dose ^TM work? Next Choice One Dose^TM is one pill with levonorgestrel, a hormone that has been used in many birth control pills for over 35 years. Next Choice One Dose^TM contains a higher dose of levonorgestrel than birth control pills, but works in a similar way to prevent pregnancy. It works mainly by stopping the release of an egg from the ovary. It is possible that levonorgestrel tablet 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).

How can I get the best results from Next Choice One Dose ^TM ? You have only a few days to try to prevent pregnancy after unprotected sex. The sooner you take Next Choice One Dose ^TM tablet , the better it works. Next Choice One Dose^TM tablet should be taken as soon as possible within 72 hours (3 days) after unprotected sex.

How effective is Next Choice One Dose ^TM ? The sooner you take Next Choice One Dose^TM tablet, the better it will work. Take Next Choice One Dose^TM tablet as soon as possible after unprotected sex. If it is taken as soon as possible within 72 hours (3 days) after unprotected 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.

How will I know if Next Choice One Dose ^TM 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. You should get a pregnancy test and follow up with your healthcare professional.

What if I am already pregnant and use Next Choice One Dose ^TM ? There is no medical evidence that Next Choice One Dose^TM would harm a developing baby. If you take Next Choice One Dose^TM (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. The pregnancy will continue. Next Choice One Dose^TM will not work if you are already pregnant.

What should I do if my menstrual period is delayed beyond 1 week and I have severe lower stomach (abdominal) pain? If you have severe lower stomach (abdominal) pain about 3 to 5 weeks after taking levonorgestrel tablet, you may have a pregnancy outside the uterus, which is called a tubal pregnancy. A tubal pregnancy requires immediate medical treatment, so you should see a healthcare professional right away.

Can I use Next Choice One Dose ^TM for regular birth control? No. Next Choice One Dose^TM should not be used for regular birth control. It is an emergency or backup method to be used if your regular birth control fails or is used incorrectly or if you have sex without birth control. You should protect yourself against STDs and pregnancy every time you have sex. If you have unprotected sex again after taking Next Choice One Dose^TM, it will not help protect you from getting pregnant.

How often can I use Next Choice One Dose ^TM ? Next Choice One Dose^TM is meant for emergency protection only, and is not designed to be used frequently. If you find that you need to use emergency contraception often, talk to your healthcare professional and learn about methods of birth control and STD prevention that are right for you.

Will I experience any side effects from Next ChoiceOne Dose ^TM ? When used as directed, Next Choice One Dose^TM is safe for women. Some women will have mild, temporary side effects, such as menstrual changes, nausea, lower stomach (abdominal) pain, tiredness, headache, dizziness, breast pain and vomiting. These are similar to the side effects that some women have when taking regular birth control pills. Some women taking Next Choice One Dose^TM will 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.

What warnings should I know about when using Next Choice One Dose ^TM ? Next Choice One Dose ^TM  does not protect against the AIDS virus (HIV) or other sexually transmitted diseases (STDs).

Do not use:

• If you are already pregnant (because it will not work)
• If you are allergic to levonorgestrel or any of the ingredients in Next Choice One Dose^TM
• For regular birth control

When using this product, you may have :

• Menstrual changes
• Nausea
• Lower stomach (abdominal) pain
• Tiredness
• Headache
• Dizziness
• Breast pain
• Vomiting

Keep out of reach of children. In case of overdose, get medical help or contact a Poison Control Center right away at 1-800-222-1222.

What are the directions for using Next Choice One Dose ^TM ? Women 17 years of age and older:

• Take Next Choice One Dose^TM tablet as soon as possible within 72 hours (3 days) after unprotected sex.
• If you vomit within 2 hours of taking the medication, call a healthcare professional to find out if you should repeat the dose.

Prescription only for women younger than age 17. If you are younger than age 17, see a healthcare professional.

What should I do if I have questions about Next Choice One Dose ^TM ? If you have questions or need more information about this product, call our toll-free number, 1-866-9WATSON (1-866-992-8766), visit Watson Next Choice One Dose^TM Web Site, or ask a healthcare professional.

Other information Tablet is enclosed in a buler seal. Do not use if the buler seal is broken.

Store at 20° to 25°C (68° to 77°F) [See USP Controlled Room Temperature].

Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

Active ingredient: levonorgestrel 1.5 mg

Inactive ingredients: colloidal silicon dioxide, corn starch, FD&C Yellow #6, lactose monohydrate, magnesium stearate, and povidone

Protect yourself in more ways than one! If you are sexually active, but you are not ready for a pregnancy, it is important to use regular pregnancy protection. There are many types of birth control. Whichever type you choose, it is important to use your regular birth control method as directed. This ensures that you have effective protection against pregnancy every time you have sex.

But things do not always go as planned. For example, if you were using a condom and it broke or slipped, or if you did not use your regular birth control as you should have, or if you did not use any birth control, Next Choice One Dose^TM may work for you. Next Choice One Dose^TM is an emergency contraceptive that helps prevent pregnancy after unprotected sex or when your birth control fails or is not used correctly.

Remember, Next Choice One Dose^TM is only for emergency pregnancy prevention. There are many other products that work for regular birth control that are available by prescription or over-the-counter.

There is also another form of protection to think about when you have sex: protection against sexually transmitted diseases (STDs). Some common STDs are HIV/AIDS, chlamydia, genital herpes, gonorrhea, hepatitis, human papilloma virus (HPV), genital warts, syphilis, and trichomonas. Some of these STDs can be very serious and can lead to infertility (inability to have a baby), problems during pregnancy, chronic illness, and even death.

All sexually active women are at risk of catching STDs because they may not know that their partner has an STD (the partner himself may not know). If your partner uses a latex condom correctly each and every time you have sex with him, this will help reduce, but not eliminate, the chance that you will catch an STD.

No other birth control methods will effectively protect you from STDs. The female condom may give you some STD protection, but it is not as effective as a male latex condom.

For more information on STDs, call the Centers for Disease Control and Prevention (CDC) AIDS/STD Hotline. The CDC phone numbers are 1-800-342-AIDS (2437) for English, 1-800-344-7432 for Spanish, or 1-800-243-7889 for hearing impaired, TDD.

Be sure to protect yourself against pregnancy and STDs by using some form of birth control plus a latex condom. Of course, not having sex is the most effective way to prevent pregnancy and stay free of STDs.

Next Choice One Dose^TM is used to prevent pregnancy after unprotected sex.

Next Choice One Dose^TM should not be used for regular birth control, if you are already pregnant (because it will not work), or if you are allergic to levonorgestrel or any of the ingredients in Next Choice One Dose^TM.

The sooner you take Next Choice One Dose^TM tablet, the better it will work.

Next Choice One Dose^TM  does not protect against the AIDS virus (HIV) or other sexually transmitted diseases (STDs)

Common side effects associated with the use of Next Choice One Dose^TM include menstrual changes, nausea, lower stomach (abdominal) pain, tiredness, headache, dizziness, breast pain and vomiting.

Manufactured by: Watson Laboratories, Inc. Corona, CA 92880 USA

Distributed by: Watson Pharma, Inc. Parsippany, NJ 07054 USA

Phone: 1-866-9WATSON (1-866-992-8766)www.mynextchoiceonedose.com

Revised: October 2012                                                      205049-1