5.1 Ectopic Pregnancy

Ectopic pregnancies account for approximately 2% of all 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 is not a contraindication to use of this emergency contraceptive method. Healthcare providers, however, should consider the possibility of an ectopic pregnancy in women who become pregnant or complain of lower abdominal pain after taking Next ChoiceTM. A follow-up physical or pelvic examination is recommended if there is any doubt concerning the general health or pregnancy status of any woman after taking Next ChoiceTM.

5.2 Existing Pregnancy

Next ChoiceTM is not effective in terminating an existing pregnancy.

5.3 Effects on Menses

Some women may experience spotting a few days after taking Next ChoiceTM. Menstrual bleeding patterns are often irregular among women using progestin-only oral contraceptives and women using levonorgestrel for postcoital and emergency contraception. If there is a delay in the onset of expected menses beyond 1 week, consider the possibility of pregnancy.

5.4 STI/HIV

Next ChoiceTM does not protect against HIV infection (AIDS) or other sexually transmitted infections (STIs).

5.5 Physical Examination and Follow-up

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

5.6 Fertility Following Discontinuation

A rapid return of fertility is likely following treatment with Next ChoiceTM for emergency contraception; therefore, routine contraception should be continued or initiated as soon as possible following use of Next ChoiceTM to ensure ongoing prevention of pregnancy.

5.7 Presence of FD&C Yellow #6

Next ChoiceTM contains FD&C Yellow #6 as a color additive.

6.1 Clinical Trial Experience

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in clinical practice. A double-blind, controlled clinical trial in 1,955 evaluable women compared the efficacy and safety of levonorgestrel tablets (one 0.75 mg tablet of levonorgestrel taken within 72 hours of unprotected intercourse, and one tablet taken 12 hours later) to the Yuzpe regimen (two tablets each containing 0.25 mg levonorgestrel and 0.05 mg ethinyl estradiol, taken within 72 hours of intercourse, and two tablets taken 12 hours later).

The most common adverse events (>10%) in the clinical trial for women receiving levonorgestrel tablets included menstrual changes (26%), nausea (23%), abdominal pain (18%), fatigue (17%), headache (17%), dizziness (11%), and breast tenderness (11%). Table 1 lists those adverse events that were reported in >5% of levonorgestrel tablets users.

6.2 Postmarketing Experience

The following adverse reactions have been identified during post-approval use of Next ChoiceTM. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.

Gastrointestinal Disorders

Abdominal Pain, Nausea, Vomiting

General Disorders and Administration Site Conditions

Fatigue

Nervous System Disorders

Dizziness, Headache

Reproductive System and Breast Disorders

Dysmenorrhea, Irregular Menstruation, Oligomenorrhea, Pelvic Pain

8.1 Pregnancy

Many studies have found no harmful effects on fetal development associated with longterm 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 ChoiceTM 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 and the Yuzpe regimen (another form of emergency contraception). 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 tablets.

8.8 Renal Impairment

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

12.1 Mechanism of Action

Emergency contraceptive pills are not effective if a woman is already pregnant. Next ChoiceTM 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, they may inhibit implantation (by altering the endometrium). It is not effective once the process of implantation has begun.

12.3 Pharmacokinetics

Absorption

No specific investigation of the absolute bioavailability of levonorgestrel tablets 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 levonorgestrel tablets (0.75 mg) administered to 16 women under fasting conditions, the mean maximum serum concentration of levonorgestrel was 14.1 ng/mL at an average of 1.6 hours. See Table 2.

Cmax = maximum concentration

Tmax = time to maximum concentration

CL = clearance

Vd = volume of distribution

t1/2 = elimination half life

AUCinf = area under the drug concentration curve from time 0 to infinity

Effect of Food: The effect of food on the rate and the extent of levonorgestrel absorption following single oral administration of levonorgestrel 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.

Specific Populations

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 on pharmacokinetics of levonorgestrel tablets. However, clinical trials demonstrated a higher pregnancy rate in Chinese women with both levonorgestrel tablets and the Yuzpe regimen (another form of emergency contraception). 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 tablets.

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

Drug-Drug Interactions

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

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 μg/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 μg/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.

17.1 Information for Patients

• Take Next ChoiceTM 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 either 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 ChoiceTM, in order to be evaluated for an ectopic pregnancy.
• After taking Next ChoiceTM, 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 ChoiceTM as routine contraception.
• Next ChoiceTM is not effective in terminating an existing pregnancy.
• Next ChoiceTM does not protect against HIV-infection (AIDS) and other sexually transmitted diseases/infections.
• For women younger than age 17 years, Next ChoiceTM is available only by prescription.
• Next ChoiceTM contains FD&C Yellow #6 as a color additive.

Manufactured by: Watson Laboratories, Inc.

Corona, CA 92880 USA

Distributed by: Watson Pharma, Inc.

Corona, CA 92880 USA

Phone: 1 -866-9WATSON (1-866-992-8766)

www.mynextchoice.com

Issued: August 2009

190229-1

0809B

Repacked by:
H.J. Harkins Company, Inc.
Grover Beach, CA 93433