INFORMATION FOR PATIENTS SECTION.

17 PATIENT COUNSELING INFORMATION. 17.1 Information for Patients. Take Plan One-Step as soon as possible and not more than 72 hours after unprotected intercourse or 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 to weeks after taking Plan One-Step, in order to be evaluated for an ectopic pregnancy.After taking Plan One-Step, consider the possibility of pregnancy if your period is delayed more than one week beyond the date you expected your period.Do not use Plan One-Step as routine contraception.Plan One-Step is not effective in terminating an existing pregnancy.Plan One-Step does not protect against HIV-infection (AIDS) and other sexually transmitted diseases/infections.For women younger than age 17 years, Plan One-Step is available only by prescription. Take Plan One-Step as soon as possible and not more than 72 hours after unprotected intercourse or 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 to weeks after taking Plan One-Step, in order to be evaluated for an ectopic pregnancy.. After taking Plan One-Step, consider the possibility of pregnancy if your period is delayed more than one week beyond the date you expected your period.. Do not use Plan One-Step as routine contraception.. Plan One-Step is not effective in terminating an existing pregnancy.. Plan One-Step does not protect against HIV-infection (AIDS) and other sexually transmitted diseases/infections.. For women younger than age 17 years, Plan One-Step is available only by prescription.. Mfg. by Gedeon Richter, Ltd., Budapest, Hungaryfor Duramed Pharmaceuticals, Inc.Subsidiary of Barr Pharmaceuticals, Inc.Pomona, New York 10970Phone: 1-800-330-1271Website: www.PlanBOneStep.com Revised: August 200911001524Relabeled by:Rebel Distributors CorpThousand Oaks, CA 91320.

ADVERSE REACTIONS SECTION.

6 ADVERSE REACTIONS. The most common adverse reactions (>=10%) in clinical trials included heavier menstrual bleeding (31%), nausea (14%), lower abdominal pain (13%), fatigue (13%), headache (10%), and dizziness (10%). (6.1)To report SUSPECTED ADVERSE REACTIONS, contact Barr Laboratories at 1-800-330-1271 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch 6.1 Clinical Trials Experience. Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in clinical practice.Plan One-Step was studied in randomized, double-blinded multicenter clinical trial. In this study, all women who had received at least one dose of study medication were included in the safety analysis: 1,379 women in the Plan One-Step group, and 1,377 women in the Plan group (2 doses of 0.75 mg levonorgestrel taken 12 hours apart). The mean age of women given Plan One-Step was 27 years. The racial demographic of those enrolled was 54% Chinese, 12% Other Asian or Black, and 34% were Caucasian in each treatment group. 1.6% of women in the Plan One-Step group and 1.4% in Plan group were lost to follow-up. The most common adverse events (>10%) in the clinical trial for women receiving Plan One-Step included heavier menstrual bleeding (30.9%), nausea (13.7%), lower abdominal pain (13.3%), fatigue (13.3%), and headache (10.3%). Table lists those adverse events that were reported in 4% of Plan One-Step users.Table 1. Adverse Events in 4% of Women, by FrequencyMost Common Adverse Events(MedDRA)Plan One-StepN 1359 (%)Heavier menstrual bleeding30.9Nausea13.7Lower abdominal pain13.3Fatigue13.3Headache10.3Dizziness9.6Breast tenderness8.2Delay of menses (> days)4.5. 6.2 Postmarketing Experience. The following adverse reactions have been identified during post-approval use of Plan (2 doses of 0.75 mg levonorgestrel taken 12 hours apart). Because these reactions are reported voluntarily from population of uncertain size, it is not always possible to reliably estimate their frequency or establish causal relationship to drug exposure. Gastrointestinal DisordersAbdominal Pain, Nausea, VomitingGeneral Disorders and Administration Site ConditionsFatigueNervous System DisordersDizziness, HeadacheReproductive System and Breast DisordersDysmenorrhea, Irregular Menstruation, Oligomenorrhea, Pelvic Pain.

CARCINOGENESIS & MUTAGENESIS & IMPAIRMENT OF FERTILITY SECTION.

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 years at approximately ug/day, to dogs for years at up to 0.125 mg/kg/day, or to rhesus monkeys for 10 years at up to 250 ug/kg/day. In another 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.

CLINICAL PHARMACOLOGY SECTION.

12 CLINICAL PHARMACOLOGY. 12.1 Mechanism of Action. Emergency contraceptive pills are not effective if woman is already pregnant. Plan One-Step 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. AbsorptionFollowing single dose administration of Plan One-Step 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 Plan One-Step (levonorgestrel) tablet 1.5 mg to 30 Healthy Female Volunteers under Fasting ConditionsMean (+- SD)Cmax (ng/mL)AUCt (ng.hr/mL)N=29 AUCinf (ng.hr/mL) Tmax (hr)median (range) t1/2 (hr)Levonorgestrel19.1 9.7)294.8 208.8)307.5( 218.5)1.7 (1.0-4.0)27.5 5.6)Cmax maximum concentrationAUCt area under the drug concentration curve from time to time of last determinable concentrationAUCinf area under the drug concentration curve from time to infinityTmax time to maximum concentrationt1/2 elimination half lifeEffect of Food: The effect of food on the rate and the extent of levonorgestrel absorption following single oral administration of Plan One-Step has not been evaluated. DistributionThe 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 lesser extent, serum albumin.MetabolismFollowing absorption, levonorgestrel is conjugated at the 17-OH position to form sulfate conjugates and, to lesser extent, glucuronide conjugates in plasma. Significant amounts of conjugated and unconjugated 3, 5-tetrahydrolevonorgestrel are also present in plasma, along with much smaller amounts of 3, 5-tetrahydrolevonorgestrel and 16hydroxylevonorgestrel. Levonorgestrel and its phase 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. ExcretionAbout 45% of levonorgestrel and its metabolites are excreted in the urine and about 32% are excreted in feces, mostly as glucuronide conjugates. Specific Populations PediatricThis product is not intended for use in the premenarcheal population, and pharmacokinetic data are not available for this population.GeriatricThis product is not intended for use in postmenopausal women, and pharmacokinetic data are not available for this population.RaceNo formal studies have evaluated the effect of race. However, clinical trials demonstrated higher pregnancy rate in Chinese women with both Plan and the Yuzpe regimen (another form of emergency contraception). There was non-statistically significant increased rate of pregnancy among Chinese women in the Plan One-Step 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 ImpairmentNo formal studies were conducted to evaluate the effect of hepatic disease on the disposition of Plan One-Step.Renal ImpairmentNo formal studies were conducted to evaluate the effect of renal disease on the disposition of Plan One-Step.Drug-Drug InteractionsNo formal drug-drug interaction studies were conducted with Plan One-Step [see DRUG INTERACTIONS (7)].

CLINICAL STUDIES SECTION.

14 CLINICAL STUDIES. 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 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. single dose of 1.5 mg of levonorgestrel (Plan One-Step) was administered to women allocated into group 1. Two doses of 0.75 mg levonorgestrel 12 hours apart (Plan B) were administered to women in group 2. In the Plan One-Step group, 16 pregnancies occurred in 1,198 women and in the Plan 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 womans menstrual cycle. Among women receiving Plan One-Step, 84% of expected pregnancies were prevented and among those women taking Plan B, 79% of expected pregnancies were prevented. The expected pregnancy rate of 8% (with no contraceptive use) was reduced to approximately 1% with Plan One-Step.Emergency contraceptives are not as effective as routine contraception since their failure rate, while low based on 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 days after the expected time.

DOSAGE & ADMINISTRATION SECTION.

2 DOSAGE AND ADMINISTRATION. Take Plan One-Step orally as soon as possible within 72 hours after unprotected intercourse or known or suspected contraceptive failure. Efficacy is better if the tablet is taken as soon as possible after unprotected intercourse. Plan One-Step can be used at any time during the menstrual cycle.If vomiting occurs within two hours of taking the tablet, consideration should be given to repeating the dose. One tablet taken orally as soon as possible within 72 hours after unprotected intercourse. Efficacy is better if the tablet is taken as soon as possible after unprotected intercourse. (2).

DRUG INTERACTIONS SECTION.

7 DRUG INTERACTIONS. 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 griseofulvinoxcarbazepine phenytoin rifampin St. Johns wort topiramate Significant changes (increase or decrease) in the plasma levels of the progestin have been noted in some cases of co-administration 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.. barbiturates bosentan carbamazepine felbamate griseofulvin. oxcarbazepine phenytoin rifampin St. Johns wort topiramate Drugs or herbal products that induce certain enzymes, such as CYP3A4, may decrease the effectiveness of progestin-only pills. (7).

INDICATIONS & USAGE SECTION.

1 INDICATIONS AND USAGE. Plan B(R) One-Step is progestin-only emergency contraceptive indicated for prevention of pregnancy following unprotected intercourse or known or suspected contraceptive failure. To obtain optimal efficacy, the tablet should be taken as soon as possible within 72 hours of intercourse. Plan One-Step is available only by prescription for women younger than age 17 years, and available over the counter for women 17 years and older.Plan One-Step is not indicated for routine use as contraceptive.. Plan One-Step is progestin-only emergency contraceptive indicated for prevention of pregnancy following unprotected intercourse or known or suspected contraceptive failure. Plan One-Step is available only by prescription for women younger than age 17 years, and available over the counter for women 17 years and older. Plan One-Step is not intended for routine use as contraceptive. (1).

NONCLINICAL TOXICOLOGY SECTION.

13 NONCLINICAL TOXICOLOGY. 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 years at approximately ug/day, to dogs for years at up to 0.125 mg/kg/day, or to rhesus monkeys for 10 years at up to 250 ug/kg/day. In another 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.

PACKAGE LABEL.PRINCIPAL DISPLAY PANEL.

PRINCIPAL DISPLAY PANEL. FOR CLINIC USE ONLY. NOT FOR RESALE.NDC 21695-973-01Plan BOne-Step(R) (levonorgestrel) tablet, 1.5 mgEmergency ContraceptiveReduces the chance of pregnancy after unprotected sex (if regular birth control method fails or after sex without birth control)Not for regular birth control.Rx only for womenyounger than age 17One TabletOne DoseoTake as soon as possible within 72 hours (3 days) after unprotected sex. The sooner you take it, the better Plan One-Step(R) will work.1 Tablet Levonorgestrel 1.5mgoNot for regular birth control.Plan One-Step(R) should be used only in emergencies.oDoes not protect against HIV/AIDS or other STDs.Drug FactsActive ingredient PurposeLevonorgestrel 1.5mg........................Emergency contraceptiveUse reduces chance of pregnancy after unprotected sex(if contraceptive failed or if you did not use birth control)Warnings Allergy alert: Do not use if you have ever had an allergic reaction to levonorgestrelSexually transmitted diseases (STDs) alert: This product does not protect against HIV/AIDS or other STDsDo not use if you are already pregnant (because it will not work) for regular birth controlWhen using this product you may have menstrual changes nausea lower stomach (abdominal) pain tiredness headache dizziness breast pain vomitingKeep out of reach of children. In case of overdose, get medical help or contact Poison Control center right away.Directions women 17 years of age or older: take tablet as soon as possible within 72 hours (3 days) after unprotected sex. The sooner you take it the better it will work. if you vomit within hours of taking the medication, call 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 healthcare professional.Other information before using this product read the enclosed consumer information leaflet for complete directions and information this product is not recommended for regular birth control. It does not work as well as most other birth control methods used correctly. this product works mainly by preventing ovulation (egg release). It may also prevent fertilization of released egg (joining of sperm and egg) or attachment of fertilized egg to the uterus (implantation). when used correctly every time you have sex, latex condoms greatly reduce, but do not eliminate, the risk of pregnancy and the risk of catching or spreading HIV, the virus that causes AIDS. See condom labeling for additional STD information. tablet is enclosed in blister seal. Do not use if the blister seal is broken. store at 20-25C (68-77F)Inactive ingredientscolloidal silicon dioxide, corn starch, lactose monohydrate, magnesium stearate, potato starch, talcQuestions or commentsFor more information or to speak to healthcare professional,call 1-800-330-1271, 24 hours day/7 days week.Visit our Web site at www.PlanBOneStep.com Plan One-Step 1.5mg.

PHARMACOKINETICS SECTION.

12.3 Pharmacokinetics. AbsorptionFollowing single dose administration of Plan One-Step 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 Plan One-Step (levonorgestrel) tablet 1.5 mg to 30 Healthy Female Volunteers under Fasting ConditionsMean (+- SD)Cmax (ng/mL)AUCt (ng.hr/mL)N=29 AUCinf (ng.hr/mL) Tmax (hr)median (range) t1/2 (hr)Levonorgestrel19.1 9.7)294.8 208.8)307.5( 218.5)1.7 (1.0-4.0)27.5 5.6)Cmax maximum concentrationAUCt area under the drug concentration curve from time to time of last determinable concentrationAUCinf area under the drug concentration curve from time to infinityTmax time to maximum concentrationt1/2 elimination half lifeEffect of Food: The effect of food on the rate and the extent of levonorgestrel absorption following single oral administration of Plan One-Step has not been evaluated. DistributionThe 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 lesser extent, serum albumin.MetabolismFollowing absorption, levonorgestrel is conjugated at the 17-OH position to form sulfate conjugates and, to lesser extent, glucuronide conjugates in plasma. Significant amounts of conjugated and unconjugated 3, 5-tetrahydrolevonorgestrel are also present in plasma, along with much smaller amounts of 3, 5-tetrahydrolevonorgestrel and 16hydroxylevonorgestrel. Levonorgestrel and its phase 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. ExcretionAbout 45% of levonorgestrel and its metabolites are excreted in the urine and about 32% are excreted in feces, mostly as glucuronide conjugates. Specific Populations PediatricThis product is not intended for use in the premenarcheal population, and pharmacokinetic data are not available for this population.GeriatricThis product is not intended for use in postmenopausal women, and pharmacokinetic data are not available for this population.RaceNo formal studies have evaluated the effect of race. However, clinical trials demonstrated higher pregnancy rate in Chinese women with both Plan and the Yuzpe regimen (another form of emergency contraception). There was non-statistically significant increased rate of pregnancy among Chinese women in the Plan One-Step 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 ImpairmentNo formal studies were conducted to evaluate the effect of hepatic disease on the disposition of Plan One-Step.Renal ImpairmentNo formal studies were conducted to evaluate the effect of renal disease on the disposition of Plan One-Step.Drug-Drug InteractionsNo formal drug-drug interaction studies were conducted with Plan One-Step [see DRUG INTERACTIONS (7)].

SPL UNCLASSIFIED SECTION.

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. history of ectopic pregnancy is not 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 Plan One-Step. 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 Plan One-Step.

USE IN SPECIFIC POPULATIONS SECTION.

8 USE IN SPECIFIC POPULATIONS. 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)Plan One-Step is not intended for use in premenarcheal (8.4) or postmenopausal females (8.5). 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). Plan One-Step 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 Plan One-Step 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 higher pregnancy rate in Chinese women with both Plan and the Yuzpe regimen (another form of emergency contraception). There was non-statistically significant increased rate of pregnancy among Chinese women in the Plan One-Step 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 Plan One-Step. 8.8 Renal Impairment. No formal studies were conducted to evaluate the effect of renal disease on the disposition of Plan One-Step.

WARNINGS AND PRECAUTIONS SECTION.

5 WARNINGS AND PRECAUTIONS. Ectopic pregnancy: Women who become pregnant or complain of lower abdominal pain after taking Plan One- Step should be evaluated for ectopic pregnancy. (5.1)Plan One-Step is not effective in terminating an existing pregnancy. (5.2)Effect on menses: Plan One-Step may alter the next expected menses. If menses is delayed beyond week, pregnancy should be considered. (5.3)STI/HIV: Plan One-Step does not protect against STI/HIV. (5.4). Ectopic pregnancy: Women who become pregnant or complain of lower abdominal pain after taking Plan One- Step should be evaluated for ectopic pregnancy. (5.1). Plan One-Step is not effective in terminating an existing pregnancy. (5.2). Effect on menses: Plan One-Step may alter the next expected menses. If menses is delayed beyond week, pregnancy should be considered. (5.3). STI/HIV: Plan One-Step does not protect against STI/HIV. (5.4). 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. history of ectopic pregnancy is not 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 Plan One-Step. 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 Plan One-Step.. 5.2 Existing Pregnancy. Plan One-Step is not effective in terminating an existing pregnancy.. 5.3 Effects on Menses Some women may experience spotting few days after taking Plan One-Step. 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 delay in the onset of expected menses beyond week, consider the possibility of pregnancy.. 5.4 STI/HIV. Plan One-Step does not protect against HIV infection (AIDS) or other sexually transmitted infections (STIs).. 5.5 Physical Examination and Follow-up. physical examination is not required prior to prescribing Plan One-Step. 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 Plan One-Step.. 5.6 Fertility Following Discontinuation. rapid return of fertility is likely following treatment with Plan One-Step for emergency contraception; therefore, routine contraception should be continued or initiated as soon as possible following use of Plan One-Step to ensure ongoing prevention of pregnancy.