DailyMed Label: Juleber

DailyMed Label: Juleber

2024

DailyMed Prescription

Juleber

Desogestrel and Ethinyl Estradiol

Northstar Rx LLC

NDC: 16714-464

NDC: 16714-464

NDC: 16714-464

NDC: 16714-464

NDC: 16714-464

NDC: 16714-464

JULEBER™ (desogestrel and ethinyl estradiol tablets, USP) provide an oral contraceptive regimen of 21 orange tablets each containing 0.15 mg desogestrel (13-ethyl-11-methylene-18,19-dinor-17 alpha-pregn-4-en-20-yn-17-ol), and 0.03 mg ethinyl estradiol (19-nor-17 alpha-pregna-1,3,5 (10)-trien-20-yne-3,17, diol). Each "active" orange tablet with "S3" debossed on one side contains the following inactive ingredients: lactose monohydrate, pregelatinized corn starch, povidone, stearic acid, vitaminE, HPMC/hypromellose, titanium dioxide, macrogol/polyethylene glycol, D&C Yellow #10 Aluminum Lake, FD&C Yellow #6 Aluminium Lake, Iron Oxide Yellow, FD&C Red #40 Aluminum Lake, FD&C Blue #2 Aluminum Lake. Each "inactive" reminder white, biconvex, round tablets with "P" debossed on one side and " N " on the other side contains the following inactive ingredients: titanium dioxide, polydextrose, hypromellose, triacetin, polyethylene glycol, lactose, magnesium stearate, and pregelatinized corn starch. The 21 orange tablets meet USP Dissolution Test 2. image-01

JULEBER™ is indicated for the prevention of pregnancy in women who elect to use oral contraceptives as a method of contraception. Oral contraceptives are highly effective. Table I lists the typical accidental pregnancy rates for users of combined oral contraceptives and other methods of contraception. The efficacy of these contraceptive methods, except sterilization, the IUD, and the Norplant System depends upon the reliability with which they are used. Correct and consistent use of these methods can result in lower failure rates. In a clinical trial with desogestrel and ethinyl estradiol tablets 1,195 subjects completed 11,656 cycles and a total of 10 pregnancies were reported. This represents an overall user-efficacy (typical user-efficacy) pregnancy rate of 1.12 per 100 women-years. This rate includes patients who did not take the drug correctly. TABLE I: 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. % of Women Experiencing an Unintended Pregnancy within the First Year of Use % of Women Continuing Use at One Year 3 Method Typical Use 1 Perfect Use 2 (1) (2) (3) (4) Chance 4 85 85 Spermicides 5 26 6 40 Periodic abstinence 25 63 Calendar 9 Ovulation Method 3 Sympto-Thermal 6 2 Post-Ovulation 1 Withdrawal 19 4 Cap 7 Parous Women 40 26 42 Nulliparous Women 20 9 56 Sponge Parous Women 40 20 42 Nulliparous Women 20 9 56 Diaphragm 7 20 6 56 Condom 8 Female (Reality) ® 21 5 56 Male 14 3 61 Pill 5 71 Progestin Only 0.5 Combined 0.1 IUD Progesterone T 2.0 1.5 81 Copper T380A 0.8 0.6 78 LNg 20 0.1 0.1 81 Depo-Provera 0.3 0.3 70 Norplant ® and Norplant-2 ® 0.05 0.05 88 Female sterilization 0.5 0.5 100 Male sterilization 0.15 0.10 100 Emergency Contraceptive Pills: Treatment initiated within 72 hours after unprotected intercourse reduces the risk of pregnancy by at least 75%. 9 Lactation 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 accidental 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 accidental 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 percents 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 percent 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 phases. 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 FDA 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 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 of duration of breastfeeds is reduced, bottle feeds are introduced, or the baby reaches 6 months of age. JULEBER™ has not been studied for and is not indicated for use in emergency contraception .

To achieve maximum contraceptive effectiveness, JULEBER™ must be taken exactly as directed and at intervals not exceeding 24 hours. JULEBER™ may be initiated using either a Sunday start or a Day 1 start. NOTE: Each cycle pack dispenser is preprinted with the days of the week, starting with Sunday, to facilitate a Sunday start regimen. Six different “day label sticker” are provided with each cycle pack dispenser in order to accommodate a Day 1 start regimen. In this case, the patient should place the self-adhesive “day label sticker” that corresponds to her starting day over the preprinted days. IMPORTANT: The possibility of ovulation and conception prior to initiation of use of JULEBER™ should be considered. DAY 1 START The dosage of JULEBER TM for the initial cycle of therapy is one orange "active" tablet administered daily from the 1st day through the 21st day of the menstrual cycle, counting the first day of menstrual flow as "Day 1". Tablets are taken without interruption as follows: One orange "active" tablet daily for 21 days, then one white "reminder" tablet daily for 7 days. After 28 tablets have been taken, a new course is started and an orange "active" tablet is taken the next day. The use of JULEBER TM for contraception may be initiated 4 weeks postpartum in women who elect not to breastfeed. When the tablets are administered during the postpartum period, the increased risk of thromboembolic disease associated with the postpartum period must be considered. (See CONTRAINDICATIONS and WARNINGS concerning thromboembolic disease. See also PRECAUTIONS Nursing Mothers .) If the patient starts on JULEBER TM postpartum, and has not yet had a period, she should be instructed to use another method of contraception until an orange "active" tablet has been taken daily for 7 days. The possibility of ovulation and conception prior to initiation of medication should be considered. If the patient misses one (1) orange "active" tablet in Weeks 1, 2, or 3, the orange "active" tablet should be taken as soon as she remembers. If the patient misses two (2) orange "active" tablets in Week 1 or Week 2, the patient should take two (2) orange "active" tablets the day she remembers and two (2) orange "active" tablets the next day; and then continue taking one (1) orange "active" tablet a day until she finishes the pack. The patient should be instructed to use a back-up method of birth control such as condoms or spermicide if she has sex in the seven (7) days after missing pills. If the patient misses two (2) orange "active" tablets in the third week or misses three (3) or more orange "active" tablets in a row, the patient should throw out the rest of the pack and start a new pack that same day. The patient should be instructed to use a back-up method of birth control if she has sex in the seven (7) days after missing pills. SUNDAY START When taking JULEBER TM , the first orange "active" tablet should be taken on the first Sunday after menstruation begins. If the period begins on Sunday, the first orange "active" tablet is taken on that day. If switching directly from another oral contraceptive, the first orange "active" tablet should be taken on the first Sunday after the last ACTIVE tablet of the previous product. Tablets are taken without interruption as follows: One orange "active" tablet daily for 21 days, then one white "reminder" tablet daily for 7 days. After 28 tablets have been taken, a new course is started and an orange "active" tablet is taken the next day (Sunday). When initiating a Sunday start regimen, another method of contraception should be used until after the first 7 consecutive days of administration. The use of JULEBER TM for contraception may be initiated 4 weeks postpartum. When the tablets are administered during the postpartum period, the increased risk of thromboembolic disease associated with the postpartum period must be considered. (See CONTRAINDICATIONS and WARNINGS concerning thromboembolic disease. See also PRECAUTIONS Nursing Mothers .) If the patient starts on JULEBER TM postpartum, and has not yet had a period, she should be instructed to use another method of contraception until an orange "active" tablet has been taken daily for 7 days. The possibility of ovulation and conception prior to initiation of medication should be considered. If the patient misses one (1) orange active tablet in Weeks 1, 2, or 3, the orange "active" tablet should be taken as soon as she remembers. If the patient misses two (2) orange "active" tablets in Week 1 or Week 2, the patient should take two (2) orange "active" tablets the day she remembers and two (2) orange "active" tablets the next day; and then continue taking one (1) orange "active" tablet a day until she finishes the pack. The patient should be instructed to use a back-up method of birth control such as a condom or spermicide if she has sex in the seven (7) days after missing pills. If the patient misses two (2) orange "active" tablets in the third week or misses three (3) or more orange "active" tablets in a row, the patient should continue taking one orange "active" tablet every day until Sunday. On Sunday the patient should throw out the rest of the pack and start a new pack that same day. The patient should be instructed to use a back-up method of birth control if she has sex in the seven (7) days after missing pills. ADDITIONAL INSTRUCTIONS FOR ALL DOSING REGIMENS Breakthrough bleeding, spotting, and amenorrhea are frequent reasons for patients discontinuing oral contraceptives. In breakthrough bleeding, as in all cases of irregular bleeding from the vagina, nonfunctional causes should be borne in mind. In undiagnosed persistent or recurrent abnormal bleeding from the vagina, adequate diagnostic measures are indicated to rule out pregnancy or malignancy. If pathology has been excluded, time or a change to another formulation may solve the problem. Changing to an oral contraceptive with a higher estrogen content, while potentially useful in minimizing menstrual irregularity, should be done only if necessary since this may increase the risk of thromboembolic disease. Use of oral contraceptives in the event of a missed menstrual period: 1. If the patient has not adhered to the prescribed schedule, the possibility of pregnancy should be considered at the time of the first missed period and oral contraceptive use should be discontinued if pregnancy is confirmed. 2. If the patient has adhered to the prescribed regimen and misses two consecutive periods, pregnancy should be ruled out.

Oral contraceptives should not be used in women who currently have the following conditions: ● Thrombophlebitis or thromboembolic disorders ● A past history of deep vein thrombophlebitis or thromboembolic disorders ● Known thrombophilic conditions ● Cerebral vascular or coronary artery disease (current or history) ● Valvular heart disease with complications ● Persistent blood pressure values of ≥160 mm Hg systolic or ≥100 mm Hg diastolic 102 ● Diabetes with vascular involvement ● Headaches with focal neurological symptoms ● Major surgery with prolonged immobilization ● Current diagnosis of, or history of, breast cancer, which may be hormone-sensitive ● Carcinoma of the endometrium or other known or suspected estrogen-dependent neoplasia ● Undiagnosed abnormal genital bleeding ● Cholestatic jaundice of pregnancy or jaundice with prior pill use ● Acute or chronic hepatocellular disease with abnormal liver function ● Hepatic adenomas or carcinomas ● Known or suspected pregnancy ● Hypersensitivity to any component of this product ● Are receiving Hepatitis C drug combinations containing ombitasvir/ paritaprevir/ritonavir, with or without dasabuvir, due to the potential for ALT elevations (see section 5 in WARNINGS, Risk of Liver Enzyme Elevations with Concomitant Hepatitis C Treatment ).

Patients should be counseled that this product does not protect against HIV infection (AIDS) and other sexually transmitted diseases. It is good medical practice for all women to have annual history and physical examinations, including women using oral contraceptives. The physical examination, however, may be deferred until after initiation of oral contraceptives if requested by the woman and judged appropriate by the clinician. The physical examination should include special reference to blood pressure, breasts, abdomen and pelvic organs, including cervical cytology, and relevant laboratory tests. In case of undiagnosed, persistent or recurrent abnormal vaginal bleeding, appropriate measures should be conducted to rule out malignancy. Women with a strong family history of breast cancer or who have breast nodules should be monitored with particular care. Women who are being treated for hyperlipidemias should be followed closely if they elect to use oral contraceptives. Some progestogens may elevate LDL levels and may render the control of hyperlipidemias more difficult. If jaundice develops in any woman receiving oral contraceptives, the medication should be discontinued. Steroid hormones may be poorly metabolized in patients with impaired liver function. Oral contraceptives may cause some degree of fluid retention. They should be prescribed with caution, and only with careful monitoring, in patients with conditions which might be aggravated by fluid retention. Women with a history of depression should be carefully observed and the drug discontinued if depression recurs to a serious degree. Contact lens wearers who develop visual changes or changes in lens tolerance should be assessed by an ophthalmologist. Consult the labeling of concurrently-used drugs to obtain further information about interactions with hormonal contraceptives or the potential for enzyme alterations. Effects of Other Drugs on Combined Hormonal Contraceptives Substances decreasing the plasma concentrations of COCs and potentially diminishing the efficacy of COCs: Drugs or herbal products that induce certain enzymes, including cytochrome P450 3A4 (CYP3A4), may decrease the plasma concentrations of COCs and potentially diminish the effectiveness of CHCs or increase breakthrough bleeding. Some drugs or herbal products that may decrease the effectiveness of hormonal contraceptives include phenytoin, barbiturates, carbamazepine, bosentan, felbamate, griseofulvin, oxcarbazepine, rifampicin, topiramate, rifabutin, rufinamide, aprepitant, and products containing St. John's wort. Interactions between hormonal contraceptives and other drugs may lead to breakthrough bleeding and/or contraceptive failure. Counsel women to use an alternative method of contraception or a back-up method when enzyme inducers are used with CHCs, and to continue back-up contraception for 28 days after discontinuing the enzyme inducer to ensure contraceptive reliability. Substances increasing the plasma concentrations of COCs: Co-administration of atorvastatin or rosuvastatin and certain COCs containing EE increase AUC values for EE by approximately 20-25%. Ascorbic acid and acetaminophen may increase plasma EE concentrations, possibly by inhibition of conjugation. CYP3A4 inhibitors such as itraconazole, voriconazole, fluconazole, grapefruit juice, or ketoconazole may increase plasma hormone concentrations. Human immunodeficiency virus (HIV)/ Hepatitis C virus (HCV) protease inhibitors and non-nucleoside reverse transcriptase inhibitors: Significant changes (increase or decrease) in the plasma concentrations of estrogen and/or progestin have been noted in some cases of co-administration with HIV protease inhibitors (decrease [e.g., nelfinavir, ritonavir, darunavir/ritonavir, (fos)amprenavir/ritonavir, lopinavir/ritonavir, and tipranavir/ritonavir] or increase [e.g., indinavir and atazanavir/ritonavir]) /HCV protease inhibitors (decrease [e.g., boceprevir and telaprevir]) or with non-nucleoside reverse transcriptase inhibitors (decrease [e.g., nevirapine] or increase [e.g., etravirine]). Concomitant Use with HCV Combination Therapy – Liver Enzyme Elevation Do not co-administer JULEBER™ with HCV drug combinations containing ombitasvir/paritaprevir/ ritonavir, with or without dasabuvir, due to potential for ALT elevations (see section 5 in WARNINGS, Risk of Liver Enzyme Elevations with Concomitant Hepatitis C Treatment ). Colesevelam: Colesevelam, a bile acid sequestrant, given together with a combination oral hormonal contraceptive, has been shown to significantly decrease the AUC of EE. A drug interaction between the contraceptive and colesevelam was decreased when the two drug products were given 4 hours apart. Effects of Combined Hormonal Contraceptives on Other Drugs COCs containing EE may inhibit the metabolism of other compounds (e.g., cyclosporine, prednisolone, theophylline, tizanidine, and voriconazole) and increase their plasma concentrations. COCs have been shown to decrease plasma concentrations of acetaminophen, clofibric acid, morphine, salicylic acid, temazepam and lamotrigine. Significant decrease in plasma concentration of lamotrigine has been shown, likely due to induction of lamotrigine glucuronidation. This may reduce seizure control; therefore, dosage adjustments of lamotrigine may be necessary. Women on thyroid hormone replacement therapy may need increased doses of thyroid hormone because serum concentrations of thyroid-binding globulin increases with use of COCs. Certain endocrine and liver function tests and blood components may be affected by oral contraceptives: a. Increased prothrombin and factors VII, VIII, IX, and X; decreased antithrombin 3; increased norepinephrine-induced platelet aggregability. b. Increased thyroid binding globulin (TBG) leading to increased circulating total thyroid hormone, as measured by protein-bound iodine (PBI), T4 by column or by radioimmunoassay. Free T3 resin uptake is decreased, reflecting the elevated TBG, free T4 concentration is unaltered. c. Other binding proteins may be elevated in serum. d. Sex hormone binding globulins are increased and result in elevated levels of total circulating sex steroids however, free or biologically active levels either decrease or remain unchanged. e. Triglycerides may be increased and levels of various other lipids and lipoproteins may be affected. f. Glucose tolerance may be decreased. g. Serum folate levels may be depressed by oral contraceptive therapy. This may be of clinical significance if a woman becomes pregnant shortly after discontinuing oral contraceptives. See WARNINGS . Pregnancy Category X. (see CONTRAINDICATIONS and WARNINGS) . Small amounts of oral contraceptive steroids have been identified in the milk of nursing mothers and a few adverse effects on the child have been reported, including jaundice and breast enlargement. In addition, oral contraceptives given in the postpartum period may interfere with lactation by decreasing the quantity and quality of breast milk. If possible, the nursing mother should be advised not to use oral contraceptives but to use other forms of contraception until she has completely weaned her child. Safety and efficacy of norethindrone and ethinyl estradiol tablets has been established in women of reproductive age. 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 this product before menarche is not indicated. This product has not been studied in women over 65 years of age and is not indicated in this population.

To report SUSPECTED ADVERSE REACTIONS, contact Northstar Rx LLC. at 1-800-206-7821 or FDA at 1-800-FDA-1088 or

JULEBER™ (desogestrel and ethinyl estradiol tablets, USP) contain 21 round orange tablets, and 7 round white tablets in a blister card (NDC 16714-464-01). Each orange tablet (debossed with "S3" on one side) contains 0.15 mg desogestrel and 0.03 mg ethinyl estradiol. Each white tablet (debossed with "P" on one side and " N " on the other side) contains inert ingredients. JULEBER™ is available in the following configurations: Carton of 1 NDC 16714-464-02 Carton of 3 NDC 16714-464-03 Carton of 6 NDC 16714-464-04 Store at 20° to 25°C (68° to 77°F) [See USP Controlled Room Temperature]. Rx Only

Combined oral contraceptives act by suppression of gonadotropins. Although the primary mechanism of this action is inhibition of ovulation, other alterations include changes in the cervical mucus which increase the difficulty of sperm entry into the uterus, and changes in the endometrium which reduce the likelihood of implantation. Receptor binding studies, as well as studies in animals, have shown that 3-keto-desogestrel, the biologically active metabolite of desogestrel, combines high progestational activity with minimal intrinsic androgenicity. 91,92 The relevance of this latter finding in humans is unknown. Desogestrel is rapidly and almost completely absorbed and converted into 3-ketodesogestrel, its biologically active metabolite. Following oral administration, the relative bioavailability of desogestrel, as measured by serum levels of 3-keto-desogestrel, is approximately 84%. In the third cycle of use after a single dose of desogestrel and ethinyl estradiol tablets, maximum concentrations of 3-keto-desogestrel of 2,805 ± 1,203 pg/mL (mean ± SD) are reached at 1.4 ± 0.8 hours. The area under the curve (AUC 0 -∞) is 33,858 ± 11,043 pg/mL*hr after a single dose. At steady state, attained from at least day 19 onwards, maximum concentrations of 5,840 ± 1,667 pg/mL are reached at 1.4 ± 0.9 hours. The minimum plasma levels of 3-keto-desogestrel at steady state are 1,400 ± 560 pg/mL. The AUC 0-24 at steady state is 52,299 ± 17,878 pg/mL*hr. The mean AUC 0 -∞ for 3-keto-desogestrel at single dose is significantly lower than the mean AUC 0-24 at steady state. This indicates that the kinetics of 3-keto-desogestrel are non-linear due to an increase in binding of 3-keto-desogestrel to sex hormone-binding globulin in the cycle, attributed to increased sex hormone-binding globulin levels which are induced by the daily administration of ethinyl estradiol. Sex hormone-binding globulin levels increased significantly in the third treatment cycle from day 1 (150 ± 64 nmol/L) to day 21 (230 ± 59 nmol/L). The elimination half-life for 3-keto-desogestrel is approximately 38 ± 20 hours at steady state. In addition to 3-keto-desogestrel, other phase I metabolites are 3α -OH-desogestrel, 3β -OH desogestrel, and 3α -OH-5α -H-desogestrel. These other metabolites are not known to have any pharmacologic effects, and are further converted in part by conjugation (phase II metabolism) into polar metabolites, mainly sulfates and glucuronides. Ethinyl estradiol is rapidly and almost completely absorbed. In the third cycle of use after a single dose of desogestrel and ethinyl estradiol tablets, the relative bioavailability is approximately 83%. In the third cycle of use after a single dose of desogestrel and ethinyl estradiol tablets, maximum concentrations of ethinyl estradiol of 95 ± 34 pg/mL are reached at 1.5 ± 0.8 hours. The AUC 0 -∞ is 1,471 ± 268 pg/mL*hr after a single dose. At steady state, attained from at least day 19 onwards, maximum ethinyl estradiol concentrations of 141 ± 48 pg/mL are reached at about 1.4 ± 0.7 hours. The minimum serum levels of ethinyl estradiol at steady state are 24 ± 8.3 pg/mL. The AUC 0-24 , at steady state is 1,117 ± 302 pg/mL*hr. The mean AUC 0 -∞ for ethinyl estradiol following a single dose during treatment cycle 3 does not significantly differ from the mean AUC 0-24 at steady state. This finding indicates linear kinetics for ethinyl estradiol. The elimination half-life is 26 ± 6.8 hours at steady state. Ethinyl estradiol is subject to a significant degree of presystemic conjugation (phase II metabolism). Ethinyl estradiol escaping gut wall conjugation undergoes phase I metabolism and hepatic conjugation (phase II metabolism). Major phase I metabolites are 2-OH-ethinyl estradiol and 2-methoxy-ethinyl estradiol. Sulfate and glucuronide conjugates of both ethinyl estradiol and phase I metabolites, which are excreted in bile, can undergo enterohepatic circulation.

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