DailyMed Label: Bekyree

DailyMed Label: Bekyree

2023

DailyMed Prescription

Bekyree

desogestrel and ethinyl estradiol and ethinyl estradiol

Lupin Pharmaceuticals, Inc.

NDC: 68180-275

NDC: 68180-299

NDC: 68180-318

NDC: 68180-340

NDC: 68180-275

NDC: 68180-275

Bekyree™ (desogestrel and ethinyl estradiol tablets USP and ethinyl estradiol tablets USP) provide an oral contraceptive regimen of 21 white round biconvex tablets each containing 0.15 mg desogestrel (13-ethyl-11-methylene-18,19-dinor-17 alpha-pregn-4-en- 20-yn-17-ol), 0.02 mg ethinyl estradiol (19-nor-17 alpha-pregna-1,3,5 (10)-trien-20-yne-3,17-diol), and inactive ingredients which include colloidal silicon dioxide, corn starch, lactose monohydrate, magnesium stearate, povidone, stearic acid, talc, vitamin E and opadry white, a film coating made of hypromellose, polyethylene glycol, and titanium dioxide, followed by 2 inert green, mottled, round, biconvex tablets with the following inactive ingredients: corn starch, lactose monohydrate, magnesium stearate, D&C Yellow No. 10 Aluminum Lake, FD&C Blue No. 2 Aluminum Lake and FD&C Yellow No. 6 Aluminum Lake. Bekyree   also contains 5 yellow round biconvex tablets containing 0.01 mg ethinyl estradiol (19-nor-17 alpha-pregna-1,3,5 (10)-trien-20-yne-3,17-diol) and inactive ingredients which include colloidal silicon dioxide, corn starch, lactose monohydrate, magnesium stearate, povidone, stearic acid, talc, vitamin E and opadry yellow, a film coating made of FD&C Yellow No. 5 Aluminum Lake, hypromellose, iron oxide yellow, polyethylene glycol, and titanium dioxide. The molecular weights for desogestrel and ethinyl estradiol are 310.5 and 296.40 respectively. The structural formulas are as follows: Desogestrel and Ethinyl Estradiol Tablets USP, 0.15 mg/0.02 mg meet USP Dissolution Test 2. Desogestrel Ethinyl Estradiol USP

Bekyree (desogestrel and ethinyl estradiol tablets USP and ethinyl estradiol tablets USP) are indicated for the prevention of pregnancy in women who elect to use this product as a method of contraception. Oral contraceptives are highly effective. Table II lists the typical accidental pregnancy rates for users of combination oral contraceptives and other methods of contraception. The efficacy of these contraceptive methods, except sterilization, depends upon the reliability with which they are used. Correct and consistent use of these methods can result in lower failure rates. TABLE II: 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. Among couples attempting to avoid pregnancy, the percentage who continue to use a method for one year. b    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. c     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. d    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. e     Foams, creams, gels, vaginal suppositories, and vaginal film. f     Cervical mucus (ovulation) method supplemented by calendar in the pre-ovulatory and basal body temperature in the post-ovulatory phases. g    With spermicidal cream or jelly. h    Without spermicides. % of Women Experiencing an Unintended Pregnancy within the First Year of Use % of Women Continuing Use at One Year a Method Typical Use b (2) Perfect Use c (3) (4) (1) Chance d 85 85 Spermicides e 26 6 40 Periodic abstinence 25 63 Calendar 9 Ovulation Method 3 Sympto-Thermal f 2 Post-Ovulation 1 Withdrawal 19 4 Cap g Parous Women 40 26 42 Nulliparous Women 20 9 56 Sponge Parous Women 40 20 42 Nulliparous Women 20 9 56 Diaphragm g 20 6 56 Condom h 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 T 380A 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

To achieve maximum contraceptive effectiveness, Bekyree (desogestrel/ethinyl estradiol and ethinyl estradiol) tablets must be taken exactly as directed and at intervals not exceeding 24 hours. Bekyree may be initiated using either a Sunday start or a Day 1 start. NOTE: Each blister pack is preprinted with the days of the week, starting with Sunday, to facilitate a Sunday start regimen. Six different "day label strips" are provided with each blister pack in order to accommodate a Day 1 start regimen. In this case, the patient should place the self-adhesive "day label strip" that corresponds to her starting day over the preprinted days. IMPORTANT: The possibility of ovulation and conception prior to initiation of use of Bekyree should be considered. The use of Bekyree 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   for Nursing mothers) . If the patient starts on Bekyree postpartum, and has not yet had a period, she should be instructed to use another method of contraception until a white tablet has been taken daily for 7 days. SUNDAY START When initiating a Sunday start regimen, another method of contraception should be used until after the first 7 consecutive days of administration. Using a Sunday start, tablets are taken daily without interruption as follows: The first white tablet should be taken on the first Sunday after menstruation begins (if menstruation begins on Sunday, the first white tablet is taken on that day). One white tablet is taken daily for 21 days, followed by 1 green (inert) tablet daily for 2 days and 1 yellow (active) tablet daily for 5 days. For all subsequent cycles, the patient then begins a new 28 tablet regimen on the next day (Sunday) after taking the last yellow tablet. [If switching from a Sunday start oral contraceptive, the first Bekyree (desogestrel/ethinyl estradiol and ethinyl estradiol) tablets should be taken on the second Sunday after the last tablet of a 21 day regimen or should be taken on the first Sunday after the last inactive tablet of a 28 day regimen.] If a patient misses 1 white tablet, she should take the missed tablet as soon as she remembers. If the patient misses 2 consecutive white tablets in Week 1 or Week 2, the patient should take 2 tablets the day she remembers and 2 tablets the next day; thereafter, the patient should resume taking 1 tablet daily until she finishes the blister pack. The patient should be instructed to use a back-up method of birth control if she has intercourse in the 7 days after missing pills. If the patient misses 2 consecutive white tablets in the third week or misses 3 or more white tablets in a row at any time during the cycle, the patient should keep taking 1 white tablet daily until the next Sunday. On Sunday the patient should throw out the rest of that blister pack and start a new blister pack that same day. The patient should be instructed to use a back-up method of birth control if she has intercourse in the 7 days after missing pills. DAY 1 START Counting the first day of menstruation as "Day 1", tablets are taken without interruption as follows: One white tablet daily for 21 days, one green (inert) tablet daily for 2 days followed by 1 yellow (ethinyl estradiol) tablet daily for 5 days. For all subsequent cycles, the patient then begins a new 28 tablet regimen on the next day after taking the last yellow tablet. [If switching directly from another oral contraceptive, the first white tablet should be taken on the first day of menstruation which begins after the last ACTIVE tablet of the previous product.] If a patient misses 1 white tablet, she should take the missed tablet as soon as she remembers. If the patient misses 2 consecutive white tablets in Week 1 or Week 2, the patient should take 2 tablets the day she remembers and 2 tablets the next day; thereafter, the patient should resume taking 1 tablet daily until she finishes the cycle pack. The patient should be instructed to use a back-up method of birth control if she has intercourse in the 7 days after missing pills. If the patient misses 2 consecutive white tablets in the third week or if the patient misses 3 or more white tablets in a row at any time during the cycle, the patient should throw out the rest of that cycle pack and start a new cycle pack that same day. The patient should be instructed to use a back-up method of birth control if she has intercourse in the 7 days after missing pills. ALL ORAL CONTRACEPTIVES 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, non-functional 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 both pregnancy and pathology have been excluded, time or a change to another preparation 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: 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 until pregnancy is ruled out. If the patient has adhered to the prescribed regimen and misses two consecutive periods, pregnancy should be ruled out before continuing oral contraceptive use.

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 Cerebral vascular or coronary artery disease Current diagnosis of, or history of, breast cancer, which may be hormone-sensitive Undiagnosed abnormal genital bleeding Cholestatic jaundice of pregnancy or jaundice with prior pill use Hepatic adenomas or carcinomas Are receiving Hepatitis C drug combinations containing ombitasvir/paritaprevir/ritonavir, with or without dasabuvir, due to the potential for ALT elevations (see 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 infections. 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 such drugs, 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. Contact lens wearers who develop visual changes or changes in lens tolerance should be assessed by an ophthalmologist. Reduced efficacy and increased incidence of breakthrough bleeding and menstrual irregularities have been associated with concomitant use of rifampin. A similar association, though less marked, has been suggested with barbiturates, phenylbutazone, phenytoin sodium, carbamazepine and possibly with griseofulvin, ampicillin, and tetracyclines (72). Combined hormonal contraceptives have been shown to significantly decrease plasma concentrations of lamotrigine when co-administered, likely due to induction of lamotrigine glucuronidation. This may reduce seizure control; therefore, dosage adjustments of lamotrigine may be necessary. Concomitant Use with Hepatitis C Virus (HCV) Combination Therapy – Liver Enzyme Elevation: Co-administration of Bekyree with HCV drug combinations containing ombitasvir/paritaprevir/ritonavir, with or without dasabuvir, due to potential for ALT elevations (see CONTRAINDICATIONS and WARNINGS, RISK OF LIVER ENZYME ELEVATIONS WITH CONCOMITANT HEPATITIS C TREATMENT ) . Co-administration of Bekyree and glecaprevir/pibrentasvir is not recommended due to potential for ALT elevations. Consult the labeling of the concurrently-used drug to obtain further information about interactions with hormonal contraceptives or the potential for enzyme alterations. Certain endocrine and liver function tests and blood components may be affected by oral contraceptives: Increased prothrombin and factors VII, VIII, IX and X; decreased antithrombin 3; increased norepinephrine-induced platelet aggregability. 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. Other binding proteins may be elevated in serum. 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. High-density lipoprotein cholesterol (HDL-C) and triglycerides may be increased, while low-density lipoprotein cholesterol (LDL-C) and total cholesterol (Total-C) may be decreased or unchanged. Glucose tolerance may be decreased. 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 section. Discontinue Bekyree if pregnancy occurs because there is no reason to use COCs in pregnancy. See   WARNINGS sections . Small amounts of oral contraceptive steroids have been identified in human milk 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 Bekyree (desogestrel/ethinyl estradiol and ethinyl estradiol) tablets have 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 contains FD+C Yellow No. 5 (tartrazine) which may cause allergic-type reactions (including bronchial asthma) in certain susceptible persons. Although the overall incidence of FD+C Yellow No. 5 (tartrazine) sensitivity in the general population is low, it is frequently seen in patients who also have aspirin hypersensitivity.

An increased risk of the following serious adverse reactions has been associated with the use of oral contraceptives (see WARNINGS section):

Reduced efficacy and increased incidence of breakthrough bleeding and menstrual irregularities have been associated with concomitant use of rifampin. A similar association, though less marked, has been suggested with barbiturates, phenylbutazone, phenytoin sodium, carbamazepine and possibly with griseofulvin, ampicillin, and tetracyclines (72). Combined hormonal contraceptives have been shown to significantly decrease plasma concentrations of lamotrigine when co-administered, likely due to induction of lamotrigine glucuronidation. This may reduce seizure control; therefore, dosage adjustments of lamotrigine may be necessary. Concomitant Use with Hepatitis C Virus (HCV) Combination Therapy – Liver Enzyme Elevation: Co-administration of Bekyree with HCV drug combinations containing ombitasvir/paritaprevir/ritonavir, with or without dasabuvir, due to potential for ALT elevations (see CONTRAINDICATIONS and WARNINGS, RISK OF LIVER ENZYME ELEVATIONS WITH CONCOMITANT HEPATITIS C TREATMENT ) . Co-administration of Bekyree and glecaprevir/pibrentasvir is not recommended due to potential for ALT elevations. Consult the labeling of the concurrently-used drug to obtain further information about interactions with hormonal contraceptives or the potential for enzyme alterations.

Bekyree (desogestrel and ethinyl estradiol tablets USP and ethinyl estradiol tablets USP) are available in cartons (NDC 68180-275-73) containing three pouches, each pouch (NDC 68180-275-71) containing a blister of 28 tablets (NDC 68180-275-71). Each blister (28 tablets) contains in the following order: 21 white, round, biconvex film-coated tablets, debossed with "L" on one side and "J2" on the other side each containing desogestrel 0.15 mg and ethinyl estradiol 0.02 mg. 2 inert green, mottled, round, biconvex tablets, debossed with "LU" on one side and "L22" on the other side. 5 yellow, round, biconvex film-coated tablets, debossed with "L" on one side and "J1" on the other side each containing ethinyl estradiol 0.01 mg. Store at 25°C (77°F); excursions permitted to 15 to 30°C (59 to 86°F) [see USP Controlled Room Temperature].

Combination 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 the endometrium (which reduce the likelihood of implantation). Receptor binding studies, as well as studies in animals, have shown that etonogestrel, 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. Absorption Desogestrel is rapidly and almost completely absorbed and converted into etonogestrel, its biologically active metabolite. Following oral administration, the relative bioavailability of desogestrel compared to a solution, as measured by serum levels of etonogestrel, is approximately 100%. Bekyree   provide two different regimens of ethinyl estradiol; 0.02 mg in the combination tablet [white] as well as 0.01 mg in the yellow tablet. Ethinyl estradiol is rapidly and almost completely absorbed. After a single dose of desogestrel and ethinyl estradiol combination tablet [white], the relative bioavailability of ethinyl estradiol is approximately 93% while the relative bioavailability of the 0.01 mg ethinyl estradiol tablet [yellow] is 99%. The effect of food on the bioavailability of Bekyree following oral administration has not been evaluated. The pharmacokinetics of etonogestrel and ethinyl estradiol following multiple dose administration of Bekyree was determined during the third cycle in 17 subjects. Plasma concentrations of etonogestrel and ethinyl estradiol reached steady-state by Day 21. The AUC (0–24) for etonogestrel at steady-state on Day 21 was approximately 2.2 times higher than AUC (0–24) on Day 1 of the third cycle. The pharmacokinetic parameters of etonogestrel and ethinyl estradiol during the third cycle following multiple dose administration of Bekyree are summarized in Table I. TABLE I: MEAN (SD) PHARMACOKINETIC PARAMETERS OF Bekyree OVER A 28-DAY DOSING PERIOD IN THE THIRD CYCLE (n=17). Etonogestrel Day Dose Desogestrel mg C m a x pg / mL T m a x h t 1 / 2 h AUC 0 - 2 4 pg / mL . hr CL / F   L / h 1 0.15 2503.6 (987.6) 2.4 (1) 29.8 (16.3) 17,832 (5674) 5.4 (2.5) 21 0.15 4091.2 (1186.2) 1.6 (0.7) 27.8 (7.2) 39,391 (12,134) 4.4 (1.4) C m a x - measured peak concentration T m a x - observed time of peak concentration t 1 / 2 - elimination half-life, calculated by 0.693/K e l i m AUC 0 - 2 4 -area under the concentration-time curve calculated by the linear trapezoidal rule (Time 0 to 24 hours CL/F-apparent clearance Ethinyl  Estradiol Day Dose mg C m a x pg / mL T m a x h t 1 / 2 h AUC 0 - 2 4 pg / mL . hr CL / F  L / h 1 0.02 51.9 (15.4) 2.9 (1.2) 16.5 (4.8) 566 (173)   1 25.7 (9.1) 21 0.02 62.2 (25.9) 2 (0.8) 23.9 (25.5) 597 (127)   1 35.1 (8.2) 24 0.01 24.6 (10.8) 2.4 (1) 18.8 (10.3) 246 (65) 43.6 (12.2) 28 0.01 35.3 (27.5) 2.1 (1.3) 18.9 (8.3) 312 (62) 33.2 (6.6) Distribution Etonogestrel, the active metabolite of desogestrel, was found to be 99% protein bound, primarily to sex hormone-binding globulin (SHBG). Ethinyl estradiol is approximately 98.3% bound, mainly to plasma albumin. Ethinyl estradiol does not bind to SHBG, but induces SHBG synthesis. Desogestrel, in combination with ethinyl estradiol, does not counteract the estrogen-induced increase in SHBG, resulting in lower serum levels of free testosterone (96–99). Metabolism Desogestrel: Desogestrel is rapidly and completely metabolized by hydroxylation in the intestinal mucosa and on first pass through the liver to etonogestrel. Other metabolites (i.e., 3α-OH-desogestrel, 3β-OH-desogestrel, and 3α-OH-5α-H-desogestrel) with no pharmacologic actions also have been identified and these metabolites may undergo glucuronide and sulfate conjugation. Ethinyl Estradiol: 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. Excretion Etonogestrel and ethinyl estradiol are excreted in urine, bile, and feces. At steady state, on Day 21, the elimination half-life of etonogestrel is 27.8±7.2 hours and the elimination half-life of ethinyl estradiol for the combination tablet is 23.9±25.5 hours. For the 0.01 mg ethinyl estradiol tablet [yellow], the elimination half-life at steady state, Day 28, is 18.9±8.3 hours. Special Populations Race There is no information to determine the effect of race on the pharmacokinetics of Bekyree. Hepatic Insufficiency No formal studies were conducted to evaluate the effect of hepatic disease on the disposition of Bekyree. Renal Insufficiency No formal studies were conducted to evaluate the effect of renal disease on the disposition of Bekyree. Drug-Drug Interactions Interactions between desogestrel/ethinyl estradiol and other drugs have been reported in the literature. No formal drug-drug interaction studies were conducted (see PRECAUTIONS section) .

Bekyree™ desogestrel and ethinyl estradiol tablets USP, 0.15 mg/0.02 mg and ethinyl estradiol tablets USP,0.01 mg NDC 68180-275-71 Blister Label: 28 Tablets Bekyree™ desogestrel and ethinyl estradiol tablets USP, 0.15 mg/0.02 mg and ethinyl estradiol tablets USP,0.01 mg NDC 68180-275-71 Pouch Label: 1 Blister of 28 Tablets Bekyree™ desogestrel and ethinyl estradiol tablets USP, 0.15 mg/0.02 mg and ethinyl estradiol tablets USP,0.01 mg NDC 68180-275-73 Carton Label: 3 Blisters of 28 Tablets each blister pouch carton