Tydemy
Drospirenone, Ethinyl Estradiol and Levomefolate Calcium and Levomefolate Calcium · Kit
Uses
Tydemy is a combination of drospirenone, a progestin and ethinyl estradiol, an estrogen containing a folate, indicated for use by females of reproductive potential to: Prevent pregnancy. ( 1.1 ) Raise folate levels in females of reproductive potential who choose to use an oral contraceptive for contraception. ( 1.2 ) 1.1 Oral Contraceptive Tydemy TM is indicated for use by females of reproductive potential to prevent pregnancy. 1.2 Folate Supplementation Tydemy is indicated in females of reproductive potential who choose to use an oral contraceptive as their method of contraception, to raise folate levels for the purpose of reducing the risk of a neural tube defect in a pregnancy conceived while taking the product or shortly after discontinuing the product.
Dosage and administration
Take one tablet daily by mouth at the same time every day. ( 2.1 ) Tablets must be taken in the order directed on the blister pack. ( 2.1 ) 2.1 How to Take Tydemy Take one tablet by mouth at the same time every day. The failure rate may increase when pills are missed or taken incorrectly. To achieve maximum contraceptive effectiveness, Tydemy must be taken as directed, in the order directed on the blister pack. Single missed pills should be taken as soon as remembered. 2.2 How to Start Tydemy Instruct the patient to begin taking Tydemy either on the first day of her menstrual period (Day 1 Start) or on the first Sunday after the onset of her menstrual period (Sunday Start). Day 1 Start During the first cycle of Tydemy use, instruct the patient to take one orange Tydemy daily, beginning on Day 1 of her menstrual cycle. (The first day of menstruation is Day 1.) She should take one orange Tydemy daily for 21 consecutive days, followed by one light orange tablet, containing levomefolate alone, daily on Days 22 through 28. Tydemy should be taken in the order directed on the package at the same time each day, preferably after the evening meal or at bedtime with some liquid, as needed. Tydemy can be taken without regard to meals. If Tydemy is first taken later than the first day of the menstrual cycle, Tydemy should not be considered effective as a contraceptive until after the first 7 consecutive days of product administration. Instruct the patient to use a non-hormonal contraceptive as back-up during the first 7 days. The possibility of ovulation and conception prior to initiation of medication should be considered. Sunday Start During the first cycle of Tydemy use, instruct the patient to take one orange Tydemy daily, beginning on the first Sunday after the onset of her menstrual period. She should take one orange Tydemy daily for 21 consecutive days, followed by one light orange tablet, containing levomefolate alone, daily on Days 22 through 28. Tydemy should be taken in the order directed on the package at the same time each day, preferably after the evening meal or at bedtime with some liquid, as needed. Tydemy can be taken without regard to meals. Tydemy should not be considered effective as a contraceptive until after the first 7 consecutive days of product administration. Instruct the patient to use a non-hormonal contraceptive as back-up during the first 7 days. The possibility of ovulation and conception prior to initiation of medication should be considered. The patient should begin her next and all subsequent 28-day regimens of Tydemy on the same day of the week that she began her first regimen, following the same schedule. She should begin taking her orange tablets on the next day after ingestion of the last light orange folate tablet, regardless of whether or not a menstrual period has occurred or is still in progress. Anytime a subsequent cycle of Tydemy is started later than the day following administration of the last light orange tablet, the patient should use another method of contraception until she has taken an orange Tydemy daily for seven consecutive days. When switching from a different birth control pill When switching from another birth control pill, Tydemy should be started on the same day that a new pack of the previous oral contraceptive would have been started. When switching from a method other than a birth control pill When switching from a transdermal patch or vaginal ring, Tydemy should be started when the next application would have been due. When switching from an injection, Tydemy should be started when the next dose would have been due. When switching from an intrauterine contraceptive or an implant, Tydemy should be started on the day of removal. Withdrawal bleeding usually occurs within 3 days following the last orange tablet. If spotting or breakthrough bleeding occurs while taking Tydemy, instruct the patient to continue taking Tydemy by the regimen described above. Counsel her that this type of bleeding is usually transient and without significance; however, advise her that if the bleeding is persistent or prolonged, she should consult her healthcare provider. Although the occurrence of pregnancy is low if Tydemy is taken according to directions, if withdrawal bleeding does not occur, consider the possibility of pregnancy. If the patient has not adhered to the prescribed dosing schedule (missed one or more active tablets or started taking them on a day later than she should have), consider the possibility of pregnancy at the time of the first missed period and take appropriate diagnostic measures. If the patient has adhered to the prescribed regimen and misses two consecutive periods, rule out pregnancy. Discontinue Tydemy if pregnancy is confirmed. The risk of pregnancy increases with each active orange tablet missed. If breakthrough bleeding occurs following missed tablets, it will usually be transient and of no consequence. If the patient misses one or more light orange tablets, she should still be protected against pregnancy provided she begins taking a new cycle of orange tablets on the proper day. For postpartum women who do not breastfeed or after a second trimester abortion, start Tydemy no earlier than 4 weeks postpartum due to the increased risk of thromboembolism. If the patient starts Tydemy postpartum and has not yet had a period, evaluate for possible pregnancy, and instruct her to use an additional method of contraception until she has taken Tydemy for 7 consecutive days. 2.3 Missed Doses Table 1: Instructions for Tydemy Missed Doses If one orange active tablet is missed Take it as soon as possible. Take the next tablet at the regular time. This means two tablets may be taken in one day. A back-up birth control method is not required if the patient has sex. If two orange active tablets in a row are missed in Week 1 or Week 2 Take two tablets as soon as possible and two tablets the next day.
Dosage forms and strengths
Tydemy (drospirenone, ethinyl estradiol and levomefolate calcium tablets and levomefolate calcium tablets) is available in blister pack containing 28 tablets packed in a pouch. Such three pouches are packaged in a carton. Each blister contains 28 orange and light orange, round shaped, biconvex film-coated tablets in the following order: 21 orange tablets each containing 3 mg drospirenone (DRSP), 0.03 mg ethinyl estradiol (EE) and 0.451 mg levomefolate calcium debossed with "LU" on one side and "J63" on other side. 7 light orange tablets each containing 0.451 mg levomefolate calcium debossed with "LU" on one side and "J62" on other side. Tydemy consists of 28 film-coated, biconvex tablets in the following order ( 3 ): 21 orange tablets, each containing 3 mg drospirenone (DRSP), 0.03 mg ethinyl estradiol (EE) and 0.451 mg levomefolate calcium, 7 light orange tablets, each containing 0.451 mg levomefolate calcium.
Contraindications
Tydemy is contraindicated in females who are known to have or develop the following conditions: Renal impairment Adrenal insufficiency A high risk of arterial or venous thrombotic diseases. Examples include women who are known to: Smoke, if over age 35 [see Boxed Warning and Warnings and Precautions ( 5.1 )] Have deep vein thrombosis or pulmonary embolism, now or in the past [see Warnings and Precautions ( 5.1 )] Have cerebrovascular disease [see Warnings and Precautions ( 5.1 )] Have coronary artery disease [see Warnings and Precautions ( 5.1 )] Have thrombogenic valvular or thrombogenic rhythm diseases of the heart (for example, subacute bacterial endocarditis with valvular disease, or atrial fibrillation) [see Warnings and Precautions ( 5.1 )] Have inherited or acquired hypercoagulopathies [see Warnings and Precautions ( 5.1 )] Have uncontrolled hypertension [see Warnings and Precautions ( 5.6 )] Have diabetes mellitus with vascular disease [see Warnings and Precautions ( 5.8 )] Have headaches with focal neurological symptoms or have migraine headaches with or without aura if over age 35 [see Warnings and Precautions ( 5.9 )] Undiagnosed abnormal uterine bleeding [see Warnings and Precautions ( 5.10 )] Current diagnosis of, or history of, breast cancer, which may be hormone-sensitive [see Warnings and Precautions ( 5.3 )] Liver tumor (benign or malignant) or liver disease [see Warnings and Precautions ( 5.4 ) and Use in Specific Populations ( 8.7 )] Use of Hepatitis C drug combinations containing ombitasvir/paritaprevir/ritonavir, with or without dasabuvir due to the potential for ALT elevations [see Warnings and Precautions ( 5.5 ) and Drug Interactions ( 7.3 )] . Renal impairment ( 4 ) Adrenal insufficiency ( 4 ) A high risk of arterial or venous thrombotic diseases ( 4 ) Undiagnosed abnormal uterine bleeding ( 4 ) Breast cancer ( 4 ) Liver tumors or liver disease ( 4 ) Co-administration with Hepatitis C drug combinations containing ombitasvir, paritaprevir/ritonavir, with or without dasabuvir ( 4 )
Warnings and precautions
Vascular risks : Stop Tydemy if a thrombotic event occurs. Stop at least 4 weeks before and through 2 weeks after major surgery. Start no earlier than 4 weeks after delivery, in women who are not breastfeeding. ( 5.1 ) COCs containing DRSP may be associated with a higher risk of venous thromboembolism (VTE) than COCs containing levonorgestrel or some other progestins. Before initiating Tydemy in a new COC user or a woman who is switching from a contraceptive that does not contain DRSP, consider the risks and benefits of a DRSP-containing COC in light of her risk of a VTE. ( 5.1 ) Hyperkalemia : DRSP has anti-mineralocorticoid activity. Do not use in patients predisposed to hyperkalemia. Check serum potassium concentration during the first treatment cycle in women on long-term treatment with medications that may increase serum potassium concentration. ( 5.2 , 7.1 , 7.2 ) Liver disease : Discontinue Tydemy if jaundice occurs. ( 5.4 ) High blood pressure : Do not prescribe Tydemy for women with uncontrolled hypertension or hypertension with vascular disease. ( 5.6 ) Carbohydrate and lipid metabolic effects : Monitor prediabetic and diabetic women taking Tydemy. Consider an alternate contraceptive method for women with uncontrolled dyslipidemia. ( 5.8 ) Headache : Evaluate significant change in headaches and discontinue Tydemy if indicated. ( 5.9 ) Uterine bleeding : Evaluate irregular bleeding or amenorrhea. ( 5.10 ) 5.1 Thromboembolic Disorders and Other Vascular Problems Stop drospirenone, ethinyl estradiol and levomefolate calcium tablets and levomefolate calcium tablets if an arterial or venous thrombotic (VTE) event occurs. Based on presently available information on DRSP-containing COCs with 0.03 mg ethinyl estradiol (that is, Yasmin ® ), DRSP-containing COCs may be associated with a higher risk of venous thromboembolism (VTE) than COCs containing the progestin levonorgestrel or some other progestins. Epidemiologic studies that compared the risk of VTE reported that the risk ranged from no increase to a three-fold increase. Before initiating use of drospirenone, ethinyl estradiol and levomefolate calcium tablets and levomefolate calcium tablets in a new COC user or a woman who is switching from a contraceptive that does not contain DRSP, consider the risks and benefits of a DRSP-containing COC in light of her risk of a VTE. Known risk factors for VTE include smoking, obesity, and family history of VTE, in addition to other factors that contraindicate use of COCs [see Contraindications ( 4 )] . A number of studies have compared the risk of VTE for users of Yasmin ® (which contains 0.03 mg of EE and 3 mg of DRSP) to the risk for users of other COCs, including COCs containing levonorgestrel. Those that were required or sponsored by regulatory agencies are summarized in Table 2. Table 2: Estimates (Hazard Ratios) of Venous Thromboembolism Risk in Current Users of Yasmin ® Compared to Users of Oral Contraceptives that Contain Other Progestins a) "New users" -no use of combination hormonal contraception for at least the prior 6 months b) Includes low-dose COCs containing the following progestins: norgestimate, norethindrone, levonorgestrel, desogestrel, norgestrel, medroxyprogesterone, or ethynodiol diacetate c) Includes low-dose COCs containing the following progestins: levonorgestrel, desogestrel, dienogest, chlormadinone acetate, gestodene, cyproterone acetate, norgestimate, or norethindrone d) Includes low-dose COCs containing the following progestins: norgestimate, norethindrone, or levonorgestrel Epidemiologic Study (Author, Year of Publication) Population Studied Comparator Product (all are low-dose COCs; with ≤ 0.04 mg of EE) Hazard Ratio (HR) (95% CI) i3 Ingenix (Seeger 2007) Initiators, including new users a All COCs available in the US during the conduct of the study b HR: 0.9 (0.5 to 1.6) EURAS (Dinger 2007) Initiators, including new users a All COCs available in Europe during the conduct of the study c HR: 0.9 (0.6 to 1.4) Levonorgestrel/EE HR: 1.0 (0.6 to 1.8) "FDA-funded study" (2011) New users a Other COCs available during the course of the study d HR: 1.8 (1.3 to 2.4) Levonorgestrel/0.03 mg EE HR: 1.6 (1.1 to 2.2) All users (i.e., initiation and continuing use of study combination hormonal contraception) Other COCs available during the course of the study d HR: 1.7 (1.4 to 2.1) Levonorgestrel/0.03 mg EE HR: 1.5 (1.2 to 1.8) In addition to these "regulatory studies," other studies of various designs have been conducted. Overall, there are two prospective cohort studies (see Table 2): the US post-approval safety study Ingenix [Seeger 2007], the European post-approval safety study EURAS (European Active Surveillance Study) [Dinger 2007]. An extension of the EURAS study, the Long-Term Active Surveillance Study (LASS), did not enroll additional subjects, but continued to assess VTE risk. There are three retrospective cohort studies: one study in the US funded by the FDA (see Table 2), and two from Denmark [Lidegaard 2009, Lidegaard 2011]. There are two case-control studies: the Dutch MEGA study analysis [van Hylckama Vlieg 2009] and the German case-control study [Dinger 2010]. There are two nested case-control studies that evaluated the risk of non-fatal idiopathic VTE: the PharMetrics study [Jick 2011] and the GPRD study [Parkin 2011]. The results of all of these studies are presented in Figure 1. Figure 1: VTE Risk with Yasmin ® Relative to LNG-Containing COCs (adjusted risk # ) Risk ratios displayed on logarithmic scale; risk ratio < 1 indicates a lower risk of VTE for DRSP, > 1 indicates an increased risk of VTE for DRSP.
Side effects
The following serious adverse reactions with the use of COCs are discussed elsewhere in the labeling: Serious cardiovascular events and stroke [see Boxed Warning and Warnings and Precautions ( 5.1 )] Vascular events [see Warnings and Precautions ( 5.1 )] Liver disease [see Warnings and Precautions ( 5.4 )] The most frequent adverse reactions (≥ 2%) in contraception and folate clinical trials are premenstrual syndrome (12.4%), headache/migraine (10.3%), breast pain/tenderness/discomfort (8.1%), nausea/vomiting (4.4%), mood changes (2.3%) and abdominal pain/tenderness/discomfort (2.2%). ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Lupin Pharmaceuticals, Inc. at 1-800-399-2561 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, the adverse reaction rates observed cannot be directly compared to rates in other clinical trials and may not reflect the rates observed in practice. Contraception and Folate Supplementation Clinical Trials The data provided reflect the experience with the use of Yasmin ® (3 mg DRSP/0.03 mg EE) in the adequate and well-controlled studies for contraception (N=2,837) and folate supplementation (N=172). For contraception, the US pivotal clinical study (N=326) for the oral contraception indication for Yasmin ® was a multicenter, open-label trial in healthy women aged 18 to 35 who were treated with Yasmin ® for up to 13 cycles. The second contraceptive pivotal study (N=442) was a multicenter, randomized, open-label comparative European study of Yasmin ® vs. 0.150 mg desogestrel/0.03 mg EE conducted in healthy women aged 17 to 40 who were treated for up to 26 cycles. The primary efficacy study using drospirenone, ethinyl estradiol and levomefolate calcium tablets and levomefolate calcium tablets for folate supplementation was a randomized, single-center European trial in 172 healthy, female subjects aged 18 to 40 years comparing the pharmacodynamic effects of Yasmin ® + 0.451 mg levomefolate calcium to Yasmin ® co-administered with folic acid during 24 weeks of treatment followed by 20 weeks of open-label Yasmin ® . The adverse reactions seen across the 2 indications overlapped and are reported using the frequencies from the pooled dataset. The most common adverse reactions (≥ 2% of users) were: premenstrual syndrome (12.4%), headache/migraine (10.3%), breast pain/tenderness/discomfort (8.1%), nausea/vomiting (4.4%), mood changes (depression, depressed mood, irritability, mood swings, mood altered and affect lability (2.3%), and abdominal pain/discomfort/tenderness (2.2%). Adverse Reactions (≥ 1%) Leading to Study Discontinuation Contraception Clinical Trials Of 2,837 women, 6.7% discontinued from the clinical trials due to an adverse reaction; the most frequent adverse reaction leading to discontinuation was headache/migraine (1.5%). Folate Clinical Trial There were no subjects who discontinued due to an adverse reaction. Serious Adverse Reactions: Contraception Clinical Trials : depression, pulmonary embolism, toxic skin eruption, and uterine leiomyoma. Folate Supplementation Clinical Trial : none reported in the clinical trial 6.2 Postmarketing Experience Five studies that compared breast cancer risk between ever-users (current or past use) of COCs and never-users of COCs reported no association between ever use of COCs and breast cancer risk, with effect estimates ranging from 0.90 - 1.12 (Figure 3). Three studies compared breast cancer risk between current or recent COC users (<6 months since last use) and never users of COCs (Figure 3). One of these studies reported no association between breast cancer risk and COC use. The other two studies found an increased relative risk of 1.19 - 1.33 with current or recent use. Both of these studies found an increased risk of breast cancer with current use of longer duration, with relative risks ranging from 1.03 with less than one year of COC use to approximately 1.4 with more than 8-10 years of COC use. Figure 3: Relative Studies of Risk of Breast Cancer with Combined Oral Contraceptives RR = relative risk; OR = odds ratio; HR = hazard ratio. "ever COC" are females with current or past COC use; "never COC use" are females that never used COCs. The following adverse reactions have been identified during post-approval use of Yasmin ® . 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. Adverse reactions, including fatalities, are grouped into System Organ Classes and ordered by frequency. Vascular disorders: Venous and arterial thromboembolic events (including pulmonary emboli, deep vein thrombosis, intracardiac thrombosis, intracranial venous sinus thrombosis, sagittal sinus thrombosis, retinal vein occlusion, myocardial infarction and stroke), hypertension Hepatobiliary disorders: Gallbladder disease Immune system disorders: Hypersensitivity Metabolism and nutrition disorders: Hyperkalemia Skin and subcutaneous tissue disorders: Chloasma Image
Drug interactions
Consult the labeling of all concurrently-used drugs to obtain further information about interactions with hormonal contraceptives or the potential for enzyme alterations . Drugs or herbal products that induce certain enzymes (for example, CYP3A4) may decrease the effectiveness of COCs or increase breakthrough bleeding. Counsel patients to use a back-up or alternative method of contraception when enzyme inducers are used with COCs. ( 7.1 ) 7.1 Effects of Other Drugs on Combined Oral Contraceptives Substances diminishing the efficacy of COCs: Drugs or herbal products that induce certain enzymes, including cytochrome P450 3A4 (CYP3A4), may decrease the effectiveness of COCs 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, rifampin, topiramate and products containing St.John's wort. Interactions between oral 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 COCs, 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 with certain COCs containing EE increase AUC values for EE by approximately 20%. Ascorbic acid and acetaminophen may increase plasma EE concentrations, possibly by inhibition of conjugation. Concomitant administration of moderate or strong CYP3A4 inhibitors such as azole antifungals (e.g., ketoconazole, itraconazole, voriconazole, fluconazole), verapamil, macrolides (e.g., clarithromycin, erythromycin), diltiazem, and grapefruit juice can increase the plasma concentrations of the estrogen or the progestin or both. In a clinical drug-drug interaction study conducted in premenopausal women, once daily co-administration of DRSP 3 mg/EE 0.02 mg containing tablets with strong CYP3A4 inhibitor, ketoconazole 200 mg twice daily for 10 days resulted in a moderate increase of DRSP systemic exposure. The exposure of EE was increased mildly [see Warnings and Precautions ( 5.2 ) and Clinical Pharmacology ( 12.3 )] . 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 progestin have been noted in some cases of co-administration with HIV/HCV protease inhibitors or with non-nucleoside reverse transcriptase inhibitors. Antibiotics: There have been reports of pregnancy while taking hormonal contraceptives and antibiotics, but clinical pharmacokinetic studies have not shown consistent effects of antibiotics on plasma concentrations of synthetic steroids. 7.2 Effects of Combined Oral Contraceptives on Other Drugs COCs containing EE may inhibit the metabolism of other compounds. COCs have been shown to significantly decrease plasma concentrations of lamotrigine, likely due to induction of lamotrigine glucuronidation. This may reduce seizure control; therefore, dosage adjustments of lamotrigine may be necessary. Consult the labeling of the concurrently-used drug to obtain further information about interactions with COCs or the potential for enzyme alterations. COCs Increasing the Plasma Concentrations of CYP450 Enzymes : In clinical studies, administration of a hormonal contraceptive containing EE did not lead to any increase or only to a weak increase in plasma concentrations of CYP3A4 substrates (e.g., midazolam) while plasma concentrations of CYP2C19 substrates (e.g., omeprazole and voriconazole) and CYP1A2 substrates (e.g., theophylline and tizanidine) can have a weak or moderate increase. Clinical studies did not indicate an inhibitory potential of DRSP towards human CYP enzymes at clinically relevant concentrations [see Clinical Pharmacology ( 12.3 )]. Women on thyroid hormone replacement therapy may need increased doses of thyroid hormone because serum concentration of thyroid-binding globulin increases with use of COCs. Potential to Increase Serum Potassium Concentration : There is a potential for an increase in serum potassium concentration in women taking Tydemy with other drugs that may increase serum potassium concentration [see Warnings and Precautions ( 5.2 ) and Clinical Pharmacology ( 12.3 )]. 7.3 Concomitant Use of HCV Combination Therapy – Liver Enzyme Elevation Do not co-administer Tydemy with HCV drug combinations containing ombitasvir/paritaprevir/ritonavir, with or without dasabuvir, due to potential for ALT elevations [see Warnings and Precautions ( 5.5 )] . 7.4 Effects of Folates on Other Drugs Folates may modify the pharmacokinetics or pharmacodynamics of certain antifolate drugs, e.g., antiepileptics (such as phenytoin), methotrexate or pyrimethamine, and may result in a decreased pharmacological effect of the antifolate drug. 7.5 Effects of Other Drugs on Folates Several drugs have been reported to reduce folate concentrations by inhibition of the dihydrofolate reductase enzyme (e.g., methotrexate and sulfasalazine) or by reducing folate absorption (e.g., cholestyramine), or via unknown mechanisms (e.g., antiepileptics such as carbamazepine, phenytoin, phenobarbital, primidone and valproic acid). 7.6 Interference with Laboratory Tests The use of contraceptive steroids may influence the results of certain laboratory tests, such as coagulation factors, lipids, glucose tolerance, and binding proteins. DRSP causes an increase in plasma renin activity and plasma aldosterone induced by its mild anti-mineralocorticoid activity. Folates may mask vitamin B12 deficiency [see Warnings and Precautions ( 5.13 ) and Drug Interactions ( 7.2 )] .
Use in specific populations
Lactation: Can reduce milk production in breast-feeding females ( 8.2 ) 8.1 Pregnancy Risk Summary There is no use for contraception in pregnancy; therefore, drospirenone, ethinyl estradiol and levomefolate calcium tablets and levomefolate calcium tablets should be discontinued during pregnancy. Epidemiologic studies and meta-analyses have not found an increased risk of genital or non-genital birth defects (including cardiac anomalies and limb-reduction defects) following exposure to CHCs before conception or during early pregnancy. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2 to 4 percent and 15 to 20 percent, respectively. Data Human Data A retrospective database study of women in Norway, that included 44,734 pregnancies of which 368 were women who inadvertently took drospirenone/ethinyl estradiol during the first trimester of a pregnancy, found there were no adverse effects on pre-term birth, small for gestational age, or birth weight Z-scores. Post-marketing adverse event data on the use of drospirenone, ethinyl estradiol and levomefolate calcium tablets and levomefolate calcium tablets in pregnant women suggest that frequencies of miscarriage and congenital anomalies were not higher than the estimated background risk in the general population. 8.2 Lactation Risk Summary DRSP is present in human milk. After a single oral administration of 3 mg DRSP/0.03 mg EE tablets, DRSP concentration in breast milk over the 24-h period ranged from 1.4 to 7.0 ng/mL, with a mean ± standard deviation value of 3.7 ± 1.9 ng/mL. The estimated mean infant dose was 0.003 mg/day, which is about 0.1% of maternal dose (see Data). There is limited information on the effects of drospirenone, ethinyl estradiol and levomefolate calcium tablets and levomefolate calcium tablets on the breast-fed infant. CHCs can reduce milk production in breast- feeding females. This reduction can occur at any time but is less likely to occur once breast-feeding is well-established. When possible, advise the nursing female to use other methods of contraception until she discontinues breast-feeding [See also Dosage and Administration ( 2.2 )]. Increase in folate concentration in milk is not expected (see Data). The developmental and health benefits of breast-feeding should be considered along with the mother's clinical need for drospirenone, ethinyl estradiol and levomefolate calcium tablets and levomefolate calcium tablets and any potential adverse effects on the breast-fed child from drospirenone, ethinyl estradiol and levomefolate calcium tablets and levomefolate calcium tablets or from the underlying maternal condition. Data Human Data An open-label study evaluated the degree of DRSP transfer into milk within 72 hours following a single oral administration of 3 mg DRSP/0.03 mg EE tablets to 6 healthy lactating women who were 1 week to 3 months post- partum. DRSP was present in breast milk with a mean Cmax of 13.5 ng/mL, while the mean Cmax in serum of lactating women was 30.8 ng/mL. The DRSP concentration in breast milk over the 24-hour period following dosing ranged from 1.4 to 7.0 ng/mL, with a mean ± standard deviation value of 3.7 ± 1.9 ng/mL. Based on single dose data, the maximal daily infant dose of DRSP was calculated to be 0.003 mg/day, which represented a mean of 0.1% of the maternal dose. A study in approximately 60 lactating women demonstrated no significant differences in folate concentrations in milk between women who received 416 mcg/day [6S]-5-methyltetrahydrofolate or 400 mcg/day folic acid and women who received placebo over a 16-week period. Studies to date indicate there is no adverse effect of folate on nursing infants. 8.4 Pediatric Use Safety and efficacy of drospirenone, ethinyl estradiol and levomefolate calcium tablets and levomefolate calcium tablets has been established in women of reproductive age. Efficacy is expected to be the same for postpubertal adolescents under the age of 18 and for users 18 years and older. Use of this product before menarche is not indicated. 8.5 Geriatric Use Drospirenone, ethinyl estradiol and levomefolate calcium tablets and levomefolate calcium tablets has not been studied in postmenopausal women and is not indicated in this population. 8.6 Patients with Renal Impairment Drospirenone, ethinyl estradiol and levomefolate calcium tablets and levomefolate calcium tablets is contraindicated in patients with renal impairment [see Contraindications ( 4 ) and Warnings and Precautions ( 5.2 )] . In subjects with creatinine clearance (CLcr) of 50 to 79 mL/min, serum DRSP concentrations were comparable to those in a control group with CLcr ≥ 80 mL/min. In subjects with CLcr of 30 to 49 mL/min, serum DRSP concentrations were on average 37% higher than those in the control group. In addition, there is a potential to develop hyperkalemia in subjects with renal impairment whose serum potassium is in the upper reference range, and who are concomitantly using potassium-sparing drugs [see Clinical Pharmacology ( 12.3 )] . 8.7 Patients with Hepatic Impairment Drospirenone, ethinyl estradiol and levomefolate calcium tablets and levomefolate calcium tablets is contraindicated in patients with hepatic disease [see Contraindications ( 4 ) and Warnings and Precautions ( 5.4 )] . The mean exposure to DRSP in women with moderate liver impairment is approximately three times higher than the exposure in women with normal liver function. Drospirenone, ethinyl estradiol and levomefolate calcium tablets and levomefolate calcium tablets has not been studied in women with severe hepatic impairment. 8.8 Race No clinically significant difference was observed between the pharmacokinetics of DRSP or EE in Japanese versus Caucasian women [see Clinical Pharmacology ( 12.3 )] .
Pregnancy
8.1 Pregnancy Risk Summary There is no use for contraception in pregnancy; therefore, drospirenone, ethinyl estradiol and levomefolate calcium tablets and levomefolate calcium tablets should be discontinued during pregnancy. Epidemiologic studies and meta-analyses have not found an increased risk of genital or non-genital birth defects (including cardiac anomalies and limb-reduction defects) following exposure to CHCs before conception or during early pregnancy. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2 to 4 percent and 15 to 20 percent, respectively. Data Human Data A retrospective database study of women in Norway, that included 44,734 pregnancies of which 368 were women who inadvertently took drospirenone/ethinyl estradiol during the first trimester of a pregnancy, found there were no adverse effects on pre-term birth, small for gestational age, or birth weight Z-scores. Post-marketing adverse event data on the use of drospirenone, ethinyl estradiol and levomefolate calcium tablets and levomefolate calcium tablets in pregnant women suggest that frequencies of miscarriage and congenital anomalies were not higher than the estimated background risk in the general population.
Pediatric use
8.4 Pediatric Use Safety and efficacy of drospirenone, ethinyl estradiol and levomefolate calcium tablets and levomefolate calcium tablets has been established in women of reproductive age. Efficacy is expected to be the same for postpubertal adolescents under the age of 18 and for users 18 years and older. Use of this product before menarche is not indicated.
Geriatric use
8.5 Geriatric Use Drospirenone, ethinyl estradiol and levomefolate calcium tablets and levomefolate calcium tablets has not been studied in postmenopausal women and is not indicated in this population.
Overdosage
There have been no reports of serious ill effects from overdose, including ingestion by children. Overdosage may cause withdrawal bleeding in females and nausea. DRSP is a spironolactone analogue which has anti-mineralocorticoid properties. Serum concentration of potassium and sodium, and evidence of metabolic acidosis, should be monitored in cases of overdose. Levomefolate calcium doses of 17 mg/day (37-fold higher than the levomefolate calcium dose of Tydemy) were well tolerated after long-term treatment up to 12 weeks.
Description
Tydemy (drospirenone, ethinyl estradiol and levomefolate calcium tablets and levomefolate calcium tablets) provides an oral contraceptive regimen consisting of 28 film-coated tablets that contain the active ingredients specified for each tablet below: 21 orange tablets each containing 3 mg DRSP, 0.03 mg EE, and 0.451 mg levomefolate calcium 7 light orange tablets each containing 0.451 mg levomefolate calcium The inactive ingredients in the orange tablets are ascorbic acid, corn starch, croscarmellose sodium, ferric oxide red, ferric oxide yellow, hypromellose, lactose monohydrate, low-substituted hydroxypropyl cellulose, magnesium stearate, polyethylene glycol, pregelatinized starch, talc and titanium dioxide. The light orange tablets contain 0.451 mg of levomefolate calcium. The inactive ingredients in the light orange tablets are ascorbic acid, corn starch, croscarmellose sodium, ferric oxide yellow, ferric oxide red, hypromellose, lactose monohydrate, low-substituted hydroxypropyl cellulose, magnesium stearate, polyethylene glycol, pregelatinised starch, talc and titanium dioxide. Drospirenone (2', S ,6 R ,7 R ,8 R ,9 S ,10 R ,13 S ,14 S ,15 S ,16 S ) - 1,3',4',6,7,8,9,10,11,12,13,14,15, 16,20,21-Hexadecadydro-10,13-dimethylspirol[17 H -dicyclopropa [6,7:15,16] cyclopenta [a] phenanthrene-17, 2', (5' H )-furan] -3, 5' (2 H ) dione) is a synthetic progestational compound and has a molecular weight of 366.49 and a molecular formula of C 24 H 30 O 3 . Ethinyl estradiol (19-nor-17α-pregna-1,3,5(10)-trien-20-yne-3,17-diol) is a synthetic estrogenic compound and has a molecular weight of 296.40 and a molecular formula of C 20 H 24 O 2 . Levomefolate Calcium (N-{4-[[((6S)-2-amino-3,4,5,6,7,8-hexahydro-5-methyl-4-oxo-6-pteridinyl) methyl] amino] benzoyl}-L-glutamic acid, calcium salt) is a synthetic calcium salt of levomefolate (L-5-methyl-THF), which is a metabolite of vitamin B 9 and has a molecular weight of 497.5 and a molecular formula of C 20 H 23 CaN 7 O 6 . The structural formulas are as follows: Image
Mechanism of action
12.1 Mechanism of Action COCs lower the risk of becoming pregnant primarily by suppressing ovulation.
How supplied
16.1 How Supplied Tydemy (drospirenone, ethinyl estradiol and levomefolate calcium tablets and levomefolate calcium tablets) is available in blister pack containing 28 tablets packed in a pouch (NDC 68180-904-71). Such three pouches are packaged in a carton (NDC 68180-904-73). Each blister contains 28 film-coated tablets in the following order: 21 orange, round shaped, biconvex film-coated tablets debossed with "LU" on one side and "J63" on other side each containing 3 mg drospirenone, 0.03 mg ethinyl estradiol and 0.451 mg levomefolate calcium. 7 light orange, round shaped, biconvex film-coated tablets debossed with "LU" on one side and "J62" on other side each containing 0.451 mg levomefolate calcium. 16.2 Storage Store at 25ºC (77ºF); excursions permitted to 15º to 30ºC (59º to 86ºF) [See USP Controlled Room Temperature]. 16.1 How Supplied Tydemy (drospirenone, ethinyl estradiol and levomefolate calcium tablets and levomefolate calcium tablets) is available in blister pack containing 28 tablets packed in a pouch (NDC 68180-904-71). Such three pouches are packaged in a carton (NDC 68180-904-73). Each blister contains 28 film-coated tablets in the following order: 21 orange, round shaped, biconvex film-coated tablets debossed with "LU" on one side and "J63" on other side each containing 3 mg drospirenone, 0.03 mg ethinyl estradiol and 0.451 mg levomefolate calcium. 7 light orange, round shaped, biconvex film-coated tablets debossed with "LU" on one side and "J62" on other side each containing 0.451 mg levomefolate calcium.
Patient information
Advise the patient to read the FDA-approved patient labeling (Patient Information). Counsel patients that cigarette smoking increases the risk of serious cardiovascular events from COC use, and that women who are over 35 years old and smoke should not use COCs. Counsel patients that the increased risk of VTE compared to non-users of COCs is greatest after initially starting a COC or restarting (following a 4-week or greater pill-free interval) the same or a different COC. Counsel patients about the information regarding the risk of VTE with DRSP-containing COCs compared to COCs that contain levonorgestrel or some other progestins. Counsel patients that Tydemy does not protect against HIV-infection (AIDS) and other sexually transmitted diseases. Counsel patients on Warnings and Precautions associated with COCs. Counsel patients that Tydemy contains DRSP. Drospirenone may increase potassium. Patients should be advised to inform their healthcare provider if they have kidney, liver or adrenal disease because the use of Tydemy in the presence of these conditions could cause serious heart and health problems. They should also inform their healthcare provider if they are currently on daily, long-term treatment (NSAIDs, potassium-sparing diuretics, potassium supplementation, ACE inhibitors, angiotensin-II receptor antagonists, heparin or aldosterone antagonists) for a chronic condition or taking strong CYP3A4 inhibitors. Inform patients that Tydemy is not indicated during pregnancy. If pregnancy occurs during treatment with Tydemy, instruct the patient to stop further intake. However, women should be advised on the continued need of sufficient folate intake. Counsel patients to take one tablet daily by mouth at the same time every day. Instruct patients what to do in the event pills are missed. Counsel patients to use a back-up or alternative method of contraception when enzyme inducers are used with COCs. Counsel patients who are breastfeeding or who desire to breastfeed that COCs may reduce breast milk production. This is less likely to occur if breastfeeding is well established. Counsel any patient who starts COCs postpartum, and who has not yet had a period, to use an additional method of contraception until she has taken an orange tablet for 7 consecutive days. Counsel patients that amenorrhea may occur. Rule out pregnancy in the event of amenorrhea in two or more consecutive cycles. Counsel patients to report whether they are taking folate supplements. Tydemy contains the equivalent of 0.4 mg (400 mcg) of folic acid. Counsel patients to maintain folate supplementation if they discontinue Tydemy due to pregnancy. ® The brands listed are trademarks of their respective owners and are not trademarks of Lupin Pharmaceuticals, Inc. The makers of these brands are not affiliated with and do not endorse Lupin Pharmaceuticals, Inc. or its products. Distributed by: Lupin Pharmaceuticals, Inc. Naples, FL 34108 United States Manufactured by: Lupin Limited Pithampur (M.P.) - 454 775 India Revised: February 2025 Image
Label text from the FDA structured product label by Lupin Pharmaceuticals, Inc. (revised Dec 29, 2025). Long sections are shortened; the complete label is on DailyMed.
Tydemy NDC products (1)
| NDC | Strength & form | Labeler | Type |
|---|---|---|---|
| 68180-904 | Kit | Lupin Pharmaceuticals, Inc. | ANDA |
Tydemy recalls
- D-1081-2023 Aug 9, 2023 · Class I · Terminated
Failed Stability Specification and Failed Impurities/Degradation Specifications: out of specification for inactive content ascorbic acid and MTHFRC-7impurity test
Frequently asked questions
What is Tydemy used for?
Tydemy is a combination of drospirenone, a progestin and ethinyl estradiol, an estrogen containing a folate, indicated for use by females of reproductive potential to: Prevent pregnancy. ( 1.1 ) Raise folate levels in females of reproductive potential who choose to use an oral contraceptive for contraception. ( 1.2 ) 1.1 Oral Contraceptive Tydemy TM is indicated for use by females of reproductive…
What are the side effects of Tydemy?
The following serious adverse reactions with the use of COCs are discussed elsewhere in the labeling: Serious cardiovascular events and stroke [see Boxed Warning and Warnings and Precautions ( 5.1 )] Vascular events [see Warnings and Precautions ( 5.1 )] Liver disease [see Warnings and Precautions ( 5.4 )] The most frequent adverse reactions (≥ 2%) in contraception and folate clinical trials are… See the full label for the complete list.
Who makes Tydemy?
Tydemy is listed by 1 labeler in the FDA NDC directory, including Lupin Pharmaceuticals, Inc..
Has Tydemy been recalled?
The FDA enforcement database lists 1 recall for Tydemy, most recently D-1081-2023 (class i): Failed Stability Specification and Failed Impurities/Degradation Specifications: out of specification for inactive content ascorbic acid and MTHFRC-7impurity…