Yasmin
drospirenone and ethinyl estradiol · Kit
• Women over 35 years old who smoke should not use Yasmin. ( 4 )
• Cigarette smoking increases the risk of serious cardiovascular events from combination oral contraceptive (COC) use. ( 4 )
Uses
Yasmin ® is indicated for use by females of reproductive potential to prevent pregnancy. Yasmin is a combination of drospirenone, a progestin, and ethinyl estradiol, an estrogen, indicated for use by females of reproductive potential to prevent pregnancy. ( 1 )
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 Yasmin 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, Yasmin 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 Yasmin Instruct the patient to begin taking Yasmin 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 Yasmin use, instruct the patient to take one yellow Yasmin daily, beginning on Day 1 of her menstrual cycle. (The first day of menstruation is Day 1.) She should take one yellow Yasmin daily for 21 consecutive days, followed by one white tablet daily on Days 22 through 28. Yasmin 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. Yasmin can be taken without regard to meals. If Yasmin is first taken later than the first day of the menstrual cycle, Yasmin 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 Yasmin use, instruct the patient to take one yellow Yasmin daily, beginning on the first Sunday after the onset of her menstrual period. She should take one yellow Yasmin daily for 21 consecutive days, followed by one white tablet daily on Days 22 through 28. Yasmin 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. Yasmin can be taken without regard to meals. Yasmin 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 Yasmin on the same day of the week that she began her first regimen, following the same schedule. She should begin taking her yellow tablets on the next day after ingestion of the last white tablet, regardless of whether or not a menstrual period has occurred or is still in progress. Anytime a subsequent cycle of Yasmin is started later than the day following administration of the last white tablet, the patient should use another method of contraception until she has taken a yellow Yasmin daily for seven consecutive days. When switching from a different birth control pill When switching from another birth control pill, Yasmin 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, Yasmin should be started when the next application would have been due. When switching from an injection, Yasmin should be started when the next dose would have been due. When switching from an intrauterine contraceptive or an implant, Yasmin should be started on the day of removal. Withdrawal bleeding usually occurs within 3 days following the last yellow tablet. If spotting or breakthrough bleeding occurs while taking Yasmin, instruct the patient to continue taking Yasmin 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 Yasmin 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 Yasmin if pregnancy is confirmed. The risk of pregnancy increases with each active yellow 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 white tablets, she should still be protected against pregnancy provided she begins taking a new cycle of yellow tablets on the proper day. For postpartum women who do not breastfeed or after a second trimester abortion, start Yasmin no earlier than 4 weeks postpartum due to the increased risk of thromboembolism. If the patient starts Yasmin 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 Yasmin for 7 consecutive days. 2.3 Missed Doses Table 1: Instructions for Yasmin Missed Doses If one yellow 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 yellow 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. Then take one tablet a day until the pack is finished.
Dosage forms and strengths
Yasmin (drospirenone/ethinyl estradiol) tablets are available in blister packs. Each blister pack contains 28 film-coated, round, bi-convex tablets in the following order:
• 21 yellow tablets each containing 3 mg drospirenone (DRSP) and 0.03 mg ethinyl estradiol (EE) embossed with a “DO” in a regular hexagon on one side
• 7 inert white tablets embossed with a “DP” in a regular hexagon on one side Yasmin consists of 28 film-coated, biconvex tablets in the following order ( 3 ):
• 21 yellow tablets, each containing 3 mg drospirenone (DRSP) and 0.03 mg ethinyl estradiol (EE)
• 7 inert white tablets
Contraindications
Yasmin 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 ( 7.2 )]
• 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 Yasmin 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 Yasmin 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 Yasmin if jaundice occurs. ( 5.4 )
• High blood pressure : Do not prescribe Yasmin for women with uncontrolled hypertension or hypertension with vascular disease. ( 5.6 )
• Carbohydrate and lipid metabolic effects : Monitor prediabetic and diabetic women taking Yasmin. Consider an alternate contraceptive method for women with uncontrolled dyslipidemia. ( 5.8 )
• Headache : Evaluate significant change in headaches and discontinue Yasmin if indicated. ( 5.9 )
• Uterine bleeding : Evaluate irregular bleeding or amenorrhea. ( 5.10 ) 5.1 Thromboembolic Disorders and Other Vascular Problems Stop Yasmin if an arterial or venous thrombotic (VTE) event occurs. Based on presently available information on 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 Yasmin 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 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 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 "New users" - no use of combination hormonal contraception for at least the prior 6 months All COCs available in the US during the conduct of the study Includes low-dose COCs containing the following progestins: norgestimate, norethindrone, levonorgestrel, desogestrel, norgestrel, medroxyprogesterone, or ethynodiol diacetate HR: 0.9 (0.5-1.6) EURAS (Dinger 2007) Initiators, including new users All COCs available in Europe during the conduct of the study Includes low-dose COCs containing the following progestins: levonorgestrel, desogestrel, dienogest, chlormadinone acetate, gestodene, cyproterone acetate, norgestimate, or norethindrone HR: 0.9 (0.6-1.4) Levonorgestrel/EE HR: 1.0 (0.6-1.8) FDA-funded study” (2011) New users Other COCs available during the course of the study Includes low-dose COCs containing the following progestins: norgestimate, norethindrone, or levonorgestrel HR: 1.8 (1.3-2.4) Levonorgestrel/0.03 mg EE HR: 1.6 (1.1-2.2) All users (i.e., initiation and continuing use of study combination hormonal contraception) Other COCs available during the course of the study HR: 1.7 (1.4-2.1) Levonorgestrel/0.03 mg EE HR: 1.5 (1.2-1.8) 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%) are premenstrual syndrome (13.2%), headache /migraine (10.7%), breast pain/tenderness/discomfort (8.3%), nausea/vomiting (4.5%), abdominal pain/tenderness/discomfort (2.3%), mood changes (2.3%). ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Bayer HealthCare Pharmaceuticals Inc. at 1-888-842-2937 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. 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). The US pivotal clinical study (N=326) was a multicenter, open-label trial in healthy women aged 18 -35 who were treated for up to 13 cycles. The second 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 17-40 who were treated for up to 26 cycles. The most common adverse reactions (≥ 2% of users) were: premenstrual syndrome (13.2%), headache/migraine (10.7%), breast pain/tenderness/discomfort (8.3%), nausea/vomiting (4.5%) abdominal pain/discomfort/tenderness (2.3%) and mood changes (depression, depressed mood, irritability, mood swings, mood altered and affect lability (2.3%). Adverse Reactions (≥ 1%) Leading to Study Discontinuation : 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%). Serious Adverse Reactions : Depression, pulmonary embolism, toxic skin eruption, and uterine leiomyoma. 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 Figure 3: Relative Studies of Risk of Breast Cancer with Combined Oral Contraceptives
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 and 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 Yasmin with other drugs that may increase serum potassium concentration [see Warnings and Precautions ( 5.2 ) and Clinical Pharmacology ( 12.3 )]. 7.3 Concomitant Use with HCV Combination Therapy – Liver Enzyme Elevation Do not co-administer Yasmin 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 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 [see Warnings and Precautions ( 5.12 ) 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, Yasmin 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 Yasmin 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 Yasmin 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 )]. The developmental and health benefits of breast-feeding should be considered along with the mother’s clinical need for Yasmin and any potential adverse effects on the breast-fed child from Yasmin 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 C max of 13.5 ng/mL, while the mean C max 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. 8.4 Pediatric Use Safety and efficacy of Yasmin 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 Yasmin has not been studied in postmenopausal women and is not indicated in this population. 8.6 Patients with Renal Impairment Yasmin is contraindicated in patients with renal impairment [see Contraindications ( 4 ) and Warnings and Precautions ( 5.2 )] . In subjects with creatinine clearance (CLcr) of 50–79 mL/min, serum DRSP concentrations were comparable to those in a control group with CLcr ≥ 80 mL/min. In subjects with CLcr of 30–49 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 Yasmin 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. Yasmin 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, Yasmin 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 Yasmin 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 Yasmin 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 Yasmin 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.
Description
Yasmin (drospirenone/ethinyl estradiol) tablets provide an oral contraceptive regimen consisting of 28 film-coated tablets that contain the ingredients specified for each tablet below:
• 21 yellow tablets each containing 3 mg DRSP and 0.03 mg EE
• 7 inert white tablets
• The inactive ingredients in the yellow tablets are lactose monohydrate NF, corn starch NF, pregelatinized starch NF, povidone 25000 NF, magnesium stearate NF, hypromellose USP, macrogol 6000 NF, titanium dioxide USP, talc USP, and ferric oxide pigment, yellow NF. The white inert film-coated tablets contain lactose monohydrate NF, microcrystalline cellulose NF, magnesium stearate NF, hypromellose USP, talc USP, and titanium dioxide USP. Drospirenone (6R,7R,8R,9S,10R,13S,14S,15S,16S,17S)-1,3',4',6,6a,7,8,9,10,11,12,13, 14,15,15a,16-hexadecahydro-10,13-dimethylspiro-[17H-dicyclopropa-[6,7:15,16] cyclopenta[a]phenanthrene-17,2'(5H)-furan]-3,5'(2H)-dione) is a synthetic progestational compound and has a molecular weight of 366.5 and a molecular formula of C 24 H 30 O 3 . Ethinyl estradiol (19-nor-17α-pregna 1,3,5(10)-triene-20-yne-3,17-diol) is a synthetic estrogenic compound and has a molecular weight of 296.4 and a molecular formula of C 20 H 24 O 2 . The structural formulas are as follows: Structural Formulas
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 Yasmin (drospirenone/ethinyl estradiol) tablets are available in packages of three blister packs (NDC 50419-402-03). The film-coated tablets are rounded with biconvex faces, one side is embossed with a regular hexagon shape with DO or DP. Each blister pack contains 28 film-coated tablets in the following order:
• 21 round, biconvex, yellow, film-coated tablets with embossed “DO” in a regular hexagon on one side each containing 3 mg drospirenone and 0.03 mg ethinyl estradiol
• 7 round, biconvex, white, film-coated tablets with embossed “DP” in a regular hexagon on one side 16.2 Storage Store at 25°C (77°F); excursions permitted to 15-30°C (59-86°F) [see USP Controlled Room Temperature].
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 Yasmin does not protect against HIV infection (AIDS) and other sexually transmitted diseases.
• Counsel patients on Warnings and Precautions associated with COCs.
• Counsel patients that Yasmin 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 Yasmin 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 Yasmin is not indicated during pregnancy. If pregnancy occurs during treatment with Yasmin, instruct the patient to stop further 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 a yellow 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. Manufactured for: Bayer HealthCare Pharmaceuticals Inc. Whippany, NJ 07981 Manufactured in Germany ©2015 Bayer HealthCare Pharmaceuticals Inc. All Rights Reserved Bayer HealthCare Pharmaceuticals Inc.
Label text from the FDA structured product label by Bayer HealthCare Pharmaceuticals Inc. (revised May 19, 2023). Long sections are shortened; the complete label is on DailyMed.
Yasmin NDC products (1)
| NDC | Strength & form | Labeler | Type |
|---|---|---|---|
| 50419-402 | Kit | Bayer HealthCare Pharmaceuticals Inc. | NDA |
Frequently asked questions
What is Yasmin used for?
Yasmin ® is indicated for use by females of reproductive potential to prevent pregnancy. Yasmin is a combination of drospirenone, a progestin, and ethinyl estradiol, an estrogen, indicated for use by females of reproductive potential to prevent pregnancy. ( 1 )
What are the side effects of Yasmin?
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%) are premenstrual syndrome (13.2%),… See the full label for the complete list.
Who makes Yasmin?
Yasmin is listed by 1 labeler in the FDA NDC directory, including Bayer HealthCare Pharmaceuticals Inc..