Loryna
Drospirenone and Ethinyl Estradiol Tablets · Kit
• Women over 35 years old who smoke should not use d rospirenone and ethinyl estradiol ( 4 ).
• Cigarette smoking increases the risk of serious cardiovascular events from combination oral contraceptive (COC) use. ( 4 ) Boxed Warning Section WARNING TO WOMEN WHO SMOKE Do not use drospirenone and ethinyl estradiol tablets if you smoke cigarettes and are over 35…
Uses
Loryna (drospirenone and ethinyl estradiol tablets) is an estrogen/progestin COC, indicated for use by women to: Prevent pregnancy. ( 1.1 ) Treat symptoms of premenstrual dysphoric disorder (PMDD) for women who choose to use an oral contraceptive for contraception. ( 1.2 ) Treat moderate acne for women at least 14 years old only if the patient desires an oral contraceptive for birth control. ( 1.3 ) 1.1 Oral Contraceptive Loryna (drospirenone and ethinyl estradiol tablets) are indicated for use by women to prevent pregnancy. 1.2 Premenstrual Dysphoric Disorder (PMDD) Loryna is also indicated for the treatment of symptoms of premenstrual dysphoric disorder (PMDD) in women who choose to use an oral contraceptive as their method of contraception. The effectiveness of Loryna for PMDD when used for more than three menstrual cycles has not been evaluated. The essential features of PMDD according to the Diagnostic and Statistical Manual-4th edition (DSM-IV) include markedly depressed mood, anxiety or tension, affective lability, and persistent anger or irritability. Other features include decreased interest in usual activities, difficulty concentrating, lack of energy, change in appetite or sleep, and feeling out of control. Physical symptoms associated with PMDD include breast tenderness, headache, joint and muscle pain, bloating and weight gain. In this disorder, these symptoms occur regularly during the luteal phase and remit within a few days following onset of menses; the disturbance markedly interferes with work or school, or with usual social activities and relationships with others. Diagnosis is made by healthcare providers according to DSM-IV criteria, with symptomatology assessed prospectively over at least two menstrual cycles. In making the diagnosis, care should be taken to rule out other cyclical mood disorders. Loryna has not been evaluated for the treatment of premenstrual syndrome (PMS). 1.3 Acne Loryna tablets are indicated for the treatment of moderate acne vulgaris in women at least 14 years of age, who have no known contraindications to oral contraceptive therapy and have achieved menarche. Drospirenone and ethinyl estradiol tablets should be used for the treatment of acne only if the patient desires an oral contraceptive for birth control.
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 Loryna (drospirenone and ethinyl estradiol tablets) 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 and PMDD effectiveness, drospirenone and ethinyl estradiol tablets must be taken exactly 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 Loryna (drospirenone and ethinyl estradiol tablets) Instruct the patient to begin taking Loryna tablets 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 Loryna tablets use, instruct the patient to take one peach drospirenone and ethinyl estradiol tablet daily, beginning on Day 1 of her menstrual cycle. (The first day of menstruation is Day 1.) She should take one peach Loryna tablet daily for 24 consecutive days, followed by one white inert tablet daily on Days 25 through 28. Loryna tablets 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. Loryna tablets can be taken without regard to meals. If drospirenone and ethinyl estradiol tablets are first taken later than the first day of the menstrual cycle, Loryna tablets 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 Loryna tablets use, instruct the patient to take one peach Loryna tablet daily, beginning on the first Sunday after the onset of her menstrual period. She should take one peach Loryna tablet daily for 24 consecutive days, followed by one white inert tablet daily on Days 25 through 28. Loryna tablets 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. Loryna tablets can be taken without regard to meals. Loryna tablets 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 Loryna tablets on the same day of the week that she began her first regimen, following the same schedule. She should begin taking her peach 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 Loryna tablets are 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 peach Loryna tablets daily for seven consecutive days. When switching from a different birth control pill When switching from another birth control pill, Loryna tablets 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, Loryna tablets should be started when the next application would have been due. When switching from an injection, Loryna tablets should be started when the next dose would have been due. When switching from an intrauterine contraceptive or an implant, Loryna tablets should be started on the day of removal. Withdrawal bleeding usually occurs within 3 days following the last peach tablet. If spotting or breakthrough bleeding occurs while taking Loryna tablets, instruct the patient to continue taking Loryna tablets 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 Loryna tablets are 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 Loryna tablets if pregnancy is confirmed. The risk of pregnancy increases with each active peach tablet missed. For additional patient instructions regarding missed pills, see the "WHAT TO DO IF YOU MISS PILLS" section in the FDA Approved Patient Labeling . 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 peach tablets on the proper day. For postpartum women who do not breastfeed or after a second trimester abortion, start Loryna tablets no earlier than 4 weeks postpartum due to the increased risk of thromboembolism. If the patient starts on Loryna tablets 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 Loryna tablets for 7 consecutive days.
Dosage forms and strengths
Loryna (drospirenone and ethinyl estradiol tablets, USP) is available in blister packs. Each blister pack (28 film-coated tablets) contains in the following order:
• 24 peach tablets each containing 3 mg drospirenone (DRSP) and 0.02 mg ethinyl estradiol (EE)
• 4 white inert tablets Loryna (drospirenone and ethinyl estradiol tablets) consists of 28 film-coated tablets in the following order ( 3 ):
• 24 peach tablets, each containing 3 mg drospirenone (DRSP) and 0.02 mg ethinyl estradiol (EE)
• 4 white inert tablets
Contraindications
Loryna 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 tumors, benign or malignant, or liver disease [ see WARNINGS AND PRECAUTIONS ( 5.4 ) and USE IN SPECIFIC POPULATIONS ( 8.7 )] Pregnancy, because there is no reason to use COCs during pregnancy [ see WARNINGS AND PRECAUTIONS ( 5.11 ) and USE IN SPECIFIC POPULATIONS ( 8.1 )] 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 or other estrogen- or progestin-sensitive cancer ( 4 ) Liver tumors or liver disease ( 4 ) Pregnancy ( 4 ) Co-administration with Hepatitis C drug combinations containing ombitasvir, paritaprevir/ritonavir, with or without dasabuvir ( 4 )
Warnings and precautions
• Vascular risks : Stop drospirenone and ethinyl estradiol 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 drospirenone and ethinyl estradiol 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 drospirenone and ethinyl estradiol if jaundice occurs. ( 5.4 )
• High blood pressure : Do not prescribe drospirenone and ethinyl estradiol for women with uncontrolled hypertension or hypertension with vascular disease. ( 5.5 )
• Carbohydrate and lipid metabolic effects : Monitor prediabetic and diabetic women taking drospirenone and ethinyl estradiol. Consider an alternate contraceptive method for women with uncontrolled dyslipidemia. ( 5.7 )
• Headache : Evaluate significant change in headaches and discontinue drospirenone and ethinyl estradiol if indicated. ( 5.8 )
• Uterine bleeding : Evaluate irregular bleeding or amenorrhea. ( 5.9 ) 5.1 Thromboembolic Disorders and Other Vascular Problems Stop Drospirenone and ethinyl estradiol 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 and ethinyl estradiol 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 1 . Table 1: 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 a All COCs available in the US during the conduct of the study b HR: 0.9 (0.5-1.6) EURAS (Dinger 2007) Initiators, including new users a All COCS available in Europe during the conduct of the study c Levonorgestrel/EE HR: 0.9 (0.6-1.4) HR: 1 (0.6-1.8) “FDA-funded study” (2011) New users a All users (i.e., initiation and continuing use of study combination hormonal contraception) Other COCs available during the course of the study d Levonorgestrel/0.03 mg EE Other COCs available during the course of the study d Levonorgestrel/0.03 mg EE HR: 1.8 (1.3-2.4) HR: 1.6 (1.1-2.2) HR: 1.7 (1.4-2.1) HR: 1.5 (1.2-1.8) 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 In addition to these “regulatory studies,” other studies of various designs have been conducted. Overall, there are two prospective cohort studies (see Table 1): 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 1), 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. 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 ) ] Adverse reactions commonly reported by COC users are:
• Irregular uterine bleeding
• Nausea
• Breast tenderness
• Headache The most frequent adverse reactions (≥ 2%) in contraception and acne clinical trials were: headache/migraine (6.7%), menstrual irregularities (4.7%), nausea/vomiting (4.2%), breast pain/tenderness (4.0%) and mood changes (2.2%). ( 6.1 ) The most frequent adverse reactions (≥ 2%) in PMDD clinical trials were: menstrual irregularities (24.9%), nausea (15.8%), headache (13.0%), breast tenderness (10.5%), fatigue (4.2%), irritability (2.8%), decreased libido (2.8%), increased weight (2.5%), and affect lability (2.1%). ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Xiromed, LLC. At 1-844-XIROMED (844-947-6633) or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch 6.1 Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. Contraception and Acne Clinical Trials The data provided reflect the experience with the use of drospirenone and ethinyl estradiol in the adequate and well-controlled studies for contraception (N=1,056) and for moderate acne vulgaris (N=536). For contraception, a Phase 3, multicenter, multinational, open-label study was conducted to evaluate safety and efficacy up to one year in 1,027 women aged 17 to 36 who took at least one dose of drospirenone and ethinyl estradiol. A second Phase 3 study was a single center, open-label, active-controlled study to evaluate the effect of 7 28-day cycles of drospirenone and ethinyl estradiol on carbohydrate metabolism, lipids and hemostasis in 29 women aged 18 to 35. For acne, two multicenter, double-blind, randomized, placebo-controlled studies, in 536 women aged 14 to 45 with moderate acne vulgaris who took at least one dose of drospirenone and ethinyl estradiol, evaluated the safety and efficacy during up to 6 cycles. 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: headache/migraine (6.7%), menstrual irregularities (including vaginal hemorrhage [primarily spotting] and metrorrhagia (4.7%), nausea/vomiting (4.2%), breast pain/tenderness (4%) and mood changes (mood swings, depression, depressed mood and affect lability) (2.2%). PMDD Clinical Trials Safety data from trials for the indication of PMDD are reported separately due to differences in study design and setting in the Contraception and Acne studies as compared to the PMDD clinical program. Two (one parallel and one crossover designed) multicenter, double-blind, randomized, placebo-controlled trials for the secondary indication of treating the symptoms of PMDD evaluated safety and efficacy of drospirenone and ethinyl estradiol during up to 3 cycles among 285 women aged 18–42, diagnosed with PMDD and who took at least one dose of drospirenone and ethinyl estradiol. Common adverse reactions (≥ 2% of users) were: menstrual irregularities (including vaginal hemorrhage [primarily spotting] and metrorrhagia) (24.9%), nausea (15.8%), headache (13.0%), breast tenderness (10.5%), fatigue (4.2%), irritability (2.8%), decreased libido (2.8%), increased weight (2.5%), and affect lability (2.1%). Adverse Reactions (≥1%) Leading to Study Discontinuation: Contraception Clinical Trials Of 1,056 women, 6.6% discontinued from the clinical trials due to an adverse reaction; the most frequent adverse reactions leading to discontinuation were headache/migraine (1.6%) and nausea/vomiting (1.0%). Acne Clinical Trials Of 536 women, 5.4% discontinued from the clinical trials due to an adverse reaction; the most frequent adverse reaction leading to discontinuation was menstrual irregularities (including menometrorrhagia, menorrhagia, metrorrhagia and vaginal hemorrhage) (2.2%) . PMDD Clinical Trials Of 285 women, 11.6% discontinued from the clinical trials due to an adverse reaction; the most frequent adverse reactions leading to discontinuation were: nausea/vomiting (4.6%), menstrual irregularity (including vaginal hemorrhage, menorrhagia, menstrual disorder, menstruation irregular and metrorrhagia) (4.2%), fatigue (1.8%), breast tenderness (1.4%), depression (1.4%), headache (1.1%), and irritability (1.1%). Serious Adverse Reactions Contraception Clinical Trials: migraine and cervical dysplasia Acne Clinical Trials: none reported in the clinical trials PMDD Clinical Trials : cervical dysplasia 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.
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 drospirenone and ethinyl estradiol 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 drospirenone and ethinyl estradiol 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 ( 5.13 ) and DRUG INTERACTIONS ( 7.2 ) ] .
Use in specific populations
Nursing Mothers: Not recommended; can decrease milk production. ( 8.3 ) 8.1 Pregnancy Risk Summary There is no use for contraception in pregnancy; therefore, Loryna 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 too DRSP/EE 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 Loryna in pregnant women suggest that frequencies of miscarriage and congenical 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 Loryna 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 Loryna and any potential adverse effects on the breast-fed child from Loryna 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. 8.3 Nursing Mothers When possible, advise the nursing mother to use other forms of contraception until she has weaned her child. Estrogen-containing COCs can reduce milk production in breastfeeding mothers. This is less likely to occur once breastfeeding is well-established; however, it can occur at any time in some women. Small amounts of oral contraceptive steroids and/or metabolites are present in breast milk. After oral administration of 3 mg DRSP/0.03 mg EE (Yasmin) tablets, about 0.02% of the DRSP dose was excreted into the breast milk of postpartum women within 24 hours. This results in a maximal daily dose of about 0.003 mg DRSP in an infant. 8.4 Pediatric Use Safety and efficacy of drospirenone and ethinyl estradiol have 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 and ethinyl estradiol have not been studied in postmenopausal women and is not indicated in this population. 8.6 Patients with Renal Impairment Drospirenone and ethinyl estradiol 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 levels 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 and ethinyl estradiol 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 and ethinyl estradiol 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, Loryna 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 too DRSP/EE 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 Loryna in pregnant women suggest that frequencies of miscarriage and congenical anomalies were not higher than the estimated background risk in the general population.
Pediatric use
8.4 Pediatric Use Safety and efficacy of drospirenone and ethinyl estradiol have 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 and ethinyl estradiol have 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
Loryna (drospirenone and ethinyl estradiol tablets, USP) provides an oral contraceptive regimen consisting of 24 peach active film-coated tablets each containing 3 mg of drospirenone and 0.02 mg of ethinyl estradiol and 4 white inert film coated tablets. Each active tablet consists of black iron oxide, croscarmellose sodium, lactose fast flo, polyethylene glycol, magnesium stearate, polysorbate 80, polyvinyl alcohol, povidone K-30, pregelatinized starch, talc, titanium dioxide, red iron oxide, yellow iron oxide. The inert tablet consists of andydrous lactose, magnesium stearate, povidone K-30, polyethylene glycol, polyvinyl alcohol-part hydrolyzed, talc and titanium dioxide. 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: Structure formula
Mechanism of action
12.1 Mechanism of Action COCs lower the risk of becoming pregnant primarily by suppressing ovulation. Other possible mechanisms may include cervical mucus changes that inhibit sperm penetration and the endometrial changes that reduce the likelihood of implantation.
How supplied
16.1 How Supplied Loryna (drospirenone and ethinyl estradiol tablets, USP) 3 mg/0.02 mg are available as follows: Each blister card contains 24 active tablets and 4 inactive tablets. The 24 active tablets are peach, round, film-coated, debossed with SZ on one side and U2 on the other side. The 4 inert tablets are white, round, film-coated, debossed with SZ on one side and J1 on the other side. NDC 70700-114-85, one carton containing 3 blister cards 16.2 Storage Store at 20° to 25º C (68° to 77º 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 Loryna tablets do not protect against HIV-infection (AIDS) and other sexually transmitted diseases.
• Counsel patients on Warnings and Precautions associated with COCs.
• Counsel patients that Loryna tablets contain 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 Loryna tablets 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 Loryna tablets are not indicated during pregnancy. If pregnancy occurs during treatment with Loryna tablets, 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. See “WHAT TO DO IF YOU MISS PILLS” section in FDA-APPROVED PATIENT LABELING .
• 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 peach 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. LORYNA® is a registered trademark of Xiromed Pharma España, S.L. Manufactured by Laboratorios Leon Farma S.A., Spain For Xiromed, LLC., Florham Park, NJ 07932 Product of Spain PI-114-04 Rev. 07/2023
Label text from the FDA structured product label by Xiromed, LLC. (revised Jul 10, 2023). Long sections are shortened; the complete label is on DailyMed.
Loryna NDC products (2)
| NDC | Strength & form | Labeler | Type |
|---|---|---|---|
| 63629-2336 | Kit | Bryant Ranch Prepack | ANDA |
| 70700-114 | Kit | Xiromed, LLC. | ANDA |
Frequently asked questions
What is Loryna used for?
Loryna (drospirenone and ethinyl estradiol tablets) is an estrogen/progestin COC, indicated for use by women to: Prevent pregnancy. ( 1.1 ) Treat symptoms of premenstrual dysphoric disorder (PMDD) for women who choose to use an oral contraceptive for contraception. ( 1.2 ) Treat moderate acne for women at least 14 years old only if the patient desires an oral contraceptive for birth control. (…
What are the side effects of Loryna?
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 ) ] Adverse reactions commonly reported by COC users are: •Irregular uterine bleeding… See the full label for the complete list.
Who makes Loryna?
Loryna is listed by 2 labelers in the FDA NDC directory, including Bryant Ranch Prepack, Xiromed, LLC..