Daysee Drug Information
Generic name: LEVONORGESTREL AND ETHINYL ESTRADIOL
Uses of Daysee
Daysee™ is indicated for use by females of reproductive potential to prevent pregnancy. Daysee is a combination of levonorgestrel, a progestin, and ethinyl estradiol, an estrogen, indicated for use by females of reproductive to potential prevent pregnancy.
Dosage & Administration of Daysee
| If one light blue tablet is missed | Take the missed tablet as soon as possible. Take the next tablet at the regular time. Continue taking one tablet a day until the pack is finished. A back-up birth control method is not required if the patient has sex. |
|---|---|
| If two light blue tablet in a row are missed | Take the two missed tablets as soon as possible, and the next two tablets the next day. Continue taking one tablet a day until the pack is finished. Use additional nonhormonal contraception (such as condoms and spermicide) until tablets have been taken for 7 days after missing tablets. |
| If three or more light blue pills in a row are missed | Throw away the missed pills. Continue taking one tablet every day as indicated on the pack until the pack is finished. Bleeding may occur during the week following the missed tablets. Use additional nonhormonal contraception (such as condoms and spermicide) until tablets have been taken for 7 days after missing tablets. |
| If any of the seven mustard tablets are missed | Throw away the missed tablets. Continue taking the remaining tablets until the pack is finished. A backup birth control method is not needed. |
Side Effects of Daysee
Clinical Trial 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 the rates in the clinical trials of another drug and may not reflect the rates observed in practice. The clinical trial that evaluated the safety and efficacy of Daysee was a 12-month, randomized, multicenter, open-label study, which enrolled women aged 18 to 40, of whom 1,006 took at least one dose of Daysee. Adverse Reactions Leading to Study Discontinuation: 16.3% of the women discontinued from the clinical trial due to an adverse reaction; the most common adverse reactions (≥ 1% of women) leading to discontinuation were irregular and/or heavy uterine bleeding (5.9%), weight gain (2.4%), mood changes (1.5%), and acne (1.0%). Common Treatment-Emergent Adverse Reactions (≥ 5% of women) : irregular and/or heavy uterine bleeding (17%), weight gain (5%), acne (5%). Serious Adverse Reactions: migraine, cholecystitis, cholelithiasis, pancreatitis, abdominal pain, and major depressive disorder.
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 to 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: Relevant 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 Daysee. Because these reactions are reported voluntarily from a population of uncertain size, it is not possible to reliably estimate their frequency of establish a causal relationship to drug exposure.
Gastrointestinal disorders : abdominal distension, vomiting General disorders and administration site conditions: Chest pain, fatigue, malaise, edema peripheral, pain Immune system disorders: hypersensitivity reaction Investigations : blood pressure increased Musculoskeletal and connective tissue disorders : muscle spasms, pain in extremity Nervous system disorders : dizziness, loss of consciousness Psychiatric disorders : insomnia Reproductive and breast disorders : dysmenorrhea Respiratory, thoracic and mediastinal disorders : pulmonary embolism, pulmonary thrombosis Skin and subcutaneous tissue disorders : alopecia Vascular disorders : thrombosis Figure 3
Warnings & Cautions for Daysee
Thromboembolic and Other Vascular Conditions Stop Daysee if an arterial or deep
venous thrombotic/thrombembolic event occurs. Stop Daysee if there is unexplained loss of vision, proptosis, diplopia, papilledema, or retinal vascular lesions and evaluate for retinal vein thrombosis immediately. Discontinue Daysee during prolonged immobilization.
If feasible, stop Daysee at least 4 weeks before and through 2 weeks after major surgery, or other surgeries known to have an elevated risk of thromboembolism. Start Daysee no earlier than 4 weeks after delivery, in women who are not breastfeeding. The risk of postpartum thromboembolism decreases after the third postpartum week, whereas the risk of ovulation increases after the third postpartum week.
Before starting Daysee evaluate any past medical history or family history of thrombotic or thromboembolic disorders and consider whether the history suggests an inherited or acquired hypercoagulopathy. Daysee is contraindicated in women with a high risk of arterial or venous/thromboembolic diseases . Arterial Events COCs increase the risk of cardiovascular events and cerebrovascular events, such as myocardial infarction and stroke. The risk is greater among older women (> 35 years of age), smokers, and females with hypertension, dyslipidemia, diabetes, or obesity.
Daysee is contraindicated in women over 35 years of age who smoke . Cigarette smoking increases the risk of serious cardiovascular events from COC use. This risk increases with age, particularly in women over 35 years of age, and with the number of cigarettes smoked. Venous Events Use of COCs increases the risk of venous thromboembolic events (VTEs), such as deep vein thrombosis and pulmonary embolism.
Risk factors for VTEs include smoking, obesity, and family history of VTE, in addition to other factors that contraindicate use of CHCs . While the increased risk of VTE associated with use of COCs is well-established, the rates of VTE are even greater during pregnancy, and especially during the postpartum period (see Figure 1). The rate of VTE in females using COCs has been estimated to be 3 to 9 cases per 10,000 woman years. The risk of VTE is highest during the first year of use of a COC and when restarting hormonal contraception after a break of four weeks or longer. The risk of thromboembolic disease due to COCs gradually disappears after COC use is discontinued.
Figure 1 shows the risk of developing a VTE for women who are not pregnant and do not use oral contraceptives, for women who use oral contraceptives, and for women in the postpartum period. To put the risk of developing a VTE into perspective: If 10,000 women who are not pregnant and do not use oral contraceptives are followed for one year, between 1 and 5 of these women will develop a VTE. Use of Daysee provides women with more hormonal exposure on a yearly basis than conventional monthly oral contraceptives containing the same strength synthetic estrogens and progestins (an additional 9 and 13 weeks of exposure to progestin and estrogen, respectively, per year).
Liver Disease Elevated Liver Enzymes Daysee is contraindicated in women with acute
viral hepatitis or severe (decompensated) cirrhosis of the liver . Acute liver test abnormalities may necessitate the discontinuation of Daysee until the liver tests return to normal and Daysee causation has been excluded. Discontinue Daysee if jaundice develops. Liver Tumors Daysee is contraindicated in women with benign or malignant liver tumors . COCs increase the risk of hepatic adenomas.
An estimate of the attributable risk is 3.3 cases/100,000 COC users. Rupture of hepatic adenomas may cause death from abdominal hemorrhage. Studies have shown an increased risk of developing hepatocellular carcinoma in long-term (> 8 years) COC users.
The attributable risk of liver cancers in COC users is less than one case per million users.
Hypertension Daysee is contraindicated in women with uncontrolled hypertension or hypertension with
vascular disease . For all women, including those with well-controlled hypertension, monitor blood pressure at routine visits and stop Daysee if blood pressure rises significantly. An increase in blood pressure has been reported in women taking COCs, and this increase is more likely in older women and with extended duration of use. The effect of COCs on blood pressure may vary according to the progestin in the COC.
Risk of Liver Enzyme Elevations with
Concomitant Hepatitis C Treatment During clinical trials with the Hepatitis C combination drug regimen that contains obmitasvir/paritaprevir/ritonavir, with or without dasabuvir, ALT elevations greater than 5 times the upper limit of normal (ULN), including some cases greater than 20 times the ULN, were significantly more frequent in women using ethinyl estradiol-containing medications, such as Daysee. Discontinue Daysee prior to starting therapy with the combination drug regimen ombitasvir/paritaprevir/ritonavir, with or without dasabuvir . Daysee can be restarted approximately 2 weeks following completion of treatment with the Hepatitis C combination drug regimen.
Age-related Considerations
The risk for cardiovascular disease and prevalence of risk factors for cardiovascular disease increases with age. Certain conditions, such as smoking and migraine headache without aura, that do not contraindicate COC use in younger females, are contraindications to use in women over 35 years of age . Consider the presence of underlying risk factors that may increase the risk of cardiovascular disease or VTE, particularly before initiating a COC for women over 35 years, such as: Hypertension Diabetes Dyslipidemia Obesity
Gallbladder Disease Studies suggest a small increased relative risk of developing gallbladder
disease among COC users. Use of COCs, including Daysee, may also worsen existing gallbladder disease. A past history of COC-related cholestasis predicts an increased risk with subsequent COC use.
Females with a history of pregnancy-related cholestasis may be at an increased risk for COC-related cholestasis.
Adverse Carbohydrate and Lipid Metabolic Effects Hyperglycemia Daysee is contraindicated in diabetic
women over age 35, or females who have diabetes with hypertension, nephropathy, retinopathy, neuropathy, other vascular disease, or females with diabetes of > 20 years duration . Daysee may decrease glucose tolerance. Carefully monitor prediabetic and diabetic women who are taking Daysee. Dyslipidemia Consider alternative contraception for women with uncontrolled dyslipidemia.
Daysee may cause adverse lipid changes. Women with hypertriglyceridemia, or a family history thereof, may have an increase in serum triglyceride concentrations when using Daysee, which may increase the risk of pancreatitis.
Headache Daysee is contraindicated in females who have headaches with focal neurological
symptoms or have migraine headaches with aura, and in women over 35 years of age who have migraine headaches with or without aura . If a woman taking Daysee develops new headaches that are recurrent, persistent, or severe, evaluate the cause and discontinue Daysee if indicated. Consider discontinuation of Daysee if there is an increased frequency or severity of migraine during COC use (which may be prodromal of a cerebrovascular event).
Bleeding Irregularities and Amenorrhea Unscheduled Bleeding and Spotting Women using Daysee may
experience unscheduled (breakthrough or intracyclic) bleeding and spotting, especially during the first 3 months of use. Bleeding irregularities may resolve over time or by changing to a different contraceptive product. If unscheduled bleeding persists or occurs after previously regular cycles, evaluate for causes such as pregnancy or malignancy.
When prescribing Daysee, the occurrence of fewer planned menses (4 per year instead of 13 per year) should be weighed against the occurrence of increased unscheduled bleeding and/or spotting. The primary clinical trial (PSE-301) that evaluated the efficacy of Daysee also assessed unscheduled bleeding. The participants in the 12-month clinical trial (N=1,006) completed the equivalent of 8,681 28-day cycles of exposure and were composed primarily of women who had used oral contraceptives previously (89%) as opposed to new users (11%). A total of 82 (8.2%) of the women discontinued Daysee, at least in part, due to bleeding or spotting.
Scheduled (withdrawal) bleeding and/or spotting remained fairly constant over time, with an average of 3 days of bleeding and/or spotting per each 91-day cycle. Unscheduled bleeding and unscheduled spotting decreased over successive 91-day cycles. Table 1 below presents the number of days with unscheduled bleeding in treatment cycles 1 and 4. Table 2 presents the number of days with unscheduled spotting in treatment cycles 1 and 4. Table 2: Total Number of Days with Unscheduled Bleeding Q1 = Quartile 1: 25% of women had this number of days of unscheduled bleeding Median: 50% of women had ≤ this number of days of unscheduled bleeding Q3 = Quartile 3: 75% of women had ≤ this number of days of unscheduled bleeding 91-Day Treatment Cycle Days per 84-Day Interval Days per 28-Day Interval Q1 Median Q3 Mean Mean 1 st 1 4 10 6.9 1.7 4 th 0 1 4 3.2
Table 3: Total Number of Days with Unscheduled Spotting Q1 = Quartile
1: 25% of women had ≤ this number of days of unscheduled spotting Median: 50% of women had ≤ this number of days of unscheduled spotting Q3 = Quartile 3: 75% of women had ≤ this number of days of unscheduled spotting 91-Day Treatment Cycle Days per 84-Day Interval Days per 28-Day Interval Q1 Median Q3 Mean Mean 1 st 1 4 11 7.4 1.9 4 th 0 2 7 4.4
Figure 2 shows the percentage of Daysee subjects participating in trial
PSE-301 with ≥ 7 days or ≥ 20 days of unscheduled bleeding and/or spotting, or only unscheduled bleeding, during each 91-day treatment cycle. Figure 2: Percent of Women Taking Daysee who Reported Unscheduled Bleeding and/or Spotting or only Unscheduled Bleeding If unscheduled spotting or bleeding occurs, instruct the patient to continue on the same regimen. If the bleeding is persistent or prolonged, advise the patient to consult her healthcare provider.
Amenorrhea and Oligomenorrhea Women who use Daysee may experience absence of scheduled (withdrawal) bleeding, even if they are not pregnant. If scheduled bleeding does not occur, consider the possibility of pregnancy. After discontinuation of Daysee, amenorrhea or oligomenorrhea may occur, especially if these conditions were pre-existent. 5.10 Depression Carefully observe women with a history of depression and discontinue Daysee if depression recurs to a serious degree.
Data on the association of COCs with the onset of depression or exacerbation of existing depression are limited. 5.11 Malignant Neoplasms Breast Cancer Daysee is contraindicated in females who currently have or have had breast cancer because breast cancer may be hormonally sensitive. Epidemiology studies have not found a consistent association between use of combined oral contraceptives (COCs) and breast cancer risk. Studies do not show an association between ever (current or past) use of COCs and risk of breast cancer.
However, some studies report a small increase in the risk of breast cancer among current or recent users (<6 months since last use) and current users with longer duration of COC use . Cervical Cancer Some studies suggest that COCs are associated with an increase in the risk of cervical cancer or intraepithelial neoplasia. However, there is controversy about the extent to which these findings are due to differences in sexual behavior and other factors. 5.12 Effect on Binding Globulins The estrogen component of Daysee may raise the serum concentrations of thyroxine-binding globulin, sex hormone-binding globulin, and cortisol-binding globulin. The dose of replacement thyroid hormone or cortisol therapy may need to be increased. 5.13 Hereditary Angioedema In females with hereditary angioedema, exogenous estrogens, including Daysee, may induce or exacerbate symptoms of hereditary angioedema. 5.14 Chloasma Chloasma may occur with Daysee use, especially in women with a history of chloasma gravidarum.
Advise women with a history of chloasma to avoid exposure to the sun or ultraviolet radiation while using Daysee. Figure 1 Figure 2
Drug Interactions with Daysee
Effects of Other Drugs on Combined Oral Contraceptives Substances Decreasing the Plasma
Concentrations of COCs and Potentially Diminishing the Efficacy of COCs: Table 4 includes substances that demonstrated an important drug interaction with Daysee. Table 4: Significant Drug Interactions Involving Substances That Affect COCs Metabolic Enzyme Inducers Clinical effect Concomitant use of COCs with metabolic enzyme inducers may decrease the plasma concentrations of the estrogen and/or progestin component of COCs. Decreased exposure of the estrogen and/or progestin component of COCs may potentially diminish the effectiveness of COCs and may lead to contraceptive failure or an increase in breakthrough bleeding.
Prevention or management Counsel females to use an alternative method of contraception or a backup method when enzyme inducers are used with COCs. Continue backup contraception for 28 days after discontinuing the enzyme inducer to maintain contraceptive reliability. Examples Aprepitant, barbiturates, bosentan, carbamazepine, efavirenz, felbamate, griseofulvin, oxcarbazepine, phenytoin, rifampin, rifabutin, rufinamide, topiramate, products containing St.
John's wort Induction potency of St. John's wort may vary widely based on preparation., and certain protease inhibitors (see separate section on protease inhibitors below). Colesevelam Clinical effect Concomitant use of COCs with colesevelam significantly decreases systemic exposure of ethinyl estradiol. Decreased exposure of the estrogen component of COCs may potentially reduce contraceptive efficacy or result in an increase in breakthrough bleeding, depending on the strength of ethinyl estradiol in the CHC. Prevention or management Administer 4 or more hours apart to attenuate this drug interaction.
Substances increasing the systemic exposure of COCs: Co-administration of atorvastatin or rosuvastatin and COCs containing ethinyl estradiol increase systemic exposure of ethinyl estradiol by approximately 20 to 25 percent. Ascorbic acid and acetaminophen may increase systemic exposure of ethinyl estradiol, possibly by inhibition of conjugation. CYP3A inhibitors such as itraconazole, voriconazole, fluconazole, grapefruit juice, or ketoconazole may increase systemic exposure of the estrogen and/or progestin component of COCs.
Human immunodeficiency virus (HIV)/hepatitis C virus (HCV) protease inhibitors and non-nucleoside reverse transcriptase inhibitors: Significant decreases in systemic exposure of the estrogen and/or progestin have been noted when COCs are co-administered with some HIV protease inhibitors (e.g., nelfinavir, ritonavir, darunavir/ritonavir, (fos)amprenavir/ritonavir, lopinavir/ritonavir, and tipranavir/ritonavir), some HCV protease inhibitors (e.g., boceprevir and telaprevir), and some non-nucleoside reverse transcriptase inhibitors (e.g., nevirapine). In contrast, significant increases in systemic exposure of the estrogen and/or progestin have been noted when COCs are co-administered with certain other HIV protease inhibitors (e.g., indinavir and atazanavir/ritonavir) and with other non-nucleoside reverse transcriptase inhibitors (e.g., etravirine).
Effects of Combined Oral Contraceptives on Other Drugs Table 5 provides significant
drug interaction information for drugs co-administered with Daysee. Table 5: Significant Drug Interaction Information for Drugs Co-Administered With COCs Lamotrigine Clinical effect Concomitant use of COCs with lamotrigine may significantly decrease systemic exposure of lamotrigine due to induction of lamotrigine glucuronidation. Decreased systemic exposure of lamotrigine may reduce seizure control.
Prevention or management Dose adjustment may be necessary. Consult the approved product labeling for lamotrigine. Thyroid Hormone Replacement Therapy or Corticosteroid Replacement Therapy Clinical effect Concomitant use of COCs with thyroid hormone replacement therapy or corticosteroid replacement therapy may increase systemic exposure of thyroid-binding and cortisol-binding globulin . Prevention or management The dose of replacement thyroid hormone or cortisol therapy may need to be increased.
Consult the approved product labeling for the therapy in use . Other Drugs Clinical effect Concomitant use of COCs may decrease systemic exposure of acetaminophen, morphine, salicylic acid, and temazepam. Concomitant use with ethinyl estradiol-containing COCs may increase systemic exposure of other drugs (e.g., cyclosporine, prednisolone, theophylline, tizanidine, and voriconazole). Prevention or management The dosage of drugs that can be affected by this interaction may need to be increased. Consult the approved product labeling for the concomitantly used drug.
Concomitant Use with Hepatitis C Virus (HCV) Combination Therapy – Liver Enzyme
Elevation Co-administration of Daysee with HCV drug combinations containing ombitasvir/paritaprevir/ritonavir, with or without dasabuvir is contraindicated due to potential for ALT elevations . Co-administration of Daysee and glecaprevir/pibrentasvir is not recommended due to potential for ALT elevations.
Effect on Laboratory Tests
The use of COCs may influence the results of certain laboratory tests, such as coagulation factors, lipids, glucose tolerance, and binding proteins.
Pregnancy Safety for Daysee
Pregnancy Risk Summary There is no use for contraception in pregnancy; therefore, Daysee 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 COCs 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.
Pediatric Use of Daysee
Pediatric Use Safety and efficacy of Daysee have been established in women of reproductive age. Safety and efficacy are expected to be the same for postpubertal adolescents under the age of 18 as for users 18 years and older. Use of Daysee before menarche is not indicated.
Contraindications for Daysee
Daysee is contraindicated in females who are known to have or develop the following conditions: A high risk of arterial or venous thrombotic diseases. Examples include females who are known to: Smoke, if over age 35. Have current or history of deep vein thrombosis or pulmonary embolism. Have cerebrovascular disease Have coronary artery disease.
Have thrombogenic valvular or thrombogenic rhythm diseases of the heart (for example, subacute bacterial endocarditis with valvular disease, or atrial fibrillation). Have inherited or acquired hypercoagulopathies. Have uncontrolled hypertension or hypertension with vascular disease. Have diabetes mellitus and are over age 35, diabetes mellitus with hypertension or with vascular disease or other end-organ damage, or diabetes mellitus of >20 years duration.
Have headaches with focal neurological symptoms, migraine headaches with aura, or over age 35 with any migraine headaches. Current diagnosis of, or history of, breast cancer, which may be hormone sensitive. Liver tumors, acute viral hepatitis, or severe (decompensated) cirrhosis.
Undiagnosed abnormal uterine bleeding Use of Hepatitis C drug combinations containing ombitasvir/paritaprevir/ritonavir, with or without dasabuvir, due to the potential for ALT elevations. A high risk of arterial or venous thrombotic diseases Undiagnosed abnormal uterine bleeding Breast cancer Liver tumors or liver disease, acute viral hepatitis or decompensated cirrhosis Co-administration with Hepatitis C drug combinations containing ombitasvir/paritaprevir/ritonavir, with or without dasabuvir.
Overdosage Information for Daysee
There have been no reports of serious ill effects from overdose of oral contraceptives, including ingestion by children. Overdosage may cause uterine bleeding in females and nausea.
Clinical Studies of Daysee
In a 12-month, multicenter, randomized, open-label clinical trial, 1,006 women aged 18 to 40 were studied to assess the safety and efficacy of Daysee, completing the equivalent of 8,681 28-day cycles of exposure. The racial demographic of those enrolled was: Caucasian (80%), African-American (11%), Hispanic (5%), Asian (2%), and Other (2%). There were no exclusions for body mass index (BMI) or weight. The weight range of those women treated was 91 to 360 lbs., with a mean weight of 156 lbs.
Among the women in the trial, 63% were current or recent hormonal contraceptive users, 26% were prior users (who had used hormonal contraceptives in the past but not in the 6 months prior to enrollment), and 11% were new starts. Of treated women, 14.8% were lost to follow-up, 16.3% discontinued due to an adverse event, and 12.9% discontinued by withdrawing their consent. The pregnancy rate (Pearl Index ) in women aged 18 to 35 years was 1.34 pregnancies per 100 women-years of use (95% confidence interval 0.54 to 2.75), based on 7 pregnancies that occurred after the onset of treatment and within 14 days after the last combination pill.
Cycles in which conception did not occur, but which included the use of backup contraception, were not included in the calculation of the PI. The PI includes patients who did not take the drug correctly.
Drug information sourced from the FDA. This content is for informational purposes only and does not constitute medical advice. Consult a healthcare professional before making any medication decisions.
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