Velivet Drug Information

To achieve maximum contraceptive effectiveness, Velivet tablets must be taken exactly as directed, at the same time every day, and at intervals not exceeding 24 hours. Velivet tablets may be initiated using either a Sunday start or a Day 1 start. NOTE: Seven different "day label strips" are provided to accommodate the selected start regimen.

The patient should place the self-adhesive "day label strip" that corresponds to her starting day on the blister card above the first row of tablets. During the First Cycle of Use IMPORTANT: The possibility of ovulation and conception prior to initiation of use of Velivet tablets should be considered. A woman can begin to take Velivet tablets either on the first Sunday after the onset of her menstrual period (Sunday Start) or on the first day of her menstrual period (Day 1 Start). When switching from another oral contraceptive, Velivet tablets should be started on the same day that a new pack of the previous oral contraceptive would have been started.

Sunday Start When initiating a Sunday start regimen, another method of contraception, such as condoms or spermicide, should be used for the first 7 consecutive days of taking Velivet tablets. Using a Sunday start, tablets are taken daily without interruption as follows: The first beige tablet should be taken on the first Sunday after menstruation begins (if menstruation begins on Sunday, the first beige tablet is taken on that day). Tablets are then taken sequentially following the arrows marked on the dispenser. One beige tablet is taken daily for 7 days, followed by 1 orange tablet daily for 7 days, 1 pink tablet daily for 7 days, and then 1 white (inactive) tablet daily for 7 days.

For all subsequent cycles, the patient then begins a new 28 tablet regimen on the next day (Sunday) after taking the last white (inactive) tablet. If a patient misses 1 active tablet in Weeks 1, 2, or 3, she should take the missed tablet as soon as she remembers. If the patient misses 2 consecutive active tablets in Week 1 or Week 2, the patient should take 2 tablets the day she remembers and 2 tablets the next day; thereafter, the patient should resume taking 1 tablet daily until she finishes the cycle pack.

The patient should be instructed to use a back-up method of birth control (such as condoms or spermicide) if she has intercourse in the 7 days after she restarts her pills. If the patient misses 2 consecutive pink (active) tablets in the third week or misses 3 or more active tablets in a row at any time during the cycle, the patient should keep taking 1 active tablet daily until the next Sunday. On Sunday the patient should throw out the rest of that cycle pack and start a new cycle pack that same day.

The patient should be instructed to use a back-up method of birth control if she has intercourse in the 7 days after restarting her pills. Complete instructions to facilitate patient counseling on proper pill usage can be found in Detailed Patient Labeling (" HOW TO TAKE THE PILL " section). Day 1 Start Counting the first day of menstruation as "Day 1", the first beige tablet should be taken on the first day of menstrual bleeding. Tablets are then taken sequentially without interruption as follows: One beige tablet daily for 7 days, then 1 orange tablet daily for 7 days, followed by 1 pink tablet daily for 7 days and then 1 white (inactive) tablet daily for 7 days.

For all subsequent cycles, the patient then begins a new 28 tablet regimen on the next day after taking the last white (inactive) tablet. If a patient misses 1 active tablet in Weeks 1, 2, or 3, she should take the missed tablet as soon as she remembers. If the patient misses 2 consecutive active tablets in Week 1 or Week 2, the patient should take 2 tablets the day she remembers and 2 tablets the next day; thereafter, the patient should resume taking 1 tablet daily until she finishes the cycle pack.

The patient should be instructed to use a back-up method of birth control (such as condoms or spermicide) if she has intercourse in the 7 days after she restarts her pills. If the patient misses 2 consecutive pink tablets in the third week or misses 3 or more active tablets in a row at any time during the cycle, the patient should throw out the rest of that cycle pack and start a new cycle pack that same day. The patient should be instructed to use a back-up method of birth control if she has intercourse in the 7 days after restarting her pills.

Complete instructions to facilitate patient counseling on proper pill usage can be found in Detailed Patient Labeling (" HOW TO TAKE THE PILL " section). ADDITIONAL INSTRUCTIONS FOR BOTH SUNDAY AND DAY 1 STARTS If Spotting or Breakthrough Bleeding Occurs Breakthrough bleeding, spotting, and amenorrhea are frequent reasons for patients discontinuing oral contraceptives. In breakthrough bleeding, as in all cases of irregular bleeding from the vagina, non-functional causes should be considered. In undiagnosed persistent or recurrent abnormal bleeding from the vagina, adequate diagnostic measures are indicated to rule out pregnancy or malignancy.

If both pregnancy and pathology have been excluded, time or a change to another preparation may solve the problem. Changing to an oral contraceptive with a higher estrogen content, while potentially useful in minimizing menstrual irregularity, should be done only if necessary since this may increase the risk of thromboembolic disease. Use of Velivet in The Event of a Missed Menstrual Period 1. If the patient has not adhered to the prescribed schedule, the possibility of pregnancy should be considered at the time of the first missed period and oral contraceptive use should be discontinued if pregnancy is confirmed. 2. If the patient has adhered to the prescribed regimen and misses two consecutive periods, pregnancy should be ruled out.

Oral contraceptive use should be discontinued if pregnancy is confirmed. Use of Velivet Postpartum The use of Velivet for contraception may be initiated 4 to 6 weeks postpartum in women who elect not to breastfeed. When the tablets are administered during the postpartum period, the increased risk of thromboembolic disease associated with the postpartum period must be considered (see CONTRAINDICATIONS and WARNINGS concerning thromboembolic disease.

See also PRECAUTIONS, Nursing Mothers ). If the patient starts on Velivet postpartum, and has not yet had a period, she should be instructed to use another method of contraception until a beige tablet has been taken daily for 7 consecutive days.

Post Marketing 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 1). Three studies compared breast cancer risk between current or recent COC users (<6 months since last use) and never users of COCs (Figure 1). 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 to 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 to 10 years of COC use.

Figure 1 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. An increased risk of the following serious adverse reactions has been associated with the use of oral contraceptives (see WARNINGS section): Thrombophlebitis and venous thrombosis with or without embolism Arterial thromboembolism Pulmonary embolism Myocardial infarction Cerebral hemorrhage Cerebral thrombosis Hypertension Gallbladder disease Hepatic adenomas or benign liver tumors There is evidence of an association between the following conditions and the use of oral contraceptives: Mesenteric thrombosis Retinal thrombosis The following adverse reactions have been reported in patients receiving oral contraceptives and are believed to be drug-related: Nausea Vomiting Gastrointestinal symptoms (such as abdominal pain, cramps and bloating) Breakthrough bleeding Spotting Change in menstrual flow Amenorrhea Temporary infertility after discontinuation of treatment Edema/fluid retention Melasma/chloasma which may persist Breast changes: tenderness, pain, enlargement, and secretion Decrease in serum folate levels Exacerbation of porphyria Aggravation of varicose veins Change in weight or appetite (increase or decrease) Change in cervical ectropion and secretion Possible diminution in lactation when given immediately postpartum Cholestatic jaundice Migraine headache Rash (allergic) Mood changes, including depression Vaginitis, including candidiasis Change in corneal curvature (steepening) Intolerance to contact lenses Exacerbation of systemic lupus erythematosus Exacerbation of chorea Anaphylactic/anaphylactoid reactions, including urticaria, angioedema, and severe reactions with respiratory and circulatory symptoms The following adverse reactions have been reported in users of oral contraceptives and the association has been neither confirmed nor refuted: Pre-menstrual syndrome Cataracts Cystitis-like syndrome Headache Nervousness Dizziness Hirsutism Loss of scalp hair Erythema multiforme Dysmenorrhea Pancreatitis Erythema nodosum Hemorrhagic eruption Impaired renal function Hemolytic uremic syndrome Acne Changes in libido Colitis Budd-Chiari Syndrome Optic neuritis, which may lead to partial or complete loss of vision 1

8. Drug Interactions Changes in contraceptive effectiveness associated with coadministration of other drugs : a. Anti-infective agents and anticonvulsants Contraceptive effectiveness may be reduced when hormonal contraceptives are coadministered with some antibiotics, anticonvulsants, and other drugs that increase metabolism of contraceptive steroids. This could result in unintended pregnancy or breakthrough bleeding.

Examples include barbiturates, rifampin, phenylbutazone, phenytoin, carbamazepine, felbamate, oxcarbazepine, topiramate, and griseofulvin. Since desogestrel is mainly metabolized by the cytochrome P450 2C9 enzyme (CYP 2C9) to form etonogestrel, the active progestin, there is a possibility of interaction with CYP 2C9 substrates or inhibitors (such as: ibuprofen, piroxicam, naproxen, phenytoin, fluconazole, diclofenac, tolbutamide, glipizide, celecoxib, sulfamethoxazole, isoniazid, torsemide, irbesartan, losartan, and valsartan). The clinical relevance of these interactions is unknown. b. Anti-HIV protease inhibitors Several of the anti-HIV protease inhibitors have been studied with coadministration of oral combination hormonal contraceptives; significant changes (increase and decrease) in the plasma levels of the estrogen and progestin have been noted in some cases.

The efficacy and safety of these oral contraceptive products may be affected with coadministration of anti-HIV protease inhibitors. Healthcare providers should refer to the label of the individual anti-HIV protease inhibitors for further drug-drug interaction information. Concomitant Use with HCV Combination Therapy – Liver Enzyme Elevation Do not co-administer Velivet (desogestrel and ethinyl estradiol tablets) with HCV drug combinations containing ombitasvir/paritaprevir/ritonavir, with or without dasabuvir, due to potential for ALT elevations (see WARNINGS, Risk of Liver Enzyme Elevations with Concomitant Hepatitis C Treatment ). c.

Herbal products Herbal products containing St. John’s Wort (hypericum perforatum) may induce hepatic enzymes (cytochrome P450) and p-glycoprotein transporter and may reduce the effectiveness of contraceptive steroids. This may also result in breakthrough bleeding.

Increase in plasma hormone levels associated with coadministered drugs : Coadministration of atorvastatin and certain ethinyl estradiol containing oral contraceptives increased AUC values for ethinyl estradiol by approximately 20%. Ascorbic acid and acetaminophen may increase plasma ethinyl estradiol levels, possibly by inhibition of conjugation. CYP 3A4 inhibitors such as itraconazole or ketoconazole may increase plasma hormone levels. Changes in plasma levels of coadministered drugs : Combination hormonal contraceptives containing some synthetic estrogens (e.g., ethinyl estradiol) may inhibit the metabolism of other compounds.

Increased plasma concentrations of cyclosporine, prednisolone, and theophylline have been reported with concomitant administration of oral contraceptives. Decreased plasma concentrations of acetaminophen and increased clearance of temazepam, salicylic acid, morphine, and clofibric acid have been noted when these drugs were administered with oral contraceptives. No formal drug-drug interaction studies were conducted with Velivet.

11. Pregnancy See CONTRAINDICATIONS and WARNINGS sections.

13. Pediatric Use Safety and efficacy of Velivet tablets have been established in women of reproductive age. Safety and efficacy are expected to be the same for postpubertal adolescents under the age of 16 and for users 16 years and older. Use of this product before menarche is not indicated.

Oral contraceptives should not be used in women who currently have the following conditions: Thrombophlebitis or thromboembolic disorders A past history of deep vein thrombophlebitis or thromboembolic disorders Cerebral vascular or coronary artery disease (current or history) Valvular heart disease with thrombogenic complications Severe hypertension Diabetes with vascular involvement Headaches with focal neurological symptoms Major surgery with prolonged immobilization Current diagnosis of, or history of, breast cancer, which may be hormone-sensitive Undiagnosed abnormal genital bleeding Cholestatic jaundice of pregnancy or jaundice with prior hormonal contraceptive use Hepatic tumors (benign or malignant) or active liver disease Known or suspected pregnancy Heavy smoking (≥ 15 cigarettes per day) and over age 35 Hypersensitivity to any of the components of Velivet (desogestrel and ethinyl estradiol tablets) Are receiving Hepatitis C drug combinations containing ombitasvir/paritaprevir/ritonavir, with or without dasabuvir, due to the potential for ALT elevations (see WARNINGS, Risk of Liver Enzyme Elevations with Concomitant Hepatitis C Treatment ).

Serious ill effects have not been reported following acute ingestion of large doses of oral contraceptives by young children. Overdosage may cause nausea, and withdrawal bleeding may occur in females. NON-CONTRACEPTIVE HEALTH BENEFITS The following non-contraceptive health benefits related to the use of oral contraceptives are supported by epidemiologic studies which largely utilized oral contraceptive formulations containing estrogen doses exceeding 0.035 mg of ethinyl estradiol or 0.05 mg of mestranol. 73 to 78 Effects on menses: increased menstrual cycle regularity decreased blood loss and decreased incidence of iron deficiency anemia decreased incidence of dysmenorrhea Effects related to inhibition of ovulation: decreased incidence of functional ovarian cysts decreased incidence of ectopic pregnancies Effects from long-term use: decreased incidence of fibroadenomas and fibrocystic disease of the breast decreased incidence of acute pelvic inflammatory disease decreased incidence of endometrial cancer decreased incidence of ovarian cancer