Aranelle Drug Information

To achieve maximum contraceptive effectiveness, oral contraceptives must be taken exactly as directed and at intervals not exceeding 24 hours. For a DAY 1 START, count the first day of menstrual flow as Day 1 and the first light yellow tablet is then taken on Day 1. For a SUNDAY START when menstrual flow begins on or before Sunday, the first light yellow tablet is taken on that day. With either a DAY 1 START or SUNDAY START, 1 light yellow tablet is taken for 7 days, then 1 white tablet for 9 days, then 1 light yellow tablet for 5 days, then 1 peach tablet (inert) for 7 days, whether bleeding has stopped or not.

With either a DAY 1 START or SUNDAY START 1 tablet is taken each day at the same time for 28 days. After all 28 tablets are taken, whether bleeding has stopped or not, the same dosage schedule is repeated beginning on the following day. INSTRUCTIONS TO PATIENTS To achieve maximum contraceptive effectiveness, the oral contraceptive pill must be taken exactly as directed and at intervals not exceeding 24 hours.

Important: Women should be instructed to use an additional method of protection until after the first 7 days of administration in the initial cycle. Due to the normally increased risk of thromboembolism occurring postpartum, women should be instructed not to initiate treatment with oral contraceptives earlier than 4 weeks after a full-term delivery. If pregnancy is terminated in the first 12 weeks, the patient should be instructed to start oral contraceptives immediately or within 7 days.

If pregnancy is terminated after 12 weeks, the patient should be instructed to start oral contraceptives after 2 weeks. 33, 77 If spotting or breakthrough bleeding should occur, the patient should continue the medication according to the schedule. Should spotting or breakthrough bleeding persist, the patient should notify her physician. If the patient misses 1 pill, she should be instructed to take it as soon as she remembers and then take the next pill at the regular time.

The patient should be advised that missing a pill can cause spotting or light bleeding and that she may be a little sick to her stomach on the days she takes the missed pill with her regularly scheduled pill. If the patient has missed more than one pill, see DETAILED PATIENT LABELING, HOW TO TAKE THE PILL, WHAT TO DO IF YOU MISS PILLS. Use of oral contraceptives in the event of a missed menstrual period: If the patient has not adhered to the prescribed dosage regimen, the possibility of pregnancy should be considered after the first missed period and oral contraceptives should be withheld until pregnancy has been ruled out. If the patient has adhered to the prescribed regimen and misses 2 consecutive periods, pregnancy should be ruled out before continuing the contraceptive regimen.

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. 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. An increased risk of the following serious adverse reactions has been associated with the use of oral contraceptives (see WARNINGS section): Thrombophlebitis Arterial thromboembolism Pulmonary embolism Myocardial infarction Cerebral hemorrhage Cerebral thrombosis Hypertension Gallbladder disease Hepatic adenomas, carcinomas or benign liver tumors There is evidence of an association between the following conditions and the use of oral contraceptives, although additional confirmatory studies are needed: 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 cramps and bloating) Breakthrough bleeding Spotting Change in menstrual flow Amenorrhea Temporary infertility after discontinuation of treatment Edema Melasma which may persist Breast changes: tenderness, enlargement, secretion Change in weight (increase or decrease) Change in cervical erosion and secretion Diminution in lactation when given immediately postpartum Cholestatic jaundice Migraine Rash (allergic) Mental depression Reduced tolerance to carbohydrates Vaginal candidiasis Change in corneal curvature (steepening) Intolerance to contact lenses 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 Changes in appetite Cystitis-like syndrome Headache Nervousness Dizziness Hirsutism Loss of scalp hair Erythema multiforme Erythema nodosum Hemorrhagic eruption Vaginitis Porphyria Impaired renal function Hemolytic uremic syndrome Budd-Chiari syndrome Acne Changes in libido Colitis figure 1

7. Drug Interactions Reduced efficacy and increased incidence of breakthrough bleeding and menstrual irregularities have been associated with concomitant use of rifampin. A similar association though less marked, has been suggested with barbiturates, phenylbutazone, phenytoin sodium, and possibly with griseofulvin, ampicillin and tetracyclines. 76 Concomitant Use with HCV Combination Therapy – Liver Enzyme Elevation Do not coadminister Aranelle ® 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 ).

10. Pregnancy See CONTRAINDICATIONS and WARNINGS sections.

12. Pediatric Use Safety and efficacy of Aranelle ® 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 the product before menarche is not indicated.

Oral contraceptives should not be used in women who 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 diagnosis of, or history of, breast cancer, which may be hormone-sensitive Undiagnosed abnormal genital bleeding Cholestatic jaundice of pregnancy or jaundice with prior pill use Hepatic adenomas, carcinomas or benign liver tumors Known or suspected pregnancy Are receiving Hepatitis C 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 ).

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.