PRODUCT MONOGRAPH - Lolo

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2 PRODUCT MONOGRAPH INCLUDING PATIENT MEDICATION INFORMATION Pr LOLO Norethindrone acetate and ethinyl estradiol tablets, Mfr Std norethindrone acetate 1 mg ethinyl estradiol mg Ethinyl estradiol tablets, Mfr Std ethinyl estradiol mg Oral Contraceptive Allergan Inc. 85 Enterprise Blvd., Suite 500 Markham, ON L6G 0B5 Date of Initial Approval: December 10, 2013 Date of Revision October 24, 2019 Submission Control No: 229630 Page 2 of 53 RECENT MAJOR LABEL CHANGES CONTRAINDICATIONS, October 2019 WARNINGS AND PRECAUTIONS, October 2019 DRUG INTERACTIONS, October 2019 PATIENT MEDICATION INFORMATION, October 2019 Page 3 of 53 TABLE OF CONTENTS PART I: HEALTH PROFESSIONAL INFORMATION.

3 4 1 INDICATIONS .. 4 Pediatrics (<18 years) .. 4 Geriatrics .. 4 2 CONTRAINDICATIONS .. 4 3 SERIOUS WARNINGS AND PRECAUTIONS BOX .. 5 4 DOSAGE AND ADMINISTRATION .. 5 Dosing Considerations .. 5 Recommended Dose and Dosage Adjustment .. 6 Administration .. 6 Missed Dose .. 7 5 OVERDOSAGE .. 8 6 DOSAGE FORMS, STRENGTHS, COMPOSITION AND PACKAGING .. 8 7 WARNINGS AND PRECAUTIONS .. 9 Special Populations .. 16 Pregnant Women ..16 Breast-feeding ..16 Pediatrics ..16 Geriatrics ..17 Body Mass Index (BMI) ..17 8 ADVERSE REACTIONS .. 17 Adverse Reaction Overview .. 17 Clinical Trial Adverse 18 Less Common Clinical Trial Adverse Reactions .. 19 Abnormal Laboratory Findings: Hematologic, Clinical Chemistry and Other Quantitative Data.

4 20 Clinical Trial Adverse Reactions (Pediatrics) .. 20 Post-Market Adverse Reactions .. 20 9 DRUG INTERACTIONS .. 21 Overview .. 21 Drug-Drug Interactions .. 22 Drug-Food Interactions .. 26 Drug-Herb Interactions .. 26 Drug-Laboratory Test Interactions .. 26 Drug-Lifestyle Interactions .. 27 10 ACTION AND CLINICAL PHARMACOLOGY .. 27 Mechanism of Action .. 27 Pharmacodynamics .. 27 Pharmacokinetics .. 28 11 STORAGE, STABILITY AND DISPOSAL .. 31 12 SPECIAL HANDLING INSTRUCTIONS .. 31 PART II: SCIENTIFIC INFORMATION .. 32 13 PHARMACEUTICAL INFORMATION .. 32 14 CLINICAL TRIALS .. 33 Trial Design and Study Demographics .. 33 Study Results .. 34 15 NON-CLINICAL TOXICOLOGY .. 36 PATIENT MEDICATION INFORMATION.

5 40 Page 4 of 53 LOLO norethindrone acetate and ethinyl estradiol tablets ethinyl estradiol tablets PART I: HEALTH PROFESSIONAL INFORMATION 1 INDICATIONS LOLO (norethindrone acetate and ethinyl estradiol) is indicated for the prevention of pregnancy. In a one year (thirteen 28-day cycles) multicenter open-label clinical trial 1,582 women were studied to assess the safety and efficacy of LOLO . In this study 1,270 women 18 to 35 years of age were studied to assess the efficacy of LOLO , completing the equivalent of 12,482 28-day evaluable cycles of exposure. The pregnancy rate (Pearl Index [PI]) in women 18-35 years of age was pregnancies per 100 women-years of use (see CLINICAL TRIALS). The efficacy of LOLO in women with a body mass index >35 kg/m2 has not been evaluated.

6 Exposure to exogenous estrogen with LOLO is less than with other combined oral contraceptives with similar synthetic estrogens. Any benefits from the lower estrogen exposure provided by LOLO have not been evaluated. Pediatrics (<18 years) No data are available to Health Canada; therefore, Health Canada has not authorized an indication for pediatric use. Geriatrics No data are available to Health Canada; therefore, Health Canada has not authorized an indication for geriatric use. 2 CONTRAINDICATIONS LOLO should not be used in women with: a history of or actual thrombophlebitis or thromboembolic disorders (such as deep vein thrombosis or pulmonary embolism); a history of or actual cerebrovascular disorders; a history of or actual myocardial infarction or coronary artery disease; valvular heart disease with complications; history of or actual prodromi of a thrombosis ( , transient ischaemic attack, angina pectoris); active liver disease, or history of or actual benign or malignant liver tumours; known or suspected carcinoma of the breast; carcinoma of the endometrium or other known or suspected estrogen-dependent Page 5 of 53 neoplasia; undiagnosed abnormal vaginal bleeding.

7 Steroid-dependent jaundice, cholestatic jaundice, history of jaundice of pregnancy; any ocular lesion arising from ophthalmic vascular disease, such as partial or complete loss of vision or defect in visual fields; known or suspected pregnancy; current or history of migraine with focal aura; history of or actual pancreatitis if associated with severe hypertriglyceridaemia; presence of severe or multiple risk factor(s) for arterial or venous or thrombosis such as: o severe hypertension (persistent values of 160/100 mmHg) o uncontrolled hypertension o hereditary or acquired predisposition for venous or arterial thrombosis such as Factor V Leiden mutation and activated protein C (APC-) resistance, antithrombin-III-deficiency, protein C deficiency, protein S deficiency, hyperhomocysteinemia ( , due to MTHFR C677T, A1298 mutations), prothrombin mutation G20210A, and antiphospholipid-antibodies (anticardiolipin antibodies, lupus anticoagulant) o severe dyslipoproteinemia o over age 35 and smoke o diabetes mellitus with vascular involvement o major surgery associated with an increased risk of postoperative thromboembolism o prolonged immobilization Use with the Hepatitis C virus (HCV)

8 Combination drug regimen ombitasvir, paritaprevir, ritonavir with or without dasabuvir (see WARNINGS AND PRECAUTIONS). hypersensitivity to this drug or to any ingredient in the formulation or component of the container. For a complete listing, see the DOSAGE FORMS, COMPOSITION AND PACKAGING section of the PRODUCT MONOGRAPH . 3 SERIOUS WARNINGS AND PRECAUTIONS BOX Serious Warnings and Precautions Cigarette smoking increases the risk of serious cardiovascular events associated with the use of hormonal contraceptives. This risk increases with age, particularly in women over 35 years of age, and with the number of cigarettes smoked. For this reason, LOLO should not be used by women who are over 35 years of age and smoke (see Cardiovascular section below).

9 Patients should be counselled that birth control pills DO NOT PROTECT against sexually transmitted infections (STIs) including HIV/AIDS. For protection against STIs, it is advisable to use latex or polyurethane condoms IN COMBINATION WITH birth control pills. 4 DOSAGE AND ADMINISTRATION Dosing Considerations To achieve maximum contraceptive effectiveness, LOLO should be taken exactly as Page 6 of 53 directed and at intervals not exceeding 24 hours. LOLO tablets may be administered without regard to meals. LOLO provides a regimen consisting of 24 blue estrogen-progestin tablets, 2 white estrogen-only tablets, and 2 lilac placebo tablets. Recommended Dose and Dosage Adjustment During the first cycle of use: The possibility of ovulation and conception prior to initiation of medication should be considered.

10 The patient is instructed to begin taking LOLO on either Day 1 of menstruation (Day 1 Start) or the first Sunday after the onset of menstruation (Sunday Start). If menstruation begins on a Sunday, the first tablet (blue) is taken that day. One blue tablet should be taken daily for 24 consecutive days followed by one white tablet for 2 consecutive days, followed by one lilac tablet daily for 2 consecutive days. During the first cycle with a Sunday start, contraceptive reliance should not be placed on LOLO until a blue tablet has been taken daily for 7 consecutive days and a non-hormonal back-up method of birth control (such as latex or polyurethane condoms or spermicide) should be used during those 7 days. LOLO is effective from the first day of therapy if the tablets are begun on the first day of the menstrual cycle.