Cryselle

INDICATIONS AND USAGE Cryselle is indicated for use by females of reproductive potential to prevent pregnancy. In a study of 1,287 women with a total of 11,085 cycles or 852.7 women-years of usage, the pregnancy rate in women age 15 to 40 years was approximately 1 pregnancy per 100 women-years of use.

CONTRAINDICATIONS Cryselle 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 women who are known to: o Smoke, if over age 35 o Have deep-vein thrombosis or pulmonary embolism, now or in the past o Have inherited or acquired coagulopathies o Have cerebrovascular disease o Have coronary artery disease o Have thrombogenic valvular or thrombogenic rhythm diseases of the heart (for example, subacute bacterial endocarditis with valvular disease or atrial fibrillation) o Have uncontrolled hypertension o Have diabetes mellitus with vascular disease o Headaches with focal neurological symptoms or migraine headaches with aura o Women over age 35 with any migraine headaches • Liver tumors, benign or malignant, or liver disease • Undiagnosed abnormal uterine bleeding • Pregnancy, because there is no reason to use COCs during pregnancy • Current diagnosis or history of breast cancer, which may be hormone sensitive • Hypersensitivity to any of the components of Cryselle Women who 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 ).

ADVERSE REACTIONS An increased risk of the following serious adverse reactions (see Warnings section for additional information) has been associated with the use of oral contraceptives: Serious cardiovascular events and stroke [see Boxed Warning ] Vascular events Liver disease Adverse reactions commonly reported by COC users are: Irregular uterine bleeding Nausea Breast tenderness Headache 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 clinical practice. The safety of Cryselle was evaluated in 1,343 healthy women of child-bearing potential who participated in 9 clinical trials and received at least one dose of Cryselle for contraception. Subjects were exposed for a total of 11,085 cycles, with 429 women completing one year of exposure. Subjects ranged in age from 15 to 40 years. Demographics were 69% Caucasian, 28% Black, and 3% other. Common Adverse Reactions (≥ 2% of women): Weight increase (11%) Cervical erosion (9%) Weight decrease (6%) Acne (4%) Dysmenorrhea (4%) Vaginal discharge (4%) Abdominal pain, cramps, and bloating (3%) Appetite increase (3%) Depression (3%) Nervousness (3%) Chloasma/melasma (2%) Fatigue (2%) Varicose veins, aggravation of (2%) A total of 8% of subjects discontinued the trials prematurely due to an adverse reaction, most commonly due to unscheduled bleeding, spotting, headache (including migraine), nausea, acne, changes in menstrual flow, weight increase, nervousness, high blood pressure, and depression. 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 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 8-10 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. The following additional adverse drug reactions have been reported from worldwide postmarketing experience with Cryselle. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure. Arterial Events: Arterial thromboembolism, Myocardial infarction, Cerebral hemorrhage Eye Disorder: Optic neuritis, which may lead to partial or complete loss of vision, Intolerance to contact lenses, Change (steepening) in corneal curvature Gastrointestinal Disorders: Colitis, Nausea, Pancreatitis Hepatobiliary Disorders: Gallbladder disease, Cholestatic jaundice, Budd-Chiari syndrome Immune System Disorders: Anaphylactic/anaphylactoid reactions, including urticaria, angioedema, and severe reactions with respiratory and circulatory symptoms Metabolism and Nutrition Disorders: Carbohydrate and lipid effects, Porphyria, exacerbation of Porphyria Neoplasms, Benign, Malignant, and Unspecified: Carcinoma of the reproductive organs and breasts , Hepatic neoplasia (including hepatic adenomas or benign liver tumors) Psychiatric Disorders: Mood changes Reproductive System and Breast Disorders: Tempora …

8. Nursing Mothers Advise the nursing mother to use other forms of contraception, when possible, until she has weaned her child. 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.

DESCRIPTION Cryselle ® is a combination oral contraceptive containing the progestational compound norgestrel, USP and the estrogenic compound ethinyl estradiol, USP. Norgestrel is designated as (2) (±)-13-Ethyl-17-hydroxy-18,19-dinor-17α-pregn-4-en-20-yn-3-one and ethinyl estradiol is designated as (19-nor-17α-pregna-1,3,5 (10)-trien-20-yne-3,17-diol). Each white active Cryselle tablet contains 0.3 mg norgestrel, USP and 0.03 mg ethinyl estradiol, USP. The inactive ingredients present are hypromellose, lactose monohydrate, magnesium stearate, microcrystalline cellulose, polyethylene glycol and pregelatinized corn starch. The light-green inactive tablets also contain D&C Yellow No. 10 Aluminum Lake, FD&C Blue No. 1 Aluminum Lake and FD&C Yellow No. 6 Aluminum Lake. Norgestrel, USP C 21 H 28 O 2 MW: 312.45 Ethinyl Estradiol, USP C 20 H 24 O 2 MW: 296.40 Norgestrel Strustural Formula Ethinyl Estradiol Structural Formula

HOW SUPPLIED Cryselle ® (norgestrel and ethinyl estradiol tablets USP), 0.3 mg/0.03 mg are available in packages of 1 blister card dispenser (NDC 71205-803-28), each containing 28 tablets as follows: 21 active, white, round, film-coated, biconvex tablets debossed with dp on one side and 543 on the other side and 7 inert, round, light-green colored, uncoated tablets debossed dp and 331. Store at 20o to 25°C (68° to 77o F) [See USP Controlled Room Temperature]. KEEP THIS AND ALL MEDICATIONS OUT OF THE REACH OF CHILDREN. Teva Pharmaceuticals USA, Inc. North Wales, PA 19454 Relabeled By: Proficient Rx LP Thousand Oaks, CA 91320 Rev. G 7/2022