SLYND

1 Dosing Considerations There is a potential for an increase in serum potassium concentration in women taking SLYND with other drugs that may increase serum potassium concentration (for example, ACE inhibitors, angiotensin-II receptor antagonists, potassium-sparing diuretics, potassium supplementation, heparin, aldosterone antagonists, and NSAIDS (see Warnings and Precautions-Hyperkalemia).

2 Recommended Dose and Dosage Adjustment One SLYND (white active or green inert tablets) is swallowed whole once daily. SLYND should be started using a Day 1 Start (Table 1). Take one tablet daily for 28 consecutive days: one white active tablet daily the first 24 days and one green inert tablet daily during the 4 following days.

Tablets should be taken every day at about the same time of the day so that the interval between two tablets is 24 hours. It is very important to take SLYND as directed; however, some patients may miss a pill from time to time. 2 Pharmacodynamics).

SLYND® (drospirenone tablets) Product Monograph Page 5 of 40 SLYND is not intended for use in prepubertal or in postmenopausal women. 4 Administration Table 1: Instructions for Starting SLYND or Switching from Another Contraceptive Method to SLYND Starting SLYND Start SLYND in women who are not currently using hormonal contraception (Day 1 Start) Important: Consider the possibility of ovulation and conception prior to initiation of this product.

Tablet color: • SLYND active tablets are white (Day 1 to Day 24). • SLYND inert tablets are green (Day 25 to Day 28). Day 1 Start: • Take first white active tablet on the first day of menses. • Take subsequent white active tablets once daily at the same time each day for a total of 24 days.

• Take one green inert tablet daily for 4 days and at the same time of day that active tablets were taken. • Begin each subsequent pack after taking the last inactive tablet. Switching from another contraceptive method to SLYND Start SLYND: • A combined oral contraceptive (COC) • On the day when the new pack of the previous COC would have started.

• Transdermal patch • On the day when next application would have been scheduled. • Vaginal ring • On the day when next insertion would have been scheduled. • Injection • On the day when next injection would have been scheduled. 5 Missed Dose Table 2: Instructions for Missed SLYND • If one white active tablet is missed Take the missed tablet as soon as possible.

2 Clinical Trial Adverse Reactions Because clinical trials are conducted under very specific conditions, the adverse reaction rates observed in the clinical trials may not reflect the rates observed in practice and should not be compared to the rates in the clinical trials of another drug.

Adverse reaction information from clinical trials is useful for identifying drug-related adverse events and for approximating rates. The safety of SLYND (n= 2598) has been assessed in adult women in three Phase 3 clinical trials (CF111/301, CF111/302 and CF111/303; see Clinical Trials) as well as in one phase II clinical trial (CF111/205).

The overall mean time of SLYND exposure is 236 days, ranging from 197 to 328 days. All adverse reactions from clinical trials reported in Table 4 and Table 5 are listed by system organ class (SOC) and presented by preferred term. 2%).

No major differences between both BMI subgroups or as compared to the total population were observed regarding treatment-emergent adverse events. 1 Clinical Trial Adverse Reactions – Pediatrics The following lists the adverse reactions reported in at least 2% of subjects that occurred in adolescents aged 12-17 years (CF111/304).

9%). 7% of subjects). Across all Phase 3 studies in adults, the only laboratory abnormalities reported as serious adverse events were blood potassium increased (one subject) and hyperkalemia (six subjects). 1% of subjects overall); the only preferred terms leading to discontinuation of more than one subject across the Phase 3 studies in adults were gamma- glutamyltransferase increased (three subjects) and hyperkalemia (two subjects).

In the Phase 3 study in adolescents (CF111/304), abnormal laboratory values were reported as adverse events in the SOCs of blood and lymphatic system […]

Carcinogenesis and Mutagenesis Breast Cancer:

A meta-analysis from 54 epidemiological studies reported a slight increased relative risk of having breast cancer in women using combined oral contraceptives (COCs), without evidence for causation. The risk of having breast cancer diagnosed in users of progestogen-only preparations is possibly of similar magnitude to that associated with COCs.

However, for progestogen-only preparations, the evidence is based on much smaller populations of users and so is less conclusive than that for COCs. Increasing age and a strong family history are the most significant risk factors for the development of breast cancer.

Other established risk factors include obesity, nulliparity, and late age for first full-term pregnancy. Women receiving oral contraceptives (OCs) should be instructed in self-examination of their breasts. They should notify their physicians whenever any masses are detected.

A yearly clinical breast examination is also recommended.

Cervical Cancer:

Some studies suggest that use of combination hormonal contraceptives containing progestin and estradiol has been associated with an increase in the risk of cervical cancer or Route of Administration Dosage Form/ Strength/Composition Non-medicinal Ingredients Oral Tablet 4 mg drospirenone Anhydrous lactose, colloidal silicon dioxide, magnesium stearate, microcrystalline cellulose, polyethylene glycol, polyvinyl alcohol partially hydrolyzed, talc and titanium dioxide.

Oral Tablet Inert Colloidal silicon dioxide, corn starch, FD&C blue 2 aluminum lake, hypromellose, lactose monohydrate, magnesium stearate, polysorbate, povidone, titanium dioxide, triacetin, and yellow ferric oxide SLYND® (drospirenone tablets) Product Monograph Page 8 of 40 intraepithelial neoplasia.

SLYND is contraindicated in women who are hypersensitive to this drug or to any ingredient in the formulation, including any non-medicinal ingredient, or component of the container. For a complete listing, see Dosage Forms, Strengths, Composition and Packaging.

SLYND is contraindicated in women with the following conditions: • Renal impairment • Adrenal insufficiency • Presence or history of cervical cancer or progestin sensitive cancers • Liver tumors, benign or malignant, or hepatic impairment • Undiagnosed abnormal uterine bleeding.