VLOOP

1 Dosing Considerations • Pregnant women: VLOOP should not be used in women who are pregnant. 4 DRUG-DRUG INTERACTION section. • Discontinue medication: Please see 7 WARNINGS AND PRECAUTIONS section. 2 Recommended Dose and Dosage Adjustment To achieve maximum contraceptive effectiveness, VLOOP must be used as directed (see When to Start VLOOP below).

One VLOOP is inserted in the vagina by the woman herself. As VLOOP is designed to be a once-a-month contraceptive regimen the ring is to remain in place continuously for three weeks. It is removed for a one-week break, during which a withdrawal bleed usually occurs.

A new ring is inserted no more than one week after removal of the last ring. The provided stickers are to be placed on the appropriate dates on a calendar to remind the woman to insert and remove the ring. Advise women to regularly check for the presence of VLOOP in the vagina (for example, before and after intercourse).

3 Drug-Behavioural Interactions, Expulsion). Health Canada has not authorized an indication for pediatric and geriatric use. 4 Administration The user can choose the insertion position that is most comfortable to her, for example, standing with one leg up, squatting, or lying down.

The ring is to be compressed and inserted into the vagina until it feels comfortable. The exact position of VLOOP inside the vagina is not critical for the contraceptive effect of the ring. The vaginal ring must be inserted on the appropriate day and left in place for three consecutive weeks.

This means that the ring is removed three weeks later on the same day of the week as it was inserted and at about the same time. VLOOP can be removed by hooking the index finger under the forward rim or by grasping the rim between the index and middle finger and pulling it out.

The used ring should be placed in the sachet (foil pouch) and discarded in a waste receptacle out of the reach and sight of children and pets (do not flush in toilet). The withdrawal bleeding usually starts 2-3 days after removal of the ring and may not have finished before the next ring is inserted.

In order to maintain contraceptive effectiveness, the new ring must be inserted one week after the previous one was removed even if menstrual bleeding has not finished. For example, if VLOOP is inserted on Wednesday at 22:00 h the ring should be removed again on the Wednesday 3 weeks later at about 22:00 h.

, retinal thrombosis (See 7 WARNINGS AND PRECAUTIONS) • Myocardial infarction • Cerebral thrombosis • Cerebral hemorrhage • Hypertension (See 7 WARNINGS AND PRECAUTIONS; 2 CONTRAINDICATIONS) • Benign and malignant hepatic tumors • Gallbladder disease • Congenital anomalies The following adverse reactions also have been reported in patients receiving CHCs: Nausea and vomiting constitute the most common adverse reactions and occur in approximately 10% of patients during the first cycle.

2 Clinical Trial Adverse Reactions Clinical trials are conducted under very specific conditions. The adverse reaction rates observed in the clinical trials; therefore, 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 may be useful in identifying and approximating rates of adverse drug reactions in real-world use. The most common treatment-related adverse events seen in the two pivotal clinical studies were headache, vaginitis, and leukorrhea (Table 2).

These adverse events as well as the incidence of acne, breast tenderness, and nausea which are typical of contraceptives were low. 6 *Total n=2,322 subjects Cervical cytology was assessed in 2,039 women during treatment with etonogestrel / ethinyl estradiol slow release vaginal ring.

For the majority of subjects, the cervical Pap smear result was Pap I at screening and at last assessment. 3%). Clinically relevant shifts of particular note occurred for 7 subjects with a Pap result of I at screening to a Pap result of IIIb / IV (high-grade SIL) at last assessment.

In summary, changes to abnormal cervical cytology occurred in a low percentage of the subjects. 0%, respectively). 6%, respectively), partly due to the adverse events device-related events and vaginal discomfort, which were only reported in the etonogestrel / ethinyl estradiol slow release vaginal ring group.

, Cardiovascular and Hematologic): o Severe hypertension (persistent values of ≥160 / 110 mmHg). o Known predisposition for venous or arterial thrombosis, with or without hereditary involvement such as Activated Protein C (APC-) resistance (including Factor V Leiden), antithrombin-III deficiency, protein C deficiency, protein S deficiency, hyperhomocysteinemia and antiphospholipid antibodies (anticardiolipin antibodies, lupus anticoagulant).

o Severe dyslipoproteinemia. o Smoking, if over age 35. o Diabetes mellitus with vascular involvement (see 7 WARNINGS AND PRECAUTIONS, Endocrine and Metabolism, Diabetes). o Major surgery with prolonged immobilization (see 7 WARNINGS AND PRECAUTIONS, General).

VLOOP (Etonogestrel / Ethinyl Estradiol slow release vaginal ring) Page 6 of 70 • History of migraine with focal neurological symptoms (see 7 WARNINGS AND PRECAUTIONS, Neurologic, Migraine and Headache). • Any ocular lesion arising from ophthalmic vascular disease, such as partial or complete loss of vision or defect in visual fields.

• Pancreatitis or a history thereof if associated with severe hypertriglyceridemia. • Presence or history of severe hepatic disease as long as liver function values have not returned to normal. 4 Drug-Drug Interactions). • Presence or history of liver tumors (benign or malignant).

• Known or suspected malignant conditions of the genital organs or the breasts, if sex steroid- influenced. • Undiagnosed vaginal bleeding. • Known or suspected pregnancy. • Hypersensitivity to VLOOP or to any ingredient in the formulation or component of the container.

For a complete listing, see 6 DOSAGE FORMS, STRENGTHS, COMPOSITION AND PACKAGING. 3 SERIOUS WARNINGS AND PRECAUTIONS BOX Serious Warnings and Precautions • Cigarette smoking increases the risk of serious cardiovascular events from combination hormonal contraceptive (CHC) use.

VLOOP should not be used in the presence of any of the conditions listed below. Should any of the conditions appear for the first time during the use of VLOOP, it should be removed immediately. • Presence or history of venous thrombosis, with or without pulmonary embolism.

, angina pectoris or transient ischemic attack). • Valvular heart disease with complications. • Presence of a severe or multiple risk factor(s) for arterial or venous thrombosis (see 7 WARNINGS AND PRECAUTIONS, Cardiovascular and Hematologic): o Severe hypertension (persistent values of ≥160 / 110 mmHg).

o Known predisposition for venous or arterial thrombosis, with or without hereditary involvement such as Activated Protein C (APC-) resistance (including Factor V Leiden), antithrombin-III deficiency, protein C deficiency, protein S deficiency, hyperhomocysteinemia and antiphospholipid antibodies (anticardiolipin antibodies, lupus anticoagulant).

o Severe dyslipoproteinemia. o Smoking, if over age 35. o Diabetes mellitus with vascular involvement (see 7 WARNINGS AND PRECAUTIONS, Endocrine and Metabolism, Diabetes). o Major surgery with prolonged immobilization (see 7 WARNINGS AND PRECAUTIONS, General).

VLOOP (Etonogestrel / Ethinyl Estradiol slow release vaginal ring) Page 6 of 70 • History of migraine with focal neurological symptoms (see 7 WARNINGS AND PRECAUTIONS, Neurologic, Migraine and Headache). • Any ocular lesion arising from ophthalmic vascular disease, such as partial or complete loss of vision or defect in visual fields.

• Pancreatitis or a history thereof if associated with severe hypertriglyceridemia. • Presence or history of severe hepatic disease as long as liver function values have not returned to normal. 4 Drug-Drug Interactions). • Presence or history of liver tumors (benign or malignant).