VIORELE (Page 6 of 12)

6. Emotional disorders

Women with a history of depression should be carefully observed and the drug discontinued if depression recurs to a serious degree.

7. Contact lenses

Contact lens wearers who develop visual changes or changes in lens tolerance should be assessed by an ophthalmologist.

8. 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, carbamazepine and possibly with griseofulvin, ampicillin, and tetracyclines (72).

Combined hormonal contraceptives have been shown to significantly decrease plasma concentrations of lamotrigine when co-administered, likely due to induction of lamotrigine glucuronidation. This may reduce seizure control; therefore, dosage adjustments of lamotrigine may be necessary.

Consult the labeling of the concurrently-used drug to obtain further information about interactions with hormonal contraceptives or the potential for enzyme alterations.

Concomitant Use with HCV Combination Therapy — Liver Enzyme Elevation

Do not co-administer VIORELE 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).

9. Interactions with laboratory tests

Certain endocrine and liver function tests and blood components may be affected by oral contraceptives:

1.

Increased prothrombin and factors VII, VIII, IX and X; decreased antithrombin 3; increased norepinephrine-induced platelet aggregability.

2.

Increased thyroid binding globulin (TBG) leading to increased circulating total thyroid hormone, as measured by protein-bound iodine (PBI), T4 by column or by radioimmunoassay. Free T3 resin uptake is decreased, reflecting the elevated TBG; free T4 concentration is unaltered.

3.

Other binding proteins may be elevated in serum.

4.

Sex hormone-binding globulins are increased and result in elevated levels of total circulating sex steroids; however, free or biologically active levels either decrease or remain unchanged.

5.

High-density lipoprotein cholesterol (HDL-C) and triglycerides may be increased, while low-density lipoprotein cholesterol (LDL-C) and total cholesterol (Total-C) may be decreased or unchanged.

6.

Glucose tolerance may be decreased.

7.

Serum folate levels may be depressed by oral contraceptive therapy. This may be of clinical significance if a woman becomes pregnant shortly after discontinuing oral contraceptives.

10. Carcinogenesis

See WARNINGS section.

11. Pregnancy

Pregnancy Category X (see CONTRAINDICATIONS and WARNINGS sections).

12. Nursing mothers

Small amounts of oral contraceptive steroids have been identified in the milk of nursing mothers and a few adverse effects on the child have been reported, including jaundice and breast enlargement. In addition, oral contraceptives given in the postpartum period may interfere with lactation by decreasing the quantity and quality of breast milk. If possible, the nursing mother should be advised not to use oral contraceptives but to use other forms of contraception until she has completely weaned her child.

13. Pediatric use

Safety and efficacy of VIORELE has been established in women of reproductive age. Safety and efficacy are expected to be the same for post-pubertal adolescents under the age of 16 and for users 16 years and older. Use of this product before menarche is not indicated.

INFORMATION FOR THE PATIENT

See Patient Labeling Printed Below

ADVERSE REACTIONS

An increased risk of the following serious adverse reactions has been associated with the use of oral contraceptives (see WARNINGS section):

•

Thrombophlebitis and venous thrombosis with or without embolism

•

Arterial thromboembolism

•

Pulmonary embolism

•

Myocardial infarction

•

Cerebral hemorrhage

•

Cerebral thrombosis

•

Hypertension

•

Gallbladder disease

•

Hepatic adenomas or benign liver tumors

There is evidence of an association between the following conditions and the use of oral contraceptives:

•

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

•

Acne

•

Changes in libido

•

Colitis

•

Budd-Chiari Syndrome

OVERDOSAGE

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.

NON-CONTRACEPTIVE HEALTH BENEFITS

The following non-contraceptive health benefits related to the use of oral contraceptives are supported by epidemiologic studies which largely utilized oral contraceptive formulations containing estrogen doses exceeding 0.035 mg of ethinyl estradiol or 0.05 mg of mestranol (73-78).

Effects on menses:

•

increased menstrual cycle regularity

•

decreased blood loss and decreased incidence of iron deficiency anemia

•

decreased incidence of dysmenorrhea

Effects related to inhibition of ovulation:

•

decreased incidence of functional ovarian cysts

•

decreased incidence of ectopic pregnancies

Effects from long-term use:

•

decreased incidence of fibroadenomas and fibrocystic disease of the breast

•

decreased incidence of acute pelvic inflammatory disease

•

decreased incidence of endometrial cancer

•

decreased incidence of ovarian cancer