PRECAUTIONS GENERAL Patients should be counseled that this product does not protect against HIV infection (AIDS) and other sexually transmitted diseases. 1. PHYSICAL EXAMINATION AND FOLLOW-UP It is good medical practice for all women to have annual history and physical examinations, including women using oral contraceptives. The physical examination, however, may be deferred until after initiation of oral contraceptives if requested by the woman and judged appropriate by the clinician. The physical examination should include special reference to blood pressure, breasts, abdomen and pelvic organs, including cervical cytology, and relevant laboratory tests. In case of undiagnosed, persistent or recurrent abnormal vaginal bleeding, appropriate measures should be conducted to rule out malignancy. Women with a strong family history of breast cancer or who have breast nodules should be monitored with particular care. 2. LIPID DISORDERS Women who are being treated for hyperlipidemias should be followed closely if they elect to use oral contraceptives. Some progestogens may elevate LDL levels and may render the control of hyperlipidemias more difficult. 3. LIVER FUNCTION If jaundice develops in any woman receiving oral contraceptives the medication should be discontinued. Steroid hormones may be poorly metabolized in patients with impaired liver function. 4. FLUID RETENTION Oral contraceptives may cause some degree of fluid retention. They should be prescribed with caution, and only with careful monitoring, in patients with conditions which might be aggravated by fluid retention. 5. EMOTIONAL DISORDERS Women with a history of depression should be carefully observed and the drug discontinued if depression recurs to a serious degree. 6. CONTACT LENSES Contact lens wearers who develop visual changes or changes in lens tolerance should be assessed by an ophthalmologist. 7. 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, and possibly with griseofulvin, ampicillin and tetracyclines.76 Concomitant Use with HCV Combination Therapy – Liver Enzyme Elevation Do not co-administer TRI-NORINYL tablets with HCV drug combinations containing ombitasvir/paritaprevir/ritonavir, with or without dasabuvir, due to potential for ALT elevations (see Warnings, RISK OF LIVER ENZYME ELEVATIOSN WITH CONCOMITANT HEPATITIS C TREATMENT). 8. INTERACTIONS WITH LABORATORY TESTS Certain endocrine and liver function tests and blood components may be affected by oral contraceptives: a. Increased prothrombin and factors VII, VIII, IX, and X; decreased antithrombin 3; increased norepinephrine-induced platelet aggregability. b. 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. c. Other binding proteins may be elevated in serum. d. Sex steroid binding globulins are increased and result in elevated levels of total circulating sex steroids and corticoids; however, free or biologically active levels remain unchanged. e. Triglycerides may be increased. f. Glucose tolerance may be decreased. g. 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. 9. CARCINOGENESIS See WARNINGS section. 10. PREGNANCY Pregnancy Category X See CONTRAINDICATIONS and WARNINGS sections. 11. 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. 12. PEDIATRIC USE Safety and efficacy of Tri-Norinyl have been established in women of reproductive age. Safety and efficacy are expected to be the same for postpubertal adolescents under the age of 16 and for users 16 years and older. Use of the product before menarche is not indicated. INFORMATION FOR THE PATIENT See PATIENT LABELING printed below.