Consider discontinuation of ORTHO-CYCLEN or ORTHO TRI-CYCLEN in the case of increased frequency or severity of migraine during COC use (which may be prodromal of a cerebrovascular event).

5.7 Bleeding Irregularities and Amenorrhea
Unscheduled Bleeding and Spotting

Unscheduled (breakthrough or intracyclic) bleeding and spotting sometimes occur in patients on COCs, especially during the first three months of use. If bleeding persists or occurs after previously regular cycles, check for causes such as pregnancy or malignancy. If pathology and pregnancy are excluded, bleeding irregularities may resolve over time or with a change to a different contraceptive product.

In clinical trials of ORTHO-CYCLEN and ORTHO TRI-CYCLEN, the frequency and duration of breakthrough bleeding and/or spotting was assessed in 1,647 patients (21,275 eva luable cycles) and 4,826 patients (35,546 eva luable cycles), respectively. A total of 100 (7.5%) women discontinued ORTHO-CYCLEN and 231 (4.8%) women discontinued ORTHO TRI-CYCLEN, at least in part, due to bleeding or spotting. Based on data from the clinical trials, 14–34% of women using ORTHO-CYCLEN experienced unscheduled bleeding per cycle in the first year; for ORTHO TRI-CYCLEN, the respective numbers were 13–38%. The percent of women who experienced breakthrough/unscheduled bleeding tended to decrease over time.

Amenorrhea and Oligomenorrhea

Women who use ORTHO-CYCLEN or ORTHO TRI-CYCLEN may experience amenorrhea. Some women may experience amenorrhea or oligomenorrhea after discontinuation of COCs, especially when such a condition was pre-existent.

If scheduled (withdrawal) bleeding does not occur, consider the possibility of pregnancy. If the patient has not adhered to the prescribed dosing schedule (missed one or more active tablets or started taking them on a day later than she should have), consider the possibility of pregnancy at the time of the first missed period and take appropriate diagnostic measures. If the patient has adhered to the prescribed regimen and misses two consecutive periods, rule out pregnancy.

5.8 COC Use Before or During Early PregnancyExtensive epidemiological studies have revealed no increased risk of birth defects in women who have used oral contraceptives prior to pregnancy. Studies also do not suggest a teratogenic effect, particularly in so far as cardiac anomalies and limb reduction defects are concerned, when oral contraceptives are taken inadvertently during early pregnancy. Discontinue ORTHO-CYCLEN or ORTHO TRI-CYCLEN use if pregnancy is confirmed.

Administration of COCs to induce withdrawal bleeding should not be used as a test for pregnancy [see Use in Specific Populations (8.1)].

5.9 DepressionCarefully observe women with a history of depression and discontinue ORTHO-CYCLEN or ORTHO TRI-CYCLEN if depression recurs to a serious degree.

5.10 Carcinoma of Breast and CervixORTHO-CYCLEN and ORTHO TRI-CYCLEN are contraindicated in women who currently have or have had breast cancer because breast cancer may be hormonally sensitive [see Contraindications (4)].
There is substantial evidence that COCs do not increase the incidence of breast cancer. Although some past studies have suggested that COCs mi