"The U.S. Food and Drug Administration on Wednesday approved a request by Danco Laboratories to expand authorized use of its abortion pill Mifeprex (mifepristone), formerly known as RU-486, to 70 days of gestation from 49 days.
Ortho Tri-Cyclen / Ortho-Cyclen
Thromboembolic Disorders And Other Vascular Problems
- Stop ORTHO-CYCLEN or ORTHO TRI-CYCLEN if an arterial thrombotic event or venous thromboembolic (VTE) event occurs.
- Stop ORTHO-CYCLEN or ORTHO TRI-CYCLEN if there is unexplained loss of vision, proptosis, diplopia, papilledema, or retinal vascular lesions. Evaluate for retinal vein thrombosis immediately [see ADVERSE REACTIONS].
- If feasible, stop ORTHO-CYCLEN or ORTHO TRI-CYCLEN at least 4 weeks before and through 2 weeks after major surgery or other surgeries known to have an elevated risk of VTE as well as during and following prolonged immobilization.
- Start ORTHO-CYCLEN or ORTHO TRI-CYCLEN no earlier than 4 weeks after delivery, in women who are not breastfeeding. The risk of postpartum VTE decreases after the third postpartum week, whereas the risk of ovulation increases after the third postpartum week.
- The use of COCs increases the risk of VTE. However, pregnancy increases the risk of VTE as much or more than the use of COCs. The risk of VTE in women using COCs is 3 to 9 cases per 10,000 woman-years. The risk of VTE is highest during the first year of use of COCs and when restarting hormonal contraception after a break of 4 weeks or longer. The risk of thromboembolic disease due to COCs gradually disappears after use is discontinued.
- Use of COCs also increases the risk of arterial thromboses such as strokes and myocardial infarctions, especially in women with other risk factors for these events. COCs have been shown to increase both the relative and attributable risks of cerebrovascular events (thrombotic and hemorrhagic strokes). This risk increases with age, particularly in women over 35 years of age who smoke.
- Use COCs with caution in women with cardiovascular disease risk factors.
Impaired Liver Function
Do not use ORTHO-CYCLEN or ORTHO TRI-CYCLEN in women with liver disease, such as acute viral hepatitis or severe (decompensated) cirrhosis of liver [see CONTRAINDICATIONS]. Acute or chronic disturbances of liver function may necessitate the discontinuation of COC use until markers of liver function return to normal and COC causation has been excluded. Discontinue ORTHO-CYCLEN or ORTHO TRI-CYCLEN if jaundice develops.
ORTHO-CYCLEN and ORTHO TRI-CYCLEN are contraindicated in women with benign and malignant liver tumors [see CONTRAINDICATIONS]. Hepatic adenomas are associated with COC use. An estimate of the attributable risk is 3.3 cases/100,000 COC users. Rupture of hepatic adenomas may cause death through intra-abdominal hemorrhage.
Studies have shown an increased risk of developing hepatocellular carcinoma in long-term ( > 8 years) COC users. However, the risk of liver cancers in COC users is less than one case per million users.
High Blood Pressure
ORTHO-CYCLEN and ORTHO TRI-CYCLEN are contraindicated in women with uncontrolled hypertension or hypertension with vascular disease [see CONTRAINDICATIONS]. For women with well-controlled hypertension, monitor blood pressure and stop ORTHO-CYCLEN and ORTHO TRI-CYCLEN if blood pressure rises significantly.
An increase in blood pressure has been reported in women taking COCs, and this increase is more likely in older women with extended duration of use. The incidence of hypertension increases with increasing concentrations of progestin.
Studies suggest a small increased relative risk of developing gallbladder disease among COC users. Use of COCs may worsen existing gallbladder disease. A past history of COC-related cholestasis predicts an increased risk with subsequent COC use. Women with a history of pregnancy-related cholestasis may be at an increased risk for COC related cholestasis.
Carbohydrate And Lipid Metabolic Effects
Carefully monitor prediabetic and diabetic women who take ORTHO-CYCLEN or ORTHO TRICYCLEN. COCs may decrease glucose tolerance.
Women with hypertriglyceridemia, or a family history thereof, may be at an increased risk of pancreatitis when using COCs.
If a woman taking ORTHO-CYCLEN or ORTHO TRI-CYCLEN develops new headaches that are recurrent, persistent, or severe, evaluate the cause and discontinue ORTHO-CYCLEN or ORTHO TRI-CYCLEN if indicated.
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).
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 evaluable cycles) and 4,826 patients (35,546 evaluable 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.
COC Use Before Or During Early Pregnancy
Extensive 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].
Carefully observe women with a history of depression and discontinue ORTHO-CYCLEN or ORTHO TRI-CYCLEN if depression recurs to a serious degree.
Carcinoma Of Breast And Cervix
- ORTHO-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]. There is substantial evidence that COCs do not increase the incidence of breast cancer. Although some past studies have suggested that COCs might increase the incidence of breast cancer, more recent studies have not confirmed such findings.
- Some studies suggest that COC use has been associated with an increase in the risk of cervical cancer or intraepithelial neoplasia. However, there continues to be controversy about the extent to which such findings may be due to differences in sexual behavior and other factors.
Effect On Binding Globulins
The estrogen component of COCs may raise the serum concentrations of thyroxine-binding globulin, sex hormone-binding globulin, and cortisol-binding globulin. The dose of replacement thyroid hormone or cortisol therapy may need to be increased.
A woman who is taking COCs should have a yearly visit with her healthcare provider for a blood pressure check and for other indicated healthcare.
Chloasma may occasionally occur, especially in women with a history of chloasma gravidarum. Women with a tendency to chloasma should avoid exposure to the sun or ultraviolet radiation while taking ORTHO TRI-CYCLEN or ORTHO-CYCLEN.
Patient Counseling Information
See FDA-approved patient labeling (PATIENT INFORMATION and Instructions for Use).
Counsel patients about the following information:
- Cigarette smoking increases the risk of serious cardiovascular events from COC use, and that women who are over 35 years old and smoke should not use COCs [see BOXED WARNING].
- Increased risk of VTE compared to non-users of COCs is greatest after initially starting a COC or restarting (following a 4-week or greater pill-free interval) the same or a different COC [see WARNINGS AND PRECAUTIONS].
- ORTHO-CYCLEN and ORTHO TRI-CYCLEN do not protect against HIV infection (AIDS) and other sexually transmitted infections.
- ORTHO-CYCLEN and ORTHO TRI-CYCLEN are not to be used during pregnancy; if pregnancy occurs during use of ORTHO-CYCLEN or ORTHO TRI-CYCLEN instruct the patient to stop further use [see WARNINGS AND PRECAUTIONS].
- Take one tablet daily by mouth at the same time every day. Instruct patients what to do in the event tablets are missed [see DOSAGE AND ADMINISTRATION].
- Use a back-up or alternative method of contraception when enzyme inducers are used with ORTHO-CYCLEN or ORTHO TRI-CYCLEN [see DRUG INTERACTIONS].
- COCs may reduce breast milk production; this is less likely to occur if breastfeeding is well established [see Use in Specific Populations)].
- Women who start COCs postpartum, and who have not yet had a period, should use an additional method of contraception until they have taken an active tablet for 7 consecutive days [see DOSAGE AND ADMINISTRATION].
- Amenorrhea may occur. Consider pregnancy in the event of amenorrhea at the time of the first missed period. Rule out pregnancy in the event of amenorrhea in two or more consecutive cycles [see WARNINGS AND PRECAUTIONS].
Carcinogenesis, Mutagenesis, Impairment Of Fertility
[See WARNINGS AND PRECAUTIONS and Use in Specific Populations]
Use In Specific Populations
There is little or no increased risk of birth defects in women who inadvertently use COCs during early pregnancy. Epidemiologic studies and meta-analyses have not found an increased risk of genital or non-genital birth defects (including cardiac anomalies and limb reduction defects) following exposure to low dose COCs prior to conception or during early pregnancy.
Do not administer COCs to induce withdrawal bleeding as a test for pregnancy. Do not use COCs during pregnancy to treat threatened or habitual abortion.
Advise the nursing mother to use other forms of contraception, when possible, until she has weaned her child. COCs can reduce milk production in breastfeeding mothers. This is less likely to occur once breastfeeding is well-established; however, it can occur at any time in some women. Small amounts of oral contraceptive steroids and/or metabolites are present in breast milk.
Safety and efficacy of ORTHO-CYCLEN Tablets and ORTHO TRI-CYCLEN Tablets have been established in women of reproductive age. Efficacy is expected to be the same for postpubertal adolescents under the age of 18 and for users 18 years and older. Use of this product before menarche is not indicated.
There was no significant difference between ORTHO TRI-CYCLEN Tablets and placebo in mean change in total lumbar spine (L1-L4) and total hip bone mineral density between baseline and Cycle 13 in 123 adolescent females with anorexia nervosa in a double-blind, placebo-controlled, multicenter, one-year treatment duration clinical trial for the Intent To Treat (ITT) population.
ORTHO-CYCLEN and ORTHO TRI-CYCLEN have not been studied in postmenopausal women and are not indicated in this population.
The pharmacokinetics of ORTHO-CYCLEN and ORTHO TRI-CYCLEN have not been studied in subjects with hepatic impairment. However, steroid hormones may be poorly metabolized in patients with hepatic impairment. Acute or chronic disturbances of liver function may necessitate the discontinuation of COC use until markers of liver function return to normal and COC causation has been excluded. [See CONTRAINDICATIONS and WARNINGS AND PRECAUTIONS]
The pharmacokinetics of ORTHO-CYCLEN and ORTHO TRI-CYCLEN have not been studied in women with renal impairment.This monograph has been modified to include the generic and brand name in many instances.
Last reviewed on RxList: 5/15/2015
Additional Ortho Tri-Cyclen / Ortho-Cyclen Information
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