Low-Ogestrel (Page 3 of 7)

2. ESTIMATES OF MORTALITY FROM CONTRACEPTIVE USE

One study gathered data from a variety of sources which have estimated the mortality rates associated with different methods of contraception at different ages (see Table III).⁴¹ These estimates include the combined risk of death associated with contraceptive methods plus the risk attributable to pregnancy in the event of method failure. Each method of contraception has its specific benefits and risks. The study concluded that with the exception of oral contraceptive users 35 and older who smoke and 40 and older who do not smoke, mortality associated with all methods of birth control is low and below that associated with childbirth. The observation of a possible increase in risk of mortality with age for oral contraceptive users is based on data gathered in the 1970s but not reported in the U.S. until 1983.^16,41 However, current clinical practice involves the use of lower estrogen dose formulations combined with careful restriction of oral contraceptive use to women who do not have the various risk factors listed in this labeling.

Because of these changes in practice and, also, because of some limited new data which suggest that the risk of cardiovascular disease with the use of oral contraceptives may now be less than previously observed,^{78, 79} the Fertility and Maternal Health Drugs Advisory Committee was asked to review the topic in 1989. The Committee concluded that although cardiovascular disease risks may be increased with oral contraceptive use after age 40 in healthy non-smoking women (even with the newer low-dose formulations), there are greater potential health risks associated with pregnancy in older women and with the alternative surgical and medical procedures which may be necessary if such women do not have access to effective and acceptable means of contraception.

Therefore, the Committee recommended that the benefits of oral contraceptive use by healthy non-smoking women over 40 may outweigh the possible risks. Of course, older women, as all women who take oral contraceptives, should take the lowest possible dose formulation that is effective.⁸⁰

TABLE III: ESTIMATED ANNUAL NUMBER OF BIRTH-RELATED OR METHOD- RELATED DEATHS ASSOCIATED WITH CONTROL OF FERTILITY PER 100,000 NONSTERILE WOMEN, BY FERTILITY CONTROL METHOD ACCORDING TO AGE

Method of control and outcome	15–19	20–24	25–29	30–34	35–39	40–44
Estimates adapted from H.W. Ory, Table 3 41
* Deaths are birth-related † Deaths are method-related
No fertility	7.0	7.4	9.1	14.8	25.7	28.2
control methods *
Oral contraceptives	0.3	0.5	0.9	1.9	13.8	31.6
non-smoker †
Oral contraceptives	2.2	3.4	6.6	13.5	51.1	117.2
smoker †
IUD †	0.8	0.8	1.0	1.0	1.4	1.4
Condom *	1.1	1.6	0.7	0.2	0.3	0.4
Diaphragm/Spermicide *	1.9	1.2	1.2	1.3	2.2	2.8
Periodic abstinence *	2.5	1.6	1.6	1.7	2.9	3.6

3. CARCINOMA OF THE BREAST AND REPRODUCTIVE ORGANS

Numerous epidemiological studies have been performed on the incidence of breast, endometrial, ovarian, and cervical cancer in women using oral contraceptives. The overwhelming evidence in the literature suggests that use of oral contraceptives is not associated with an increase in the risk of developing breast cancer, regardless of the age and parity of first use or with most of the marketed brands and doses.^42–44 The Cancer and Steroid Hormone (CASH) study also showed no latent effect on the risk of breast cancer for at least a decade following long-term use.⁴³ A few studies have shown a slightly increased relative risk of developing breast cancer,^44–47 although the methodology of these studies, which included differences in examination of users and non-users and differences in age at start of use, has been questioned.^47–49 Some studies have reported an increased relative risk of developing breast cancer, particularly at a younger age. This increased relative risk appears to be related to duration of use.^{81, 82}

Some studies suggest that oral contraceptive use has been associated with an increase in the risk of cervical intraepithelial neoplasia in some populations of women.^50–53 However, there continues to be controversy about the extent to which such findings may be due to differences in sexual behavior and other factors.

In spite of many studies of the relationship between oral contraceptive use and breast or cervical cancers, a cause and effect relationship has not been established.

4. HEPATIC NEOPLASIA

Benign hepatic adenomas are associated with oral contraceptive use although the incidence of benign tumors is rare in the United States. Indirect calculations have estimated the attributable risk to be in the range of 3.3 cases per 100,000 for users, a risk that increases after 4 or more years of use.⁵⁴ Rupture of rare, benign, hepatic adenomas may cause death through intra-abdominal hemorrhage.^55–56

Studies in the United States and Britain have shown an increased risk of developing hepatocellular carcinoma in long-term (>8 years) oral contraceptive users.^57–59 However, these cancers are extremely rare in the United States and the attributable risk (the excess incidence) of liver cancers in oral contraceptive users approaches less than 1 per 1,000,000 users.

5. RISK OF LIVER ENZYME ELEVATIONS WITH CONCOMITANT HEPATITIS C TREATMENT

During clinical trials with the Hepatitis C combination drug regimen that contains ombitasvir/paritaprevir/ritonavir, with or without dasabuvir, ALT elevations greater than 5 times the upper limit of normal (ULN), including some cases greater than 20 times the ULN, were significantly more frequent in women using ethynyl estradiol-containing medications such as COCs. Discontinue Low-Ogestrel tablets prior to starting therapy with the combination drug regimen ombitasvir/paritaprevir/ritonavir, with or without dasabuvir [see Contraindications (4)]. Low-Ogestrel tablets can be restarted approximately 2 weeks following completion of treatment with the combination drug regimen.