✅ Uses & Indications
INDICATIONS AND USAGE Xarah Fe is indicated for the prevention of pregnancy in women who elect to use combined oral contraceptives as a method of contraception. Xarah Fe is indicated for the treatment of moderate acne vulgaris in females, ≥ 15 years of age, who have no known contraindications to combined oral contraceptive therapy, desire oral contraception, have achieved menarche, and are unresponsive to topical anti-acne medications. Xarah Fe should be used for the treatment of acne only if the patient desires a combined oral contraceptive for birth control and plans to stay on it for at least 6 months. Combined oral contraceptives are highly effective for pregnancy prevention. Table 2 lists the typical accidental pregnancy rates for users of combination oral contraceptives and other methods of contraception. The efficacy of these contraceptive methods, except sterilization, depends upon the reliability with which they are used. Correct and consistent use of methods can result in lower failure rates. Table 2. Percentage of Women Experiencing an Unintended Pregnancy During the First Year of Typical Use and the First Year of Perfect Use of Contraception and the Percentage Continuing Use at the End of the First Year. United States. Emergency Contraceptives Pills: Treatment initiated within 72 hours after unprotected intercourse reduces the risk of pregnancy by at least 75%. è Lactational Amenorrhea Method: LAM is a highly effective, temporary method of contraception. ð Source: Trussell J, The Essentials of Contraception. In Hatcher RA, Trussell J, Stewart F, Cates W, Stewart GK, Kowel D, Guest F, Contraceptive Technology : Seventeenth Revised Edition. New York NY: Irvington Publishers, 1998. % of Women Experiencing an Unintended Pregnancy within the First Year of Use % of Women Continuing Use at One Year ‡ Method (1) Typical Use * (2) Perfect Use † (3) (4) Chance § 85 85 Spermicides ¶ 26 6 40 Periodic Abstinence 25 63 Calendar 9 Ovulation Method 3 Symptothermal #Þ 2 Post-ovulation 1 Cap ß Parous Women 40 26 42 Nulliparous Women 20 9 56 Sponge Parous Women 40 20 42 Nulliparous Women 20 9 56 Diaphragm ß 20 6 56 Withdrawal 19 4 Condom à Female (Reality ® ) 21 5 56 Male 14 3 61 Pill 5 71 Progestin only 0.5 Combined 0.1 IUD Progesterone T 2.0 1.5 81 Copper T380A 0.8 0.6 78 LNG 20 0.1 0.1 81 Depo-Provera ® 0.3 0.3 70 Norplant ® and Norplant-2 ® 0.05 0.05 88 Female Sterilization 0.5 0.5 100 Male Sterilization 0.15 0.10 100 ‡ Among couples attempting to avoid pregnancy, the percentage who continue to use a method for 1 year. * Among typical couples who initiate use of a method (not necessarily for the first time), the percentage who experience an accidental pregnancy during the first year if they do not stop use for any other reason. † Among couples who initiate use of a method (not necessarily for the first time) and who use it perfectly (both consistently and correctly), the percentage who experience an accidental pregnancy during the first year if they do not stop use for any other reason. § The percentages becoming pregnant in columns (2) and (3) are based on data from populations where contraception is not used and from women who cease using contraception in order to become pregnant. Among such populations, about 89% become pregnant within one year. This estimate was lowered slightly (to 85%) to represent the percent who would become pregnant within one year among women now relying on reversible methods of contraception if they abandoned contraception altogether. ¶ Foams, creams, gels, vaginal suppositories, and vaginal film. #Þ Cervical mucus (ovulation) method supplemented by calendar in the pre-ovulatory and basal body temperature in the post-ovulatory phases. ß With spermicidal cream or jelly. à Without spermicides. è The treatment schedule is one dose within 72 hours after unprotected intercourse, and a second dose 12 hours after the first dose. The Food and Drug Administration has declared the following brands of combined oral contraceptives to be safe and effective for emergency contraception: Ovral ® (1 dose is 2 white pills), Alesse ® (1 dose is 5 pink pills), Nordette ® or Levlen ® (1 dose is 4 light-orange pills), Lo/Ovral ® (1 dose is 4 white pills), Triphasil ® or Tri-Levlen ® (1 dose is 4 yellow pills). ð However, to maintain effective protection against pregnancy, another method of contraception must be used as soon as menstruation resumes, the frequency or duration of breastfeeds is reduced, bottle feeds are introduced, or the baby reaches 6 months of age. Xarah Fe were evaluated for the treatment of acne vulgaris in two randomized, double-blind, placebo-controlled, multicenter, Phase 3, six (28-day) cycle studies. A total of 296 patients received Xarah Fe and 295 received placebo. Mean age at enrollment for both groups was 24 years. At six months each study demonstrated a statistically significant difference between Xarah Fe and placebo for mean change from baseline in lesion counts (see Table 3 and Figure 2). Each study also demonstrated overall treatment success in the investigator’s global evaluation. Patients with severe androgen excess were not studied. Table 3. Acne Vulgaris Indication Pooled Data 376-403 and 376-404 Observed Means at Six Months and at Baseline* Intent To Treat Population Xarah Fe N=296 Placebo N=295 Difference in Counts Between Xarah Fe and Placebo at Six Months (95% CI) † Number of Lesions Counts % reduction Counts % reduction INFLAMMATORY LESIONS Baseline Mean 29 29 Six Month Mean 14 52% 17 41% 3 (±2) NON-INFLAMMATORY LESIONS Baseline Mean 44 43 Six Month Mean 27 38% 32 25% 5 (±3.5) TOTAL LESIONS Baseline Mean 74 72 Six Month Mean 42 43% 49 32% 7 (±5) *Numbers rounded to nearest integer † Limits for 95% Confidence Interval; not adjusted for baseline differences Xarah Fe users who started with about 74 acne lesions had about 42 lesions after 6 months of treatment. Placebo users who started with about 72 acne lesions had about 49 lesions after the same duration of treatment. Figure 2. Mean Percent Reduction in Total Lesion Counts From Baseline to Each 28-Day Cycle and Mean Total Lesion Counts at Each Cycle Following Administration of Xarah Fe and Placebo (Statistically significant differences were not found in both studies individually until cycle 6) Figure 2. Mean Percent Reduction in Total Lesion Counts From Baseline to Each 28-Day Cycle and Mean Total Lesion Counts at Each Cycle Following Administration of Norethindrone acetate and ethinyl estradiol tablets and ferrous fumarate tablets and Placebo (Statistically significant differences were not found in both studies individually until cycle 6)
📏 Dosage & Administration
DOSAGE AND ADMINISTRATION The tablet blister has been designed to make Xarah Fe dosing as easy and as convenient as possible. The tablets are arranged in four rows of seven tablets each, with the days of the week appearing on the tablet blister above the first row of tablets. Note: Each tablet blister has been preprinted with the days of the week, starting with Sunday, to facilitate a Sunday-Start regimen. Six different day label strips have been provided with the Detailed Patient & Brief Summary Patient Package Insert in order to accommodate a Day-1 Start regimen. If the patient is using the Day-1 Start regimen, she should place the self-adhesive day label strip that corresponds to her starting day over the preprinted days. Important: The patient should be instructed to use an additional method of protection until after the first week of administration in the initial cycle when utilizing the Sunday-Start regimen. The possibility of ovulation and conception prior to initiation of use should be considered. Dosage and Administration for 28-Day Dosage Regimen To achieve maximum contraceptive effectiveness, Xarah Fe should be taken exactly as directed and at intervals not exceeding 24 hours. Xarah Fe provides a continuous administration regimen. These tablets are to be taken in the following order: one white to off white each day for five days, then light purple tablet each day for seven days, followed by one purple tablet each day for nine days, and then one brown non-hormone tablet each day for seven days. The ferrous fumarate tablets are present to facilitate ease of drug administration via a 28-day regimen and do not serve any therapeutic purpose. There is no need for the patient to count days between cycles because there are no “off-tablet days”. A. Sunday-Start Regimen: The patient begins taking the first white to off white tablet from the top row of the blister (labeled Sunday) on the first Sunday after menstrual flow begins. When menstrual flow begins on Sunday, the first white to off white tablet is taken on the same day. The patient takes one white to off white tablet daily for 5 days. The last purple tablet in the blister will be taken on a Saturday. Upon completion of all 21 tablets, and without interruption, the patient takes one brown tablet daily for 7 days. Upon completion of this first course of tablets, the patient begins a second course of 28-day tablets, without interruption, the next day (Sunday), starting with the Sunday white to off white tablet in the top row. Adhering to this regimen of one tablet daily for 21 days, followed without interruption by one brown tablet daily for 7 days, the patient will start all subsequent cycles on a Sunday. B. Day-1 Start Regimen: The first day of menstrual flow is Day 1. The patient places the self-adhesive day label strip that corresponds to her starting day over the preprinted days on the tablet blister. She starts taking one tablet daily, beginning with the first white to off white tablet in the top row. After the last purple tablet (at the end of the third row) has been taken, the patient will then take the brown tablets for a week (7 days). For all subsequent cycles, the patient begins a new 28 tablet regimen on the eighth day after taking her last purple tablet, again starting with the first tablet in the top row after placing the appropriate day label strip over the preprinted days on the tablet blister. Following this regimen of 21 tablets and 7 brown tablets, the patient will start all subsequent cycles on the same day of the week as the first course. Tablets should be taken regularly at the same time each day and can be taken without regard to meals. It should be stressed that efficacy of medication depends on strict adherence to the dosage schedule. Special Notes on Administration Menstruation usually begins two or three days, but may begin as late as the fourth or fifth day, after the brown tablets have been started. In any event, the next course of tablets should be started without interruption. If spotting occurs while the patient is taking white to off white tablets, continue medication without interruption. If the patient forgets to take one or more active tablets, the following is suggested: One tablet is missed • take tablet as soon as remembered • take next tablet at the regular time Two consecutive tablets are missed (Week 1 or Week 2) • take two tablets as soon as remembered • take two tablets the next day • use another birth control method for seven days following the missed tablets Two consecutive tablets are missed (Week 3) Sunday-Start Regimen: • take one tablet daily until Sunday • discard remaining tablets • start new pack of tablets immediately (Sunday) • use another birth control method for seven days following the missed tablets Day-1 Start Regimen: • discard remaining tablets • start new pack of tablets that same day • use another birth control method for seven days following the missed tablets Three (or more) consecutive tablets are missed Sunday-Start Regimen: • take one tablet daily until Sunday • discard remaining tablets • start new pack of tablets immediately (Sunday) • use another birth control method for seven days following the missed tablets Day-1 Start Regimen: • discard remaining tablets • start new pack of tablets that same day • use another birth control method for seven days following the missed tablets The possibility of ovulation occurring increases with each successive day that scheduled active tablets are missed. While there is little likelihood of ovulation occurring if only one active tablet is missed, the possibility of spotting or bleeding is increased. This is particularly likely to occur if two or more consecutive active tablets are missed. If the patient forgets to take any of the seven brown tablets in week four, those brown tablets that were missed are discarded and one brown tablet is taken each day until the pack is empty. A back-up birth control method is not required during this time. A new pack of tablets should be started no later than the eighth day after the last active tablet was taken. In the rare case of bleeding which resembles menstruation, the patient should be advised to discontinue medication and then begin taking tablets from a new tablet blister on the next Sunday or the first day (Day 1) depending on her regimen. Persistent bleeding which is not controlled by this method indicates the need for reexamination of the patient, at which time nonfunctional causes should be considered. Use of Combined Oral Contraceptives in the Event of a Missed Menstrual Period 1. If the patient has not adhered to the prescribed dosage regimen, the possibility of pregnancy should be considered after the first missed period and combined oral contraceptives should be withheld until pregnancy has been ruled out. 2. If the patient has adhered to the prescribed regimen and misses two consecutive periods, pregnancy should be ruled out before continuing the contraceptive regimen. After several months on treatment, bleeding may be reduced to a point of virtual absence. This reduced flow may occur as a result of medication, in which event it is not indicative of pregnancy. Acne The timing of initiation of dosing with Xarah Fe for acne should follow the guidelines for use of Xarah Fe as a combined oral contraceptive. Consult the DOSAGE AND ADMINISTRATION section for Xarah Fe oral contraceptives.
💊 Side Effects
ADVERSE REACTIONS An increased risk of the following serious adverse reactions has been associated with the use of combined oral contraceptives (see WARNINGS section): • Thrombophlebitis • 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 combined oral contraceptives, although additional confirmatory studies are needed: • Mesenteric thrombosis • Retinal thrombosis The following adverse reactions have been reported in patients receiving combined 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 • Mood swings • 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 combined 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 • Budd-Chiari syndrome • Acne • Changes in libido • Colitis Post Marketing Experience Five studies that compared breast cancer risk between ever-users (current or past use) of COCs and never-users of COCs reported no association between ever use of COCs and breast cancer risk, with effect estimates ranging from 0.90 - 1.12 (Figure 4). Three studies compared breast cancer risk between current or recent COC users (<6 months since last use) and never users of COCs (Figure 4). One of these studies reported no association between breast cancer risk and COC use. The other two studies found an increased relative risk of 1.19 - 1.33 with current or recent use. Both of these studies found an increased risk of breast cancer with current use of longer duration, with relative risks ranging from 1.03 with less than one year of COC use to approximately 1.4 with more than 8-10 years of COC use. Figure 4. Relevant Studies of Risk of Breast Cancer with Combined Oral Contraceptive Use RR = relative risk; OR = odds ratio; HR = hazard ratio. “ever COC” are females with current or past COC use; “never COC use” are females that never used COCs. Figure 4. Risk of Breast Cancer with Combined Oral Contraceptive Use
⚠️ Warnings & Precautions
WARNINGS The use of combined oral contraceptives is associated with increased risks of several serious conditions including myocardial infarction, thromboembolism, stroke, hepatic neoplasia, and gallbladder disease, although the risk of serious morbidity or mortality is very small in healthy women without underlying risk factors. The risk of morbidity and mortality increases significantly in the presence of other underlying risk factors such as hypertension, hyperlipidemias, obesity, and diabetes. Practitioners prescribing combined oral contraceptives should be familiar with the following information relating to these risks. The information contained in this package insert is principally based on studies carried out in patients who used combined oral contraceptives with higher formulations of estrogens and progestogens than those in common use today. The effect of long-term use of the combined oral contraceptives with lower formulations of both estrogens and progestogens remains to be determined. Throughout this labeling, epidemiological studies reported are of two types: retrospective or case control studies and prospective or cohort studies. Case control studies provide a measure of the relative risk of a disease, namely, a ratio of the incidence of a disease among combined oral contraceptive users to that among nonusers. The relative risk does not provide information on the actual clinical occurrence of a disease. Cohort studies provide a measure of attributable risk, which is the difference in the incidence of disease between combined oral contraceptive users and nonusers. The attributable risk does provide information about the actual occurrence of a disease in the population (adapted from References 8 and 9 with the author's permission). For further information, the reader is referred to a text on epidemiological methods. 1. Thromboembolic Disorders and Other Vascular Problems a. Myocardial infarction An increased risk of myocardial infarction has been attributed to combined oral contraceptive use. This risk is primarily in smokers or women with other underlying risk factors for coronary artery disease such as hypertension, hypercholesterolemia, morbid obesity, and diabetes. The relative risk of heart attack for current combined oral contraceptive users has been estimated to be two to six. The risk is very low under the age of 30. Smoking in combination with combined oral contraceptive use has been shown to contribute substantially to the incidence of myocardial infarctions in women in their mid-thirties or older with smoking accounting for the majority of excess cases. Mortality rates associated with circulatory disease have been shown to increase substantially in smokers over the age of 35 and non-smokers over the age of 40 (Figure 3) among women who use combined oral contraceptives. Figure 3. Circulatory Disease Mortality Rates per 100,000 Woman Years by Age, Smoking Status and Combined Oral Contraceptive Use Adapted from P.M. Layde and V. Beral Combined oral contraceptives may compound the effects of well-known risk factors, such as hypertension, diabetes, hyperlipidemias, age and obesity. In particular, some progestogens are known to decrease HDL cholesterol and cause glucose intolerance, while estrogens may create a state of hyperinsulinism. Combined oral contraceptives have been shown to increase blood pressure among users (see Section 10 in WARNINGS ). Similar effects on risk factors have been associated with an increased risk of heart disease. Combined oral contraceptives must be used with caution in women with cardiovascular disease risk factors. Figure 3. Circulatory Disease Mortality Rates per 100,000 Woman Years by Age, Smoking Status and Oral Contraceptive Use b. Thromboembolism An increased risk of thromboembolic and thrombotic disease associated with the use of combined oral contraceptives is well established. Case control studies have found the relative risk of users compared to nonusers to be 3 for the first episode of superficial venous thrombosis, 4 to 11 for deep vein thrombosis or pulmonary embolism, and 1.5 to 6 for women with predisposing conditions for venous thromboembolic disease. Cohort studies have shown the relative risk to be somewhat lower, about 3 for new cases and about 4.5 for new cases requiring hospitalization. The risk of thromboembolic disease due to combined oral contraceptives is not related to length of use and disappears after combined oral contraceptive pill use is stopped. A two- to four-fold increase in relative risk of postoperative thromboembolic complications has been reported with the use of combined oral contraceptives. The relative risk of venous thrombosis in women who have predisposing conditions is twice that of women without such medical conditions. If feasible, combined oral contraceptives should be discontinued at least 4 weeks prior to and for 2 weeks after elective surgery of a type associated with an increase in risk of thromboembolism and during and following prolonged immobilization. Since the immediate postpartum period is also associated with an increased risk of thromboembolism, combined oral contraceptives should be started no earlier than 4 to 6 weeks after delivery in women who elect not to breastfeed. c. Cerebrovascular disease Combined oral contraceptives have been shown to increase both the relative and attributable risks of cerebrovascular events (thrombotic and hemorrhagic strokes), although, in general, the risk is greatest among older (> 35 years), hypertensive women who also smoke. Hypertension was found to be a risk factor for both users and nonusers, for both types of strokes, while smoking interacted to increase the risk for hemorrhagic strokes. In a large study, the relative risk of thrombotic strokes has been shown to range from 3 for normotensive users to 14 for users with severe hypertension. The relative risk of hemorrhagic stroke is reported to be 1.2 for non-smokers who used combined oral contraceptives, 2.6 for smokers who did not use combined oral contraceptives, 7.6 for smokers who used oral contraceptives, 1.8 for normotensive users, and 25.7 for users with severe hypertension. The attributable risk is also greater in older women. d. Dose-related risk of vascular disease from combined oral contraceptives A positive association has been observed between the amount of estrogen and progestogen in combined oral contraceptives and the risk of vascular disease. A decline in serum high-density lipoproteins (HDL) has been reported with many progestational agents. A decline in serum high-density lipoproteins has been associated with an increased incidence of ischemic heart disease. Because estrogens increase HDL cholesterol, the net effect of a combined oral contraceptive depends on a balance achieved between doses of estrogen and progestin and the nature of the progestin used in the contraceptives. The amount and activity of both hormones should be considered in the choice of a combined oral contraceptive. Minimizing exposure to estrogen and progestogen is in keeping with good principles of therapeutics. For any particular combined oral contraceptive, the dosage regimen prescribed should be one which contains the least amount of estrogen and progestogen that is compatible with the needs of the individual patient. New acceptors of combined oral contraceptive agents should be started on preparations containing the lowest dose of estrogen which produces satisfactory results for the patient. e. Persistence of risk of vascular disease There are two studies which have shown persistence of risk of vascular disease for ever-users of combined oral contraceptives. In a study in the United States, the risk of developing myocardial infarction after discontinuing combined oral contraceptives persists for at least 9 years for women 40-49 years who had used combined oral contraceptives for 5 or more years, but this increased risk was not demonstrated in other age groups. In another study in Great Britain, the risk of developing cerebrovascular disease persisted for at least 6 years after discontinuation of combined oral contraceptives, although excess risk was very small. However, both studies were performed with combined oral contraceptive formulations containing 50 mcg or higher of estrogens. 2. Estimates of Mortality from Combined Oral Contraceptive Use One study gathered data from a variety of sources which have estimated the mortality rate associated with different methods of contraception at different ages (Table 4). 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 combined 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 combined oral contraceptive users is based on data gathered in the 1970’s but not reported until 1983. However, current clinical practice involves the use of lower estrogen dose formulations combined with careful restriction of combined 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 combined oral contraceptives may now be less than previously observed (Porter JB, Hunter J, Jick H, et al. Oral contraceptives and nonfatal vascular disease. Obstet Gynecol 1985;66:1-4; and Porter JB, Hershel J, Walker AM. Mortality among oral contraceptive users. Obstet Gynecol 1987;70:29-32), 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 combined oral contraceptive use after age 40 in healthy nonsmoking 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 combined oral contraceptive use by healthy non-smoking women over 40 may outweigh the possible risks. Of course, older women, as all women who take combined oral contraceptives, should take the lowest possible dose formulation that is effective. Table 4. 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 No fertility control methods* 7.0 7.4 9.1 14.8 25.7 28.2 Oral contraceptives non-smoker** 0.3 0.5 0.9 1.9 13.8 31.6 Oral contraceptives smoker** 2.2 3.4 6.6 13.5 51.1 117.2 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 * Deaths are birth-related. ** Deaths are method-related. Adapted from H.W. Ory 3. Malignant Neoplasms Breast Cancer Norethindrone acetate and ethinyl estradiol tablets and ferrous fumarate tablets are contraindicated in females who currently have or have had breast cancer because breast cancer may be hormonally sensitive (see Contraindications ). Epidemiology studies have not found a consistent association between use of combined oral contraceptives (COCs) and breast cancer risk. Studies do not show an association between ever (current or past) use of COCs and risk of breast cancer. However, some studies report a small increase in the risk of breast cancer among current or recent users ( 8 years) combined oral contraceptive users. However, these cancers are extremely rare in the US, and the attributable risk (the excess incidence) of liver cancers in combined oral contraceptive users approaches less than one per million 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 ethinyl estradiol-containing medications such as COCs. Discontinue norethindrone acetate and ethinyl estradiol tablets and ferrous fumarate tablets prior to starting therapy with the combination drug regimen ombitasvir/paritaprevir/ritonavir, with or without dasabuvir (see Contraindications ). Norethindrone acetate and ethinyl estradiol tablets and ferrous fumarate tablets can be restarted approximately 2 weeks following completion of treatment with the combination drug regimen. 6. Ocular Lesions There have been clinical case reports of retinal thrombosis associated with the use of combined oral contraceptives. Combined oral contraceptives should be discontinued if there is unexplained partial or complete loss of vision; onset of proptosis or diplopia; papilledema; or retinal vascular lesions. Appropriate diagnostic and therapeutic measures should be undertaken immediately. 7. Oral Contraceptive Use Before and During Early Pregnancy Extensive epidemiological studies have revealed no increased risk of birth defects in women who have used combined oral contraceptives prior to pregnancy. Studies also do not suggest a teratogenic effect, particularly insofar as cardiac anomalies and limb reduction defects are concerned, when taken inadvertently during early pregnancy. The administration of combined oral contraceptives to induce withdrawal bleeding should not be used as a test for pregnancy. Combined oral contraceptives should not be used during pregnancy to treat threatened or habitual abortion. It is recommended that for any patient who has missed two consecutive periods, pregnancy should be ruled out before continuing oral contraceptive use. If the patient has not adhered to the prescribed schedule, the possibility of pregnancy should be considered at the time of the first missed period. Combined oral contraceptive use should be discontinued if pregnancy is confirmed. 8. Gallbladder Disease Earlier studies have reported an increased lifetime relative risk of gallbladder surgery in users of combined oral contraceptives and estrogens. More recent studies, however, have shown that the relative risk of developing gallbladder disease among oral contraceptive users may be minimal. The recent findings of minimal risk may be related to the use of combined oral contraceptive formulations containing lower hormonal doses of estrogens and progestogens. 9. Carbohydrate and Lipid Metabolic Effects Combined oral contraceptives have been shown to cause glucose intolerance in a significant percentage of users. Combined oral contraceptives containing greater than 75 mcg of estrogens cause hyperinsulinism, while lower doses of estrogen cause less glucose intolerance. Progestogens increase insulin secretion and create insulin resistance, this effect varying with different progestational agents. However, in the non-diabetic woman, combined oral contraceptives appear to have no effect on fasting blood glucose. Because of these demonstrated effects, prediabetic and diabetic women should be carefully observed while taking combined oral contraceptives. A small proportion of women will have persistent hypertriglyceridemia while on the pill. As discussed earlier (see WARNINGS 1a. and 1d. ), changes in serum triglycerides and lipoprotein levels have been reported in combined oral contraceptive users. 10. Elevated Blood Pressure An increase in blood pressure has been reported in women taking combined oral contraceptives and this increase is more likely in older combined oral contraceptive users and with continued use. Data from the Royal College of General Practitioners and subsequent randomized trials have shown that the incidence of hypertension increases with increasing concentrations of progestogens. Women with a history of hypertension or hypertension-related diseases or renal disease should be encouraged to use another method of contraception. If women elect to use combined oral contraceptives, they should be monitored closely, and if significant elevation of blood pressure occurs, combined oral contraceptives should be discontinued. For most women, elevated blood pressure will return to normal after stopping combined oral contraceptives, and there is no difference in the occurrence of hypertension among ever and never users. 11. Headache The onset or exacerbation of migraine or development of headache with a new pattern which is recurrent, persistent, or severe requires discontinuation of combined oral contraceptives and evaluation of the cause. 12. Bleeding Irregularities Breakthrough bleeding and spotting are sometimes encountered in patients on combined oral contraceptives, especially during the first three months of use. Non-hormonal causes should be considered, and adequate diagnostic measures taken to rule out malignancy or pregnancy in the event of prolonged breakthrough bleeding, as in the case of any abnormal vaginal bleeding. If pathology has been excluded, time or a change to another formulation may solve the problem. In the event of amenorrhea, pregnancy should be ruled out. Some women may encounter post-pill amenorrhea or oligomenorrhea, especially when such a condition was preexistent. 13. Hereditary Angioedema In women with hereditary angioedema, exogenous estrogens may induce or exacerbate symptoms of angioedema. 14. Chloasma Chloasma may occur with norethindrone acetate and ethinyl estradiol tablets and ferrous fumarate tablets, especially in women with a history of chloasma gravidarum. Advise women with a history of chloasma to avoid exposure to the sun or ultraviolet radiation while taking norethindrone acetate and ethinyl estradiol tablets and ferrous fumarate tablets.
🔄 Drug Interactions
No interactions listed. Consult your pharmacist.
🚫 Contraindications
CONTRAINDICATIONS Combined oral contraceptives should not be used in women who currently have the following: A high risk of arterial or venous thrombotic diseases. Examples include women who are known to: Smoke, if over age 35 Have cerebrovascular disease Have coronary artery disease Have current or history of deep vein thrombosis or pulmonary embolism Have thrombogenic valvular or thrombogenic rhythm diseases of the heart Have inherited or acquired hypercoagulopathies Have uncontrolled hypertension or hypertension with vascular disease Have headaches with focal neurological symptoms, migraine headaches with aura, or over age 35 with any migraine headaches Have diabetes mellitus and are over age 35, diabetes mellitus with hypertension or with vascular disease or end-organ damage, or diabetes mellitus of > 20 years duration Current diagnosis of, or history of, breast cancer, which may be hormone-sensitive Carcinoma of the endometrium or other known or suspected estrogen-dependent neoplasia Undiagnosed abnormal genital bleeding Cholestatic jaundice of pregnancy or jaundice with prior pill use Hepatic adenomas or carcinomas Known or suspected pregnancy Are receiving Hepatitis C drug combinations containing ombitasvir/paritaprevir/ritonavir, with or without dasabuvir, due to the potential for ALT elevations (see Warnings, RISK OF LIVER ENZYME ELEVATIONS WITH CONCOMITANT HEPATITIS C TREATMENT ) .
📦 Storage & Handling
HOW SUPPLIED Xarah Fe (Norethindrone Acetate and Ethinyl Estradiol Tablets, USP and Ferrous Fumarate Tablets) is available in blister packs each containing 28 tablets. The first five white to off white tablets each contain 1 mg of norethindrone acetate and 20 mcg of ethinyl estradiol; the next seven light purple tablets each contain 1 mg of norethindrone acetate and 30 mcg of ethinyl estradiol; the next nine purple tablets each contain 1 mg of norethindrone acetate and 35 mcg of ethinyl estradiol; and the last seven (brown) tablets each contain 75 mg ferrous fumarate. Carton (NDC 70700-310-85) of 3 tri-laminated aluminum pouches, each pouch (NDC 70700-310-84) containing blister of 28 tablets. Store at 20° to 25°C (68° to 77°F). [See USP for Controlled Room Temperature.] Protect from light. Store tablets in blister sleeve when not in use. Keep this and all medication out of the reach of children. REFERENCES AVAILABLE UPON REQUEST The brands listed are trademarks of their respective owners.