Nordette Information
Nordette (Levonorgestrel)
Nordette (Levonorgestrel) Description
21 light-orange Nordette (Levonorgestrel) -28 tablets, each containing 0.15 mg of levonorgestrel, ((-)-13 beta-ethyl-17-alpha-ethinyl-17-beta-hydroxygon-4-en-3-one), a totally synthetic progestogen, and 0.03 mg of ethinyl estradiol, (19-nor-17α-pregna-1,3,5 (10)-trien-20-yne-3,17-diol), and 7 pink inert tablets. The inactive ingredients present are cellulose, D&C Red 30, FD&C Yellow 6, lactose, magnesium stearate, and polacrilin potassium.
Nordette (Levonorgestrel) Clinical Pharmacology
Combination oral contraceptives act by suppression of gonadotropins. Although the primary mechanism of this action is inhibition of ovulation, other alterations include changes in the cervical mucus (which increase the difficulty of sperm entry into the uterus) and the endometrium (which reduce the likelihood of implantation).
Nordette (Levonorgestrel) Indications And Usage
Oral contraceptives are indicated for the prevention of pregnancy in women who elect to use this product as a method of contraception.
Oral contraceptives are highly effective. Table I 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 and the IUD, depends upon the reliability with which they are used. Correct and consistent use of methods can result in lower failure rates.
Nordette (Levonorgestrel) Contraindications
Combination oral contraceptives should not be used in women with any of the following conditions:
Thrombophlebitis or thromboembolic disorders.
A past history of deep-vein thrombophlebitis or thromboembolic disorders.
Cerebral-vascular or coronary artery disease.
Thrombogenic valvulopathies.
Thrombogenic rhythm disorders.
Diabetes with vascular involvement.
Uncontrolled hypertension.
Known or suspected carcinoma of the breast.
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, or active liver disease, as long as liver function has not returned to normal.
Known or suspected pregnancy.
Hypersensitivity to any of the components of Nordette (Levonorgestrel) -28 (levonorgestrel and ethinyl estradiol tablets).
Nordette (Levonorgestrel) Warnings
Cigarette smoking increases the risk of serious cardiovascular side effects from oral contraceptive use. This risk increases with age and with the extent of smoking (in epidemiologic studies, 15 or more cigarettes per day was associated with a significantly increased risk) and is quite marked in women over 35 years of age. Women who use oral contraceptives should be strongly advised not to smoke.
The use of oral contraceptives is associated with increased risks of several serious conditions including venous and arterial thrombotic and thromboembolic events (such as myocardial infarction, thromboembolism, and stroke), hepatic neoplasia, gallbladder disease, and hypertension, 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 certain inherited or acquired thrombophilias, hypertension, hyperlipidemias, obesity, and diabetes.
Practitioners prescribing oral contraceptives should be familiar with the following information relating to these risks.
The information contained in this package insert is based principally on studies carried out in patients who used oral contraceptives with higher formulations of estrogens and progestogens than those in common use today. The effect of long-term use of the 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 disease, namely, a ratio of the incidence of a disease among oral contraceptive users to that among non-users. 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 oral contraceptive users and non-users. The attributable risk does provide information about the actual occurrence of a disease in the population. For further information, the reader is referred to a text on epidemiological methods.
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 III). 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 less than 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 1970’s—but not reported until 1983. 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, 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 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 oral contraceptive use by healthy nonsmoking 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.
A meta-analysis from 54 epidemiological studies reported that there is a slightly increased relative risk (RR=1.24) of having breast cancer diagnosed in women who are currently using combination oral contraceptives compared to never-users. The increased risk gradually disappears during the course of the 10 years after cessation of combination oral contraceptive use. These studies do not provide evidence for causation. The observed pattern of increased risk of breast cancer diagnosis may be due to earlier detection of breast cancer in combination oral contraceptive users, the biological effects of combination oral contraceptives, or a combination of both. Because breast cancer is rare in women under 40 years of age, the excess number of breast cancer diagnoses in current and recent combination oral contraceptive users is small in relation to the lifetime risk of breast cancer. Breast cancers diagnosed in ever-users tend to be less advanced clinically than the cancers diagnosed in never-users.
Some studies suggest that oral contraceptive use has been associated with an increase in the risk of cervical intraepithelial neoplasia or invasive cervical cancer in some populations of women. 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 and cervical cancers, a cause-and-effect relationship has not been established.
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/100,000 for users, a risk that increases after four or more years of use. Rupture of rare, benign, hepatic adenomas may cause death through intra-abdominal hemorrhage.
Studies from Britain have shown an increased risk of developing hepatocellular carcinoma in long-term (>8 years) oral contraceptive users. However, these cancers are extremely rare in the U.S., and the attributable risk (the excess incidence) of liver cancers in oral contraceptive users approaches less than one per million users.
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 insofar as cardiac anomalies and limb-reduction defects are concerned, when taken inadvertently during early pregnancy (see section).
The administration of oral contraceptives to induce withdrawal bleeding should not be used as a test for pregnancy. 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. Oral contraceptive use should be discontinued if pregnancy is confirmed.
Oral contraceptives have been shown to cause glucose intolerance in a significant percentage of users. Oral contraceptives containing greater than 75 micrograms 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 nondiabetic woman, 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 oral contraceptives.
A small proportion of women will have persistent hypertriglyceridemia while on the pill. As discussed earlier (see , 1a. and 1d.), changes in serum triglycerides and lipoprotein levels have been reported in oral contraceptive users.
An increase in blood pressure has been reported in women taking oral contraceptives, and this increase is more likely in older 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 quantities 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 with hypertension elect to use oral contraceptives, they should be monitored closely, and if significant elevation of blood pressure occurs, oral contraceptives should be discontinued (see section). For most women, elevated blood pressure will return to normal after stopping oral contraceptives, and there is no difference in the occurrence of hypertension among ever- and never-users.
Breakthrough bleeding and spotting are sometimes encountered in patients on oral contraceptives, especially during the first three months of use. The type and dose of progestogen may be important. If bleeding persists or recurs, nonhormonal causes should be considered and adequate diagnostic measures taken to rule out malignancy or pregnancy in the event of 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 if the oral contraceptive has not been taken according to directions prior to the first missed withdrawal bleed or if two consecutive withdrawal bleeds have been missed.
Some women may encounter post-pill amenorrhea or oligomenorrhea (possibly with anovulation), especially when such a condition was preexistent.
Nordette (Levonorgestrel) Precautions
Patients should be counseled that this product does not protect against HIV infection (AIDS) and other sexually transmitted diseases.
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. (See , 1d.)
In patients with familial defects of lipoprotein metabolism receiving estrogen-containing preparations, there have been case reports of significant elevations of plasma triglycerides leading to pancreatitis.
Interactions between ethinyl estradiol and other substances may lead to decreased or increased serum ethinyl estradiol concentrations. Decreased ethinyl estradiol plasma concentrations may cause an increased incidence of breakthrough bleeding and menstrual irregularities and may possibly reduce efficacy of the combination oral contraceptive.
Combination OCs have been shown to significantly decrease plasma concentrations of lamotrigine likely due to induction of lamotrigine glucuronidation. This may reduce seizure control; therefore, dosage adjustments of lamotrigine may be necessary. Consult the labeling of the concurrently-used drug to obtain further information about interactions with COCs or the potential for enzyme alterations.
Reduced ethinyl estradiol concentrations have been associated with concomitant use of substances that induce hepatic microsomal enzymes, such as rifampin, rifabutin, barbiturates, phenylbutazone, phenytoin sodium, griseofulvin, topiramate, some protease inhibitors, modafinil, and possibly St. John’s wort.
Substances that may decrease plasma ethinyl estradiol concentrations by other mechanisms include any substance that reduces gut transit time and certain antibiotics (e.g. ampicillin and other penicillins, tetracyclines) by a decrease of enterohepatic circulation of estrogens.
During concomitant use of ethinyl estradiol containing products and substances that may lead to decreased plasma steroid hormone concentrations, it is recommended that a nonhormonal back-up method of birth control be used in addition to the regular intake of Nordette (Levonorgestrel) -28 (levonorgestrel and ethinyl estradiol tablets). If the use of a substance which leads to decreased ethinyl estradiol plasma concentrations is required for a prolonged period of time, combination oral contraceptives should not be considered the primary contraceptive.
After discontinuation of substances that may lead to decreased ethinyl estradiol plasma concentrations, use of a nonhormonal back-up method of birth control is recommended for 7 days. Longer use of a back-up method is advisable after discontinuation of substances that have led to induction of hepatic microsomal enzymes, resulting in decreased ethinyl estradiol concentrations. It may take several weeks until enzyme induction has completely subsided, depending on dosage, duration of use, and rate of elimination of the inducing substance.
Some substances may increase plasma ethinyl estradiol concentrations. These include:
Ethinyl estradiol may interfere with the mechanism of other drugs by inhibiting hepatic microsomal enzymes or by inducing hepatic drug conjugation, particularly glucuronidation. Accordingly, tissue concentrations may be either increased (e.g. cyclosporine, theophylline, corticosteroids) or decreased.
The prescribing information of concomitant medications should be consulted to identify potential interactions.
Nordette (Levonorgestrel) Adverse Reactions
An increased risk of the following serious adverse reactions (see section for additional information) has been associated with the use of oral contraceptives:
Thromboembolic disorders and other vascular problems (including thrombophlebitis, arterial thromboembolism, pulmonary embolism, myocardial infarction, cerebral hemorrhage, cerebral thrombosis), carcinoma of the reproductive organs, hepatic neoplasia (including hepatic adenomas or benign liver tumors), ocular lesions (including retinal vascular thrombosis), gallbladder disease, carbohydrate and lipid effects, elevated blood pressure, and headache.
The following adverse reactions have been reported in patients receiving oral contraceptives and are believed to be drug-related:
Nausea
Vomiting
Gastrointestinal symptoms (such as abdominal pain, cramps and bloating)
Breakthrough bleeding
Spotting
Change in menstrual flow
Amenorrhea
Temporary infertility after discontinuation of treatment
Edema/fluid retention
Melasma/chloasma which may persist
Breast changes: tenderness, pain, enlargement, secretion
Change in weight or appetite (increase or decrease)
Change in cervical erosion and secretion
Diminution in lactation when given immediately postpartum
Cholestatic jaundice
Rash (allergic)
Mood changes, including depression
Vaginitis, including candidiasis
Change in corneal curvature (steepening)
Intolerance to contact lenses
Mesenteric thrombosis
Decrease in serum folate levels
Exacerbation of systemic lupus erythematosus
Exacerbation of porphyria
Exacerbation of chorea
Aggravation of varicose veins
Anaphylactic/anaphylactoid reactions, including urticaria, angioedema, and severe reactions with respiratory and circulatory symptoms.
The following adverse reactions have been reported in users of oral contraceptives, and the association has been neither confirmed nor refuted:
Congenital anomalies
Premenstrual syndrome
Cataracts
Optic neuritis, which may lead to partial or complete loss of vision
Cystitis-like syndrome
Nervousness
Dizziness
Hirsutism
Loss of scalp hair
Erythema multiforme
Erythema nodosum
Hemorrhagic eruption
Impaired renal function
Hemolytic uremic syndrome
Budd-Chiari syndrome
Acne
Changes in libido
Colitis
Sickle-cell disease
Cerebral-vascular disease with mitral valve prolapse
Lupus-like syndromes
Pancreatitis
Dysmenorrhea
Nordette (Levonorgestrel)
Nordette (Levonorgestrel) Noncontraceptive Health Benefits
The following noncontraceptive health benefits related to the use of oral contraceptives are supported by epidemiological studies which largely utilized oral contraceptive formulations containing doses exceeding 0.035 mg of ethinyl estradiol or 0.05 mg of mestranol.
Increased menstrual cycle regularity.
Decreased blood loss and decreased incidence of iron-deficiency anemia.
Decreased incidence of dysmenorrhea.
Decreased incidence of functional ovarian cysts.
Decreased incidence of ectopic pregnancies.
Decreased incidence of fibroadenomas and fibrocystic disease of the breast.
Decreased incidence of acute pelvic inflammatory disease.
Decreased incidence of endometrial cancer.
Decreased incidence of ovarian cancer.
Nordette (Levonorgestrel) Dosage And Administration
To achieve maximum contraceptive effectiveness, Nordette (Levonorgestrel) -28 (levonorgestrel and ethinyl estradiol tablets, 0.15mg/0.03mg) must be taken exactly as directed and at intervals not exceeding 24 hours.
The dosage of Nordette (Levonorgestrel) -28 is one light-orange tablet daily for 21 consecutive days, followed by one pink inert tablet daily for 7 consecutive days, according to prescribed schedule.
It is recommended that tablets be taken at the same time each day, preferably after the evening meal or at bedtime.
During the first cycle of medication, the patient is instructed to begin taking Nordette (Levonorgestrel) -28 on the first Sunday after the onset of menstruation. If menstruation begins on a Sunday, the first tablet (light-orange) is taken that day. One light-orange tablet should be taken daily for 21 consecutive days, followed by one pink inert tablet daily for 7 consecutive days. Withdrawal bleeding should usually occur within three days following discontinuation of light-orange tablets and may not have finished before the next pack is started. During the first cycle, contraceptive reliance should not be placed on Nordette (Levonorgestrel) -28 until a light-orange tablet has been taken daily for 7 consecutive days and a nonhormonal back-up method of birth control should be used during those 7 days. The possibility of ovulation and conception prior to initiation of medication should be considered.
The patient begins her next and all subsequent 28-day courses of tablets on the same day of the week (Sunday) on which she began her first course, following the same schedule: 21 days on light-orange tablets—7 days on pink inert tablets. If in any cycle the patient starts tablets later than the proper day, she should protect herself by using another method of birth control until she has taken a light-orange tablet daily for 7 consecutive days.
When the patient is switching from a 21-day regimen of tablets, she should wait 7 days after her last tablet before she starts Nordette (Levonorgestrel) -28. She will probably experience withdrawal bleeding during that week. She should be sure that no more than 7 days pass after her previous 21-day regimen. When the patient is switching from a 28-day regimen of tablets, she should start her first pack of Nordette (Levonorgestrel) -28 on the day after her last tablet. She should not wait any days between packs. The patient may switch any day from a progestin-only pill and should begin Nordette (Levonorgestrel) -28 the next day. If switching from an implant or injection, the patient should start Nordette (Levonorgestrel) -28 on the day of implant removal or, if using an injection, the day the next injection would be due. In switching from a progestin-only pill, injection or implant, the patient should be advised to use a nonhormonal back-up method of birth control for the first 7 days of tablet-taking.
If spotting or breakthrough bleeding occurs, the patient is instructed to continue on the same regimen. This type of bleeding is usually transient and without significance; however, if the bleeding is persistent or prolonged, the patient is advised to consult her physician. Although the occurrence of pregnancy is highly unlikely if Nordette (Levonorgestrel) -28 is taken according to directions, if withdrawal bleeding does not occur, the possibility of pregnancy must be considered. If the patient has not adhered to the prescribed schedule (missed one or more tablets or started taking them on a day later than she should have), the probability of pregnancy should be considered at the time of the first missed period and appropriate diagnostic measures taken before the medication is resumed. If the patient has adhered to the prescribed regimen and misses two consecutive periods, pregnancy should be ruled out before continuing the contraceptive regimen.
For additional patient instructions regarding missed pills, see the “WHAT TO DO IF YOU MISS PILLS” section in the below.
Any time the patient misses two or more light-orange tablets, she should also use another method of contraception until she has taken a light-orange tablet daily for seven consecutive days. If the patient misses one or more pink tablets, she is still protected against pregnancy she begins taking light-orange tablets again on the proper day.
If breakthrough bleeding occurs following missed light-orange tablets, it will usually be transient and of no consequence. While there is little likelihood of ovulation occurring if only one or two light-orange tablets are missed, the possibility of ovulation increases with each successive day that scheduled light-orange tablets are missed.
Nordette (Levonorgestrel) -28 may be initiated no earlier than day 28 postpartum in the non-lactating mother or after a second trimester abortion due to the increased risk for thromboembolism (see , , and concerning thromboembolic disease). The patient should be advised to use a nonhormonal back-up method for the first 7 days of tablet taking. However, if intercourse has already occurred, pregnancy should be excluded before the start of combined oral contraceptive use or the patient must wait for her first menstrual period.
In the case of first trimester abortion, if the patient starts Nordette (Levonorgestrel) -28 immediately, additional contraceptive measures are not needed. It is to be noted that early resumption of ovulation may occur if Parlodel (bromocriptine mesylate) has been used for the prevention of lactation.
Nordette (Levonorgestrel) How Supplied
Nordette (Levonorgestrel) -28 Tablets (levonorgestrel and ethinyl estradiol, 0.15mg/0.03mg) are available in packages of 6 compact dispensers, each containing 28 Tablets:
Store at 20º to 25°C (68° to 77º F) [See USP Controlled Room Temperature].
References available upon request.
Iss. 10/2010
Nordette (Levonorgestrel) Brief Summary Patient Package Insert
Oral contraceptives, also known as “birth-control pills” or “the pill,” are taken to prevent pregnancy, and when taken correctly, have a failure rate of less than 1% per year when used without missing any pills. The average failure rate of large numbers of pill users is 5% per year when women who miss pills are included. For most women oral contraceptives are also free of serious or unpleasant side effects. However, forgetting to take pills considerably increases the chances of pregnancy.
For the majority of women, oral contraceptives can be taken safely. But there are some women who are at high risk of developing certain serious diseases that can be life-threatening or may cause temporary or permanent disability or death. The risks associated with taking oral contraceptives increase significantly if you:
You should not take the pill if you suspect you are pregnant or have unexplained vaginal bleeding.
Nordette (Levonorgestrel) Detailed Patient Labeling
Any woman who considers using oral contraceptives (the birth-control pill or the pill) should understand the benefits and risks of using this form of birth control. This leaflet will give you much of the information you will need to make this decision and will also help you determine if you are at risk of developing any of the serious side effects of the pill. It will tell you how to use the pill properly so that it will be as effective as possible. However, this leaflet is not a replacement for a careful discussion between you and your healthcare provider. You should discuss the information provided in this leaflet with him or her, both when you first start taking the pill and during your revisits. You should also follow your healthcare provider’s advice with regard to regular check-ups while you are on the pill.
Oral contraceptives or “birth-control pills” or “the pill” are used to prevent pregnancy and are more effective than other nonsurgical methods of birth control. When they are taken correctly, the chance of becoming pregnant is less than 1% when used perfectly, without missing any pills. Average failure rates are 5% per year. The chance of becoming pregnant increases with each missed pill during the menstrual cycle.
In comparison, average failure rates for other nonsurgical methods of birth control during the first year of use are as follows:
Nordette (Levonorgestrel) Principal Display Panel
1 PACKAGE containing6 COMPACTS of28 TABLETS each
Nordette (Levonorgestrel) 28
21 light-orange tablets, each containing 0.15 mg levonorgestrel with 0.03 mg ethinyl estradiol, and 7 pink inert tablets.
Rx only
AN ORAL CONTRACEPTIVE
Usual Dosage:
See enclosed information
Store at 20° to 25° C (68° to 77°F) [See USP Controlled Room Temperature].
