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Nordette Side Effects

Generic Name: ethinyl estradiol / levonorgestrel

Note: This page contains side effects data for the generic drug ethinyl estradiol / levonorgestrel. It is possible that some of the dosage forms included below may not apply to the brand name Nordette.

For the Consumer

Applies to ethinyl estradiol / levonorgestrel: tablets

Check with your doctor if any of these most COMMON side effects persist or become bothersome:

Acne; breast tenderness or enlargement; changes in appetite; changes in sexual interest; changes in weight; dizziness; hair loss; headache; nausea; stomach cramps or bloating; unusual spotting or bleeding; vomiting.

Seek medical attention right away if any of these SEVERE side effects occur while taking ethinyl estradiol / levonorgestrel:

Severe allergic reactions (rash; hives; itching; difficulty breathing; tightness in the chest; swelling of the mouth, face, lips, or tongue); breast discharge; breast lumps; calf or leg pain, swelling, or tenderness; change in amount of urine produced; change in vaginal secretions; changes in vision or speech; confusion; coughing of blood; crushing chest pain or heaviness in the chest; dark-colored urine; depression; difficulty sleeping; difficulty wearing contact lenses; fainting; fluid retention (swelling of the fingers and ankles); lack of energy; light-colored bowel movements; mental or mood changes; missed menstrual period; numbness of an arm or leg; one-sided weakness; persistent headache or migraines; persistent or recurrent abnormal vaginal bleeding; persistent or severe dizziness; severe pain or tenderness in the stomach; shortness of breath; sudden partial or complete loss of vision; sudden severe headache or vomiting; tiredness; vaginal irritation or discharge; weakness; yellowing of the skin or eyes.

For Healthcare Professionals

Applies to ethinyl estradiol / levonorgestrel: oral tablet

Cardiovascular

Cardiovascular side effects of hypertension and edema have been attributed to the estrogen component of this combination product. Significant blood pressure increases generally occurred only in women receiving high-dose estrogen products (50 mcg or more of ethinyl estradiol or equivalent daily). Exogenous estrogens may exert cardioprotective effects due to favorable changes in lipid profiles, however, beneficial effects may be partially or completely offset by alterations in lipid profiles induced by exogenous progestins.[Ref]

Detailed information concerning the effects of oral contraceptive therapy on lipid metabolism is available in the Endocrine paragraph of this side effect monograph.

Early investigations of high dose estrogen combinations (50 mcg or more of ethinyl estradiol or equivalent daily) suggested that women may be at increased risk of cardiovascular complications (myocardial infarction, stroke, and vascular thrombosis, including venous thromboembolism). More recent investigations of low dose estrogen combinations have suggested that oral contraceptive use is not associated with an increased risk of serious cardiovascular complications in healthy non smoking women up to the age of 45. Oral contraceptive use for women aged 35 to 44 who smoke or who have preexisting systemic diseases that may affect the cardiovascular system is not recommended.

Some investigators have suggested that even low dose products may result in adverse lipid metabolism and a woman's cardiovascular risk factors should be assessed before a decision is made to use oral contraceptive combinations.

The frequency of both subarachnoid hemorrhage and thrombotic stroke has been increased in women taking oral contraceptive hormones, however, the risk of these effects with low dose formulations appear to be very small for young women without underlying cardiovascular disease or other risk factors.[Ref]

General

Women taking oral contraceptive combinations have experienced several noncontraceptive health benefits. These benefits have included protection against two malignant neoplasms (endometrial carcinoma and ovarian cancer). In addition, use of oral contraceptive combinations has decreased the frequency of benign breast tumors, the risk of ovarian cysts, the risk of ectopic pregnancy, menstrual irregularity, the incidences of iron deficiency anemia, dysmenorrhea, and pelvic inflammatory disease.

Many of the adverse effects experienced by women on oral contraceptive combination products are related to a relative excess or deficiency of the estrogen and progestin components of these formulations. The following categorizes many of the frequent adverse effects by relative excess or deficiency of these components.

Progestin Excess:

Acne, oily skin
Breast tenderness
Depression
Tiredness, fatigue
Hair loss
Hypertension
Increased appetite
Weight gain
Cholestatic jaundice

Progestin Deficiency:

Late breakthrough bleeding
Amenorrhea
Hypermenorrhea

Estrogen Excess:

Nausea
Headache
Melasma
Hypertension
Breast tenderness
Edema

Estrogen Deficiency:

Early/midcycle breakthrough bleeding
Increased spotting
Hypomenorrhea[Ref]

A number of studies have suggested that use of oral contraceptives decreased the risk of ovarian cancer. Specifically, the risk of epithelial ovarian cancers is decreased by 40%. The protection against ovarian cancer may last for 10 to 15 years after discontinuation of oral contraceptives. After long term use (12 years), the risk of ovarian cancer is decreased by as much as 80%.

The risk of endometrial cancer is decreased by approximately 50%. Protection may last for 15 years after discontinuation and may be greatest for nulliparous women who may be at higher risk for endometrial carcinoma than other women.

The incidence of hospitalization for pelvic inflammatory disease has been approximately 50% lower in women taking oral contraceptives. The reason for the decrease in the frequency (or severity) of pelvic inflammatory disease in women taking oral contraceptives has not been fully elucidated.

Some recent studies have suggested that the decrease in frequency of functional ovarian cysts reported with some older formulations may not occur in women taking newer low dose formulations.

One recent study (The Nurses' Health Study) has suggested that long term use of oral contraceptives is safe and does not adversely affect long term risk for mortality.[Ref]

Gastrointestinal

Nausea, a relatively common gastrointestinal side effect, has occurred in approximately 10% of treated women during the first cycles of therapy. Some early reports suggested an association between oral contraceptive use and gallbladder disease.[Ref]

Cases of oral contraceptive induced esophageal ulceration and geographic tongue have been reported rarely.

More recent studies have suggested that the risk of gallbladder disease is minimal.[Ref]

Oncologic

Oral contraceptive combinations have been studied extensively for oncologic side effects. A number of studies have examined a possible relationship between the use of oral contraceptives and the development of breast cancer. Many of the studies have reported conflicting results. A committee of the World Health Organization evaluated these studies and the risks of breast cancer and concluded that: "Numerous studies have found no overall association between oral contraceptive use and risk of breast cancer." In addition, the same committee also examined a possible relationship between oral contraceptive use and neoplasms of the uterine cervix and concluded that: "There are insufficient data to draw any firm conclusions regarding the effects of combined oral contraceptives on the risk of cervical adenocarcinoma."[Ref]

The World Health Organization committee also noted that some studies "have found a weak association between long-term use of oral contraceptives and breast cancer diagnosed before the age of 36, and perhaps up to the age 45....It is unclear whether this observed association is attributable to bias, the development of new cases of cancer, or accelerated growth of existing cancers."

The World Health Organization committee further concluded that there is no increased risk of breast cancer in women over the age of 45 who have previously taken oral contraceptives. In addition, studies suggest that use of oral contraceptives does not place specific groups of women (like those with a family history of breast cancer) at higher or lower risk, and variations in the hormonal content of oral contraceptives do not influence the risk of breast cancer.

In general, studies evaluating the potential risk of cervical cancer in patients taking oral contraceptives have been complicated by the large number of confounding factors which make investigations into the epidemiology of this neoplasm difficult. Some studies have suggested that women taking oral contraceptives are at increased risk of dysplasia, epidermoid carcinoma, and adenocarcinoma of the cervix. However, other studies have not found such an association.[Ref]

Endocrine

Endocrine effects have included complex alterations in plasma lipid profiles.[Ref]

All progestins which occur in commercially available oral contraceptive combinations have adverse effects on lipid profiles. These progestins exert antiestrogen and androgen effects and decrease HDL (and HDL2) cholesterol levels and increase LDL cholesterol levels. The estrogen component of oral contraceptive combinations exert opposing effects. Consequently, alterations in lipid profiles are related to the relative amount and potency of the specific estrogen and progestin in a given product. (Levonorgestrel exerts potent progestin, antiestrogen, and androgen effects.)[Ref]

Hepatic

The rate of death due to hepatocellular carcinoma in the United States has not changed during the last 25 years (a time during which use of oral contraceptive hormones has increased dramatically).

A committee of the World Health Organization has reported that in developing countries where hepatitis B virus infection and hepatocellular carcinoma are common, "short term use of oral contraceptives does not appear to be associated with an increased risk. Data on the effects of long term use are scarce."

A recent Italian case control study of women with hepatocellular carcinoma has suggested that the relative risk of hepatocellular carcinoma is 2.2 for oral contraceptive users compared to women who never used oral contraceptives.

A similar American case control study from 1989 also reported a strong association between oral contraceptive use and hepatocellular carcinoma but concluded that: "If this observed association is causal, the actual number of cases of liver cancer in the United States attributable to oral contraceptive use is small. Therefore, these findings do not have public health importance in the United States and other Western nations."[Ref]

Hepatic side effects have included focal nodular hyperplasia, intrahepatic cholestasis, liver cell adenomas, hepatic granulomas, hepatic hemangiomas and well differentiated hepatocellular carcinomas, which have been reported rarely in association with estrogen therapy and therapy with oral contraceptive combinations.[Ref]

Hematologic

Cases of venous thrombosis, pulmonary embolism (sometimes fatal), and arterial thrombosis have been reported rarely.

Previous thrombotic disease is considered a contraindication to use of oral contraceptive combinations.[Ref]

A hematologic concern has been the risk of thromboembolism associated with exogenous estrogens. Because the dose of exogenous estrogens is low in most commercially available preparations, the risk of thromboembolism is minimal for most women. Risk is greater in women who are over age 35, smoke, and/or with a history of previous thrombotic diseases. The incidence of venous thrombosis in women with inherited clotting defects has been greater and developed sooner (within the first six months to one year of therapy).[Ref]

Genitourinary

A common genitourinary side effect has been breakthrough bleeding and spotting, especially during the first several cycles of oral contraceptive use. Nonhormonal causes of such bleeding should be excluded. In addition, oral contraceptive use may cause conception delay.[Ref]

Some women have experienced oligomenorrhea and amenorrhea following termination or oral contraceptive use.[Ref]

Psychiatric

Psychiatric side effects have included depression and precipitation of panic disorder.[Ref]

Immunologic

Immunologic side effects have included rare cases of oral contraceptive induced systemic lupus erythematosus.

Nervous system

Nervous system side effects have been rare. A case of chorea has been reported in association with oral contraceptives.

Ocular

Ocular side effects have included rare cases of retinal thrombosis. In addition, the manufacturers of oral contraceptive products report that some patients have developed changes in contact lens tolerance.[Ref]

Respiratory

A case of fatal pulmonary venooclusive disease has been reported.

Metabolic

Despite the potentially adverse effects of oral contraceptives on lipid levels and glucose tolerance, some investigators have suggested that young diabetic women without existing vascular disease or severe lipidemias may be candidates for low dose oral contraceptive combinations with appropriate clinical monitoring of patient response and tolerance.[Ref]

Metabolic side effects have resulted in altered carbohydrate metabolism. The suggested effect that oral contraceptive combinations may have on glucose tolerance has been varied. Decreased glucose tolerance has been observed, however, studies with low dose preparations have suggested that decreased glucose tolerance due to oral contraceptive combinations generally has been minimal.[Ref]

References

1. Petitti DB, Sidney S, Bernstein A, Wolf S, Quesenberry C, Ziel HK "Stroke in users of low-dose oral contraceptives." N Engl J Med 335 (1996): 8-15

2. Poulter NR, Chang CL, Farley TMM, Meirik O, Marmot MG "Haemorrhagic stroke, overall stroke risk, and combined oral contraceptives: results of an international, multicentre, case-control study." Lancet 348 (1996): 505-10

3. Lidegaard O "Oral contraception and risk of a cerebral thromboembolic attack: results of a case-control study." BMJ 306 (1993): 956-63

4. Derman RJ "Oral contraceptives and cardiovascular risk. Taking a safe course of action." Postgrad Med 88 (1990): 119-22

5. Peterson HB, Lee NC "Long-term health risks and benefits of oral contraceptive use." Obstet Gynecol Clin North Am 17 (1990): 775-88

6. "Oral contraceptives and neoplasia. WHO Scientific Group." World Health Organ Tech Rep Ser 817 (1992): 1-46

7. "Product Information. Ortho-Novum (oral contraceptive combination pill)." Ortho Pharmaceutical Corporation, Raritan, NJ.

8. Lanes SF, Birmann B, Walker AM, Singer S "Oral contraceptive type and functional ovarian cysts." Am J Obstet Gynecol 166 (1992): 956-61

9. Brinton LA "Oral contraceptives and cervical neoplasia." Contraception 43 (1991): 581-95

10. Sillero-Arenas M, Rodriguez-Contreras R, Delgado-Rodriguez M, Bueno-Cavanillas A, Galvez-Vargas R "Patterns of research. Oral contraceptives and cervical cancer." Acta Obstet Gynecol Scand 70 (1991): 143-8

11. Ewertz M "Oral contraceptives and breast cancer risk in Denmark." Eur J Cancer 28A (1992): 1176-81

12. Zondervan KT, Carpenter LM, Painter R, Vessey MP "Oral contraceptives and cervical cancer - further findings from the oxford family planning association contraceptive study." Br J Cancer 73 (1996): 1291-7

13. Olsson H, Moller TR, Ranstam J "Early oral contraceptive use and breast cancer among premenopausal women: final report from a study in southern Sweden." J Natl Cancer Inst 81 (1989): 1000-4

14. Rettig BA, Lemon HM "Cancers related to contraceptive use." Br J Cancer 74 (1996): 1509-10

15. Rosenberg L, Palmer JR, Clarke EA, Shapiro S "A case-control study of the risk of breast cancer in relation to oral contraceptive use." Am J Epidemiol 136 (1992): 1437-44

16. Kjaer K, Hagen C, Sando SH, Eshoj O "Contraception in women with IDDM. An epidemiological study." Diabetes Care 15 (1992): 1585-90

17. Steinberg WM "Oral contraception: risks and benefits." Adv Contracept 5 (1989): 219-28

18. Spellacy WN, Ellingson AB, Tsibris JC "The effects of two triphasic oral contraceptives on carbohydrate metabolism in women during 1 year of use." Fertil Steril 51 (1989): 71-4

19. Mooney MJ, Nyreen MR, Hall RA, Carter PL "Hepatic adenoma presenting as a right lower quadrant mass." Am Surg 59 (1993): 229-31

20. Conter RL, Longmire WP Jr "Recurrent hepatic hemangiomas. Possible association with estrogen therapy." Ann Surg 207 (1988): 115-9

21. Beaumont V, Lemort N, Beaumont JL "Oral contraceptives, sex steroid-induced antibodies and vascular thrombosis: results from 1318 cases." Eur Heart J 12 (1991): 1219-24

22. Lidegaard O "Oral contraceptives, pregnancy and the risk of cerebral thromboembolism: the influence of diabetes, hypertension, migraine and previous thrombotic disease." Br J Obstet Gynaecol 102 (1995): 153-9

23. Miwa LJ, Edmunds AL, Shaefer MS, Raynor SC "Idiopathic thromboembolism associated with triphasic oral contraceptives." DICP 23 (1989): 773-5

24. Boerrigter PJ, Ellman H, Dolker M "International clinical experience with a new low-dose, monophasic oral contraceptive containing levonorgestrel 100 mu g and ethinyl estradiol 20 mu g." Clin Ther 21 (1999): 118-27

25. Archer DF, Maheux R, DelConte A, OBrien FB "Efficacy and safety of a low-dose monophasic combination oral contraceptive containing 100 mu g levonorgestrel and 20 mu g ethinyl estradiol (Alesse (R))." Am J Obstet Gynecol 181 (1999): s39-44

26. Reisman H, Martin D, Gast MJ "A multicenter randomized comparison of cycle control and laboratory findings with oral contraceptive agents containing 100 mu g levonorgestrel with 20 mu g ethinyl estradiol or triphasic norethindrone with ethinyl estradiol." Am J Obstet Gynecol 181 (1999): s45-52

27. Ushiroyama T, Okamoto Y, Toyoda K, Sugimoto O "A case of panic disorder induced by oral contraceptive." Acta Obstet Gynecol Scand 71 (1992): 78-80

It is possible that some side effects of Nordette may not have been reported. These can be reported to the FDA here. Always consult a healthcare professional for medical advice.

Disclaimer: Every effort has been made to ensure that the information provided is accurate, up-to-date and complete, but no guarantee is made to that effect. In addition, the drug information contained herein may be time sensitive and should not be utilized as a reference resource beyond the date hereof. This material does not endorse drugs, diagnose patients, or recommend therapy. This information is a reference resource designed as supplement to, and not a substitute for, the expertise, skill , knowledge, and judgement of healthcare practitioners in patient care. The absence of a warning for a given drug or combination thereof in no way should be construed to indicate safety, effectiveness, or appropriateness for any given patient. Drugs.com does not assume any responsibility for any aspect of healthcare administered with the aid of materials provided. The information contained herein is not intended to cover all possible uses, directions, precautions, warnings, drug interactions, allergic reactions, or adverse effects. If you have questions about the substances you are taking, check with your doctor, nurse, or pharmacist.

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