|Birth control pill (Photo credit: Wikipedia)|
For the Consumer
Applies to drospirenone / ethinyl estradiol: oral tablet
Get emergency medical help if you have any of these signs of an allergic reaction while taking drospirenone / ethinyl estradiol: hives; difficult breathing; swelling of your face, lips, tongue, or throat.
Stop using birth control pills and call your doctor at once if you have a serious side effect such as:
- sudden numbness or weakness, especially on one side of the body;
- sudden and severe headache, confusion, problems with vision, speech, or balance;
- chest pain or heavy feeling, pain spreading to the arm or shoulder, nausea, sweating, general ill feeling;
- sudden cough, wheezing, rapid breathing, coughing up blood;
- pain, swelling, warmth, or redness in one or both legs;
- a change in the pattern or severity of migraine headaches;
- nausea, upper stomach pain, itching, loss of appetite, dark urine, clay-colored stools, jaundice (yellowing of the skin or eyes);
- swelling in your hands, ankles, or feet;
- a breast lump; or
- symptoms of depression (sleep problems, weakness, tired feeling, mood changes).
Less serious side effects of drospirenone / ethinyl estradiol may include:
- mild nausea (especially when you first start taking this medicine), vomiting, bloating, stomach cramps;
- breast tenderness or swelling, nipple discharge;
- freckles or darkening of facial skin, increased hair growth, loss of scalp hair;
- changes in weight or appetite;
- problems with contact lenses;
- vaginal itching or discharge; or
- changes in your menstrual periods, decreased sex drive.
This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects.
For Healthcare Professionals
Applies to drospirenone / ethinyl estradiol: oral tablet
Many of the adverse effects experienced by women on oral contraceptive combination products have been 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.
Acne, oily skin
Late breakthrough bleeding
Early/mid-cycle breakthrough bleeding
General side effects have included exacerbations of systemic lupus erythematosus, porphyria, chorea, and a possible diminution in lactation when given immediately postpartum. Flu syndrome, tooth disorder, infection, accidental injury, and weight gain have been reported in postmarketing experience.
A number of studies have suggested that use of oral contraceptives decreases 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 is 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.
Cardiovascular side effects of the estrogen component of this combination drug may be significant and have included hypertension. However, significant blood pressure increases generally occur only in women receiving high-dose estrogen products (50 mcg or more of ethinyl estradiol or equivalent daily). Estrogens have also been associated with edema. Other cardiovascular side effects have included aggravation of varicose veins.
Some early investigations of women taking high dose estrogen combinations (50 mcg or more of ethinyl estradiol or equivalent daily) suggested that such women may be at increased risk of cardiovascular complications (myocardial infarction, stroke, and vascular thrombosis, including venous thromboembolism). However, more recent large investigations of women taking 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. (For women aged 35 to 44 who smoke or who have preexisting systemic diseases that may affect the cardiovascular system, use of oral contraceptives is not recommended.)
However, some investigators have suggested that even the new low dose products may result in adverse effects on lipid metabolism and should prompt careful review of a woman’s cardiovascular risk factors before a decision to use oral contraceptive combinations is made.
The frequency of both subarachnoid hemorrhage and thrombotic stroke has been reported by some investigators to be higher in women taking oral contraceptive hormones. However, other investigators have suggested that the risk of these effects for women using newer low dose formulations are very small for young women without underlying cardiovascular disease or other risk factors.
Endocrine and metabolic side effects have included complex alterations in plasma lipid profiles and carbohydrate metabolism. In addition, oral contraceptive use has been reported to cause conception delay.
All the progestins which occur in commercially available oral contraceptive combinations have adverse effects on lipid profiles. Specifically, these progestins exert antiestrogen and androgen effects and decrease HDL (and HDL2) cholesterol levels and increase LDL cholesterol levels. However, the estrogens in 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.
A number of investigations have suggested that oral contraceptive combinations may decrease glucose tolerance. However, some recent studies with low dose preparations have suggested that decreases in glucose tolerance due to oral contraceptive combinations are generally minimal.
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 provided that they receive close monitoring for adverse metabolic effects.
Gastrointestinal side effects have included nausea, which occurs in approximately 10% of treated women and may be more frequent during the first cycles of therapy. Some early reports suggested an association between oral contraceptive use and gallbladder disease. Abdominal pain and gastroenteritis have been reported in postmarketing experience.
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.
Oncologic side effects related to oral contraceptive use have been studied extensively. 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”.
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.
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.”
Hepatic side effects reported rarely in association with estrogen therapy and therapy with oral contraceptive combinations have included focal nodular hyperplasia, intrahepatic cholestasis, liver cell adenomas, hepatic granulomas, hepatic hemangiomas and well-differentiated hepatocellular carcinomas.
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.
Hematologic side effects including thromboembolism have been associated with the use of exogenous estrogens. However, because the dose of exogenous estrogens is low in most commercially available preparations, the risk is minimal for most women (except women who are over age 35 and smoke and women with a previous history of thrombotic diseases).
Genitourinary side effects have included breakthrough bleeding and spotting, especially during the first several cycles of oral contraceptive use. Non-hormonal causes of such bleeding should be excluded. Vaginitis, dysmenorrhea, and candidiasis have been reported. Metrorrhagia, suspicious Papanicolaou smear, vaginal moniliasis, menorrhagia, urinary tract infection, breast pain, dysmenorrhea, menstrual disorder, amenorrhea, and urine abnormality have been reported in postmarketing experience.
Some women have experienced oligomenorrhea and amenorrhea following termination of oral contraceptive use.
Psychiatric side effects have included mood changes, depression and precipitation of panic disorder.
Immunologic side effects have included rare reports of oral contraceptive-induced systemic lupus erythematosus.
A case of fatal pulmonary occlusive disease has been associated with oral contraceptive therapy.
Nervous system side effects have included chorea, which has been reported once in association with oral contraceptives. Headache and asthenia have been reported in postmarketing experience.
Ocular side effects have included retinal thrombosis, which has been reported rarely. In addition, the manufacturers of oral contraceptive products report that some patients have developed changes in contact lens tolerance. Postmarketing experience has included very rare reports of eye inflammation including iritis and uveitis. Optic neuritis, which may lead to partial or complete loss of vision, has been reported.
Metabolic side effects reported with the use of drospirenone have included increased serum potassium levels.
Musculoskeletal side effects have included very rare postmarketing reports of osteonecrosis of the jaw. Arthralgia has been reported in postmarketing experience.
Hypersensitivity side effects have included anaphylactic/anaphylactoid reactions, including urticaria, angioedema, and severe reactions with respiratory and circulatory symptoms.
Respiratory side effects have included upper respiratory infection, sinusitis, pharyngitis, sore throat, rhinitis, and bronchitis in postmarketing reports.