Breast tenderness or mastalgia (1.2%), breast pain (2.2%), breast enlargement, and breast discharge or secretion have been reported in patients receiving oral contraceptives such as drospirenone and are believed to be drug-related.[64244] Galactorrhea and lactation suppression may also occur.

Breakthrough bleeding (spotting) (1.7%) and metrorrhagia (2.8%) are sometimes encountered, especially during the first 3 months of oral contraceptive use such as drospirenone. Change in menstrual flow (menstrual irregularity) (1.2%) and amenorrhea have also been reported and are believed to be drug-related. Other adverse effects may include dysmenorrhea (1.9%), menorrhagia, oligomenorrhea, and pelvic pain. Based on subject diaries from 4 clinical trials of drospirenone, 64.4% of females experienced unscheduled bleeding at Cycle 1. This percentage decreased to 40.3% by cycle 13. A total of 91 out of 2593 subjects (0.4%) discontinued drospirenone due to menstrual bleeding disorders including metrorrhagia, menstrual irregular, vaginal hemorrhage, menorrhagia, uterine hemorrhage, and amenorrhea. In the event of breakthrough vaginal bleeding, consider nonhormonal causes and take adequate diagnostic measures to rule out malignancy or pregnancy. If pathology has been excluded, time or a change to another formulation may solve the problem. In the event of amenorrhea, rule out pregnancy. Some women may encounter post-pill amenorrhea or oligomenorrhea, especially when such a condition was pre-existent.[64244]

Weight gain was reported in 1.9% of patients receiving drospirenone.[64244]

Nausea was reported in 1.8% of patients receiving drospirenone.[64244]

Libido decrease was reported in 1.3% of patients receiving drospirenone.[64244]

Headache was reported in 2.7% of patients receiving drospirenone.[64244]

Acne vulgaris was reported in 3.8% of patients receiving drospirenone.[64244]

The antimineralocorticoid actions of 3 mg of drospirenone are comparable to 25 mg of spironolactone and may cause hyperkalemia in predisposed patients. Most females with hyperkalemia in the clinical development studies of drospirenone had mild potassium elevations and/or isolated increases that returned to normal while still on study medication. No concurrent adverse reactions were attributed to hyperkalemia. In the pivotal trial, 2 females (0.2%) with persistent potassium elevations discontinued drospirenone. It is essential to avoid drospirenone in patients with adrenal insufficiency, hepatic disease, or renal disease, who are at higher risk for hyperkalemia from drospirenone.[64244]

Drospirenone does not protect against human immunodeficiency virus (HIV) infection or other sexually transmitted disease. Patients with known HIV infection or acquired immunodeficiency syndrome (AIDS) should be aware that the use of this oral hormonal contraceptive (OC) will not prevent the transmission of HIV or other sexually-transmitted diseases to their partner(s).[64244]

Drospirenone has antimineralocorticoid activity and may increase serum potassium. Because of the antimineralocorticoid activity, drospirenone may predispose certain patients to hyperkalemia or impaired adrenal function; thus drospirenone is contraindicated in patients with renal impairment (i.e., CrCl less than 80 mL/minute), renal disease, renal failure, or adrenal insufficiency. Females receiving daily, long-term treatment for chronic conditions or diseases with medications that may increase serum potassium concentration should have their serum potassium concentration checked prior to starting treatment and during the first treatment cycle. Such medications include potassium-sparing medications or strong CYP3A4 inhibitors. Monitor females taking drospirenone who later develop medical conditions and/or begin medication that put them at an increased risk for hyperkalemia.[64244]

Drospirenone is contraindicated in patients with hepatic disease, jaundice, or hepatic tumors (benign or hepatocellular cancer). The mean exposure to drospirenone in females with moderate hepatic impairment is approximately 3 times higher than the exposure in females with normal liver function. Increased drospirenone exposure increases risks for hyperkalemia and other side effects. Discontinue drospirenone use if jaundice or acute or chronic disturbances of liver function develop. Do not resume use until markers of liver function return to normal and drospirenone causation has been excluded.[64244]

Epidemiological studies have not indicated an association between progestin-only preparations and an increased risk of arterial or venous thromboembolism. When prescribing drospirenone, consider the increased risk of thromboembolism inherent in the postpartum period and in females with a known history of thromboembolism, including myocardial infarction or stroke. Discontinue drospirenone if arterial or venous thromboembolic events occur.[64244] Tobacco smoking increases the risk of serious cardiovascular disease, myocardial infarction, and stroke. Women who use oral contraceptives should be strongly advised not to smoke. There are no studies definitely linking progestin-only pill (POP) use to an increased risk of heart attack or stroke.[48201] Despite the caution against use in patients with known thrombotic disease, progestin-only contraceptives are generally the hormonal contraceptives of choice in patients with a potential risk for thrombosis when reliable contraception must be ensured and the risks of hormonal therapy are acceptable; advantages of these methods usually outweigh proven or theoretical risks.[48201] When multiple risk factors exist for thromboembolic disease (e.g., tobacco smoking, women 35 years and older, diabetes, cerebrovascular disease, hypercoagulopathy, valvular or ischemic heart disease, severe hypertension, etc.), the risk of thromboembolic disease may increase; determine individual risk vs. benefit for use of the progestin-only contraceptive. The increase in the risk of thrombosis from newer progestin-only contraceptives (e.g.,drospirenone) is still substantially less than with combined oral contraceptives containing both estrogen and progestin.[48201] Consider discontinuing drospirenone, if feasible, in case of prolonged immobilization due to major surgery or illness, since these situations increase risk for thromboembolism.[64244]

Drospirenones should be used cautiously in patients with diabetes mellitus. Although the effects appear to be minimal during therapy with progestins, altered glucose tolerance secondary to decreased insulin sensitivity has been reported during hormonal contraceptive therapy.[64244]

Use drospirenone with caution in a patient with a history of migraine, particularly migraine with aura or if the patient is 35 years of age or older. The onset or exacerbation of migraine or the development of headache with a new pattern that is recurrent, persistent, or severe requires evaluation of the cause.[48201]

Mood disorders, like depression, may be aggravated in women taking exogenous hormones. Women with a history of depression may need special monitoring. Data on the association of progestin-only contraceptive products with onset of depression or exacerbation of depression are limited. If significant depression occurs, drospirenone should be discontinued.[64244]

Drospirenone is contraindicated in patients with known or suspected progestin-sensitive cancers, such as breast cancer. Progestin-only oral contraceptives do not appear to cause breast cancer. However patients who have or have had a cancer that may be sensitive to hormones should not use hormonal contraceptives.[64244] [48201]

Drospirenone is contraindicated in undiagnosed abnormal vaginal bleeding and in patients with known or suspected progestin-sensitive cancers of reproductive organs, such as cervical cancer or uterine cancer. Women who use hormonal contraceptives may have a higher chance of getting cervical cancer. However, the increased risk observed with some hormonal contraceptives may be due to other reasons such as having more sexual partners and exposure to the human papilloma virus (HPV).[64244]

Patients should be instructed that menstrual irregularity may occur and to notify their prescriber of any persistent changes in bleeding patterns; these may require medical evaluation. Some women may experience unscheduled (breakthrough or intracyclic) bleeding and spotting especially during the first 3 months of use of drospirenone. Bleeding irregularities may resolve over time or by changing to a different contraceptive product. If bleeding persists or occurs after previously regular cycles, evaluate for the cause, including malignancy. If scheduled bleeding does not occur, consider the possibility that the patient may be pregnant, particularly if the patient has not adhered to the prescribed dosing schedule, or if the patient has adhered to the prescribed dosing schedule and misses 2 consecutive menstrual periods.[64244]

Discontinue drospirenone if pregnancy occurs, because there is no reason to use hormonal contraceptives during pregnancy. Epidemiologic studies and meta-analyses have not found an increased risk of genital or nongenital birth defects (including cardiac anomalies and limb-reduction defects) following maternal use of oral contraceptive progestins before conception or during early pregnancy.[64244]

Be alert to the possibility of ectopic pregnancy in females who become pregnant or complain of lower abdominal pain while on drospirenone. Progestin-only oral contraceptive users have a higher absolute rate of ectopic pregnancy than do users of other hormonal contraceptives, but the risk is still lower than individuals using no method.[64244] [48201]

Progestin-only oral contraceptives are considered compatible with breast-feeding.[48201] Negligible amounts of drospirenone are excreted into breast milk during routine contraceptive use, resulting in infant plasma levels that are approximately 1.5% of those found in maternal plasma, even with exclusive breast-feeding. At therapeutic doses of drospirenone, no effects on breastfed newborns/infants are anticipated. In general, no adverse effects have been found on milk production or on the health, growth, or development of the infant with use of progestin-only oral contraceptives. When prescribing drospirenone, consider the increased risk of thromboembolism inherent in the postpartum period or if the postpartum individual has increased thromboembolic risk.[64244] Alternate contraceptive agents to consider for the breast-feeding individual include non-hormonal contraceptive methods (e.g., copper IUD, barrier methods) and other progestin-only contraceptives (e.g., medroxyprogesterone contraceptive injections, norgestrel oral contraceptive, levonorgestrel IUDs).[48201]

Treatment with drospirenone leads to decreased estradiol serum levels in treated females. It is unknown if this may cause a clinically relevant loss of bone mineral density (osteopenia).[64244]