Drug Profile

Do Not Use: These drugs can cause increased blood levels of potassium and blood clots and are no more effective than other oral contraceptives in preventing pregnancy.

The birth-control combination of ethinyl estradiol with drospirenone (GIANVI, YASMIN, YAZ, ZARAH) was approved by the Food and Drug Administration (FDA) in April 2001.

Combination birth control pills containing the hormones estrogen and progestin are referred to as combined hormonal oral contraceptives. In the case of YASMIN, the estrogen is ethinyl estradiol and the progestin is drospirenone. The difference between the combination drug drospirenone with ethinyl estradiol and other birth control pills on the market is that drospirenone was never marketed in the U.S. before 2001 and is unlike other progestins available in this country.

Drospirenone is a close chemical cousin of spironolactone (ALDACTONE), a diuretic (water pill) that causes the body to retain potassium. A 3-milligram (mg) dose of drospirenone (the amount in a daily birth-control pill) is equivalent to 25 mg of spironolactone.

Drospirenone and ethinyl estradiol as a Do Not Use drug

Two facts form Public Citizen's basis for listing drospirenone and ethinyl estradiol as a Do Not Use drug. First, drospirenone causes elevated levels of potassium in the blood, which may cause serious heart and other health conditions, such as a change in the acid balance of the blood and muscle weakness. Second, there is no evidence that drospirenone and ethinyl estradiol is superior in any way to older contraceptive products.

Two large studies, one from the Netherlands and one from Denmark, have found increased risk of blood clots in women using oral contraceptives that contain drospirenone. The finding in both studies was a significantly increased risk of venous blood clots in women using drospirenone-containing pills. In the studies, the combination of drospirenone and ethinyl estradiol was the main drug of this type tested. (Read more in the May 2011 Worst Pills, Best Pills News.)

The studies also confirmed that oral contraceptive pills containing desogestrel (another progestin) can increase the user’s risk of life-threatening blood clots compared with second-generation birth-control pills.[2][3]

Another study published in 2012 found that use of drospirenone-containing combined hormonal contraceptives in new users was associated with a higher risk of thrombotic events (blockage of veins by a blood clot) than us of a low-dose estrogen combined hormonal contraceptive.[4]

FDA advisory committee shuts out scientific opinions

Less than 48 hours from the beginning of a December 2011 FDA advisory committee meeting to discuss the risks of blood clots due to the birth control pills YAZ and YASMIN, Health Research Group director Dr. Sidney Wolfe was notified in a phone call from the FDA’s Advisors and Consultants Office that he could not participate in that meeting as a member of the Drug Safety and Risk Management Advisory Committee because of what the agency called his “intellectual conflict of interest.” The reason for the purported conflict of interest was the two drugs’ status on WorstPills.org as Do Not Use drugs.

Disqualifying advisory committee members because they have views on scientific matters threatens the utility of advisory committees in several ways. First, it deprives agencies of advice from the very experts most qualified to give it — those who have actual knowledge of and research experience concerning the subjects to be addressed by the committee. Second, it deters qualified scientists from accepting appointments to advisory committees out of concern that their very expertise may become a matter of distracting controversy. And finally, it encourages politicization of scientific matters as interested parties seek to exclude scientists whose views are inconvenient to them.

Studies show …

In December 2011, Health Canada issued an advisory informing the public that birth control pills containing drospirenone may have a risk of blood clots that is 1.5 to three times higher than that of other birth-control pills. The agency recommended that health care providers assess the risk and the benefits of this medication when prescribing it to patients.[5]

Drugs that increase the level of potassium in the blood

In addition to drospirenone, a number of prescription and nonprescription drugs can contribute to increased levels of potassium in the blood. These include:

• nonsteroidal anti-inflammatory drugs (NSAIDs) — such as ibuprofen (MOTRIN), naproxen (ALEVE), phenylbutazone (BUTAZOLIDIN) and celecoxib (CELEBREX) — when taken long-term and daily for the treatment of arthritis and other problems
• potassium-sparing diuretics, such as spironolactone, triamterene (DYRENIUM) and amiloride (MIDAMOR)
• potassium supplementation that includes the use of unregulated dietary supplements labeled as containing potassium
• angiotensin-converting enzyme (ACE) inhibitors, such as captopril (CAPOTEN) and enalapril (VASOTEC)
• angiotensin receptor blockers, also known as angiotensin-II receptor antagonists, such as losartan (COZAAR) and valsartan (DIOVAN)
• heparin, an injectable blood thinner that is rarely used outside of the hospital

YASMIN’s product label requires that a blood test be done during the first month of use to check the potassium level if the above-listed drugs are also being taken. This blood test is not required for any other birth control pill on the market.

In March 2014 the Medicines and Healthcare products Regulatory Agency (MHRA, an agency in the U.K. similar to the FDA) issued a drug safety update that St. John’s wort, when used with hormonal contraceptives, reduces the effectiveness of the contraceptives and increases the risk of unplanned pregnancy.[6]

Regulatory actions surrounding drospirenone and ethinyl estradiol

2010: In April, the FDA issued a safety-labeling change to the drug product information for drospirenone and ethinyl estradiol regarding data from studies on thromboembolic disorders (blood clots) and other vascular problems in women using drospirenone and ethinyl estradiol.[7]

2011: In February, the French medical journal Prescrire International published information from four studies concerning the use of oral contraceptives containing the progestin drospirenone and the increased risk of blood clots. Two of the reviewed studies showed increases in the risk of blood clots in women taking drospirenone. The other two reviewed studies found no increase in the risk of blood clots in women taking the drug. However, these two “negative” studies were funded by Bayer, the manufacturer of drospirenone-containing pills YASMIN and YAZ.

In March, the FDA issued more safety information concerning the use of the drospirenone-ethinyl estradiol combination pill and an increased risk of developing blood clots, known as venous thromboembolism (VTE). The FDA stated that data from a large safety study found that the risk of VTE is highest during the first year of drospirenone-ethinyl estradiol use and greatest during the first six months of drospirenone-ethinyl estradiol use.[8]

In May, the FDA issued yet another statement that it was continuing to investigate information from two published studies evaluating the increased risk of developing VTE in women who use birth control pills containing drospirenone and would continue to communicate any new safety information to the public as it becomes available.[9]

In September, the FDA announced that it had not reached a conclusion on the potential increased risk of blood clots with the use of drospirenone-containing birth control pills. It stated that it was continuing its review of data from a separate FDA-funded study.[10]

In October, the results of the final report of the FDA-funded study were released. (Click here to read the details of the study.) The investigators concluded:

In conclusion, the study results … provides another positive finding to the increasing body of evidence linking DRSP [drospirenone/ethinyl estradiol tablet] to increased risk of VTE relative to standard CHC pills. DRSP was associated with higher risk of ATE [arterial thrombotic events] in new users overall with this finding restricted to women in the 35-55 years age group only.

2012: In April 2012, the FDA updated the drug product label of drospirenone-containing products to state that these products may be associated with a higher risk of blood clots than other progestin-containing pills. The update includes the following information:

The revised drug labels will state that some studies reported as high as a threefold increase in the risk of blood clots for drospirenone-containing products when compared to products containing levonorgestrel or some other progestins, but other studies found no additional risk of blood clots with drospirenone-containing products.[11]

2017: In March, the labeling for the seizure drug valproate (DEPAKENE) was revised to warn that using hormonal contraceptives containing estrogen with valproate may cause an increased rate of seizures.[12]