The Association Between Drospirenone and Hyperkalemia

A Comparative-safety Study

Steven T Bird; Salvatore R Pepe; Mahyar Etminan; Xinyue Liu; James M Brophy; Joseph AC Delaney


BMC Clin Pharmacol. 2011;11(23):1-6. 

In This Article


Data Source

The IMS Lifelink™ Health Plan Claims Database contains paid claims data from over 102 managed care plans in the United States. The database contains fully adjudicated medical and pharmacy claims for over 68 million patients, including inpatient and outpatient diagnoses and procedures (International Classification of Diseases, 9th Revision, Clinical Modification format) in addition to retail and mail order prescription records. The data is representative of US residents with private health insurance in terms of geography, age, and gender. The Lifelink™ database is subject to quality checks to ensure data quality and to minimize error rates.[14]

Cohort Description

A retrospective cohort was developed, evaluating women in the Lifelink™ Claims database between January 1st, 1997 and December 31st, 2009. All women between 18–46 years of age with the first prescription for an OC containing ethinyl estradiol (0.35 ug or less) and one of the following progestins were included in the cohort: desogestrel, drospirenone, ethynodiol diacetate, levonorgestrel, norethindrone acetate, norethindrone, norgestimate, and norgestrel. All patients who met these inclusion criteria were analyzed in the utilization portion of the study.

For the hyperkalemia analysis, in order to include only new users, patients were excluded if they did not have at least 180 days of enrollment history prior to their first claim for an OC. Patients were also excluded if they had a prior diagnosis of hyperkalemia. Censoring was performed if a patient switched to another OC during the study period, on the final day of OC possession (determined from the final prescription date and day supply), before a gap in OC possession of 30 or more days, at the event of hyperkalemia, and at the end of the study period, December 31st, 2009. Evaluation of hyperkalemia was performed using a diagnostic ICD-9 code (276.7).

Statistical Analysis

OCs and Hyperkalemia Cox proportional hazard models were used to estimate the time to first occurrence of hyperkalemia. The primary analysis used a new user design and compared OCs containing drospirenone with OCs containing levonorgestrel. Levonorgestrel was chosen a priori as a reference based on its high utilization, lack of association with hyperkalemia, and use as a reference in previous OC comparative-safety studies.[15–21] All estimates were adjusted by age, calendar time, chronic kidney disease, diabetes mellitus, hypertension, inflammatory bowel disease, obesity,[22] polycystic ovary syndrome, premenstrual tension syndrome (premenstrual syndrome and premenstrual dysphoric disorder), smoking status, and concomitant medications known to cause hyperkalemia. The following medications were adjusted for: angiotensin-converting enzyme inhibitors (ACE)/angiotensin receptor blockers (ARB), non-steroidal anti-inflammatory drugs (NSAID), spironolactone, and other medications (cyclosporine, diuretics, heparin, penicillin G, tacrolimus, and trimethoprim).

Utilization Concomitant utilization of drospirenone and spironolactone was analyzed during the entire study period. Logistic regression was used to form odds ratios (OR) comparing the odds for receiving concomitant spironolactone and drospirenone therapy against the odds of receiving concomitant spironolactone and levonorgestrel therapy. ORs were also formed calculating the odds of receiving spironolactone while on other progestin-containing OCs compared to levonorgestrel. To evaluate compliance with potassium monitoring for patients taking concomitant drospirenone and spironolactone, the percentage of patients who had a blood serum potassium assay (CPT-4 84132) during the first 180 days of concomitant therapy was calculated.

This study was approved by the University of Florida IRB. All calculations were performed in SAS software version 9.2.


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