The association between drospirenone and hyperkalemia: a comparative-safety study

BMC Clin Pharmacol. 2011 Dec 30;11:23. doi: 10.1186/1472-6904-11-23.

Abstract

Background: Drospirenone/ethinyl-estradiol is an oral contraceptive (OC) that possesses unique antimineralocorticoid activity. It is conjectured that drospirenone, taken alone or concomitantly with spironolactone, may be associated with an increased risk of hyperkalemia.

Methods: A retrospective cohort study was conducted evaluating women between 18-46 years of age in the Lifelink™ Health Plan Claims Database. The study was restricted to new users of OCs between 1997-2009. Cox proportional hazards models were used to estimate the time to first occurrence of hyperkalemia diagnosis. The main analysis compared OCs containing drospirenone with OCs containing levonorgestrel, a second generation OC not known to impact potassium homeostasis. Logistic regression evaluated concomitant prescribing of drospirenone and spironolactone

Results: The cohort included 1,148,183 women, averaging 28.8 years of age and 280 days of OC therapy. 2325 cases of hyperkalemia were identified. The adjusted hazard ratio (HR) for hyperkalemia with drospirenone compared to levonorgestrel was 1.10 (95%CI 0.95-1.26). There was an increased risk of hyperkalemia with norethindrone HR 1.15 (95%CI: 1.00-1.33) and norgestimate HR 1.27 (95%CI: 1.11-1.46). Other OCs were unassociated with hyperkalemia. The odds of receiving spironolactone while taking drospirenone were 2.66 (95%CI 2.53-2.80) times higher than the odds of receiving spironolactone and levonorgestrel. Only 6.5% of patients taking drospirenone and spironolactone had a serum potassium assay within 180 days of starting concomitant therapy.

Conclusions: A clinically significant signal for hyperkalemia with drospirenone was not demonstrated in the current study. Despite the bolded warning for hyperkalemia with joint drospirenone and spironolactone administration, physicians are actually using them together preferentially, and are not following the recommended potassium monitoring requirements in the package insert.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Androstenes / administration & dosage
  • Androstenes / adverse effects*
  • Cohort Studies
  • Contraceptives, Oral, Combined / adverse effects
  • Contraceptives, Oral, Combined / therapeutic use
  • Ethinyl Estradiol / administration & dosage
  • Ethinyl Estradiol / adverse effects
  • Female
  • Follow-Up Studies
  • Humans
  • Hyperkalemia / chemically induced*
  • Levonorgestrel / therapeutic use
  • Logistic Models
  • Proportional Hazards Models
  • Retrospective Studies
  • Risk Factors
  • Spironolactone / therapeutic use

Substances

  • Androstenes
  • Contraceptives, Oral, Combined
  • drospirenone and ethinyl estradiol combination
  • Spironolactone
  • Ethinyl Estradiol
  • Levonorgestrel
  • drospirenone