Concomitant use of dronedarone and digoxin (or statins) and the risk of digitalis intoxication (or rhabdomyolysis and myopathy)-- a post-marketing cohort study using the US Clinformatics DataMart® (formerly LabRx®) database

Study identification

• PURI:
  https://redirect.ema.europa.eu/resource/36369
• EU PAS number:
  EUPAS18153
• Study ID:
  36369
• Official title and acronym:
  Concomitant use of dronedarone and digoxin (or statins) and the risk of digitalis intoxication (or rhabdomyolysis and myopathy)-- a post-marketing cohort study using the US Clinformatics DataMart® (formerly LabRx®) database
• DARWIN EU® study:
  No
• Study countries:
  United States
• Study description:
  This was a cohort study using existing database to evaluate if the concomitant use of dronedarone increases the risk of dose-related digitalis intoxication in digoxin users and the risk of rhabdomyolysis and myopathy in statin users.The study population consisted of 2 cohorts of patients identified from the Clinformatics DataMart® (formerly LabRx®) database who were at least 18 years old, had a diagnosis of atrial fibrillation (AF) or flutter (AFL), and filled a prescription of digoxin or statins between July 20, 2009 and March 31, 2016 (the date of the latest data available for this study). The cohort entry date was the date on which the first prescription of digoxin or statins was dispensed in the study period.Exposure of interest was concurrent use of dronedarone in digoxin or statins users. The concomitant use of dronedarone and digoxin (or statins) was defined as the treatment period during which a patient was on both drugs. Digoxin (or statins) alone was defined as the treatment period during which a patient was on digoxin (or statins), but not on dronedarone.The respective outcomes of interest were digitalis intoxication in digoxin users and rhabdomyolysis/ myopathy in statin users. Digitalis intoxication was defined by the presence of the International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9) codes 972.1 or E942.1 or tenth Revision, Clinical Modification (ICD-10) codes T46,xxxA or T46.0X5x.The covariates in the multivariate analyses included age at baseline, gender, the number of diagnoses of AF/AFL and history of comorbidities including congestive heart failure (CHF), diabetes, hypertension, stroke, myocardial infarction, and renal failure within 180 days prior to a patient’s cohort entry date, average dose of digoxin (or statins), the use of major medications with potent interactions with digoxin (or statins), and the calendar year of cohort entry date.Cox proportional hazards regression models were fit to obtain.
• Study status:
  Finalised

Research institutions and networks

Institutions

Sanofi

Study timelines

Date when funding contract was signed

Planned: 01/03/2011

Actual: 01/03/2011

Study start date

Planned: 20/07/2009

Actual: 20/07/2009

Date of final study report

Planned: 21/12/2016

Actual: 21/12/2016

Sources of funding

Pharmaceutical company and other private sector 

More details on funding

Sanofi

Study protocol

Initial protocol

DRONEC05911 protocol

Regulatory

• Was the study required by a regulatory body?:
  Yes
• Is the study required by a Risk Management Plan (RMP)?:
  EU RMP category 3 (required)

Other study registration identification numbers and links

Study code: DRONE_C_05911