Canrenone

Table of contents

• What is canrenone?
• How does canrenone work?
• Which conditions is canrenone used or studied for?
• How is canrenone given?
• What do the clinical trials show?
• What side effects are known?

What is canrenone?

Canrenone is a synthetic chemical substance that belongs to the class of mineralocorticoid receptor antagonists, also called aldosterone antagonists.^[2] It is the active metabolite of spironolactone, a widely used diuretic and heart failure medicine.^[4] Canrenone is authorised as a medicine, according to registry records from the EU Clinical Trials Information System.^[1] It is also known by the names aldadiene and phanurane.^[2] In the registered trial, canrenone appears as one of many medicines in a heart failure treatment programme, where its role is listed as a test substance in two trials.^[1]

How does canrenone work?

Canrenone blocks the action of aldosterone by binding to the mineralocorticoid receptor.^[2] Aldosterone is a hormone that makes the body retain sodium and water and lose potassium; blocking its receptor helps the body remove excess fluid and retain potassium. Laboratory research has also shown that canrenoic acid, the main metabolite of canrenone, blocks certain potassium channels in heart muscle cells, including hKv1.5, Kv4.3 and Kv7.1+minK channels.^[3] These channels help control the electrical activity and rhythm of the heart.^[3]

Which conditions is canrenone used or studied for?

Canrenone is studied in the following condition:

• Heart failure — a condition in which the heart cannot pump blood well enough to meet the body's needs. The registered trial includes canrenone as part of a programme of heart failure medicines.^[1]

Canrenone is also relevant to heart failure with reduced ejection fraction (HFrEF), a form of heart failure in which the lower left chamber of the heart pumps out a reduced amount of blood with each beat. A cross-sectional study measured canrenone concentrations in 64 patients treated for HFrEF with oral spironolactone.^[4]

How is canrenone given?

In the registered trial, canrenone is listed as a medicine for buccal use, meaning it is placed in the mouth.^[1] The trial lists two strengths: 100 mg and 50 mg.^[1] The same trial also lists potassium canrenoate, a related substance, at 100 mg and 50 mg for buccal use.^[1]

What do the clinical trials show?

One Phase 3 trial is registered for canrenone in heart failure.^[1] The trial, titled "Pharmacological optimization in prevention in Heart Failure: A Sex-gap?", is authorised but not yet recruiting.^[1] It plans to enrol 368 participants.^[1]

The trial has two parts. The retrospective part describes how heart failure medicines are currently prescribed nationally and examines sex-related differences in prescribing, using national registry data.^[1] The prospective part randomly assigns women with heart failure to either up-titration of guideline-directed medical therapy, following the STRONG-HF titration programme, or usual care.^[1] The main outcome measured at 12 months is all-cause mortality, readmission to hospital for heart failure, or worsening heart failure.^[1] Other outcomes include quality of life, adherence to medication, and side effects.^[1]

The trial lists many heart failure medicines as interventions, including canrenone, spironolactone, eplerenone, potassium canrenoate, sacubitril valsartan, dapagliflozin, empagliflozin, bisoprolol, carvedilol, metoprolol, nebivolol, ramipril, enalapril, lisinopril, perindopril, trandolapril, captopril, quinapril, fosinopril, losartan, valsartan, candesartan, irbesartan, olmesartan, and finerenone.^[1]

What side effects are known?

The registered trial lists side effects as one of the outcomes it will measure, but no specific side-effect data for canrenone are reported in the registry record.^[1] A cross-sectional study noted that patients with detectable canrenone concentrations had significantly higher potassium concentrations than those without detectable concentrations.^[4] High potassium is a known concern with aldosterone antagonists, but the source does not report specific side-effect frequencies for canrenone.^[4]