Products
Perindopril is commercially available in the form of film-coated tablets and has been approved in many countries since 1989 (Coversum N, generic). It is also approved as a fixed combination with indapamide (Coversum N combi, generic) or amlodipine (Coveram, generic). Generic of the fixed combination with amlodipine was first registered in many countries in 2014. In the same year, a fixed combination of perindopril, indapamide, and amlodipine was also approved (Coveram plus, generic). In 2016, a fixed combination with bisoprolol was registered (Cosyrel).
Structure and properties
Perindopril (C19H32N2O5, Mr = 368.47 g/mol) is present in drugs as tertiary butylamine or as arginine salt. The original Coversum originally contained 4 mg or 8 mg of the tertiary butylamine salt. The arginine salt was developed because the tertiary butylamine salt is not stable enough in warm climates with high humidity. In many countries, the new salt was introduced shortly before the patent expired (5 mg or 10 mg). The generics that were subsequently marketed all continued to contain the tertiary butylamine salt at 4 mg or 8 mg. However, the amount of perindopril contained in the drugs is identical and the drugs are bioequivalent. In 2013, Mepha launched a generic drug containing perindopril tosylate at 5 and 10 mg for the first time. Perindopril is an analog of enalapril and, like it, is a prodrug and a peptidomimetic. The prodrug is more lipophilic and absorbable and is converted to the active form, perindoprilat, a dicarboxylic acid, in the liver by ester hydrolysis.
Effects
Perindopril (ATC C09AA04) has antihypertensive and weak diuretic properties. It lowers preload and afterload and reduces left ventricular hypertrophy. The effects are due to inhibition of angiotensin converting enzyme (ACE), which converts angiotensin I to the vasoconstrictor angiotensin II.
Indications
- Arterial hypertension
- Heart failure
- Stable coronary artery disease (only in combination with indapamide).
- Stroke recurrence prophylaxis
Dosage
According to the professional information. Usually the tablets are taken in the morning before or during breakfast.
Contraindications
- Hypersensitivity (also to other ACE inhibitors).
- Renal insufficiency
- Pregnancy and lactation
- Children
- Concurrent use of aliskiren in patients with diabetes mellitus or impaired renal function.
For complete precautions, see the drug label.
Interactions
Other antihypertensive agents and diuretics may potentiate the antihypertensive effect. Potassium-sparing diuretics and potassium may cause hyperkalemia, especially in renal insufficiency. Perindopril may reduce the elimination of lithium. Combination with antidiabetic agents and insulins may rarely result in hypoglycemia.
Adverse effects
The most common adverse effects include a dry irritable cough, low blood pressure with palpitations, headache, dizziness, weakness, sensory disturbances, balance disturbances, tinnitus, visual and taste disturbances, digestive disturbances, and skin rashes.