Coversyl4 mg

Coversyl is an angiotensin-converting enzyme (ACE) inhibitor. It is the arginine-salt form of perindopril, an alternative to the more commonly used erbumine (tert-butylamine) salt, and is chosen mainly for its improved chemical stability. The clinical uses of the two salt forms are the same because both release the same active moiety, perindopril.

Established / approved uses

• Essential hypertension - used alone or in combination with other antihypertensive agents (e.g. a thiazide diuretic or a calcium channel blocker) to lower blood pressure.
• Stable coronary artery disease - used to reduce the risk of cardiovascular death, non-fatal myocardial infarction, or cardiac arrest with successful resuscitation in patients with a history of myocardial infarction and/or revascularization.

Guideline-supported / adjunct use

• Chronic heart failure - used as an adjunct to standard heart-failure therapy (diuretics, beta-blockers, mineralocorticoid-receptor antagonists) in stable patients, under close medical supervision, in countries where it carries this indication.

Coversyl is not indicated for use in children, and it is not a first-line agent for hypertensive emergencies.

Each tablet of Perindopril Arginine contains perindopril arginine, equivalent to a specific amount of perindopril free base (commonly available as 2 mg, 4 mg, and 8 mg strengths, corresponding to smaller free-base equivalents than the erbumine salt because arginine is a heavier counter-ion). Tablets also contain standard pharmaceutical excipients such as microcrystalline cellulose, colloidal silicon dioxide, and magnesium stearate. Exact strength and excipients vary by manufacturer and market; refer to the specific product label for the precise composition.

Coversyl belongs to the angiotensin-converting enzyme (ACE) inhibitor class of medicines. It is a non-sulfhydryl ACE inhibitor formulated as the arginine salt of perindopril, which was developed to provide better long-term stability than the older erbumine salt while delivering an identical active drug (perindopril, converted in the body to its active metabolite perindoprilat).

By blocking the ACE enzyme, Coversyl reduces the formation of angiotensin II, a potent vasoconstrictor, and decreases aldosterone secretion. This lowers peripheral vascular resistance and blood pressure, reduces cardiac workload, and provides protective effects in patients with stable coronary artery disease and heart failure.

Coversyl belongs to the angiotensin-converting enzyme (ACE) inhibitor class of cardiovascular drugs, used primarily as antihypertensive and cardioprotective agents.

Perindopril Arginine is a prodrug. After oral administration it is rapidly absorbed and hydrolyzed in the liver to its active metabolite, perindoprilat, which is a potent and specific inhibitor of angiotensin-converting enzyme (ACE, kininase II).

• ACE inhibition prevents conversion of angiotensin I to the vasoconstrictor angiotensin II, and reduces breakdown of bradykinin.
• Reduced angiotensin II lowers systemic vascular resistance and blood pressure without causing significant reflex tachycardia.
• Reduced aldosterone secretion leads to modest natriuresis and helps limit potassium loss.
• In coronary artery disease, Perindopril Arginine is thought to improve endothelial function and reduce the risk of ischemic cardiac events.

Pharmacokinetics: Peak plasma concentration of perindopril occurs at about 1 hour, with a short elimination half-life of roughly 1-1.5 hours; the active metabolite perindoprilat has a longer effective half-life supporting once-daily dosing. Perindoprilat is eliminated mainly by the kidneys, so dose adjustment is required in renal impairment.

Coversyl tablets are taken by mouth, once daily, preferably in the morning before a meal, with a glass of water. Food may reduce the rate and extent of absorption of perindopril, so consistent timing relative to meals is recommended. Tablets should be swallowed whole and not crushed or chewed unless the specific product is scored and instructed otherwise by a physician or pharmacist.

The following interactions with Coversyl are clinically significant and well documented:

• Potassium-sparing diuretics, potassium supplements, and potassium-containing salt substitutes: increased risk of hyperkalemia; combine only with careful monitoring.
• Lithium: Coversyl can reduce lithium excretion, raising serum lithium levels and the risk of lithium toxicity; monitor lithium levels closely if co-administration cannot be avoided.
• NSAIDs (including selective COX-2 inhibitors) and high-dose aspirin: may reduce the antihypertensive effect of Coversyl and increase the risk of renal impairment, particularly in volume-depleted or elderly patients.
• Other antihypertensives and diuretics: additive blood-pressure-lowering effect; symptomatic hypotension can occur, especially with the first dose after diuretic use.
• Aliskiren: combined use is contraindicated in patients with diabetes or renal impairment, and not generally recommended in others, due to increased risk of hyperkalemia, hypotension, and renal impairment (dual RAAS blockade).
• Angiotensin receptor blockers (ARBs) or other RAAS-acting agents: dual blockade is generally not recommended for the same reasons as above.
• Antidiabetic agents (insulin, sulfonylureas): ACE inhibitors may enhance the blood-glucose-lowering effect, increasing hypoglycemia risk, especially in the first weeks of combined treatment.
• Gold injections (sodium aurothiomalate): rare nitritoid reactions (flushing, nausea, hypotension) have been reported.

Common: persistent dry cough, headache, dizziness, asthenia (weakness/fatigue), mood disturbances, sleep disturbances, and paresthesia.

Less common: taste disturbance (dysgeusia), nausea, abdominal pain, dyspepsia, skin rash, pruritus, and mild elevations in blood urea or creatinine.

Rare but serious: angioedema of the face, lips, tongue, glottis, and/or larynx (requires immediate discontinuation and emergency care - see Precautions and Warnings), hyperkalemia, neutropenia/agranulocytosis, hepatic dysfunction, and acute renal failure.

Patients should seek prompt medical attention for swelling of the face or throat, difficulty breathing or swallowing, or signs of infection (fever, sore throat) while taking Coversyl.

Pregnancy: Coversyl is contraindicated in pregnancy. Drugs that act on the renin-angiotensin system, including Coversyl, can cause fetal injury and death when used during the second and third trimesters, including oligohydramnios, fetal growth restriction, skull hypoplasia, renal failure, and death. If pregnancy is detected, Coversyl should be discontinued as soon as possible and, where appropriate, alternative antihypertensive therapy should be started under medical supervision.

Lactation: It is not known whether perindopril is excreted in human breast milk in clinically significant amounts. Because of the potential for adverse effects in a nursing infant, Coversyl should generally be avoided during breastfeeding; a physician should be consulted to weigh the benefits of breastfeeding against the potential risk, and an alternative agent with a better-established lactation safety profile should be considered.

Fetal toxicity (see also Contraindications and Pregnancy)

Coversyl must be discontinued immediately if pregnancy is detected, due to the risk of fetal injury and death.

Angioedema

Angioedema of the face, lips, tongue, glottis, and/or larynx can occur at any time during treatment with Coversyl, including after long-term use. If angioedema involves the tongue, glottis, or larynx, or causes airway obstruction, it is a medical emergency: discontinue Coversyl immediately and seek emergency treatment. Patients with a prior history of angioedema unrelated to ACE-inhibitor use may still be at increased risk.

Hypotension

Symptomatic hypotension can occur, particularly after the first dose, in volume- or salt-depleted patients (e.g. those on diuretics, a low-salt diet, dialysis, or with vomiting/diarrhea), or in patients with heart failure. Correct volume depletion, where possible, before starting Coversyl, and monitor closely after the first dose and after any dose increase.

Renal artery stenosis and renal function

In patients with bilateral renal artery stenosis, or stenosis in a single functioning kidney, Coversyl can precipitate acute renal failure. Renal function should be monitored during therapy, particularly in patients with pre-existing renal impairment, heart failure, or those on concomitant nephrotoxic drugs.

Hyperkalemia

Coversyl can raise serum potassium. Risk is increased in renal impairment, diabetes mellitus, and with concomitant use of potassium-sparing diuretics, potassium supplements, or potassium-containing salt substitutes. Periodic monitoring of serum potassium is recommended.

Neutropenia/agranulocytosis

Rare cases of neutropenia and agranulocytosis have been reported, more frequently in patients with collagen vascular disease, renal impairment, or those on concomitant immunosuppressants. Periodic blood count monitoring should be considered in at-risk patients.

Cough

A persistent, dry, non-productive cough is a recognized class effect of ACE inhibitors, including Coversyl, and typically resolves after discontinuation. It should be distinguished from other causes of cough before being attributed to the medicine.

Surgery/anesthesia

Coversyl may contribute to hypotension during major surgery or anesthesia; inform the anesthesia team that the patient is taking Coversyl.

Overdose with Coversyl most commonly causes symptomatic hypotension, which may present as dizziness, light-headedness, fainting, or shock; less commonly, electrolyte disturbances, renal impairment, hyperventilation, tachycardia, palpitations, bradycardia, anxiety, or cough have been reported.

If overdose is suspected, seek immediate medical attention or contact a poison control center/emergency services right away. Do not attempt to manage a suspected overdose at home. Treatment is generally supportive and may include intravenous volume expansion with normal saline and close monitoring of blood pressure, renal function, and electrolytes in a medical facility; perindopril/perindoprilat can be removed by hemodialysis in severe cases.

Store at room temperature (below 30°C), away from light and moisture. Keep out of reach of children.

Renal impairment

Dose reduction is required based on creatinine clearance (see Dosage and Administration). Coversyl should be used with caution and close monitoring of renal function and serum potassium in these patients.

Hepatic impairment

Formal dosing recommendations in hepatic impairment are limited; use Coversyl with caution and appropriate monitoring, as ACE inhibitors are hydrolyzed in the liver to their active metabolites.

Elderly

Start at the lower end of the dosing range (4 mg or less daily) and titrate slowly, as elderly patients may have reduced renal function and greater sensitivity to blood-pressure-lowering effects.

Pediatric patients

Safety and efficacy of Coversyl have not been established in children; its use in this population is not recommended.

Black patients

ACE inhibitors, including Coversyl, may be less effective at lowering blood pressure in Black patients when used as monotherapy, and this population may have a higher reported incidence of angioedema; combination therapy may be needed to achieve blood pressure goals.

Coversyl is generally used long-term as maintenance therapy for hypertension, stable coronary artery disease, or chronic heart failure. There is no fixed treatment duration; therapy is continued for as long as clinically indicated and tolerated, with periodic review of blood pressure control, renal function, and serum potassium by the prescribing physician. Coversyl should not be stopped abruptly without medical advice, except when required urgently (e.g. pregnancy detection or angioedema).

Angiotensin-Converting Enzyme (ACE) Inhibitor; Antihypertensive; Cardiovascular agent

Perindopril Arginine is hydrolyzed after absorption to its active metabolite, perindoprilat, which competitively inhibits angiotensin-converting enzyme (ACE). ACE normally converts angiotensin I to angiotensin II, a potent vasoconstrictor that also stimulates aldosterone release, and it degrades the vasodilator bradykinin. By inhibiting ACE, Perindopril Arginine reduces angiotensin II formation and increases bradykinin levels, resulting in vasodilation, reduced peripheral vascular resistance, lower aldosterone secretion, and a fall in blood pressure, along with reduced cardiac afterload.

D

The safety and efficacy of Coversyl have not been established in pediatric patients. Coversyl is not recommended for use in children and adolescents, and it is contraindicated for the specific purpose of managing hypertension in children given the lack of adequate pediatric data. If treatment of hypertension is needed in a child, alternative agents with established pediatric safety data should be considered under specialist supervision.