Pendoril Plus0.625 mg+2 mg

Pendoril Plus is a fixed-dose combination of a thiazide-like diuretic (indapamide) and an angiotensin-converting enzyme (ACE) inhibitor (perindopril arginine), indicated for the treatment of essential hypertension.

Established Uses

• Hypertension not adequately controlled on monotherapy: Pendoril Plus is indicated in patients whose blood pressure is not adequately controlled with either indapamide or perindopril arginine alone.
• Substitution (replacement) therapy: Pendoril Plus may be used as substitution therapy in patients already adequately controlled on the individual components (perindopril arginine and indapamide) given concurrently at the same doses, for the convenience of a single daily tablet.

Not First-Line Initial Therapy

Pendoril Plus is generally not used as first-line initial therapy for hypertension; it is intended for patients who require combination treatment after the individual components have been trialed or titrated separately, consistent with standard hypertension management guidelines.

Each tablet of Indapamide + Perindopril Arginine contains two active ingredients:

• Perindopril Arginine — an angiotensin-converting enzyme (ACE) inhibitor, commonly available in strengths such as 2.5 mg, 5 mg, or 10 mg (equivalent to perindopril erbumine 2 mg, 4 mg, or 8 mg respectively).
• Indapamide — a thiazide-like (sulfonamide-derived) diuretic, commonly available in strengths such as 0.625 mg or 1.25 mg.

Typical fixed-dose combinations of Indapamide + Perindopril Arginine pair matching doses of each component (for example, perindopril arginine 2.5 mg with indapamide 0.625 mg, or perindopril arginine 5 mg with indapamide 1.25 mg); exact strengths and inactive ingredients vary by manufacturer and market.

Pendoril Plus combines two complementary antihypertensive mechanisms in a single tablet: a thiazide-like diuretic and an ACE inhibitor. This combination is used when blood pressure control is insufficient with a single antihypertensive agent, or as convenient once-daily substitution therapy for patients already stable on the two individual medicines.

Perindopril arginine is the arginine salt form of perindopril, an ACE inhibitor prodrug that is hydrolyzed in the liver to its active metabolite, perindoprilat. Indapamide is a sulfonamide-derived diuretic with mild diuretic and vasodilatory antihypertensive properties. Together, the components of Pendoril Plus produce additive blood-pressure-lowering effects, while their opposing influences on serum potassium (indapamide can lower it, perindopril can raise it) tend to partially offset one another, though electrolyte monitoring is still required.

Pendoril Plus belongs to the therapeutic class of fixed-dose combination antihypertensives, specifically combining:

• A thiazide-like diuretic (indapamide), and
• An Angiotensin-Converting Enzyme (ACE) inhibitor (perindopril arginine).

This class is used in the management of hypertension, and Pendoril Plus is classified under cardiovascular/antihypertensive combination therapy.

Indapamide + Perindopril Arginine exerts its antihypertensive effect through two complementary mechanisms:

Perindopril Arginine (ACE Inhibitor Component)

Perindopril is a prodrug hydrolyzed to perindoprilat, which inhibits angiotensin-converting enzyme, blocking conversion of angiotensin I to angiotensin II. This reduces angiotensin II-mediated vasoconstriction and aldosterone secretion, lowers peripheral vascular resistance, and reduces blood pressure without significant reflex tachycardia. ACE inhibition also reduces bradykinin degradation, contributing to vasodilation (and to the characteristic dry cough side effect).

Indapamide (Thiazide-like Diuretic Component)

Indapamide inhibits sodium reabsorption in the cortical diluting segment of the distal renal tubule, increasing excretion of sodium, chloride, and water. At antihypertensive doses, its blood-pressure-lowering effect is thought to result predominantly from reduced peripheral vascular resistance (a direct vasodilatory effect) rather than diuresis alone.

The combined mechanism of Indapamide + Perindopril Arginine produces greater blood pressure reduction than either component alone, with onset of antihypertensive effect typically within days to a few weeks and maximal effect with continued regular use.

Pendoril Plus should be taken by mouth, once daily, preferably in the morning and before a meal, with a glass of water. The tablet should be swallowed whole and taken at approximately the same time each day to maintain consistent blood pressure control. It should not be taken with excessive alcohol, and potassium-containing salt substitutes should be avoided unless directed by a physician.

Pendoril Plus has several clinically significant drug interactions:

• Potassium-sparing diuretics, potassium supplements, and salt substitutes: Concomitant use with Pendoril Plus increases the risk of hyperkalemia due to the ACE inhibitor component; this combination generally should be avoided unless potassium is closely monitored.
• Lithium: Pendoril Plus can reduce renal lithium clearance, leading to increased serum lithium levels and toxicity; concurrent use requires careful monitoring of lithium levels.
• NSAIDs (including selective COX-2 inhibitors): May reduce the antihypertensive effect of Pendoril Plus and, particularly in volume-depleted or elderly patients, increase the risk of acute renal impairment (the "triple whammy" effect when a diuretic, an ACE inhibitor, and an NSAID are combined).
• Other antihypertensive agents and vasodilators: Additive blood-pressure-lowering effect with Pendoril Plus, which may require dose adjustment.
• Aliskiren: Concomitant use with Pendoril Plus is contraindicated in patients with diabetes mellitus or renal impairment, due to increased risk of hyperkalemia, hypotension, and renal impairment; use in other patients should generally be avoided.
• Angiotensin receptor blockers (ARBs) or other renin-angiotensin system agents: Dual blockade with Pendoril Plus is not recommended due to increased risk of hypotension, hyperkalemia, and renal impairment.
• Sacubitril/valsartan: Must not be co-administered with Pendoril Plus; an ACE inhibitor must not be started within 36 hours of the last dose of sacubitril/valsartan, due to the risk of angioedema.
• Gliptins (DPP-4 inhibitors, e.g., vildagliptin) and mTOR inhibitors (e.g., sirolimus, everolimus): May increase the risk of angioedema when combined with the ACE inhibitor component of Pendoril Plus.
• Drugs that can prolong the QT interval or predispose to torsades de pointes: Combined with the hypokalemia risk from the indapamide component of Pendoril Plus, caution and electrolyte monitoring are advised.

Pendoril Plus is generally well tolerated, but may cause the following adverse effects:

Common

• Dry, persistent cough (a characteristic class effect of the ACE inhibitor component)
• Dizziness, headache
• Hypotension, including symptomatic orthostatic hypotension (especially after the first dose or a dose increase)
• Asthenia (weakness/fatigue)
• Paresthesia
• Gastrointestinal disturbances (nausea, constipation, abdominal pain, dry mouth)
• Muscle cramps
• Electrolyte disturbances: hypokalemia, hyponatremia (from the indapamide component), or hyperkalemia (from the perindopril arginine component)

Less Common / Serious

• Angioedema (rare but potentially life-threatening; see Precautions and Warnings)
• Renal impairment or increase in serum creatinine
• Elevated blood uric acid, precipitation of gout
• Rash and other hypersensitivity skin reactions; rare photosensitivity reactions
• Blood dyscrasias (leukopenia, neutropenia, agranulocytosis, thrombocytopenia) — rare
• Impaired glucose tolerance

Patients taking Pendoril Plus who experience swelling of the face, lips, tongue, or throat, or difficulty breathing, should seek emergency medical care immediately.

Pregnancy: Pendoril Plus is contraindicated during pregnancy. ACE inhibitors, including the perindopril arginine component, can cause injury and death to the developing fetus when used during the second and third trimesters, including oligohydramnios, fetal renal failure, hypoplasia of the fetal skull, and neonatal death; first-trimester exposure has also been associated with an increased risk of major congenital malformations. When pregnancy is detected, Pendoril Plus should be discontinued as soon as possible and the patient switched to an antihypertensive considered safer in pregnancy, unless continued use is considered lifesaving.

Lactation: It is not established whether perindopril or indapamide are excreted into human breast milk in clinically significant amounts, but thiazide-type/thiazide-like diuretics are known to pass into breast milk and can suppress lactation. Because of the potential for adverse effects in a nursing infant, a decision should be made whether to discontinue nursing or discontinue Pendoril Plus, taking into account the importance of the drug to the mother; use only if clearly needed and if potential benefit justifies potential risk, and only under close medical supervision.

Boxed Warnings

• Fetal Toxicity: Pendoril Plus can cause injury and death to the developing fetus when used during pregnancy. Discontinue as soon as possible once pregnancy is detected (see Pregnancy and Lactation).
• Angioedema: The ACE inhibitor component of Pendoril Plus can cause angioedema of the face, lips, tongue, glottis, and/or larynx, which can occur at any time during treatment and can be life-threatening if it involves the airway. Angioedema is more common with the first dose or after a dose increase, and patients with a history of ACE-inhibitor-associated angioedema are at increased risk; Pendoril Plus must be discontinued immediately and emergency treatment given if angioedema occurs.

Other Precautions

• Hypotension: Symptomatic hypotension may occur, particularly in volume- or salt-depleted patients, after the first dose or a dose increase; correct volume depletion before starting Pendoril Plus where possible.
• Renal artery stenosis: In patients with bilateral renal artery stenosis (or stenosis in a solitary kidney), Pendoril Plus may precipitate acute renal failure; renal function should be monitored closely.
• Hyperkalemia: Risk factors include renal impairment, diabetes, concomitant potassium-sparing agents, and use of potassium supplements/salt substitutes; monitor serum potassium periodically during treatment with Pendoril Plus.
• Electrolyte and fluid balance: Periodic monitoring of serum sodium, potassium, and renal function is recommended, particularly at initiation and after dose changes, and in patients at risk of electrolyte disturbances (elderly patients, diuretic co-therapy, vomiting/diarrhea).
• Renal impairment: Use with caution and adjust dose in mild-to-moderate impairment; monitor renal function.
• Hepatic impairment: Use with caution; rarely, ACE inhibitors have been associated with a syndrome starting with cholestatic jaundice and progressing to fulminant hepatic necrosis.
• Cough: A persistent dry cough is a known class effect and may require discontinuation if troublesome.
• Surgery/anesthesia: Pendoril Plus may increase the risk of hypotension during major surgery or anesthesia with hypotensive agents; inform the anesthesiologist/surgeon of use.
• Race: ACE inhibitors, including the perindopril arginine component of Pendoril Plus, may cause a higher rate of angioedema in Black patients compared with non-Black patients.

Overdose with Pendoril Plus most commonly presents as marked hypotension, which may be accompanied by dizziness, drowsiness, electrolyte disturbances (hyponatremia, hypokalemia), acute renal failure, and, rarely, bradycardia or shock.

There is no specific antidote. Anyone who has taken more than the prescribed dose of Pendoril Plus, or who shows signs of overdose, should seek immediate medical attention or contact emergency services/a poison control center. Management in a hospital setting is generally supportive and may include intravenous volume/saline expansion for hypotension, close monitoring of vital signs, renal function, and electrolytes; gastric decontamination may be considered if presenting soon after ingestion, under medical supervision.

Store Pendoril Plus at room temperature (below 30°C), protected from light and moisture. Keep the medicine in its original packaging until the time of use. Keep out of reach of children.

Renal Impairment

Use Pendoril Plus with caution in patients with mild-to-moderate renal impairment, with dose adjustment and monitoring of renal function and electrolytes; it is contraindicated in severe renal impairment (see Contraindications).

Hepatic Impairment

Use Pendoril Plus with caution in mild-to-moderate hepatic impairment; it is contraindicated in severe hepatic impairment or hepatic encephalopathy.

Elderly

Elderly patients should be started on the lowest available strength of Pendoril Plus, with careful blood pressure and renal function monitoring, given increased susceptibility to hypotension and age-related decline in renal function.

Race

ACE inhibitors, including the perindopril arginine component of Pendoril Plus, may be less effective in lowering blood pressure and may carry a higher risk of angioedema in Black patients compared with other populations.

Pediatric Population

Safety and efficacy of Pendoril Plus in children and adolescents under 18 years have not been established; its use is not recommended in this population (see Pediatric Use).

Pendoril Plus is intended for long-term, ongoing use in the management of chronic hypertension. Treatment should continue for as long as clinically indicated to maintain blood pressure control, with periodic clinical review, blood pressure measurement, and monitoring of renal function and electrolytes. Pendoril Plus should not be stopped abruptly without medical advice, as this may lead to a rebound rise in blood pressure.

Indapamide + Perindopril Arginine is a fixed-dose combination of a thiazide-like diuretic (indapamide) and an angiotensin-converting enzyme (ACE) inhibitor (perindopril arginine), classified within the broader drug class of antihypertensive combination agents.

Indapamide + Perindopril Arginine lowers blood pressure through two complementary and additive mechanisms. The perindopril arginine component inhibits angiotensin-converting enzyme, preventing conversion of angiotensin I to the potent vasoconstrictor angiotensin II and reducing aldosterone secretion, thereby lowering peripheral vascular resistance. The indapamide component inhibits sodium and chloride reabsorption in the distal renal tubule, promoting natriuresis and exerting a direct vasodilatory effect on arterial smooth muscle. Together, the two mechanisms in Indapamide + Perindopril Arginine provide greater antihypertensive efficacy than either agent alone.

D

The safety and efficacy of Pendoril Plus in pediatric patients (under 18 years of age) have not been established. Pendoril Plus is therefore not recommended for use in children and adolescents, and should only be considered in this population under specialist supervision if no suitable alternative is available and the potential benefit is judged to outweigh the risk.