Perindopril + Indapamide

Pharmacologic Category

Angiotensin-Converting Enzyme (ACE) Inhibitor; Antihypertensive; Diuretic, Thiazide-Related

Dosing: Adult

Hypertension: Oral: Note: Dosage must be individualized.

Arcosyl products: Initial: Perindopril arginine 2.5 mg/indapamide 0.625 mg once daily; may adjust dose based on blood pressure response to perindopril arginine 5 mg/indapamide 1.25 mg once daily. Maintenance dose: Perindopril arginine 2.5 to 10 mg/indapamide 0.625 to 2.5 mg once daily.

Coversyl products: Initial: Perindopril erbumine 2 mg/indapamide 0.625 mg once daily; may adjust dose based on blood pressure response to perindopril erbumine 4 to 8 mg/indapamide 1.25 mg once daily. Maintenance dose: Perindopril erbumine 2 to 8 mg/indapamide 0.625 to 2.5 mg once daily.

Dosing: Geriatric

Refer to adult dosing; use with caution.

Dosing: Renal Impairment: Adult

GFR ≥60 mL/minute/1.73 m2: No dosage adjustment necessary.

GFR 30 to 59 mL/minute/1.73 m2: There are no specific dosage recommendations provided in the manufacturer's labeling; use lower doses with caution (perindoprilat exposure may be increased). Use of perindopril erbumine 8 mg/indapamide 1.25 mg, perindopril erbumine 8 mg/indapamide 2.5 mg, and perindopril arginine 10 mg/indapamide 2.5 mg is contraindicated.

GFR <30 mL/minute/1.73 m2: Use is contraindicated.

Hemodialysis: Dialyzable.

Dosing: Hepatic Impairment: Adult

There are no dosage adjustments provided in the manufacturer's labeling; use with caution (perindoprilat systemic exposure is increased in hepatic impairment). Use is contraindicated in patients with severe impairment or hepatic encephalopathy.

Calculations

• Glomerular Filtration Rate by Abbreviated MDRD
• Glomerular Filtration Rate by Abbreviated MDRD (SI units)
• Glomerular Filtration Rate by MDRD
• Glomerular Filtration Rate by MDRD (IDMS-Traceable SCr)
• Glomerular Filtration Rate by MDRD (SI units)
• Glomerular Filtration Rate Estimate in African Americans by AASK Equation

Use: Labeled Indications

Note: Not approved in the US.

Hypertension: Management of mild to moderate hypertension. Note: Arcosyl Plus LD or Coversyl Plus LD may be used as initial treatment; Arcosyl Plus, Coversyl Plus, and Coversyl Plus HD are not indicated for initial treatment.

Clinical Practice Guidelines

See individual agents.

Administration: Oral

Administer prior to a meal in the morning.

Storage/Stability

Store at 15°C to 30°C (59°F to 86°F).

Medication Safety Issues

Safety concerns:

Geriatric Patients: High-Risk Medication:

Contraindications

Hypersensitivity to perindopril, indapamide, any other component of the formulation, or sulfonamide-derived drugs; hereditary/idiopathic angioedema or history of angioedema related to previous treatment with an ACE inhibitor; hypokalemia; severe hepatic impairment; hepatic encephalopathy; pregnant women, women planning a pregnancy, and women of reproductive potential not using adequate contraception; breastfeeding; moderate renal impairment (GFR 30 to 59 mL/minute/1.73 m2) (Arcosyl Plus, Coversyl Plus, and Coversyl Plus HD only); severe renal impairment (GFR <30 mL/minute/1.73 m2); concomitant use with aliskiren-containing drugs in patients with diabetes or moderate to severe renal impairment (GFR <60 mL/minute/1.73 m2); concomitant use with antiarrhythmic agents causing torsades de pointes; concomitant use with sacubitril/valsartan; hereditary problems of galactose intolerance, glucose-galactose malabsorption, or the Lapp lactase deficiency; extracorporeal treatments leading to contact of blood with negatively charged surfaces; unilateral or bilateral renal artery stenosis

Documentation of allergenic cross-reactivity for ACE inhibitors is limited. However, because of similarities in chemical structure and/or pharmacologic actions, the possibility of cross-sensitivity cannot be ruled out with certainty.

Note: Although the product labeling states this medication is contraindicated with other sulfonamide-containing drug classes, the scientific basis of this statement has been challenged. See “Warnings/Precautions” for more detail.

Warnings/Precautions

Concerns related to adverse effects:

• Angioedema: At any time during treatment (especially following first dose), angioedema may occur rarely with ACE inhibitors; it may involve the head and neck (potentially compromising airway) or the intestine (presenting with abdominal pain). Black patients and patients with idiopathic or hereditary angioedema or previous angioedema associated with ACE inhibitor therapy may be at an increased risk. Risk may also be increased with concomitant use of mTOR inhibitor (eg, everolimus), dipeptidyl peptidase 4 inhibitors (eg, sitagliptin), or neprilysin inhibitor (eg, sacubitril) therapy. Prolonged frequent monitoring may be required especially if tongue, glottis, or larynx are involved as they are associated with airway obstruction. Patients with a history of airway surgery may have a higher risk of airway obstruction. Aggressive early and appropriate management is critical. Use in patients with idiopathic or hereditary angioedema or previous angioedema associated with ACE inhibitor therapy is contraindicated.

• Cholestatic jaundice: A rare toxicity associated with ACE inhibitors includes cholestatic jaundice, which may progress to fulminant hepatic necrosis (some fatal); discontinue if marked elevation of hepatic transaminases or jaundice occurs. Consider discontinuing therapy when appropriate if symptoms of hepatic impairment (eg, fever, malaise, muscle pain, rash) present within the first weeks to months of therapy.

• CNS depression: Perindopril may impair physical or mental abilities; patients must be cautioned about performing tasks that require mental alertness (eg, operating machinery or driving).

• Cough: An ACE inhibitor cough is a dry, hacking, nonproductive one that usually occurs within the first few months of treatment and should generally resolve within 1 to 4 weeks after discontinuation of the ACE inhibitor. Other causes of cough should be considered (eg, pulmonary congestion in patients with heart failure) and excluded prior to discontinuation.

• Dermatologic reactions: Maculopapular pruritic rashes have been reported with ACE inhibitors which may or may not recur when switched to another ACE inhibitor (cross reactivity has been reported). Severe reactions (eg, lichenoid eruptions, psoriasis, pemphigus like rash, rosacea, Stevens-Johnson syndrome) rarely have been observed. Severe dermatological effects have also been reported with indapamide; in most cases resolution occurred within 2 weeks of indapamide discontinuation.

• Dysgeusia: Suppression of taste or a metallic sensation in the mouth has been reported commonly with high doses of ACE inhibitors; usually occurs in the first weeks of treatment and may disappear within 1 to 3 months.

• Electrolyte disturbances: Hyperkalemia may occur with ACE inhibitors; risk factors include renal impairment, diabetes mellitus, elderly patients, intercurrent events (in particular, dehydration), acute cardiac decompensation, metabolic acidosis, and concomitant use of potassium-sparing diuretics, potassium supplements, potassium-containing salts, and/or any drug associated with increases in serum potassium. Use cautiously, if at all, with these agents and monitor potassium closely. Indapamide may cause hypokalemia, hypochloremia, hyponatremia, hypophosphatemia, and/or hypercalcemia. Use is contraindicated in patients with hypokalemia. Patients with a long QT interval (congenital or iatrogenic) are also at risk of hypokalemia.

• Hematologic effects: Another ACE inhibitor, captopril, has been associated with neutropenia with myeloid hypoplasia and agranulocytosis; anemia and thrombocytopenia have also occurred. Patients with renal impairment are at high risk of developing neutropenia. Patients with both renal impairment and collagen vascular disease (eg, systemic lupus erythematosus) are at an even higher risk of developing neutropenia. Periodically monitor CBC with differential in these patients.

• Hypersensitivity reactions: Anaphylactic/anaphylactoid reactions can occur with ACE inhibitors. Severe anaphylactoid reactions may be seen during hemodialysis with high-flux dialysis membranes (eg, polyacrylonitrile [PAN]), and rarely, during low density lipoprotein apheresis with dextran sulfate cellulose. Rare cases of anaphylactoid reactions have been reported in patients undergoing sensitization treatment with hymenoptera (bee, wasp) venom while receiving ACE inhibitors.

• Hypotension/syncope: Symptomatic hypotension with or without syncope can occur with ACE inhibitors (usually with the first several doses); effects are most often observed in volume-depleted patients; correct volume depletion prior to initiation; close monitoring of patient is required especially with initial dosing and dosing increases; blood pressure must be lowered at a rate appropriate for the patient's clinical condition. Although dose reduction may be necessary, hypotension is not a reason for discontinuation of future ACE inhibitor use especially in patients with heart failure where a reduction in systolic blood pressure is a desirable observation.

• Photosensitivity: Photosensitization may occur.

• Proteinuria: Total urinary proteins <1 g/day have been reported (<1%) with ACE inhibitors; nephrotic syndrome occurred in about one-fifth of proteinuric patients. In most cases, proteinuria subsided or cleared within six months (whether or not ACE inhibitor was continued).

• Renal function deterioration: May be associated with deterioration of renal function and/or increases in BUN and serum creatinine, particularly in patients with low renal blood flow (eg, renal artery stenosis, heart failure) whose GFR is dependent on efferent arteriolar vasoconstriction by angiotensin II; deterioration may result in oliguria, acute renal failure, and progressive azotemia. Small increases in serum creatinine may occur following initiation; consider discontinuation only in patients with progressive and/or significant deterioration in renal function (Bakris 2000).

• Sulfonamide (“sulfa”) allergy: The FDA-approved product labeling for many medications containing a sulfonamide chemical group includes a broad contraindication in patients with a prior allergic reaction to sulfonamides. There is a potential for cross-reactivity between members of a specific class (eg, two antibiotic sulfonamides). However, concerns for cross-reactivity have previously extended to all compounds containing the sulfonamide structure (SO2NH2). An expanded understanding of allergic mechanisms indicates cross-reactivity between antibiotic sulfonamides and nonantibiotic sulfonamides may not occur or at the very least this potential is extremely low (Brackett 2004; Johnson 2005; Slatore 2004; Tornero 2004). In particular, mechanisms of cross-reaction due to antibody production (anaphylaxis) are unlikely to occur with nonantibiotic sulfonamides. T-cell-mediated (type IV) reactions (eg, maculopapular rash) are less well understood and it is not possible to completely exclude this potential based on current insights. In cases where prior reactions were severe (Stevens-Johnson syndrome/toxic epidermal necrolysis), some clinicians choose to avoid exposure to these classes.

Disease-related concerns:

• Aldosteronism: Use is not recommended in patients with primary aldosteronism; these patients generally will not respond to anti-hypertensive drugs acting through inhibition of the renin-angiotensin system.

• Aortic stenosis: Use perindopril with caution in patients with aortic stenosis or mitral valve; may reduce coronary perfusion resulting in ischemia.

• Bariatric surgery: Dehydration: Avoid diuretics in the immediate postoperative period after bariatric surgery; electrolyte disturbances and dehydration may occur. Diuretics may be resumed, if indicated, once oral fluid intake goals are met (Ziegler 2009).

• Cardiovascular disease: Initiation of therapy in patients with ischemic heart disease, heart failure, or cerebrovascular disease warrants close observation due to the potential consequences posed by falling blood pressure (eg, MI, stroke). Fluid replacement if needed may restore blood pressure; therapy may then be resumed. Discontinue therapy in patients whose hypotension recurs. Initial perindopril dose reduction recommended for patients with heart failure; clearance of active metabolite (perindoprilat) is reduced in these patients. Use is not recommended in renovascular hypertension or heart failure.

• Collagen vascular disease: Use perindopril with caution in patients with collagen vascular disease especially with concomitant renal impairment; may be at increased risk for hematologic toxicity. Indapamide may exacerbate or activate systemic lupus erythematosus (SLE).

• Diabetes: Use with caution in patients with prediabetes or diabetes mellitus; may see a change in glucose control.

• Gout: Hyperuricemia has been observed with indapamide use. In certain patients with a history of gout, a familial predisposition to gout, or chronic renal failure, gout can be precipitated by indapamide.

• Hepatic impairment: Use with caution in patients with hepatic impairment; elevations of liver enzymes and/or serum bilirubin have been reported with perindopril. Prior to initiation of therapy obtain baseline transaminase and bilirubin levels. In cirrhosis, avoid electrolyte and acid/base imbalances that might lead to hepatic encephalopathy. Contraindicated in patients with severe hepatic impairment or hepatic encephalopathy.

• Hypertrophic cardiomyopathy (HCM) with outflow tract obstruction: Use with caution in patients with HCM and outflow tract obstruction since reduction in afterload may worsen symptoms associated with this condition (ACCF/AHA [Gersh 2011]).

• Renal artery stenosis: Use is contraindicated in patients with unilateral or bilateral renal artery stenosis.

• Renal impairment: Use with caution in patients with renal impairment; dosage adjustment may be needed. Avoid rapid dosage escalation which may lead to further renal impairment. Patients with renal impairment may be at increased risk for hematologic toxicity. Use may be contraindicated in moderate and/or severe renal impairment. Refer to contraindications.

Concurrent drug therapy issues:

• Drug-drug interactions: Potentially significant interactions may exist, requiring dose or frequency adjustment, additional monitoring, and/or selection of alternative therapy. Consult drug interactions database for more detailed information.

Special populations:

• Black patients: ACE inhibitors' effectiveness is less in black patients than in non-blacks. In addition, ACE inhibitors cause a higher rate of angioedema in black than in non-black patients.

• Pregnancy: [Canadian Boxed Warning]: Drugs that act on the renin-angiotensin system can cause injury and death to the developing fetus. Discontinue as soon as possible once pregnancy is detected.

Dosage form specific issues:

• Lactose: Some formulations may contain lactose; use in patients with Lapp lactose deficiency, glucose-galactose malabsorption, or hereditary problems of galactose intolerance is contraindicated.

Other warnings/precautions:

• Surgery: In patients on chronic ACE inhibitor therapy, intraoperative hypotension may occur with induction and maintenance of general anesthesia; use with caution before, during, or immediately after major surgery. Cardiopulmonary bypass, intraoperative blood loss, or vasodilating anesthesia increases endogenous renin release. Use of ACE inhibitors perioperatively will blunt angiotensin II formation and may result in hypotension. Discontinuation of therapy prior to surgery is controversial. If continued preoperatively, avoidance of hypotensive agents during surgery is prudent (Hillis 2011).

Geriatric Considerations

See individual agents. Combination products are not recommended as first-line treatment. Use only if doses of individual agents correspond to the combination available.

Pregnancy Considerations

[Canadian Boxed Warning]: Drugs that act directly on the renin-angiotensin system can cause injury and death to the developing fetus. Discontinue as soon as possible once pregnancy is detected. Also see individual agents.

Breast-Feeding Considerations

It is not known if perindopril or indapamide are present in breast milk. Use is contraindicated in breastfeeding women. Also see individual agents.

Lexicomp Pregnancy & Lactation, In-Depth

• Perindopril

Briggs' Drugs in Pregnancy & Lactation

• Indapamide
• Perindopril

Adverse Reactions

Also see individual agents.

1% to 10%:

Central nervous system: Headache (8%), dizziness (1% to 2%)

Endocrine & metabolic: Hypokalemia (2% to 7%), hyperkalemia (1%)

Gastrointestinal: Nausea and vomiting (2%), dyspepsia (1% to 2%)

Neuromuscular & skeletal: Arthralgia (1%)

Renal: Increased blood urea nitrogen (4%)

Respiratory: Cough (3% to 6%), upper respiratory tract infection (2%), bronchitis (1%)

Frequency not defined:

Cardiovascular: Transient ischemic attacks

Central nervous system: Loss of consciousness

Renal: Renal colic

<1%, postmarketing, and/or case reports: Abscess (periapical), abdominal pain, acute renal failure, acute rhinitis, agranulocytosis, allergic rhinitis, altered salivation, angina pectoris, angioedema, anorexia, anxiety, aplastic anemia, arthritis (periarthritis of shoulder), asthma, atrial fibrillation, back pain, benign prostatic hyperplasia, bloating, blurred vision, brachial plexopathy, bradycardia, bronchospasm, bullous rash, cardiac arrhythmia, cataract, cerebrovascular accident, chest pain, cholestatic hepatitis, colitis, confusion, conjunctivitis, constipation, cystitis, decreased hemoglobin, dehydration, depression, dermatitis, diaphoresis, diarrhea, disturbed sleep, drowsiness, dysgeusia, dyspnea, dysuria, ECG abnormality, eczema, edema, eosinophilia, eosinophilic pneumonitis, epigastric pain, epistaxis, erythema multiforme, erythroderma, esophagitis, exacerbation of psoriasis, exfoliative dermatitis, falling, fever, flushing, fungal skin infection, gastritis, gastroenteritis (infective and non-infective), gout, hemolytic anemia, hepatic cytolysis, hepatitis, herpes zoster, hyperbilirubinemia, hypercalcemia, hyperosmolar coma, hypersensitivity reaction, hypertension, hyponatremia, hypotension, impacted cerumen, impotence, increased liver enzymes, increased serum creatinine, increased serum glucose, increased serum transaminases, increased uric acid, interstitial nephritis, intestinal infection, laryngitis, leukopenia, ligament disorder, limb pain, localized infection (skin and subcutaneous tissues), loss of libido, lower back pain, maculopapular rash, malaise, male genital disease (penis disorders), metabolic alkalosis, migraine, mood disorder, muscle cramps, myalgia, myocardial infarction, myopathy, myopia (acute), neck pain, neoplasm (female genital organs), nervousness, neutropenia, optic neuritis, orthostatic hypotension, osteoarthrosis (local), otitis media, pallor, palpitations, pancreatitis, paresthesia, pemphigoid, pemphigus, peripheral edema, pharyngeal disease, pharyngitis, polyuria, prolonged QT interval on ECG, pruritus, purpura, Raynaud phenomenon, reflux esophagitis, renal insufficiency, respiratory insufficiency, rhabdomyolysis, rhinitis, sciatica, sensory disturbance (skin), SIADH, sinusitis, skin photosensitivity, skin rash, sprain (ankle, knee, leg), Stevens-Johnson syndrome, syncope, systemic lupus erythematosus (aggravation), tachycardia, tendon disease (enthesopathy of elbow region), tetany, thrombocytopenia, tinnitus, tonsillitis, torsades de pointes, toxic epidermal necrolysis, tracheitis, uremia, urinary frequency, urinary incontinence, urinary tract infection, vasculitis, venous insufficiency, ventricular tachycardia, vertigo, visual disturbance, xerostomia, weakness, weight loss

Allergy and Idiosyncratic Reactions

• ACE Inhibitor Allergy/Hypersensitivity
• Thiazide/Thiazide-Related Diuretic Allergy

Toxicology

• Angiotensin-Converting Enzyme (ACE) Inhibitors

Metabolism/Transport Effects

None known.

Drug Interactions Open Interactions

Ajmaline: Sulfonamides may enhance the adverse/toxic effect of Ajmaline. Specifically, the risk for cholestasis may be increased. Risk C: Monitor therapy

Alcohol (Ethyl): May enhance the orthostatic hypotensive effect of Thiazide and Thiazide-Like Diuretics. Risk C: Monitor therapy

Alfuzosin: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy

Aliskiren: May enhance the hyperkalemic effect of Angiotensin-Converting Enzyme Inhibitors. Aliskiren may enhance the hypotensive effect of Angiotensin-Converting Enzyme Inhibitors. Aliskiren may enhance the nephrotoxic effect of Angiotensin-Converting Enzyme Inhibitors. Management: Aliskiren use with ACEIs or ARBs in patients with diabetes is contraindicated. Combined use in other patients should be avoided, particularly when CrCl is less than 60 mL/min. If combined, monitor potassium, creatinine, and blood pressure closely. Risk D: Consider therapy modification

Allopurinol: Angiotensin-Converting Enzyme Inhibitors may enhance the potential for allergic or hypersensitivity reactions to Allopurinol. Risk C: Monitor therapy

Allopurinol: Thiazide and Thiazide-Like Diuretics may enhance the potential for allergic or hypersensitivity reactions to Allopurinol. Thiazide and Thiazide-Like Diuretics may increase the serum concentration of Allopurinol. Specifically, Thiazide Diuretics may increase the concentration of Oxypurinol, an active metabolite of Allopurinol. Risk C: Monitor therapy

Alteplase: Angiotensin-Converting Enzyme Inhibitors may enhance the adverse/toxic effect of Alteplase. Specifically, the risk for angioedema may be increased. Risk C: Monitor therapy

Amifostine: Blood Pressure Lowering Agents may enhance the hypotensive effect of Amifostine. Management: When amifostine is used at chemotherapy doses, blood pressure lowering medications should be withheld for 24 hours prior to amifostine administration. If blood pressure lowering therapy cannot be withheld, amifostine should not be administered. Risk D: Consider therapy modification

Aminolevulinic Acid (Systemic): Photosensitizing Agents may enhance the photosensitizing effect of Aminolevulinic Acid (Systemic). Risk X: Avoid combination

Aminolevulinic Acid (Topical): Photosensitizing Agents may enhance the photosensitizing effect of Aminolevulinic Acid (Topical). Risk C: Monitor therapy

Amphetamines: May diminish the antihypertensive effect of Antihypertensive Agents. Risk C: Monitor therapy

Angiotensin II: Angiotensin-Converting Enzyme Inhibitors may enhance the therapeutic effect of Angiotensin II. Risk C: Monitor therapy

Angiotensin II Receptor Blockers: May enhance the adverse/toxic effect of Angiotensin-Converting Enzyme Inhibitors. Angiotensin II Receptor Blockers may increase the serum concentration of Angiotensin-Converting Enzyme Inhibitors. Management: In US labeling, use of telmisartan and ramipril is not recommended. It is not clear if any other combination of an ACE inhibitor and an ARB would be any safer. Consider alternatives to the combination when possible. Risk D: Consider therapy modification

Angiotensin-Converting Enzyme Inhibitors: Thiazide and Thiazide-Like Diuretics may enhance the hypotensive effect of Angiotensin-Converting Enzyme Inhibitors. Thiazide and Thiazide-Like Diuretics may enhance the nephrotoxic effect of Angiotensin-Converting Enzyme Inhibitors. Risk C: Monitor therapy

Anticholinergic Agents: May increase the serum concentration of Thiazide and Thiazide-Like Diuretics. Risk C: Monitor therapy

Antidiabetic Agents: Thiazide and Thiazide-Like Diuretics may diminish the therapeutic effect of Antidiabetic Agents. Risk C: Monitor therapy

Antidiabetic Agents: Hyperglycemia-Associated Agents may diminish the therapeutic effect of Antidiabetic Agents. Risk C: Monitor therapy

Antipsychotic Agents (Second Generation [Atypical]): Blood Pressure Lowering Agents may enhance the hypotensive effect of Antipsychotic Agents (Second Generation [Atypical]). Risk C: Monitor therapy

Aprotinin: May diminish the antihypertensive effect of Angiotensin-Converting Enzyme Inhibitors. Risk C: Monitor therapy

AzaTHIOprine: Angiotensin-Converting Enzyme Inhibitors may enhance the myelosuppressive effect of AzaTHIOprine. Risk C: Monitor therapy

Barbiturates: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy

Benperidol: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy

Beta2-Agonists: May enhance the hypokalemic effect of Thiazide and Thiazide-Like Diuretics. Risk C: Monitor therapy

Bile Acid Sequestrants: May decrease the absorption of Thiazide and Thiazide-Like Diuretics. The diuretic response is likewise decreased. Management: Consider separating administraton of bile acid sequestrants and thiazide diuretics by at least 4 hours. Monitor for decreased therapeutic effects of thiazide diuretics if coadministered with a bile acid sequestrant. Risk D: Consider therapy modification

Brigatinib: May diminish the antihypertensive effect of Antihypertensive Agents. Brigatinib may enhance the bradycardic effect of Antihypertensive Agents. Risk C: Monitor therapy

Brimonidine (Topical): May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy

Bromperidol: May diminish the hypotensive effect of Blood Pressure Lowering Agents. Blood Pressure Lowering Agents may enhance the hypotensive effect of Bromperidol. Risk X: Avoid combination

Calcium Salts: Thiazide and Thiazide-Like Diuretics may decrease the excretion of Calcium Salts. Continued concomitant use can also result in metabolic alkalosis. Risk C: Monitor therapy

CarBAMazepine: Thiazide and Thiazide-Like Diuretics may enhance the adverse/toxic effect of CarBAMazepine. Specifically, there may be an increased risk for hyponatremia. Risk C: Monitor therapy

Cardiac Glycosides: Thiazide and Thiazide-Like Diuretics may enhance the adverse/toxic effect of Cardiac Glycosides. Specifically, cardiac glycoside toxicity may be enhanced by the hypokalemic and hypomagnesemic effect of thiazide diuretics. Risk C: Monitor therapy

Corticosteroids (Orally Inhaled): May enhance the hypokalemic effect of Thiazide and Thiazide-Like Diuretics. Risk C: Monitor therapy

Corticosteroids (Systemic): May enhance the hypokalemic effect of Thiazide and Thiazide-Like Diuretics. Risk C: Monitor therapy

Cyclophosphamide: Thiazide and Thiazide-Like Diuretics may enhance the adverse/toxic effect of Cyclophosphamide. Specifically, granulocytopenia may be enhanced. Risk C: Monitor therapy

Dapoxetine: May enhance the orthostatic hypotensive effect of Angiotensin-Converting Enzyme Inhibitors. Risk C: Monitor therapy

Dexketoprofen: May enhance the adverse/toxic effect of Sulfonamides. Risk C: Monitor therapy

Dexmethylphenidate: May diminish the therapeutic effect of Antihypertensive Agents. Risk C: Monitor therapy

Diacerein: May enhance the therapeutic effect of Diuretics. Specifically, the risk for dehydration or hypokalemia may be increased. Risk C: Monitor therapy

Diazoxide: Thiazide and Thiazide-Like Diuretics may enhance the adverse/toxic effect of Diazoxide. Risk C: Monitor therapy

Diazoxide: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy

Dichlorphenamide: Thiazide and Thiazide-Like Diuretics may enhance the hypokalemic effect of Dichlorphenamide. Risk C: Monitor therapy

Dipeptidyl Peptidase-IV Inhibitors: May enhance the adverse/toxic effect of Angiotensin-Converting Enzyme Inhibitors. Specifically, the risk of angioedema may be increased. Risk C: Monitor therapy

Dofetilide: Thiazide and Thiazide-Like Diuretics may enhance the QTc-prolonging effect of Dofetilide. Thiazide and Thiazide-Like Diuretics may increase the serum concentration of Dofetilide. Management: Although hydrochlorothiazide is specifically cited as a contraindication, the risk likely extends to all thiazide and thiazide-like diuretics and may be even greater with chlorthalidone or bendroflumethiazide. Consider alternatives when possible. Risk D: Consider therapy modification

Drospirenone: Angiotensin-Converting Enzyme Inhibitors may enhance the hyperkalemic effect of Drospirenone. Risk C: Monitor therapy

DULoxetine: Blood Pressure Lowering Agents may enhance the hypotensive effect of DULoxetine. Risk C: Monitor therapy

Eplerenone: May enhance the hyperkalemic effect of Angiotensin-Converting Enzyme Inhibitors. Risk C: Monitor therapy

Everolimus: May enhance the adverse/toxic effect of Angiotensin-Converting Enzyme Inhibitors. Specifically, the risk of angioedema may be increased. Risk C: Monitor therapy

Ferric Gluconate: Angiotensin-Converting Enzyme Inhibitors may enhance the adverse/toxic effect of Ferric Gluconate. Risk C: Monitor therapy

Ferric Hydroxide Polymaltose Complex: Angiotensin-Converting Enzyme Inhibitors may enhance the adverse/toxic effect of Ferric Hydroxide Polymaltose Complex. Specifically, the risk for angioedema or allergic reactions may be increased. Risk C: Monitor therapy

Fexinidazole [INT]: Thiazide and Thiazide-Like Diuretics may enhance the arrhythmogenic effect of Fexinidazole [INT]. Risk X: Avoid combination

Gelatin (Succinylated): Angiotensin-Converting Enzyme Inhibitors may enhance the adverse/toxic effect of Gelatin (Succinylated). Specifically, the risk of a paradoxical hypotensive reaction may be increased. Risk C: Monitor therapy

Gold Sodium Thiomalate: Angiotensin-Converting Enzyme Inhibitors may enhance the adverse/toxic effect of Gold Sodium Thiomalate. An increased risk of nitritoid reactions has been appreciated. Risk C: Monitor therapy

Grass Pollen Allergen Extract (5 Grass Extract): Angiotensin-Converting Enzyme Inhibitors may enhance the adverse/toxic effect of Grass Pollen Allergen Extract (5 Grass Extract). Specifically, ACE inhibitors may increase the risk of severe allergic reaction to Grass Pollen Allergen Extract (5 Grass Extract). Risk X: Avoid combination

Heparin: May enhance the hyperkalemic effect of Angiotensin-Converting Enzyme Inhibitors. Risk C: Monitor therapy

Heparins (Low Molecular Weight): May enhance the hyperkalemic effect of Angiotensin-Converting Enzyme Inhibitors. Risk C: Monitor therapy

Herbs (Hypertensive Properties): May diminish the antihypertensive effect of Antihypertensive Agents. Risk C: Monitor therapy

Herbs (Hypotensive Properties): May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy

Hypotension-Associated Agents: Blood Pressure Lowering Agents may enhance the hypotensive effect of Hypotension-Associated Agents. Risk C: Monitor therapy

Icatibant: May diminish the antihypertensive effect of Angiotensin-Converting Enzyme Inhibitors. Risk C: Monitor therapy

Ipragliflozin: May enhance the adverse/toxic effect of Thiazide and Thiazide-Like Diuretics. Specifically, the risk for intravascular volume depletion may be increased. Risk C: Monitor therapy

Iron Dextran Complex: Angiotensin-Converting Enzyme Inhibitors may enhance the adverse/toxic effect of Iron Dextran Complex. Specifically, patients receiving an ACE inhibitor may be at an increased risk for anaphylactic-type reactions. Management: Follow iron dextran recommendations closely regarding both having resuscitation equipment and trained personnel on-hand prior to iron dextran administration and the use of a test dose prior to the first therapeutic dose. Risk D: Consider therapy modification

Ivabradine: Thiazide and Thiazide-Like Diuretics may enhance the arrhythmogenic effect of Ivabradine. Risk C: Monitor therapy

Lanthanum: May decrease the serum concentration of Angiotensin-Converting Enzyme Inhibitors. Management: Administer angiotensin-converting enzyme inhibitors at least two hours before or after lanthanum. Risk D: Consider therapy modification

Levodopa-Containing Products: Blood Pressure Lowering Agents may enhance the hypotensive effect of Levodopa-Containing Products. Risk C: Monitor therapy

Levosulpiride: Thiazide and Thiazide-Like Diuretics may enhance the adverse/toxic effect of Levosulpiride. Risk X: Avoid combination

Licorice: May enhance the hypokalemic effect of Thiazide and Thiazide-Like Diuretics. Risk C: Monitor therapy

Lithium: Thiazide and Thiazide-Like Diuretics may decrease the excretion of Lithium. Management: Condsider reducing the lithium dose by 50% upon initiation of a thiazide diuretic. Monitor for increased lithium therapeutic/toxic effects if a thiazide is initiated/dose increased, or decreased effects if a thiazide is discontinued/dose decreased. Risk D: Consider therapy modification

Lithium: Angiotensin-Converting Enzyme Inhibitors may increase the serum concentration of Lithium. Management: Lithium dosage reductions will likely be needed following the addition of an ACE inhibitor. Monitor patient response to lithium closely following addition or discontinuation of concurrent ACE inhibitor treatment. Risk D: Consider therapy modification

Loop Diuretics: May enhance the hypotensive effect of Angiotensin-Converting Enzyme Inhibitors. Loop Diuretics may enhance the nephrotoxic effect of Angiotensin-Converting Enzyme Inhibitors. Risk C: Monitor therapy

Lormetazepam: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy

Mecamylamine: Thiazide and Thiazide-Like Diuretics may enhance the adverse/toxic effect of Mecamylamine. Management: Consider avoiding the use of mecamylamine and thiazide diuretics. If combined, mecamylamine prescribing information suggests reducing the mecamylamine dose by 50% in order to avoid excessive hypotension. Risk D: Consider therapy modification

Methenamine: Thiazide and Thiazide-Like Diuretics may diminish the therapeutic effect of Methenamine. Risk C: Monitor therapy

Methylphenidate: May diminish the antihypertensive effect of Antihypertensive Agents. Risk C: Monitor therapy

Molsidomine: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy

Multivitamins/Fluoride (with ADE): May enhance the hypercalcemic effect of Thiazide and Thiazide-Like Diuretics. Risk C: Monitor therapy

Multivitamins/Minerals (with ADEK, Folate, Iron): Thiazide and Thiazide-Like Diuretics may enhance the hypercalcemic effect of Multivitamins/Minerals (with ADEK, Folate, Iron). Risk C: Monitor therapy

Multivitamins/Minerals (with AE, No Iron): Thiazide and Thiazide-Like Diuretics may increase the serum concentration of Multivitamins/Minerals (with AE, No Iron). Specifically, thiazide diuretics may decrease the excretion of calcium, and continued concomitant use can also result in metabolic alkalosis. Risk C: Monitor therapy

Naftopidil: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy

Neuromuscular-Blocking Agents (Nondepolarizing): Thiazide and Thiazide-Like Diuretics may enhance the neuromuscular-blocking effect of Neuromuscular-Blocking Agents (Nondepolarizing). Risk C: Monitor therapy

Nicergoline: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy

Nicorandil: May enhance the hyperkalemic effect of Angiotensin-Converting Enzyme Inhibitors. Risk C: Monitor therapy

Nicorandil: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy

Nitroprusside: Blood Pressure Lowering Agents may enhance the hypotensive effect of Nitroprusside. Risk C: Monitor therapy

Nonsteroidal Anti-Inflammatory Agents: Angiotensin-Converting Enzyme Inhibitors may enhance the adverse/toxic effect of Nonsteroidal Anti-Inflammatory Agents. Specifically, the combination may result in a significant decrease in renal function. Nonsteroidal Anti-Inflammatory Agents may diminish the antihypertensive effect of Angiotensin-Converting Enzyme Inhibitors. Risk C: Monitor therapy

Nonsteroidal Anti-Inflammatory Agents: Thiazide and Thiazide-Like Diuretics may enhance the nephrotoxic effect of Nonsteroidal Anti-Inflammatory Agents. Nonsteroidal Anti-Inflammatory Agents may diminish the therapeutic effect of Thiazide and Thiazide-Like Diuretics. Risk C: Monitor therapy

Obinutuzumab: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Management: Consider temporarily withholding blood pressure lowering medications beginning 12 hours prior to obinutuzumab infusion and continuing until 1 hour after the end of the infusion. Risk D: Consider therapy modification

Opioid Agonists: May enhance the adverse/toxic effect of Diuretics. Opioid Agonists may diminish the therapeutic effect of Diuretics. Risk C: Monitor therapy

OXcarbazepine: Thiazide and Thiazide-Like Diuretics may enhance the adverse/toxic effect of OXcarbazepine. Specifically, there may be an increased risk for hyponatremia. Risk C: Monitor therapy

Pentoxifylline: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy

Pholcodine: Blood Pressure Lowering Agents may enhance the hypotensive effect of Pholcodine. Risk C: Monitor therapy

Phosphodiesterase 5 Inhibitors: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy

Porfimer: Photosensitizing Agents may enhance the photosensitizing effect of Porfimer. Risk C: Monitor therapy

Potassium Salts: May enhance the hyperkalemic effect of Angiotensin-Converting Enzyme Inhibitors. Risk C: Monitor therapy

Potassium-Sparing Diuretics: May enhance the hyperkalemic effect of Angiotensin-Converting Enzyme Inhibitors. Risk C: Monitor therapy

Pregabalin: Angiotensin-Converting Enzyme Inhibitors may enhance the adverse/toxic effect of Pregabalin. Specifically, the risk of angioedema may be increased. Risk C: Monitor therapy

Promazine: Thiazide and Thiazide-Like Diuretics may enhance the QTc-prolonging effect of Promazine. Risk X: Avoid combination

Prostacyclin Analogues: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy

Quinagolide: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy

Racecadotril: May enhance the adverse/toxic effect of Angiotensin-Converting Enzyme Inhibitors. Specifically, the risk for angioedema may be increased with this combination. Risk C: Monitor therapy

Ranolazine: May enhance the adverse/toxic effect of Angiotensin-Converting Enzyme Inhibitors. Risk C: Monitor therapy

Reboxetine: May enhance the hypokalemic effect of Thiazide and Thiazide-Like Diuretics. Risk C: Monitor therapy

Sacubitril: Angiotensin-Converting Enzyme Inhibitors may enhance the adverse/toxic effect of Sacubitril. Specifically, the risk of angioedema may be increased with this combination. Risk X: Avoid combination

Salicylates: May enhance the nephrotoxic effect of Angiotensin-Converting Enzyme Inhibitors. Salicylates may diminish the therapeutic effect of Angiotensin-Converting Enzyme Inhibitors. Risk C: Monitor therapy

Selective Serotonin Reuptake Inhibitors: May enhance the hyponatremic effect of Thiazide and Thiazide-Like Diuretics. Risk C: Monitor therapy

Sirolimus: May enhance the adverse/toxic effect of Angiotensin-Converting Enzyme Inhibitors. Risk C: Monitor therapy

Sodium Phosphates: Angiotensin-Converting Enzyme Inhibitors may enhance the nephrotoxic effect of Sodium Phosphates. Specifically, the risk of acute phosphate nephropathy may be enhanced. Management: Consider avoiding this combination by temporarily suspending treatment with ACEIs, or seeking alternatives to oral sodium phosphate bowel preparation. If the combination cannot be avoided, maintain adequate hydration and monitor renal function closely. Risk D: Consider therapy modification

Sodium Phosphates: Diuretics may enhance the nephrotoxic effect of Sodium Phosphates. Specifically, the risk of acute phosphate nephropathy may be enhanced. Management: Consider avoiding this combination by temporarily suspending treatment with diuretics, or seeking alternatives to oral sodium phosphate bowel preparation. If the combination cannot be avoided, hydrate adequately and monitor fluid and renal status. Risk D: Consider therapy modification

Tacrolimus (Systemic): Angiotensin-Converting Enzyme Inhibitors may enhance the hyperkalemic effect of Tacrolimus (Systemic). Risk C: Monitor therapy

Temsirolimus: May enhance the adverse/toxic effect of Angiotensin-Converting Enzyme Inhibitors. Risk C: Monitor therapy

Thiazide and Thiazide-Like Diuretics: May enhance the hypotensive effect of Angiotensin-Converting Enzyme Inhibitors. Thiazide and Thiazide-Like Diuretics may enhance the nephrotoxic effect of Angiotensin-Converting Enzyme Inhibitors. Risk C: Monitor therapy

TiZANidine: May enhance the hypotensive effect of Angiotensin-Converting Enzyme Inhibitors. Risk C: Monitor therapy

Tolvaptan: May enhance the hyperkalemic effect of Angiotensin-Converting Enzyme Inhibitors. Risk C: Monitor therapy

Topiramate: Thiazide and Thiazide-Like Diuretics may enhance the hypokalemic effect of Topiramate. Thiazide and Thiazide-Like Diuretics may increase the serum concentration of Topiramate. Management: Monitor for increased topiramate levels/adverse effects (e.g., hypokalemia) with initiation/dose increase of a thiazide diuretic. Closely monitor serum potassium concentrations with concomitant therapy. Topiramate dose reductions may be necessary. Risk D: Consider therapy modification

Toremifene: Thiazide and Thiazide-Like Diuretics may enhance the hypercalcemic effect of Toremifene. Risk C: Monitor therapy

Trimethoprim: May enhance the hyperkalemic effect of Angiotensin-Converting Enzyme Inhibitors. Risk C: Monitor therapy

Urapidil: May interact via an unknown mechanism with Angiotensin-Converting Enzyme Inhibitors. Management: Avoid concomitant use of urapidil and angiotensin-converting enzyme (ACE) inhibitors. Risk D: Consider therapy modification

Urokinase: May enhance the adverse/toxic effect of Angiotensin-Converting Enzyme Inhibitors. Specifically, the risk of angioedema may be increased. Risk C: Monitor therapy

Verteporfin: Photosensitizing Agents may enhance the photosensitizing effect of Verteporfin. Risk C: Monitor therapy

Vitamin D Analogs: Thiazide and Thiazide-Like Diuretics may enhance the hypercalcemic effect of Vitamin D Analogs. Risk C: Monitor therapy

Yohimbine: May diminish the antihypertensive effect of Antihypertensive Agents. Risk C: Monitor therapy

Food Interactions

See individual agents.

Test Interactions

See individual agents.

Monitoring Parameters

Blood pressure; BUN, serum creatinine and electrolytes; hepatic function (baseline and as clinically indicated); uric acid and glucose (as appropriate); urea (when concomitant use of potassium-sparing diuretics, potassium supplements, potassium-containing salt substitutes, drugs associated with increase in serum potassium, or other RAAS inhibitors is necessary); if patient has collagen vascular disease and/or renal impairment, periodically monitor CBC with differential.

Product Availability

Not available in the US

Dosage Forms: Canada

Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Tablet, Oral:

Coversyl Plus: Perindopril erbumine 4 mg and indapamide 1.25 mg

Coversyl Plus HD: Perindopril erbumine 8 mg and indapamide 2.5 mg

Coversyl Plus LD: Perindopril erbumine 2 mg and indapamide 0.625 mg

Generic: Perindopril erbumine 2 mg and indapamide 0.625 mg, Perindopril erbumine 4 mg and indapamide 1.25 mg, Perindopril erbumine 8 mg and indapamide 2.5 mg

Anatomic Therapeutic Chemical (ATC) Classification

• C09BA04

Generic Available (US)

May be product dependent

Mechanism of Action

Perindopril: Prevents conversion of angiotensin I to angiotensin II, a potent vasoconstrictor; results in lower levels of angiotensin II which, in turn, causes an increase in plasma renin activity and a reduction in aldosterone secretion.

Indapamide: Enhances sodium, chloride, and water excretion by interfering with the transport of sodium ions across the renal tubular epithelium; diuretic effect is localized at the proximal segment of the distal tubule of the nephron.

Pharmacodynamics/Kinetics

See individual agents.

Local Anesthetic/Vasoconstrictor Precautions

No information available to require special precautions

Effects on Dental Treatment

Key adverse event(s) related to dental treatment: Indapamide: Palpitations, flushing, rhinorrhea, xerostomia and changes in salivation (normal salivary flow resumes upon discontinuation). Patients may experience orthostatic hypotension as they stand up after treatment; especially if lying in dental chair for extended periods of time. Use caution with sudden changes in position during and after dental treatment.

Effects on Bleeding

No information available to require special precautions

Related Information

• Indapamide
• Perindopril

Index Terms

Indapamide and Perindopril; Indapamide and Perindopril Arginine; Indapamide and Perindopril Erbumine; Perindopril Arginine and Indapamide; Perindopril Erbumine and Indapamide

References

2019 American Geriatrics Society Beers Criteria Update Expert Panel. American Geriatrics Society 2019 updated AGS Beers Criteria for Potentially Inappropriate Medication Use in Older Adults. J Am Geriatr Soc. 2019;67(4):674-694. doi: 10.1111/jgs.15767.[PubMed 30693946]

Arcosyl Plus/Arcosyl Plus LD (perindopril/indapamide) [product monograph]. Laval, Quebec, Canada: Servier Canada Inc; June 2018.

Bakris GL, Weir MR. Angiotensin-converting enzyme inhibitor-associated elevations in serum creatinine: is this a cause for concern? Arch Intern Med. 2000;160(5):685-693.[PubMed 10724055]

Brackett CC, Singh H, Block JH. Likelihood and mechanisms of cross-allergenicity between sulfonamide antibiotics and other drugs containing a sulfonamide functional group. Pharmacotherapy. 2004;24(7):856-870.[PubMed 15303450]

Cooper WO, Hernandez-Diaz S, Arbogast PG, et al, “Major Congenital Malformations After First-Trimester Exposure to ACE Inhibitors,” N Engl J Med, 2006, 354(23):2443-51.[PubMed 16760444]

Coversyl Plus (perindopril/indapamide) [product monograph]. Laval, Quebec, Canada: Servier Canada Inc; July 2019.

Funder JW, Carey RM, Mantero F, et al. The management of primary aldosteronism: case detection, diagnosis, and treatment: an Endocrine Society Clinical Practice Guideline. J Clin Endocrinol Metab. 2016;101(5):1889-1916. doi: 10.1210/jc.2015-4061.[PubMed 26934393]

Gersh BJ, Maron BJ, Bonow RO, et al; American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines; American Association for Thoracic Surgery; American Society of Echocardiography; American Society of Nuclear Cardiology; Heart Failure Society of America; Heart Rhythm Society; Society for Cardiovascular Angiography and Interventions; Society of Thoracic Surgeons. 2011 ACCF/AHA guideline for the diagnosis and treatment of hypertrophic cardiomyopathy: a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines. Circulation. 2011;124(24):e783-e831.[PubMed 22068434]

Hillis LD, Smith PK, Anderson JL, et al. 2011 ACCF/AHA Guideline for Coronary Artery Bypass Graft Surgery: A Report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines. Circulation. 2011, 124(23):2610-42.[PubMed 22064600]

Johnson KK, Green DL, Rife JP, Limon L. Sulfonamide cross-reactivity: fact or fiction? [published correction appears in Ann Pharmacother. 2005;39(7-8):1373]. Ann Pharmacother. 2005;39(2):290-301.[PubMed 15644481]

Lapostolle F, Borron SW, Bekka R, et al, “Lingual Angioedema After Perindopril Use,” Am J Cardio, 1998, 81(4): 523.[PubMed 9485152]

Moser M and Black HR, “The Role of Combination Therapy in the Treatment of Hypertension,” Am J Hypertens, 1998, 11(6 Pt 2):73-8.[PubMed 9655566]

Mourad JJ, Waeber B, Zannad F, et al, "Comparison of Different Therapeutic Strategies in Hypertension: A Low-Dose Combination of Perindopril/Indapamide Versus a Sequential Monotherapy or a Stepped-Care Approach," J Hypertens, 2004, 22(12):2379-86.[PubMed 15614033]

Myers MG, Asmar R, Leenen FH, et al, “Fixed Low-Dose Combination Therapy in Hypertension − A Dose Response Study of Perindopril and Indapamide,” J Hypertens, 2000, 18(3):317-25.[PubMed 10726719]

Quan A , “Fetopathy Associated With Exposure to Angiotensin Converting Enzyme Inhibitors and Angiotensin Receptor Antagonists,” Early Hum Dev, 2006, 82(1):23-8.[PubMed 16427219]

Slatore CG, Tilles SA. Sulfonamide hypersensitivity. Immunol Allergy Clin North Am. 2004;24(3):477-490.[PubMed 15242722]

Tornero P, De Barrio M, Baeza ML, Herrero T. Cross-reactivity among p-amino group compounds in sulfonamide fixed drug eruption: diagnostic value of patch testing. Contact Dermatitis. 2004;51(2):57-62.[PubMed 15373844]

Ziegler O, Sirveaux MA, Brunaud L, Reibel N, Quilliot D. Medical follow up after bariatric surgery: nutritional and drug issues. General recommendations for the prevention and treatment of nutritional deficiencies. Diabetes Metab. 2009;35(6, pt 2):544-557. doi: 10.1016/S1262-3636(09)73464-0.[PubMed 20152742]

Brand Names: International

Acertil Plus (HK, KR, TW); Acertil Plus Arginine (KR); Adwipril Plus (EG); Bioprexum Plus (ID); Biprel (CN); BiPreterax (AR, BB, BM, BS, BZ, CO, DE, FR, GY, JM, NL, PE, PH, PK, PR, SR, TT, VE); Bipreterax (BH, ES, JO); Bipreterax Arginine (AE, JO, KW, LB, SA); Civersyl Plus (IE); Co-Prenessa (RO); Coversum Combi (DE); Coversyl Comp (DK, FI, SE); Coversyl Plus (AU, BE, BR, EG, GB, IN, LU, MT, MY, PH, SG, TH, UY, VN); Daparindo (EG); Indapril (BD); Inopil Plus (BD); Midopril (BD); Noliprel (BG, CZ, EE, LT, PL, RU); Noliterax (LV); Pendrex Plus (IE); Pericard Plus (BD); Periloz Plus (VN); Perindo Combi (AU); Peripril Plus (PH); Predonium (HK, NZ); Predonium DS (NZ); Prestarium (EE); Pretanix Komb (HU); Preterax (AR, AT, BB, BE, BH, BM, BS, BZ, CH, CO, CR, DO, FR, GR, GT, GY, HN, IT, JM, LU, MT, MX, NI, NL, PA, PE, PH, PK, PR, PY, SG, SR, SV, TR, TT, TW, VE); Preterax Arginine (AE, KW, LB, SA); Preterax Forte (CH); Prexanil Combi (HR)

Last Updated 4/22/20