When pregnancy is detected, discontinue perindopril/amlodipine as soon as possible. Drugs that act directly on the renin-angiotensin system can cause injury and death to the developing fetus.
Hypertension: Oral: Initial: Perindopril 3.5 mg/amlodipine 2.5 mg once daily; adjust dose to response in 7- to 14-day intervals; maximum dose: perindopril 14 mg/amlodipine 10 mg per day.
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
CrCl 30 to 80 mL/minute: Maximum dose: Perindopril 7 mg/amlodipine 5 mg per day.
CrCl <30 mL/minute: Use is not recommended.
Hemodialysis: Perindopril and perindoprilat are dialyzable. Amlodipine is not dialyzable.
There are dosage adjustments provided in the manufacturer’s labeling. Perindoprilat bioavailability is increased and amlodipine clearance is decreased with hepatic impairment.
Refer to adult dosing.
The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified. Frequency not always defined.
1% to 10%:
Cardiovascular: Peripheral edema (2% to 7%), exacerbation of angina pectoris, hypotension, myocardial infarction (more likely in patients with severe obstructive coronary artery disease)
Central nervous system: Dizziness (3%), headache (3%)
Dermatologic: Skin rash
Endocrine & metabolic: Hyperkalemia (2%)
Gastrointestinal: Diarrhea, nausea
Renal: Renal insufficiency
Respiratory: Cough (3%)
Hypersensitivity to perindopril, other ACE inhibitors, amlodipine, or any component of the formulation; hereditary or idiopathic angioedema, with or without previous ACE inhibitor treatment; concomitant use with aliskiren in patients with diabetes; concomitant use or within 36 hours of switching to or from a neprilysin inhibitor (eg, sacubitril).
Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
Canadian labeling: Additional contraindications (not in US labeling): Hypersensitivity to other dihydropyridine derivatives; renal impairment (CrCl <60 mL/minute); pregnant women, women planning to become pregnant, or women of childbearing potential not using adequate contraceptive; breastfeeding; mitral valve stenosis and left ventricular outflow tract obstruction (eg, aortic stenosis, hypertrophic cardiomyopathy); heart failure; bilateral renal artery stenosis or renal artery stenosis in a single functioning kidney; concomitant use with aliskiren-containing drugs in patients with moderate to severe renal impairment (GFR <60 mL/minute/1.73 m2); extracorporeal treatment leading to contact of blood with negatively charged surfaces; hereditary problems of galactose intolerance, glucose-galactose malabsorption, or congenital lactase deficiency.
Concerns related to adverse effects:
• Angina/MI: Increased angina and/or MI has occurred with initiation or dosage titration of dihydropyridine calcium channel blockers, especially in patients with severe obstructive coronary artery disease in the absence of concurrent beta-blockade.
• 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) 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 is contraindicated in patients with a history of angioedema with or without previous ACE inhibitor treatment.
• Cholestatic jaundice: A rare toxicity associated with ACE inhibitors includes cholestatic jaundice, which may progress to fulminant hepatic necrosis; discontinue if marked elevation of hepatic transaminases or jaundice occurs.
• 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.
• 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.
• Hyperkalemia: May occur with ACE inhibitors; risk factors include renal dysfunction, diabetes mellitus, concomitant use of potassium-sparing diuretics, potassium supplements and/or potassium-containing salts. Use cautiously, if at all, with these agents and monitor potassium closely.
• Hypersensitivity reactions: Anaphylactic/anaphylactoid reactions can occur with ACE inhibitors. Severe anaphylactoid reactions may be seen during hemodialysis (eg, CVVHD) with high-flux dialysis membranes (eg, AN69), 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.
• Renal function deterioration: Perindopril 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).
Disease-related concerns:
• Aortic stenosis: Use with extreme caution in patients with severe aortic stenosis; may reduce coronary perfusion resulting in ischemia.
• Cardiovascular disease: Initiation of therapy in patients with ischemic heart disease 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.
• 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.
• Hepatic impairment: Use with caution in patients with hepatic impairment.
• Hypertrophic cardiomyopathy with left ventricular outflow tract obstruction: Use with caution in patients with hypertrophic cardiomyopathy and left ventricular outflow tract obstruction since reduction in afterload may worsen symptoms associated with this condition (AHA/ACC [Ommen 2024]).
• Renal artery stenosis: Use perindopril with caution in patients with unstented unilateral or bilateral renal artery stenosis. When unstented bilateral renal artery stenosis is present, use is generally avoided due to the elevated risk of deterioration in renal function unless possible benefits outweigh risks.
• Renal impairment: Use with caution in patients with mild to moderate renal impairment (CrCl ≥30 mL/minute); not recommended in patients with severe renal impairment (CrCl <30 mL/minute).
Special populations:
• Black patients: ACE inhibitors effectiveness is less in black patients than in non-black patients. In addition, ACE inhibitors cause a higher rate of angioedema in black than in non-black patients.
• Pregnancy: [US 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.
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. However, discontinuation of therapy prior to surgery is controversial. If continued preoperatively, avoidance of hypotensive agents during surgery is prudent (Hillis 2011).
The perindopril component in the perindopril/amlodipine combination product is provided as perindopril arginine and differs from single-ingredient perindopril formulations that are available as perindopril erbumine. Perindopril arginine 5 mg is equivalent to perindopril erbumine 4 mg.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Tablet, Oral:
Prestalia: Perindopril arginine 3.5 mg and amlodipine 2.5 mg, Perindopril arginine 7 mg and amlodipine 5 mg, Perindopril arginine 14 mg and amlodipine 10 mg
No
Tablets (Prestalia Oral)
3.5-2.5 mg (per each): $6.81
7-5 mg (per each): $6.81
14-10 mg (per each): $6.81
Disclaimer: A representative AWP (Average Wholesale Price) price or price range is provided as reference price only. A range is provided when more than one manufacturer's AWP price is available and uses the low and high price reported by the manufacturers to determine the range. The pricing data should be used for benchmarking purposes only, and as such should not be used alone to set or adjudicate any prices for reimbursement or purchasing functions or considered to be an exact price for a single product and/or manufacturer. Medi-Span expressly disclaims all warranties of any kind or nature, whether express or implied, and assumes no liability with respect to accuracy of price or price range data published in its solutions. In no event shall Medi-Span be liable for special, indirect, incidental, or consequential damages arising from use of price or price range data. Pricing data is updated monthly.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Tablet, Oral:
Viacoram: Perindopril arginine 3.5 mg and amlodipine 2.5 mg, Perindopril arginine 7 mg and amlodipine 5 mg, Perindopril arginine 14 mg and amlodipine 10 mg
Generic: Perindopril arginine 3.5 mg and amlodipine 2.5 mg, Perindopril arginine 7 mg and amlodipine 5 mg, Perindopril arginine 14 mg and amlodipine 10 mg
Administer with or without food.
Hypertension: Management of hypertension.
Refer to individual components.
Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the drug interactions program by clicking on the “Launch drug interactions program” link above.
Alfuzosin: May increase hypotensive effects of Blood Pressure Lowering Agents. Risk C: Monitor
Aliskiren: May increase hyperkalemic effects of Angiotensin-Converting Enzyme Inhibitors. Aliskiren may increase nephrotoxic effects of Angiotensin-Converting Enzyme Inhibitors. Aliskiren may increase hypotensive effects 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 increase hypersensitivity effects of Allopurinol. Risk C: Monitor
ALPRAZolam: CYP3A4 Inhibitors (Weak) may increase serum concentration of ALPRAZolam. Risk C: Monitor
Alteplase: Angiotensin-Converting Enzyme Inhibitors may increase adverse/toxic effects of Alteplase. Specifically, the risk for angioedema may be increased. Risk C: Monitor
Amifostine: Blood Pressure Lowering Agents may increase hypotensive effects of Amifostine. Management: When used at chemotherapy doses, hold blood pressure lowering medications for 24 hours before amifostine administration. If blood pressure lowering therapy cannot be held, do not administer amifostine. Use caution with radiotherapy doses of amifostine. Risk D: Consider Therapy Modification
Amphetamines: May decrease antihypertensive effects of Antihypertensive Agents. Risk C: Monitor
Angiotensin II Receptor Blockers: May increase adverse/toxic effects of Angiotensin-Converting Enzyme Inhibitors. Angiotensin II Receptor Blockers may increase serum concentration of Angiotensin-Converting Enzyme Inhibitors. Management: 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 when possible. Monitor blood pressure, renal function, and potassium if combined. Risk D: Consider Therapy Modification
Angiotensin II: Angiotensin-Converting Enzyme Inhibitors may increase therapeutic effects of Angiotensin II. Risk C: Monitor
Antipsychotic Agents (Second Generation [Atypical]): Blood Pressure Lowering Agents may increase hypotensive effects of Antipsychotic Agents (Second Generation [Atypical]). Risk C: Monitor
Aprotinin: May decrease antihypertensive effects of Angiotensin-Converting Enzyme Inhibitors. Risk C: Monitor
Arginine: May increase hypotensive effects of Blood Pressure Lowering Agents. Risk C: Monitor
Atosiban: Calcium Channel Blockers may increase adverse/toxic effects of Atosiban. Specifically, there may be an increased risk for pulmonary edema and/or dyspnea. Risk C: Monitor
AzaTHIOprine: Angiotensin-Converting Enzyme Inhibitors may increase myelosuppressive effects of AzaTHIOprine. Risk C: Monitor
Barbiturates: May increase hypotensive effects of Blood Pressure Lowering Agents. Risk C: Monitor
Benperidol: May increase hypotensive effects of Blood Pressure Lowering Agents. Risk C: Monitor
Brigatinib: May decrease antihypertensive effects of Antihypertensive Agents. Brigatinib may increase bradycardic effects of Antihypertensive Agents. Risk C: Monitor
Brimonidine (Topical): May increase hypotensive effects of Blood Pressure Lowering Agents. Risk C: Monitor
Bromperidol: May decrease hypotensive effects of Blood Pressure Lowering Agents. Blood Pressure Lowering Agents may increase hypotensive effects of Bromperidol. Risk X: Avoid
Calcium Salts: May decrease therapeutic effects of Calcium Channel Blockers. Risk C: Monitor
CarBAMazepine: CYP3A4 Inhibitors (Weak) may increase serum concentration of CarBAMazepine. Risk C: Monitor
Charcoal, Activated: May decrease serum concentration of AmLODIPine. Risk C: Monitor
Clofazimine: May increase serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Risk C: Monitor
CycloSPORINE (Systemic): Calcium Channel Blockers (Dihydropyridine) may increase serum concentration of CycloSPORINE (Systemic). CycloSPORINE (Systemic) may increase serum concentration of Calcium Channel Blockers (Dihydropyridine). Risk C: Monitor
CYP3A4 Inducers (Moderate): May decrease serum concentration of AmLODIPine. Risk C: Monitor
CYP3A4 Inducers (Strong): May decrease serum concentration of AmLODIPine. Risk C: Monitor
CYP3A4 Inhibitors (Moderate): May increase serum concentration of AmLODIPine. Risk C: Monitor
CYP3A4 Inhibitors (Strong): May increase serum concentration of AmLODIPine. Risk C: Monitor
Dantrolene: May increase hyperkalemic effects of Calcium Channel Blockers. Dantrolene may increase negative inotropic effects of Calcium Channel Blockers. Risk X: Avoid
Dapoxetine: May increase orthostatic hypotensive effects of Angiotensin-Converting Enzyme Inhibitors. Risk C: Monitor
Dapoxetine: May increase orthostatic hypotensive effects of Calcium Channel Blockers. Risk C: Monitor
Dexmethylphenidate: May decrease therapeutic effects of Antihypertensive Agents. Risk C: Monitor
Diazoxide: May increase hypotensive effects of Blood Pressure Lowering Agents. Risk C: Monitor
Dipeptidyl Peptidase-IV Inhibitors: May increase adverse/toxic effects of Angiotensin-Converting Enzyme Inhibitors. Specifically, the risk of angioedema may be increased. Risk C: Monitor
Drospirenone-Containing Products: May increase hyperkalemic effects of Angiotensin-Converting Enzyme Inhibitors. Risk C: Monitor
DULoxetine: Blood Pressure Lowering Agents may increase hypotensive effects of DULoxetine. Risk C: Monitor
Everolimus: May increase adverse/toxic effects of Angiotensin-Converting Enzyme Inhibitors. Specifically, the risk of angioedema may be increased. Risk C: Monitor
Ferric Gluconate: Angiotensin-Converting Enzyme Inhibitors may increase adverse/toxic effects of Ferric Gluconate. Risk C: Monitor
Ferric Hydroxide Polymaltose Complex: Angiotensin-Converting Enzyme Inhibitors may increase adverse/toxic effects of Ferric Hydroxide Polymaltose Complex. Specifically, the risk for angioedema or allergic reactions may be increased. Risk C: Monitor
Finerenone: Angiotensin-Converting Enzyme Inhibitors may increase hyperkalemic effects of Finerenone. Risk C: Monitor
Finerenone: CYP3A4 Inhibitors (Weak) may increase serum concentration of Finerenone. Risk C: Monitor
Flibanserin: CYP3A4 Inhibitors (Weak) may increase serum concentration of Flibanserin. Risk C: Monitor
Flunarizine: May increase therapeutic effects of Antihypertensive Agents. Risk C: Monitor
Fusidic Acid (Systemic): May increase serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Management: Consider avoiding this combination if possible. If required, monitor patients closely for increased adverse effects of the CYP3A4 substrate. Risk D: Consider Therapy Modification
Gelatin (Succinylated): Angiotensin-Converting Enzyme Inhibitors may increase adverse/toxic effects of Gelatin (Succinylated). Specifically, the risk of a paradoxical hypotensive reaction may be increased. Risk C: Monitor
Grass Pollen Allergen Extract (5 Grass Extract): Angiotensin-Converting Enzyme Inhibitors may increase adverse/toxic effects 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
Heparin: May increase hyperkalemic effects of Angiotensin-Converting Enzyme Inhibitors. Risk C: Monitor
Heparins (Low Molecular Weight): May increase hyperkalemic effects of Angiotensin-Converting Enzyme Inhibitors. Risk C: Monitor
Herbal Products with Blood Pressure Increasing Effects: May decrease antihypertensive effects of Antihypertensive Agents. Risk C: Monitor
Herbal Products with Blood Pressure Lowering Effects: May increase hypotensive effects of Blood Pressure Lowering Agents. Risk C: Monitor
Hypotension-Associated Agents: Blood Pressure Lowering Agents may increase hypotensive effects of Hypotension-Associated Agents. Risk C: Monitor
Icatibant: May decrease antihypertensive effects of Angiotensin-Converting Enzyme Inhibitors. Risk C: Monitor
Iloperidone: May increase hypotensive effects of Blood Pressure Lowering Agents. Risk C: Monitor
Indoramin: May increase hypotensive effects of Antihypertensive Agents. Risk C: Monitor
Inhalational Anesthetics: May increase hypotensive effects of Calcium Channel Blockers. Risk C: Monitor
Iron Dextran Complex: Angiotensin-Converting Enzyme Inhibitors may increase adverse/toxic effects of Iron Dextran Complex. Specifically, patients receiving an ACE inhibitor may be at an increased risk for anaphylactic-type reactions. Risk C: Monitor
Isocarboxazid: May increase antihypertensive effects of Antihypertensive Agents. Risk X: Avoid
Ixabepilone: CYP3A4 Inhibitors (Weak) may increase serum concentration of Ixabepilone. Risk C: Monitor
Lanthanum: May decrease serum concentration of Angiotensin-Converting Enzyme Inhibitors. Management: Administer angiotensin-converting enzyme (ACE) inhibitors at least two hours before or after lanthanum. Risk D: Consider Therapy Modification
Lemborexant: CYP3A4 Inhibitors (Weak) may increase serum concentration of Lemborexant. Management: The maximum recommended dosage of lemborexant is 5 mg, no more than once per night, when coadministered with weak CYP3A4 inhibitors. Risk D: Consider Therapy Modification
Levodopa-Foslevodopa: Blood Pressure Lowering Agents may increase hypotensive effects of Levodopa-Foslevodopa. Risk C: Monitor
Lithium: Angiotensin-Converting Enzyme Inhibitors may increase serum concentration of Lithium. Management: Lithium dosage reductions will likely be needed following the addition of an ACE inhibitor. Monitor for increased concentrations/toxic effects of lithium if an ACE inhibitor is initiated/dose increased, or if switching between ACE inhibitors. Risk D: Consider Therapy Modification
Lomitapide: CYP3A4 Inhibitors (Weak) may increase serum concentration of Lomitapide. Management: Patients on lomitapide 5 mg/day may continue that dose. Patients taking lomitapide 10 mg/day or more should decrease the lomitapide dose by half. The lomitapide dose may then be titrated up to a max adult dose of 30 mg/day. Risk D: Consider Therapy Modification
Loop Diuretics: May increase hypotensive effects of Angiotensin-Converting Enzyme Inhibitors. Loop Diuretics may increase nephrotoxic effects of Angiotensin-Converting Enzyme Inhibitors. Risk C: Monitor
Loop Diuretics: May increase hypotensive effects of Antihypertensive Agents. Risk C: Monitor
Lormetazepam: May increase hypotensive effects of Blood Pressure Lowering Agents. Risk C: Monitor
Lovastatin: AmLODIPine may increase serum concentration of Lovastatin. Risk C: Monitor
Magnesium Sulfate: May increase adverse/toxic effects of Calcium Channel Blockers (Dihydropyridine). Specifically, the risk of hypotension or muscle weakness may be increased. Risk C: Monitor
Melatonin: May decrease antihypertensive effects of Calcium Channel Blockers (Dihydropyridine). Risk C: Monitor
Metergoline: May decrease antihypertensive effects of Blood Pressure Lowering Agents. Blood Pressure Lowering Agents may increase orthostatic hypotensive effects of Metergoline. Risk C: Monitor
Methylphenidate: May decrease antihypertensive effects of Antihypertensive Agents. Risk C: Monitor
Midazolam: CYP3A4 Inhibitors (Weak) may increase serum concentration of Midazolam. Risk C: Monitor
Molsidomine: May increase hypotensive effects of Blood Pressure Lowering Agents. Risk C: Monitor
Naftopidil: May increase hypotensive effects of Blood Pressure Lowering Agents. Risk C: Monitor
Neuromuscular-Blocking Agents (Nondepolarizing): Calcium Channel Blockers may increase neuromuscular-blocking effects of Neuromuscular-Blocking Agents (Nondepolarizing). Risk C: Monitor
Nicergoline: May increase hypotensive effects of Blood Pressure Lowering Agents. Risk C: Monitor
Nicorandil: May increase hyperkalemic effects of Angiotensin-Converting Enzyme Inhibitors. Risk C: Monitor
Nicorandil: May increase hypotensive effects of Blood Pressure Lowering Agents. Risk C: Monitor
NiMODipine: CYP3A4 Inhibitors (Weak) may increase serum concentration of NiMODipine. Risk C: Monitor
Nitroprusside: Blood Pressure Lowering Agents may increase hypotensive effects of Nitroprusside. Risk C: Monitor
Nonsteroidal Anti-Inflammatory Agents (Topical): May decrease therapeutic effects of Angiotensin-Converting Enzyme Inhibitors. Risk C: Monitor
Nonsteroidal Anti-Inflammatory Agents: May decrease antihypertensive effects of Angiotensin-Converting Enzyme Inhibitors. Angiotensin-Converting Enzyme Inhibitors may increase adverse/toxic effects of Nonsteroidal Anti-Inflammatory Agents. Specifically, the combination may result in a significant decrease in renal function. Risk C: Monitor
Obinutuzumab: May increase hypotensive effects 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
Pentoxifylline: May increase hypotensive effects of Blood Pressure Lowering Agents. Risk C: Monitor
Perazine: May increase hypotensive effects of Antihypertensive Agents. Risk C: Monitor
Pholcodine: Blood Pressure Lowering Agents may increase hypotensive effects of Pholcodine. Risk C: Monitor
Phosphodiesterase 5 Inhibitors: May increase hypotensive effects of Blood Pressure Lowering Agents. Risk C: Monitor
Pimozide: CYP3A4 Inhibitors (Weak) may increase serum concentration of Pimozide. Risk X: Avoid
Polyethylene Glycol-Electrolyte Solution: Angiotensin-Converting Enzyme Inhibitors may increase nephrotoxic effects of Polyethylene Glycol-Electrolyte Solution. Risk C: Monitor
Potassium Salts: May increase hyperkalemic effects of Angiotensin-Converting Enzyme Inhibitors. Risk C: Monitor
Potassium-Sparing Diuretics: May increase hyperkalemic effects of Angiotensin-Converting Enzyme Inhibitors. Risk C: Monitor
Prazosin: Antihypertensive Agents may increase hypotensive effects of Prazosin. Risk C: Monitor
Pregabalin: Angiotensin-Converting Enzyme Inhibitors may increase adverse/toxic effects of Pregabalin. Specifically, the risk of angioedema may be increased. Risk C: Monitor
Prostacyclin Analogues: May increase hypotensive effects of Blood Pressure Lowering Agents. Risk C: Monitor
Quinagolide: May increase hypotensive effects of Blood Pressure Lowering Agents. Risk C: Monitor
Racecadotril: May increase adverse/toxic effects of Angiotensin-Converting Enzyme Inhibitors. Specifically, the risk for angioedema may be increased with this combination. Risk C: Monitor
Ranolazine: May increase adverse/toxic effects of Angiotensin-Converting Enzyme Inhibitors. Risk C: Monitor
Red Yeast Rice: AmLODIPine may increase serum concentration of Red Yeast Rice. Risk C: Monitor
Sacubitril: Angiotensin-Converting Enzyme Inhibitors may increase adverse/toxic effects of Sacubitril. Specifically, the risk of angioedema may be increased with this combination. Risk X: Avoid
Salicylates: May decrease therapeutic effects of Angiotensin-Converting Enzyme Inhibitors. Salicylates may increase nephrotoxic effects of Angiotensin-Converting Enzyme Inhibitors. Risk C: Monitor
Silodosin: May increase hypotensive effects of Blood Pressure Lowering Agents. Risk C: Monitor
Simvastatin: AmLODIPine may increase serum concentration of Simvastatin. Management: Dose of simvastatin should not exceed 20 mg daily if coadministering with amlodipine. If coadministering with simvastatin and amlodipine, close laboratory and clinical monitoring for signs and symptoms of rhabdomyolysis is warranted. Risk D: Consider Therapy Modification
Sincalide: Drugs that Affect Gallbladder Function may decrease therapeutic effects of Sincalide. Management: Consider discontinuing drugs that may affect gallbladder motility prior to the use of sincalide to stimulate gallbladder contraction. Risk D: Consider Therapy Modification
Sirolimus (Conventional): CYP3A4 Inhibitors (Weak) may increase serum concentration of Sirolimus (Conventional). Risk C: Monitor
Sirolimus (Protein Bound): CYP3A4 Inhibitors (Weak) may increase serum concentration of Sirolimus (Protein Bound). Management: Reduce the dose of protein bound sirolimus to 56 mg/m2 when used concomitantly with a weak CYP3A4 inhibitor. Risk D: Consider Therapy Modification
Sodium Phosphates: Angiotensin-Converting Enzyme Inhibitors may increase nephrotoxic effects of Sodium Phosphates. Specifically, the risk of acute phosphate nephropathy may be enhanced. Risk C: Monitor
Sparsentan: May increase adverse/toxic effects of Angiotensin-Converting Enzyme Inhibitors. Risk X: Avoid
Tacrolimus (Systemic): Angiotensin-Converting Enzyme Inhibitors may increase hyperkalemic effects of Tacrolimus (Systemic). Risk C: Monitor
Tacrolimus (Systemic): Calcium Channel Blockers (Dihydropyridine) may increase serum concentration of Tacrolimus (Systemic). Risk C: Monitor
Tacrolimus (Systemic): CYP3A4 Inhibitors (Weak) may increase serum concentration of Tacrolimus (Systemic). Risk C: Monitor
Temsirolimus: May increase adverse/toxic effects of Angiotensin-Converting Enzyme Inhibitors. Specifically, the risk of angioedema may be increased. Risk C: Monitor
Terazosin: Antihypertensive Agents may increase hypotensive effects of Terazosin. Risk C: Monitor
Thiazide and Thiazide-Like Diuretics: May increase hypotensive effects of Angiotensin-Converting Enzyme Inhibitors. Thiazide and Thiazide-Like Diuretics may increase nephrotoxic effects of Angiotensin-Converting Enzyme Inhibitors. Risk C: Monitor
Tolvaptan: May increase hyperkalemic effects of Angiotensin-Converting Enzyme Inhibitors. Risk C: Monitor
Triazolam: CYP3A4 Inhibitors (Weak) may increase serum concentration of Triazolam. Risk C: Monitor
Trimethoprim: May increase hyperkalemic effects of Angiotensin-Converting Enzyme Inhibitors. Management: Consider avoiding coadministration if possible. If combined, monitor serum potassium closely, particularly for patients with other risk factors (eg, renal impairment, older age, and other medications that increase potassium. Risk X: Avoid
Ubrogepant: CYP3A4 Inhibitors (Weak) may increase serum concentration of Ubrogepant. Management: In patients taking weak CYP3A4 inhibitors, the initial and second dose (given at least 2 hours later if needed) of ubrogepant should be limited to 50 mg. Risk D: Consider Therapy Modification
Urapidil: And Angiotensin-Converting Enzyme Inhibitors may interact via an unclear mechanism. Management: Avoid concomitant use of urapidil and angiotensin-converting enzyme (ACE) inhibitors. Risk D: Consider Therapy Modification
Urokinase: May increase adverse/toxic effects of Angiotensin-Converting Enzyme Inhibitors. Specifically, the risk of angioedema may be increased. Risk C: Monitor
See Individual agents.
[US 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. See individual agents.
Amlodipine is present in breast milk (Naito 2015); it is not known if perindopril is present in breast milk. Due to the potential for serious adverse reactions in the breastfeeding infant, the manufacturer's labeling recommends discontinuing breastfeeding or discontinuing therapy. See individual agents.
Blood pressure; renal function and electrolytes; if patient has collagen vascular disease and/or renal impairment, periodically monitor CBC with differential. If doses > perindopril 7 mg/amlodipine 5 mg once daily are required in patients >65 years of age, monitor blood pressure up to 2 weeks following up titration.
Amlodipine: Inhibits calcium ion from entering the “slow channels” or select voltage-sensitive areas of vascular smooth muscle and myocardium during depolarization, a relaxation of coronary vascular smooth muscle and coronary vasodilation; amlodipine directly acts on vascular smooth muscle to produce peripheral arterial vasodilation reducing peripheral vascular resistance and blood pressure.
Perindopril: Prevents conversion of angiotensin I to angiotensin II, increases plasma renin activity, and reduces aldosterone secretion.
See individual agents.