(per IN doe pril & am LOE di peen)
Hypertension: Treatment of hypertension in patients not adequately controlled with monotherapy or as initial therapy in patients that require multiple antihypertensives for adequate control
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 mellitus
Canadian labeling: Additional contraindications (not in US labeling): Hypersensitivity to other dihydropyridine derivatives; renal impairment (CrCl <60 mL/minute); pregnant women or women planning to become pregnant; breast-feeding women; 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 charges surfaces; hereditary problems of galactose intolerance, glucose-galactose malabsorption, or Lapp lactase deficiency
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:
US labeling: 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 once daily
Canadian labeling: Initial: Perindopril 3.5 mg/amlodipine 2.5 mg once daily; adjust dose to response in 4 week intervals to perindopril 7 mg/amlodipine 5 mg once daily and then if necessary, to perindopril 14 mg/amlodipine 10 mg once daily; maximum dose: perindopril 14 mg/amlodipine 10 mg once daily
Not recommended in patients >65 years.
CrCl ≥60 mL/minute: No dosage adjustment necessary.
CrCl <60 mL/minute: There are no dosage adjustments provided in the manufacturers labeling (has not been studied); use is not recommended (US labeling) or contraindicated (Canadian labeling).
Hemodialysis: Perindopril and perindoprilat are dialyzable. Amlodipine is not dialyzable.
There are no dosage adjustments provided in the manufacturers labeling (has not been studied); use is not recommended.
Oral:
US labeling: Administer with or without food.
Canadian labeling: Administer in the morning before a meal.
Store at 25 ‚ °C (77 ‚ °F); excursions are permitted between 15 ‚ °C and 30 ‚ °C (59 ‚ °F and 86 ‚ °F). Protect from moisture and light.
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
Alfuzosin: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy
Aliskiren: May enhance the hyperkalemic effect of ACE Inhibitors. Aliskiren may enhance the hypotensive effect of ACE Inhibitors. Aliskiren may enhance the nephrotoxic effect of ACE 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. Consider therapy modification
Allopurinol: ACE Inhibitors may enhance the potential for allergic or hypersensitivity reactions to Allopurinol. Consider therapy modification
Alpha1-Blockers: May enhance the hypotensive effect of Calcium Channel Blockers. 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. Consider therapy modification
Amodiaquine: CYP2C8 Inhibitors may increase the serum concentration of Amodiaquine. Avoid combination
Amphetamines: May diminish the antihypertensive effect of Antihypertensive Agents. Monitor therapy
Angiotensin II Receptor Blockers: May enhance the adverse/toxic effect of ACE Inhibitors. Angiotensin II Receptor Blockers may increase the serum concentration of ACE 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. Consider therapy modification
Antifungal Agents (Azole Derivatives, Systemic): May enhance the adverse/toxic effect of Calcium Channel Blockers. Specifically, itraconazole may enhance the negative inotropic effects of verapamil or diltiazem. Antifungal Agents (Azole Derivatives, Systemic) may decrease the metabolism of Calcium Channel Blockers. Fluconazole and isavuconazonium likely exert weaker effects than other azoles and are addressed in separate monographs. Management: Concurrent use of felodipine or nisoldipine with itraconazole is specifically contraindicated. Frequent monitoring is warranted with any such combination; calcium channel blocker dose reductions may be required. Exceptions: Fluconazole; Isavuconazonium Sulfate. Consider therapy modification
Antihepaciviral Combination Products: May increase the serum concentration of AmLODIPine. Management: Reduce amlodipine dose by at least 50% and monitor for increased amlodipine effects (eg, hypotension) if an antihepaciviral combination product is initiated. Consider therapy modification
Antipsychotic Agents (Second Generation [Atypical]): Blood Pressure Lowering Agents may enhance the hypotensive effect of Antipsychotic Agents (Second Generation [Atypical]). Monitor therapy
Aprepitant: May increase the serum concentration of CYP3A4 Substrates. Monitor therapy
Aprotinin: May diminish the antihypertensive effect of ACE Inhibitors. Monitor therapy
ARIPiprazole: CYP3A4 Inhibitors (Weak) may increase the serum concentration of ARIPiprazole. Management: Monitor for increased aripiprazole pharmacologic effects. Aripiprazole dose adjustments may or may not be required based on concomitant therapy and/or indication. Consult full interaction monograph for specific recommendations. Monitor therapy
Atosiban: Calcium Channel Blockers may enhance the adverse/toxic effect of Atosiban. Specifically, there may be an increased risk for pulmonary edema and/or dyspnea. Monitor therapy
AzaTHIOprine: ACE Inhibitors may enhance the myelosuppressive effect of AzaTHIOprine. Monitor therapy
Barbiturates: May increase the metabolism of Calcium Channel Blockers. Management: Monitor for decreased therapeutic effects of calcium channel blockers with concomitant barbiturate therapy. Calcium channel blocker dose adjustments may be necessary. Nimodipine Canadian labeling contraindicates concomitant use with phenobarbital. Monitor therapy
Barbiturates: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy
Bosentan: May decrease the serum concentration of CYP3A4 Substrates. Monitor therapy
Brimonidine (Topical): May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy
Calcium Channel Blockers (Nondihydropyridine): Calcium Channel Blockers (Dihydropyridine) may enhance the hypotensive effect of Calcium Channel Blockers (Nondihydropyridine). Calcium Channel Blockers (Nondihydropyridine) may increase the serum concentration of Calcium Channel Blockers (Dihydropyridine). Monitor therapy
Calcium Salts: May diminish the therapeutic effect of Calcium Channel Blockers. Monitor therapy
Canagliflozin: May enhance the hyperkalemic effect of ACE Inhibitors. Canagliflozin may enhance the hypotensive effect of ACE Inhibitors. Monitor therapy
CarBAMazepine: May increase the metabolism of Calcium Channel Blockers (Dihydropyridine). Management: Consider calcium channel blocker (CCB) dose adjustments or alternative therapy in patients receiving concomitant carbamazepine. Nimodipine Canadian labeling contraindicates concurrent use with carbamazepine. Consider therapy modification
Ciprofloxacin (Systemic): ACE Inhibitors may enhance the arrhythmogenic effect of Ciprofloxacin (Systemic). Monitor therapy
Clopidogrel: Calcium Channel Blockers may diminish the therapeutic effect of Clopidogrel. Monitor therapy
Conivaptan: May increase the serum concentration of CYP3A4 Substrates. Avoid combination
CycloSPORINE (Systemic): May decrease the metabolism of Calcium Channel Blockers (Dihydropyridine). Monitor therapy
CYP3A4 Inducers (Moderate): May decrease the serum concentration of CYP3A4 Substrates. Monitor therapy
CYP3A4 Inducers (Strong): May increase the metabolism of CYP3A4 Substrates. Management: Consider an alternative for one of the interacting drugs. Some combinations may be specifically contraindicated. Consult appropriate manufacturer labeling. Consider therapy modification
CYP3A4 Inhibitors (Moderate): May decrease the metabolism of CYP3A4 Substrates. Monitor therapy
CYP3A4 Inhibitors (Strong): May decrease the metabolism of CYP3A4 Substrates. Consider therapy modification
Dabrafenib: May decrease the serum concentration of CYP3A4 Substrates. Management: Seek alternatives to the CYP3A4 substrate when possible. If concomitant therapy cannot be avoided, monitor clinical effects of the substrate closely (particularly therapeutic effects). Consider therapy modification
Dapoxetine: May enhance the orthostatic hypotensive effect of ACE Inhibitors. Monitor therapy
Dapoxetine: May enhance the orthostatic hypotensive effect of Calcium Channel Blockers. Monitor therapy
Dasatinib: May increase the serum concentration of CYP3A4 Substrates. Monitor therapy
Deferasirox: May decrease the serum concentration of CYP3A4 Substrates. Monitor therapy
Diazoxide: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy
Dofetilide: CYP3A4 Inhibitors (Weak) may increase the serum concentration of Dofetilide. Monitor therapy
DPP-IV Inhibitors: May enhance the adverse/toxic effect of ACE Inhibitors. Specifically, the risk of angioedema may be increased. Monitor therapy
Drospirenone: ACE Inhibitors may enhance the hyperkalemic effect of Drospirenone. Monitor therapy
DULoxetine: Blood Pressure Lowering Agents may enhance the hypotensive effect of DULoxetine. Monitor therapy
Efavirenz: May decrease the serum concentration of Calcium Channel Blockers. Monitor therapy
Enzalutamide: May decrease the serum concentration of CYP3A4 Substrates. Management: Concurrent use of enzalutamide with CYP3A4 substrates that have a narrow therapeutic index should be avoided. Use of enzalutamide and any other CYP3A4 substrate should be performed with caution and close monitoring. Consider therapy modification
Eplerenone: May enhance the hyperkalemic effect of ACE Inhibitors. Monitor therapy
Everolimus: May enhance the adverse/toxic effect of ACE Inhibitors. Specifically, the risk of angioedema may be increased. Monitor therapy
Ferric Gluconate: ACE Inhibitors may enhance the adverse/toxic effect of Ferric Gluconate. Monitor therapy
Ferric Hydroxide Polymaltose Complex: ACE Inhibitors may enhance the adverse/toxic effect of Ferric Hydroxide Polymaltose Complex. Specifically, the risk for angioedema or allergic reactions may be increased. Monitor therapy
Flibanserin: CYP3A4 Inhibitors (Weak) may increase the serum concentration of Flibanserin. Monitor therapy
Fluconazole: May increase the serum concentration of Calcium Channel Blockers. Monitor therapy
Fosaprepitant: May increase the serum concentration of CYP3A4 Substrates. Monitor therapy
Fosphenytoin: Calcium Channel Blockers may increase the serum concentration of Fosphenytoin. Management: Monitor for phenytoin toxicity with concomitant use of a calcium channel blocker (CCB) or decreased phenytoin effects with CCB discontinuation. Monitor for decreased CCB therapeutic effects. Nimodipine Canadian labeling contraindicates use with phenytoin. Consider therapy modification
Fusidic Acid (Systemic): May increase the serum concentration of CYP3A4 Substrates. Avoid combination
Gold Sodium Thiomalate: ACE Inhibitors may enhance the adverse/toxic effect of Gold Sodium Thiomalate. An increased risk of nitritoid reactions has been appreciated. Monitor therapy
Grapefruit Juice: May increase the serum concentration of AmLODIPine. Management: The Canadian product Viacoram (perindopril/amlodipine) states that concurrent grapefruit juice is not recommended. US labeling for similar amlodipine-containing combination products states that there is no evidence of a significant interaction. Monitor therapy
Grass Pollen Allergen Extract (5 Grass Extract): ACE 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). Consider therapy modification
Heparin: May enhance the hyperkalemic effect of ACE Inhibitors. Monitor therapy
Heparin (Low Molecular Weight): May enhance the hyperkalemic effect of ACE Inhibitors. Monitor therapy
Herbs (Hypertensive Properties): May diminish the antihypertensive effect of Antihypertensive Agents. Monitor therapy
Herbs (Hypotensive Properties): May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy
HYDROcodone: CYP3A4 Inhibitors (Weak) may increase the serum concentration of HYDROcodone. Monitor therapy
Hypotension-Associated Agents: Blood Pressure Lowering Agents may enhance the hypotensive effect of Hypotension-Associated Agents. Monitor therapy
Icatibant: May diminish the antihypertensive effect of ACE Inhibitors. Monitor therapy
Idelalisib: May increase the serum concentration of CYP3A4 Substrates. Avoid combination
Iron Dextran Complex: ACE 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. Consider therapy modification
Ivacaftor: May increase the serum concentration of CYP3A4 Substrates. Monitor therapy
Lanthanum: May decrease the serum concentration of ACE Inhibitors. Management: Administer angiotensin-converting enzyme inhibitors at least two hours before or after lanthanum. Consider therapy modification
Levodopa: Blood Pressure Lowering Agents may enhance the hypotensive effect of Levodopa. Monitor therapy
Lithium: ACE 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. Consider therapy modification
Lomitapide: CYP3A4 Inhibitors (Weak) may increase the 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. Consider therapy modification
Loop Diuretics: May enhance the hypotensive effect of ACE Inhibitors. Loop Diuretics may enhance the nephrotoxic effect of ACE Inhibitors. Monitor therapy
Luliconazole: May increase the serum concentration of CYP3A4 Substrates. Monitor therapy
Macrolide Antibiotics: May decrease the metabolism of Calcium Channel Blockers. Management: Consider using a noninteracting macrolide. Felodipine Canadian labeling specifically recommends avoiding its use in combination with clarithromycin. Exceptions: Azithromycin (Systemic); Fidaxomicin; Roxithromycin; Spiramycin. Consider therapy modification
Magnesium Salts: Calcium Channel Blockers may enhance the adverse/toxic effect of Magnesium Salts. Magnesium Salts may enhance the hypotensive effect of Calcium Channel Blockers. Monitor therapy
Melatonin: May diminish the antihypertensive effect of Calcium Channel Blockers (Dihydropyridine). Monitor therapy
Methylphenidate: May diminish the antihypertensive effect of Antihypertensive Agents. Monitor therapy
MiFEPRIStone: May increase the serum concentration of CYP3A4 Substrates. Management: Minimize doses of CYP3A4 substrates, and monitor for increased concentrations/toxicity, during and 2 weeks following treatment with mifepristone. Avoid cyclosporine, dihydroergotamine, ergotamine, fentanyl, pimozide, quinidine, sirolimus, and tacrolimus. Consider therapy modification
Mitotane: May decrease the serum concentration of CYP3A4 Substrates. Management: Doses of CYP3A4 substrates may need to be adjusted substantially when used in patients being treated with mitotane. Consider therapy modification
Molsidomine: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy
Nafcillin: May increase the metabolism of Calcium Channel Blockers. Consider therapy modification
Naftopidil: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy
Netupitant: May increase the serum concentration of CYP3A4 Substrates. Monitor therapy
Neuromuscular-Blocking Agents (Nondepolarizing): Calcium Channel Blockers may enhance the neuromuscular-blocking effect of Neuromuscular-Blocking Agents (Nondepolarizing). Monitor therapy
Nicergoline: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy
Nicorandil: May enhance the hyperkalemic effect of ACE Inhibitors. Monitor therapy
Nicorandil: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy
NiMODipine: CYP3A4 Inhibitors (Weak) may increase the serum concentration of NiMODipine. Monitor therapy
Nitroprusside: Blood Pressure Lowering Agents may enhance the hypotensive effect of Nitroprusside. Monitor therapy
Nonsteroidal Anti-Inflammatory Agents: ACE 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 ACE Inhibitors. 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. Consider therapy modification
Osimertinib: May increase the serum concentration of CYP3A4 Substrates. Osimertinib may decrease the serum concentration of CYP3A4 Substrates. Monitor therapy
Palbociclib: May increase the serum concentration of CYP3A4 Substrates. Monitor therapy
Pentoxifylline: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy
Phenytoin: Calcium Channel Blockers may increase the serum concentration of Phenytoin. Phenytoin may decrease the serum concentration of Calcium Channel Blockers. Management: Avoid use of nimodipine or nifedipine with phenytoin. Monitor for phenytoin toxicity and/or decreased calcium channel blocker effects with any concurrent use. Consider therapy modification
Phosphodiesterase 5 Inhibitors: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy
Pimozide: CYP3A4 Inhibitors (Weak) may increase the serum concentration of Pimozide. Avoid combination
Potassium Salts: May enhance the hyperkalemic effect of ACE Inhibitors. Monitor therapy
Potassium-Sparing Diuretics: May enhance the hyperkalemic effect of ACE Inhibitors. Monitor therapy
Pregabalin: ACE Inhibitors may enhance the adverse/toxic effect of Pregabalin. Specifically, the risk of angioedema may be increased. Monitor therapy
Prostacyclin Analogues: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy
Quinagolide: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy
QuiNIDine: Calcium Channel Blockers (Dihydropyridine) may decrease the serum concentration of QuiNIDine. Calcium Channel Blockers (Dihydropyridine) may increase the serum concentration of QuiNIDine. QuiNIDine may increase the serum concentration of Calcium Channel Blockers (Dihydropyridine). Monitor therapy
Rifamycin Derivatives: May decrease the serum concentration of Calcium Channel Blockers. This primarily affects oral forms of calcium channel blockers. Management: The labeling for some US and Canadian calcium channel blockers contraindicate use with rifampin, however recommendations vary. Consult appropriate labeling. Consider therapy modification
Sacubitril: ACE Inhibitors may enhance the adverse/toxic effect of Sacubitril. Specifically, the risk of angioedema may be increased with this combination. Avoid combination
Salicylates: May enhance the nephrotoxic effect of ACE Inhibitors. Salicylates may diminish the therapeutic effect of ACE Inhibitors. Monitor therapy
Siltuximab: May decrease the serum concentration of CYP3A4 Substrates. Monitor therapy
Simeprevir: May increase the serum concentration of CYP3A4 Substrates. Monitor therapy
Simvastatin: AmLODIPine may increase the serum concentration of Simvastatin. Management: Avoid the concurrent use of amlodipine with simvastatin when possible. If used together, avoid doses of simvastatin greater than 20 mg/day (for adults). Consider therapy modification
Sirolimus: May enhance the adverse/toxic effect of ACE Inhibitors. Monitor therapy
Sodium Phosphates: ACE 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. Consider therapy modification
St Johns Wort: May decrease the serum concentration of CYP3A4 Substrates. Management: Consider an alternative for one of the interacting drugs. Some combinations may be specifically contraindicated. Consult appropriate manufacturer labeling. Consider therapy modification
Stiripentol: May increase the serum concentration of CYP3A4 Substrates. Management: Use of stiripentol with CYP3A4 substrates that are considered to have a narrow therapeutic index should be avoided due to the increased risk for adverse effects and toxicity. Any CYP3A4 substrate used with stiripentol requires closer monitoring. Consider therapy modification
Tacrolimus (Systemic): Calcium Channel Blockers (Dihydropyridine) may increase the serum concentration of Tacrolimus (Systemic). Monitor therapy
Temsirolimus: May enhance the adverse/toxic effect of ACE Inhibitors. Monitor therapy
Thiazide and Thiazide-Like Diuretics: May enhance the hypotensive effect of ACE Inhibitors. Thiazide and Thiazide-Like Diuretics may enhance the nephrotoxic effect of ACE Inhibitors. Monitor therapy
TiZANidine: CYP1A2 Inhibitors (Weak) may increase the serum concentration of TiZANidine. Management: Avoid these combinations when possible. If combined use cannot be avoided, initiate tizanidine at an adult dose of 2 mg and increase in 2-4 mg increments based on patient response. Monitor for increased effects of tizanidine, including adverse reactions. Consider therapy modification
Tocilizumab: May decrease the serum concentration of CYP3A4 Substrates. Monitor therapy
Tolvaptan: May enhance the hyperkalemic effect of ACE Inhibitors. Monitor therapy
Trimethoprim: May enhance the hyperkalemic effect of ACE Inhibitors. Monitor therapy
Yohimbine: May diminish the antihypertensive effect of Antihypertensive Agents. Monitor therapy
Blood pressure; serum creatinine and potassium, periodic CBC with differential
See Individual agents.
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%)
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). African-Americans 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) 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.
- 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.
- 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 patients 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: May be associated with deterioration of renal function and/or increases in serum creatinine, particularly in patients with low renal blood flow (eg, renal artery stenosis, heart failure) whose glomerular filtration rate (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.
Disease-related concerns:
- Aortic stenosis: Use amlodipine with extreme caution in patients with severe aortic stenosis; may reduce coronary perfusion resulting in ischemia. The Canadian labeling contraindicates use in this patient population.
- 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.
- Heart failure: Not recommended in patients with heart failure.
- Hepatic impairment: Not recommended in patients with hepatic impairment.
- Hypertrophic cardiomyopathy (HCM) with outflow tract obstruction: Use amlodipine with caution in patients with HCM and outflow tract obstruction since reduction in afterload may worsen symptoms associated with this condition. The Canadian labeling contraindicates use in this patient population.
- Renal artery stenosis: Use perindopril with caution in patients with unstented unilateral/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. The Canadian labeling contraindicates use in bilateral renal artery stenosis or renal artery stenosis in a single functioning kidney.
- Renal impairment: Not recommended in patients with CrCl <60 mL/minute.
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.
Dosage forms specific issues:
- Lactose: Formulation may contain lactose. The Canadian labeling contraindicates use in patients with hereditary problems of galactose intolerance, glucose-galactose malabsorption, or Lapp lactase deficiency.
Special populations:
- Elderly: Not recommended in patients > 65 years.
- Pregnancy: [US 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.
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).
D
The Canadian labeling contraindicates use in women who are pregnant or planning to become pregnant.
[US 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. See individual agents.
Amlodipine is a dihydropyridine calcium channel antagonist that inhibits transmembrane influx of calcium ions into vascular smooth muscle and cardiac muscle producing 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 is a prodrug for perindoprilat, which acts as a competitive inhibitor of angiotensin-converting enzyme (ACE); 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.
- Discuss specific use of drug and side effects with patient as it relates to treatment. (HCAHPS: During this hospital stay, were you given any medicine that you had not taken before? Before giving you any new medicine, how often did hospital staff tell you what the medicine was for? How often did hospital staff describe possible side effects in a way you could understand?)
- Patient may experience headache. Have patient report immediately to prescriber signs of kidney problems (urinary retention, blood in urine, change in amount of urine passed, weight gain), signs of high potassium (abnormal heartbeat, confusion, dizziness, passing out, weak, shortness of breath, numbness or tingling feeling), severe dizziness, passing out, cough that will not go away, angina, shortness of breath, excessive weight gain, swelling of arms or legs, severe abdominal pain, nausea, vomiting, or dysphagia (HCAHPS).
- Educate patient about signs of a significant reaction (eg, wheezing; chest tightness; fever; itching; bad cough; blue skin color; seizures; or swelling of face, lips, tongue, or throat). Note: This is not a comprehensive list of all side effects. Patient should consult prescriber for additional questions.
Intended Use and Disclaimer: Should not be printed and given to patients. This information is intended to serve as a concise initial reference for healthcare professionals to use when discussing medications with a patient. You must ultimately rely on your own discretion, experience and judgment in diagnosing, treating and advising patients.