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ALERT: U.S. Boxed Warning
The FDA-approved labeling includes a boxed warning. See Warnings/Precautions section and/or refer to product labeling for additional detail.
Medication Safety Issues
Sound-alike/look-alike issues:
Lisinopril may be confused with fosinopril, Lioresal®, Risperdal®
Prinivil® may be confused with Plendil®, Pravachol®, Prevacid®, Prilosec®, Proventil®
Zestril® may be confused with Desyrel®, Restoril®, Vistaril®, Zetia®, Zostrix®
International issues:
Acepril® [Denmark] may be confused with Accupril® which is a brand name for quinapril in the U.S.
Acepril®: Brand name for enalapril in Hungary and Switzerland; brand name for captopril in Great Britain
Carace® [Ireland; Great Britain] may be confused with Carac™ which is a brand name for fluorouracil in the U.S.
Zetril® may be confused with Nostril® which is a brand name for chlorhexidine/cetrimonium in France
Pronunciation
(lyse IN oh pril)
U.S. Brand Names
Generic Available
Yes
Canadian Brand Names
Pharmacologic Category
Pharmacologic Category Synonyms
Use: Labeled Indications
Treatment of hypertension, either alone or in combination with other antihypertensive agents; adjunctive therapy in treatment of heart failure (HF); treatment of acute myocardial infarction (MI) within 24 hours in hemodynamically-stable patients to improve survival
Pregnancy Risk Factor
C (1st trimester); D (2nd and 3rd trimesters)
Pregnancy Considerations
Due to adverse events observed in some animal studies, lisinopril is considered pregnancy category C during the first trimester. Based on human data, lisinopril is considered pregnancy category D if used during the second and third trimesters (per the manufacturer; however, one study suggests that fetal injury may occur at anytime during pregnancy). Lisinopril crosses the placenta. First trimester exposure to ACE inhibitors may cause major congenital malformations. An increased risk of cardiovascular and/or central nervous system malformations was observed in one study; however, an increased risk of teratogenic events was not observed in other studies. Second and third trimester use of an ACE inhibitor is associated with oligohydramnios. Oligohydramnios due to decreased fetal renal function may lead to fetal limb contractures, craniofacial deformation, and hypoplastic lung development. The use of ACE inhibitors during the second and third trimesters is also associated with anuria, hypotension, renal failure (reversible or irreversible), skull hypoplasia, and death in the fetus/neonate. Chronic maternal hypertension itself is also associated with adverse events in the fetus/infant. ACE inhibitors are not recommended during pregnancy to treat maternal hypertension or heart failure. Those who are planning a pregnancy should be considered for other medication options if an ACE inhibitor is currently prescribed or the ACE inhibitor should be discontinued as soon as possible once pregnancy is detected. The exposed fetus should be monitored for fetal growth, amniotic fluid volume, and organ formation. Infants exposed to an ACE inhibitor in utero, especially during the second and third trimester, should be monitored for hyperkalemia, hypotension, and oliguria.[U.S. Boxed Warning]: Based on human data, ACE inhibitors can cause injury and death to the developing fetus when used in the second and third trimesters. ACE inhibitors should be discontinued as soon as possible once pregnancy is detected.
Lactation
Excretion in breast milk unknown/not recommended
Breast-Feeding Considerations
It is not known if lisinopril is excreted in breast milk. Breast-feeding is not recommended by the manufacturer.
Contraindications
Hypersensitivity to lisinopril or any component of the formulation; angioedema related to previous treatment with an ACE inhibitor; patients with idiopathic or hereditary angioedema
Warnings/Precautions
Boxed warnings:
• Pregnancy: See “Special populations” below.
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). African-Americans may be at an increased risk. 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; 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 1-4 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 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.
• Neutropenia/agranulocytosis: Another ACE Inhibitor, captopril, has been associated with rare cases of agranulocytosis, neutropenia, or leukopenia with myeloid hypoplasia. 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.
• 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 with 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 with caution in patients with collagen vascular disease especially with concomitant renal impairment; may be at increased risk for hematologic toxicity.
• 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.
• Renal artery stenosis: Use 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.
• Renal impairment: Use with caution in pre-existing renal insufficiency; dosage adjustment may be needed. Avoid rapid dosage escalation which may lead to further renal impairment.
Special populations:
• Pediatrics: Safety and efficacy have not been established in children <6 years of age or with a Clcr ?30 mL/minute.
• Pregnancy: [U.S. Boxed Warning]: Based on human data, ACEIs can cause injury and death to the developing fetus when used in the second and third trimesters. ACEIs should be discontinued as soon as possible once pregnancy is detected.
Other warnings/precautions:
• Surgery: 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.
Adverse Reactions
Note: Frequency ranges include data from hypertension and heart failure trials. Higher rates of adverse reactions have generally been noted in patients with CHF. However, the frequency of adverse effects associated with placebo is also increased in this population.
1% to 10%:
Cardiovascular: Orthostatic effects (1%), hypotension (1% to 4%)
Central nervous system: Headache (4% to 6%), dizziness (5% to 12%), fatigue (3%)
Dermatologic: Rash (1% to 2%)
Endocrine & metabolic: Hyperkalemia (2% to 5%)
Gastrointestinal: Diarrhea (3% to 4%), nausea (2%), vomiting (1%), abdominal pain (2%)
Genitourinary: Impotence (1%)
Hematologic: Decreased hemoglobin (small)
Neuromuscular & skeletal: Chest pain (3%), weakness (1%)
Renal: BUN increased (2%); deterioration in renal function (in patients with bilateral renal artery stenosis or hypovolemia); serum creatinine increased (often transient)
Respiratory: Cough (4% to 9%), upper respiratory infection (1% to 2%)
<1%: Acute renal failure, alopecia, anaphylactoid reactions, angioedema, anuria, arrhythmia, arthralgia, arthritis, asthma, ataxia, azotemia, bilirubin increased, bone marrow suppression, bronchospasm, cardiac arrest, cutaneous pseudolymphoma, decreased libido, gout, hemolytic anemia, hepatic necrosis, hepatitis, hyponatremia, leukopenia, jaundice (cholestatic), MI, neutropenia, oliguria, orthostatic hypotension, pancreatitis, paresthesia, pemphigus, peripheral neuropathy, photosensitivity, pleural effusion, pulmonary embolism, pulmonary infiltrates, Stevens-Johnson syndrome, stroke, syncope, systemic lupus erythematosus, thrombocytopenia, TIA, toxic epidermal necrolysis, transaminases increased, tremor, urticaria, vasculitis, vertigo, vision loss, volume overload, vomiting, weight gain/loss, wheezing, xerostomia
In addition, a syndrome which may include fever, myalgia, arthralgia, interstitial nephritis, vasculitis, rash, eosinophilia, positive ANA, and elevated ESR has been reported with ACE inhibitors.
Drug Interactions
Allopurinol: ACE Inhibitors may enhance the potential for allergic or hypersensitivity reactions to Allopurinol. Risk D: Consider therapy modification
Angiotensin II Receptor Blockers: May enhance the adverse/toxic effect of ACE Inhibitors. Risk C: Monitor therapy
Antacids: May decrease the serum concentration of ACE Inhibitors. Risk C: Monitor therapy
Aprotinin: May diminish the antihypertensive effect of ACE Inhibitors. Risk C: Monitor therapy
Azathioprine: ACE Inhibitors may enhance the neutropenic effect of Azathioprine. Risk C: Monitor therapy
CycloSPORINE: ACE Inhibitors may enhance the nephrotoxic effect of CycloSPORINE. Risk D: Consider therapy modification
Diazoxide: May enhance the hypotensive effect of Antihypertensives. Risk C: Monitor therapy
Eplerenone: May enhance the hyperkalemic effect of ACE Inhibitors. Risk C: Monitor therapy
Ferric Gluconate: ACE Inhibitors may enhance the adverse/toxic effect of Ferric Gluconate. Risk C: Monitor therapy
Gold Sodium Thiomalate: ACE Inhibitors may enhance the adverse/toxic effect of Gold Sodium Thiomalate. An increased risk of nitritoid reactions has been appreciated. Risk C: Monitor therapy
Herbs (Hypertensive Properties): May diminish the antihypertensive effect of Antihypertensives. Risk C: Monitor therapy
Herbs (Hypotensive Properties): May enhance the hypotensive effect of Antihypertensives. Risk C: Monitor therapy
Lithium: ACE Inhibitors may increase the serum concentration of Lithium. Risk D: Consider therapy modification
Loop Diuretics: May enhance the hypotensive effect of ACE Inhibitors. Specifically, postural hypotension which can accompany ACE Inhibitor initiation. Loop Diuretics may enhance the nephrotoxic effect of ACE Inhibitors. Risk C: Monitor therapy
Methylphenidate: May diminish the antihypertensive effect of Antihypertensives. Risk C: Monitor therapy
Nonsteroidal Anti-Inflammatory Agents: May diminish the antihypertensive effect of ACE Inhibitors. Risk C: Monitor therapy
Potassium Salts: May enhance the hyperkalemic effect of ACE Inhibitors. Risk C: Monitor therapy
Potassium-Sparing Diuretics: May enhance the hyperkalemic effect of ACE Inhibitors. Risk C: Monitor therapy
Prostacyclin Analogues: May enhance the hypotensive effect of Antihypertensives. Risk C: Monitor therapy
Rituximab: Antihypertensives may enhance the hypotensive effect of Rituximab. Risk D: Consider therapy modification
Salicylates: May diminish the antihypertensive effect of ACE Inhibitors. They may also diminish other beneficial pharmacodynamic effects desired for the treatment of CHF. The effects are likely dose-related. 100 mg doses aspirin appear to cause no problems, whereas 300 mg doses appear to significantly affect ACE Inhibitor efficacy. Risk C: Monitor therapy
Sirolimus: May enhance the adverse/toxic effect of ACE Inhibitors. Risk C: Monitor therapy
Temsirolimus: May enhance the adverse/toxic effect of ACE Inhibitors. Risk C: Monitor therapy
Thiazide Diuretics: May enhance the hypotensive effect of ACE Inhibitors. Specifically, postural hypotension which can accompany ACE Inhibitor initiation. Thiazide Diuretics may enhance the nephrotoxic effect of ACE Inhibitors. Risk C: Monitor therapy
Trimethoprim: May enhance the hyperkalemic effect of ACE Inhibitors. Risk C: Monitor therapy
Ethanol/Nutrition/Herb Interactions
Food: Potassium-containing salt substitutes may increase risk of hyperkalemia.
Herb/Nutraceutical: Avoid bayberry, blue cohosh, cayenne, ephedra, ginger, ginseng (American), kola, licorice (may worsen hypertension). Avoid black cohosh, California poppy, coleus, golden seal, hawthorn, mistletoe, periwinkle, quinine, shepherd's purse (may have increased antihypertensive effect).
Mechanism of Action
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 causes an increase in plasma renin activity and a reduction in aldosterone secretion; a CNS mechanism may also be involved in hypotensive effect as angiotensin II increases adrenergic outflow from CNS; vasoactive kallikreins may be decreased in conversion to active hormones by ACE inhibitors, thus reducing blood pressure
Pharmacodynamics/Kinetics
Onset of action: 1 hour
Peak effect: Hypotensive: Oral: ~6 hours
Duration: 24 hours
Absorption: Well absorbed; unaffected by food
Protein binding: 25%
Metabolism: Not metabolized
Bioavailability: Decreased with NYHA Class II-IV heart failure
Half-life elimination: 11-12 hours
Time to peak: ~7 hours
Excretion: Primarily urine (as unchanged drug)
Dosage
Oral:
Hypertension:
Children ?6 years: Initial: 0.07 mg/kg once daily (up to 5 mg); increase dose at 1- to 2-week intervals; doses >0.61 mg/kg or >40 mg have not been evaluated.
Adults: Usual dosage range (JNC 7): 10-40 mg/day
Not maintained on diuretic: Initial: 10 mg/day
Maintained on diuretic: Initial: 5 mg/day
Note: Antihypertensive effect may diminish toward the end of the dosing interval especially with doses of 10 mg/day. An increased dose may aid in extending the duration of antihypertensive effect. Doses up to 80 mg/day have been used, but do not appear to give greater effect.
Elderly: Initial: 2.5-5 mg/day; increase doses 2.5-5 mg/day at 1- to 2-week intervals; maximum daily dose: 40 mg
Patients taking diuretics should have them discontinued 2-3 days prior to initiating lisinopril if possible. Restart diuretic after blood pressure is stable if needed. If diuretic cannot be discontinued prior to therapy, begin with 5 mg with close supervision until stable blood pressure. In patients with hyponatremia (<130 mEq/L), start dose at 2.5 mg/day
Heart failure: Adults: Initial: 2.5-5 mg once daily; then increase by no more than 10 mg increments at intervals no less than 2 weeks to a maximum daily dose of 40 mg. Usual maintenance: 5-40 mg/day as a single dose. Target dose: 20-40 mg once daily (ACC/AHA 2005 Heart Failure Guidelines)
Note: If patient has hyponatremia (serum sodium <130 meq/L) or renal impairment (Clcr <30 mL/minute or creatinine >3 mg/dL), then initial dose should be 2.5 mg/day
Acute myocardial infarction (within 24 hours in hemodynamically stable patients): Oral: 5 mg immediately, then 5 mg at 24 hours, 10 mg at 48 hours, and 10 mg every day thereafter for 6 weeks. Patients should continue to receive standard treatments such as thrombolytics, aspirin, and beta-blockers.
Dosing adjustment in renal impairment:
Hypertension:
Adults: Initial doses should be modified and upward titration should be cautious, based on response (maximum: 40 mg/day)
Clcr >30 mL/minute: Initial: 10 mg/day
Clcr 10-30 mL/minute: Initial: 5 mg/day
Hemodialysis: Initial: 2.5 mg/day; dialyzable (50%)
Children: Use in not recommended in pediatric patients with GFR <30 mL/minute/1.73 m2
Heart failure: Adults: Clcr <30 mL/minute or creatinine >3 mg/dL): Initial: 2.5 mg/day
Administration: Oral
Watch for hypotensive effects within 1-3 hours of first dose or new higher dose.
Monitoring Parameters
BUN, serum creatinine, renal function, WBC, and potassium; if patient has collagen vascular disease and/or renal impairment, periodically monitor CBC with differential
Test Interactions
May cause false-positive results in urine acetone determinations using sodium nitroprusside reagent
Dietary Considerations
Use potassium-containing salt substitutes cautiously in patients with diabetes, patients with renal dysfunction, or those maintained on potassium supplements or potassium-sparing diuretics.
Patient Education
Do not take any new medication during therapy unless approved by prescriber. Take exactly as directed; do not discontinue without consulting prescriber. Take first dose at bedtime. Take all doses on an empty stomach, 1 hour before or 2 hours after meals. Do not use potassium supplement or salt substitutes without consulting prescriber. This drug does not eliminate need for diet or exercise regimen as recommended by prescriber. May cause dizziness, fainting, or lightheadedness (use caution when driving or engaging in tasks that require alertness until response to drug is known); postural hypotension (use caution when rising from lying or sitting position or climbing stairs); or nausea, vomiting, abdominal pain, dry mouth, or transient loss of appetite (small frequent meals, frequent mouth care, sucking lozenges, or chewing gum may help), report if these persist. Report chest pain or palpitations; mouth sores; fever or chills; swelling of extremities, face, mouth, or tongue; skin rash; numbness, tingling, or pain in muscles; respiratory difficulty or unusual cough; other persistent adverse reactions. Pregnancy/breast-feeding precautions: Inform prescriber if you are or intend to become pregnant. This drug should not be used in the 2nd or 3rd trimester of pregnancy. Consult prescriber for appropriate contraceptive measures if necessary or if you suspect you might be pregnant. Breast-feeding is not recommended.
Geriatric Considerations
Due to frequent decreases in glomerular filtration (also creatinine clearance) with aging, elderly patients may have exaggerated responses to ACE inhibitors. Differences in clinical response due to hepatic changes are not observed. ACE inhibitors may be preferred agents in elderly patients with congestive heart failure and diabetes mellitus. Diabetic proteinuria is reduced and insulin sensitivity is enhanced. In general, the side effect profile is favorable in the elderly and causes little or no CNS confusion. Use lowest dose recommendations initially. Many elderly may be volume depleted due to diuretic use and/or blunted thirst reflex resulting in inadequate fluid intake.
Anesthesia and Critical Care Concerns/Other Considerations
Due to decreases in glomerular filtration (also creatinine clearance) with aging, severe congestive heart failure and renal failure, these patients may experience renal dysfunction with ACE inhibitor administration.
ACE inhibitor therapy may elicit rapid increases in potassium and creatinine, especially when used in patients with bilateral renal artery stenosis. When ACE inhibition is introduced in patients with pre-existing diuretic therapy who are hypovolemic, the ACE inhibitor may induce acute hypotension. Concomitant NSAID therapy may attenuate blood pressure control. Because of the potent teratogenic effects of ACE inhibitors, these drugs should be avoided, if possible, when treating women of childbearing potential not on effective birth control measures.
Cardiovascular Considerations
Congestive Heart Failure: The ACC/AHA 2005 Heart Failure Guidelines recommend that ACE inhibitors be used in patients with a reduced EF (with or without heart failure symptoms) unless contraindicated. ACE inhibitors decrease morbidity and mortality in patients with asymptomatic and symptomatic left ventricular dysfunction. In this situation, they decrease hospitalizations for, and retard progression to, congestive heart failure. When used in patients with heart failure, the target dose should be achieved, if possible. Lower daily doses of ACE inhibitors have demonstrated the same mortality effects as high doses, but have not decreased hospitalizations to the extent that high-dose ACE inhibitors have, as demonstrated in the ATLAS study (Packer M, 1999).
Hypertension: The ALLHAT study (ALLHAT Collaborative Group, 2002) compared CV outcomes of lisinopril, amlodipine, or chlorthalidone in hypertensive patients having at least one other risk factor for coronary heart disease. Investigators found no difference between the groups on the primary outcome of fatal coronary disease or nonfatal MI. The ACC/AHA 2005 Heart Failure Guidelines suggest that ACE inhibitors or angiotensin receptor blockers (ARBs) can be beneficial in patients with hypertension and LVH without symptoms of heart failure. JNC 7 suggests that patients can benefit from treatment with an ACE inhibitor if they have hypertension and heart failure, acute myocardial infarction, high coronary disease risk, diabetes, chronic kidney disease, or history of stroke.
Vascular Disease: The ACC/AHA 2005 Heart Failure Guidelines suggest that ACE inhibitors can be useful in preventing heart failure in patients who have a history of atherosclerotic vascular disease, diabetes, or hypertension with associated cardiovascular risk factors. The HOPE trial (Heart Outcomes Prevention Evaluation Study Investigators, 2000) investigated the value of an ACE inhibitor (ramipril 5-10 mg daily) versus placebo in patients who had evidence of vascular disease or diabetes (one other cardiovascular risk factor) and were at least 55 years of age. Patients were excluded if they had a low ejection fraction, heart failure, or were on an ACE inhibitor. The primary outcome was a composite of death from cardiovascular cause, myocardial infarction, or stroke; 9297 patients were enrolled and randomized. Ramipril significantly reduced the risk of death from CV causes, MI, or stroke over placebo. New cases of diabetes were also reduced in the ramipril group. In the EUROPA trial, patients with stable coronary artery disease (at low risk for cardiovascular events) received perindopril or placebo and were evaluated for incidence of cardiovascular events after four years of treatment. In this randomized, placebo-controlled, prospective study, 12,218 patients received either perindopril (8 mg/day, n=6110) or placebo (n=6108) and were assessed for the primary endpoint of a cardiovascular event, defined as cardiovascular death, myocardial infarction, or cardiac arrest. The study population was well balanced with respect to baseline demographics and concomitant medication use (including beta-blockers, platelet inhibitors, antihyperlipidemics, calcium channel blockers, nitrates, and diuretics). Intent-to-treat analysis revealed that 603 (10%) of placebo patients experienced the primary endpoint of a cardiovascular event compared to 488 (8%) of perindopril-receiving patients, for a 20% relative risk reduction (p=0.0003). This result was not influenced by presence of other comorbidities (eg, diabetes, hypertension) or concomitant beta-blocker, calcium channel blocker, or lipid-lowering therapies. Withdrawal from the study (postrandomization) due to adverse reactions was similar between treatment groups. Number needed to treat analysis suggests that treatment of 50 patients over a 4-year period will prevent one major cardiovascular event.
Acute Coronary Syndromes: In the treatment of unstable angina/non-ST-segment elevation MI, ACE inhibitors are recommended when hypertension persists despite treatment with nitroglycerin and a beta-blocker in patients with LV systolic dysfunction or CHF and in ischemic patients with diabetes (Class I). ACE inhibitors are also recommended for all post-ACS individuals (Class IIa). According to 2004 ACC/AHA STEMI guidelines, an ACE inhibitor should be administered orally within the first 24 hours of STEMI to patients with anterior infarction, pulmonary congestion, or LVEF <0.4, in the absence of hypotension or known contraindications to this class of medicines. In the emergency management of complicated STEMI, a short-acting ACEI (eg, captopril 1-6.25 mg) may be added once the patient's systolic blood pressure is >100 mm Hg and not <30 mm Hg below baseline. The VALIANT trial evaluated the effects of valsartan (target dose: 160 mg twice daily), captopril (target dose: 50 mg twice daily), and the combination (target doses: valsartan 80 mg twice daily and captopril 150 mg once daily) in a randomized, double-blind trial of patients with acute MI (0.5-10 days post-MI) complicated by left ventricular systolic dysfunction, heart failure, or both. Enrollment in the study numbered 14,703 patients and followed for a median of 24.7 months. There was no difference in the primary endpoint (all cause mortality) among the 3 groups. There was no difference in incidence of CV death, recurrent MI, or hospitalization for heart failure either. Hypotension and renal dysfunction occurred significantly more often in the valsartan group than captopril alone. Cough, rash, and taste disturbances occurred more often in the captopril group. The authors (Pfeffer MA, 2003) concluded that valsartan is as effective as captopril in patients who are at high risk for cardiovascular events after MI. Combining valsartan with captopril increased the rate of adverse events without improving survival.
Potential Adverse Events: ACE inhibitor therapy may elicit rapid increases in potassium and creatinine, especially when used in patients with bilateral renal artery stenosis. When ACE inhibition is introduced in patients with pre-existing diuretic therapy who are hypovolemic, the ACE inhibitor may induce acute hypotension. In those patients experiencing cough on an ACE inhibitor, the ACE inhibitor may be discontinued and, if necessary, ARB therapy instituted. Because of the potent teratogenic effects of ACE inhibitors, these drugs should be avoided, if possible, when treating women of childbearing potential not on effective birth control measures.
Drug Interactions: Concomitant indomethacin therapy may blunt the reduction in sitting and 24-hour ambulatory diastolic blood pressure. Use of NSAIDs should be avoided or limited, with monitoring of blood pressure control in this setting. In patients with heart failure, NSAID use may be associated with an increased risk for fluid accumulation and edema.
Dental Health: Effects on Dental Treatment
Key adverse event(s) related to dental treatment: Orthostatic effects.
Dental Health: Vasoconstrictor/Local Anesthetic Precautions
No information available to require special precautions
Mental Health: Effects on Mental Status
May cause dizziness or fatigue; may rarely cause sedation, insomnia, or depression
Mental Health: Effects on Psychiatric Treatment
May cause neutropenia; use caution with clozapine and carbamazepine; may decrease lithium clearance resulting in an increase in serum lithium levels and potential lithium toxicity; monitor serum lithium levels
Nursing: Physical Assessment/Monitoring
Assess patient carefully for use cautions prior to beginning therapy. Assess potential for interactions with other pharmacological agents or herbal products patient is taking that may impact fluid balance or cardiac status. Patient should be monitored for adverse reactions following first dose, following any increase in dose and regularly during therapy (eg, angioedema that may potentially affect airway or intestine, hypovolemia, postural hypotension, or anaphylactic reaction). Evaluate results of laboratory tests and therapeutic effectiveness on a (normotensive) regular basis. Teach patient proper use, possible side effects/appropriate interventions, and adverse symptoms to report.
Dosage Forms
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Tablet: 2.5 mg, 5 mg, 10 mg, 20 mg, 30 mg, 40 mg
Prinivil®: 5 mg, 10 mg, 20 mg
Zestril®: 2.5 mg, 5 mg, 10 mg, 20 mg, 30 mg, 40 mg
Pricing: U.S. (www.drugstore.com)
Tablets (Lisinopril)
2.5 mg (30): $12.99
5 mg (30): $14.89
10 mg (30): $12.99
20 mg (30): $13.99
30 mg (30): $20.99
40 mg (30): $19.99
Tablets (Prinivil)
2.5 mg (60): $42.99
5 mg (60): $65.99
20 mg (90): $104.51
Tablets (Zestril)
2.5 mg (30): $36.39
5 mg (30): $47.83
10 mg (30): $51.99
20 mg (30): $51.91
30 mg (30): $68.63
40 mg (30): $72.79
Extemporaneously Prepared
Preparation of oral suspension (1 mg/mL): Note: Mix in a polyethylene terephthalate bottle. Add 10 mL of purified water (USP) to a bottle containing ten lisinopril 20 mg tablets (total 200 mg). Shake for at least 1 minute; then add 30 mL Bicitra® and 160 mL Ora-Sweet SF™ and shake gently to suspend contents. Store at 25°C (77°F); stable for up to 4 weeks.
References
ALLHAT Officers and Coordinators for the ALLHAT Collaborative Research Group, "Major Outcomes in High-Risk Hypertensive Patients Randomized to Angiotensin-Converting Enzyme Inhibitor or Calcium Channel Blocker vs Diuretic: The Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT)," JAMA, 2002, 288(23):2981-97.
Antman EM, Anbe SC, Alpert JS, et al, “ACC/AHA Guidelines for the Management of Patients With ST-Elevation Myocardial Infarction - Executive Summary: A Report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Writing Committee to Revise the 1999 Guidelines for the Management of Patients With Acute Myocardial Infarction),” Circulation, 2004, 110(5):588-636. Available at: http://www.circulationaha.org/cgi/content/full/110/5/588. Last accessed October 26, 2004.
Braunwald E, Antman EM, Beasley JW, et al, “ACC/AHA 2002 Guideline Update for the Management of Patients With Unstable Angina and Non-ST-Segment Elevation Myocardial Infarction - Summary Article: A Report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Committee on the Management of Patients With Unstable Angina),” J Am Coll Cardiol, 2002, 40(7):1366-74. Available at: http://www.acc.org/clinical/guidelines/unstable/incorporated/index.htm. Accessed May 20, 2003.
Chase MP, Fiarman GS, Scholz FJ, et al, “Angioedema of the Small Bowel Due to an Angiotensin-Converting Enzyme Inhibitor,” J Clin Gastroenterol, 2000, 31(3):254-7.
Chobanian AV, Bakris GL, Black HR, et al, “The Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure: The JNC 7 Report,” JAMA, 2003, 289(19):2560-71.
Conlin P, Moore T, Swartz S, et al, “Effect of Indomethacin on Blood Pressure Lowering by Captopril and Losartan in Hypertensive Patients,” Hypertension, 2000, 36(3):461-5.
“Consensus Recommendations for the Management of Chronic Heart Failure. On Behalf of the Membership of the Advisory Council to Improve Outcomes Nationwide in Heart Failure,” Am J Cardiol, 1999, 83(2A):1A-38A.
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.
Fox KM and EURopean Trial on Reduction of Cardiac Events With Perindopril in Stable Coronary Artery Disease Investigators, "Efficacy of Perindopril in Reduction of Cardiovascular Events Among Patients With Stable Coronary Artery Disease: Randomised, Double-Blind, Placebo-Controlled, Multicentre Trial (The EUROPA Study)," Lancet, 2003, 362(9386):782-8.
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