Lisinopril

Pronunciation

(lyse IN oh pril)

U.S. Brand Names

Prinivil®; Zestril®

Generic Available

Yes

Canadian Brand Names

Apo-Lisinopril®; Prinivil®; Zestril®

Use

Treatment of hypertension, either alone or in combination with other antihypertensive agents; adjunctive therapy in treatment of CHF (afterload reduction); treatment of acute myocardial infarction within 24 hours in hemodynamically-stable patients to improve survival; treatment of left ventricular dysfunction after myocardial infarction

Pregnancy Risk Factor

C/D (2nd and 3rd trimesters)

Pregnancy Implications

Cranial defects, hypocalvaria/acalvaria, oligohydramnios, persistent anuria following delivery, hypotension, renal defects, renal dysgenesis/dysplasia, renal failure, pulmonary hypoplasia, limb contractures secondary to oligohydramnios, and stillbirth reported. ACE inhibitors should be avoided during pregnancy, particularly in the 2nd and 3rd trimesters.

Lactation

Excretion in breast milk unknown/not recommended

Contraindications

Hypersensitivity to lisinopril or any component of the formulation; angioedema related to previous treatment with an ACE inhibitor; bilateral renal artery stenosis; pregnancy (2nd and 3rd trimesters)

Warnings/Precautions

Anaphylactic reactions can occur. Angioedema can occur at any time during treatment (especially following first dose). Angioedema may involve head and neck (potentially affecting the airway) or the intestine (presenting with abdominal pain). Careful blood pressure monitoring with first dose (hypotension can occur especially in volume-depleted patients). Dosage adjustment needed in renal impairment. Use with caution in hypovolemia; collagen vascular diseases; valvular stenosis (particularly aortic stenosis); hyperkalemia; or before, during, or immediately after anesthesia. Avoid rapid dosage escalation, which may lead to renal insufficiency. Rare toxicities associated with ACE inhibitors include cholestatic jaundice (which may progress to hepatic necrosis) and neutropenia/agranulocytosis with myeloid hyperplasia. If patient has renal impairment then a baseline WBC with differential and serum creatinine should be evaluated and monitored closely during the first 3 months of therapy. Hypersensitivity reactions may be seen during hemodialysis with high-flux dialysis membranes (eg, AN69). Deterioration in renal function can occur with initiation. Use with caution in unilateral renal artery stenosis and pre-existing renal insufficiency. Safety and efficacy have not been established in children <6 years of age.

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 (2% to 2%)

<1%: Acute renal failure, alopecia, anaphylactoid reactions, angioedema, anuria, arrhythmia, arthralgia, arthritis, asthma, ataxia, azotemia, blurred vision, bone marrow suppression, bronchitis, bronchospasm, cardiac arrest, cerebrovascular accident, confusion, constipation, decreased libido, dehydration, diabetes mellitus, diaphoresis, diplopia, dyspepsia, edema, epistaxis, erythema, flatulence, flushing, gastrointestinal cramps, gout, heartburn, hepatitis, hyperkalemia, hyponatremia, increased bilirubin, infiltrates, insomnia, irritability, jaundice (cholestatic), laryngitis, memory impairment, muscle cramps, MI, nasal congestion, nervousness, neutropenia, oliguria, orthostatic hypotension, palpitation, pancreatitis, paresthesia, paroxysmal nocturnal dyspnea, pemphigus, peripheral edema, peripheral neuropathy, pharyngitis, photophobia, photosensitivity, pleural effusion, pulmonary embolism, renal dysfunction, rhinitis, rhinorrhea, sinusitis, somnolence, Stevens-Johnson syndromes, stroke, systemic lupus erythematosus, thrombocytopenia, TIA, tinnitus, 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.

Overdosage/Toxicology

Mild hypotension has been the primary toxic effect seen with acute overdose. Bradycardia may also occur; hyperkalemia occurs even with therapeutic doses, especially in patients with renal insufficiency and those taking NSAIDs. Treatment and is symptomatic and supportive.

Drug Interactions

Allopurinol: Case reports (rare) indicate a possible increased risk of hypersensitivity reactions when combined with lisinopril.

Alpha1 blockers: Hypotensive effect increased.

Aspirin: The effects of ACE inhibitors may be blunted by aspirin administration, particularly at higher dosages (see Cardiovascular Considerations) and/or increase adverse renal effects.

Diuretics: Hypovolemia due to diuretics may precipitate acute hypotensive events or acute renal failure.

Insulin: Risk of hypoglycemia may be increased.

Lithium: Risk of lithium toxicity may be increased; monitor lithium levels, especially the first 4 weeks of therapy.

Mercaptopurine: Risk of neutropenia may be increased.

NSAIDs: May attenuate hypertensive efficacy; effect has been seen with captopril and may occur with other ACE inhibitors; monitor blood pressure. May increase adverse renal effects.

Potassium-sparing diuretics (amiloride, spironolactone, triamterene): Increased risk of hyperkalemia.

Potassium supplements may increase the risk of hyperkalemia.

Trimethoprim (high dose) may increase the risk of hyperkalemia.

Ethanol/Nutrition/Herb Interactions

Herb/Nutraceutical: Avoid dong quai if using for hypertension (has estrogenic activity). Avoid ephedra, yohimbe, ginseng (may worsen hypertension). Avoid garlic (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%

Half-life elimination: 11-12 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: Initial: 10 mg/day; increase doses 5-10 mg/day at 1- to 2-week intervals; maximum daily dose: 40 mg

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,

Congestive heart failure: Adults: Initial: 5 mg; 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. Patients should start/continue standard therapy, including diuretics, beta-blockers, and digoxin, as indicated.

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:

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

Administration

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

Test Interactions

May cause false-positive results in urine acetone determinations using sodium nitroprusside reagent; increased potassium (S); increased serum creatinine/BUN

Patient Education

Inform prescriber of all prescriptions, OTC medications, or herbal products you are taking, and any allergies you have. Do not take any new medication during therapy unless approved by prescriber. Do not use potassium supplement or salt substitutes without consulting 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. 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. Breast-feeding is not recommended.

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.

Cardiovascular Considerations

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. 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 that 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. When used in patients with heart failure, the target dose or maximum tolerated dose, should be achieved, if possible. Lower daily doses of ACE inhibitors have not demonstrated the same cardioprotective effects. ACE inhibitors have renal protective effects in patients with proteinuria and possibly cardioprotective effects in high-risk patients.

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, angiotensin receptor blocker therapy instituted. Concomitant NSAID therapy may attenuate blood pressure control; use of NSAIDs should be avoided or limited, with monitoring of blood pressure control. In the setting of heart failure, NSAID use may be associated with an increased risk for fluid accumulation and edema. 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.

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).

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

Dosage Forms

[DSC] = Discontinued product

Tablet: 2.5 mg, 5 mg, 10 mg, 20 mg, 30 mg, 40 mg

Prinivil®: 2.5 mg [DSC], 5 mg, 10 mg, 20 mg, 30 mg, 40 mg

Zestril®: 2.5 mg, 5 mg, 10 mg, 20 mg, 30 mg, 40 mg

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

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, 110:588-636. 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.

"Guidelines for the Evaluation and Management of Heart Failure. Report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Committee on Evaluation and Management of Heart Failure)," Circulation , 1995, 92(9):2764-84.

Hunt SA, Baker DW, Chin MH, et al, "ACC/AHA Guidelines for the Evaluation and Management of Chronic Heart Failure in the Adult: Executive Summary. A Report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Committee to Revise the 1995 Guidelines for the Evaluation and Management of Heart Failure)," J Am Coll Cardiol , 2001, 38(7):2101-13.

"K/DOQI Clinical Practice Guidelines for Chronic Kidney Disease: Evaluation, Classification, and Stratification. Kidney Disease Outcome Quality Initiative," Am J Kidney Dis , 2002, 39(2 Suppl 2):1-246. Available at: http://www.kidney.org/professionals/doqi/kdoqi/toc.htm. Accessed August 1, 2003.

Konstam MA, "Heart Failure Evaluation and Care of Patients With Left Ventricular Systolic Dysfunction," Rockville, MD: U.S. Department of Health and Human Services, Public Health Service, Agency for Health Care Policy and Research, 1994. Clinical Practice Guideline: Number 94-0612.

Packer M, Poole-Wilson PA, Armstrong PW, et al, "Comparative Effects of Low and High Doses of the Angiotensin-Converting Enzyme Inhibitor, Lisinopril, on Morbidity and Mortality in Chronic Heart Failure," Circulation , 1999, 100(23):2312-8.

Pfeffer MA, Greaves SC, Arnold JM, et al, "Early Versus Delayed Angiotensin-Converting Enzyme Inhibition Therapy in Acute Myocardial Infarction. The Healing and Early Afterload Reducing Therapy Trial," Circulation , 1997, 95(12):2643-51.

Ryan TJ, Antman EM, Brooks NH, et al, "1999 Update: ACC/AHA Guidelines for the Management of Patients With Acute Myocardial Infarction: Executive Summary and Recommendations: A Report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Committee on Management of Acute Myocardial Infarction)," Circulation , 1999, 100(9):1016-30.

Smoger SH and Sayed MA, "Simultaneous Mucosal and Small Bowel Angioedema Due to Captopril," South Med J , 1998, 91(11):1060-3.

International Brand Names

Acemin® (AT); Acepril® (DK); Acerbon® (DE); Acerdil® (CL); Acerilin® (TR); Acetan® (AT); Alapril® (IT); Alfaken® (MX); Apo-Lisinopril® (CA); Carace® (GB, IE); Carsipril® (DO); Cipril® (IN); Coric® (DE); Dapril® (CZ, RU, SG, SK, UA); Diroton® (CZ, PL); Doneka® (ES); Doxapril® (AR); Ecapril® (PT); Ecopril® (BD); Eupril® (DO); Farpresse® (PT); Fisopril® (BD); Hexal-Lisinopril® (ZA); Inhibril® (TR); Inopril® (EG, KW, LB, SY); Interpril® (ID); Iricil® (ES); Irumed® (CZ, HR, SI); Lanatin® (DK); Likenil® (ES); Linoril® (IN); Lipreren® (CL); Lipril® (BD, IE, IN, PT, RO); Lisi AbZ® (DE); Lisibeta® (DE); Lisidoc® (DE); Lisigamma® (DE); Lisi-Hennig® (DE); Lisihexal® (AT, DE, PL); LisiLich® (DE); Lisinal® (AR); Lisinogen® (DK); Lisinopril 1A Pharma® (DE); Lisinopril 2K® (DK); Lisinopril AAA-Pharma® (DE); Lisinopril AL® (DE); Lisinopril Alpharma® (DK, SE); Lisinopril Alter® (ES); Lisinopril Arcana® (AT); Lisinopril Arrow® (SE); Lisinopril AWD® (DE); Lisinopril AZU® (DE); Lisinopril Bayvit® (ES); Lisinopril Biochemie® (DE, DK, FI, SE); Lisinopril Cinfa® (ES); Lisinopril Cinfamed® (ES); Lisinopril® (CL, GB, NO); Lisinopril Copyfarm® (SE); Lisinopril-corax® (DE); Lisinopril Farmabion® (ES); Lisinopril Geminis® (ES); Lisinopril Generics® (FI); Lisinopril Heumann® (DE); Lisinopril NM Pharma® (SE); Lisinopril Pliva® (DK, SE); Lisinopril Ranbaxy® (SE); Lisinopril Ratio® (DO); Lisinopril-ratiopharm® (DE); Lisinopril Ratiopharm® (ES); Lisinopril ratiopharm® (FI, SE); Lisinopril Sandoz® (DE); Lisinopril Stada® (DE, DK, SE, SG); Lisinopril TAD® (DE); Lisinopril Tamarang® (ES); Lisinopril-Teva® (DE); lisinopril von ct® (DE); Lisinoratio® (PL); Lisinostad® (AT); Lisinotyrol® (AT); Lisipril® (CO, DO, FI); Lisipril-D® (DO); Lisiprol® (PL); Lisi-Puren® (DE); Lisitril® (CH); Lisocard® (LB, RO); Lisodura® (DE); Lisodur® (AU); Lisopress® (HU, IE); Lisopril® (BD, CH); Lisoril® (IN, RU, SG); Lispril® (IE, TH); Listril® (RO); Longes® (JP); Loril® (YU); Neopril® (BD); Noperten® (ID); Novatec® (BE, LU, NL); Presiten® (DO); Presokin® (CL); Prilosin® (ZA); Prinil® (CH); Prinivil® (AR, AT, AU, BR, CA, CZ, ES, FR, HK, HU, IT, MX, NO, NZ, PL, RO, SG, YU); Prinvil® (ZA); Renotens® (ZA); Rilace® (TR); Rowenopril® (DO, EC); Secubar® (ES); Sedotensil® (AR); Sinopren® (ZA); Sinopryl® (RO, TR); Tensikey® (ES); Tensopril® (AR, IL); Tensyn® (CO); Tersif® (AR); Tonolysin® (RO); Tonotensil® (CL); Vivatec® (DK, FI, NO, SE); Zesger® (IE); Zestan® (IE); Zestril® (AR, AU, BD, BE, BR, CA, CH, CL, CY, DK, ES, FI, FR, GB, HK, ID, IE, IT, KW, LB, LU, MT, MX, NL, NO, NZ, PT, SE, SG, TH, TR, ZA); Zetomax® (ZA)

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