No

Angiotensin-Converting Enzyme (ACE) Inhibitors

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

C/D (2nd and 3rd trimesters)

Clinical effects on the fetus: No data available on crossing the placenta. 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.

Breast-feeding/lactation: Crosses into breast milk; American Academy of Pediatrics considers compatible with breast-feeding.

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

Anaphylactic reactions can occur. Angioedema can occur at any time during treatment (especially following first dose). 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. Neutropenia/agranulocytosis with myeloid hyperplasia can rarely occur. 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.

Note: Frequency ranges include data from hypertension and heart failure trials. Higher rates of adverse reactions have generally been noted in patients with congestive heart failure. However, the frequency of adverse effects associated with placebo is also increased in this population.

Cardiovascular: Orthostatic effects (1.2%), hypotension (1.2% to 4.4%)

Central nervous system: Headache (4.4% to 5.7%), dizziness (5.4% to 11.8%), fatigue (2.5%), weakness (1.3%)

Dermatologic: Rash (1.3% to 1.7%)

Endocrine and metabolic: Hyperkalemia (2.2% to 4.8%)

Gastrointestinal: Diarrhea (2.7% to 3.7%), nausea (2.0%), vomiting (1.1%), abdominal pain (2.2%)

Genitourinary: Impotence (1%)

Hematologic: Decreased hemoglobin (small)

Neuromuscular & skeletal: Chest pain (3.4%)

Renal: Increased serum creatinine (often transient), increased BUN (2%); deterioration in renal function (in patients with bilateral renal artery stenosis or hypovolemia)

Respiratory: Cough (3.5% to 8.5%), upper respiratory infection (1.5% to 2.1%)

>1% but less than or equal to frequency in patients receiving placebo: Chest pain, back pain, angina, dyspnea, pruritus

<1% (Limited to important or life-threatening symptoms): Angioedema, anaphylactoid reactions, edema, cardiac arrest, myocardial infarction, cerebrovascular accident, pulmonary embolism, arrhythmia, palpitation, TIA, paroxysmal nocturnal dyspnea, orthostatic hypotension, peripheral edema, vasculitis, pancreatitis, hepatitis, jaundice (cholestatic), vomiting, heartburn, gastrointestinal cramps, constipation, flatulence, xerostomia, bone marrow suppression, neutropenia, thrombocytopenia, diabetes mellitus, weight loss, dehydration, volume overload, gout, weight gain, arthritis, arthralgia, stroke, ataxia, memory impairment, tremor, peripheral neuropathy, paresthesia, confusion, insomnia, somnolence, irritability, nervousness, bronchospasm, infiltrates, asthma, pleural effusion, bronchitis, wheezing, epistaxis, laryngitis, sinusitis, pharyngitis, rhinitis, rhinorrhea, urticaria, alopecia, photosensitivity, pemphigus, erythema, flushing, diaphoresis, toxic epidermal necrolysis, Stevens-Johnson syndromes, vision loss, diplopia, blurred vision, tinnitus, photophobia, acute renal failure, oliguria, anuria, azotemia, renal dysfunction, dyspepsia, muscle cramps, paresthesia, decreased libido, vertigo, nasal congestion, increased transaminases, increased bilirubin, hyperkalemia, hyponatremia, gout.

Case reports: Hepatitis, systemic lupus erythematosus. In addition, a syndrome which may include fever, myalgia, arthralgia, interstitial nephritis, vasculitis, rash, eosinophilia and positive ANA, and elevated ESR has been reported with ACE inhibitors.

Mild hypotension has been the only 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

Following initiation of essential overdose management, toxic symptom treatment and supportive treatment should be initiated. Hypotension usually responds to I.V. fluids or Trendelenburg positioning.

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

Alpha₁ blockers: Hypotensive effect increased.

Aspirin and NSAIDs may decrease ACE inhibitor efficacy 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.

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.

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

Onset of action: 1 hour

Peak hypotensive effect: Oral: Within 6 hours

Duration: 24 hours

Absorption: Well absorbed; unaffected by food

Protein binding: 25%

Half-life: 11-12 hours

Elimination: Almost entirely excreted in urine as unchanged drug

Hypertension:

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: 5 mg initially with diuretics and digitalis; may be increase in no greater than 10 mg increments at intervals no less than 2 weeks to a maximum of 40 mg/day. Usual maintenance: 5-40 mg/day as a single dose

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:

Cl_cr 10-50 mL/minute: Administer 50% to 75% of normal dose.

Cl_cr <10 mL/minute: Administer 25% to 50% of normal dose.

Hemodialysis: Dialyzable (50%)

Serum calcium levels, BUN, serum creatinine, renal function, WBC, and potassium

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

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. ACE inhibitors are also indicated in patients postmyocardial infarction in whom left ventricular ejection fraction is <40%. 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.

May cause dizziness or fatigue; may rarely cause sedation, insomnia, or depression

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

No information available to require special precautions

No effects or complications reported

Take exactly as directed; do not discontinue without consulting prescriber. Take first dose at bedtime. This drug does not eliminate need for diet or exercise regimen as recommended by prescriber. Do not take potassium supplements or salt substitutes containing potassium without consulting prescriber. May cause dizziness, fainting, 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); 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; skin rash; numbness, tingling, or pain in muscles; difficulty in breathing or unusual cough; or other persistent adverse reactions. Pregnancy precautions: Do not get pregnant while taking this medication; use appropriate barrier contraceptive measures.

May cause depression in some patients; discontinue if angioedema of the face, extremities, lips, tongue, or glottis occurs; watch for hypotensive effects within 1-3 hours of first dose or new higher dose

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

Brown NJ, Ray WA, Snowden M, et al, "Black Americans Have an Increased Rate of Angiotensin-Converting Enzyme Inhibitor-Associated Angioedema," Clin Pharmacol Ther, 1996, 60(1):8-13.

Chase SL and Sutton JD, "Lisinopril: A New Angiotensin-Converting Enzyme Inhibitor," Pharmacotherapy, 1989, 9(3):120-30.

Dawson AH, Harvey D, Smith AJ, et al, "Lisinopril Overdose," Lancet, 1990, 335(8687):487-8.

Hargreaves MR and Benson MK, "Inhaled Sodium Cromoglycate in Angiotensin-Converting Enzyme Inhibitor Cough," Lancet, 1995, 345(8941):13-6.

Harrison BD, Laidlaw ST, and Reilly JT, "Fatal Aplastic Anaemia Associated With Lisinopril," Lancet, 1995, 346(8969):247-8.

Herings RM, deBoer A, Stricker BH, et al, "Hypoglycaemia Associated With Use of Inhibitors of Angiotensin Converting Enzyme," Lancet, 1995, 345(8959):1195-8.

Konstam MA, Drakup K, Baker DW, et al, "Heart Failure: Evaluation and Care of Patients With Left Ventricular Systolic Dysfunction," Clinical Practice Guideline No 11, Rockville, MD: Agency for Health Care Policy and Research, Public Health Service, U.S. Department of Health and Human Services, 1994.

Kuo DC and Barish RA, "Isolated Uvular Angioedema Associated With ACE Inhibitor Use," J Emerg Med, 1995, 13(3):327-30.

McAreavey D and Robertson JIS, "Angiotensin Converting Enzyme Inhibitors and Moderate Hypertension," Drugs, 1990, 40(3):326-45.

Raia JJ Jr, Barone JA, Byerly WG, et al, "Angiotensin-Converting Enzymes Inhibitors: A Comparative Review," DICP, 1990, 24(5):506-25.

Williams JF, Bristow MR, Fowler MB, et al, "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)," J Am Coll Cardiol, 1995, 26:1376-8.

Woo OF, "Captopril and Related Drugs," Poisoning and Drug Overdose, 2nd ed, Olson KR, ed, East Norwalk, CT: Appleton and Lange, 1994, 117-8.