Dosing and uses of Prinivil, Zestril (lisinopril)
Adult dosage forms and strengths
tablet
- 2.5mg
- 5mg
- 10mg
- 20mg
- 30mg
- 40mg
oral solution
- 1mg/mL (Qbrelis)
Acute Myocardial Infarction
5 mg PO within 24 hours of onset of symptoms of acute MI, THEN 5 mg after 24 hours, 10 mg after 48 hours, and 10 mg qDay for 6 weeks
If patient has low systolic blood pressure (ie, ≤120 mm Hg) when treatment initiated or during the first 3 days, administer a lower dose of 2.5 mg
If hypotension occurs (systolic BP ≤100 mm Hg), a daily maintenance dose of 5 mg may be given, with temporary reductions to 2.5 mg if needed
Dosing considerations
- Discontinue with prolonged hypotension (ie, systolic BP <90 mm Hg for >1 hr)
Hypertension
Uncomplicated essential hypertension
Not taking diuretic: 10 mg PO qDay initially; usual range is 20-40 mg/day as single daily dose
Dosing considerations
- Taking diuretic: Discontinue diuretic for 2-3 days before initiating lisinopril to reduce chance of hypotension; may resume diuretic if blood pressure is not controlled; if diuretic cannot be discontinued, initial dose of lisinopril 5 mg should be used under supervision for at least 2 hours and until blood pressure has stabilized for at least 1 hour
Heart Failure
Adjunctive therapy with diuretics and (usually) digitalis
5 mg PO qDay initially; increase by ≤10 mg no more frequent than 2 week intervals to 20-40 mg PO qDay
Patients with hypnatremia (<130 mEq/L serum sodium): 2.5 mg PO qDay initially; increase by ≤10 mg no more frequent than 2 week intervals to 20-40 mg PO qDay
Usual effective dosage range: 5-40 mg PO qDay (Zestril); 5-20 mg PO qDay (Prinivil)
Dosage modifications
Renal impairment
- Acute myocardial infarction: Use caution in renal dysfunction (serum creatinine >2 mg/dL)
- Hypertension and CrCl >30 mL/min: 10 mg PO qDay initially; not to exceed 40 mg/day
- Hypertension and CrCl 10-30 mL/min: 5 mg PO qDay initially; not to exceed 40 mg/day
- Hypertension and CrCl <10 mL/min or hemodialysis: 2.5 mg PO qDay initially; not to exceed 40 mg/day
- Heart failure and CrCl <30 mL/min: 2.5 mg PO qDay initially; not to exceed 40 mg/day
Diabetic Nephropathy (Off-label)
Initial: 5 mg PO qDay (with diuretic)
May gradually increase dose according to blood pressure response; dosage range is 20-40 mg/day
Dosing considerations
- Long-term treatment with ACE inhibitors, usually combined with diuretics, reduces blood pressure and albuminuria and protects kidney function in patients with hypertension, diabetes mellitus, and nephropathy
Pediatric dosage forms and strengths
tablet
- 2.5mg
- 5mg
- 10mg
- 20mg
- 30mg
- 40mg
oral solution
- 1mg/mL (Qbrelis)
Hypertension
Indicated for hypertension in pediatric patients aged ≥6 yr to lower blood pressure
Age <6 years or GFR <30 mL/min/1.73m²: Safety and efficacy not established
≥6 years and GFR ≥30 mL/min/1.73m²: 0.07 mg/kg PO qDay initially, not to exceed 5 mg/day; may slowly titrate upward and adjusted according to blood pressure; not to exceed 0.61 mg/kg/day or >40 mg/day
Primary Hypertension (Orphan)
Oral solution: Orphan designation for treatment of primary hypertension with complications and secondary hypertension in pediatric patients (ages 0 through 16 years of age)
Sponsors
- codaDose, Inc; 5659 Southfield Drive; Flowery Branch, GA 30542
- Silvergate Pharmaceuticals, Inc; 6251 Greenwood Plaza Blvd, Suite 101; Greenwood Village, CO 80111
Geriatric dosage forms and strengths
Hypertension
Uncomplicated essential hypertension
Consider lower initial dose of 2.5-5 mg and titrate to response in the elderly
Usual range is 20-40 mg/day as single daily dose
Adjust dose to blood pressure response; doses up to 80 mg have been used but do not appear to have a greater effect
Dosing considerations
Taking diuretic: Discontinue diuretic for 2-3 days before initiating lisinopril to reduce chance of hypotension; may resume diuretic if blood pressure is not controlled; if diuretic cannot be discontinued, initial dose of lisinopril 2.5 mg should be used under supervision for at least 2 hours and until blood pressure has stabilized for at least 1 hour
Prinivil, Zestril (lisinopril) adverse (side) effects
>10%
Dizziness (5-12%)
1-10%
Cough (4-9%)
Headache (4-6%)
Hyperkalemia (2-5%)
Diarrhea (3-4%)
Hypotension (1-4%)
Chest pain (3%)
Fatigue (3%)
Nausea/vomiting (2%)
Kidney disease, of AMI patients (2%)
Rash (1-2%)
<1%
Immune hypersensitivity reaction
Psoriasis
Angioedema of the face, lips, throat; intestinal angioedema
Anuria
Atrial tachycardia
Acute renal failure
Arthralgia
Alopecia
Atrial fibrillation
Bone marrow suppression
Cutaneous pseudolymphoma
Hypersomnia
Leukopenia
Mood changes
Pancreatitis
Skin infections
Warnings
Black box warnings
Discontinue as soon as possible when pregnancy is detected; affects renin-angiotensin system, causing oligohydramnios, which may result in fetal injury and/or death
Contraindications
Hypersensitivity to lisinopril/other ACE inhibitors
History of ACE inhibitor-induced angioedema, hereditary or idiopathic angioedema
Coadministration with aliskiren in patients with diabetes mellitus or with renal impairment (ie, GFR <60 mL/min/1.73m²
Cautions
Anaphylactoid reactions reported in some patients dialyzed with high-flux membranes
Hematologic effects including agranulocytosis and neutropenia/agranulocytosis reported especially in patients with renal impairment and collagen vascular disease; monitor CBC periodically with differentiaL
Less effective in African Americans
Excessive hypotension with concomitant diuretics, hypovolemia, hyponatremia may occur
Risk of hyperkalemia, especially in patients with renal impairment or DM or in patients taking concomitant K+-elevating drugs
ACE inhibition also causes an increase in bradykinin levels, which putatively mediates angioedema; in comparison with other patients, a higher incidence of angioedema caused by ACE inhibitors has been observed in black patients
A dry hacking cough may occur within a few months of initiating drug therapy with ACE inhibitors; exclude other causes of cough before discontinuing therapy
Cholestatic jaundice associated with ACE inhibitors; discontinue if marked elevation of hepatic transaminases or jaundice occurs
Coadministration with mTOR inhibitors (eg, temsirolimus, everolimus) may increased risk for angioedema
Discontinue STAT if patient becomes pregnant
Use caution in patients with renal impairment; renal deterioration reported in patients with low renal blood flow
Use caution in patients with severe aortic stenosis, cardiovascular disease, collagen vascular disease, hypertrophic cardiomyopathy
Dual blockade of the renin-angiotensin-aldosterone system (ie, ARB plus an ACE inhibitor) in patients with established atherosclerotic disease or heart failure or with diabetes with end organ damage is associated with a higher frequency of hypotension, syncope, hyperkalemia, and changes in renal function (including acute renal failure), as compared with use of a single renin-angiotensin-aldosterone system agent; limit dual blockade to individually defined cases, with close monitoring of renal function
Neonates with history of in utero exposure: If oliguria or hypotension occurs, support of blood pressure and renal perfusion; exchange transfusions or dialysis may be required
Angioedema of the face, extremities, lips, tongue, glottis and/or larynx, including some fatal reactions, at any time during treatment; patients with involvement of the tongue, glottis or larynx are likely to experience airway obstruction, especially patients with history of airway surgery; promptly discontinue and provide appropriate therapy and monitoring until complete and sustained resolution of signs and symptoms of angioedema has occurred
Intestinal angioedema reported; patients presented with abdominal pain (with or without nausea or vomiting); in some cases there was no prior history of facial angioedema and C-1 esterase levels were normal; symptoms resolved after stopping the ACE inhibitor
Hypotension may occur sometimes complicated by oliguria, progressive azotemia, acute renal failure or death; patients at risk of excessive hypotension include heart failure with systolic blood pressure below 100 mmHg, ischemic heart disease, cerebrovascular disease, hyponatremia, high dose diuretic therapy, renal dialysis, or severe volume and/or salt depletion of any etiology; in such patients initiate therapy under medical supervision and follow such patients for the first two weeks of treatment and whenever dose of lisinopril and/or diuretic is increased; avoid use in patients who are hemodynamically unstable after acute MI; symptomatic hypotension also possible in patients with severe aortic stenosis or hypertrophic cardiomyopathy
Patients undergoing major surgery or during anesthesia with agents that produce hypotension, lisinopril may block angiotensin II formation secondary to compensatory renin release; if hypotension occurs and considered to be due to this mechanism, it can be corrected by volume expansion
Monitor renal function periodically; changes in renal function including acute renal failure can be caused by drugs that inhibit renin-angiotensin system; patients whose renal function may depend in part on activity of the renin-angiotensin system (eg, patients with renal artery stenosis, chronic kidney disease, severe congestive heart failure, post-myocardial infarction or volume depletion) may be at particular risk of developing acute renal failure; consider withholding or discontinuing therapy in patients who develop a clinically significant decrease in renal function
Pregnancy and lactation
Pregnancy category: d
Discontinue as soon as pregnancy detected; during the second and third trimesters of pregnancy, drugs that act directly on the renin-angiotensin system have been associated with fetal injury, including hypotension, neonatal skull hypoplasia, anuria, reversible and irreversible renal failure, and death
Lactation: Not known if excreted into breast milk; not recommended
Pregnancy categories
A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.
B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.
C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.
D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.
X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.
NA: Information not available.
Pharmacology of Prinivil, Zestril (lisinopril)
Mechanism of action
Angiotensin converting enzyme (ACE) inhibitors dilate arteries and veins by competively inhibiting the conversion of angiotensin I to angiotensin II (a potent endogenous vasoconstrictor) and by inhibiting bradykinin metabolism; these actions result in preload and afterload reductions on the heart
ACE inhibitors also promote sodium and water excretion by inhibiting angiotensin-II induced aldosterone secretion; elevation in potassium may also be observed
ACE inhibitors also elicit renoprotective effects through vasodilation of renal arterioles
ACE inhibitors reduce cardiac and vascular remodeling associated with chronic hypertension, heart failure, and myocardial infarction
Absorption
Bioavailability: 25%
Onset: 1 hr (initial); 6 hr (peak)
Duration: 24 hr
Peak plasma time: 6-8 hr
Therapeutic plasma concentration: 1-5 ng/mL
Distribution
Protein bound: 25%
Vd: 124 L
Metabolism
Does not undergo metabolism
Elimination
Half-life: 12 hr
Renal clearance: 106 mL/min
Total body clearance: 250 mL/min
Excretion: Excreted unchanged entirely in the urine
Dialysis: Removed by hemodialysis
