LISINOPRIL
Clinical safety rating: avoid
NSAIDs may diminish the antihypertensive effect Lithium levels may be increased Risk of angioedema can occur at any time discontinue immediately.
Lisinopril is an angiotensin-converting enzyme (ACE) inhibitor. It inhibits ACE, which converts angiotensin I to angiotensin II, a potent vasoconstrictor. This results in decreased plasma angiotensin II, leading to decreased vasoconstriction, reduced aldosterone secretion, decreased sodium and water retention, and lower blood pressure.
| Metabolism | Lisinopril does not undergo significant hepatic metabolism; it is excreted unchanged by the kidneys. |
| Excretion | Renal: 100% unchanged via glomerular filtration and tubular secretion; negligible biliary/fecal elimination. |
| Half-life | Terminal half-life approximately 12 hours (range 11–13 hours); clinical context: once-daily dosing for hypertension and heart failure; accumulation occurs with renal impairment. |
| Protein binding | 25% bound to plasma proteins (primarily albumin). |
| Volume of Distribution | Approximately 1.2 L/kg; indicates extensive distribution into tissues. |
| Bioavailability | Oral: 25% (range 20–30%), unaffected by food. |
| Onset of Action | Oral: 1 hour for antihypertensive effect; peak effect at 4–6 hours. |
| Duration of Action | Approximately 24 hours; once-daily dosing provides sustained blood pressure reduction over 24 hours. |
| Molecular Weight | 441.53 |
Initial: 5-10 mg orally once daily. Maintenance: 10-40 mg orally once daily. Max: 80 mg/day.
| Dosage form | TABLET |
| Renal impairment | CrCl 30-60 mL/min: start 5 mg/day; CrCl 10-29 mL/min: start 2.5 mg/day; CrCl <10 mL/min or dialysis: start 2.5 mg/day on dialysis days. |
| Liver impairment | No dose adjustment required for mild to moderate hepatic impairment. Use caution in severe impairment. |
| Pediatric use | Children ≥6 years: initial 0.07 mg/kg (up to 5 mg) orally once daily; titrate to max 0.61 mg/kg (up to 40 mg)/day. |
| Geriatric use | Start at 2.5-5 mg orally once daily due to reduced renal function and increased sensitivity; titrate slowly. |
| 1st trimester | Contraindicated: associated with fetal renal impairment, oligohydramnios, skull ossification defects, and hypotension. Risk of fetal malformations, especially if used in the first trimester. |
| 2nd trimester | Avoid: risk of oligohydramnios, fetal renal dysfunction, and skull ossification defects. ACE inhibitors during the second and third trimesters are associated with fetal and neonatal toxicity. |
| 3rd trimester | Avoid: increased risk of neonatal hypotension, renal failure, and hyperkalemia. Oligohydramnios may occur, leading to fetal limb contractures and pulmonary hypoplasia. |
Clinical note
NSAIDs may diminish the antihypertensive effect Lithium levels may be increased Risk of angioedema can occur at any time discontinue immediately.
| FDA category | Contraindicated |
| Placental transfer | Crosses the placenta; detectable in cord blood and amniotic fluid. Fetal exposure leads to decreased renal perfusion and oligohydramnios, particularly in the second and third trimesters. |
■ FDA Black Box Warning
WARNING: FETAL TOXICITY. When pregnancy is detected, discontinue lisinopril as soon as possible. Drugs that act directly on the renin-angiotensin system can cause injury and death to the developing fetus.
| Common Effects | heart failure |
| Serious Effects |
History of angioedema related to previous ACE inhibitor therapyHereditary or idiopathic angioedemaPregnancy (especially second and third trimesters)Concomitant use with aliskiren in patients with diabetes mellitusHypersensitivity to lisinopril or any ACE inhibitor
| Precautions | Angioedema: Risk of angioedema, especially in patients with history of angioedema unrelated to ACE inhibitors., Hypotension: Symptomatic hypotension may occur, especially in volume-depleted patients., Renal impairment: Monitor renal function; may cause or worsen renal impairment., Hyperkalemia: Risk of hyperkalemia, especially in patients with renal impairment, diabetes, or those using potassium-sparing diuretics., Cough: Dry, persistent cough may occur., Hepatic failure: Rare but serious; discontinue if jaundice or marked elevation of liver enzymes occurs. |
Loading safety data…
| Breastfeeding | Lisinopril is excreted into breast milk in low concentrations. Due to the potential for adverse effects on the nursing infant's renal function and blood pressure, caution is advised. Use only if clearly needed and monitor the infant for signs of hypotension or renal impairment. |
| Lactation Rating | L3 (Moderately Safe) |
| Teratogenic Risk | First trimester: No increased risk of major congenital malformations based on epidemiological data. Second and third trimesters: Fetal toxicity including oligohydramnios, fetal renal dysfunction, skull ossification defects, and neonatal hypotension, renal failure, and death. Category D in second and third trimesters; Category C in first trimester. |
| Fetal Monitoring | Monitor fetal ultrasound for oligohydramnios and renal function. Serial fetal growth scans. Assess neonatal renal function and blood pressure postpartum. Maternal monitoring: renal function (serum creatinine, BUN), serum potassium, and blood pressure. |
| Fertility Effects | No well-documented effects on fertility. ACE inhibitors may rarely cause reversible infertility in males via unknown mechanisms. No evidence of clinically significant impact. |
| Food/Dietary | Avoid potassium-rich foods (e.g., bananas, oranges, potatoes, tomatoes, spinach, avocados) in large amounts if taking potassium supplements or potassium-sparing diuretics. Limit salt intake to control blood pressure. Use of salt substitutes containing potassium chloride may increase risk of hyperkalemia. Alcohol may enhance hypotensive effects; limit consumption. |
| Clinical Pearls | Monitor serum creatinine and potassium within 1-2 weeks of initiation and after dose increases. Lisinopril has a long half-life (12 hours) allowing once-daily dosing. Cough (dry, persistent) is a common adverse effect; consider switching to an ARB if intolerable. Avoid in patients with bilateral renal artery stenosis or unilateral stenosis in a solitary kidney. Angioedema risk is highest in African American patients; use caution. In heart failure, start at 2.5-5 mg daily and titrate slowly. For post-MI, start within 24 hours if hemodynamically stable. Reduce dose in renal impairment (CrCl <30 mL/min: start at 5 mg/day). |
| Patient Advice | Take exactly as prescribed, usually once daily. Do not stop without consulting your doctor. · Avoid salt substitutes containing potassium unless approved by your doctor. · Report any signs of angioedema: swelling of face, lips, tongue, or difficulty breathing immediately. · You may experience a persistent dry cough; notify your doctor if bothersome. · Stay hydrated but avoid dehydration from excessive sweating or vomiting. · Dizziness may occur, especially when standing up quickly; rise slowly. · Do not take this medication if you are pregnant or planning to become pregnant. · Keep all follow-up appointments for blood tests to monitor kidney function and potassium levels. |