ZESTRIL
Clinical safety rating: caution
Comprehensive clinical and safety monograph for ZESTRIL (ZESTRIL).
Lisinopril competes with angiotensin I for binding to angiotensin-converting enzyme (ACE), inhibiting its activity, thereby preventing conversion of angiotensin I to angiotensin II, a potent vasoconstrictor. This leads to decreased blood pressure, reduced aldosterone secretion, and decreased sodium and water retention.
| Metabolism | Lisinopril is not metabolized by the liver; it is excreted unchanged in the urine. No significant metabolism via CYP450 enzymes. |
| Excretion | Primarily renal (approximately 70% unchanged), with the remainder excreted as inactive metabolites via feces and urine. |
| Half-life | Terminal elimination half-life is about 12 hours for lisinopril; in heart failure, half-life may be prolonged. Steady-state achieved in 2-3 days. |
| Protein binding | Lisinopril does not bind to plasma proteins (0% binding). |
| Volume of Distribution | Approximately 1.5 L/kg, indicating limited tissue penetration and distribution primarily into extracellular fluid. |
| Bioavailability | Oral: 25-30% (variable, not significantly affected by food). |
| Onset of Action | Oral: 1 hour for initial antihypertensive effect; maximal effect on renin-angiotensin system occurs within 2-4 hours. |
| Duration of Action | Antihypertensive effect persists for 24 hours with once-daily dosing; full therapeutic benefit may require 2-4 weeks of therapy. |
| Molecular Weight | 441.52 Da |
| Action Class | Angiotensin-converting enzyme (ACE) inhibitors |
| Brand Substitutes | Lisir 10mg Tablet, L.P.L. 10mg Tablet, Listen 10mg Tablet, Nivant 10mg Tablet, Normopril 10mg Tablet, Lisitec 5mg Tablet, Lisir 5mg Tablet, Nivant 5mg Tablet, Dilace 5mg Tablet, Linark 5mg Tablet |
10 mg orally once daily initially; titrate to 20-40 mg orally once daily. Maximum 80 mg/day.
| Dosage form | TABLET |
| Renal impairment | Initial dose 5 mg orally once daily if CrCl 10-30 mL/min; 2.5 mg if CrCl <10 mL/min (including dialysis). Titrate based on response and tolerance. |
| Liver impairment | No specific Child-Pugh modifications; initiate at 5 mg orally once daily and titrate carefully due to potential hypotension. |
| Pediatric use | 0.07 mg/kg (up to 5 mg) orally once daily initially; titrate to a maximum of 0.6 mg/kg (up to 40 mg) once daily. |
| Geriatric use | Initiate at 2.5-5 mg orally once daily; monitor renal function and adjust dose based on CrCl; use lowest effective dose. |
| 1st trimester | Contraindicated due to increased risk of fetal renal impairment and oligohydramnios; also associated with teratogenic effects (skull ossification defects) in animal studies. |
| 2nd trimester | Contraindicated; may cause fetal hypotension, renal failure, and oligohydramnios; use in second trimester associated with fetal abnormalities. |
| 3rd trimester | Contraindicated; high risk of fetal and neonatal morbidity and death related to oligohydramnios, anuria, and renal tubular dysplasia. |
Clinical note
Comprehensive clinical and safety monograph for ZESTRIL (ZESTRIL).
| Placental transfer | Crosses the placenta in humans; measured in cord blood at concentrations similar to maternal plasma, indicating significant transfer. |
| Breastfeeding | Excreted into breast milk in low concentrations; limited data suggest no adverse effects on nursing infants, but caution is advised due to potential for hypotension and renal effects in neonates, especially premature infants. |
■ FDA Black Box Warning
Fetal toxicity: Drugs acting directly on the renin-angiotensin system can cause injury and death to the developing fetus. Discontinue as soon as pregnancy is detected.
| Serious Effects |
History of angioedema related to previous ACE inhibitor therapyConcomitant use with aliskiren in patients with diabetes mellitusPregnancy (all trimesters)Concomitant use with neprilysin inhibitors (e.g., sacubitril)
| Precautions | Angioedema (including intestinal angioedema), Hypotension (especially in volume-depleted patients), Hyperkalemia (risk factors: renal impairment, diabetes, concomitant potassium supplements or K-sparing diuretics), Renal function impairment (increase in BUN and creatinine), Hepatic failure (rare, cholestatic jaundice progressing to fulminant necrosis), Cough (nonproductive, persistent), Neutropenia/agranulocytosis (more common in patients with collagen vascular disease and renal impairment) |
| Food/Dietary | Avoid salt substitutes containing potassium chloride; can lead to hyperkalemia. High-potassium foods (bananas, oranges, potatoes, spinach) may increase risk of hyperkalemia if consumed in large amounts. Use caution with alcohol as it may potentiate hypotensive effects. |
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| Lactation Rating | L3: Moderately safe |
| Teratogenic Risk | Use of ZESTRIL (lisinopril) during pregnancy is associated with fetal and neonatal morbidity and mortality. First trimester exposure carries a low absolute risk of teratogenicity, but consistent evidence of increased risk of congenital malformations, particularly cardiovascular and central nervous system defects, exists. Second and third trimester exposure is associated with oligohydramnios, fetal renal dysfunction, skull ossification defects, hypotension, and anuria. Lisinopril is contraindicated in pregnancy. |
| Fetal Monitoring | Maternal monitoring includes blood pressure, renal function, serum potassium, and uric acid. Fetal monitoring requires serial ultrasound to assess amniotic fluid volume and fetal growth, especially during the second and third trimesters. If oligohydramnios occurs, discontinuation of lisinopril is recommended unless necessary for maternal survival. Neonates exposed in utero should be observed for hypotension, oliguria, and hyperkalemia. |
| Fertility Effects | No specific studies have evaluated lisinopril's effect on human fertility. Animal studies have not shown impaired fertility. However, ACE inhibitors may theoretically affect reproductive function via angiotensin II modulation. No definitive conclusion is available. |
| Clinical Pearls | Zestril (lisinopril) is a long-acting ACE inhibitor. Monitor serum creatinine and potassium levels within 1-2 weeks of initiation. Can cause persistent dry cough due to bradykinin accumulation; angioedema risk is higher in African American patients. Avoid in pregnancy (category D). |
| Patient Advice | Take exactly as prescribed, usually once daily; do not double doses. · Report any swelling of face, lips, or throat immediately (possible angioedema). · May cause dizziness, especially during first doses; avoid driving until known effects. · Do not use potassium supplements or salt substitutes without consulting your doctor. · If you become pregnant, stop the medication and notify your physician right away. · Common side effects: dry cough, headache, dizziness, and fatigue. |