PRINIVIL
Clinical safety rating: caution
Comprehensive clinical and safety monograph for PRINIVIL (PRINIVIL).
Lisinopril is an angiotensin-converting enzyme inhibitor that decreases angiotensin II production, reducing vasoconstriction and aldosterone secretion, leading to decreased blood pressure.
| Metabolism | Lisinopril is not metabolized and is excreted unchanged in the urine. |
| Excretion | Renal excretion accounts for approximately 60% of total clearance, primarily as unchanged lisinopril; fecal excretion accounts for negligible amounts. |
| Half-life | Terminal elimination half-life is approximately 12 hours, with accumulation noted in renal impairment; effective half-life at steady state extends to 30-50 hours in patients with creatinine clearance <30 mL/min. |
| Protein binding | Lisinopril is not significantly bound to plasma proteins other than ACE; protein binding is less than 10%. |
| Volume of Distribution | Approximately 2 L/kg, indicating extensive tissue distribution; does not cross blood-brain barrier readily. |
| Bioavailability | Oral bioavailability is 25-60%, with interindividual variability; food does not affect absorption. |
| Onset of Action | Oral: 1 hour for initial reduction in blood pressure; maximal effect within 6 hours. |
| Duration of Action | 24 hours; once-daily dosing provides sustained blood pressure control over 24 hours, with trough-to-peak ratio ~50-60%. |
Initial dose 10 mg orally once daily; titrate to target dose of 20-40 mg daily based on blood pressure response.
| Dosage form | TABLET |
| Renal impairment | GFR >30 mL/min: 10 mg daily; GFR 10-30 mL/min: 5 mg daily; GFR <10 mL/min or hemodialysis: 2.5 mg daily on dialysis days. |
| Liver impairment | Child-Pugh Class A: 5 mg daily; Class B: 2.5 mg daily; Class C: not recommended. |
| Pediatric use | Children ≥6 years: initial 0.07 mg/kg (up to 5 mg) once daily; titrate to maximum 0.6 mg/kg (up to 40 mg) daily. |
| Geriatric use | Initiate at 2.5-5 mg daily; adjust cautiously due to age-related renal impairment. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for PRINIVIL (PRINIVIL).
| Breastfeeding | Lisinopril is excreted into human breast milk in low concentrations (M/P ratio ~0.02). Limited data suggest no adverse effects in full-term infants. However, caution is advised in preterm infants or those with impaired renal function. Consider alternative agents with established safety. |
| Teratogenic Risk | First trimester: Increased risk of congenital malformations (cardiovascular, CNS, renal) based on human data. Second and third trimesters: Fetal renal dysfunction, oligohydramnios, skull ossification defects, hypotension, and anuria. High risk of neonatal renal failure and death if exposed after 20 weeks. |
■ 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 possible once pregnancy is detected.
| Serious Effects |
["Hypersensitivity to lisinopril or any ACE inhibitor","History of angioedema related to previous ACE inhibitor therapy","Concomitant use with aliskiren in patients with diabetes"]
| Precautions | ["Angioedema","Hypotension","Hyperkalemia","Renal impairment","Hepatic failure","Cough","Neutropenia/agranulocytosis"] |
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| Fetal Monitoring | Assess fetal renal function via ultrasound for amniotic fluid volume every 4 weeks after 20 weeks gestation. Monitor maternal blood pressure, serum creatinine, and potassium levels periodically. Serial fetal growth scans recommended. |
| Fertility Effects | No significant impairment of fertility reported in animal studies or human data. However, ACE inhibitors may affect the renin-angiotensin system in reproductive tissues; clinical significance unknown. |