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%. |
| Molecular Weight | 405.5 |
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 | Use during the first trimester is associated with potential teratogenic risk; however, the absolute risk is low. Studies have shown an increased risk of cardiovascular and central nervous system malformations with first-trimester exposure to ACE inhibitors. |
| 2nd trimester | Use during the second trimester is contraindicated due to risk of fetal renal dysfunction, oligohydramnios, and skull ossification defects. |
| 3rd trimester | Use during the third trimester is contraindicated due to risk of fetal renal dysfunction, oligohydramnios, and neonatal hypotension and renal failure. |
Clinical note
Comprehensive clinical and safety monograph for PRINIVIL (PRINIVIL).
| Placental transfer | Lisinopril crosses the placenta. It is a small molecule (molecular weight 405.5 Da) and is not highly protein bound, facilitating transfer. |
| Breastfeeding | Small amounts of lisinopril are excreted into breast milk. The effects on the nursing infant are unknown, but due to the potential for adverse effects on renal function in the newborn, caution is advised. Consider alternative medications, especially in preterm or jaundiced 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 possible once pregnancy is detected.
| Serious Effects |
History of angioedema related to previous ACE inhibitor therapyHereditary or idiopathic angioedemaConcomitant use with aliskiren in patients with diabetes mellitus
| Precautions | Angioedema, Hypotension, Hyperkalemia, Renal impairment, Hepatic failure, Cough, Neutropenia/agranulocytosis |
| Food/Dietary | Avoid high-potassium foods (bananas, oranges, spinach, potatoes with skin) if on concurrent potassium-sparing diuretics or if renal impairment is present. Alcohol may enhance hypotensive effects. |
Loading safety data…
| Lactation Rating | L3 (Moderately Safe) |
| 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. |
| 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. |
| Clinical Pearls | Monitor serum creatinine and potassium within 2 weeks of initiation. Use with caution in renal artery stenosis; can cause acute renal failure. angioedema risk is higher in African American patients. Discontinue if pregnancy is detected (ACE inhibitors cause fetal toxicity). |
| Patient Advice | Take exactly as prescribed; do not skip doses or double up. · Avoid salt substitutes containing potassium unless approved by your doctor. · Report any swelling of lips, face, or throat immediately (angioedema). · If you become pregnant, stop the drug and call your doctor right away. · May cause dizziness; avoid driving until you know how you react. |