PERINDOPRIL ERBUMINE
Clinical safety rating: avoid
Contraindicated (not allowed)
Perindopril is a prodrug that is hydrolyzed to perindoprilat, a competitive inhibitor of angiotensin-converting enzyme (ACE). It blocks the conversion of angiotensin I to angiotensin II, reducing vasoconstriction, aldosterone secretion, and catecholamine release, leading to decreased blood pressure.
| Metabolism | Perindopril is a prodrug that is hydrolyzed by esterases in the liver to the active metabolite perindoprilat. Perindoprilat is further metabolized to inactive metabolites. |
| Excretion | Perindopril is extensively metabolized to perindoprilat. Approximately 75% of an oral dose is excreted in urine (as perindoprilat and metabolites) and 25% in feces (mainly as perindoprilat). Less than 5% is excreted unchanged in urine. Biliary excretion is minimal. |
| Half-life | The terminal elimination half-life of perindopril is 1.5–3 hours, but for the active metabolite perindoprilat it is 30–120 hours, due to slow dissociation from tissue ACE. This long half-life supports once-daily dosing for 24-hour blood pressure control. |
| Protein binding | Perindopril is approximately 60% bound to plasma proteins, primarily albumin. Perindoprilat is 10–20% bound (to ACE and other proteins). |
| Volume of Distribution | Volume of distribution is approximately 0.5–0.7 L/kg (about 35 L for a 70 kg adult) for perindopril and 0.2–0.3 L/kg for perindoprilat, indicating distribution mainly into extracellular fluid and minimal tissue binding. |
| Bioavailability | Oral bioavailability of perindopril is approximately 75% (range 65–85%). Food reduces conversion to perindoprilat but does not significantly affect overall bioavailability. The absolute bioavailability of active perindoprilat is about 30–40% due to first-pass metabolism. |
| Onset of Action | Oral: Antihypertensive effect begins within 1–2 hours after a single dose. Peak effect is achieved in 4–8 hours. There is no IV formulation. |
| Duration of Action | Oral: Duration of antihypertensive effect is at least 24 hours after a single dose, allowing once-daily administration. Steady state is achieved in 3–6 days. Maximal effects may require 2–4 weeks of therapy. |
| Molecular Weight | 460.6 |
2.5–10 mg orally once daily; initial dose 2.5 mg for hypertension, 4 mg for stable coronary artery disease; titrate based on response.
| Dosage form | TABLET |
| Renal impairment | GFR ≥60 mL/min: no adjustment; GFR 30-59 mL/min: 2.5 mg once daily initially, max 5 mg; GFR 15-29 mL/min: 2.5 mg every other day; GFR <15 mL/min or dialysis: avoid use. |
| Liver impairment | Child-Pugh A: no adjustment necessary; Child-Pugh B: reduce dose or prolong interval; Child-Pugh C: contraindicated. |
| Pediatric use | Not approved for use in children; safety and efficacy not established. |
| Geriatric use | Initiate at 2.5 mg once daily; titrate slowly due to decreased renal function and increased risk of hypotension. |
| 1st trimester | Avoid; associated with increased risk of congenital malformations (renal, cardiac) if exposure occurs during organogenesis. Use only if no alternative. |
| 2nd trimester | Contraindicated; risk of fetal renal impairment, oligohydramnios, and pulmonary hypoplasia. |
| 3rd trimester | Contraindicated; risk of neonatal hypotension, anuria, and renal failure. |
Clinical note
NSAIDs may diminish the antihypertensive effect Lithium levels may be increased Risk of angioedema can occur at any time discontinue immediately.
| Placental transfer | Crosses the placenta; detected in fetal circulation at levels comparable to maternal. |
| Breastfeeding | Excreted into human milk in low amounts; however, due to potential for neonatal renal effects, use with caution in breastfeeding women, especially with preterm or low-birth-weight 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.
| Common Effects | heart failure |
| Serious Effects |
Hypersensitivity to perindopril or any ACE inhibitorHistory of angioedema related to previous ACE inhibitor therapyHereditary or idiopathic angioedemaPregnancy (second and third trimesters)Concomitant use with aliskiren in patients with diabetes mellitus or renal impairment (GFR <60 mL/min)
| Precautions | Angioedema: Risk of angioedema, especially in black patients., Hypotension: Symptomatic hypotension may occur, particularly in volume-depleted patients., Renal impairment: Monitor renal function; risk of renal failure in patients with bilateral renal artery stenosis., Hyperkalemia: Risk increases with renal impairment, diabetes, and concomitant use of potassium-sparing diuretics or supplements., Cough: Persistent dry cough is common., Hepatic failure: Rare but reported. |
Loading safety data…
| Lactation Rating | L3 (Moderately Safe) |
| Teratogenic Risk | First trimester: Limited human data; animal studies show fetal toxicity at high doses. Second and third trimesters: Fetal renin-angiotensin system suppression leading to oligohydramnios, fetal calvarial hypoplasia, anuria, reversible/irreversible renal failure, hypotension, and death. |
| Fetal Monitoring | Monitor fetal ultrasound for oligohydramnios and renal function; maternal blood pressure and renal function; serial fetal biometry. |
| Fertility Effects | No clinical data on fertility effects; animal studies show no impairment. |
| Food/Dietary | Avoid potassium-rich foods (bananas, oranges, spinach, potatoes) in large amounts. Salt substitutes containing potassium chloride should be used only under medical supervision. High-fat meals may slightly delay absorption but do not affect overall bioavailability. |
| Clinical Pearls | Measure serum creatinine and electrolytes before initiation and at regular intervals. Monitor for cough, angioedema, and hypotension. Avoid in pregnancy (category D). Use with caution in renal artery stenosis. Adjust dose in renal impairment (CrCl <30 mL/min). Concomitant use with aliskiren increases risk of hyperkalemia in diabetes. |
| Patient Advice | Take once daily at the same time, with or without food. · Avoid salt substitutes containing potassium without consulting your doctor. · Report persistent dry cough, swelling of face/lips, or difficulty breathing immediately. · Rise slowly from sitting or lying down to prevent dizziness. · Drink adequate fluids unless otherwise directed. · Use contraception and inform your doctor if you plan to become pregnant. · Do not stop taking suddenly without medical advice. |