ACEON
Clinical safety rating: caution
Comprehensive clinical and safety monograph for ACEON (ACEON).
ACEON (perindopril) is an angiotensin-converting enzyme (ACE) inhibitor. It inhibits ACE, which converts angiotensin I to angiotensin II, a potent vasoconstrictor. This results in decreased vasopressor activity, reduced aldosterone secretion, and lower peripheral vascular resistance, leading to antihypertensive effects.
| Metabolism | Perindopril is extensively metabolized via hydrolysis to its active metabolite, perindoprilat, primarily by esterases. Perindoprilat undergoes further metabolism to inactive metabolites. Minor CYP450 involvement (CYP3A4 and CYP2C9) may contribute, but esterase-mediated hydrolysis is the predominant pathway. |
| Excretion | Renal: approximately 30% as perindopril and 20% as perindoprilat; fecal: approximately 50% as metabolites. |
| Half-life | Perindoprilat: terminal half-life ~30 hours (up to 120 hours in elderly or heart failure due to prolonged terminal phase from slow dissociation from ACE binding); perindopril: ~1.5 hours. |
| Protein binding | Perindopril: 60%; perindoprilat: 20% (predominantly albumin). |
| Volume of Distribution | Perindopril: 0.2 L/kg; perindoprilat: 0.16 L/kg. |
| Bioavailability | Oral: 65-75% (perindopril); perindoprilat: 25-30% after metabolism. |
| Onset of Action | Oral: 1-2 hours; maximal effect at 4-8 hours. |
| Duration of Action | 24 hours (supports once-daily dosing); anti-hypertensive effect sustained over 24 h with trough/peak ratio ~75-100%. |
Initial: 4 mg orally once daily; titrate to 8-32 mg daily in 1-2 divided doses. Typical maintenance: 8-16 mg daily.
| Dosage form | TABLET |
| Renal impairment | CrCl 30-60 mL/min: initial 2 mg/day; max 8 mg/day. CrCl 10-29 mL/min: initial 2 mg/day; max 4 mg/day. Hemodialysis: initial 2 mg on dialysis days; max 4 mg/day. |
| Liver impairment | No specific guidelines for Child-Pugh; caution in severe hepatic impairment due to reduced prodrug conversion. |
| Pediatric use | Safety and efficacy not established; no approved dosing. |
| Geriatric use | Start at 2 mg/day; titrate slowly due to increased hypotensive risk and decreased renal function. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for ACEON (ACEON).
| Breastfeeding | Excreted in human milk in minimal amounts (M/P ratio ~0.02); considered compatible with breastfeeding for full-term infants, but caution in preterm or renal impairment. |
| Teratogenic Risk | First trimester: Potential risk of fetal malformations (neural tube defects, cardiovascular) based on animal data; second and third trimesters: Fetal oligohydramnios, renal dysfunction, skull ossification defects, hypotension, hyperkalemia, and death (ACE inhibitor fetopathy). Use contraindicated in pregnancy. |
| Fetal Monitoring |
■ FDA Black Box Warning
Fetal Toxicity: Drugs that act 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 therapy","Hereditary or idiopathic angioedema","Pregnancy (second and third trimesters)","Concomitant use with aliskiren in patients with diabetes mellitus","Hypersensitivity to perindopril or any component of the formulation"]
| Precautions | ["Angioedema: Risk of angioedema, including life-threatening cases. Discontinue immediately and manage appropriately.","Fetal toxicity: See black box warning.","Hypotension: Excessive hypotension may occur, especially in volume-depleted or salt-depleted patients.","Renal impairment: Monitor renal function; dose adjustment required in renal impairment.","Hyperkalemia: Risk of hyperkalemia, particularly in patients with renal impairment, diabetes, or those taking potassium-sparing diuretics or potassium supplements.","Cough: Persistent dry cough may occur.","Hepatic failure: Rare cases of hepatic failure reported."] |
| Food/Dietary |
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| Monitor maternal blood pressure, renal function, electrolytes; fetal ultrasound for growth, amniotic fluid index, and renal anatomy; neonatal monitoring for hypotension, oliguria, hyperkalemia. |
| Fertility Effects | No known adverse effects on human fertility; animal studies show no impairment. |
| Avoid high-potassium foods (e.g., bananas, oranges, potatoes, tomatoes, spinach, avocados) and salt substitutes containing potassium. No specific food restrictions but maintain consistent salt intake. Grapefruit juice not known to interact. Alcohol may enhance hypotensive effect. |
| Clinical Pearls | ACEON (perindopril erbumine) is a long-acting ACE inhibitor. Monitor renal function and electrolytes before and during therapy. Reduce dose in elderly and renal impairment. Avoid in pregnancy (category D). May cause angioedema; black patients have higher risk. Use with caution in patients with renal artery stenosis. Combination with diuretics may cause hypotension. |
| Patient Advice | Take exactly as prescribed, usually once daily with or without food. · Do not use potassium supplements or salt substitutes containing potassium without consulting your doctor. · Report any signs of infection (fever, sore throat) or swelling of face, lips, tongue, or difficulty breathing immediately. · May cause dizziness; avoid driving or operating machinery until you know how you react. · If you become pregnant, stop taking and contact your doctor immediately. · Stay hydrated, but avoid dehydration from excessive sweating, vomiting, or diarrhea. |