perindopril erbumine
Aceon

Available forms
Available by prescription only
Tablets: 2 mg, 4 mg, 8 mg

Indications and dosages
 Essential hypertension. Adults: Initially, 4 mg P.O. once daily. Increase dosage until blood pressure is controlled or to a maximum of 16 mg/day; usual maintenance dose is 4 to 8 mg once daily; may be given in two divided doses.
Elderly patients: Initially, 4 mg P.O. daily as one dose or in two divided doses. Dosage increases exceeding 8 mg/day should occur only under close medical supervision.
≡ Dosage adjustment. For renally impaired patients, initially, 2 mg P.O. daily with a maximum maintenance dose of 8 mg daily. Don’t use in patients with creatinine clearance less than 30 ml/minute. For patients taking diuretics: initially, 2 to 4 mg P.O. daily as one dose or in two divided doses with close medical supervision for several hours and until blood pressure has stabilized. Adjust dosage based on patient’s blood pressure response.

Pharmacodynamics
Antihypertensive action: A prodrug that is converted by the liver to the active metabolite perindoprilat. Perindoprilat is thought to lower blood pressure through inhibition of ACE activity, thereby preventing the conversion of angiotensin I to angiotensin II, a potent vasoconstrictor. Inhibition of ACE results in decreased vasoconstriction and decreased aldosterone, thus reducing sodium and water retention and lowering blood pressure.

Pharmacokinetics
Absorption: Rapidly absorbed after oral administration. Absolute oral bioavailability around 75%. Plasma level of perindopril and perindoprilat increased about twofold in elderly patients.
Distribution: Perindopril and perindoprilat about 60% and 10% to 20% bound to plasma proteins, respectively. Drug interaction resulting from effects on protein-binding aren’t anticipated.
Metabolism: Perindopril extensively metabolized by liver to perindoprilat.
Excretion: About 4% to 12% of dose excreted in urine as unchanged drug. Reduced drug clearance in elderly patients and in those with heart failure or renal insufficiency.

Contraindications and precautions
Contraindicated in patients hypersensitive to perindopril or other ACE inhibitors and in those with history of angioedema secondary to ACE inhibitors. Also contraindicated in pregnant women.
  Use cautiously in patients with history of angioedema unrelated to ACE inhibitor therapy. Also use cautiously in patients with impaired renal function, heart failure, ischemic heart disease, cerebrovascular disease or renal artery stenosis, and in patients with collagen vascular disease, such as systemic lupus erythematosus or scleroderma.

Interactions
Drug-drug. Diuretics: Causes additive hypotensive effect. Monitor patient closely.
Lithium: Increases serum lithium level; may cause lithium toxicity. Use of a diuretic may further increase risk of lithium toxicity. Use together cautiously; monitor serum lithium level.
Potassium-sparing diuretics (amiloride, spironolactone, triamterene), potassium supplements, other drugs capable of increasing serum potassium (cyclosporine, heparin, indomethacin): Causes additive hyperkalemic effect. Use together cautiously; monitor serum potassium level frequently.
Drug-herb. Capsaicin: Increases risk of cough. Discourage use together.
Drug-food. Salt substitutes that contain potassium: Increases risk of hyperkalemia. Tell patient to use together cautiously.

Adverse reactions
CNS: dizziness, asthenia, sleep disorder, paresthesia, depression, somnolence, nervousness, headache, fever.
CV: palpitations, edema, chest pain, abnormal ECG.
EENT: rhinitis, sinusitis, ear infection, pharyngitis, tinnitus, seasonal allergy.
GI: dyspepsia, diarrhea, abdominal pain, nausea, vomiting, flatulence.
GU: proteinuria, urinary tract infection, male sexual dysfunction, menstrual disorder.
Musculoskeletal: back pain, hypertonia, neck pain, joint pain, myalgia, arthritis, low or upper extremity pain.
Respiratory: cough, upper respiratory tract infection.
Skin: rash.
Other: viral infection, injury.

Effects on lab test results
• May increase ALT and triglyceride levels.

Overdose and treatment
Hypotension would be the most likely result of perindopril overdose.
 Treatment should be symptomatic and supportive. Discontinue perindopril and observe patient closely. Treat dehydration, electrolyte imbalances, and hypotension using established protocols.

Special considerations
• Monitor renal function before and periodically throughout therapy. Drug shouldn’t be used in patients with creatinine clearance less than 30 ml/ minute.
• Angioedema involving face, limbs, lips, tongue, glottis, and larynx has been reported in patients treated with perindopril. Stop drug and observe patient until swelling disappears. If swelling is confined to face and lips, it probably will resolve without treatment, but antihistamines may be useful in relieving symptoms. Angioedema involving with tongue, glottis, or larynx may be fatal because of airway obstruction. Appropriate therapy, such as S.C. epinephrine solution, should be promptly administered.
• Patients with history of angioedema unrelated to ACE inhibitor therapy may be at increased risk for angioedema while receiving an ACE inhibitor.
• Excessive hypotension can occur when drug is given with diuretics. If possible, diuretic therapy should be stopped 2 to 3 days before starting perindopril to decrease potential for excessive hypotensive response. If it isn’t possible to stop diuretic, consider starting with a lower dose of perindopril or decreasing diuretic dose.
• Hypotension can occur when initiating therapy or adjusting doses in patients who have been volume- or salt-depleted as a result of prolonged diuretic therapy, dietary salt restriction, dialysis, diarrhea, or vomiting. Volume and salt depletion should be corrected before starting drug.
• Monitor patients at risk for hypotension closely during start of therapy and for the first 2 weeks of treatment, and whenever perindopril dosage or concomitant diuretic is increased. If severe hypotension occurs, place patient in supine position and treat symptomatically.
• Other ACE inhibitors have been linked to agranulocytosis and neutropenia. Monitor CBC with differential before therapy, especially in renally impaired patients with systemic lupus erythematosus or scleroderma.
• Monitor serum potassium levels closely.
• ACE inhibitors have rarely been linked to a syndrome of cholestatic jaundice, fulminant hepatic necrosis, and death. Stop drug in patients who develop jaundice or marked elevations of hepatic enzyme levels during therapy.
Breast-feeding patients
• It isn’t known if drug appears in breast milk. Use cautiously in breast-feeding women.
Pediatric patients
• Safety and effectiveness of drug in children haven’t been established.
Geriatric patients
• Plasma levels of perindopril and perindoprilat in patients older than age 70 are about twice those observed in younger patients. With the exception of dizziness and possibly rash, adverse effects don’t appear to increase in elderly patients. Doses above 8 mg/day should be administered cautiously and under close medical supervision.

Patient education
• Inform patient that angioedema, including laryngeal edema, can occur during therapy, especially with first dose. Advise patient to stop taking drug and immediately report any signs or symptoms of angioedema (swelling of face, limbs, eyes, lips, or tongue; hoarseness; or difficulty in swallowing or breathing).
• Advise patient to report promptly any sign of infection (such as sore throat, fever) or jaundice (yellowing of eyes or skin).
• Explain to patient that chronic dry cough may occur. Advise patient to avoid OTC preparations to treat the cough and to report cough if it develops.
• Advise patient to avoid salt substitutes containing potassium unless instructed otherwise.
• Caution patient that light-headedness may occur, especially during first few days of therapy. Advise patient to report light-headedness and, if fainting occurs, to stop drug and call promptly.
• Caution patient that inadequate fluid intake or excessive perspiration, diarrhea, or vomiting can lead to an excessive drop in blood pressure.
• Advise woman of childbearing age of consequences of second and third trimester exposure to drug. Advise her to call immediately if pregnancy is suspected.

Reactions may be common, uncommon, life-threatening, or COMMON AND LIFE THREATENING.
◆ Canada only
◇ Unlabeled clinical use