Perindopril (Perindopril Erbumine)

Indications
Oral
Hypertension
Adult: As erbumine: Initially, 4 mg once daily. 1st dose preferably given at bedtime. Patients with renovascular hypertension, volume depletion, severe hypertension: Initially, 2 mg once daily. Max: 8 mg daily. Patients on diuretics: Withdraw diuretics 2 or 3 days before perindropil therapy. Resume later if required. If diuretic cannot be discontinued, an initial dose of 2 mg once daily may be given.
Elderly: As erbumine: Initially, 2 mg once daily. May be progressively increased to 4 mg after 1 mth then to 8 mg if needed according to renal function.
CrCl (ml/min)Dosage Recommendation
30-602 mg daily.
15-302 mg on alternate days.
<152 mg on dialysis days.

Oral
Heart failure
Adult: As erbumine: Initially, 2 mg in the morning. Increase by 2-mg increments at no <2 wk intervals to a maintenance dose of 4 mg/day.
CrCl (ml/min)Dosage Recommendation
30-602 mg daily.
15-302 mg on alternate days.
<152 mg on dialysis days.

Oral
Stable ischaemic heart disease
Adult: As erbumine: Initially, 4 mg once daily for 2 wk then titrate up to a maintenance dose of 8 or 10 mg once daily if tolerated.
Elderly: As erbumine: Initially, 2 mg once daily on the 1st wk, increase as tolerated to 4 mg once daily on the 2nd wk, then increase again as tolerated to a maintenance dose of 8 mg once daily.
CrCl (ml/min)Dosage Recommendation
30-602 mg daily.
15-302 mg on alternate days.
<152 mg on dialysis days.


Special Populations: Renal impairment: CrCl >60 mL/min: 4 mg/day; 30-60 mL/min: 2 mg/day; 15-29 mL/min: 2 mg every other day; <15 mL/min: 2 mg on the day of dialysis. Maintenance dose: 2 mg daily or on alternate days, depending on the ° of impairment. Hepatic impairment: No dosage adjustment needed. Patients receiving diruetics: Discontinue diuretics 2 or 3 days before starting perindopril, resumed later if necessary.
Contraindications
History of angioedema related to previous ACE inhibitor treatment. Pregnancy (2nd/3rd trimesters).
Warnings / Precautions
History of airway surgery. Withdraw if there is significant increase in LFTs. Risk factors for hyperkalaemia; monitor potassium closely. Patients dependent on renin-angiotensin-aldosterone system; consider withdrawal in patients with progressive deterioration in renal function. Collagen vascular disease. Hypovolaemia; monitor BP with the 1st dose. Unilateral renal artery stenosis and pre-existing renal insufficiency; valvular aortic stenosis. Before, during, or immediately after anaesthesia. May impair ability to drive or operate machinery. Lactation.
Adverse Reactions
Headache, dizziness, sleep disorders, depression, fever, nervousness, somnolence; cough, upper respiratory tract infection, sinusitis, rhinitis, pharyngitis; oedema, chest pain, abnormal ECG, palpitation; rash; hyperkalaemia, elevated triglycerides, menstrual disorder; nausea, diarrhoea, vomiting, dyspepsia, abdominal pain, flatulence: UTI, sexual dysfunction; increased LFTs; weakness, musculoskeletal pain, upper and lower extremity pain, hypertonia, paraesthesia; proteinuria; tinnitus, ear infection; viral infection, allergy.
Potentially Fatal: Anaphylactoid reactions, angioedema.
Overdose Reactions
Symptom: Mild hypotension, bradycardia, hyperkalaemia (especially in patients with renal insufficiency), circulatory shock, renal failure, hyperventilation, tachycardia, palpitations, dizziness, anxiety, and cough. Treatment: Symptomatic and supportive. Haemodialysis may be beneficial.
Drug Interactions
Excessive BP reduction may occur in patients on diuretics. Increased risk of hyperkalaemia with potassium supplements, potassium-sparing diuretics, trimethoprim. May increase lithium levels/toxicity. May increase hypersensitivity reactions to allopurinol. Effects may be reduced by aspirin or other NSAIDs and/or adverse renal effects may be increased. May increase nephrotoxicity of ciclosporin. May increase the adverse/toxic effects (nitritoid reaction) of gold sodium thiomalate. Increased risk of hypoglycaemia with insulin. Increased risk of neutropenia with mercaptopurine.
See Below for More perindopril Drug Interactions
Food Interactions
Conversion to active form reduced with food. Ephedra, yohimbe and ginseng may worsen hypertension. Garlic may increase antihypertensive effect.
Mechanism of Actions
Perindopril is a prodrug of perindoprilat, which is a competitive ACE inhibitor. Perindoprilat prevents conversion of angiotensin I to angiotensin II. It acts as a vasodilator and it reduces peripheral resistance.
Onset: Within 1 hr; max effect at about 4-8 hr.
Duration: 24 hr.
Absorption: Rapidly absorbed from the GI tract. Bioavailability: 65-75%. Peak plasma concentrations of perindoprilat: 3-4 hr after an oral dose of perindopril.
Distribution: Protein-binding: Perindopril: 60%. Perindoprilat: 10-20%.
Metabolism: Mainly hepatic; extensively metabolised to perindoprilat (active metabolite) and inactive metabolites. Food may reduce the conversion to perindoprilat.
Excretion: Mainly via urine (as unchanged drug, as metabolites). Elimination half-life of perindoprilat: 25-30 hr or longer; excretion reduced in renal impairment. Both drug and active metabolite are dialysable.
Administration
Should be taken on an empty stomach. (Take before meals.)
Storage Conditions
Oral: Store at 20-25°C (68-77°F). Protect from moisture.
ATC Classification
C09AA04 - perindopril ; Belongs to the class of ACE inhibitors. Used in the treatment of cardiovascular disease.
Storage
Oral: Store at 20-25°C (68-77°F). Protect from moisture.
Available As
  • Perindopril (Perindopril Erbumine) 2 mg
  • Perindopril (Perindopril Erbumine) 4 mg
  • Perindopril (Perindopril Erbumine) 8 mg
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