Peripril
Perindopril
Indication
Mild to moderate hypertension and essential hypertension (maintenance therapy).
Hypertension with diabetes, chronic renal disease and ischaemic heart disease.
Stable coronary artery disease.
Dosage and Administration
Usual adult dose for Hypertension:
Initial dose: 4 mg orally once a day
Maintenance dose: 4 to 8 mg orally per day in 1 or 2 divided dose
Maximum dose: 16 mg/day.
Usual adult dose for Coronary Artery Disease: Initial dose: 4 mg orally once a day for 2 weeks Maintenance dose: 8 mg orally once a day Dose adjustment in geriatric patients:
Due to greater bioavailability and lower renal clearance of the drugs in elderly subjects, dose reduction of 50% is recommended.
Renal Dose adjustments:
Mild to moderate renal dysfunction (Creatinine clearance 30 mL/min or greater):
Initial dose: 2 mg/day Maximum dose: 8 mg/day
Severe renal dysfunction (Creatinine Clearance less than 30 mL/min): Not Recommended.
Composition
Each film-coated caplet contains:
Perindopril Erbumine B.P ... 4 mg.
Description
Perindopril is a long-acting Angiotensin Converting Enzyme Inhibitor (ACEI). Chemically, it is 2-Methylpropan- 2-amine (2S, 3aS, 7aS)-1-[(2S)-2-[[(I S)-1-(ethoxycarbonyl) butyl]amino] propanoyl]octahydro-1 H-indole-2-carboxylate. The empirical formula of perindopril erbumine is C23H43N305 and its m...
Clinical Pharmacology
Perindopril is a competitive inhibitor of angiotensin converting enzyme and so prevents the conversion of angiotensin I to angiotensin IL Angiotensin II is a potent peripheral vasoconstrictor which stimulates aldosterone secretion by the adrenal cortex, leading to increase peripheral vascular resist...
Perindopril also inhibits the degradation of bradykinin (also a substrate for ACE); an endogenous vasodilator occurring in blood vessel walls. These bradykinin may stimulate cough and can enhance release of nitric oxide and prostacyclin causing vasodilatation and fall in blood pressure.
Pharmacokinetics
Absorption: Well absorbed after oral administration Onset of action: Peak effect: 1 - 2 hrs
Peak plasma concentration: 3-7 hrs after perindopril administration
Bioavailability: Perindopril - 75%, perindoprilat - 25% Distribution: Approximately 60% of circulating perindopril is bound to plasma proteins and only 10 - 20% of perindoprilat is bound. Small amount enters breast milk. Metabolism: Perindopril is extensively metabolized following oral administratio...
Elimination: Approximately 75% of the dose is excreted by kidney and around 25% of the drug is eliminated in faeces.
The Plasma t1/2 of parent drug is 0.8 - 1 hr. Perindoprilat has a t1/2 of 3 - 10 hrs with prolonged terminal t1/2 of 2s - 120 hrs. .
Contraindication
Pregnancy (2nd and 3rd trimester), hypersensity to perindopril or any component of the formulation, angioedema, related to previous treatment with an ACE inhibitor, hereditary or idiopathic angioedema, bilateral renal artery stenosis, severe hypotension, hyponatremic patient, cardiogenic shock, aort...
Precaution
Anaphylactoid and possibly related reactions, hypotension, fetal toxicity, neutropenia / agranulocytosis with myeloid hyperplasia, impaired renal function, unilateral renal artery stenosis and pre-existing renal insufficiency, hyperkalaemia, cough, hepatic failure and surgery/anesthesia.
Adverse Effects
Adverse effects tend to be dose related and more frequent in patients with impaired renal functions. The commonest adverse effects are skin rashes, pruritus, fever and eosinophilia, persistent dry cough and taste disturbances. Transient hypotension may occur at the start of therapy. This can be mini...
Drug Interaction
Increased Effects/ Toxicity:
Potassium supplements, co-trimoxazole (high dose), angiotensin 11 receptor antagonists (candesartan, losartan, irbesartan, etc.), or potassium sparing diuretics (amiloride, spironolactone, triamterene) may result in elevated serum potassium levels when combined with perindopril.
ACEI effects may be increased by phenothiazine or probenecid.
ACET may increase serum concentrations/effects of digoxin, lithium and sulfonylurea.
Diuretics have additive hypotensive effects with ACEI and hypovolaemia increases the potential for adverse renal effects of ACEI.
In patients with compromised renal function, co administration with NSAIDs may result in further deterioration of renal function.
NSAIDs, specifically indomethacin, may reduce the hypotensive effect of ACET.
Allopurinol and ACE inhibitors may cause a higher risk of hypersensitivity reaction when taken concurrently. Decreased Effects: Aspirin (high dose) may reduce the therapeutic effects of ACEI.
Rifampin may decrease the effect of ACEI.
Antacids may decrease the bioavailability of ACEI; separate administration time by 1 - 2 hrs.
Storage
Store below 30°C in cool and dry place. Protect from light and moisture. Keep out of reach and sight of children.
Presentation
3 x 10's Alu-Alu Blisters.