Information about Impendo

Composition:
Each tablet contains:
4 mg perindopril tertbutylamine (equivalent to 3.34 mg perindopril) and 5 mg amlodipine (as besilate).
or
4 mg perindopril tertbutylamine (equivalent to 3.34 mg perindopril) and 10 mg amlodipine (as besilate).
or
8 mg perindopril tertbutylamine (equivalent to 6.68 mg perindopril) and 5 mg amlodipine (as besilate).
or
8 mg perindopril tertbutylamine (equivalent to 6.68 mg perindopril) and 10 mg amlodipine (as besilate).
CLINICAL PHARMACOLOGY:
Perindopril:
Perindopril is an inhibitor of the enzyme that converts angiotensin I into angiotensin II (Angiotensin Converting Enzyme ACE).
Inhibition of ACE results in a reduction of angiotensin II in the plasma, which leads to increased plasma renin activity and reduced secretion of aldosterone.
Amlodipine:
Amlodipine is a calcium antagonist and inhibits the influx of calcium ions into cardiac and vascular smooth muscle. The mechanism of the anti-hypertensive action is due to a direct relaxant effect on vascular smooth muscle.
Pharmacokinetics:
Perindopril: the absorption of perindopril is rapid and the peak concentration is achieved within 1 hour. The plasma half-life of perindopril is equal to 1 hour.
Perindopril is a prodrug .it acts through its active metabolite, Perindoprilat.
The volume of distribution is approximately 0.2 l/kg for unbound perindoprilat. Protein binding of perindoprilat to plasma proteins is 20%. Perindoprilat is eliminate din the urine and the terminal half-life of the unbound fraction is approximately 17 hours, resulting in steady-state within 4 days.
Elimination of perindoprilat is decreased in the elderly, and also in patients with heart or renal failure.
Amlodipine: After oral administration of therapeutic doses, amlodipine is well absorbed with peak blood levels between 6-12 hours post dose. Absolute bioavailability has been estimated to be between 64 and 80%. The volume of distribution is approximately 21 l/kg. Its bioavailability is not influenced by food. 97.5% of circulating amlodipine is bound to plasma proteins. Elimination half-life is about 35-50 hours.
INDICATIONS AND USAGE:
Impendo (Perindopril/Amlodipine) tablets is indicated as substitution therapy for treatment of essential hypertension and/or stable coronary artery disease.
CONTRAINDICATIONS:
Linked to perindopril:
Hypersensitivity to perindopril or any other ACE inhibitor.
History of angioedema associated with previous ACE inhibitor therapy.
Hereditary or idiopathic angioedema.
Second and third trimesters of pregnancy.
Linked to amlodipine:
Severe hypotension.
Shock, including carcinogenic shock.
Obstruction of the outflow-tract of the left ventricle (e.g., high grade aortic stenosis),
Haemodynamically unstable heart failure after acute myocardial infarction.
WARNINGS & Precautions:
Warnings Linked to perindopril:
Hypersensitivity/Angioedema.
Anaphylactoid reactions during low-density lipoproteins (LDL) apheresis.
Anaphylactoid reactions during desensitization.
Pregnancy:
Precautions for use:
Hypotension: Symptomatic hypotension likely to occur in patients who have been volume-depleted. In patients at high risk of symptomatic hypotension, blood pressure, renal function and serum potassium should be monitored closely during treatment with Perindopril/Amlodipine. Similar considerations apply to patients with ischaemic heart or cerebrovascular disease in whom an excessive fall in blood pressure could result in a myocardial infarction or cerebrovascular accident.
Aortic and mitral valve stenosis / hypertrophic cardiomyopathy:
As with other ACE inhibitors, perindopril should be given with caution to patients with mitral valve stenosis and obstruction in the outflow of the left ventricle such as aortic stenosis or hypertrophic cardiomyopathy.
Renal impairment:
In cases of renal impairment an individual dose titration with the mono components is recommended. Routine monitoring of potassium and creatinine are part of normal medical practice for patients with renal impairment
Hepatic failure:
Patients receiving ACE inhibitors who develop jaundice or marked elevations of hepatic enzymes should discontinue the ACE inhibitor and receive appropriate medical follow-up.
Ethnic differences:
ACE inhibitors cause a higher rate of angioedema and less effective in lowering blood pressure in black people than in non-blacks.
Surgery/Anaesthesia:
The treatment should be discontinued one day prior to the surgery.
Hyperkalaemia:
Hyperkalaemia can cause serious, sometimes fatal arrhythmias.
If concomitant use of perindopril and any of the Risk factors (renal insufficiency, diabetes mellitus, potassium supplements or potassium containing salt substitutes; or those patients taking other drugs associated with increases in serum potassium,
is deemed appropriate, they should be used with caution and with frequent monitoring of serum potassium.
Diabetic patients:
In diabetic patients treated with oral antidiabetic agents or insulin, glycaemic control should be closely monitored during the first month of treatment with an ACE inhibitor.
Linked to amlodipine:
Patients with impaired hepatic function:
half-life of amlodipine is prolonged in patients with impaired liver function. The drug should therefore be administered with caution in these patients and with a close monitoring of the hepatic enzymes.
Patients with heart failure:
Patients with cardiac failure should be treated with caution.
Linked to Perindopril/Amlodipine:
The concomitant use of Perindopril/Amlodipine with lithium, potassium-sparing diuretics or potassium supplements is not recommended.
Pregnancy and lactation:
Impendo is not recommended during the first trimester of pregnancy.
Impendo is contraindicated during the second and third trimesters of pregnancy.
Impendo is not recommended during lactation.
Drug Interaction:
Linked to perindopril:
Concomitant use not recommended:
Potassium sparing diuretics, potassium supplements or potassium-containing salt substitutes: If concomitant use is indicated because of demonstrated hypokalaemia, they should be used with caution and with frequent monitoring of serum potassium.
Lithium: Reversible increases in serum lithium concentrations and toxicity (severe neurotoxicity) have been reported during concurrent use of ACE inhibitors. If the combination proves necessary, careful monitoring of serum lithium levels is recommended.
Estramustine: Risk of increased adverse effects such as angioneurotic oedema (angioedema).
Concomitant use which requires special care:
When ACE-inhibitors are administered simultaneously with non-steroidal anti-inflammatory drugs attenuation of the antihypertensive effect may occur. Concomitant use of ACE-inhibitors and NSAIDs may lead to an increased risk of worsening of renal function, including possible acute renal failure, and an increase in serum potassium, especially in patients with poor pre-existing renal function. The combination should be administered with caution, especially in the elderly. Patients should be adequately hydrated and consideration should be given to monitoring renal function after initiation of concomitant therapy, and periodically thereafter.
Anti-diabetic agents (insulin, hypoglycaemic sulphonamides). The use of angiotensin converting enzyme inhibitors may increase the hypoglycaemic effect in diabetic receiving treatment with insulin or with hypoglycaemic sulphonamides.
Concomitant use to be taken into consideration:
Diuretics: Patients on diuretics, and especially those who are volume and/or salt depleted, may experience excessive reduction in blood pressure after initiation of therapy with an ACE inhibitor.
Sympathomimetics: Sympathomimetics may reduce the antihypertensive effects of ACE inhibitors.
Gold: Nitritoid reactions (symptoms include facial flushing, nausea, vomiting and hypotension) have been reported rarely in patients on therapy with injectable gold (sodium aurothiomalate) and concomitant ACE inhibitor therapy including perindopril.
Linked to amlodipine:
Concomitant use which requires special care:
CYP3A4inhibitors: plasma concentration of amlodipine increased.
CYP3A4inducers: lower plasma concentration of amlodipine.
Concomitant use to be taken into consideration:
Beta-blockers used in heart failure: Risk of hypotension, heart weakness in patients with cardiac heart failure, be it latent or uncontrolled.
Other’s combinations:
Concomitant use which requires special care:
Baclofen. Potentiation of antihypertensive effect. Monitoring of blood pressure and renal
function, and dose adjustment of the antihypertensive if necessary.
Concomitant use to be taken into consideration:
Antihypertensive agents (such as beta-blockers) and vasodilators: Concomitant use of these agents may increase the hypotensive effects of perindopril and amlodipine.
Concomitant use with nitroglycerine and other nitrates or other vasodilators, may further reduce blood pressure and therefore should be considered with caution.
Corticosteroids, tetracosactide: reduction in antihypertensive effect (salt and water retention due to corticosteroids).
Alpha-blockers (prazosin, alfuzosin, doxazosin, tamsulosin, terazosin): increased antihypertensive effect and increased risk of orthostatic hypotension.
Amifostine: may potentiate the antihypertensive effect of amlodipine.
Tricyclic antidepressants/antipsychotics/anaesthetics: increased antihypertensive effect and increased risk of orthostatic hypotension.
ADVERSE REACTIONS:
Mood changes, Somnolence, Dizziness, Headache, Paraesthesia, Vertigo, Visual disturbances, Tinnitus, Syncope, Palpitations, Flushing, Hypotension, Dyspnoea, Rhinitis, Cough, Bronchospasm, Abdominal pain, nausea, Vomiting, Dyspepsia, Dry mouth, Dysgeusia, Diarrhoea, constipation, Sweating, Pruritus, Rash, Muscle cramps, Impotence, Oedema, peripheral oedema, Fatigue, Asthenia.
OVERDOSAGE:
There is no information on overdose with Impendo in humans.
For amlodipine, large over dosage could result in excessive peripheral vasodilatation with subsequent marked and probably prolonged systemic hypotension
For perindopril, overdose of ACE inhibitors may include hypotension, circulatory shock, electrolyte disturbances, renal failure, hyperventilation, tachycardia, palpitations, bradycardia, dizziness, anxiety, and cough.
The recommended treatment of overdose is intravenous infusion of normal saline solution. If hypotension occurs, the patient should be placed in the shock position. If available, treatment with angiotensin II infusion and/or intravenous catecholamines may also be considered.
Perindopril can be removed from the systemic circulation by haemodialysis.
Pacemaker therapy is indicated for treatment-resistant bradycardia. Vital signs, serum electrolytes and creatinine concentrations should be monitored continuously.
DOSAGE AND ADMINISTRATION:
Oral route.
One tablet per day as a single dose, preferably to be taken in the morning and before a meal.
Impendo can be administered in patients with Clcr ≥ 60 ml/min.
Pack size:
14 tablets for all strengths.
Storage condition:
Store in the original package in order to protect from light & moisture.
Store below 25 ºC.