Impendo

Therapeutic Group: Cardio-Vascular Drugs Chemical Composition: PERINDOPRIL / AMLODIPINE License by : Unipharma Dosage form: Tablets
Information about Impendo

Tablets

1. Composition

Each tablet contains:

4mg perindopriltert butylamine(equivalent to 3.34mg perindopril) and 5mg amlodipine (asbesilate).

or

4mg perindopriltert butylamine(equivalent to 3.34mg perindopril) and 10mg amlodipine (asbesilate).

or

8mg perindopriltert butylamine(equivalent to 6.68mg perindopril) and 5mg amlodipine (asbesilate).

or

8mg perindopriltert butylamine(equivalent to 6.68mg perindopril) and 10mg amlodipine (asbesilate).


2. CLINICAL PHARMACOLOGY

Perindopril:

Perindopril isan inhibitor of the enzyme that converts angiotensin I into angiotensin II(Angiotensin Converting Enzyme ACE).

Inhibition ofACE 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 acalcium antagonist and inhibits the influx of calcium ions into cardiac and vascular smooth muscle. The mechanism of the anti hypertensive action is due toa direct relaxant effect on vascular smooth muscle.

Pharmacokinetics

Perindopril:the absorption of perindopril is rapid and the peak concentration is achievedwithin 1 hour. The plasma half-life of perindopril is equal to 1 hour.

Perindopril is a prodrug .itacts through its active metabolite,Perindoprilate.

The volume ofdistribution is approximately 0.2 l/kg for unbound perindoprilat. Proteinbinding 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 bioavailabilityhas 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 isabout 35-50 hours.


3.INDICATIONS AND USAGE

Impendo(Perindopril/Amlodipine) tablets is indicated as substitution therapy for treatment of essential hypertension and/or stable coronary artery disease.


4.CONTRAINDICATIONS

Linked to perindopril:

-Hypersensitivityto perindopril or any other ACE inhibitor.

-History of angioedema associated with previous ACE inhibitor therapy.

-Hereditaryor idiopathic angioedema.

-Second and third trimesters of pregnancy.

 

Linked to amlodipine:

-Severehypotension.

-Shock,including carcinogenic shock.

-Obstruction of the outflow-tract of the left ventricle (e.g. high grade aortic stenosis),

-Haemodynamicallyunstable heart failure after acute myocardial infarction.


5.WARNINGS & Precautions

Warnings Linked to perindopril:

-Hypersensitivity/Angioedema.

-Anaphylactoidreactions during low-density lipoproteins (LDL) apheresis.

-Anaphylactoidreactions during desensitization.

-Pregnancy.

 

 

Precautions for use:

-Hypotension:Symptomatic hypotension likely to occur in patients who have beenvolume-depleted . In patients at high risk of symptomatic hypotension, blood pressure, renal function and serum potassium should be monitored closely duringtreatment with Perindopril/Amlodipine. Similar considerations apply to patients with ischaemic heart or cerebrovascular disease in whom an excessive fall inblood pressure could result in a myocardial infarction or cerebrovascularaccident.

-Aortic and mitral valve stenosis / hypertrophic cardiomyopathy:

As with otherACE inhibitors, perindopril should be given with caution to patients withmitral

valve stenosisand obstruction in the outflow of the left ventricle such as aortic stenosis or

hypertrophiccardiomyopathy.

-Renalimpairement:

In cases of renal impairment an individual dose titration with the monocomponents is recommended .Routine monitoring of potassium and creatinine are part of normalmedical practice for patients with renal impairment

-Hepaticfailure:

Patients receiving ACE inhibitors who develop jaundice or marked elevations of hepatic enzymes should discontinue the ACE inhibitor and receive appropriate medical follow-up.

-Ethnicdifferences:

ACE inhibitors cause a higher rate of angioedema andless effective in lowering blood pressure in black people than innon-blacks.

-Surgery/Anaesthesia:

 The treatment should be discontinued one dayprior to the surgery.

-Hyperkaelemia

Hyperkaelemia  can cause serious, sometimes fatalarrhythmias.

If concomitantuse of perindopril and any of the Risk factors (renal insufficiency, diabetesmellitus, potassium supplements or potassium containing salt substitutes; or those patients taking other drugs associated with increases in serum potassium,

is deemedappropriate, they should be used with caution and with frequent monitoring of serum potassium.

-Diabeticpatients:

In diabeticpatients treated with oral antidiabetic agents or insulin, glycaemic controlshould

be closely monitored during the first month of treatment with an ACE inhibitor.

 

Linked toamlodipine:

-Patients with impaired hepatic function:

half-life of amlodipineis 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 concomitantuse of Perindopril/Amlodipine with lithium, potassium-sparing diuretics orpotassium supplements is not recommended

 

6.Pregnancy andlactation

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.

7.Drug Interaction:

Linked to perindopril

  • Concomitant use not recommended:

-Potassiumsparing diuretics, potassium supplements or potassium-containing saltsubstitutes: If concomitant use is indicated because of demonstratedhypokalaemia, they should be used with caution and with frequent monitoring of serum potassium.

-Lithium: Reversibleincreases in serum lithium concentrations and toxicity (severe neurotoxicity)have been reported during concurrent use of ACE inhibitors. If the combinationproves 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-steroidalanti-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.

 

-Antidiabeticagents (insulin, hypoglycaemic sulphonamides). The use of angiotensinconverting enzyme inhibitors may increase the hypoglycaemic effect in diabeticsreceiving 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 saltdepleted, may experience excessive reduction in blood pressure after initiationof therapy with an ACE inhibitor.

-Sympathomimetics:Sympathomimetics may reduce the antihypertensive effects of ACE inhibitors.

-Gold: Nitritoidreactions (symptoms include facial flushing, nausea, vomiting and hypotension)have been reported rarely in patients on therapy with injectable gold (sodiumaurothiomalate) 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.

 

Others 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: Concomitantuse of these agents may increase the hypotensive effects of perindopril andamlodipine.

– Concomitantuse with nitroglycerine and other nitrates or other vasodilators, may further

reduce bloodpressure and therefore should be considered with caution.

–Corticosteroids, tetracosactide: reduction in antihypertensive effect (salt andwater

retention dueto 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.

– Tricyclicantidepressants/antipsychotics/anaesthetics: increased antihypertensive effectand increased risk of orthostatic hypotension.

 

8.ADVERSE REACTIONS

Mood changes,Somnolence, Dizziness, Headache, Paresthaesia, 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.


9.OVERDOSAGE

There is noinformation on overdose with Impendo in humans.

For amlodipine,large over dosage could result in excessive peripheral vasodilatation withsubsequent marked and probably prolonged systemic hypotension

Forperindopril, overdose of ACE inhibitors may include hypotension, circulatoryshock, 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

withangiotensin 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.


10.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 inpatients with Clcr ≥ 60 ml/min.


11.Pack size:

14 tablets for all strengths.


12.Storage condition:

Store in the original package in order to protect from light & moisture.

Store below 250 C.