Information about IMPENDO PLUS

Composition:
Each film coated tablet contains:
3.395 mg perindopril equivalent to 5 mg perindopril arginine, 1.25 mg indapamide and 6.935 mg amlodipine besilate equivalent to 5 mg of amlodipine.
Or 3.395 mg perindopril equivalent to 5 mg perindopril arginine, 1.25 mg indapamide     and13.870 mg amlodipine besilate equivalent to 10mg of amlodipine.
 Or 6.790 mg perindopril equivalent to 10 mg perindopril arginine, 2.5 mg indapamide and6.935 mg amlodipine besilate equivalent to 5 mg of amlodipine.
Pharmacokinetic:
Perindopril:
- Absorption and bioavailability:
After oral administration, the absorption of perindopril is rapid and the peak concentration is achieved within 1 hour (perindopril is a prodrug and perindoprilat the active metabolite). The plasma half-life of perindopril is equal to 1 hour. As ingestion of food decreases conversion to perindoprilat, hence bioavailability, perindopril arginine should be administered orally in a single daily dose in the morning before a meal.
- Distribution:
The volume of distribution is approximately 0.2 L/kg for unbound perindoprilat. Protein binding of perindoprilat to plasma proteins is 20.
- Biotransformation:
Perindopril is a prodrug. Twenty seven percent of the administered perindopril dose reaches the bloodstream as the active metabolite perindoprilat. In addition to active perindoprilat, perindopril yields five metabolites, all inactive. The peak plasma concentration of perindoprilat is achieved within 3 to 4 hours.
- Elimination:
Perindoprilat is eliminated in the urine and the terminal half-life of the unbound fraction is approximately 17 hours, resulting in steady-state within 4 days.
Indapamide:
- Absorption:
Indapamide is rapidly and completely absorbed from the digestive tract.
The peak plasma level is reached in humans approximately one hour after oral administration of the product.
- Distribution:
Plasma protein binding is 79 %.
- Metabolism and Elimination:
The elimination half-life is between 14 and 24 hours (average 18 hours). Repeated administration does not produce accumulation.
Elimination is mainly in the urine (70 % of the dose) and faeces (22 %) in the form of inactive metabolites.
Amlodipine:
- Absorption and Bioavailability:
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 bioavailability of amlodipine is not affected by food intake.
- Distribution:
The volume of distribution is approximately 21 L/kg. In vitro studies have shown that approximately 97.5% of circulating amlodipine is bound to plasma proteins.
- Metabolism:
Amlodipine is extensively metabolised by the liver to inactive metabolites with 10% of the parent compound and 60% of metabolites excreted in the urine.
- Elimination:
The terminal plasma elimination half-life is about 35-50 hours and is consistent with once daily dosing.
Indications:
Indicated as substitution therapy for treatment of essential hypertension, in patients already controlled with perindopril/indapamide fixed dose combination and amlodipine, taken at the same dose level.
Contraindications:
- Dialysis patients.
- Patients with untreated decompensated heart failure.
- Severe renal impairment (creatinine clearance below 30 mL/min).
- Moderate renal impairment (creatinine clearance below 60 mL/min) for Impendo Plus doses containing 10mg/2.5mg of perindopril/indapamide combination (i.e., Impendo Plus 10mg/2.5mg/5mg and 10mg/2.5mg/10mg).
- Hypersensitivity to the active substances, to other sulphonamides, to dihydropyridine derivatives, any other ACE inhibitor or to any of the excipients.
- History of angioedema (Quincke's oedema) associated with previous ACE inhibitor therapy.
- Hereditary/idiopathic angioedema.
- Second and third trimesters of pregnancy.
- Lactation.
- Hepatic encephalopathy.
- Severe hepatic impairment.
- Hypokalaemia.
- Severe hypotension.
- Shock, including cardiogenic shock.
- Obstruction of the outflow-tract of the left ventricle (e.g. high grade aortic stenosis).
- Haemodynamically unstable heart failure after acute myocardial infarction.
- Concomitant use of Impendo Plus with aliskiren-containing products in patients with diabetes mellitus or renal impairment (GFR < 60mL/min/1.73m2).
Pregnancy:
The use of ACE inhibitors is not recommended during the first trimester of pregnancy.
The use of ACE inhibitors is contra-indicated during the second and third trimesters of pregnancy.
Breastfeeding:
Impendo Plus is contraindicated during lactation.
Dosage and administration:
One film-coated tablet per day as a single dose, preferably to be taken in the morning and before a meal.
The fixed dose combination is not suitable for initial therapy.
Special cases:
- Renal impairment:
In severe renal impairment (creatinine clearance below 30 mL/min), treatment is contraindicated.
In patients with moderate renal impairment (creatinine clearance 30-60 mL/min), Impendo Plus at the doses 10mg/2.5mg /5mg and 10mg/2.5mg/10mg is contraindicated. It is recommended to start treatment with the adequate dosage of the free combination.
Usual medical follow-up will include frequent monitoring of creatinine and potassium.
Concomitant use of perindopril with aliskiren is contraindicated in patients with renal impairment (GFR < 60 ml/min/1.73 m2).
- Hepatic impairment:
In severe hepatic impairment, Impendo Plus is contraindicated.
In patients with mild to moderate hepatic impairment, Impendo Plus should be administrated with caution, as dosage recommendations for amlodipine in these patients have not been established.
- Elderly:
Elimination of perindoprilat is decreased in the elderly.
Elderly can be treated with Impendo Plus according to renal function.
- Paediatric population:
The safety and efficacy of Impendo Plus in children and adolescents have not been established.
Overdose:
There is no information on overdosage with Impendo Plus in humans.
Storage conditions:
Store at 25 C.
Packaging:
Pack of 14 film coated Tablets for whole strengths.