Information about Tensocard
Composition:
Each Tensocard 2 mg tablet contains: perindopril erbumine 2 mg
Each Tensocard 4 mg tablet contains: perindopril erbumine 4 mg
Each Tensocard 8 mg tablet contains: perindopril erbumine 8 mg
Properties:
Perindopril is an Angiotensin Converting Enzyme Inhibitor (ACEI). This mechanism causes lower blood pressure.
Pharmacokinetics:
Following oral administration, perindopril is rapidly absorbed and is 61-85% bioavailable. Elimination is rapid, occurring predominantly via the urine. Plasma half-life is approximately 1 hour.
Biotransformation of perindopril to the active metabolite perindoprilat is approximately 20%. Peak plasma concentrations of perindopril at occur 3 to 4 hours after oral administration of Tensocard.
Indications:
TENSOCARD is indicated for:
the treatment of hypertension;
the treatment of heart failure. In such patients it is recommended that TENSOCARD be given with a diuretic and/or digoxin under close medical supervision.)
Reduction of risk of cardiovascular events (cardiovascular mortality, myocardial infarction or cardiac arrest) in patients with established coronary artery disease who are stable on concomitant therapy.
Contraindications:
TENSOCARD is contraindicated:
in patients with a history of previous hypersensitivity to the active ingredient perindopril or any of the excipient ingredients present in TENSOCARD;
during pregnancy and for lactating women;
in patients with bilateral or unilateral renal artery stenosis;
in patients with a history of hereditary and/or idiopathic angio-oedema or angio-oedema associated with previous ACE-inhibitor treatment; and
in patients haemodialysed using high-flux polyacrylonitrile ("AN69") membranes who are highly likely to experience anaphylactoid reactions if they are treated with ACE inhibitors. This combination should therefore be avoided, either by use of alternative antihypertensive drugs or alternative membranes (eg. cuprophane or polysulphone PSF).
Special Warnings and Precautions:
Hyperkalaemia:
Since ACE inhibitors reduce angiotensin II formation resulting in decreased production of aldosterone, an increase in serum potassium may be observed.
It is recommended that serum electrolytes (including sodium potassium and urea) should be measured from time to time when ACE inhibitors are given, especially when diuretics are also prescribed.
Angioedema:
Life-threatening angio-oedema has been reported with most ACE inhibitors. The overall incidence is approximately 0.1-0.2%. The aetiology is thought to be non-immunogenic and may be related to accentuated bradykinin activity.
Angio-oedema of the face, extremities, lips, tongue, glottis and/or larynx has been reported in patients treated with ACE inhibitors and has been reported on rare occasions with TENSOCARD. In such cases TENSOCARD should be promptly discontinued and the patient carefully observed until the swelling disappears.
Rarely, patients receiving ACE inhibitors during low-density lipoprotein (LDL) apheresis with dextran sulphate have experienced life-threatening anaphylactoid reactions. These reactions were avoided by temporarily withholding ACE inhibitor therapy prior to each apheresis.
Treatment of progressive angio-oedema should be aggressive, mechanical methods to secure an airway should be undertaken before massive oedema complicates oral or nasal intubation.
Patients who respond to medical treatment should be observed carefully for a possible rebound phenomenon.
The onset of angio-oedema associated with use of ACE inhibitors may be delayed for weeks or months .
Hypotension:
Hypotension has been reported in patients commencing treatment with ACE inhibitors.
Excessive hypotension is rarely seen in uncomplicated hypertension but is a potential consequence of TENSOCARD use in severely salt/volume-depleted patients with impaired renal function, those treated vigorously with diuretics, after severe diarrhoea or patients on dialysis.
In patients with severe congestive heart failure, with or without associated renal impairment, excessive hypotension has been observed.
Therefor, therapy should be started at low doses under very close supervision.
Patients with ischaemic heart or cerebrovascular disease in whom an excessive fall in blood pressure could result in myocardial infarction or cerebrovascular accident should be closely followed for the first two weeks of treatment and whenever the dose of TENSOCARD and/or diuretic is increased.
If hypotension occurs the patient should be placed in a supine position and if necessary infused with normal saline. A transient hypotensive response is not a contraindication to further doses, which can usually be given without difficulty when blood pressure has increased following volume expansion.
Impaired Renal Function:
As a consequence of inhibiting the renin-angiotensin-aldosterone system (RAAS), changes in renal function may be anticipated in susceptible individuals. In patients with severe congestive heart failure whose renal function may depend on RAAS activity, treatment with ACE inhibitors may be associated with oliguria and/or increase in blood nitrogen, and rarely with acute renal failure and/or death.
ACE inhibitors should be avoided in patients with known or suspected renal artery stenosis. When an ACE inhibitor is given to a patient with stenosis of the renal artery supplying a solitary kidney, or bilateral renal artery stenosis, acute renal insufficiency may occur.
Evaluation of the hypertensive patient should always include assessment of renal function .If deterioration in renal function has occurred after treatment with one ACE inhibitor, then usage of another class of antihypertensive agent would be preferable. Patients with unilateral renal artery disease present a special problem as deterioration of function may not be apparent from measurement of blood urea and serum creatinine.
Some ACE inhibitors have been associated with the occurrence of proteinuria (up to 0.7%) and/or decline in renal function in patients with one or more of the following characteristics: old age, pre-existing renal disease, concomitant treatment with potassium-sparing diuretics or high doses of other diuretics, limited cardiac reserve, or treatment with a non-steroidal anti-inflammatory drug.
Perindopril is dialysable with a clearance of 70mL/min.
Hepatic Failure
Rarely, ACE inhibitors have been associated with a syndrome that starts with cholestatic jaundice and progresses to fulminant hepatic necrosis and (sometimes) death. The mechanism of this syndrome is not understood. Patients receiving ACE inhibitors who develop jaundice or marked elevations of hepatic enzymes should discontinue the ACE inhibitor and receive appropriate medical follow-up.
Impaired Hepatic Function:
Biotransformation of perindopril to perindoprilat mainly occurs in the liver. Studies in patients with impaired hepatic function have shown that kinetic parameters of perindopril were not modified by hepatic failure.
The administration of perindopril leads to the formation of a glucuronoconjugate derivative of perindoprilat by a hepatic first-pass effect.
Cough:
A persistent dry (non-productive) irritating cough has been reported with most of the ACE inhibitors. The frequency of reports has been increasing since cough was first recognised as a class-effect of ACE inhibitor therapy with the incidence of cough varying between 2-15% depending upon the drug, dosage and duration of use.
The cough is often worse when lying down or at night, and has been reported more frequently in women. Patients who cough may have increased bronchial reactivity . The observed higher frequency of this side-effect in non-smokers may be due to a higher level of tolerance of smokers to cough.
The cough is most likely due to stimulation of the pulmonary cough reflex by kinins (bradykinin) and/or prostaglandins, which accumulate because of ACE inhibition. Once a patient has developed intolerable cough, the patient should be switched to another ACE inhibitor; the reaction may recur but this is not invariably the case. A change to another class of drugs may be required in severe cases.
Proteinuria:
TENSOCARD treatment has occasionally been associated with mild or transient proteinuria (<1 gram/per 24 hours). However in the majority of patients with pre-existing proteinuria treated with TENSOCARD, proteinuria disappeared or remained stable. ACE inhibitors have a real potential to delay the progression of nephropathy in diabetic as well as hypertensive patients.
Neutropenia/Agranulocytosis/Thrombocytopenia/Anaemia have been reported in patients receiving ACE inhibitor:
TENSOCARD should be used with extreme caution in patients with collagen vascular disease, immunosuppressant therapy, treatment with allopurinol or procainamide, or a combination of these complicating factors, especially if there is pre-existing impaired renal function. Some of these patients developed serious infections, which in a few instances did not respond to intensive antibiotic therapy. If TENSOCARD is used in such patients, periodic monitoring of white blood cell counts is advised and patients should be instructed to report any sign of infection.
Dermatological reactions:
characterised by maculo-papular pruritic rashes and sometimes photosensitivity has been reported with another ACE inhibitor. Rare and sometimes severe skin reactions .
Agents Causing Renin Release :
The effects of perindopril may be enhanced by concomitant administration of antihypertensive agents which cause renin release.
Dual blockade of the renin-angiotensin-aldosterone system :
Dual blockade of the renin-angiotensin-aldosterone system (e.g. by adding an angiotensin II receptor antagonist to an ACE-inhibitor) is not recommended in patients with already controlled blood pressure and should be limited to individually defined cases with close monitoring of renal function.
Surgery and Anaesthesia
In patients undergoing major surgery or who require anaesthesia, hypotension due to anaesthetic agents may be greater in patients receiving ACE inhibitors because of interference with compensatory mechanisms associated with the renin-angiotensin system.
Valvular Stenosis
There has been some concern on theoretical grounds that patients with aortic stenosis might be at particular risk of decreased coronary perfusion when treated with vasodilators, including ACE inhibitors.
Use in Pregnancy: Category D
As with all ACE inhibitors, TENSOCARD should not be taken during pregnancy. Pregnancy should be excluded before starting treatment with TENSOCARD and avoided during the treatment. If a patient intends to become pregnant, treatment with ACE inhibitors must be discontinued and replaced by another form of treatment. If a patient becomes pregnant while on ACE inhibitors, she must immediately inform her doctor to discuss a change in medication and further management.'
Perindopril or its metabolites have been shown to cross the placenta and distribute to the foetus in pregnant animals.
When ACE inhibitors have been used during the second and third trimesters of pregnancy, there have been reports of foetal hypotension, renal failure, skull hypoplasia and death.
Infants exposed in utero to ACE inhibitors should be closely observed for hypotension, oliguria, and hyperkalaemia. If such complications arise, appropriate medical treatment should be initiated to support blood pressure and renal perfusion.
Use in Lactation :
Animal studies have shown that perindopril and its metabolites are excreted in milk during lactation, but there are no human data. It is therefore recommended that TENSOCARD should not be given to lactating women as the possible effect on the newborn is unknown.
Pediatric Use:
Safety and effectiveness of Tensocard tablets in pediatric patients have not been established.
Drug Interactions:
Lithium :
Increased serum lithium levels and symptoms of lithium toxicity have been reported in patients receiving lithium concomitantly with drugs which cause elimination of sodium, including ACE inhibitors.
Diuretics
When a diuretic is added to the therapy of a patient receiving an ACE inhibitor, the antihypertensive effect is usually additive. Patients receiving diuretics, especially those in whom diuretic therapy was recently instituted or in those with intravascular volume depletion, may sometimes experience an excessive reduction of blood pressure after initiation of therapy with an ACE inhibitor. The starting dose of the ACE-inhibitor should be reduced and the patient closely observed for several hours following the initial dose of the ACE inhibitor and until the blood pressure has stabilised.
The use of an ACE inhibiting drug , an anti-inflammatory drug and a thiazide diuretic at the same time increases the risk of renal impairment.
Combined use of these medications should be accompanied by increased monitoring of serum creatinine,
And it should be used with caution particularly in elderly patients or those with pre-existing renal impairment.
Agents affecting serum potassium
The concomitant use of an ACE inhibitor with a potassium-sparing diuretic (e.g. spironolactone, triamterene, or amiloride), potassium supplement, or potassium-containing salt substitute can increase the risk of hyperkalaemia, therefore if co-administration is indicated they should be used with caution and the patient's serum potassium monitored frequently.
Antidiabetic agents (eg. insulin, hypoglycaemic sulphonylureas)
Reported with captopril and enalapril.
The use of ACE inhibitors may increase the hypoglycaemic effect in diabetics receiving treatment with insulin or with hypoglycaemic sulphonylureas.
Non-steroidal anti-inflammatory drugs:
Drugs with prostaglandin synthetase inhibitor properties (e.g. indomethacin) may diminish the antihypertensive efficacy of concomitantly-administered ACE inhibitors.
Tetracycline and other drugs that interact with magnesium
The simultaneous administration of tetracycline with an ACE inhibitor may significantly reduce the absorption of tetracycline, possibly due to the magnesium content in the ACE inhibitor tablets. This interaction should be considered if co-prescribing an ACE inhibitor and tetracycline or other drugs that interact with magnesium.
Agents Affecting Sympathetic Activity
As the sympathetic nervous system plays an important part in physiological blood pressure regulation, caution should be exercised with concomitant administration of a drug with sympathetic activity and TENSOCARD.
Effects on laboratory tests
A small reduction in haemoglobin and haematocrit has been reported. An unexplained change in prothrombin ratio was reported in one patient. Rare cases of hyperkalaemia have been noted.
Undesirable Effects:
The most frequent adverse reactions noted in clinical studies were as follows (2% - 5.3%):
Headache
Asthenia
Dizziness
Cough : ACE-inhibitor-induced cough is generally a nocturnal, dry, irritating laryngeal cough occurring at the beginning of treatment.
Other adverse reactions reported with an incidence of between 0.5% and 2% were as follows:
General symptoms: atypical chest pain, abdominal pain, faintness on standing
Cardiovascular system: palpitations, flushing, impaired peripheral circulation
Musculo-skeletal: muscle cramps
G.I. system: nausea, dry mouth, dyspepsia, diarrhoea, vomiting,epigastric pain.
Metabolic disorder: oedema
Nervous system: insomnia, drowsiness, mood disturbance, paraesthesia
Respiratory system: dyspnoea, discomfort on exertion, epistaxis
Skin and appendages: rash, pruritus, sweating
Special senses: impaired taste, visual disturbances, tinnitus
Taste disturbances: taste disturbances were reported to be common with high doses of one ACE inhibitor.
Urogenital: sexual dysfunction
DOSAGE AND ADMINISTRATION :
Food intake may reduce hepatic biotransformation of perindopril to perindoprilat. However, whilst this effect has not been shown to be clinically significant, it is recommended that TENSOCARD should be taken before meals.
Renal Impairment :
In patient with renal failure, treatment should begin with 2mg daily.
Dosage should be adjusted according to creatinine clearance. Creatinine and potassium levels should be closely monitored.
Creatinin clearance ml/min Dosage
Between 30 to 60 2 mg daily
Between 15 to 30 2 mg every 2 days
Below 15 2 mg on day of dialysis
( Prendopril is dialysable 70 ml / min )
Hypertension :
The usual starting dose of TENSOCARD is 2mg once daily, taken in the morning. Optimum control of blood pressure is achieved by increasing the dose, titrating it against the blood pressure. Dosage should be adjusted according to each patients needs and may be increased from 2mg to 4mg then to a maximum of 8mg once daily.
A starting dose of 2mg per day of TENSOCARD is recommended in the following patients who may be at risk of ACE inhibitor-induced hypotension:
Combination with a Diuretic :
The administration of TENSOCARD to patients under current diuretic therapy may induce hypotension and rarely, acute renal failure, at the beginning of the treatment. It is recommended to monitor plasma creatinine during the first month of treatment
Elderly Hypertensives :
Elderly hypertensive patients should start treatment with 2mg daily, and the dosage increased to 4mg if necessary. It is recommended that renal function be assessed before starting treatment.
Congestive Heart Failure :
Treatment of congestive heart failure with TENSOCARD should be initiated under close medical supervision.
2mg is the usual starting dose, which should be given with a diuretic and/or digitalis. This is increased to 4mg daily for maintenance.
Patients with severe hepatic or renal impairment and/or severe salt/volume depletion are particularly sensitive to ACE inhibitors. Doses in these patients should be carefully titrated as no pharmacokinetic and dose titration studies have been conducted.
Reduction of risk of cardiovascular events:
In patients with stable coronary artery disease, TENSOCARD should be introduced at a dose of 4mg once daily for two weeks, and then increased to 8mg once daily, depending on tolerance and renal function.
Elderly patients should receive 2mg once daily for one week, then 4mg once daily the next week, before increasing the dose up to 8mg once daily depending on tolerance and renal function .
OVERDOSAGE:
Limited data are available for overdosage in humans. Symptoms associated with overdosage of ACE inhibitors may include hypotension, circulatory shock, electrolyte disturbances, renal failure, hyperventilation, tachycardia, palpitations, bradycardia, dizziness, anxiety, and cough. The recommended treatment of overdosage is intravenous infusion of normal saline solution. If hypotension occurs, the patient should be placed in the shock position. Perindopril may be removed from the circulation by haemodialysis .Vital signs, serum electrolytes and creatinine concentrations should be monitored continuously.
Packaging:
Packs of 30 tablets for all strengths.
Storage:
Keep out of the reach of children.
Store in a dry place below 30°C.