Active ingredients: Perindopril
Perindopril Almus 4 mg tablets
Why is Perindopril used - Generic drug? What is it for?
Perindopril belongs to a class of drugs called ACE inhibitors, which work by dilating blood vessels, through which the heart is able to pump blood more easily.
Perindopril Almus tablets are used for:
- the treatment of high blood pressure (hypertension);
- treatment of heart failure (a condition in which the heart is unable to pump enough blood to meet the body's needs);
- reduce the risk of cardiac events, such as heart attacks, in patients with stable coronary artery disease (a condition in which the blood supply to the heart is reduced or blocked) and in those who have already suffered a heart attack and / or they underwent an operation aimed at improving the flow of blood to the heart by dilating the blood vessels.
Contraindications When Perindopril should not be used - Generic drug
Do not take Perindopril Almus
- if you are allergic (hypersensitive) to perindopril or to any of the other ingredients in the tablet or to any other ACE inhibitor (see section 6);
- if you have had symptoms such as dyspnoea, swelling of the face, tongue or throat, severe itching, rash, dizziness or fainting during previous ACE inhibitor therapy or if you have experienced these symptoms in any other circumstances (these are symptoms of a disorder called angioedema);
- if you have diabetes or impaired kidney function and you are being treated with a blood pressure lowering medicine containing aliskiren;
- if you have a hereditary tendency to develop tissue swelling or if you suffer from tissue swelling of unknown origin (hereditary or idiopathic angioedema);
- if you are more than three months pregnant (it is also better to avoid Perindopril Almus in early pregnancy - see pregnancy section).
If you think any of the above situations apply to you, do not take the tablets. Consult your doctor and follow his advice.
Precautions for use What you need to know before taking Perindopril - Generic drug
Tell your doctor BEFORE you take Perindopril Almus:
- if you are at risk of an excessive drop in blood pressure. This could be the case, among other things, if you suffer from heart failure, reduced kidney function or disturbances in the balance of salts and fluids, for example because you are taking diuretic drugs (drugs that increase urine production) or are following a low-salt diet or due to vomiting or diarrhea;
- if you have aortic stenosis (narrowing of the major blood vessels that branch off from the heart), mitral valve stenosis (narrowing of the mitral valve of the heart), hypertrophic cardiomyopathy (a heart muscle disorder), or renal artery stenosis (narrowing of the heart arteries that supply blood to the kidneys);
- if you develop hypersensitivity reactions or tissue swelling (angioedema) during treatment with perindopril or other ACE inhibitors. Angioneurotic edema occurs more frequently in black patients than in non-black patients;
- if you suffer from a heart disorder;
- if you suffer from a liver disorder;
- if you suffer from kidney problems;
- if you are undergoing dialysis;
- if you suffer from collagen disorders such as systemic lupus erythematosus or scleroderma;
- if you are on a low-salt diet or use salt substitutes that contain potassium;
- if you have a form of diabetes that is not well controlled;
- if you are taking any of the following medicines used to treat high blood pressure:
- an 'angiotensin II' receptor antagonist (AIIRA) (also known as sartans - eg valsartan, telmisartan, irbesartan), particularly if you have diabetes-related kidney problems.
- aliskiren Your doctor may check your kidney function, blood pressure, and the amount of electrolytes (eg potassium) in your blood at regular intervals. See also information under the heading "Do not take Perindopril Almus".
- if you are breast-feeding.
You should tell your doctor if you think you are pregnant (or if there is a possibility of becoming pregnant). Perindopril Almus is not recommended in early pregnancy and must not be taken if you are more than three months pregnant, as it may cause serious harm to your baby if used at that stage (see pregnancy section).
Perindopril Almus tablets are not recommended for children.
Also tell your doctor or medical staff that you are taking Perindopril Almus:
- if you have suffered from chest pain (angina pectoris);
- if you need to undergo anesthesia and / or surgery;
- if you have recently suffered from diarrhea or vomiting;
- if you are about to undergo desensitization treatment to reduce the effects of an 'allergy to bee or wasp stings;
- if you are to undergo LDL apheresis (removal of cholesterol from the blood by a machine);
- if your blood pressure is not low enough due to your ethnicity (particularly in black-skinned patients);
- if you suffer from a persistent dry cough.
Interactions Which drugs or foods can modify the effect of Perindopril - Generic drug
Tell your doctor or pharmacist if you are taking, have recently taken or might take any other medicines. In particular, in order to ensure the safety of the administration of Perindopril Almus, consult your doctor if you are taking any of the following medicines:
- other medicines to treat high blood pressure, including diuretics;
- potassium-sparing diuretics (e.g. spironolactone, triamterene or amiloride), potassium supplements and potassium-containing salt substitutes;
- medicines used to treat diabetes (insulin or tablets), used to lower blood sugar levels;
- lithium, used to treat mania or depression;
- medicines used to treat mental disorders, such as depression, anxiety, schizophrenia or other psychosis;
- allopurinol, used to treat gout;
- mmunosuppressants, used for the treatment of autoimmune disorders (e.g. rheumatoid arthritis) or for therapy following surgical transplants;
- procainamide, used to treat irregular heartbeat;
- non-steroidal anti-inflammatory drugs (NSAIDs), used to relieve pain, including aspirin (if the dose is greater than or equal to 3 g / day);
- medicines used to treat low blood pressure, shock or asthma (for example ephedrine, noradrenaline or adrenaline);
- vasodilators, including nitrates (medicinal products that dilate blood vessels);
- heparin (anticoagulant drug).
- gold (sodium aurothiomalate) for the treatment of arthritis.
Your doctor may need to change your dose and / or take other precautions: If you are taking an angiotensin II receptor antagonist (AIIRA) or aliskiren (see also information under "Do not take Perindopril Almus" and "Warnings and precautions" ).
If you are unsure about these medicinal products, please consult your doctor.
Tell your doctor or dentist before undergoing anesthesia or surgery, as your blood pressure may drop suddenly during anesthesia.
Taking Perindopril Almus with food and drink
Always take Perindopril Almus before a meal, together with an adequate amount of liquid (eg water), in order to reduce the influence of food on the effects of the medicine. Foods supplemented with potassium salt substitutes should not be used if using Perindopril Almus. Potassium concentration may rise too high. A large amount of salt (NaCl) in the diet may also reduce the antihypertensive effect of Perindopril Almus.
Warnings It is important to know that:
Pregnancy and breastfeeding
Pregnancy
You should tell your doctor if you think you are pregnant (or if there is a possibility of becoming pregnant). Your doctor will usually advise you to stop taking Perindopril Almus before you become pregnant or as soon as you know you are pregnant and will advise you to take another medicine instead of Perindopril Almus. Perindopril Almus does not. it is recommended in early pregnancy, and must not be taken if you are more than three months pregnant, as it may cause serious harm to your baby if used after the third month of pregnancy.
Feeding time
Tell your doctor if you are breastfeeding or about to start breastfeeding. Perindopril Almus is not recommended for women who are breastfeeding, and your doctor may choose another treatment if you wish to breastfeed, especially if your baby is newborn or was born prematurely. .
Ask your doctor or pharmacist for advice before taking any medicine.
Driving and using machines
No studies have been performed on the effects that Perindopril Almus may have on the ability to drive or use machines. However, although Perindopril Almus does not affect the level of alertness, some patients may experience reactions such as dizziness or weakness due to the decrease in blood pressure, especially at the start of treatment or at each dose increase. your case, your ability to drive or use machines may be impaired.
Dosage and method of use How to use Perindopril - Generic drug: Posology
Always take Perindopril Almus exactly as your doctor has told you. If in doubt, you should consult your doctor or pharmacist. Perindopril Almus can be used alone or together with other medicines to lower blood pressure.
Normal dosage is described below.
High blood pressure: The recommended starting and maintenance dose for adults is 4 mg once daily. After one month, the dosage can be increased to 8 mg per day, which is also the maximum recommended dose.
If you are over 65, the normal starting dose is 2 mg once a day. After one month, the dosage can be increased to 4 mg per day and, if necessary, to 8 mg per day.
Heart failure: treatment should be started under close medical supervision with 2 mg once daily. After two weeks, if necessary, the dosage can be increased to 4 mg per day.
Stable coronary artery disease: The normal starting dose is 4 mg once daily. After two weeks, and if the 4 mg dose is well tolerated, the dosage can be increased to 8 mg once daily.
If you are over 65, the normal starting dose is 2 mg once a day. After one week, the dosage can be increased to 4 mg once a day and after another week to 8 mg once a day.
Before increasing the dose to 8 mg, your doctor may order a blood test to check that your kidneys are working properly. If your kidney function is impaired, your doctor will adjust the dose of Perindopril Almus according to your condition. Treatment of these disorders usually lasts a lifetime.
Take the tablet (s) with a glass of water, preferably at the same time each day, in the morning before a meal. If you are already taking diuretics, your doctor may decide to reduce or even stop diuretics at the beginning of the day. treatment with Perindopril Almus.
Perindopril Almus is not suitable for pediatric use.
If you forget to take Perindopril Almus
It is important that you remember to take your dose every day. However, if you forget to take one or more doses, take another one as soon as possible, then continue with your normal dosage. Do not take a double dose to make up for the forgotten dose.
If you stop taking Perindopril Almus
If you want to stop the treatment, do not do it without first consulting your doctor: even if you feel better, you may need to continue the therapy.
If you have any further questions on the use of Perindopril Almus, ask your doctor or pharmacist
Overdose What to do if you have taken an overdose of Perindopril - Generic drug
If you take too many tablets by mistake, contact the nearest hospital emergency room or tell your doctor immediately. In case of overdose, the most common effect is a drop in blood pressure. If you experience a significant drop in blood pressure (with symptoms such as dizziness or fainting), lying down with your legs elevated may help.
Side Effects What are the side effects of Perindopril - Generic drug
Like all medicines, Perindopril Almus can cause side effects, although not everybody gets them.
These side effects are uncommon (i.e. they occur in less than 1 in 100 patients treated). However, if you experience any of the following side effects, contact your doctor immediately:
- swelling of the face, lips, mouth, tongue or throat
- difficulty in breathing
- dizziness or fainting
- unusually fast or irregular heartbeat.
These are symptoms of a severe reaction (angioedema), which can occur with all other medicines of this type (ACE inhibitors) and which needs to be treated immediately, usually in a hospital. Other possible side effects
Common (occurring in less than 1 in 10 patients treated):
- cough, shortness of breath
- dizziness caused by low blood pressure (particularly at the start of therapy, with each dose increase and when the medicine is taken concomitantly with diuretics)
- headache, dizziness, vertigo, tiredness, tingling, muscle cramps, visual disturbances (e.g. blurred vision, eye pain), tinnitus (noises in the ears)
- nausea, vomiting, abdominal pain, altered taste, indigestion, diarrhea, constipation
- rash, itching.
Uncommon (occurring in less than 1 in 100 patients treated):
- changes in mood or sleep
- bronchospasm (feeling of tightness in the chest, wheezing and shortness of breath)
- dry mouth
- kidney problems
- impotence
- sweating
Very rare (occurring in less than 1 in 10,000 patients treated):
- confusion
- irregular heartbeat, heart attack and stroke (these symptoms have been reported with ACE inhibitors used in combination with low blood pressure)
- angina pectoris (chest tightness)
- eosinophilic pneumonia (a rare type of pneumonia), rhinitis (stuffy or runny nose)
- pancreatitis (inflammation of the pancreas)
- hepatitis (inflammation of the liver)
- erythema multiforme (skin disorder caused by an allergic reaction in turn due to various causes)
- changes in blood cell counts: your doctor may decide to have blood tests done at regular intervals to monitor your plasma values.
Not known (frequency cannot be estimated from the available data):
- hypoglycemia (very low blood sugar level)
- vasculitis (inflammation of the blood vessels)
If any of the side effects gets serious, or if you notice any side effects not listed in this leaflet, please tell your doctor or pharmacist.
Expiry and Retention
Keep Perindopril Almus out of the reach and sight of children.
Do not use Perindopril Almus after the expiry date which is stated on the blister and carton. The expiry date refers to the last day of the month.
Do not store Perindopril Almus above 30 ° C. Keep Perindopril Almus in its original package in order to protect it from moisture.
Medicines should not be disposed of via wastewater or household waste. Ask your pharmacist how to throw away medicines you no longer use. This will help protect the environment.
Other_information "> Other information
What Perindopril Almus contains
The active ingredient is perindopril tert-butylamine.
Perindopril Almus 4 mg: Each tablet contains 4 mg of perindopril tert-butylamine, equivalent to 3.338 mg of perindopril.
The other ingredients are: microcrystalline cellulose, silicated microcrystalline cellulose, potassium polyacryllin, silicon dioxide, colloidal anhydrous silica, magnesium stearate and hydroxy-propyl-betadex.
What Perindopril Almus looks like and contents of the pack
Perindopril Almus 4 mg comes in the form of round, white, biconvex tablets with a break line on one side and "4" on the other. The tablet can be divided into equal halves.
Aluminum / aluminum blister.
Pack sizes: 7, 10, 14, 15, 20, 28, 30, 50, 56, 60, 90, 100, 112, 120 tablets.
Not all pack sizes may be marketed.
Source Package Leaflet: AIFA (Italian Medicines Agency). Content published in January 2016. The information present may not be up-to-date.
To have access to the most up-to-date version, it is advisable to access the AIFA (Italian Medicines Agency) website. Disclaimer and useful information.
01.0 NAME OF THE MEDICINAL PRODUCT -
PERINDOPRIL ALMUS 4 MG TABLETS
02.0 QUALITATIVE AND QUANTITATIVE COMPOSITION -
Perindopril Almus 4 mg tablets:
each tablet contains 4 mg of perindopril tert-butylamine, equivalent to 3.338 mg of perindopril. For the full list of excipients, see section 6.1.
03.0 PHARMACEUTICAL FORM -
Tablets.
4 mg: Round, white, biconvex tablets with a score line on one side and "4" on the other. The tablet can be divided into equal halves.
04.0 CLINICAL INFORMATION -
04.1 Therapeutic indications -
Hypertension: treatment of hypertension
Heart failure: treatment of congestive heart failure.
Stable arterial coronary artery disease: Reduced risk of cardiac events in patients with a history of myocardial infarction and / or revascularisation.
04.2 Posology and method of administration -
It is recommended that Perindopril Almus be administered as a single daily dose in the morning, before a meal and together with an adequate amount of liquid (eg water).
The posology should be adjusted according to the patient profile (see section 4.4, "Special warnings and precautions for use") and blood pressure response.
Hypertension
Perindopril Almus can be used on its own or as part of a combination therapy with other classes of antihypertensive agents (see sections 4.3, 4.4, 4.5 and 5.1).
The recommended starting dosage is 4 mg in a single daily administration in the morning.
In patients with strong stimulation of the renin-angiotensin-aldosterone system (particularly renovascular hypertension, salt and / or volume depletion, heart failure or severe hypertension), an excessive decrease in blood pressure may occur following administration of the starting dose. In these patients it is recommended to start treatment with a dosage of 2 mg and under medical supervision.
After one month of treatment the dosage can be increased up to 8 mg in a single daily administration.
Symptomatic hypotension may occur upon initiation of Perindopril Almus therapy, especially in patients being treated with diuretics.
Particular caution is therefore recommended, as these patients may present with salt or volume depletion.
If possible, the diuretic should be discontinued 2 to 3 days before starting treatment with Perindopril Almus (see section 4.4, "Special warnings and precautions for use").
In hypertensive patients in whom the diuretic cannot be withdrawn, treatment with Perindopril Almus should be initiated with a dose of 2 mg and renal function and potassium levels should be monitored. Subsequently, the dosage of Perindopril Almus must be adjusted according to the blood pressure response. If necessary, diuretic treatment can be reintroduced.
In elderly patients, treatment should be initiated with a dose of 2 mg which, again if necessary, can be progressively increased to 4 mg after one month of treatment and then to 8 mg, depending on renal function (see table below).
Congestive heart failure
It is recommended that treatment with Perindopril, generally combined with a non-potassium-sparing diuretic and / or digoxin and / or a beta-blocker, is instituted under close medical supervision, at the recommended starting dose of 2 mg taken in the morning. If well tolerated, this dosage can be increased, in increments of 2 mg at intervals of not less than 2 weeks, up to 4 mg, given as a single daily dose. Dosage adjustments should be made based on the individual clinical response of each single patient.
In patients with severe heart failure and other patients considered to be at high risk (patients with impaired renal function and a tendency to electrolyte disturbances and patients treated concomitantly with diuretics and / or vasodilating agents), treatment should be initiated under careful medical supervision (see section 4.4, "Special warnings and precautions for use").
In patients at high risk of symptomatic hypotension (e.g. salt-depleted patients with or without hyponatremia, patients with hypovolaemia, or patients receiving large doses of diuretics), these disturbances should be corrected, where possible, before initiating therapy with the Perindopril Almus. Blood pressure, renal function and plasma potassium concentrations should be carefully monitored both before and during treatment with Perindopril Almus (see section 4.4, "Special warnings and precautions for use").
Stable coronary artery disease
Treatment with Perindopril Almus should be started with a dose of 4 mg in a single daily intake for 2 weeks and then increased, if the previous dose is well tolerated, to 8 mg in a single daily intake, depending on the kidney function.
Elderly patients should start treatment with 2 mg in one "single daily intake for one week, then move to 4 mg once daily in the following week, and finally increase the dose to 8 mg in one" single daily intake, to depending on renal function (see Table I, "Dosage adjustments in" renal insufficiency ") Dosage should only be increased if the previous dose was well tolerated.
Dosage adjustments in renal insufficiency
In patients with renal insufficiency the dosage should be adjusted based on creatinine clearance as described in Table I (below):
Table I. Dosage adjustments in renal insufficiency
* Dialysis clearance of perindoprilat is 70 mL / min. In hemodialysis patients the dose should be
administered after dialysis.
Dosage adjustment in hepatic insufficiency
No dosage adjustment is required in patients with hepatic impairment (see sections 4.4, "Special warnings and precautions for use" and 5.2, "Pharmacokinetic properties").
Children and adolescents
Due to the lack of data on efficacy and safety of use, the use of Perindopril Almus in children and adolescents is not recommended.
04.3 Contraindications -
• Hypersensitivity to perindopril, to any of the excipients or to any other ACE inhibitor;
• history of angioedema associated with previous ACE inhibitor therapy;
• hereditary or idiopathic angioedema;
• the concomitant use of Perindopril Almus with aliskiren-containing medicines is contraindicated in patients with diabetes mellitus or renal impairment (glomerular filtration rate GFR
• second and third trimester of pregnancy (see sections 4.4 and 4.6).
04.4 Special warnings and appropriate precautions for use -
Stable coronary artery disease
If an episode of unstable angina pectoris (major or minor) occurs during the first month of treatment with perindopril, a "careful risk / benefit assessment should be made before continuing treatment."
Hypotension
ACE inhibitors can cause a drop in blood pressure. Symptomatic hypotension has been observed rarely in patients with uncomplicated hypertension and is more likely to occur in hypovolaemic patients, for example due to diuretic treatments, low salt diets, dialysis, diarrhea or vomiting, or in patients with severe renin-dependent hypertension (see sections 4.5, "Interactions with other medicinal products and other forms of interaction", and 4.8, "Undesirable effects"). Symptomatic hypotension has been observed in patients with symptomatic heart failure, whether or not associated with renal failure, which is more likely to occur in patients with severe heart failure (as confirmed by the administration of high doses of loop diuretics), from hyponatremia or impaired renal function. In patients at high risk of symptomatic hypotension, initiation of treatment and dose adjustments should be carefully monitored (see sections 4.2, "Posology and method of administration", and 4.8, "Undesirable effects"). Similar considerations apply to patients with ischemic heart disease or cerebrovascular disorders, in whom an excessive drop in blood pressure can cause myocardial infarction or cerebrovascular events.
If hypotension occurs, the patient should be placed in the supine position and, if necessary, receive an intravenous infusion of a saline solution. The occurrence of transient hypotension is not a contraindication to the administration of further doses, which can generally occur without difficulty. after the blood pressure has increased due to the expansion of the volume.
In some patients with congestive heart failure and with normal or low blood pressure, further reduction in systemic blood pressure may occur following administration of Perindopril Almus. This effect is expected and generally does not constitute a valid reason to discontinue treatment. .
If hypotension becomes symptomatic, it may be necessary to reduce the dose or discontinue treatment with Perindopril.
Stenosis of the aortic and mitral valves / hypertrophic cardiomyopathy
As with other ACE inhibitors, Perindopril Almus should be administered with caution to patients with mitral valve stenosis and left ventricular outflow obstruction such as aortic stenosis or hypertrophic cardiomyopathy.
Renal impairment
In cases of renal impairment (creatinine clearance acute renal failure, usually reversible.
In some patients with bilateral renal artery stenosis or single kidney artery stenosis treated with ACE inhibitors, an increase in plasma urea and creatinine has been observed, generally reversible upon discontinuation of treatment. This occurs mainly in patients with renal insufficiency. The concomitant presence of renovascular hypertension leads to an increased risk of severe hypotension and renal insufficiency: in these patients, treatment should be initiated under close medical supervision and with reduced and carefully titrated dosages. Since treatment with diuretics may contribute to the development of the conditions described above, the administration of diuretics should be discontinued and renal function monitored during the first weeks of therapy with Perindopril.
In some hypertensive patients with no apparent pre-existing renovascular disease, an increase (generally mild and transient) in plasma urea and creatinine has been found, especially when Perindopril is co-administered with a diuretic. This is more likely to occur. in patients with pre-existing renal impairment In these cases it may be necessary to reduce the dose and / or discontinue the diuretic and / or Perindopril Almus.
Patients on hemodialysis
Anaphylactoid reactions have been reported in patients on hemodialysis with high-flux membranes and concomitant therapy with ACE inhibitors. The use of a different type of dialysis membrane or a different class of antihypertensive agents should be considered for these patients.
Kidney transplant
There is no experience with the administration of Perindopril Almus in patients who have recently undergone a kidney transplant.
Hypersensitivity / angioedema
Angioedema of the face, limbs, lips, mucous membranes, tongue, glottis and / or larynx has been reported rarely in patients treated with ACE inhibitors, including Perindopril Almus (see section 4.8, "Undesirable effects"). . This can occur at any time during therapy: in these cases it is necessary to immediately discontinue Perindopril Almus and start careful monitoring of the patient, which must continue until the symptoms have completely resolved. In the case of edema limited to the face and lips, the complication generally resolved without any treatment, although antihistamines have been helpful in relieving symptoms. Angioedema associated with laryngeal edema can be fatal: if there is involvement of the tongue, glottis or larynx that could cause airway obstruction, emergency therapy should be rapidly adopted, which could include administering epinephrine and / or maintaining a patent airway. The patient should be placed. under strict control until the complete and lasting disappearance of symptoms.
Patients with a history of angioedema unrelated to ACE inhibitor treatment may be at increased risk of angioedema when treated with an ACE inhibitor (see section 4.3).
Intestinal angioedema has been reported rarely in patients treated with ACE inhibitors. These patients presented with abdominal pain (with or without nausea or vomiting), in some cases there had been no prior facial angioedema, and C-1 esterase levels were normal. Angioedema was diagnosed by abdominal CT scan or ultrasound or surgery and symptoms resolved after the ACE inhibitor was discontinued. Intestinal angioedema should be included in the differential diagnosis of patients treated with ACE inhibitors who present with abdominal pain.
Anaphylactoid reactions during low density lipoprotein (LDL) apheresis
There have been rare reports of life-threatening anaphylactoid reactions in patients treated with ACE inhibitors undergoing low density lipoprotein (LDL) apheresis with dextran sulphate. These reactions can be prevented by temporarily withholding ACE inhibitor treatment prior to each apheresis.
Anaphylactic reactions during a desensitization treatment
Cases of anaphylactoid reactions have been reported in patients treated with ACE inhibitors undergoing desensitizing treatment (eg against hymenoptera venom). In the same patients, these reactions were prevented by temporarily withholding treatment with ACE inhibitors, but they reappeared upon accidental re-exposure of the patient.
Hepatic insufficiency
ACE inhibitor treatment has rarely been associated with a syndrome that begins with cholestatic jaundice and progresses to fulminant hepatic necrosis and (sometimes) patient death. The mechanism of this syndrome is unknown. Patients treated with ACE inhibitors who develop jaundice or a significant increase in liver enzymes should discontinue the ACE inhibitor and be under close medical supervision (see section 4.8, "Undesirable effects").
Neutropenia / Agranulocytosis / Thrombocytopenia / Anemia
Cases of neutropenia / agranulocytosis, thrombocytopenia and anemia have been reported in patients treated with ACE inhibitors. In patients with normal renal function and in the absence of other complicating factors, neutropenia develops rarely. Sporadic cases of haemolytic anemia have been reported in patients with genetic G6-DP deficiency. Perindopril should be administered with extreme caution to patients with collagen disease, on therapy with immunosuppressive agents, with allopurinol or procainamide, or who exhibit a combination of these complicating factors, especially in the presence of a "history of renal impairment. Some of these patients. have developed severe infections, which in some cases have not responded to intensive antibiotic therapy.If these patients are treated with perindopril, it is recommended that their white blood cell counts be checked periodically and that they are advised to report any episodes of infection.
Race
ACE inhibitors can cause angioedema more frequently in black patients than in non-black patients.Like other ACE inhibitors, perindopril may be less effective in lowering blood pressure in black patients than in non-black patients, possibly due to a higher prevalence of low-renin concentrations in the black hypertensive population.
Cough
Cough has been reported following administration of ACE inhibitors, usually presenting in a dry (non-productive) and persistent form and resolving upon discontinuation of treatment. ACE inhibitor-induced cough should be considered in establishing the differential diagnosis of cough.
Surgery / anesthesia
In patients undergoing major surgery or undergoing anesthesia with agents that cause hypotension, Perindopril may block angiotensin II formation secondary to compensatory renin release. Treatment must be stopped one day before surgery. If hypotension occurs and is believed to be attributable to the above mechanism, it must be corrected by volume expansion.
Hyperkalaemia
Increased plasma potassium concentrations have been reported in some patients treated with ACE inhibitors, including perindopril. Patients at risk of developing hyperkalaemia include those with renal insufficiency or uncontrolled diabetes mellitus, those treated concomitantly with potassium-sparing diuretics, potassium supplements or potassium-containing salt substitutes, or those being treated with other drugs that cause an increase in plasma potassium (for example heparin). If concomitant use of the above mentioned drugs is deemed appropriate, regular monitoring of plasma potassium is recommended.
Diabetic patients
In diabetic patients treated with oral antidiabetic agents or with insulin, blood glucose should be closely monitored during the first month of therapy with an ACE inhibitor (see section 4.5, "Interactions with other medicinal products and other forms of interaction").
Lithium
The combination of lithium and perindopril is generally not recommended (see section 4.5, "Interactions with other medicinal products and other forms of interaction").
Potassium-sparing diuretics, potassium supplements or potassium-containing salt substitutes
The combination of perindopril with potassium-sparing diuretics, potassium supplements or potassium-containing salt substitutes is generally not recommended (see section 4.5, "Interactions with other medicinal products and other forms of interaction").
Dual blockade of the renin-angiotensin-aldosterone system (RAAS)
There is evidence that concomitant use of ACE inhibitors, angiotensin II receptor blockers or aliskiren increases the risk of hypotension, hyperkalaemia and decreased renal function (including acute renal failure). Dual blockade of the RAAS through the combined use of ACE inhibitors, angiotensin II receptor blockers or aliskiren is therefore not recommended (see sections 4.5 and 5.1).
If dual block therapy is considered absolutely necessary, this should only be done under the supervision of a specialist and with close and frequent monitoring of kidney function, electrolytes and blood pressure.
ACE inhibitors and angiotensin II receptor antagonists should not be used concomitantly in patients with diabetic nephropathy.
Pregnancy
ACE inhibitor therapy should not be initiated during pregnancy. For patients planning to become pregnant, alternative antihypertensive treatments with a proven safety profile for use in pregnancy should be used unless continued ACE inhibitor therapy is considered essential. When pregnancy is diagnosed. , treatment with ACE inhibitors should be stopped immediately and, if appropriate, alternative therapy should be started (see sections 4.3 and 4.6).
04.5 Interactions with other medicinal products and other forms of interaction -
Diuretics
After initiation of ACE inhibitor therapy, patients receiving diuretics, particularly those with salt or volume depletion, may experience an excessive reduction in blood pressure. The occurrence of hypotensive effects can be limited by discontinuing the diuretic or by expanding the blood volume and / or increasing salt intake before starting therapy with perindopril, which should be given in reduced and progressive doses.
Potassium-sparing diuretics, potassium supplements, or potassium-containing salt substitutes
Although plasma potassium concentrations usually remain within normal limits, hyperkalaemia may develop in some patients treated with perindopril. Potassium-sparing diuretics (e.g. spironolactone, triamterene or amiloride), potassium supplements or potassium-containing salt substitutes can cause significant increases in plasma potassium concentrations. Therefore, the combination of perindopril with the above-mentioned drugs is not recommended (see section 4.4, "Special warnings and precautions for use"). If concomitant use of the above drugs is deemed indicated due to established hypokalaemia, they should be used with caution and with frequent monitoring of potassium.
Lithium
Reversible increases in plasma concentrations and toxicity of lithium have been observed following concomitant administration of lithium and ACE inhibitors. The concomitant use of thiazide diuretics could further increase the risk of lithium-induced toxicity, already high during treatment with ACE inhibitors. The administration of perindopril during treatment with lithium is not recommended; however, if deemed necessary, it should be careful monitoring of plasma lithium levels performed (see section 4.4, "Special warnings and precautions for use").
Non-steroidal anti-inflammatory drugs (NSAIDs) including aspirin at a dosage ≥3 g per day
The concomitant administration of non-steroidal anti-inflammatory drugs may reduce the antihypertensive efficacy of ACE inhibitors. Furthermore, NSAIDs and ACE inhibitors exert a synergistic effect on the increase in potassium concentrations and may cause impaired renal function. These effects are generally reversible. Rarely, acute renal failure may occur, especially in patients with impaired renal function, such as the elderly or dehydrated individuals.
Antihypertensive agents and vasodilators
Concomitant administration of these drugs may increase the hypotensive effect of perindopril. Concomitant administration of nitroglycerin and other nitrates or other vasodilators may further reduce blood pressure.
Dual blockade of the renin-angiotensin-aldosterone system (RAAS) with ACE inhibitors, angiotensin II receptor antagonists or aliskiren.
Clinical trial data have shown that dual blockade of the renin-angiotensinaldosterone system (RAAS) through the combined use of ACE inhibitors, angiotensin II receptor blockers or aliskiren is associated with a higher frequency of adverse events such as hypotension. , hyperkalaemia and decreased renal function (including acute renal failure) compared with the use of a single agent active on the RAAS system (see sections 4.3, 4.4 and 5.1).
Antidiabetic agents
Epidemiological studies have suggested that concomitant administration of ACE inhibitors and antidiabetic drugs (insulin, oral hypoglycemic agents) may cause an "excessive reduction in blood glucose with the risk of hypoglycaemia. This phenomenon appears to be more likely during the first few weeks. combined treatment and in patients with renal insufficiency.
Acetyl-salicylic acid, thrombolytics, beta-blockers, nitrates
Perindopril can be administered concomitantly with acetyl-salicylic acid (when used as a thrombolytic), thrombolytics, beta-blockers and / or nitrates.
Tricyclic antidepressants / antipsychotics / anesthetics
Concomitant administration of ACE inhibitors and some anesthetics, tricyclic antidepressants and antipsychotics may cause "further decrease in blood pressure (see section 4.4," Special warnings and precautions for use ").
Sympathomimetics
Sympathomimetic agents may reduce the antihypertensive effect of ACE inhibitors.
Gold
Nitritoid reactions (symptoms include facial flushing, nausea, vomiting and hypotension) have been reported rarely in patients receiving injectable gold (sodium aurothiomalate) and concomitant therapy with ACE inhibitors including perindopril.
Antacids can reduce the bioavailability of perindopril.
04.6 Pregnancy and breastfeeding -
The use of ACE inhibitors is not recommended during the first trimester of pregnancy (see section 4.4).
The use of ACE inhibitors is contraindicated during the second and third trimesters of pregnancy (see sections 4.3 and 4.4).
Epidemiological evidence regarding the risk of teratogenicity following exposure to ACE inhibitors during the first trimester of pregnancy has not been conclusive, however a small increase in risk cannot be excluded. For patients planning pregnancy, alternative antihypertensive treatments with a proven safety profile for use in pregnancy should be used, unless continued ACE inhibitor therapy is considered essential. When pregnancy is diagnosed. , treatment with ACE inhibitors should be stopped immediately and, if appropriate, alternative therapy should be started.
Exposure to ACE inhibitors during the second and third trimester of pregnancy is known to induce fetal toxicity (decreased renal function, oligohydroamnios, skull ossification retardation) and neonatal toxicity (renal failure, hypotension, hyperkalaemia) in women ( see paragraph 5.3).
Should exposure to an ACE inhibitor have occurred from the second trimester of pregnancy, ultrasound check of renal function and skull is recommended. Neonates whose mothers have taken ACE inhibitors should be closely monitored for hypotension ( see sections 4.3 and 4.4).
Feeding time
Since no data are available regarding the use of perindopril during lactation, Perindopril Almus is not recommended and alternative treatments with a proven safety profile for use during lactation are preferred, especially when nursing a newborn or preterm infant. .
04.7 Effects on ability to drive and use machines -
No studies on the ability to drive or use machines have been performed, however when performing these activities it should be borne in mind that occasionally dizziness or fatigue may occur.
04.8 Undesirable effects -
The frequency of side effects listed below is based on the following convention:
very common (≥1 / 10); common (≥1 / 100 ma
Diagnostic tests
Elevations in plasma azotaemia and creatinine, reversible hyperkalaemia upon discontinuation of treatment may occur, especially in the presence of renal insufficiency, severe heart failure and renovascular hypertension.
An increase in liver enzymes and bilirubin has rarely been reported.
Clinical Studies
Only serious adverse events were collected in the EUROPA randomized study. Few patients reported serious adverse events: 16 of 6122 patients treated with perindopril (0.3%) and 12 of 6107 patients treated with placebo (0.2%). In patients treated with perindopril, hypotension was observed in 6 cases, angioedema in 3 and sudden cardiac arrest in 1. Compared to placebo, more patients discontinued treatment due to cough, hypotension or other intolerances to perindopril. respectively in 6.0% (n = 366) versus 2.1% (n = 129) of cases.
04.9 Overdose -
There are limited data on overdose in humans.
Symptoms associated with ACE inhibitor overdose may include hypotension, circulatory shock, electrolyte disturbance, renal failure, hyperventilation, tachycardia, palpitations, bradycardia, dizziness, anxiety and cough.
In case of overdose a treatment with an "intravenous infusion of normal saline. If hypotension occurs the patient should be positioned as in shock. If available, treatment with an" infusion of angiotensin II and / or an "may also be considered. intravenous catecholamines. Perindopril can be removed from the general circulation by hemodialysis (see section 4.4, "Special warnings and precautions for use - Patients on hemodialysis"). A pacemaker is indicated for therapy-resistant bradycardia. It is also necessary to continuously monitor vital signs, serum electrolytes and creatinine concentrations.
05.0 PHARMACOLOGICAL PROPERTIES -
05.1 "Pharmacodynamic properties -
Pharmacotherapeutic group: C09AA - ACE inhibitors. ATC code: C09A A04 perindopril.
Perindopril is an inhibitor of the converting enzyme (ACE) of angiotensin I to angiotensin II. The converting enzyme, or kinase, is an exopeptidase that enables the conversion of angiotensin I to vasoconstricting agent angiotensin II and also the degradation of the vasodilating agent bradykinin into an inactive heptapeptide. Inhibition of ACE results in a reduction of angiotensin II in plasma which in turn leads to increased plasma renin activity (by inhibition of the negative feedback mechanism of renin release) and reduced secretion of aldosterone. "ACE deactivates bradykinin, its inhibitory action also determines an increase in the activity of the kallikrein-kinin system at the circulatory and local level (and therefore also an" activation of the prostaglandin system). It is possible that this mechanism contributes to the reduction of blood pressure by ACE inhibitors and that it is partially responsible for some particular undesirable effects (for example cough).
Perindopril acts through its active metabolite, perindoprilat. The other metabolites do not show in vitro no inhibition of ACE activity.
Hypertension
Perindopril is active on all stages of hypertension: mild, moderate and severe; a reduction in systolic and diastolic blood pressure in both supine and standing positions has been observed.
Perindopril reduces peripheral vascular resistance, causing a reduction in blood pressure. As a result, there is an increase in peripheral blood flow, with no effect on heart rate.
Renal blood flow usually increases, while the glomerular filtration rate (GFR) generally remains unchanged. The peak of the antihypertensive effect occurs 4-6 hours after a single administration and is maintained for at least 24 hours: the minimum effects correspond to approximately 87% -100% of the maximum effects.
The reduction in blood pressure occurs rapidly. In responding patients, normalization is achieved after one month of treatment and is maintained without the occurrence of tachyphylaxis.
Discontinuation of treatment is not accompanied by rebound phenomena. Perindopril reduces left ventricular hypertrophy.
In humans, perindopril has been shown to possess vasodilating properties; it improves the elasticity of large arteries and reduces the media / lumen ratio of small arteries.
The addition of a thiazide diuretic results in an additive synergy. The combination of an ACE inhibitor and a thiazide also reduces the risk of hypokalaemia induced by the diuretic treatment.
Two large randomized controlled trials (ONTARGET (ONgoing Telmisartan Alone and in combination with Ramipril Global Endpoint Trial) and VA Nephron-D (The Veterans Affairs Nephropathy in Diabetes)) have examined the use of the combination of an ACE inhibitor with an antagonist of the angiotensin II receptor. ONTARGET was a study conducted in patients with a history of cardiovascular or cerebrovascular disease, or type 2 diabetes mellitus associated with evidence of organ damage. VA NEPHRON-D was a study conducted in patients with type 2 diabetes mellitus and diabetic nephropathy.
These studies did not demonstrate any significant beneficial effect on renal and / or cardiovascular outcomes and mortality, while an increased risk of hyperkalaemia, acute renal injury and / or hypotension was observed compared to monotherapy.
These results are also relevant for other ACE inhibitors and angiotensin II receptor antagonists, given their similar pharmacodynamic properties.
ACE inhibitors and angiotensin II receptor antagonists should therefore not be used simultaneously in patients with diabetic nephropathy.
ALTITUDE (Aliskiren Trial in Type 2 Diabetes Using Cardiovascular and Renal Disease Endpoints) was a study aimed at verifying the advantage of adding aliskiren to standard therapy of an ACE inhibitor or angiotensin II receptor antagonist in patients with diabetes mellitus. type 2 and chronic kidney disease, cardiovascular disease, or both. The study was terminated early due to an increased risk of adverse events. Cardiovascular death and stroke were both numerically more frequent in the aliskiren group than in the placebo group, and adverse events and serious adverse events of interest (hyperkalaemia, hypotension and renal dysfunction) were reported more frequently in the aliskiren group than in the placebo group.
Heart failure
Perindopril Almus reduces the work of the heart by reducing the pre-load and after-load. Studies conducted in patients with heart failure have shown:
• a reduction in the filling pressure of the left and right ventricles
• a decrease in total peripheral vascular resistance
• an increase in cardiac output and an improvement in the cardiac index.
In comparative studies, the first administration of 2 mg of Perindopril Almus to patients with mild to moderate heart failure did not result in any significant reduction in blood pressure compared to patients receiving placebo.
Patients with stable coronary artery disease
EUROPA is a multi-center, international, randomized, double-blind, placebo-controlled 4-year clinical trial. Twelve thousand two hundred and eighteen (12,218) patients over 18 years of age were randomized to perindopril 8 mg (n = 6110) or placebo (n = 6108). Patients had documented coronary artery disease with no clinical signs of heart failure. Overall, 90% of patients had had a previous myocardial infarction and / or a previous coronary revascularization. Most patients took the drug in addition to conventional therapy, which included platelet aggregation inhibitors, lipid-lowering agents, and beta-blockers.
The main efficacy criterion was the combination of cardiovascular mortality, non-fatal myocardial infarction and / or cardiac arrest with successful resuscitation. Treatment with perindopril 8 mg once daily demonstrated a significant absolute reduction in the primary endpoint of 1.9% (20% relative risk reduction, 95% CI [9.4; 28, 6] - p
In patients with a history of myocardial infarction and / or revascularisation, an absolute reduction in the primary endpoint of 2.2% was observed, corresponding to a RRR of 22.4% (95% CI [12.0; 31.6 ] - p
05.2 "Pharmacokinetic properties -
Following oral administration, absorption of perindopril is rapid and the peak concentration is completed within one hour. Bioavailability is between 65 and 70%.
About 20% of the total amount of perindopril absorbed is converted to perindoprilat, the active metabolite. In addition to the active perindoprilat, perindopril produces 5 metabolites, all of which are inactive. The plasma half-life of perindopril is one hour. The peak plasma concentration of perindoprilat is reached in 3-4 hours.
Since food intake reduces conversion to perindoprilat, and consequently bioavailability, Perindopril Almus should be administered orally in a single daily dose in the morning, before a meal.
The volume of distribution of unbound perindoprilat is approximately 0.2 l / kg. The protein binding is modest (the binding of perindoprilat to the angiotensin converting enzyme is less than 30%), but it is concentration-dependent.
Perindoprilat is eliminated in the urine and the half-life of the free fraction is approximately 3-5 hours. The dissociation of perindoprilat bound to the angiotensin converting enzyme leads to an "effective" elimination half-life of 25 hours, with the achievement of steady-state within 4 days.
No accumulation of perindopril was observed following repeated administration. Elimination of perindoprilat is reduced in the elderly, as well as in patients with heart or renal insufficiency.
In case of renal insufficiency it is desirable to adjust the dosage according to the degree of the insufficiency (creatinine clearance).
The dialysis clearance of perindoprilat is 70 ml / min.
In the cirrhotic patient, the kinetics of perindopril are modified: the hepatic clearance of the parent molecule is reduced by half. However, the amount of perindoprilat formed is not reduced and therefore no dosage adjustment is necessary (see also sections 4.2, "Posology and method of administration", and 4.4, "Special warnings and precautions for use").
05.3 Preclinical safety data -
In chronic oral toxicity studies (rats and monkeys) the target organ is the kidney, with reversible damage. in vitro or in vivo no mutagenicity was observed.
In reproductive toxicity studies (rats, mice, rabbits and monkeys) no signs of embryotoxicity or teratogenicity were shown. However, the class of angiotensin converting enzyme inhibitors has been shown to cause adverse effects on late fetal development, leading to fetal death and birth defects in rodents and rabbits: kidney injury and increased peri- and postnatal mortality. In long-term studies in rats and mice, no carcinogenicity was observed.
06.0 PHARMACEUTICAL INFORMATION -
06.1 Excipients -
Microcrystalline cellulose
Silicified microcrystalline cellulose
Potassium polyacryllin
Silicon dioxide
Anhydrous colloidal silica
Magnesium stearate
Hydroxy-propyl-betadex
06.2 Incompatibility "-
NA
06.3 Period of validity "-
2 years
06.4 Special precautions for storage -
Do not store at temperatures above 30 ° C.
Store the medicine in the original package in order to protect it from moisture.
06.5 Nature of the immediate packaging and contents of the package -
Aluminum / aluminum blister
Pack sizes: 7, 10, 14, 15, 20, 28, 30, 50, 56, 60, 90, 100, 112, 120 tablets.
Not all pack sizes may be marketed.
06.6 Instructions for use and handling -
No particular precautions.
07.0 HOLDER OF THE "MARKETING AUTHORIZATION" -
Sandoz Spa, L.go U. Boccioni 1, 21040 Origgio (VA)
Sales dealer: Almus S.r.l. - Via Cesarea 11/10 - 16121 Genova (GE)
08.0 MARKETING AUTHORIZATION NUMBER -
4 mg tablets 7 tablets in blister AL / AL AIC N. 038472015
4 mg tablets 10 tablets in blister AL / AL AIC N. 038472027
4 mg tablets 14 tablets in blister AL / AL AIC N. 038472039
4 mg tablets 15 tablets in blister packs AL / AL AIC N. 038472041
4 mg tablets 20 tablets in blister packs AL / AL AIC N. 038472054
4 mg tablets 28 tablets in blister packs AL / AL AIC N. 038472066
4 mg tablets 30 tablets in blister AL / AL AIC N. 038472078
4 mg tablets 50 tablets in blister AL / AL AIC N. 038472080
4 mg tablets 56 tablets in blister AL / AL AIC N. 038472092
4 mg tablets 60 tablets in blister packs AL / AL AIC N. 038472104
4 mg tablets 90 tablets in blister AL / AL AIC N. 038472116
4 mg tablets 90 tablets in blister AL / AL AIC N. 038472116
4 mg tablets 100 tablets in blister packs AL / AL AIC N. 038472128
4 mg tablets 112 tablets in blister packs AL / AL AIC N. 038472130
4 mg tablets 120 tablets in blister packs AL / AL AIC N. 038472142
09.0 DATE OF FIRST AUTHORIZATION OR RENEWAL OF THE AUTHORIZATION -
16/06/2009
