Piramil - instructions for use, doses, side effects, contraindications

active ingredient: ramipril - 2.50 / 5.00 / 10.00 mg; Excipients: microcrystalline cellulose - 296.10 / 293.60 / 289.00 mg; pregelatinized starch - 18.00 / 18.00 / 18.00 mg; silicon dioxide precipitated - 32,00 / 32,00 / 32,00 mg; glycine hydrochloride - 3.00 / 3.00 / 3.00 mg; glycerol dibehenate - 8.00 / 8.00 / 8.00 mg; iron dye oxide yellow (E-172) 0.40 / - / - mg; ferric dye oxide red (E-172) - / 0.40 / - mg.

Description:

Tablets 2.5 mg: oblong, biconvex tablets of light yellow color with a rough surface, with rare impregnations of a darker color and risk on one side.

Tablets 5.0 mg: oblong, biconvex tablets of light pink color with a rough surface, with rare impregnations of a darker color and risk on one side.

Tablets 10.0 mg: oblong, biconvex tablets white or almost white with a rough surface and a risk on one side.

Pharmacotherapeutic group:inhibitor of angiotensin-converting enzyme (ACE).

ATX: & nbsp

C.09.A.A ACE Inhibitors

C.09.A.A.05 Ramipril

Pharmacodynamics:

Ramipril is rapidly absorbed in the gastrointestinal tract and is hydrolyzed in the liver to form an active metabolite of ramiprilate. Ramiprilat is a long-acting inhibitor of the ACE enzyme, which catalyzes the conversion of angiotensin I into angiotensin I.

Ramipril causes a decrease in the level of angiotensin II in blood plasma, an increase in renin activity and a decrease in aldosterone release. Suppresses the level of kininase II, prevents the disintegration of bradykinin, enhances the synthesis of prostaglandins.Under the action of ramipril, the peripheral vessels expand and the common peripheral vascular resistance (OPSS) decreases. Arterial hypertension

Has hypotensive effect in the patient's position "lying" and "standing". Reduces OPSS (afterload), wedging pressure in the pulmonary capillaries without compensatory increase in the heart rate (heart rate).

Strengthens coronary and renal blood flow, without affecting the rate of glomerular filtration.

The onset of hypotensive action 1 to 2 hours after ingestion, the maximum effect develops 3 to 6 hours after ingestion. The action lasts no less than 24 hours.

Chronic heart failure and heart failure due to acute myocardial infarction

Ramipril reduces OPSS and, ultimately, blood pressure. Increases the minute volume of the heart and tolerance to physical activity. With prolonged use, it contributes to the reverse development of myocardial hypertrophy in patients with cardiac insufficiency of I and II functional class according to the classification NYHA, improves the blood supply of the ischemic myocardium.

Ramipril increases the survival of patients with symptoms of transient or chronic heart failure after myocardial infarction.Has cardioprotective effect, prevents coronary ischemic episodes, reduces the likelihood of developing myocardial infarction and reduces the duration of hospitalization.

Diabetic and nondiabetic nephropathy

In patients with diabetic and nondiabetic nephropathy, ramipril slows the rate of progression of renal failure and the time at which the terminal stage of renal failure occurs and, as a result, reduces the need for hemodialysis or kidney transplantation procedures. At the initial stages of diabetic or nondiabetic nephropathy ramipril reduces the severity of albuminuria.

Patients with a high risk of cardiovascular disease due to vascular lesions (diagnosed ischemic heart disease (IHD), obliterating peripheral arterial disease or stroke in

anamnesis), diabetes mellitus with at least one additional risk factor (microalbuminuria, arterial hypertension, increased plasma concentrations of total cholesterol (OX), decreased plasma concentrations of high-density lipoprotein cholesterol (HDL-C),smoking) the addition of ramipril to standard therapy significantly reduces the incidence of myocardial infarction, stroke, and mortality from cardiovascular causes.

Pharmacokinetics:

Ramipril is rapidly absorbed in the gastrointestinal tract after ingestion. Absorption does not depend on food intake.

After absorption ramipril quickly and almost completely transformed into an active metabolite ramiprilat under the action of the liver esterase enzyme. Ramiprilat approximately 6 times more inhibits ACE than ramipril. Other pharmacologically inactive metabolites have also been found.

In patients with impaired renal function, the transformation of ramipril into ramiprilat is slowed by a relatively short period of action of esterase, so the level of ramipril in blood plasma in these patients is increased.

The maximum concentration of ramipril in the blood plasma is reached within an hour after taking ramiprilata - within 2 to 4 hours after taking the drug. The bioavailability of ramipril is 60%. The association with plasma proteins reaches 73% for ramipril and 56% for ramiprilate. After taking 5 mg, the renal clearance of ramipril is 10-55 ml / min, the extra-neural clearance reaches 750 ml / min. For ramiprilat, these values are 70 - 120 ml / min and about 140 ml / min, respectively. Ramipril and ramiprilate are mainly excreted by the kidneys (40-60%). If the renal function is impaired, their excretion slows down.

The half-life of ramiprilate with prolonged use in a dose 5-10 mg once a day is 13 to 17 hours.

Indications:

arterial hypertension;
chronic heart failure (as part of combination therapy);
diabetic or nondiabetic nephropathy, preclinical and clinically pronounced stages, including those with pronounced proteinuria, especially when combined with hypertension and the presence of microalbuminuria;
reduction in the risk of myocardial infarction, stroke or cardiovascular mortality in patients at high risk of cardiovascular disease:

in patients with confirmed CHD, myocardial infarction in or without anamnesis, including patients who underwent percutaneous transluminal coronary angioplasty, coronary artery bypass grafting;
in patients with a history of stroke;
in patients with occlusive lesions of peripheral arteries;
in patients with diabetes mellitus with at least one additional risk factor (microalbuminuria, arterial hypertension, increased plasma concentrations of OX, lower plasma concentrations of HDL-C, smoking);

heart failure, developed during the first few days (from 2 to 9 days) after acute myocardial infarction.

Contraindications:

- Hypersensitivity to ramipril, other ACE inhibitors or auxiliary components of the drug;

- hereditary or idiopathic angioedema of Quincke (including the administration of ACE inhibitors in the anamnesis);

- hemodynamically significant stenosis of the renal arteries (bilateral or unilateral in the case of a single kidney);

cardiogenic shock;
primary hyperaldosteronism;
severe arterial hypotension (systolic blood pressure less than 90 mm Hg) or a condition with unstable hemodynamics;
pregnancy;
the period of breastfeeding;
age under 18 years (efficacy and safety of use not studied);
severe renal failure (creatinine clearance (CC) less than 20 ml / min / 1.73 m²);
severe hepatic insufficiency (no experience of clinical use);
hemodialysis or hemofiltration using some membranes with a negatively charged surface (high-flux membranes of polyacrylonitrile (risk of developing hypersensitivity reactions), apheresis of low-density lipoproteins using dextran sulfate (the risk of developing hypersensitivity reactions);
use in the acute stage of myocardial infarction: severe chronic heart failure (CHF) (IV functional class by classification NYHA), unstable angina, life-threatening ventricular arrhythmias, "pulmonary" heart;
as in the case of other ACE inhibitors, the combined use of ramipril and preparations containing aliskiren, in patients with diabetes mellitus or moderate or severe renal disease Insufficiency (SC less than 60 ml / min / 1.73 m²);
simultaneous use with angiotensin II receptor antagonists in patients with diabetic nephropathy;
Nephropathy, the treatment of which is carried out
glucocorti cysteroids, non-steroidal anti-inflammatory drugs (NSAIDs), immunomodulators and / or other cytotoxic drugs (clinical experience is insufficient);
hemodynamically significant aortic or mitral stenosis (risk of excessive blood pressure lowering with subsequent renal dysfunction (CC more than 20 ml / min / 1.73 m²)), hypertrophic obstructive cardiomyopathy.

Carefully:

Simultaneous application withpreparations containing aliskiren, or with angiotensin II receptor antagonists, leading to a double blockade of the renin-angiotensin-aldosterone system (RAAS), hyperkalemia, hyponatremia (including diuretics and diets with restriction of consumption of table salt), diabetes mellitus (the risk of hyperkalemia) ; chronic heart failure, especially severe or about which other drugs with antihypertensive action are taken; severe lesions of the coronary and cerebral arteries (the risk of a decrease in blood flow with excessive decrease in blood pressure); hemodynamically significant unilateral stenosis of the renal artery (in the presence of both kidneys); conditions, accompanied by a decrease in the volume of circulating blood (including diarrhea, vomiting), simultaneous use with mmunodepressants and saluretics; connective tissue diseases (including systemic lupus erythematosus, scleroderma - increased risk of developing neutropenia or agranulocytosis);
desensitizing therapy, elderly (over 65 years of age) (increased risk of concurrent liver and / or kidney and heart failure); condition after kidney transplantation, liver failure.

Pregnancy and lactation:

The use of the drug Piramil® during pregnancy and during breastfeeding is contraindicated, because the use of ramipril can adversely affect the fetus: impaired fetal kidney development, fetal and neonatal fetal pressure, renal dysfunction, hyperkalemia, hypoplasia of the skull bones, and lung hypoplasia. Pyramil® is not recommended for women planning pregnancy. In the case of pregnancy during therapy with Piramil®, as soon as possible, stop taking the drug and monitor the development of the fetus.

Women of reproductive age who receive therapy with ACE inhibitors should use effective contraception. If women of childbearing age with arterial hypertension take ACE inhibitors, then you should remember about the need in case of pregnancy

transfer of the patient to taking an antihypertensive drug from another group. In all cases, careful medical supervision is necessary.

There is no information as to whether the ramipril in breast milk. Studies in animals have shown that ramipril is released into the milk of l active rats. The use of the drug Piramil® during breastfeeding is contraindicated. If necessary, the drug Piramilbreastfeeding mother, the issue of stopping breastfeeding should be addressed.

Dosing and Administration:

Inside, regardless of food intake, without chewing, squeezed a sufficient amount (1/2 cup) of water. The dose is selected depending on the therapeutic effect and the tolerance of the drug to the patient.

Arterial hypertension

The recommended initial dose of Piramil® for patients without heart failure who do not take diuretics is 2.5 mg per day. The dose can be gradually increased every 2-3 weeks, depending on the effect and tolerability. The maximum dose is 10 mg once a day. Usually the maintenance dose is 2.5-5 mg once a day.In the absence of a satisfactory therapeutic effect with the administration of 10 mg per day of the drug Piramil®, the appointment of combined medication is recommended.

If a patient takes diuretics, they should stop taking them or lower their dose 2-3 days before starting treatment with Piramil®. For such patients, the recommended initial dose of the drug is 1.25 mg (1/2 tablets of 2.5 mg) once a day.

Chronic heart failure

The recommended initial dose of Piramil® is 1.25 mg (1/2 tablet, 2.5 mg) once a day.

The dose can be gradually increased depending on the effect and tolerability, doubling it every 1-2 weeks. Doses of 2.5 mg per day and above can be taken in one or two doses. The maximum dose is 10 mg once a day.

For patients taking high doses of diuretics, their doses should be reduced before starting treatment with Piramil®, in order to minimize the risk of symptomatic arterial hypotension.

To reduce the risk of developing myocardial infarction, stroke or cardiovascular mortality the patients with high cardiovascular risk The recommended initial dose: 2.5 mg once a day. Depending on the tolerability, the dose can be doubled after 1 week of treatment, and during the next 3 weeks of treatment, increase it to the usual maintenance dose of 10 mg once a day.

Heart failure due to acute myocardial infarction Treatment begins on the 3rd - 10th day after an acute myocardial infarction. The initial dose of the drug Piramil "is 5 mg per day (2.5 mg twice in the morning and in the evening), after two days the dose is raised to 5 mg twice a day." If the initial dose of 2.5 mg twice daily is poorly tolerated for two days, give a dose of 1.25 mg (1/2 tablets of 2.5 mg) twice a day, then increase the dose to 2.5 mg and 5 mg twice daily.The maintenance dose of Piramil® is 2, 5 - 5 mg twice a day, the maximum daily dose is 10 mg.

Diabetic and nondiabetic nephropathy

The recommended initial dose of Piramil® is 1.25 mg (1/2 tablets of 2.5 mg) once a day. Depending on the tolerability, the dose can be doubled at intervals of 2-3 weeks to a maximum dose of 5 mg per day.

If the patient takes diuretics, they should stop taking them or lower the dose 2 to 3 days before starting treatment with Piramil®; in this case

the recommended initial dose of Piramil® is 1.25 mg (1/2 tablets of 2.5 mg) once a day.

Patients with impaired renal function

For patients with impaired renal function (creatinine clearance (CC) 20-50 ml / min / 1.73 m²) the recommended initial dose of the drug Piramil® is 1.25 mg (1/2 tablets of 2.5 mg) once a day, and the maximum dose should not exceed 5 mg per day. In severe renal failure (CC below 20 ml / min / 1.73 m²) the recommended initial dose of Piramil® is 1.25 mg (1/2 tablets of 2.5 mg) once a day, if necessary, the dose can be increased to 2.5 mg per day.

Patients with hepatic impairment

In patients with impaired liver function, both the enhancement and the weakening of the therapeutic effect of Piramil® can be observed. Treatment should be started under the supervision of a doctor with a dose of 1.25 mg (1/2 tablets of 2.5 mg). The maximum dose should not exceed 2.5 mg per day.

Elderly patients (over 65 years of age)

Caution should be exercised when prescribing Piramil® to older patients in the presence of renal or hepatic insufficiency, as well as heart failure and / or simultaneous administration of diuretics.The dose should be selected individually depending on the target level of blood pressure. The initial dose is reduced to 1.25 mg per day.

Side effects:

According to the World Health Organization (WHO)

the undesirable effects are classified according to their frequency of development as follows: very often (> 1/10), often (> 1/100, <1/10), infrequently (> 1/1000, <1/100), rarely (> 1/10000, <1/1000), very rarely (<1/10000), the frequency is unknown (the frequency of occurrence of phenomena can not be determined byaccessing existing data).

From the side of the cardiovascular system

often: marked decrease in blood pressure, violation of orthostatic regulation of vascular tone (orthostatic hypotension), syncopal conditions;

infrequently: orthostatic collapse, myocardial ischemia, including the development of an attack of angina or myocardial infarction, impaired cerebral circulation (due to a sharp fall in blood pressure in patients at risk), tachycardia, arrhythmia, peripheral edema, palpitation, "flushes" of blood to the skin of the face;

rarely: occurrence or strengthening of circulatory disorders against the background of stenosing vascular lesions, vasculitis;
frequency is unknown: Raynaud's syndrome.

On the part of the organs of hematopoiesis infrequently: eosinophilia; rarely: leukopenia, including neutropenia and agranulocytosis (neutropenia and agranulocytosis are reversible and disappear with the abolition of ACE inhibitors), anemia, thrombocytopenia, lymphadenopathy, a decrease in hemoglobin;

frequency is unknown: oppression of bone marrow hematopoiesis, pancytopenia, hemolytic anemia.

From the nervous system

often: weakness, headache; infrequently: mood lability, anxiety, nervousness, paresthesia, dizziness, sleep disorders, insomnia, motor

anxiety;

rarely: tremor, imbalance, confusion;

frequency is unknown: cerebral ischemia, including stroke and transient impairment of cerebral circulation, parosmia (impaired perception of odors),

violation of psychomotor reactions, violation of concentration of attention.

From the sense organs

infrequently', visual disorders, including vagueness of the image, a violation of taste sensations;

rarely: conjunctivitis, hearing impairment tinnitus (sensation of ringing, noise in the ears).

From the respiratory system often: "dry" cough, bronchitis,

sinusitis, dyspnea; infrequently: bronchospasm, includingseverity of the course of bronchial asthma, congestion of the nose.

From the digestive system

often: inflammatory reactions in the stomach and intestines, digestive disorders, abdominal discomfort, dyspepsia, diarrhea, nausea, vomiting; infrequently: pancreatitis, increased activity of "liver" transaminases and conjugated bilirubin concentration in blood plasma, increased activity of pancreatic enzymes, intestinal angioedema, abdominal pain, gastritis, constipation, dryness of the oral mucosa;

rarely: glossitis; Cholestatic jaundice, hepatocellular lesions;

frequency is unknown: aphthous stomatitis (inflammatory reaction of the oral mucosa), acute liver failure, cholestatic or cytolytic hepatitis, incl. with a lethal outcome.

From the urinary tract rarely: impaired renal function, including the development of acute renal failure, increased allocation of urine, the enhancement of pre-existing proteinuria,increase in the concentration of urea and creatinine in the blood.

From the skin and mucous membranes often: skin rash, in particular maculopapular;

Mr.Often: angioedema, including fatal outcome (laryngeal edema can cause airway obstruction leading to death), skin itching, hyperhidrosis (increased sweating);

rarely: exfoliative dermatitis, urticaria, onycholysis (exfoliation of the nail from the soft tissues of the finger); rarely: photosensitivity reaction; frequency is unknown: toxic epidermal necrolysis, Stevens-Johnson syndrome, erythema multiforme, pemphigus (blistering rash), weight gain of psoriasis, psoriasis-like dermatitis, pemphigoid or lichenoidal exanthema or enanthema, alopecia.

From the side of the musculoskeletal system

often: muscle cramps, myalgia;

infrequently: arthralgia.

From the side of metabolism

hasto: increase of potassium content in blood;

infrequently: anorexia, decreased appetite;

frequency is unknown: the content of sodium in the blood.

From the immune system frequency is unknown:

anaphylactic or anaphylactoid reactions, an increase in the titer of antinuclear antibodies.

From the endocrine system frequency unknown: syndrome inadequate secretion of an antidiuretic hormone (SAN ADH).

From the side of the reproductive system

infrequently: transient impotence due to erectile dysfunction, decreased libido;

frequency unknown: gynecomastia.

General disorders and disorders at the site of administration

often: pain in the chest, increased fatigue; infrequently: fever; rarely: asthenia.

Overdose:

Symptoms: excessive peripheral vasodilation with development

pronounced decrease in blood pressure (BP), shock; bradycardia, disturbance of water-electrolyte balance, shock, acute renal failure, stupor.

Treatment: in mild overdose cases: gastric lavage, administration of adsorbents, sodium sulfate (preferably within the first 30 minutes after administration). It is necessary to monitor the function of vital organs. In more severe cases, measures aimed at stabilizing blood pressure: intravenous injection of 0.9% sodium chloride solution,

replacement of temporary artificial pacemaker with bradycardia resistant to drug therapy, hemodialysis. With a marked decrease in blood pressure to therapy for replenishing the volume of circulating blood and restoring the water-electrolyte balance, the introduction of a-adrenergic agonists (norepinephrine, dopamine). In the case of bradycardia, the appointment of atropine or the installation of a temporary artificial pacemaker is recommended. It is necessary to carefully monitor blood pressure, kidney function and the content of electrolytes in the blood serum.

Experience in the use of forced diuresis, changes pH urine, hemofiltration or dialysis for accelerated removal of ramipril from the body there. Hemodialysis is indicated in cases of development of renal insufficiency.

Interaction:

Interaction with other drugs

Contraindicated combinations

The use of some high-strength membranes with a negatively charged surface (for example, polyacrylonitrile membranes) during hemodialysis or hemofiltration, the use of dextran sulfate in the hypersensitivity of low-density lipoproteins may entailrisk of severe anaphylactic reactions; if the patient requires these procedures, other types of membranes should be used (in the case of plasmapheresis and haemofiltration) or transfer the patient to other antihypertensive drugs.

As in the case of other ACE inhibitors, nContraindicated joint the use of ramipril with aliskiren and aliskiren-containing drugs in patients with diabetes mellitus or moderate or severe renal failure (CC less than 60 ml / min / 1.73 m.) Simultaneous application with other ACE inhibitors increases the risk of developing renal failure (including acute renal failure), hyperkalemia.

Simultaneous use of the drug and angiotensin II receptor antagonists in patients with diabetic nephropathy is contraindicated and is not recommended in other patients.

Combinations that should be used with cautionSimultaneous application with potassium salts , potassium-sparingdiuretics (eg,

amiloride, triamterene, spironolactone), anddrugs that increase the level of potassium in the blood serum (including trimethoprim, tacrolimus, ciclosporin, angiotensin II receptor antagonists) can lead to an increase in potassium in the blood serum (regular monitoring of potassium in the blood serum is required). Hypotherapeutic agents (alfuzosin, doxazosin, prazozin, tamsulosin, terazosin), baclofen, diuretics, nitrates, tricyclic antidepressants, antipsychotics, hypnotics, narcotic analgesics, agents for general and local anesthesia reinforce anti-hypertensive effects of ramipril.

Vasopressornye sympathomimetics and other drugs that cause antihypertensive effects (for example, isoproterenol, dobutamine, dopamine, epinephrine) yless antihypertensive effect of ramipril, while regular monitoring of blood pressure is required. Simultaneous application withallopurinol, procainamide, cytostatics, immunosuppressants, corticosteroids (glucocorticosteroids and myeralocorticosteroids) and other means that can affect hematologic indices, increases the risk of developing leukopenia.

The simultaneous use of ramipril with corticosteroids is not recommended.

Lithium salts lead to an increase in the concentration of lithium in the blood serum and enhance the cardio- and neurotoxic effects of lithium. Ramipril strengthens

hypoglycemic effect hypoglycemic agents (insulin, hypoglycemic agents for oral administration (derivatives with

ulfonylureas)) up to the development of hypoglycemia. It is necessary to control the concentration of glucose. Vshdglyptanleads to an increased incidence of angioedema. Simultaneous application ramipril but with mTOR (mammalian Target of Rapamycin - target of rapamycin in mammalian cells), for example, with tessirolimus, may lead to an increased incidence of angioedema.

Combinations that follow taking into account

Non-steroidal anti-inflammatory drugs (NG1VP)(eg, acetylsalicylic acid (more than 3 g / day), inhibitors of cyclooxygenase-2 (COX₂)) can weaken the antihypertensive effect of ramipril, as well as cause a violation of kidney function, sometimes leading to the development of renal failure. Heparin can increase the potassium content in the serum. Sodium chloride can weaken the effect of ramipril.Do not use this} yule during treatment with ramipril (increased inhibitory effect of ethanol on the central nervous system (CNS)).

Estrogens weaken the antihypertensive effect (fluid retention). Desensitizing therapy with hypersensitivity to insect venoms. ACE inhibitors, including ramipril, increase the likelihood of developing severe anaphylactic or anaphylactoid reactions to insect venoms.

Special instructions:

Before starting treatment with the drug Piramil it is necessary to eliminate hyponatremia and hypovolemia. Patients who had previously taken diuretics should cancel them andwhether to lower their dose 2-3 days before the start of the drug Piramil. In this case, the condition of patients with chronic cardiac

insufficiency due to the possibility of developing their decompensation against the background of an increase in the volume of circulating blood.

After taking the first dose, as well as increasing the dose of diuretic and / or Piramil, patients should stay for 8 hours under medical supervision in view of the possibility of developing orthostatic hypotension.

Transient arterial hypotension is not a contraindication for continuing treatment with Piramil, since with the restoration of the volume of circulating blood and the normalization of blood pressure, the administration of the following doses of the drug usually does not cause arterial hypotension. In the case of repetition ofthe presence of severe arterial hypotension should reduce the dose or cancel the drug. Patients with malignant hypertension or concomitant heart failure, especially in the acute stage of myocardial infarction, should begin treatment only in a hospital.

In patients with chronic heart failure, taking Piramil may lead to a marked decrease in blood pressure, which in some cases is accompanied by oliguria or azotemia and rarely the development of acute renal failure.

In patients with increased activity of RAAS, taking the drug for the first time or at a high dose, it is necessary to regularly monitor blood pressure and kidney function, especially at the beginning of treatment, as these patients have an increased risk of excessive blood pressure lowering andof kidney function as a result of ACE inhibition.

Caution should be exercised in the treatment of elderly patients, since they may be particularly sensitive to ACE inhibitors. Care should also be taken with physical activity and / or hot weather due to the risk of increased sweating and dehydration with the development of arterial hypotension due to a decrease in the volume of circulating blood and a decrease in the sodium content in the blood.

Before and during treatment with the drug Piramil *, it is necessary to regularly monitor the kidney function (creatinine, urea), the content of potassium in the blood plasma, a general blood test, hemoglobin, functional tests of the liver.

With the development of cholestatic jaundice or a marked increase in activity

"Hepatic" transaminases should stop taking ACE inhibitors. The risk group for hyperkalemia consists of patients with renal insufficiency, diabetes mellitus, and also taking potassium-sparing diuretics, potassium preparations or potassium-containing substitutes for edible salt and preparations that increase the serum potassium content (for example, heparin).

In patients with an increased risk of developing neutropenia (with renal dysfunction,systemic connective tissue diseases) when administering the Pyramid preparation, it is necessary to monitor the total blood test once a month for the first 3-6 months of therapy, as well as the first signs of infection. If neutropenia is detected (the number of neutrophils is less than 2000 / μL) therapy with ACE inhibitors should be discontinued.

In rare cases, angiotoneurotic edema of the face, extremities, lips, tongue, larynx and / or pharynx are noted in the treatment with ACE inhibitors, including ramipril. If there is swelling that can develop suddenly in any period of treatment, stop taking the medication immediately, take emergency medical care and ensure that the patient is carefully monitored until the symptom is completely and permanently disappeared.

In patients who received ACE inhibitors, cases of intestinal

angioedema, which manifested itself in abdominal pain with nausea and vomiting or without them, in some cases, angioedema was observed simultaneously. When a patient appears on the background of treatment with ACE inhibitors, the symptoms described above should when conducting a differential diagnosis, consider the possibility of developing an intestinal angioedema. The use of ACE inhibitors, including ramipril, in patients undergoing surgery with general anesthesia, can lead to the development of arterial hypotension. It is recommended to stop taking Piramil one day before

surgical intervention. Some high-strength membranes with a negatively charged surface (for example, polyacryl nitrile membranes) should be avoided, for example, for urgent hemodialysis or hemofiltration in combination with ACE inhibitors (due to the possibility of anaphylactoid reactions in patients). In rare cases, with apheresis of low-density lipoproteins (LDL) with aor angiotensin II receptor antagonists, resulting in a double blockade of RAAS, is not recommended due to the risk of excessive reduction in blood pressure, the development of hyperkalemia and impaired renal function compared to monotherapy. Simultaneous use with angiotensin II receptor antagonists in patients with diabetic nephropathy is contraindicated (see section "Contraindications").

Effect on the ability to drive transp. cf. and fur:

Data on the adverse effects of the drug Piramil® in the recommended doses on the ability to drive vehicles or work with mechanisms there. However, because of the likelihood of side effects such as lowering blood pressure and drowsiness, it is recommended to refrain from engaging in potentially hazardous activities requiring increased concentration and speed of psychomotor reactions, including vehicle management, especially after taking the initial dose, switching to another drug , simultaneous intake of diuretics and alcohol.

Form release / dosage:

Tablets 2.5 mg, 5 mg, 10 mg

Primary packaging:

7 tablets per blister of orientated polyamide / A1 / PE / PE / A1 or oriented polyamide / A1 / PVC / A1.

Secondary packaging:

For 4 blisters together with instructions for medical use in a pack of cardboard.

Packaging:

Primary packaging:

7 tablets per blister of orientated polyamide / A1 / PE / PE / A1 or oriented polyamide / A1 / PVC / A1.

Secondary packaging:

For 4 blisters together with instructions for medical use in a pack of cardboard.

Storage conditions:

In a dry, protected from light place at a temperature of no higher than 25 ° C.

Keep out of the reach of children.

Shelf life:2 years. Do not use after expiry date.

Terms of leave from pharmacies:On prescription

Registration number:LSR-006064/08

Date of registration:31.07.2008

The owner of the registration certificate:Sandoz d.Sandoz d. Slovenia

Manufacturer: & nbsp

LEK, S.A. Poland

Information update date: & nbsp11.09.2012

Illustrated instructions

Instructions

Piramil® (Pyramil® )