Expiration date: 02/2025

The composition and form of issue:

Tablets. 1 tablet contains active substance:

ramipril 2.5, 5 or 10 mg

excipients: microcrystalline cellulose starch pregelatinized silicon dioxide precipitated glycine hydrochloride glyceryl dibehenate tablets 2.5 mg — dye iron oxide yellow pill 5 mg — dye iron oxide red 

7 PCs. in blister in the stack cartons of 4 blisters.

Description pharmaceutical form:

Pills 2.5 mg: oblong, biconvex, light yellow in color with a rough surface, with occasional splashes of darker color and mark on one side.

Tablets 5 mg: oblong, biconvex, light pink color with a rough surface, with occasional splashes of darker color and mark on one side.

Tablets 10 mg: oblong, biconvex, white or nearly white color with rough surface and scored on one side.

Pharmacokinetics:

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

After absorption, ramipril rapidly and almost completely converted to the active metabolite ramiprilat by the enzyme esterase in liver. Ramiprilat about 6 times stronger inhibits ACE than ramipril. Also found other pharmacologically inactive metabolites.

In patients with impaired renal function the transformation of ramipril into ramiprilat is slowing down, so the level of ramipril in the blood plasma of these patients increased.

Cmax ramiprila in plasma achieved within one hour after administration of ramiprilat — within 2-4 h after administration of the drug. The bioavailability of ramipril is 60%. Linking blood plasma proteins reaches 73% for ramipril and 56% for ramiprilat. After taking 5 mg kidney clearance of ramipril is 10-55 ml/min, extrarenal clearance of up to 750 ml/min. For ramiprilat these figures are equal to 70-120 ml/min 140 ml/min, respectively. Ramipril and ramiprilat is mostly excreted by the kidneys (40-60%). When violation of the kidney excretion slows them.

T1/2 of ramiprilat long-term use in a dose of 5-10 mg once a day is 13-17 h.

Description pharmacological action:

Ramipril is rapidly absorbed in the gastrointestinal tract and is hydrolyzed in the liver to form the active metabolite ramiprilat. Ramiprilat is a long-acting ACE inhibitor, the enzyme catalyzing the conversion of angiotensin I to angiotensin II.

Ramipril causes a decrease in level of angiotensin II in blood plasma, increased activity of renin and reducing aldosterone release. Suppresses the level of kinase II prevents the breakdown of bradykinin, increases the synthesis of PG. Under the action of ramipril dilate peripheral blood vessels and reduced peripheral vascular resistance.

Hypertension

Has a hypotensive effect when the patient lying and standing. It reduces peripheral vascular resistance (afterload) pressure jamming in the pulmonary capillaries without compensatory increase in heart rate. Increases coronary and renal blood flow without affecting the glomerular filtration rate.

A start of antihypertensive action is after 1-2 hours after oral administration, the maximum effect develops after 3-6 hours after ingestion. The effect persisted at least 24 h.

Congestive heart failure and heart failure due to acute myocardial infarction

Ramipril reduces peripheral vascular resistance and, ultimately, AD. Increases cardiac output and tolerance to physical activity. Long-term use promotes regression of myocardial hypertrophy in patients with heart failure stage I and II improves the blood supply to the ischemic myocardium.

Ramipril increases survival in patients with symptoms of transient or chronic cardiac insufficiency after myocardial infarction. Effect comes a month after the start of treatment and persists for 2 years after the end of therapy.

Has cardioprotective action, prevents coronary ischemic episodes, reduces the risk of myocardial infarction and reduces the duration of hospital stay.

Nephropathy

In patients with diabetic nephropathy, ramipril reduces albuminuria. Nephropathy of different aetiology ramipril slows the progression of renal failure. When insulin-dependent diabetes and severe diabetic nephropathy, ramipril reduces the severity of proteinuria. In the presence of diabetes mellitus and at least one of the risk factors (microalbuminuria, hypertension, elevated total cholesterol/low high-density cholesterol, Smoking) ramipril reduces the severity of diabetes complications.

Indications:

• hypertension
  
• chronic heart failure chronic heart failure after acute myocardial infarction in patients with stable hemodynamics
  
• diabetic and non-diabetic nephropathy.
  

Contraindications:

• hypersensitivity to ramipril, other ACE inhibitors or auxiliary components of the drug
  
• angioedema hereditary, idiopathic or due to the reception of ACE inhibitors in history
  
• bilateral renal artery stenosis, stenosis of artery only kidneys
  
• acute myocardial infarction, cardiogenic shock
  
• primary hyperaldosteronism (due to the inefficiency of the use of antihypertensive drugs, including inhibiting the renin-angiotensin system)
  
• pregnancy, lactation
  
• the age of 18 years (efficiency and safety of application not been studied).
  

With caution:

• expressed human liver and/or kidney
  
• hyperkalemia, hyponatremia, diabetes mellitus (risk of hyperkalemia)
  
• clinically significant aortic or mitral stenosis, hypertrophic cardiomyopathy, congestive heart failure, stage IV (new York classification), unstable angina, severe lesions of coronary and cerebral arteries (risk of flow reduction in the excessive decline in AD)
  
• state, accompanied by a decrease in BCC (W. diarrhea, vomiting), and patients who follow a diet with restriction of sodium simultaneous use of drugs lithium, immunosuppressants and saluretikov
  
• connective tissue diseases (including systemic lupus erythematosus, scleroderma — increased risk of neutropenia or agranulocytosis)
  
• hemodialysis or hemofiltration using polyacrylonitrile membranes (e.g. AN69), LDL apheresis with dextran sulfate, desensitizing therapy, older age (increased risk of related disorders of the liver and/or kidney and heart failure)
  
• condition after kidney transplantation.
  

Side effects:

With the use of ACE inhibitors, including ramipril, possible side effects (frequency scale: &ge1/10 — very often &ge1/100, <1/10 — often &ge1/1000, <1/100 — rare &ge1/10000, <1 / 1000th rare <1/10000, very rare).

From the CCC: often — expressed lower AD infrequently — ortostatical gipotenzia, ortostaticeski collapse, angina, myocardial infarction or cerebrovascular accident (due to a sudden drop of BP in patients at risk), tachycardia, arrhythmia, Raynaud's syndrome.

Allergic reactions: rarely — skin rash, pruritus rare urticaria, photosensitivity, angioedema of the face, lips, tongue, larynx, extremities very rarely — myalgia, myositis, arthralgia/arthritis, exudative erythema multiforme (including Stevens-Johnson syndrome), toxic epidermal necrolysis (Lyell's syndrome), pemphigus (pemphigus), vasculitis, serozit, eosinophilia.

From the digestive system: rare — dry mouth, nausea, vomiting, abdominal pain, dyspepsia, loss of appetite, diarrhea, very rarely pancreatitis, hepatitis, cholestatic jaundice, impaired liver function, stomatitis, glossitis.

CNS: frequently — fatigue, headache rarely, mood lability, paresthesia, dizziness, sleep disturbance rare (at high doses) — mental confusion, depression, anxiety, cerebrovascular accident.

The respiratory system: often — dry cough infrequently — shortness of breath, rhinitis, bronchitis rarely — bronchospasm, sinusitis, allergic alveolitis, eosinophilic pneumonitis.

With the genitourinary system: often — violation of the kidney is rare — violation of sexual function, proteinuria very rare — oliguria or anuria.

Organs of hematopoiesis: rarely — a decrease in hemoglobin concentration and hematocrit very rarely — anemia, thrombocytopenia, haemolytic anaemia, neutropenia, agranulocytosis, pancytopenia, suppression of bone marrow function, lymphadenopathy.

Neutropenia and agranulocytosis are reversible and disappear with the abolition of ACE inhibitors.

Other: often — asthenia, fever, alopecia, disturbances of taste, smell, gynecomastia, reduced potency, tinnitus very rare — hypoglycemia, disturbances of hearing and vision, muscle cramps.

The laboratory parameters: infrequently — increase of urea, creatinine, increase in liver enzymes, hyperkalemia rarely — hyperbilirubinemia, hyponatremia, the appearance of antinuclear antibodies.

Drug interactions:

Antihypertensives, diuretics, nitrates, tricyclic antidepressants, neuroleptics, hypnotics, narcotic analgesics, funds for General anesthesia — enhance hypotensive effect of ramipril.

Enhances hypoglycemic effect of sulfonylureas, and insulin.

NSAIDs can attenuate the antihypertensive effect of ramipril, and to cause impairment of renal function, sometimes leading to kidney failure. Salt may weaken the effect of ramipril.

Drugs potassium, kalisberegate dioretiki, kalisodergaszczye salt substitutes, heparin increase the risk of hyperkalemia.

In concurrent administration with lithium increases their concentration in the blood, which leads to increased neurotoxicity and cardiotoxicity of lithium preparations.

Not recommended simultaneous appointment ramiprila with corticosteroids.

Sympathomimetic can weaken gipotenzivny effect ramiprila.

Increases the risk of leukopenia, while the application with allopourinolom, cytotoxic drugs, immunosuppressants, procainamide.

You should not drink alcohol during treatment with ramipril (enhanced inhibitory effect of ethanol on the Central nervous system).

Estrogens attenuate the hypotensive effect (hold liquid).

Method of application and dose:

Inside, regardless of meals, without chewing, drinking water.

Hypertension

The recommended starting dose for patients without heart failure, is not receiving diuretics is 2.5 mg Piramal per day. The dose can gradually increase every 2-3 weeks, depending on effect and tolerability. The maximum dose is 10 mg 1 time per day.

Usually supporting dose is 2.5–5 mg 1 time per day. In the absence of a satisfactory therapeutic effect when taking 10 mg Piramal a day recommended the appointment of a combined medical treatment.

If the patient is taking diuretics, should finish taking them or reduce the dose for 2-3 days before starting treatment with Picamilon. For these patients the recommended initial dose is 1.25 mg 1 times per day.

Chronic heart failure

The recommended starting dose Piramida is 1.25 mg 1 times per day.

The dose can be gradually increase depending on effect and tolerability, doubling it every 1-2 weeks. Dose of 2.5 mg per day and above can be taken in 1-2 doses. The maximum dose is 10 mg 1 time per day.

For patients receiving high doses of diuretics, you should reduce the dose before starting treatment with Picamilon to minimize the risk of development of symptomatic arterial hypotension.

Heart failure due to acute myocardial infarction

The treatment begins 3-10 days after acute myocardial infarction. The initial dose is 2.5 mg 2 times a day, after two days the dose may be increased to 5 mg twice a day. When poor tolerability of the initial dose 2.5 mg 2 times a day should be within two days to appoint a dose of 1.25 mg 2 times a day, then increasing the dose to 2.5 and 5 mg 2 times a day. Supporting dose is 2.5–5 mg 2 times a day.

The maximum dose is 10 mg.

Nephropathy

The recommended initial dose is 1.25 mg 1 times per day. Depending on tolerability, the dose can be doubled at intervals of 2-3 weeks to a maximum dose of 5 mg per day.

If the patient is taking diuretics, should finish taking them or reduce the dose for 2-3 days before starting treatment with Paramylon in this case, the recommended starting dose Piramida is 1.25 mg 1 times per day.

Dose for patients with renal insufficiency

For patients with impaired renal function (Cl creatinine of 0.3–0.8 ml/s/1.73 m2) the recommended initial dose Piramida is 1.25 mg 1 times per day and the maximum dose should not exceed 5 mg per day. When expressed kidney failure (Cl creatinine less than 0.3 ml/s/1.73 m2) the recommended initial dose Piramida is 1.25 mg 1 times a day, if necessary dose can be increased to 2.5 mg per day.

Doses for patients with hepatic insufficiency

In patients with liver dysfunction may be observed both the increase and the weakening of therapeutic action Piramida. Treatment should begin under the supervision of a doctor with appointment dose of 1.25 mg. the Maximum dose should not exceed 2.5 mg per day.

Dose for elderly patients

Caution must be exercised in the appointment ramiprila patients in the older age group if they have renal or hepatic impairment and in heart failure and concomitant diuretics. The dose should be selected individually, depending on the target level of AD.

Overdose:

Symptoms: expressed lower AD, disruption of water and electrolyte balance, shock, acute renal failure, stupor.

Treatment. In mild cases of overdose: gastric lavage, introduction of adsorbents, sodium sulfate (preferably within 30 min after administration). You should monitor the function of vital organs. When expressed arterial hypotension, if necessary, prescribed catecholamines, angiotensin II, in/in the introduction of saline. Experience in the use of forced diuresis, changes in urine pH, hemofiltration or dialysis for accelerated excretion ramiprila from the body is not. Hemodialysis is indicated in cases of development of kidney disease.

Special instructions:

After the first dose and with increasing dose of diuretic effectively delivered and/or Piramida patients should be within 8 h under medical supervision due to the possibility of orthostatic hypotension.

Archerella transient hypotension is not a contraindication to continue treatment Picamilon, because when you restore the volume and normalize blood pressure the next dose of the drug does not usually cause symptomatic hypotension. In case of recurrence of arterial expressed hypotension should reduce the dose or stop the drug.

Patients with malignant arterial hypertension or concomitant chronic cardiac insufficiency of the decompensation should begin treatment in the hospital.

Before and during treatment with Picamilon need to regularly monitor kidney function (creatinine, urea), plasma potassium level in the blood, the blood count, hemoglobin, liver function tests.

With the development of cholestatic jaundice or marked increase in liver enzymes should stop taking ACE inhibitors.

Group risk giperkaliemii are patients with renal insufficiency, diabetes mellitus, as well as receiving kalisberegate dioretiki, potassium supplements or potassium-containing salt substitutes food and drugs promoting increase of level of potassium in the blood serum (for example heparin).

In patients with increased risk of neutropenia (when violation of the kidney, systemic diseases of connective tissue) in the appointment Pramila necessary to control blood 1 time/month during the first 3-6 months of therapy, and at the first sign of infection. Upon confirmation of neutropenia (neutrophil count of less than 2 thousand/µl) therapy with ACE inhibitors should be discontinued.

In rare cases when treated with ACE inhibitors, including ramipril, marked angioedema of face, extremities, lips, tongue, larynx and/or pharynx. With the appearance of edema, which can occur suddenly, at any period of treatment, you should immediately stop taking the drug, to take emergency measures to care, and to ensure careful monitoring of the patient until complete and sustained disappearance of symptoms.

Not recommended the use of AN69 dialysis membranes in combination with ACE inhibitors (because of the possibility of development in patients anaphylactoid reactions). In rare cases when afereze engineers dextran sulfate and concurrent use of ACE inhibitors may develop anaphylactoid reactions, to avoid that you can disinvite taking ACE inhibitors before each apheresis session and resume it at the end of the session.

Antihypertensive agents, the inhibitory system of the renin-angiotensin-tend to be ineffective in the treatment of patients with primary hyperaldosteronism, therefore, the appointment ramiprila in such cases is not recommended.

Effects on ability to drive and operate machinery

Use caution when driving and performing other work, requiring greater attention, especially when taking the starting dose, switching to another drug, simultaneous administration of diuretics.