PIRAMIL

Active material: Ramipril
When ATH: C09AA05
CCF: ACE inhibitor
ICD-10 codes (testimony): I10, I50.0, N08.3
When CSF: 01.04.01.03
Manufacturer: LEK d.d. (Slovenia)

Pharmaceutical form, composition and packaging

Pills light yellow, oblong, lenticular, with a rough surface, with occasional splashes of darker color and mark on one side.

Excipients: microcrystalline cellulose, pre-gelatinized starch, precipitated silicon dioxide, glycine hydrochloride, glyceryl dibegenat, dye iron oxide yellow.

7 PC. – blisters (4) – packs cardboard.

Pills light pink, oblong, lenticular, with a rough surface, with occasional splashes of darker color and mark on one side.

Excipients: microcrystalline cellulose, pre-gelatinized starch, precipitated silicon dioxide, glycine hydrochloride, glyceryl dibegenat, iron oxide red dye.

7 PC. – blisters (4) – packs cardboard.

Pills white or nearly white, oblong, lenticular, with the rough surface and scored on one side.

Excipients: microcrystalline cellulose, pre-gelatinized starch, precipitated silicon dioxide, glycine hydrochloride, glyceryl dibegenat.

7 PC. – blisters (4) – packs cardboard.

Pharmacological action

ACE inhibitor. Ramipril is rapidly absorbed in the digestive tract and liver is hydrolysis with the formation of the active metabolita ramiprilata. Ramiprilat is a long-acting ACE inhibitor, enzyme, catalysing making angiotenzina I angiotenzin II.

Ramipril causes a decrease in the level of angiotensin II in plasma, increased Renin activity and aldosterone release reduction. Inhibits the kinase level II, prevents the breakdown of bradykinin, increased synthesis of prostaglandins. Under the influence of ramiprila expands peripheral vessels and reduced ROUND.

Arterial hypertension

Provides gipotenzivne action in situation of a patient lying and standing. Reduces PR (afterload), jamming pressure in the lung capillaries without a compensatory increase in HEART RATE. Enhances coronary and renal blood flow, without affecting the speed clubockova filtering.

Start action hypotensive – through 1 – 2 hours after ingestion, maximal effect develops after 3-6 h after administration. The action is not less than 24 no.

Chronic heart failure and cardiac failure due to acute myocardial infarction

Ramipril reduces round and, ultimately, FROM. Increases cardiac output and tolerance to physical activity. With long-term use helps to reverse the development of myocardial hypertrophy in patients with cardiac insufficiency I and II stage; It improves blood flow to the ischemic myocardium.

Ramipril improves survival of patients with symptoms of transient or chronic heart failure after myocardial infarction. The effect occurs after only a month after the beginning of drug and lasts for 2 years after the end of therapy. Has kardioprotektornym activity, prevents coronary ischemic episodes, reduces the risk of myocardial infarction and reduces the duration of hospitalization.

Nephropathy

In patients with diabetic nephropathy ramipril reduces albuminuria. If nephropathy another etiology ramipril slows the progression of kidney failure. In insulinzawisimom diabetes and diabetic nephropathy expressed ramipril reduces the severity of proteinuria. When you have diabetes and at least one of the risk factors (mikroalьʙuminurija, hypertension, elevated levels of total cholesterol/HDL cholesterol levels low, smoking) ramipril reduces the severity of complications of diabetes mellitus.

Pharmacokinetics

Absorption

Ramipril is rapidly absorbed in the intestine after taking inside. Absorption does not depend from taking screaming. After ramipril intake quickly and almost completely transformed into the active metabolite Ramiprilat by the action of the enzyme liver esterase. Ramiprilat about 6 times stronger ingibiruet agents, Cem ramipril. Also detected other, pharmacologically inactive metabolites.

C_max ramiprila in plasma achieved within 1 h after administration, C_max ramiprilata – during 2-4 h after dosing. Bioavailability ramiprila is 60%.

Distribution

Linking blood plasma proteins reaches 73% for ramiprila and 56% for ramiprilata.

Deduction

T_1/2 ramiprilata with long-term use in dose 5-10 mg 1 times/day is 13-17 no.

Upon receiving 5 mg kidney klirens ramiprila is 10-55 ml / min, vnepochechny reaches the ground 750 ml / min. To ramiprilata these indicators are equal 70-120 mL/min and about 140 ml / min, respectively. Ramipril and Ramiprilat is mostly excreted by the kidneys (40-60%).

Pharmacokinetics in special clinical situations

In patients with impaired kidney function transformation in slowing due to Ramiprilat ramiprila relatively short period esterase, Therefore, the level of ramiprila in plasma increased in these patients.

If any of the kidneys of their excretion is slowing.

Testimony

- Arterial hypertension;

- Congestive heart failure;

-chronic heart failure after acute myocardial infarction in patients with stable hemodynamics indices;

-diabetic and non-diabetic nephropathy.

Dosage regimen

The drug is taken orally, regardless of the meal, without chewing, drinking water.

Arterial hypertension

The recommended initial dose for patients without heart failure, do not take diuretics, is 2.5 mg / day. Dose can be gradually increased every 2-3 weeks depending on the effect and tolerability. The maximum dose is 10 mg 1 time / day. Usually supporting dose is 2.5-5 mg 1 time / day. In the absence of a satisfactory therapeutic effect when administered 10 mg/day recommended the appointment of a combined drug treatment.

If the patient is taking diuretics, should finish them or reduce their dose for 2-3 days before the start of treatment Piramilom^®. For such patients, the recommended initial dose 1.25 mg 1 time / day.

Congestive heart failure

The recommended initial dose Piramila^® is 1.25 mg 1 time / day.

Dose can be gradually increased depending on the effect and tolerability, doubling it every 1-2 of the week. Doses 2.5 mg/day and above can be 1-2 admission. The maximum dose is 10 mg 1 time / day.

Patient, taking high doses of diuretics, dose should be reduced before treatment Piramilom^®, to minimize the risk of developing symptomatic arterial hypotension.

Cardiac failure due to acute myocardial infarction

Treatment begins at 3-10 days after acute myocardial infarction. The initial dose is 2.5 mg 2 times / day, through 2 SUT dose increase to 5 mg 2 times / day. Poor tolerability the initial dose 2.5 mg 2 times / day, It should be within 2 days of assign dose 1.25 mg 2 times / day, then, increasing the dose to 2.5 mg 5 mg 2 times / day. The maintenance dose is 2.5-5 mg 2 times / day. The maximum daily dose is 10 mg.

Nephropathy

The recommended starting dose is 1.25 mg 1 time / day. Depending on the portable, You can double the dose at intervals of 2-3 weeks to a maximum of – 5 mg / day.

If the patient is taking diuretics, should finish them or reduce the dose for 2-3 days before the start of treatment Piramilom^®; in this case, the recommended initial dose Piramila^® is 1.25 mg 1 time / day.

Special groups of patients

To patients with impaired renal function (CC 0.3-0.8 ml/sec/1.73 m²) the recommended initial dose Piramila^® is 1.25 mg 1 time / day, and the maximum dose should not exceed 5 mg / day. At renal insufficiency (CC less than 0.3 ml/sec/1.73 m²) the recommended initial dose Piramila^® is 1.25 mg 1 time / day, If necessary dose can be increased to 2.5 mg / day.

In patients with impaired liver function There may be a strengthening, and the weakening of therapeutic action Piramila^®. Treatment should start under the supervision of a physician with a destination dose 1.25 mg. The maximum dose does not exceed 2.5 mg / day.

Caution must be exercised in the appointment ramiprila elderly patients If they have kidney or liver failure, as well as in heart failure and simultaneous reception dioretikov. Dose should be selected individually depending on the target blood pressure level.

Side effect

The incidence of adverse events was classified as follows:: Often (≥1/10), often (≥1/100, <1/10), infrequently (≥1/1000, <1/100), rarely (≥1/10 000, <1/1000), rarely (<1/10 000).

Cardio-vascular system: often – marked reduction in blood pressure; infrequently – orthostatic hypotension, Orthostatic hypotension, angina, myocardial infarction or cerebrovascular accident (as a result of a sharp fall ad patients risk groups), tachycardia, arrhythmia, Raynaud's syndrome.

Allergic reactions: infrequently – skin rash, itch; rarely – hives, photosensitivity, angioneurotic edema of the face, lips, language, larynx, limbs; rarely – myalgia, myositis, arthralgia / arthritis, erythema multiforme exudative (incl. Stevens-Johnson syndrome), toxic epidermal necrolysis (Lyell's syndrome), pemphigus (pemphigus), vasculitis, serositis, eozinofilija.

From the digestive system: infrequently – dry mouth, nausea, vomiting, abdominal pain, dyspepsia, decreased appetite, diarrhea, increase in liver enzymes; rarely – pancreatitis, hepatitis, cholestatic jaundice, abnormal liver function, stomatitis, glossitis.

CNS: often – weakness, headache; infrequently – mood lability, paresthesia, dizziness, sleep disorders; rarely (when using high doses of) – confusion, depression, anxiety, cerebrovascular accident.

The respiratory system: often – dry cough; infrequently – breathlessness, rhinitis, bronchitis; rarely – bronchospasm, sinusitis, allergic alveolitis, eosinophilic pneumonia.

With the genitourinary system: often – impairment of renal function; rarely – sexual dysfunction, proteinuria; rarely – oliguria or anuria.

From the side of hematopoiesis: rarely – reduction of the concentration of hemoglobin and hematocrit; rarely – anemia, thrombocytopenia, gemoliticheskaya anemia, neutropenia, agranulocytosis, pancytopenia, Suppression of the bone marrow, Lymphadenopathy. Neutropenia and agranulocytosis are reversible and disappear when canceling the ACE inhibitors.

Other: infrequently – asthenia, fever, alopecia, taste disturbance, olfactory, gynecomastia, reduced potency, noise in ears; rarely – gipoglikemiâ, hearing and visual impairment, muscle cramps.

Laboratory findings: infrequently – increase of urea, creatinine, hyperkalemia; rarely – giperʙiliruʙinemija, giponatriemiya, the appearance of antinuclear antibodies.

Contraindications

-hereditary or idiopathic angioedema (incl. When taking ACE inhibitors in history);

— stenoses bilateral renal artery, stenosis of artery only kidneys;

- Acute myocardial infarction;

- Cardiogenic shock;

- Primary hyperaldosteronism (in view of the ineffectiveness of the use of antihypertensive drugs, incl. inhibiting Renin-medication system);

- Pregnancy;

- Lactation (breast-feeding);

- Up to 18 years (the efficacy and safety of not known);

-hypersensitivity to ramiprilu, other ACE inhibitors or subsidiary drug component.

FROM caution should designate product when expressed human liver and/or kidney, hyperkalemia, giponatriemii, diabetes (the risk of hyperkalemia), clinically significant aortic or mitralnom stenoze, hypertrophic cardiomyopathy, stage IV chronic heart failure (NYHA classification), unstable angina, severe coronary lesions and cerebral arteries (the danger of reducing blood flow when excessive decline in ad), states, accompanied by a decrease in the bcc (incl. diarrhea, vomiting), patients, adhering to the 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 (eg, AN69), LDL apheresis with dextran sulfate, desensitizing therapy, conditions after kidney transplantation, elderly patients (an increased risk of associated disorders of the liver and / or kidney disease and congestive heart failure),

Pregnancy and lactation

The drug is contraindicated in pregnancy and during breastfeeding.

Cautions

After the first dose, and when increasing the dosage of diuretics and / or peers^® Patients should be within 8 h under medical supervision because of the possibility of orthostatic hypotension.

Transient arterilnaya hypotension is not a contraindication to further treatment Piramilom^®, tk. When restoring the Bcc and the normalization of the level of HELL reception following doses of the drug does not usually cause symptomatic arterial hypotension. In case of recurrence of arterial expressed hypotension should reduce the dose or stop the drug. Patients with malignant arterial hypertension or related chronic cardiac insufficiency of the decompensation should start treatment in hospital.

Before and during treatment Piramilom^® There is a need to regularly monitor kidney function (creatinine, urea), the level of potassium in the blood plasma, blood count, hemoglobin, liver function tests.

In developing holetsaticescoy jaundice or expressed by increasing the level of liver enzymes should stop taking ACE inhibitors.

Risk giperkaliemii against accounted for patients with renal insufficiency, diabetes, as well as receiving kalisberegate dioretiki, drugs or potassium salt substitutes, kalisodergaszczye medicines, to increase the level of potassium in the blood serum (eg, Heparin).

In patients with increased risk of neutropenia (If the kidney function, systemic connective tissue diseases) in appointing Piramila^® needed to be monitored formula blood 1 times per month during the first 3-6 months of therapy, as well as at the first sign of infection. Upon confirmation of neutropenia (the number of Klebsiella less 2 thous. / ul) ACE inhibitors therapy should be discontinued.

In rare cases when treatment ACE inhibitors, incl. ramipril, observed angioedema of the face, limbs, lips, language, the larynx and/or pharynx. When edema, which can develop suddenly, in any period of treatment, You should immediately discontinue use of the drug, urgent medical assistance and measures to ensure thorough monitoring of the patient until the full and sustainable disappearance of symptoms.

We do not recommend the use of dialysis membranes AN69 in combination with ACE inhibitors (due to the possibility of development anaphylactoidnykh reactions in patients). In rare cases, afereze LDL with dekstransul'fatom and ACE inhibitors together may anaphylactoidnykh reactions, avoid where possible, cancelling receiving ACE inhibitors before each session Apheresis and resuming its session ends.

Antihypertensive agents, ingibiruyushtie sistemu renin-angiotensin, is usually ineffective in treating patients with primary giperal'dosteronizmom, Therefore, assigning ramiprila in such cases is not recommended.

Effects on ability to drive vehicles and management mechanisms

Use caution when driving and performing other work, requiring greater attention, especially when taking initial dose, switching to another drug, simultaneous reception dioretikov.

Overdose

Symptoms: marked reduction in blood pressure, 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 minutes after administration). Should control the function of vital organs. When expressed arterial hypotension if necessary appoint Catecholamines, Angiotensin II, I / – a physiological solution. Experience of application of forced diuresis, changes the pH of the urine, dialysis or Hemofiltration for accelerated excretion ramiprila from the body no. Hemodialysis is shown in cases where the development of renal failure.

Drug Interactions

Antihypertensive, Diuretic, nitrates, tricyclic antidepressants, neuroleptics, hypnotics, opioid analgesics, funds for general anesthesia increase gipotenzivne effect ramiprila.

Piramil^® enhances hypoglycemic effect of sulfonylurea derivatives, insulin.

NSAIDS may reduce antigipertenzivny effect ramiprila, as well as cause the kidney function, sometimes leading to development of renal failure.

Sodium chloride may weaken effect ramiprila.

Drugs potassium, potassium-sparing diuretics, kalisodergaszczye salt substitutes, heparin, ramipril with increase the risk giperkaliemii.

Together with the appointment drugs lithium increases their concentration in the blood, that leads to increased cardiotoksicski action and neurotoxic drugs lithium.

Not recommended simultaneous appointment ramiprila with corticosteroids.

Sympathomimetics may reduce gipotenzivne ramiprila.

Increases the risk of radiation while applying with allopourinolom, cytostatic drugs, immunosuppressants, prokaynamydom.

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

Estrogens weaken gipotenzivny effect (delay fluid) ramiprila.

Conditions of supply of pharmacies

The drug is released under the prescription.

Conditions and terms

The drug should be stored out of reach of children, dry, dark place at a temperature no higher than 25 ° C. Shelf life – 2 year.