Polpril

General characteristics. Structure:

Active agent - ramiprit 2,5 mg, 5 mg, 10 mg.
 
Excipients: starch prezhelatinizirovanny, structure of the case of capsules: gelatin, the water purified gland (II, III) oxide black (E 172), titanium dioxide (E 171).
 
Structure of a lid of capsules: gelatin, the water purified, FD&C Blue indigo carmine (E 132), titanium dioxide (E 171), gland (III) oxide yellow, gland (II, III) oxide black (E 172) (for a dosage of 10 mg).
 
Capsules with a dosage of 2,5 mg: a solid gelatin capsule No. 4 with the light gray case with a text "2,5" and a light green lid with a text of "R". Capsule contents – powder of white or almost white color.
 
Capsules with a dosage of 5 mg: a solid gelatin capsule No. 4 with the light gray case with a text "5" and a green lid with a text of "R". Capsule contents – powder of white or almost white color.

Capsules with a dosage of 10 mg: a solid gelatin capsule No. 4 with the light gray case with a text "10" and a dark green lid with a text of "R". Capsule contents – powder of white or almost white color.

Pharmacological properties:

Pharmacokinetics. After intake ramiprit quickly it is soaked up from digestive tract. The maximum concentration of a ramipril in a blood plasma comes within 1 hour. The maximum concentration of an active metabolite - a ramiprilat comes in 2 - 4 hours.

The volume of distribution of a ramipril and ramiprilat makes about 90 l (ramiprit) and 430 l (рамиприлат). Ramipril contacts proteins of plasma approximately for 73%, and рамиприлат for 56%.

Ramipril biotransformirutsya almost completely. Except biologically active metabolite - a ramiprilat other, inactive metabolites, including diketopiperazine ether, diketopiperazine acid, and also the connections which are formed as a result of interface reaction are identified.

After introduction in a ramipril, about 60% of active ingredients and their metabolites are defined in urine and less than 40% in Calais.

The elimination half-life of a ramipril makes not less than 13-17 hours. Constant concentration of a ramiprilat in a blood plasma, in case of use of an identical daily dose, is defined within 4 days of treatment.

At patients with an impaired renal function (the clearance of creatinine <60 ml/min.) рамиприлат is removed in smaller quantities, in proportion to clearance of creatinine. It leads to increase in concentration in plasma of a ramiprilat who is removed more slowly, than at patients with normal function of kidneys.

Pharmacodynamics. Polpril after absorption from digestive tract, is hydrolyzed in a liver to an active metabolite - the ramiprilat which is an effective inhibitor the angiotensin-the converting enzyme (ACE) with the prolonged action. Suppression angiotensin - the converting enzyme leads to decrease in formation of angiotensin ІІ, having vasoconstrictive effect, in fabrics and a blood plasma that in turn leads to decrease in secretion of Aldosteronum and, therefore, increase in potassium concentration in blood serum. Lack of negative feedback between angiotensin ІІ and secretion of a renin leads to strengthening of activity of a plasma renin what expansion of blood vessels and decrease in vascular resistance is result of.

Polpril causes the expressed decrease in peripheric resistance of arteries. At most of patients the beginning of anti-hypertensive effect of a single dose is shown in 1-2 hours after intake. The maximum action comes in 3-6 hours and continues within 24 hours. The maximum of anti-hypertensive effect is usually shown in 3-4 weeks. For maintenance of anti-hypertensive effect treatment by Polpril needs to be carried out it is long.

At use of the recommended daily dosage even at prolonged treatment resistance does not develop. Sharp cancellation of a ramipril does not cause bystry, excessive increase in pressure of blood (a syndrome of "cancellation").

At reception within not less than 6 months at patients with the inborn and acquired heart diseases Polpril exerts positive impact on a cordial hemodynamics (reduces the filling pressure of the left and right ventricles, reduces the general peripheric resistance of vessels, increases cordial emission and improves cardiac index). Ramipril increases sensitivity of fabrics to insulin, concentration of fibrinogen, stimulates synthesis of the fabric activator of plasminogen (plasminogen), promoting a thrombolysis, reduces the volume of diabetic complications (a manifest nephropathy or need of treatment by dialysis).

Indications to use:

- essential arterial hypertension

- heart failure of easy and average severity, including after acute (from 2 to 9 days) a myocardial infarction

- decrease in risk of a myocardial infarction, brain stroke or a cardiovascular disease mortality at patients with the increased risk of cardiovascular diseases (such, as, the demonstrating disease of coronary arteries of heart, a diabetes mellitus with not less, than one accessory factor of risk, an occlusal disease of peripheral arteries, existence in the anamnesis of a brain stroke).

Route of administration and doses:

Polpril at the same time is recommended to accept every day, it is not dependent on meal.

Polpril's capsules should be washed down with liquid. It is not necessary to crush them or to chew.

At treatment of patients with normal renal function use the following recommendations about dosing.

Essential arterial hypertension. Usually, the initial single dose of Polpril – 2,5 mg which is accepted once in the morning this dose is and supporting. If at such dosage within 3 weeks and it is not possible to normalize pressure any more, then it is possible to increase a dose to 5 mg a day. The maximum daily dose - 10 mg.

If the hypotensive effect of a daily dose of 5 mg of Polpril is insufficient, for increase in hypotensive effect it is necessary to consider the possibility of additional purpose of drugs from other groups (for example, diuretics or calcic antagonists).

Heart failure of easy and average severity after an acute (2 - 9-day) myocardial infarction.

In 48 hours after development of a myocardial infarction in clinically and hemodynamically stable patients the starting dose makes 2,5 mg twice a day within three days. Depending on a condition of the patient the dose of drug can be lowered to 1,25 mg in two steps or is increased.

It is possible to double a dose each 1-2 days to the maximum daily dose: on 5 mg of Polpril in the morning and in the evening (i.e. a daily dose - 10 mg).

For decrease in risk of development of a myocardial infarction, a stroke or cardiovascular death at patients with the increased cardiovascular risk. The recommended initial dose - on 2,5 mg of Polpril once a day. Depending on portability, the dose is gradually increased. In a week it is recommended to double a dose, and in 3 weeks to bring it to a usual maintenance dose of 10 mg.

Doses for patients with a renal failure. Initial dose of 1,25 mg once in the morning. The maintenance dose makes, usually, 2,5 mg a day. The maximum daily dose should not exceed 5 mg.

Perhaps excessive lowering of arterial pressure in an initiation of treatment drug, especially, at patients with the low content of salts and liquids in an organism, heart failure (especially, after an acute myocardial infarction) or heavy hypertensia.

After the first dose, and also at increase in a dose of Polpril and (or) loopback diuretics, patients are subject to medical observation for not less than 8 hours for prevention of development of uncontrollable hypotensive reaction.

Elderly patients (65 years are more senior) can have more expressed reaction to AKF inhibitor, than at sick other age categories. In this regard elderly sick and, especially, sick with risk of development of arterial hypotonia individual selection of a dose is necessary.

At malignant hypertensia and in case of heart failure, in particular, after an acute myocardial infarction, treatment by Polpril should be begun in stationary conditions.

Features of use:

At Polpril's appointment, and also at increase in its dosage and (or) loopback diuretic, it is necessary to provide medical control of a condition of patients, at least for 8 hours. Within the first week of use of drug it is recommended to control function of kidneys and a liver. Patients with a renal and liver failure need to select a drug dose individually.

Patients with considerable activation renin-angiotensin-aldosteronovoy of system are subject to risk of sharp falling of arterial pressure and deterioration in function of kidneys owing to AKF inhibition.

The patients demanding especially careful observation in an initial stage of treatment:

- the age group is more senior than 65 years,

- at the increased risk of development of sharp arterial hypotonia (for example, patients with a stenosis of the coronary vessels or vessels supplying a brain).

Before Polpril's appointment it is necessary to estimate function of kidneys. Control of function of kidneys is recommended in the first weeks of treatment, especially at patients with heart failure, with a unilateral renal artery stenosis, with a renal failure.

Short-term control of level of electrolytes and creatinine of blood, cellular composition of peripheral blood (quantity of leukocytes) is recommended, especially at purpose of treatment by the patient from risk group (having a renal failure, diseases of connecting fabric).

(Bees, wasps) and a concomitant use of one of AKF inhibitors anaphylactoid reactions (a lowering of arterial pressure, short wind, vomiting, skin allergic reactions) which can sometimes accept zhizneugrozhayushchy character can initiate the treatment directed to desensitization to poison of insects. Similar reactions can arise also after stings of insects (for example, bees, wasps). If performing desensitization to poison of insects is necessary, AKF inhibitor has to be temporarily replaced with medicine of other class, similar on action.

Before an initiation of treatment it is recommended to carry out correction of volume of the circulating blood in the presence at the patient of dehydration, a hypovolemia or loss of salts (to patients with heart failure correction is carried out taking into account the recommended volumes of infusional therapy).

Due to a possibility of development of side effects (dizziness, a visual disturbance) it is necessary to refrain from control of vehicles and service of potentially dangerous mechanisms.

Side effects:

Often> 1/100:

- headache, dizziness, fatigue

- dry cough, sinusitis, bronchitis, suffocation

- dyspepsia, diarrhea, nausea, vomiting, discomfort in a stomach

- skin rash, in particular makulopapulezny

- muscular spasms, mialgiya

- increase in level of potassium in blood

- orthostatic hypotonia, syncope

- thorax pain

Not really often ≥1/1000 to <1/100:

- myocardium ischemia, including an angina of exertion or a myocardial infarction, tachycardia, arrhythmia, tachycardia, peripheral hypostases

- eosinophilia

- paresthesia, ageusia, dysgeusia

- vision disorders, including a sight illegibility

- a bronchospasm, including an exacerbation of asthma, hypostasis mucous a nose

- pancreatitis, increase in level of pancreatic enzymes, a Quincke's disease of a small intestine, pain in an upper half of a stomach, including gastritis, a lock, dryness in a mouth

- a renal failure, including an acute renal failure, strengthening of a diuresis, increase of the available proteinuria, increase in level of urea of blood, increase in level of creatinine of blood

- Quincke's disease, itch, hyperhidrosis

- arthralgia

- anorexia, loss of appetite

- heat inflows

- fever

- increase in level of liver enzymes and/or the conjugated bilirubin

- passing erectile dysfunction, decrease in a libido

- reduced mood, uneasiness, nervousness, concern, a sleep disorder, including drowsiness

Seldom <1/10 000:

- decrease in quantity of leukocytes (including a neutropenia or an agranulocytosis), decrease in quantity of erythrocytes, hemoglobin, thrombocytes

- tremor, balance disturbance

- conjunctivitis

- hearing disorder, sonitus

- glossitis

- exfoliative dermatitis, a small tortoiseshell, онихолизис (peeling of a nail plate from a bed)

- stenosis of vessels, hypoperfusion, vasculitis

- adynamy

- cholestatic jaundice, hepatocellular defeat

- confusion of consciousness

Very seldom <1/10 000

- photosensitivity.

Frequency is unknown (it cannot be defined on the basis of available data):

- dysfunction of marrow, pancytopenia, hemolitic anemia

- cerebral ischemia, including an ischemic stroke and the tranzitorny ischemic attack, disorder of psychomotor skills, a burning sensation, disorder of sense of smell

- aphthous stomatitis

- a toxic epidermal necrolysis, Stephen's syndrome – Johnson, a mnogoformny erythema, a pemphigus, an exacerbation of psoriasis, psoriazoformny dermatitis, pemphigoid or a lichenoid dieback or an enantema, an alopecia

- decrease in level of sodium in serum

- Reynaud's syndrome

- anaphylactic or anaphylactoid reactions, increase in level of anti-nuclear antibodies

- an acute liver failure, cholestatic or cytolytic hepatitis (death comes in exceptional cases)

- gynecomastia

- disturbance of attention.

Interaction with other medicines:

The following interactions are possible during simultaneous use of drug Polpril (or other AKF inhibitors) and following medicines: 

- the potassium salts, heparin, kaliysberegayushchy diuretics and other active ingredients increasing potassium level in a blood plasma (including blockers of receptors of angiotensin II, Trimethoprimum, такролимус, cyclosporine) - development of a hyperpotassemia in this connection during treatment it is regularly necessary to control potassium concentration in blood serum is possible

- anti-hypertensive drugs (for example, diuretics) and other substances which can reduce arterial pressure (for example, nitrates, tricyclic antidepressants, anesthetics, Baclofenum, альфузозин, доксазозин, Prazozinum, тамсулозин, теразозин) - it is necessary to consider a possibility of increase in risk of emergence of hypotension

- angiotonic sympathomimetics and other drugs which can reduce anti-hypertensive effect of a ramipril (for example, Isoproterenolum, Dobutaminum, a dopamine, Epinephrinum) - it is necessary to control blood pressure regularly

- Allopyrinolum, immunodepressants, corticosteroids, procaineamide, cytostatics and other substances changing quantity of leukocytes of blood - increase probability of hematologic reactions, especially decrease in quantity of leukocytes (leukopenia)

- lithium salts - increase in concentration of lithium in blood serum and as a result is possible, potentiation of cardiotoxic and neurotoxic effect of lithium, regular control of concentration of lithium in serum is necessary

- hypoglycemic drugs (for example, sulphonylurea derivatives, guanyl guanidines), including insulin - are possible hypoglycemic reactions therefore it is necessary to control carefully glucose level in blood

- nonsteroid antiinflammatory medicines (NPVP) and acetylsalicylic acid - decrease in hypotensive effect of a ramipril, deterioration in function of kidneys and increase in level of potassium in blood serum is possible

- somnolent drugs, narcotic drugs, anesthetics - sharp arterial hypotonia can develop

- sodium chloride exponentiates decrease in anti-hypertensive effect of drug and less effective treatment of symptoms of heart failure

- vasoconstrictive drugs, sympathomimetics (for example, Epinephrinum) - there can occur decrease in anti-hypertensive effect of Polpril (regular control of arterial pressure of blood is recommended)

- antiacid drugs - reduce biological availability of AKF of blockers

- alcohol – exponentiates anti-hypertensive action of Polpril and effect of alcohol.

Contraindications:

- hypersensitivity to a ramipril, drug components, other drugs of this group

- hemodynamically significant narrowing of a renal artery (bilateral or unilateral in case of the only kidney)

- a state after transplantation of a kidney

- hemodynamically significant stenosis of an aorta or mitral valve, hypertrophic subaortic stenosis

- primary aldosteronism

- vasculomotor hypostasis in the anamnesis (hereditary, idiopathic or after administration of inhibitor angiotensin - the converting enzyme)

- pregnancy and period of a lactation

- the extracorporal treatment leading to contact of blood with negatively charged surfaces

- the expressed heart failure, unstable stenocardia, a pulmonary heart, ventricular arrhythmia

- hypotension or hemodynamically unstable state, orthostatic dysregulation.

In view of lack of therapeutic experience, drug is not appointed:

- at a nephropathy (in which treatments steroids, non-steroidal anti-inflammatory drugs, immunomodulators and (or) cytotoxic drugs are applied)

- dialysis

- primary disease of a liver or liver failure

- uncured dekompensirovanny heart failure

- children's and teenage age up to 18 years.

Overdose:

Simptomy:vyrazhenny lowering of arterial pressure, bradycardia, shock, disturbance of water and electrolytic balance, acute renal failure, vascular insufficiency.

Treatment: a gastric lavage, purpose of adsorbents (it is desirable the first 30 minutes after drug hit inside), control and maintenance of the vital functions, at a lowering of arterial pressure - introduction of agonists an alpha of 1 adrenoceptors or angiotensin II, completion of missing amount of chloride sodium and volume the ECG circulating blood with monitoring, arterial pressure and the subsequent use of system glucocorticoids.

Storage conditions:

To store in the place protected from light, at a temperature not above 25 °C. To store in the place, unavailable to children!

Issue conditions:

According to the recipe

Packaging:

On 7 capsules in a blister strip packaging from a film of the polyvinyl chloride and printing aluminum foil varnished.

On 4 planimetric packagings together with the application instruction in the state and Russian languages put in a cardboard pack.