Blokordil - instructions for use, dose, side effects, contraindications

Active substance:
12.5 mg	25 mg	50 mg
Captopril
12.50 mg	25.00 mg	50.00 mg
Excipients:
Microcrystalline cellulose
35.00 mg	70.00 mg	140.00 mg
Lactose Monohydrate
25.00 mg	50.00 mg	100.00 mg
Corn starch
5.00 mg	10.00 mg	20.00 mg
Stearic acid
2.50 mg	5.00 mg	10.00 mg

Description:

Tablets 12.5 mg: round, slightly biconcave tablets of white color, with a bevel. Tablets 25 mg: round, slightly biconcave tablets of white color, with a facet and a risk on one side.

Tablets 50 mg: round, slightly biconcave tablets of white color, with a facet and a risk on one side.

Pharmacotherapeutic group:ACE blocker

ATX: & nbsp

C.09.A.A.01 Captopril

Pharmacodynamics:

Angiotensin-converting enzyme (ACE) inhibitor. Reduces the formation of angiotensin II from angiotensin I.Reduction of angiotensin II leads to a direct decrease in the release of aldosterone. This reduces the overall peripheral vascular resistance (OPSS), blood pressure (BP), post- and preload on the myocardium. Expands arteries more than veins. It causes a decrease in the degradation of bradykinin (one of the effects of ACE) and an increase in the synthesis of prostaglandins.

The hypotensive effect does not depend on the plasma renin activity, the decrease in blood pressure is observed with normal and even decreased hormone concentration, which is caused by the action on the renin-angiotensin-aldosterone system (RAAS). Strengthens coronary and renal blood flow.

With prolonged use reduces the severity of myocardial hypertrophy and the walls of arteries of the resistive type.

Improves the blood supply of the ischemic myocardium.

Reduces the aggregation of platelets.

Helps reduce sodium content in patients with chronic heart failure (CHF).

When administered orally at a dose of 50 mg / day shows angioprotective properties in relation to the vessels of the microcirculatory bed and allows slowing the progression of chronic renal failure (CRF) in diabetic nephroangiopathy.

Decrease in blood pressure is not accompanied by reflex tachycardia and leads to a decrease in myocardial oxygen demand.

The maximum decrease in blood pressure after oral administration is observed after 60-90 minutes. The duration of the hypotensive effect is dose-dependent and reaches the optimal value within a few weeks of therapy.

Pharmacokinetics:

Absorption - fast, reaches 75% (with simultaneous intake of food suction is reduced by 30-40%), bioavailability - 35-40% (has the effect of "first pass" through the liver). The connection with blood plasma proteins (mainly with albumins) is 25-30%. Time to reach the maximum concentration in the blood plasma (114 ng / ml) with oral administration - 30-90 min. Through the blood-brain barrier and placental barrier penetrates slightly (less than 1%).

Metabolized in the liver with the formation of disulfide dimer captopril and captopril-cysteine disulfide Metabolites are pharmacologically inactive.

The half-life (T_1/2) is 3 hours. It is excreted by the kidneys 95% (40-50% unchanged), the rest - in the form of metabolites. Four hours after a single oral intake, 38% of unchanged captopril and 28% in the form of metabolites are determined in urine, after 6 hours only in the form of metabolites; in daily urine - 38% of unchanged captopril and 62% - in the form of metabolites.It is secreted with breast milk.

T_1/2in violation of function kidney - 33-32 h. Cumulates in chronic renal failure.

The pharmacokinetics of captopril in healthy elderly volunteers is the same as in healthy volunteers of a young age. Older patients with arterial hypertension and preserved renal function may take usual doses of captopril.

Indications:

- Arterial hypertension, incl. Renovascular;

- chronic heart failure (as part of combination therapy);

- a violation of the function of the left ventricle after a previous myocardial infarction in a clinically stable state;

- Diabetic nephropathy in the background of type 1 diabetes mellitus (for albuminuria more than 30 mg / day).

Contraindications:

- Hypersensitivity to captopril, other components of the drug, or other ACE inhibitors (including and in the anamnesis);

- hereditary edema of Quincke or idiopathic edema, angioedema (on the background of previous therapy with other ACE inhibitors);

- hemodynamically significant bilateral stenosis of the renal arteries or stenosis of the artery of a single kidney with azotemia;

- porphyria;

- age under 18 years (safety and efficacy not established);

- pregnancy and lactation;

- lactose intolerance, lactase deficiency or glucose-galactose malabsorption.

Carefully:

Hemodynamically significant aortic stenosis, cerebrovascular diseases (including cerebral circulatory insufficiency), cerebral ischemia, connective tissue diseases, oppression of bone marrow hematopoiesis, diabetes mellitus (risk of hyperkalemia), condition after kidney transplantation, renal and / or hepatic insufficiency, diet with restriction of consumption of table salt, conditions accompanied by a decrease in the volume of circulating blood (BCC), incl. diarrhea, vomiting; elderly age.

Pregnancy and lactation:

The drug Blokordil® is contraindicated for use during pregnancy and during breast-feeding, has a proven embryotoxic effect and penetrates into breast milk.

If you need to use the drug Blokordil® during lactation, breastfeeding should be discarded.

Dosing and Administration:

Inside, regularly, 1 hour before or 2 hours after meals, washed down with a small amount of liquid, preferably at the same time of day.

Arterial hypertension

The recommended initial dose is 12.5 mg 2 times a day.

If necessary, the dose gradually (with an interval of 2-4 weeks) is increased to achieve the optimal effect.

With mild to moderate arterial hypertension, the usual maintenance dose is 25 mg 2 times a day; the maximum dose is 50 mg twice a day.

In severe arterial hypertension, a daily dose of -150 mg (50 mg 3 times a day). The maximum daily dose is 150 mg.

In patients with malignant hypertension, the recommended initial dose is 12.5 mg or 25 mg of the drug Blocordil® 2-3 times a day.

Chronic heart failure

The initial dose of the drug Blokordil® is 12.5 mg 2-3 times a day.

If necessary, the dose may be increased 2-4 weeks before the maximum daily dose of 150 mg.

The average maintenance dose from 25 mg to 50 mg 2-3 times a day.

Violation of the function of the left ventricle (after myocardial infarction)

Therapy is usually started between the 3rd and 16th day after a myocardial infarction

The initial dose is 6.25 mg per day (captopril may be used in another dosage form: tablets of 12.5 mg with a risk). The dose gradually, within a few weeks, can be increased to 50 mg 3 times a day.

Diabetic Nephropathy

The drug Blokordil® is used in a dose of 75-100 mg per day in 2-3 divided doses. In type 1 diabetes mellitus with microalbuminuria (albumin release 30-300 mg per day), the dose of the drug is 50 mg 2 times a day. With a total protein clearance of more than 500 mg per day, the drug is effective at a dose of 25 mg 3 times per day. With a moderate degree of impaired renal function (creatinine clearance (CK) - at least 30 ml / min / 1.73 m²) the drug Blokordil® can be used in a dose of 75-100 mg / day. With a more pronounced degree of renal dysfunction (CC - less than 30 ml / min / 1.73 m²) the initial dose should not exceed 12.5 mg / day; In the future, if necessary, the dose of the drug Blokordil® is increased gradually.

If necessary, additionally apply "loop" diuretics.

Elderly patients

When using the drug Blokordil ® in elderly patients the dose is selected individually, therapy is recommended to start with a dose of 6.25 mg 2 times a day and, if possible, maintain it at this level (it is possible to use captopril in another dosage form: tablets of 12.5 mg with a risk ).

If necessary, additionally apply "loop" diuretics.

If you missed taking one dose of the drug Blokordil®, it should be taken as soon as possible,but if the time of taking the next dose is approaching, the missed tablet is not taken, and the drug intake continues according to the previous scheme. The missed drug intake should not be compensated for by a single dose increase.

Side effects:

Classification of the frequency of development of side effects of the World Health Organization (WHO):

Often	>1/10
often	from> 1/100 to <1/10
infrequently	from> 1/1000 to <1/100
rarely	from> 1/10000 to <1/1000
rarely	from <1/10000, including individual messages.

From the immune system:

- very rarely: autoimmune diseases and / or titers of antinuclear antibodies.

From the nervous system:

- often: sleep disorders, taste disorders, dizziness;

- rarely: drowsiness, headache and paresthesia, a feeling of fatigue, asthenia, general weakness;

- very rarely: confusion, depression, cerebrovascular disorders, including stroke and fainting.

From the sense organs:

- very rarely: visual impairment.

From the side of the cardiovascular system:

- rarely: tachycardia, tachyarrhythmia, exertional angina, palpitations, marked decrease in blood pressure, peripheral edema;

- very rarely: cardiac arrest, cardiogenic shock, Raynaud's syndrome.

From the respiratory system:

- often: dry, irritating (unproductive) cough, shortness of breath, bronchospasm;

- Very rarely: bronchospasm, rhinitis, allergic alveolitis / eosinophilic pneumonitis.

From the digestive system:

- often: nausea, vomiting, gastritis, abdominal pain, diarrhea, constipation, dryness of the oral mucosa;

- rarely: aphthous ulcers of the inner surface of the mucous membrane of the cheeks and tongue, hyperbilirubinemia;

- Very rarely: glossitis, peptic ulcers, pancreatitis, liver dysfunction, cholestasis (including jaundice), hepatitis, incl. necrotic, increased activity of "liver" transaminases, intestinal angioedema.

From the skin:

- often: itching, rash, alopecia;

- rarely: angioedema;

- very rarely: urticaria, Stevens-Johnson syndrome, erythema multiforme, photosensitivity in the form of erythema, pemphigoid reactions and exfoliative dermatitis.

From the side of the locomotor system apparatus:

- very rarely: myalgia, arthralgia.

From the sexual and urinary system:

- rarely: violations of kidney function, polyuria, oliguria, frequent urination;

- very rarely: nephrotic syndrome, impotence, gynecomastia.

On the part of the hematopoiesis and lymphatic system:

- Very rarely: neutropenia / agranulocytosis, pancytopenia (especially in patients with impaired renal function), anemia (aplastic or hemolytic), thrombocytopenia, lymphadenopathy, eosinophilia.

Are common:

- infrequently: chest pain, weakness;

- very rarely: fever.

Laboratory indicators:

- very rarely: proteinuria, hyperkalemia, hyponatremia, increased urea concentration, creatinine and bilirubin, increased hematocrit, leukopenia, increased erythrocyte sedimentation rate.

Overdose:

Symptoms: marked decrease in blood pressure, including collapse, myocardial infarction, acute cerebrovascular accident, thromboembolic complications.

Treatment: transfer the patient to the "lying" position on the back with the legs raised upwards; further - gastric lavage, reception of activated charcoal, intravenous injection of 0.9% sodium chloride solution, and measures aimed at restoring blood pressure and increasing bcc.

Symptomatic therapy: epinephrine (subcutaneously or intravenously), antihistamines.

Hemodialysis is effective.Hemodialysis clearance is from 4.8 l / h to 7.2 l / h, depending on the type of dialyzer used.

Peritoneal dialysis is ineffective.

Interaction:

The hypotensive effect of captopril weakens indomethacin and other non-steroidal anti-inflammatory drugs (NSAIDs), incl. selective inhibitors of cyclooxygenase-2 (sodium ion delay, a decrease in the synthesis of prostaglandins, especially against a background of low renin activity), and estrogens.

Combined use with potassium-sparing diuretics, potassium preparations, potassium supplements, salt substitutes (contain significant amounts of potassium ions) increases the risk of hyperkalemia.

The use of ACE inhibitors in patients undergoing surgery with general anesthesia can lead to a marked decrease in blood pressure, especially with the use of agents for general anesthetics that have an antihypertensive effect.

Slows the excretion of lithium drugs, increasing the concentration of lithium in the blood.

When captopril is used against the background of taking allopurinol or procainamide, the risk of Stevens-Johnson syndrome and neutropenia increases.

With simultaneous use of ACE inhibitors and preparations of gold (in / in sodium aurotomy malate) describes a symptom complex, which includes facial hyperaemia, nausea, vomiting, and decreased blood pressure.

Insulin and hypoglycemic agents for oral administration increase the risk of developing hypoglycemia.

Simultaneous administration of captopril with food or antacids slows the absorption of captopril in the gastrointestinal tract.

During the therapy with captopril, ethanol is not recommended, since ethanol strengthens the hypotensive effect of captopril.

The hypotensive effect of captopril is potentiated with simultaneous use with aldesleukin, alprostadil, beta-adrenoblockers, alpha₁adrenoblockers, central alpha₂adrenomimetics, diuretics, cardiotonics, blockers of "slow" calcium ropes, minoxidil, muscle relaxants, nitrates and vasodilators.

Antidepressants, antipsychotics, anxiolytics and hypnotics can also increase the hypotensive effect of captopril

The hypotensive effect of captopril is weakened by epoetins, estrogens and combined oral contraceptives, carbenoxolone, glucocorticosteroids and naloxone.

Probenecid reduces renal clearance of captopril and increases its serum concentrations in the blood.

The use of captopril in patients taking immunosuppressants (for example, azathioprine or cyclophosphamide), increases the risk of hematological disorders.

Special instructions:

The drug Blokordil® in a dose of 25 mg can be used for the treatment of increased blood pressure (hypertensive crisis). The patient should chew the tablet and leave it in the mouth, under the tongue until complete resorption. The effect develops within 15-30 minutes; if the effect is insufficient, after 1 hour, it is possible to re-take the drug Blocordil® at a dose of 25 mg according to the same scheme.

After taking the first dose of Blokordil ®, an arterial hypotension may develop with all of its clinical symptoms (from fainting and nausea, to acute kidney failure and / or death), especially in patients with reduced bcc or hyponatremia due to high doses of diuretics or as a result of hemodialysis.

Arterial hypotension can develop a few hours after taking the first dose of the drug. It can be avoided by the elimination of a diuretic and a salt-free diet before the use of the drug Blokordil®.

In case of repeated episodes of symptomatic arterial hypotension, it is necessary to reduce the dose of Blokordil® or to cancel therapy.

The use of the drug Blokordil ® is contraindicated in patients with bilateral stenosis of the renal arteries or stenosis of the artery of a single kidney. Due to the expansion of the delivering (efferent) arterioles of the renal glomeruli, a decrease in renal function can occur, up to acute renal failure. Before and during the therapy with the drug Blokordil®, kidney function monitoring is mandatory.

The drug Blokurdil® should be used with caution in elderly patients, as this group of patients has a higher risk of unwanted effects.

During the use of the drug Blokordil ® can develop angioedema, edema, neck, tongue, pharynx, larynx. In this case, you should immediately enter subcutaneously epinephrine (adrenaline) (at 1: 1000 dilution (0.3 or 0.5 mL) and / or provide airway patency.

On the background of therapy with the drug Blokordil®, hyperkalemia may develop, especially in patients with CRF, diabetes, with concomitant therapy with potassium-sparing diuretics (such as spironolactone, triamterene or amiloride) or simultaneous use of potassium preparations. Therefore, simultaneous administration of the drug Blocordil® and the agents described above is not recommended. If you need an additional intake of potassium drugs, for example, due to hypokalemia, you should regularly monitor the potassium content in the blood serum.

The drug Blokordil® should be used with great care in patients with connective tissue diseases and simultaneously receiving immunosuppressive therapy (allopurinol or procainamide), especially with existing impairments of kidney function. These patients can develop severe infections that are not amenable to intensive antibiotic therapy.

In the case of the use of the drug Blokordil®, it is recommended to periodically monitor the number of leukocytes in the blood. The patient should be warned that if any signs of an infectious disease (sore throat, fever) appear, you should immediately consult a doctor.

The drug Blokordil® should be used with caution in patients with diabetes mellitus.Some patients may need to reduce the dose of insulin or hypoglycemic agents for oral administration.

There are separate reports on the development of long-term, life-threatening anaphylactoid reactions in patients receiving ACE inhibitors during desensitizing therapy with the poison of Hymenoptera insects (bees, wasps). ACE inhibitors should be used with caution in patients prone to allergic reactions undergoing desensitization. The use of ACE inhibitors in patients receiving Hepaticoptera venom therapy should be avoided. Nevertheless, the development of anaphylactoid reactions can be avoided by the temporary withdrawal of the ACE inhibitor at least 24 hours before the desensitization procedure begins.

In rare cases, patients with ACE inhibitors may experience life-threatening anaphylactoid reactions during low-density lipoprotein (LDL) apheresis with dextran sulfate. To prevent anaphylactoid reactions, ACE inhibitor therapy should be discontinued before each procedure for LDL apheresis using high-flow membranes.

It is recommended to stop the use of ACE inhibitors, including the drug Blokordil®, 12 hours prior to surgery, warning the anesthesia doctor about the use of ACE inhibitors.

During therapy with ACE inhibitors, several cases of liver dysfunction with cholestatic jaundice, fulminant liver necrosis (in some cases) with a fatal outcome were reported. If against the background of therapy with the drug Blokordil® jaundice may develop or activity of "liver" transaminases may increase, the drug Blokurdil® should be immediately canceled; the patient should be under close supervision and, if necessary, receive appropriate therapy.

Effect on the ability to drive transp. cf. and fur:Care must be taken when driving vehicles and other technical devices that require a high concentration of attention and speed of psychomotor reactions, in connection with the possibility of developing side effects (excessive depression of blood pressure, dizziness, etc.).

Form release / dosage:Tablets, 12.5 mg, 25 mg and 50 mg.

Packaging:

10 tablets per blister.

2 blisters together with instructions for use will prevent the cardboard pack.

Storage conditions:

At a temperature of no higher than 25 ° C.

Keep out of the reach of children.

Shelf life:

3 of the year.

Do not use the drug after the expiration date.

Terms of leave from pharmacies:On prescription

Registration number:П N012811 / 01

Date of registration:08.12.2010

Expiration Date:Unlimited

Date of cancellation:2017-04-28

The owner of the registration certificate:KRKA, dd, Novo mesto, AOKRKA, dd, Novo mesto, AO

Manufacturer: & nbsp

KRKA, d.d. Slovenia

Representation: & nbspKRKA KRKA Slovenia

Information update date: & nbsp28.04.2017

Illustrated instructions

Instructions

Blocordil® (Blocordil®)