2010/09/20

Ampliton

Composition, structure and packing

A set of tablets:

Tablets are white or nearly white, round, ploskotsilindricheskie, with beveled and scored (5 pcs. In blister).

1 tab. amlodipine (in the form bezilata) 5 mg.

Excipients: lactose, microcrystalline cellulose, calcium stearate, sodium croscarmellose (primelloza), colloidal silicon dioxide (Aerosil).

Coated tablets pale-red, oval, biconvex, engraved on one side "CIL 2,5", with the risk - on the other side (5 pcs. In blister).

1 tab. cilazapril (in the form of monohydrate) 2.5 mg.

Excipients: lactose, corn starch, hydroxypropylmethylcellulose (gipromelloza) 3 cps, talc (sodium hydrosilicate), sodium stearyl fumarate. The composition of the shell: hydroxypropylmethylcellulose (gipromelloza) 6 cps, iron oxide red (E172), iron oxide yellow (E172), titanium dioxide (E171).

A set of tablets: The tablets of white or almost white, round, ploskotsilindricheskie, with beveled and scored (7 pcs. In blister).

1 tab. amlodipine (in the form bezilata) 5 mg.

Excipients: lactose, microcrystalline cellulose, calcium stearate, sodium croscarmellose (primelloza), colloidal silicon dioxide (Aerosil).

Coated tablets pale-red, oval, biconvex, engraved on one side "CIL 2,5", with risks - on the other side (7 pcs. In blister).

1 tab. cilazapril (in the form of monohydrate) 2.5 mg.

Excipients: lactose, corn starch, hydroxypropylmethylcellulose (gipromelloza) 3 cps, talc (sodium hydrosilicate), sodium stearyl fumarate.

The composition of the shell: hydroxypropylmethylcellulose (gipromelloza) 6 cps, iron oxide red (E172), iron oxide yellow (E172), titanium dioxide (E171).

Clinico-pharmacological group: antihypertensive drugs.

Pharmacological action

Amlodipine - calcium channel blockers II generation dihydropyridine derivative. Has antianginal and hypotensive action. Communicating with the dihydropyridine receptors, blocking calcium channels, reduces the transmembrane passage of calcium ions into the cell (to a greater extent in vascular smooth muscle cells than in cardiomyocytes).

Antianginal due to increased coronary and peripheral arteries and arterioles: angina reduces the severity of myocardial ischemia; expanding peifericheskie arterioles reduces TPVR, reduces preload on the heart, reducing myocardial oxygen demand.

Expanding the major coronary arteries and arterioles in the unaltered and ischemic myocardial zones, increases the oxygen supply to the myocardium (especially in vasospastic angina), prevents the development of constriction of the coronary arteries (including those caused by smoking). In patients with angina single daily dose increases the run-time physical activity slows the development of angina and coronary segment depression ST, reduces the frequency of angina attacks and nitroglycerin consumption. Has a long dose-dependent hypotensive effect.

Hypotensive effect due to the direct vasodilating effect on vascular smooth muscle.

When hypertension single dose provides klignicheski significant decrease in blood pressure within 24 hours (in the supine position and standing). There is no sharp decline in blood pressure, reduce exercise tolerance, left ventricular ejection fraction.

Reduces the degree of hypertrophy of the left ventricle, has antiateroskleroticheskoe and cardioprotective effect in ischemic heart disease. It has no effect on myocardial contractility and conductivity, does not cause refletornogo increase in heart rate, inhibits platelet aggregation, improves glomerular filtration rate, has a weak natriuretic effect. In diabetic nephropathy does not increase the severity of microalbuminuria. No adverse effects on metabolism and plasma lipids.

Time of effect - 2-4 hours, duration of effect - 24 hours

Cilazapril is a prodrug, rapidly converted in the body in an active form - tsilazaprilat - a specific long-acting ACE inhibitor that blocks the conversion of inactive angiotensin I to angiotensin II, which has a marked vasoconstrictor effect.

In recommended doses, the effect of cilazapril in patients with hypertension and patients with chronic heart failure remains Mr. 24 hours in patients with normal renal function during treatment tsilazaprilom concentration of potassium in the blood serum usually remains within normal limits. Patients simultaneously receiving Potassium-sparing diuretics may increase potassium.

When hypertension reduced systolic and diastolic BP, as in the "standing", and in the "lying down", usually without orthostatic reactions. Cilazapril is effective at all stages of hypertension and renal hypertension. Reflex tachycardia does not occur, although they may see minor changes in heart rate with no clinical significance. In some patients, blood pressure reduction may decrease the time of the next treatment. With long-term treatment of antihypertensive effect cilazapril saved.

After the sudden withdrawal of the drug rapidly raise blood pressure does not occur. In hypertensive patients with concomitant renal failure secondary to severe, glomerular filtration rate and renal blood flow in the treatment of tsilazaprilom usually do not change, despite the clinically significant blood pressure reduction. Antihypertensive effect of cilazapril (as the use of other ACE inhibitors) in patients blacks may be less pronounced than patients of other races. If, however, cilazapril is used in combination with hydrochlorothiazide, the differences in the effect of the drug in patients of different races is not observed.

In recommended doses, antihypertensive effects in hypertensive patients and patients with chronic heart failure up to 24 hours after oral antihypertensive effect of cilazapril typically appears during the first hour and reaches a maximum after 3-7 hours

Statement
hypertension.

Dosage regimen

Is the inside in the morning, while 1 tab. Containing amlodipine (5mg) and 1/2-1 tab. Containing cilazapril (1.25-2.5 mg). Depending on the dynamics of the blood pressure of both components in these doses can be taken 2 times per day.

The maximum dose of amlodipine - 10 mg, cilazapril - 5 mg.

Side effect

Amlodipine
Since the cardiovascular system: heart rate, shortness of breath, marked reduction of blood pressure, syncope, vasculitis, edema (swelling of the ankles and feet), a rush of blood to face, seldom - disturbances of the heart of Rome (bradycardia, ventricular tachycardia, atrial flutter), pain in chest Cage, orthostatic hypotension, in some cases - the development or exacerbation of heart failure, arrythmia, migraines.
From the side of the central nervous system and peripheral nervous system: headache, dizziness, fatigue, drowsiness, mood changes, seizures, rare - loss of consciousness, hypesthesia, nervousness, paresthesia, tremor, vertigo, asthenia, malaise, insomnia, depression, unusual dreams, and in particular cases - ataxia, apathy, agitation, amnesia.
On the part of the digestive system: nausea, vomiting, epigastric pain, rarely - increased activity of hepatic transaminases and jaundice (due to cholestasis), pancreatitis, dry mouth, flatulence, gingival hyperplasia, constipation or diarrhea, and in some cases - gastritis, increased appetite.
From the urinary system: rarely - thamuria, tenesmus, nocturia, and in some cases - dysuria, polyuria.
On the part of the reproductive system: rarely - violation of sexual function (including reduction of potency), gynecomastia. Dermatological reactions: in some cases - dermatoxerasia, alopecia, dermatitis, purpura, skin discoloration. Allergic reactions: itching, rash (including erythematous, maculopapular rash, urticaria, angioedema).
On the part of the musculoskeletal system: rarely - arthralgia, arthrosis, myalgia (with prolonged use), back pain, in some cases - myasthenia gravis.
On the part of the respiratory system: rarely - dyspnea, epistaxis, and in some cases - cough, rhinitis. On the part of metabolism: rarely - poliurikemiya, increase / decrease in body weight, hyperglycemia, increased sweating, thirst.
On the part of the hemopoietic system: rarely - thrombocytopenia, leukopenia.
From the sensory organs: rarely - visual impairment, diplopia, conjunctivitis, eye pain, ringing in the ears, in some cases - parosmiya, breach of taste, breach of accommodation, xerophthalmia. Other: in some cases - a cold clammy sweat.

Cilazapril
Since the cardiovascular system: less than 2% - marked reduction of blood pressure, weakness. In the application of ACE inhibitors in some cases - symptomatic hypotension, especially in patients with hyponatremia and hypovolemia caused by vomiting, diarrhea, previous treatment with diuretics, salt-free diet or dialysis.
From the central nervous system and peripheral nervous systems: common - headache, dizziness.
On the part of the digestive system: less than 2% - dyspepsia, and in some cases - pancreatitis, sometimes with fatal consequences.
From the urinary system: rarely - a small, mostly reversible increases in creatinine and urea nitrogen in serum (primarily in patients with renal artery stenosis or renal failure, but they are also observed in patients with normal renal function, especially for those who simultaneously receive diuretics).

In patients whose renal function depends mainly on the renin-angiotensin-aldosterone system, such as severe heart failure, with renal artery stenosis and other kidney diseases, treatment tsilazaprilom (as well as other ACE inhibitors) can lead to increased concentrations of nitrogen blood urea and serum creatinine. Although after the abolition of cilazapril and / or diuretics, these changes are usually reversible, described cases of severe renal dysfunction and, rarely - acute renal failure. Dermatological reactions: less than 2% - a rash. Allergic reactions: seldom - angioedema with the spread on the face, lips, tongue, glottis and / or larynx (required immediate removal of the drug and the appointment of appropriate therapy).
On the part of the respiratory system: less than 2% - cough.
On the part of the hemopoietic system: possible decrease in the level of hemoglobin, hematocrit and / or leukocytes.

The causal relationship of these disorders with reception cilazapril not installed.

Contraindications

Amlodipine - pronounced arterial hypotension;
collapse;
cardiogenic shock;
Pregnancy
lactation;
childhood and adolescence to 18 years (effectiveness and safety have not been established);
Hypersensitivity to amlodipine and other derivatives of dihydropyridine.

With careful use disorders of liver function, SSS (pronounced bradycardia, tahikrdiya), chronic heart failure in decompensated, with mild or moderate degree of arterial hypotension, aortic stenosis, mitral stenosis, hypertrophic obstructive cardiomyopathy, acute myocardial infarction (in 1 month after it), diabetes mellitus, lipid profile, in elderly patients.

Cilazapril - a history of angioedema (including hereditary, idiopathic, and angioedema due to the application earlier than other ACE inhibitors);
bilateral renal artery stenosis or stenosis of the artery of a sole kidney;
hyperkalaemia;
porphyria;
Pregnancy
lactation;
hemodialysis through a high-performance membranes poliakrilonitritmetallilsulfata (eg, AN69), gemofiltatsiya, LDL-apheresis.

With care use in patients with chronic renal failure (proteinuria over 1 g / day), pronounced circulatory failure, hypotension, mitral stenosis, aortic stenosis, myocardial ischemia, the inhibition of bone marrow hemopoiesis, the state after a kidney transplant, patients are on hemodialysis , diabetes, gout, hyperuricemia, a diet with restriction of salt, liver cirrhosis, conditions, soprovozhdayushihsya decrease in the bcc (including diarrhea, vomiting), in COPD patients under age 18 (safety and efficacy of not installed).

Pregnancy and lactation

The drug is contraindicated during pregnancy and lactation.

Application for violations of liver function

Precautions to apply for violations of liver function.

Application for violations of renal function

Patients with renal insufficiency may have to decrease the dose depending on the spacecraft. In renal insufficiency, renal function should be monitored in the first weeks of therapy.

Cautions

Amlodipine

In the period of treatment necessary to control body weight, sodium intake, to appoint an appropriate diet. Necessary to maintain dental hygiene and frequent visits to the dentist (to prevent soreness, bleeding and gingival hyperplasia).

Dosing regimens for elderly patients is the same as for patients of other age groups. With increasing doses must be carefully monitored in elderly patients. Despite the lack of slow calcium channel blocker withdrawal syndrome, before the cessation of treatment is recommended a gradual reduction in dose. Амлодипин не влияет на плазменные концентрации калия, глюкозы, триглицеридов, общего холестерина, ЛПНП, мочевой кислоты, креатинина и азота мочевины.

Effects on ability to drive vehicles and management mechanisms

Not reported on the effect of amlodipine on the ability to drive vehicles or operate machinery. Nevertheless, in some patients, mainly at the beginning of treatment may occur drowsiness and dizziness. When they occur, the patient must observe special precautionary measures while driving and using machinery.

Cilazapril

Cilazapril (like other ACE inhibitors) should be carefully be considered in patients with aortic stenosis. In the case of acute arterial hypotension the patient should be put horizontally in which case you may need an infusion of saline or drug that enhances the BCC. After recovery BCC tsilazaprilom treatment can continue.

However, if symptoms do not disappear, should reduce the dose or cancel the drug. BP may decrease significantly in patients with chronic heart failure receiving ACE inhibitors.

However, in clinical studies in which patients with chronic heart failure taking cilazapril at a dose of 500 mg, symptoms of arterial hypotension does not occur. Arterial hypotension can cause the application of ACE inhibitors during surgery in combination with anesthetics, which also has hypotensive action. In such cases, it can be shown by an increase in BCC in / infusion or - if the measure is ineffective - infusion of angiotensin II.

Patients with renal insufficiency may have to decrease the dose depending on the spacecraft.

In renal insufficiency, and severe heart failure need to monitor renal function in the first weeks of therapy. The simultaneous use of potassium-sparing diuretics may cause an increase in the level of potassium in the blood serum, especially in patients with renal insufficiency. Therefore, if shown the simultaneous use of these drugs in early treatment tsilazaprilom their dose should be reduced by carefully monitoring the concentration of potassium in the blood serum and kidney function.

Hemodialysis via high-performance membranes poliakrilopitritmetallilsulfata (eg, AN69), hemofiltration, or LDL-apheresis may cause patients receiving ACE inhibitors, including cilazapril, anaphylaxis or anaphylactoid reactions including life-threatening shock.

The mechanism of this phenomenon is not known exactly. Above procedures in these patients should be avoided. Anaphylactic reactions may occur in patients undergoing hyposensitization with wasp or bee venom and receiving both an ACE inhibitor. For this reason, reception cilazapril should be discontinued prior to hyposensitization. In addition, in this situation cilazapril can not replace that beta-blockers.

Applying of ACE inhibitors in patients with diabetes may potentiate the action of oral hypoglycemic drugs.

Overdose

Amlodipine

Symptoms: marked reduction of blood pressure, tachycardia, excessive peripheral vasodilatation. Treatment: gastric lavage, the appointment of activated carbon to maintain the function of the cardiovascular system, the control performance of the heart and lungs, an elevated position of the limbs, control of BCC and diuresis to restore vascular tone - the use of vasoconstrictive drugs (if no contraindications to their destination) to address effects of the blockade of calcium channels - in / at the introduction of calcium gluconate. Hemodialysis is ineffective.

Cilazapril

Data on overdose is limited. In healthy volunteers who received cilazapril in single doses up to 160 mg, undesirable effects on blood pressure were noted. Symptoms: most likely - a significant reduction in blood pressure. Treatment: Increase in BCC. According to the testimony tsilazaprilat can be partially removed from the body by hemodialysis.

Drug Interactions

Amlodipine

Inhibitors of microsomal oxidation increase the concentration of amlodipine in plasma, increasing the risk of side effects, and inducers of microsomal liver enzymes decrease. The hypotensive effect is reduced by the simultaneous use of NSAIDs, especially indomethacin (sodium retention and the blockade of prostaglandin synthesis by the kidneys), alpha-adrenostimulyatorov, estrogens (sodium retention), with simpatomimetkami. Thiazide and loop "diuretics, beta-blockers, verapamil, ACE inhibitors and nitrates increase antianginal and hypotensive effects. Amiodarone, quinidine, alpha 1-blockers, antipsychotic means (neuroleptics) and blockers of slow calcium channels may increase the hypotensive effect.

No effect on the pharmacokinetic parameters of digoxin and warfarin. Cimetidine does not affect farmakokinetku amlodipine. At simultaneous application with preparatmi lithium neurotoxicity may be increased manifestations (nausea, vomiting, diarrhea, ataxia, tremor, tinnitus). Calcium may decrease the effectiveness of blockers of slow calcium channels. Procainamide, quinidine and other drugs causing prolongation of the interval QT, reinforce the negative inotropic effect and may increase the risk of significant lengthening of the interval QT. Grapefruit juice can reduce the concentration of amlodipine in plasma, but this reduction is so small that no significant influence on the effect of amlodipine.

Cilazapril

When used in combination with other antihypertensive drugs may be additive effects and increased risk of arterial hypotension. Cilazapril is used concurrently with digoxin, nitrates, furosemide, thiazide, anticoagulants kumarinovgo some blockers and histamine H2-receptors.

This increase in digoxin concentration in blood plasma, as well as other clinically significant pharmacokinetic interaction or not observed. Combined use of potassium-sparing diuretics with tsilazaprilom may lead to an increase in potassium in the blood serum, especially in patients with renal insufficiency.

Application of cilazapril, like other ACE with NSAIDs may reduce hypotensive effects of the drug. This is not observed in patients treated with cilazapril to the appointment of NSAIDs.

Terms and Conditions of storage

List B. The drug should be stored out of reach of children, dry, dark place at temperatures not above 25 ° C. Shelf life - 3 years