Кардил®

General characteristics. Structure:

Active ingredient: 60 mg of diltiazem of a hydrochloride.

Excipients: lactoses monohydrate, the castor oil hydrogenated of aluminum the oxide hydrated, polyacrylate of disperse 30%, talc, magnesium stearate, a gipromeloza of 6 cps, sucrose, glycerin of 85%, titanium dioxide (Е 171), polysorbate 80.

Diltiazem has clinical performance at treatment of stenocardia, arterial hypertension and certain kinds of arrhythmias. Diltiazem possesses anti-hypertensive action that is shown by decrease in the systolic and diastolic ABP. Reducing the ABP, diltiazem does not cause reflex tachycardia.

Pharmacological properties:

Pharmacodynamics. Diltiazem is the antagonist of calcium ions of group of derivatives of a benzotiazepin. Reduces receipt of calcium ions through slow calcium channels of a membrane in cardiomyocytes and smooth muscle cells. Has anti-anginal, hypotensive and antiarrhytmic effect.

The action mechanism at stenocardia is caused by expansion of coronary vessels and decrease in an afterload on a myocardium. It is effective at treatment of stable stenocardia that at objective assessment is expressed in increase in duration of the period during which there was no ST segment depression when performing an exercise stress, and at value judgment – in decrease in frequency of attacks of stenocardia and need of reception of nitroglycerine. Efficiency of effect of diltiazem at treatment of unstable stenocardia is approximately equivalent to effect of nifedipine or verapamil, and the frequency of development of side effects at treatment by diltiazem is significantly lower, than at use of the specified drugs.

Diltiazem has hypotensive effect, reducing both systolic, and diastolic arterial pressure, without exerting at the same time impacts on the normal level of arterial pressure. Unlike the majority of peripheral vazodilatator, does not cause development of reflex tachycardia. Despite weak negative inotropic effect of drug, at its use the stroke output of heart and fraction of emission of a left ventricle does not decrease. At prolonged systematic use diltiazem can cause regression of a hypertrophy of a left ventricle. Drug can be used for monotherapy or with other antihypertensives as a part of a combination therapy, especially with diuretics and APF inhibitors. Diltiazem it is possible to appoint when use of blockers of β-adrenoceptors is contraindicated (treatment of patients with bronchial asthma, a diabetes mellitus or peripheral angiopatiya). Diltiazem does not make negative impact on a lipidic range of a blood plasma.

Drug oppresses calcic current in cells sinus and AV nodes, having therapeutic effect at supraventricular arrhythmias.

Pharmacokinetics. Diltiazem is completely soaked up from digestive tract after oral administration. At the first passing through a liver absolute bioavailability of diltiazem makes about 40% (individual variations of 24-74%). Bioavailability is identical to all dosage forms and is not dozozavisimy at reception of clinical doses. The maximum concentration in a blood plasma is reached approximately in 3-4 hours after reception of tablets of 60 mg (at reception of a single dose of 60 mg the maximum concentration makes 39-120 ng/ml).

About 80% of diltiazem contact proteins of plasma, albumine only about 40%. Diltiazem is effectively distributed in various fabrics. The volume of distribution of drug makes 5 l/kg, and the volume of the central vessel makes 0,9 l/kg. In blood drug is quickly distributed between plasma and blood cells. At reception of a dose of 60 mg 3 times a day the stable state is reached in 3 days. At a dose of 120-300 mg/day the stable condition of concentration in plasma fluctuates from 20 to 200 ng/ml (the minimum therapeutic concentration – about 70-100 ng/ml).

Diltiazem is metabolized by means of enzyme of CYP3A4 cytochrome and is R-glycoprotein substrate. Diltiazem is also CYP3A4 cytochrome enzyme inhibitor. In the first phase metabolism is carried out by means of deacetylation, N-demethylation and O-demethylation. Deatsetildiltiazem is an active metabolite (40-50% of activity of diltiazem); its concentration makes about 15-35% of that of diltiazem. The Pharmakodinamichesky importance of a metabolite is minimum.

Only 0,1-4% of diltiazem are removed in not changed view with urine; therefore, elimination of drug is carried out preferential in the form of metabolites. The general clearance of diltiazem makes 0,7-1,3 l/kg/h. In urine five not conjugated metabolites are found; two of them meet as well in the conjugated form. Elimination of diltiazem corresponds to single-phase kinetics. According to three-chambered model, the elimination half-life makes about 0,1 hours for the most bystry phase of distribution, 2,1 hours – for an average phase and 9,8 hours – for a final phase of elimination. T1/2 makes 4-7 hours.

At prolonged use changes in diltiazem pharmacokinetics are not revealed. Drug does not collect in an organism and does not induce own metabolism. The drug pharmacokinetics at patients with stenocardia and an impaired renal function does not differ from that at healthy volunteers

Indications to use:

Stenocardia. Arterial hypertension. Printsmetall stenocardia. For decrease in a ventricular rhythm at fibrillation of auricles.

Route of administration and doses:

Drug is used orally. The pill should be taken whole. Doses of drug select individually.

Average daily dose for adults − 180-240 mg, are also applied doses to 480 mg a day.

Usually initial dose makes 60 mg 3-4 times a day. The dose can be increased according to therapeutic effect to 120 mg 3 times a day.

At elderly patients or patients with the broken function of a liver it is recommended to begin treatment with lower dose – 30 mg 3-4 times a day.

Features of use:

Drug has to with care use to patients with heavy abnormal liver functions and kidneys. The clearance of diltiazem can be reduced at elderly patients.

Drug should be used with care the patient on an acute porphyria.

Patients need to apply diltiazem with care with insufficiency of the left auricle, bradycardia, lengthening of an interval of PQ and a stenosis of an aorta. It is also necessary to be careful during combined use of drug together with β-blockers or other drugs which reduce sokratitelny ability of heart or AV-conductivity.

Antagonists of calcium can exponentiate effects of anesthetics on formation of cordial impulses, influence conductivity, a sokratitelnost and a vascular tone.

Antagonists of calcium can promote decrease in male fertility, it needs to be taken in attention if infertility of not clear etiology is diagnosed for the patient accepting antagonists of calcium. This effect disappears at the therapy termination.

Absorption of diltiazem can be reduced at patients with long diarrhea (for example, at ulcer colitis or a disease Krone).

Drug contains lactose (67,4 mg / a tablet) and to a tsukroz (0,50 mg / a tablet). At rare hereditary intolerance of a galactose or fructose, a lactose intolerance of Lapp or malabsorption of a glucose/galactose, or tsukrazo-izomaltazny insufficiency use of drug is not shown.

Ability to influence speed of response at control of motor transport and work with other mechanisms.

At control of motor transport or work with other mechanisms it is necessary to consider that in an initiation of treatment drug the lowering of arterial pressure, dizziness and feeling of fatigue can sometimes take place. At such moments it is necessary to abstain from control of motor transport or work with other mechanisms.

Diltiazem is not primenenyat during pregnancy. Drug is not used during feeding by a breast as diltiazem is excreted in breast milk.

In need of drug use feeding by a breast should be stopped.

Children. Use of drug of this category of patients is not shown.

Side effects:

Frustration of cardiovascular system. Often: AV blockade of the I degree, sinus bradycardia. Seldom: bradycardia, AV blockade of the II-III degree, the termination of activity of a sinus node, an aggravation of symptoms of stenocardia, congestive heart failure, arterial hypotension, tachycardia, heartbeat, arrhythmia, an extrasystole, a syncope, rushes of blood to the person, peripheral hypostases, a syncope.

Disorders of a digestive tract. Often: nausea, a lock, diarrhea, dryness in an oral cavity and a throat. Seldom: anorexia, dyspepsia, vomiting, increase in body weight, ulitis, hyperplasia of gums.

Frustration from skin. Often: dieback, itch. Seldom: Stephen-Johnson's syndrome, a Quincke's disease, a toxic epidermal necrosis, exfoliative dermatitis, a lupus erythematosus, a petechia, photosensitivity, a small tortoiseshell, allergic reactions of skin, including a multiformny eritrema, a vasculitis, a lymphadenopathy, an eosinophilia. Dermatological manifestations can be temporary and can disappear, despite further reception of diltiazem. If dermatological reactions do not disappear, administration of drug should be stopped.

Gepatobilliarny frustration. Often: increase in levels of aminotransferases.
Seldom: granulematozny hepatitis, increase in level of alkaline phosphatases, SGOT, SGPT, LDH, hyperglycemia.

Frustration of the hemopoietic and lymphatic systems. Seldom: thrombocytopenia, leukopenia, lengthening of a bleeding time.

Psychiatric frustration. Seldom: confusion of consciousness, amnesia, depression, hallucinations, sleeplessness, nervousness, change of the personality, disturbance of taste and sense of smell.

Frustration of a nervous system. Seldom: gait disturbance, paresthesia, drowsiness, tremor, adynamy.

Frustration of an organ of sight. Seldom: amblyopia, irritation of eyes.

Frustration of an acoustic organ. Seldom: sonitus.

Frustration of musculoskeletal system. Seldom: ostealgia and joints, mialgiya.

Respiratory frustration. Seldom: a zadyshka, nasal bleeding, stagnation in a nose.

Disorders of an urinary system. Seldom: nocturia, polyuria, increase in level of a creatine kinase.

Frustration to reproductive system: Seldom: gynecomastia, sexual frustration.

Interaction with other medicines:

Potentiation of effect of other anti-hypertensive drugs is possible. Simultaneous use of drug with β-blockers, Amiodaronum or digoxin, can suppress AV conductivity and increase risk of development of bradycardia. Diltiazem can increase the oppressing action by heart of a halothane and izofluran. Intravenous use of salts of calcium reduces the pharmacological response to diltiazem use.

Diltiazem is initially metabolized via the CYP3A4 cytochrome enzyme mechanism. Cimetidinum as inhibitor of enzyme of CYP3A4 cytochrome can increase concentration of diltiazem in a blood plasma. Potentiation of effect of diltiazem at simultaneous use with macroleads, antifungal means, derivatives of an azol, fluoxetine, Tamoxifenum, nifedipine and inhibitors of HIV protease is possible. At simultaneous use of drugs which induce CYP3A4 cytochrome, for example, carbamazepine морицизин, phenobarbital and rifampicin, diltiazem metabolism acceleration is possible.

Diltiazem inhibits metabolism of drugs that metibolizirutsya by means of enzyme of CYP3A4 cytochrome and the R-glycoprotein. Diltiazem is also substrate for enzyme of CYP3A4 cytochrome and the R-glycoprotein. It is necessary to watch concentration in a blood plasma and side effects at use of the following drugs: carbamazepine, Phenytoinum, cyclosporine, сиролимус, такролимус, digoxin, digitoxin, Methylprednisolonum and theophylline. At simultaneous use of diltiazem and inhibitors of HMG-CoA reductase that are metabolized by means of CYP3A4 cytochrome enzyme, for example, симвастатин, аторвастатин, ловастатин and серивастатин, doses of the last have to be lowered for prevention of development of a rabdomioliz and injuries of a liver. Drug does not influence clearance of a pravastatin and fluvastatin.

At simultaneous use of diltiazem and nifedipine, a kvinidin, propranolol, a metoprolol, Imipraminum, nortriptilin, sildenafil, buspiron, midazolam, a triazolam, diazepam, an alprazolam, alfentanil and a tsisapirid, concentration of the last in a blood plasma can increase.

At simultaneous use of drugs of lithium and diltiazem the neurotoxicity therefore it is necessary to make carefully monitoring of concentration of lithium in blood serum can develop.

Contraindications:

Sick sinus syndrome.

Atrioventricular block of the II-III degree (except for patients with the functioning pacemaker).

Arterial hypotension. (systolic arterial pressure <90 mm Hg)

The expressed bradycardia (<50 уд. / mines).

WPW-syndrome.

Dekompensirovanny heart failure.

Acute myocardial infarction with complications.

Cardiogenic shock owing to intoxication digitalis drugs.

The known hypersensitivity to derivatives of a benzotiazepin.

Period of pregnancy or feeding by a breast.

Overdose:

Diltiazem in doses of 0,9-1,8 g causes intoxication of average and heavy degree in adults. Elderly patients have a dose of 2,6 g and a dose of 5,9 g at adults the dose of 10,8 g – very serious can be the cause of serious intoxication, and.

Symptoms of poisoning arise on average in 8 hours after administration of drug and include fatigue, irritation, drowsiness, bradycardia, an atrioventricular block, a cardiac standstill, hypotension, a hypothermia, a hyperglycemia, nausea.

There is no specific antidote. At treatment of intoxication use a gastric lavage and absorbent carbon. Monitoring of breath, hemodynamic indicators, electrolytic and acid-base balance is necessary.

At hypotension use intravenous administration of a dopamine or Calcii chloridum; at bradycardia and in rare instances of an atrioventricular block – intravenous administration of atropine or use of an electrocardiostimulator. In other cases a symptomatic treatment.

Storage conditions:

To store at a temperature of 15-25 °C in original packaging. To store in the place, unavailable to children.

Issue conditions:

According to the recipe

Packaging:

On 30 or 100 tablets in a bottle; on 1 bottle in cardboard packaging.