Diltiazem-Teva - instructions for use, dose, side effects, contraindications

Excipients: povidone, hypromellose, silicon colloidal dioxide, hydrogenated vegetable oil, magnesium stearate, giprolase, macrogol 4000, macrogol 6000, talc.

Each 240 mg tablet contains:

Active ingredient: diltiazema hydrochloride 240 mg

Auxiliary substances: methacrylic acid and ethacrylate copolymer, hypromellose, silicon colloidal dioxide, hydrogenated vegetable oil, magnesium stearate, giproloza, macrogol 4000, macrogol 6000, talc.

Description:

Round tablets of biconvex form, covered with a film shell of white or almost white color with engraving "120" or "240" on one side and "D" on the other.

Pharmacotherapeutic group:blocker of "slow" calcium channels.

ATX: & nbsp

C.08.D.B.01 Diltiazem

C.05.A.E.03 Diltiazem

Pharmacodynamics:

Diltiazem is a benzothiazepine derivative, a blocker of "slow" calcium channels (BCCC), reduces the intracellular content of calcium ions in cardiomyocytes and smooth muscle cells, dilates coronary and peripheral arteries and arterioles, reduces overall peripheral vascular resistance (OPSS), smooth muscle tone, strengthens coronary , cerebral and renal blood flow, reduces the heart rate (HR), has antiarrhythmic, antianginal and antihypertensive activity.

Antiarrhythmic action is caused by the suppression of the ionized calcium transport in the heart tissues, which leads to an increase in the effective refractory period and prolongation of the time spent in the atrioventricular (AV) node (has clinical significance in patients with sinus node weakness syndrome). In elderly patients, as well as in persons suffering from a syndrome of weakness of the sinus node, it may interfere with the generation of a pulse in the sinus node and cause a sinoatrial (SA) blockade.The normal atrial action potential and the rate of intraventricular conduction do not change, but with a decrease in the amplitude of atrial contraction, the rate of depolarization and the rate of conduction decrease. Anterograde effective refractory period in additional bypass beams of conduction may be shortened.

Antianginal action is caused by the expansion of peripheral arteries and arterioles and a decrease in systemic arterial pressure (afterload), which leads to a decrease in the intramyocardial stress of the heart walls and its oxygen demand. In concentrations that do not lead to the appearance of a negative inotropic effect, it causes relaxation of the smooth muscles of the coronary vessels.

Hypotensive effect is caused by dilatation of resistive vessels and a decrease in OPSS. The degree of decrease in blood pressure (BP) correlates with the initial tone of the arteries (in patients with normal arterial tone, there is a minimal effect on blood pressure level). Reduction of blood pressure is noted in both the "lying" and "standing" positions. Virtually does not cause postural arterial hypotension and reflex tachycardia.Does not affect or slightly reduces the maximum heart rate with exercise. Long-term therapy does not lead to hyperkatecholamineemia, an increase in the activity of the renin-angiotensin-aldosterone system. Reduces the renal and peripheral effects of angiotensin II. Improves diastolic relaxation of the myocardium (including in patients with obstructive hypertrophic cardiomyopathy), reduces platelet aggregation.

Has a minimal effect on the smooth muscles of the gastrointestinal tract (GIT). During a long (8 months) therapy, tolerance does not develop. Does not affect the lipid profile of the blood.

It is able to cause regression of left ventricular hypertrophy in patients with arterial hypertension.

The maximum severity of the hypotensive effect is achieved within 2 weeks.

Pharmacokinetics:

Diltiazem-Teva in a dosage of 120 mg and 240 mg is a prolonged form, which ensures a sustained release and the entry of the active substance into the blood. After ingestion, the active substance of the preparation is well absorbed from the digestive tract (90%), but because of the pronounced effect of "first passage" through the liver, bioavailability is only 40% (with prolonged use and in increasing doses, it may increase).The time to reach the maximum concentration (TCam) with ingestion is 6-14 hours. Communication with blood plasma proteins is 70-80% (with albumins - 35-40%). Intensively metabolized in the liver by deacetylation and demethylation (with the participation of cytochrome CYP3A4, CYP_3A5and CYP_3A7) from the formation of an active metabolite deacetylldithiasem, which is determined in plasma 5-10 times less than the initial preparation, and has a 2-4 times less activity. The therapeutic concentration is 20-40 ng / ml.

The half-life (T_1/2) with the intake of long-acting tablets 5-8 hours. It is excreted with bile (65%) and kidneys (35%, including 2-4% unchanged). Penetrates into breast milk.

In patients with hepatic insufficiency lengthens T_1/2 and bioavailability increases. In patients with angina and impaired renal function, the pharmacokinetics of diltiazem does not change. In the elderly, the clearance of diltiazem can decrease.

It is not excreted in hemodialysis and peritoneal dialysis.

Indications:

- prevention of angina attacks (including with Prinzmetal angina pectoris, as well as in other cases when beta-blockers are contraindicated);

- treatment of arterial hypertension;

Contraindications:

Hypersensitivity to the drug and to other derivatives of benzothiazepine, SA blockade, AV blockade II-III degree (except for patients with pacemaker), Wolff-Parkinson-White syndrome, Laun-Ganong-Levin syndrome in combination with flutter or atrial fibrillation with a pacemaker), chronic heart failure (in the stage of decompensation), acute heart failure, myocardial infarction with signs of left ventricular failure, cardiogenic shock, sinus node weakness syndrome (without neniya pacemaker), marked hypotension (systolic blood pressure less than 90 mmHg), bradycardia, ventricular tachycardia with a wide QRS complex.

Pregnancy, lactation, age under 18 years (efficacy and safety not established).

Carefully:

Use with caution in patients with severe impairment of liver and kidney function, acute porphyria, severe stenosis of the aortic aorta, mild to moderate arterial hypotension, AV blockade of the first degree, concomitant administration with beta-blockers or digoxin, chronic heart failure, with a tendency to bradycardia, in old age.

Dosing and Administration:

Tablets are taken before meals, swallowed whole without chewing and drinking a small amount of water.

The dose of the drug should be selected for each patient individually.

prolonged forms of treatment is initiated with a dose of 120 mg (Teva-Diltiazem 120 mg), 1 time per day or, if desired, 240 mg (Teva-Diltiazem 240 mg), 1 time per day.

With a good therapeutic response every 2-3 months may reduce the dose (use of the drug "Diltiazem-Teva" in other dosages).

Side effects:

From the side of the cardiovascular system: asymptomatic decrease blood pressure, rarely - bradycardia (rarely 50 beats per minute), ventricular arrythmia, development characteristics (widening) chronic heart failure, SA blockade AV block (of varying severity), a marked reduction of blood pressure, fainting, skin redness, rarely - angina , arrhythmia (including atrial and ventricular fibrillation), tachycardia, dyspnea, peripheral edema. The severity of side effects is dose-dependent.

From the side of the digestive tract: dry mouth, increased appetite, vomiting, nausea, heartburn, constipation or diarrhea,abdominal pain, impaired liver function (increased activity of "liver" transaminases); gingival hyperplasia (bleeding, soreness, swelling), paralytic obstruction of the intestine.

From the central nervous system and sensory organs: headache, general weakness, asthenia, fatigue, anxiety, dizziness, drowsiness or insomnia, depression, condition of pathological fear, extrapyramidal disorders, parkinsonism (ataxia, "masky" face, shuffling gait, stiffness of hands or feet, trembling of hands and fingers, difficulty swallowing).

When used in high doses - paresthesia, visual impairment (transient blindness).

Allergic reactions: skin rash, itching, congestion. Very rarely - multiforme exudative erythema (including Stevens-Johnson syndrome).

Other: increased photosensitivity, very rarely taking the drug leads to an increase in the activity of "hepatic" enzymes in the blood serum, hypercreatininaemia. When used in high doses - pulmonary edema (difficulty breathing, cough, stridorous dyspneahanie); rarely - thrombocytopenia, agranulocytosis, galactorrhea, weight gain.

With a sharp withdrawal of the drug can develop a syndrome of "withdrawal" with concomitant tachycardia, hypertension and worsening of the course of angina.

Overdose:

Symptoms: bradycardia, marked decrease in blood pressure, which results in collapse, AV conduction disorder, confusion, stupor, nausea, vomiting, metabolic acidosis, hyperglycemia, heart failure, cardiogenic shock, asystole.

Treatment: depending on the severity of the overdose. It is necessary to wash the stomach, appoint Activated carbon, further treatment is symptomatic. If necessary, it is recommended that atropine, beta-adrenomimetics, dopamine or dobutamine. If the AV conduction is severe, electrocardiostimulation may be required.

Hemodialysis and peritoneal dialysis are not effective.

Interaction:

Pharmacodynamic. With the simultaneous use of diltiazem with antihypertensive drugs increased hypotensive effect.

With the simultaneous administration of diltiazem and digoxin it is possible to increase the concentration of digoxin in the blood.

With simultaneous reception with antiarrhythmic agents, beta-adrenoblockers, cardiac glycosides, bradycardia may develop, AV conduction slow down, and symptoms of heart failure appear.

When used simultaneously with adenosine increased risk of prolonged bradycardia.

Salicylates additionally inhibited the ability to aggregate platelets.

Ethanol: increased hypotensive effect.

Simultaneous appointment with procainamide, quinidine and other drugs that cause prolongation of the QT interval, increases the risk of its further significant expansion.

Means for inhalation anesthesia (derivatives of hydrocarbons), antipsychotics (neuroleptics), thiazide diuretics and other substances that reduce blood pressure, enhance the hypotensive effect of diltiazem.

Possible simultaneous appointment nitrates (including prolonged forms). Strengthens cardiodepressant action of funds for general anesthesia.

Lithium salts can enhance the neurotoxic effect of diltiazem (nausea, vomiting, diarrhea, ataxia, tremor, tinnitus).

Indomethacin and other non-steroidal anti-inflammatory drugs, glucocorticosteroids and estrogens, as well as sympathomimetics, weaken the hypotensive effect.

Pharmacokinetic. The intake of food increases the absorption and bioavailability of diltiazem by 20-30%.

Simultaneous appointment with cimetidine leads to a significant increase in plasma concentrations of diltiazem, which in turn can lead to the development of its toxic effect on the cardiovascular system.

Diltiazem increases concentration theophylline and carbamazepine in blood plasma (by 40-70%) and increases the risk of their side effects on the nervous system (including ataxia, nystagmus, diplopia, headache, vomiting, confusion).

Diltiazem increases concentration cyclosporine, digoxin (50%), imipramine, lithium and midazolam. With the simultaneous use of diltiazem and cyclosporine in patients after kidney transplantation it is possible to develop intoxication, paresthesia. It is therefore necessary closely monitor the level of plasma concentrations of cyclosporine in this group of patients.

The effect of oral hypoglycemic agents (for example, chlorpropamide and glipizide) is increased.

May increase bioavailability propranolol.

Increases concentration moracisin in the blood plasma.

Phenobarbital, phenytoin, diazepam, rifampicin reduce the concentration of diltiazem.

Increases concentration in the blood quinidine, valproic acid (a dose reduction may be required).

Antiviral drugs: ritonavir can increase plasma concentrations of BCC.

Anxiolytics and hypnotics: diltiazem inhibits the metabolism of midazolam (increases its plasma concentration and increases the severity of sedation).

BCCI: elimination of nifedipine is reduced by diltiazem (plasma concentration is increased).

Diltiazem significantly increases the concentration of lovastatin in blood plasma. It also increases the action of simvastatin, so when using them simultaneously, simvastatin should be lowered. With the simultaneous use of diltiazem with lovastatin and simvastatin, control over patients is necessary because of the possibility of myopathy or rhabdomyolysis.

Special instructions:

Diltiazem with extreme caution is prescribed for patients with AV blockade of I degree and bradycardia.Caution is also needed when appointing patients with a violation of the function of the left ventricle of the heart.

Diltiazem-Teva is cautiously prescribed to patients already taking other medications, in particular, blockers β-adrenergic receptors (treatment of this group of patients should be carried out under the close supervision of the cardiologist). Diltiazem-Teva with caution prescribed to patients with renal or hepatic insufficiency; In this group of patients, if necessary, reduce the prescribed doses of the drug and monitor the content of urea and creatinine. For elderly patients, the dose is selected individually (possibly increasing T_1/2).

Diltiazem, reducing OPSS, can cause a secondary arterial hypotension, in connection with which it is necessary to monitor blood pressure (especially at the beginning of the course treatment, while therapeutic doses are not yet specified).

In case of persistent skin rashes, the drug should be discontinued. If during the therapy the patient is required to undergo surgery under general anesthesia, it is necessary to inform the anesthetist about the nature of the therapy.

Effect on the ability to drive transp. cf. and fur:Until now, it has not been established that taking diltiazem in recommended doses affects the psychomotor activity of the patient. In patients with hypersensitivity, it can (in particular at the beginning of the course of treatment) cause an excessive decrease in blood pressure, dizziness and a transient decrease in the ability to drive vehicles and engage in other potentially dangerous activities requiring increased attention, rapid mental and motor reaction.

Form release / dosage:Tablets of prolonged action, film-coated, 120 mg and 240 mg.

Packaging:

For 10 tablets in a blister of PVC / aluminum foil.

3 blisters together with instructions for use in a cardboard bundle.

Storage conditions:

Store in a dry place at a temperature of no higher than 25 ° C.

Keep out of the reach of children.

Shelf life:

Tablets 120 mg - 4 years.

Tablets 240 mg - 1.5 years.

Do not use after the expiration date stated on the package.

Terms of leave from pharmacies:On prescription

Registration number:LSR-008980/08

Date of registration:17.11.2008

The owner of the registration certificate:Teva Pharmaceutical Enterprises Co., Ltd.Teva Pharmaceutical Enterprises Co., Ltd. Israel

Manufacturer: & nbsp

TEVA Pharmaceutical Industries, Ltd. Israel

Representation: & nbspTeva Teva Israel

Information update date: & nbsp27.12.15

Illustrated instructions

Instructions

Diltiazem Teva (Diltiazem-Teva)