Description of the active substance:
This information is a reference and it is not enough that the drug has been prescribed by a doctor ..
PHARMACHOLOGIC EFFECT
Selective blocker of calcium channels of III class, benzothiazepine derivative. Has antianginal, hypotensive and antiarrhythmic action. Reduces myocardial contractility, slows AV-conduction, decreases heart rate, reduces myocardial oxygen demand, expands coronary arteries, increases coronary blood flow. Reduces the tone of smooth muscles of peripheral arteries and OPSS.
Reduces the intracellular content of calcium ions in cardiomyocytes and smooth muscle cells of blood vessels, lowers heart rate, may have a slight negative inotropic effect, increases coronary, cerebral and renal blood flow. In concentrations in which there is no negative inotropic effect, it causes the relaxation of the smooth muscles of the coronary vessels and the dilatation of both large and small arteries.
The antianginal effect is due to improved blood supply to the myocardium and a decrease in its oxygen demand as a result of decreased OPSS, systemic blood pressure (afterload), a decrease in myocardial tone and an increase in the diastolic left ventricular relaxation time.
The antiarrhythmic effect is due to the suppression of the transport of calcium ions in the heart tissues, which leads to an elongation of the effective refractory period and a slowing down of the AV node (in patients with SSSU, elderly people whose calcium channel blockage can interfere with the generation of a pulse in the sinus node and cause a sinoatrial blockade). The normal atrial action potential or intraventricular conduction does not change (normal sinus rhythm is usually unaffected), but with a decrease in the amplitude of atrial contraction, the rate of depolarization and speed of conduction decrease. Anterograde effective refractory period in additional bypass beams of conduction may be shortened. When parenteral administration causes a rapid transition of paroxysmal supraventricular tachycardia (including associated with additional bypass beams of conduction) into the sinus rhythm, as well as temporary cessation of ventricular tachycardia during flutter or atrial fibrillation.
The hypotensive effect is due to dilatation of the resistive vessels and a decrease in the OPSS. The degree of decrease in blood pressure correlates with its baseline level (with fluctuations in blood pressure within the limits of normal values, a minimal effect on blood pressure is noted). Reduces blood pressure in both horizontal and vertical position. Rarely causes postural arterial hypotension and reflex tachycardia. Does not change or slightly reduces the maximum heart rate under the load.Long-term therapy does not lead to hyperkatecholamineemia, increased activity of RAAS. Reduces the renal and peripheral effects of angiotensin II. Promotes diastolic relaxation of the myocardium with arterial hypertension, ischemic heart disease, hypertrophic obstructive cardiomyopathy, reduces platelet aggregation. It is able to cause regression of left ventricular hypertrophy in patients with arterial hypertension.
Slightly affects the smooth muscles of the gastrointestinal tract. During a long (8 months) therapy does not develop tolerance. Does not affect the lipid profile of the blood.
The beginning and duration of action depends on the dosage form used.
PHARMACOKINETICS
After intake diltiazem almost completely absorbed from the digestive tract. It is subjected to intensive metabolism at the "first passage" through the liver.Bioavailability is about 40%. Concentration in plasma is variable.
Binding to plasma proteins is about 80%. Diltiazem is excreted in breast milk. Intensively metabolized in the liver with the participation of the enzymatic system of cytochrome P 450 . One of the metabolites, desacetylldithiazel, has a 25-50% activity of unchanged substance.
T 1/2 diltiazem is 3-5 hours. It is excreted mainly in the form of metabolites with bile and urine, approximately 2-4% is excreted unchanged in the urine.
Diltiazem is poorly excreted in dialysis.
INDICATIONS
Prevention of angina attacks (including angina pectoris). Arterial hypertension. Prevention of supraventricular arrhythmias (paroxysmal supraventricular tachycardia, atrial fibrillation, atrial flutter, extrasystole).
For intravenous administration: relief of acute attacks of angina, prevention of coronary artery spasm during coronary angiography or coronary artery bypass surgery, paroxysmal ventricular tachycardia, for arresting the frequent rhythm of the ventricles with flicker or atrial flutter (with the exception of WPW syndrome).
DOSING MODE
When administered orally, the initial dose - 60 mg 3 times / day or 90 mg 2 times / day. With insufficient effectiveness, the dose is increased to 180 mg 2 times / day.Prolonged forms are applied 1-2 times / day depending on the dose.
The maximum daily intake for oral administration is 360 mg.
With IV introduction, a single dose of 300 Ојg / kg.
For IV injections, the dose is 2.8-14 Ојg / kg / min. The maximum daily dose is 300 mg.
SIDE EFFECT
From the central nervous system and peripheral nervous system: headache, dizziness, fainting, fatigue, asthenia, sleep disturbances, drowsiness, anxiety, extrapyramidal (parkinsonism) disorders (ataxia, masky face, shuffling gait, stiffness of hands or feet, trembling of hands and fingers, difficulty swallowing), depression; when used in high doses - paresthesia, tremor, visual impairment (transient loss of vision).
From the cardiovascular system: asymptomatic decrease in blood pressure; rarely - angina pectoris, arrhythmia (including flutter and fibrillation of the ventricles), bradycardia (less than 50 beats / min) or tachycardia, AV blockade II and III degree up to asystole, development or worsening of heart failure; when used in high doses and with iv administration - angina, bradycardia, AV blockade, marked decrease in blood pressure, aggravation of chronic heart failure.
On the part of the digestive system: dry mouth, increased appetite, nausea, vomiting, constipation or diarrhea, increased activity of hepatic transaminases, gingival hyperplasia (bleeding, soreness, swelling).
From the hemopoietic system: rarely - thrombocytopenia, agranulocytosis.
Allergic reactions: facial skin hyperemia, skin rash, arthritis, multi-form exudative erythema (including Stevens-Johnson syndrome).
Other: when used in high doses - pulmonary edema (difficulty breathing, cough, stridorous breathing); peripheral edema (edema of the lower limbs - ankles, feet, shins), an increase in the serum creatinine content; rarely - galactorrhea, weight gain.
CONTRAINDICATIONS
Severe bradycardia, AV blockade of II and III degree (except for patients with pacemaker), SSSU, cardiogenic shock, atrial fibrillation with WPW syndrome and Launa-Ganoga-Levina, myocardial infarction with congestive pulmonary events, arterial hypotension, chronic heart failure II B-III stage, acute heart failure, hemodynamically significant aortic stenosis, violations of liver and kidney function, pregnancy, lactation, hypersensitivity to benzothiazepine derivatives.
PREGNANCY AND LACTATION
Contraindicated in pregnancy and lactation (breastfeeding).
In experimental studies , the teratogenic effect of diltiazem was established.
APPLICATION FOR FUNCTIONS OF THE LIVER
Contraindicated in the violation of kidney function. Use with caution in renal failure.
APPLICATION FOR VIOLATIONS OF THE FUNCTION OF KIDNEYS
Contraindicated in the violation of liver function. Use with caution in liver failure.
APPLICATION FOR CHILDREN
Use with caution in children (efficacy and safety of use not investigated).
APPLICATION IN ELDERLY PATIENTS
Use with caution in elderly patients.
SPECIAL INSTRUCTIONS
They are used with caution for AV blockade of I degree, violations of intraventricular conduction, in patients prone to arterial hypotension, chronic heart failure, myocardial infarction with left ventricular failure, ventricular tachycardia with QRS complex expansion, hepatic insufficiency, renal insufficiency, in elderly patients, in children (efficacy and safety of use not investigated).
In / in apply only for emergency therapy, but if necessary, the introduction is possible within a few days. When diltiazem is introduced, careful monitoring of cardiovascular function is necessary. Against the background of a regular intake of beta-blockers should be strictly specified indications for IV diltiazem and apply it only after ECG monitoring in the intensive care unit, while the possible need to use a pacemaker should be considered.
It is not recommended simultaneous use of beta-adrenoblockers and diltiazem for parenteral administration.
Sudden abolition of diltiazem can lead to the development of an anginal attack.
Patients with impaired hepatic and / or renal function and elderly persons require a correction of the dosing regimen.
DRUG INTERACTION
When used simultaneously with beta-blockers (including with propranolol, atenolol, metoprolol, pindolol, sotalol), an additive cardiodepressive effect is possible, along with an increase in antianginal action in most patients. In patients with a previous impairment of left ventricular function or conduction disorders, the risk of developing severe and menacing bradycardia is increased.
Diltiazem inhibits the metabolism of propranolol, metoprolol, but not atenolol.
With simultaneous use with amiodarone, a negative inotropic effect, bradycardia, conduction disturbance, AV blockade is intensified.
Since diltiazem inhibits the isoenzyme CYP3A4, which is involved in the metabolism of atorvastatin, lovastatin and simvastatin, it is theoretically possible drug interactions caused by an increase in the concentrations of statins in blood plasma. The cases of development of rhabdomyolysis are described.
With simultaneous use with buspirone, the concentration of buspirone in the blood plasma increases, its therapeutic and side effects are intensified.
With the simultaneous use of vecuronium chloride, an increase in the duration of neuromuscular blockade is possible.
With simultaneous use with digoxin, digitoxin, an increase in the concentrations of digoxin and digitoxin in the blood plasma is possible.
When used simultaneously with imipramine, the concentration of imipramine in the blood plasma increases and there is a risk of unwanted changes in the ECG.
The cases of an increase in plasma concentrations of trimipramine and nortriptyline with simultaneous application with diltiazem are described.
Diltiazem increases the bioavailability of imipramine by reducing its clearance. Changes in the ECG are due to an increase in the concentration of imipramine in the blood plasma and the additive inhibitory effect of diltiazem and imipramine on AV-conduction. It is believed that diltiazem in the same way interacts with trimipramine and nortriptylin.
With simultaneous use with insulin, a case of decreasing the effectiveness of insulin is described.
Due to the inhibition of metabolism of anticonvulsants in the liver under the influence of diltiazem and decrease in their clearance from the body, it is possible to increase the concentrations of carbamazepine and phenytoin in the blood plasma with the risk of developing toxic effects.
With simultaneous application of lithium carbonate, the cases of the development of an acute syndrome of Parkinsonism, psychosis are described.
With simultaneous use with midazolam, triazolam, the concentration of midazolam and triazolam in the blood plasma increases and their effects are enhanced due to the inhibition of the isoenzyme CYP3A4 under the influence of diltiazem, with the participation of which the metabolism of these benzodiazepines is carried out.
With the simultaneous use of sodium amidotrizoatom may increase the antihypertensive effect diltiazem.
With simultaneous use with sodium nitroprusside, a significant increase in efficacy with controlled arterial hypotension is possible.
At simultaneous application with nifedipine the antihypertensive action amplifies.
Rifampicin induces the activity of liver enzymes, speeding the metabolism of diltiazem, which leads to a decrease in its effectiveness.
With simultaneous use with theophylline, a slight decrease in the metabolism of theophylline in the liver is possible, apparently due to the inhibition of the CYP1A2 isoenzyme under the influence of diltiazem.
With simultaneous use with cisapride, a case of impaired consciousness has been described, apparently due to the pronounced lengthening of the QT interval. It is believed that diltiazem inhibits the activity of the isoenzyme CYP3A4, which leads to an increase in the concentration of cisapride in the blood plasma and, possibly, to an increase in its cardiotoxicity.
With the simultaneous use of diltiazem inhibits the metabolism of cyclosporine in the liver, which leads to a decrease in its excretion and an increase in the concentration in the blood plasma. At the same time, a decrease in manifestations of nephrotoxicity and an increase in immunosuppressive action were noted.
With simultaneous use with cimetidine, the concentration of diltiazem in the blood plasma increases due to the inhibition of its oxidative metabolism in the liver under the influence of cimetidine. It is possible to enhance the effects of diltiazem.
With concomitant use with enflurane, there have been cases of violation of AV conduction of the myocardium.
