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

active ingredient: diltiazem hydrochloride [as a pellet] 90 mg or 180 mg auxiliary components: sugar grits [sucrose, molasses starch], methyl methacrylate, trimethylammonioethyl methacrylate chloride and ethyl acrylate copolymer [1: 2: 0.1]; methyl methacrylate, trimethylammonioethyl methacrylate chloride and ethyl acrylate copolymer [1: 2: 0.2]; paraffin, talc;

capsule composition:

dosage of 90 mg: titanium dioxide, dye quinoline yellow, dye sunset yellow, gelatin;

dosage of 180 mg: titanium dioxide, dye sunset yellow, dye crimson (Ponce 4R), the dye is blue patented, the dye is a diamond black, gelatin.

Description:

Capsules hard gelatinous № 4 yellow color - for a dosage of 90 mg.

Capsules hard gelatinous № 2 pink with a violet shade of color - for a dosage of 180 mg.

The contents of capsules are granules of white or almost white color.

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 derivative of benzothiazepines; has antiarrhythmic, antianginal and hypotensive activity. The "slow" calcium channel blocker reduces the intracellular calcium content in cardiomyocytes and smooth muscle cells, expands the coronary and peripheral arteries and arterioles, reduces the overall peripheral vascular resistance (OPSS), smooth muscle tone, strengthens coronary, cerebral and renal blood flow, decreases the heart rate (heart rate).

Antiarrhythmic action is caused by the suppression of transport of ionized calcium in the heart tissues, which leads to an increase in the effective refractory period and an extension of the time spent in the atrioventicular (AV) node (has clinical significance in patients with sinus node weakness syndrome, elderly patients who have calcium channel blockadecan interfere with the generation of a pulse in sinus node and cause sinoatrial (SA) 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.

Antianginal action is caused by the expansion of peripheral vessels and a decrease in systemic arterial pressure (postload), which leads to a decrease in the stress of the myocardium wall and its oxygen demand. In concentrations that do not lead to the appearance of a negative inotropic effect, it causes the relaxation of the smooth muscles of the coronary vessels and the dilatation of both large and small arteries.

Antihypertensive action is caused by dilatation of resistive vessels and a decrease in OPSS. The degree of reduction in blood pressure (BP) correlates with its baseline (in patients with normal blood pressure, a minimal effect on blood pressure is noted). Reduces blood pressure in both the "lying" and "standing" positions.Rarely causes postural arterial hypotension and refractory 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 the renin-angiotensin-aldosterone system (RAAS). Reduces the renal and peripheral effects of angiotensin II. Improves diastolic relaxation of the myocardium with arterial hypertension, coronary heart disease, 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 onset of action with oral administration is 2-3 hours. The duration of action is 12-24 hours.

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

Pharmacokinetics:

When ingested quickly and almost completely absorbed in the gastrointestinal tract (90%). Time to reach the maximum concentration in blood plasma - 6-14 hours.Values of plasma concentrations in individual patients are very different. Communication with plasma proteins is 70-80% (with albumins - 35-40%). The volume of distribution of diltiazem in the body is about 5.3 l / kg body weight.

After absorption from the gastrointestinal tract, the active substance undergoes intensive metabolism, due to the effect of "first passage" mainly through the liver. In the liver, it is metabolized by deacetylation and demethylation (with the participation of isoenzymes CYP 3A4, CYP3A5 and CYP3A7) with the formation of an active metabolite of deacetylldithiasem, which is determined in blood plasma at 5-10 times lower concentration than the original diltiazem, and has 2-4 times less activity.

Half-life with oral administration is biphasic: early - 20-30 minutes, final - 3.5 hours (5-8 hours - with high and repeated doses).

It is excreted through the intestines with bile (65%) and kidneys (35%, including 2-4% unchanged).

The pharmacokinetics of diltiazem for prolonged use does not change.

Diltiazem does not cumulate or induce its own metabolism.

In patients with angina and impaired renal function the pharmacokinetics of diltiazem does not change.

In patients with hepatic insufficiency increases bioavailability and lengthens the half-life.

In old age also the clearance of diltiazem can be reduced. It is not excreted in hemodialysis and peritoneal dialysis.

Indications:

- Prevention of paroxysmal supraventricular tachycardia;

- arterial hypertension;

- prevention of attacks of angina pectoris (including stenocardia of Prinzmetal).

Contraindications:

Hypersensitivity to the drug and to other benzothiazepine derivatives, cardiogenic shock, sinoatrial and AV blockade of II and III degree (except for patients with pacemaker), Wolff-Parkinson-White syndrome, Laun-Ganong-Levin syndrome in combination with flutter or atrial fibrillation (except for patients with pacemaker), chronic heart failure (in decompensation stage), acute heart failure, myocardial infarction with signs of left ventricular failure, sinus node weakness syndrome without the use of an artificial pacemaker, pronounced arterial hypotension (systolic blood pressure less than 90 mmHg) yrazhennaya bradycardia, ventricular tachycardia with a wide set of QRS, porphyria, pregnancy, lactation, age under 18 (efficacy and safety not established), fructose intolerance and glucose / galactose absorption impairment syndrome or iso-malase deficiency.

Carefully:Carefully Use in patients with severe impairment of liver and kidney function, severe stenosis of the aortic orifice, in the acute phase of myocardial infarction (without signs of left ventricular failure), hypertrophic obstructive cardiomyopathy (GOCMP), arterial hypotension, AV blockade of degree I, or PQ interval prolongation with simultaneous application with beta-adrenoblockers or digoxin, compensated chronic heart failure, with a tendency to bradycardia, in old age.

Pregnancy and lactation:

Diltiazem retard is contraindicated for use during pregnancy and during lactation (diltiazem penetrates into breast milk).

Women in childbearing age before the appointment of Diltiazem retard should be excluded from pregnancy.

Dosing and Administration:

Tablets should be taken orally, before meals, wholly, without chewing or crushing, with a small amount of liquid:

Initial dose drug Diltiazem retard is 1 tablet of 90 mg 2 times a day.

Average daily dose is 180-240 mg. Correction of the dosing regimen can be carried out only after 2 weeks.

The maximum dose is 360 mg / day. (only used in a hospital).

Side effects:

The most frequently observed (in many cases, the connection with the drug is not established): peripheral edema (2.4%), headache (2.1%), nausea (1.9%), dizziness (1.5%), cutaneous rash (1.3%), asthenia (1.2%).

With a frequency of less than 1%:

From the cardiovascular system: angina, arrhythmia, bradycardia (less than 50 beats per minute) or tachycardia, AV blockade, bundle branch blockage, development or worsening of heart failure, ECG changes, blood flushes, marked decrease in blood pressure, palpitations, fainting, ventricular extrasystole.

From the nervous system: sleep disturbance, amnesia, depression, gait disturbance, hallucinations, insomnia, nervousness, paresthesia, personality changes, drowsiness, tremor.

From the digestive system: dryness of the oral mucosa, anorexia, constipation or diarrhea, a taste disorder, dyspepsia, a moderate increase in the activity of alkaline phosphatase (AFP), aspartate aminotransferase (ACT), alanine aminotransferase (ALT), lactate dehydrogenase (LDH); thirst, vomiting, weight gain.

From the skin: petechiae, photosensitivity, itching, hives.

Other: amblyopia, increased activity of creatine phosphokinase (CK), dyspnea, epistaxis, eye irritation, hyperglycemia, hyperuricemia, impotence, muscle cramps, nasal congestion, nocturia, osteoarticular pain, polyuria, sexual dysfunction, ringing in the ears.

Post-marketing experience: allergic reactions ,. alopecia, angioedema (including facial edema and periorbital edema), erythema multiforme (including Stevens-Johnson syndrome), toxic epidermal necrolysis, extrapyramidal syndrome, gingival hyperplasia, hemolytic anemia, bleeding time lengthening, leukopenia, purpura, retinopathy, myopathy, thrombocytopenia, exfoliative dermatitis.

There were cases of generalized rash, which in some cases was a manifestation of leukocytoclastic vasculitis; reported cases of myocardial infarction, which is not always easy to distinguish from the manifestations of the existing disease.

Overdose:

Symptoms: pronounced bradycardia, marked decrease in blood pressure, which results in collapse, atrioventricular and sinoatrial 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 rinse the stomach, take Activated carbon, further treatment is symptomatic. If necessary, it is recommended to appoint atropine ^ isoprenaline, dopamine or dobutamine, and also, with pronounced conduction disorders, the use of electrocardiostimulation is possible.

Hemodialysis and peritoneal dialysis are ineffective.

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-blockers, cardiac glycosides, it is possible to develop bradycardia, violation of atrioventricular conduction,the appearance of symptoms of heart failure.

When used simultaneously with adenosine, increased risk of prolonged bradycardia.

Salicylates additionally inhibited the ability to aggregate platelets.

Ethanol: increased hypotensive effect.

Procainamide, quinidine and other drugs that cause lengthening of the interval QT, increase the risk of significant lengthening.

Means for inhalation anesthesia (hydrocarbon derivatives), Thiazide diuretics and other drugs that reduce blood pressure, strengthen the hypotensive effect of diltiazem.

Phenytoin reduces the effect of diltiazem.

Antipsychotic drugs (antipsychotics) increase the hypotensive effect.

Possible simultaneous appointment nitrates (including prolonged forms).

Preparations lithium may potentiate neurotoxic effects of diltiazem (nausea, vomiting, diarrhea, ataxia, tremor, and / or tinnitus).

Indomethacin and other non-steroidal anti-inflammatory drugs (NSAIDs), glucocorticosteroids and estrogens, as well as symptomatic drugs reduce the hypotensive effect.

Pharmacokinetic

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

Diltiazem increases concentration terfillin and carbamazepine in blood plasma (40-70%) and increases the risk of adverse reactions, incl. ataxia, nystagmus, diplopia, headache, vomiting, confusion, and also increases concentration cyclosporine, digoxin (up to 50%), imipramine, lithium and midazolam.

Strengthening action hypoglycemic agents for oral administration (eg, chlorpropamide and glipizide).

With the simultaneous use of diltiazem and cyclosporine in patients with a transplanted kidney, it is possible to develop intoxication, paresthesia. Therefore, it is necessary to monitor plasma concentrations of cyclosporine in this group of patients.

Eating increases the absorption and bioavailability of diltiazem up to 20-30%.

May increase bioavailability propranolol.

Increases concentration moracisin in the blood plasma.

Phenobarbital, diazepam, rifampicin reduce the concentration of diltiazem in the blood plasma.

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 (increased plasma concentration with increased sedation).

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

Diltiazem significantly increases the concentration lovastatin in the blood plasma. Also enhances the action simvastatin, so when using them simultaneously, simvastatin dose should be reduced. With the simultaneous use of diltiazem with lovastatin and simvastatin, monitoring of patients is necessary, because of the possibility of developing myositis or rhabdomyolysis.

Special instructions:

Diltiazem retard reduces conduction of the myocardium, so it should be used with extreme caution in patients with AV blockade of the I degree and bradycardia.

Caution is also needed when used in patients with left ventricular dysfunction.

Diltiazem retard with caution appoint patients already taking other drugs, in particular, beta-blockers.In this group of patients, the treatment process should be carried out under the close supervision of a cardiologist.

Diltiazem retard 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 control the concentration of urea in the urine, creatinine. In patients with impaired liver function, the daily dose should not exceed 90 mg and it is recommended to regularly monitor liver function.

For elderly patients, the dose is selected individually.

As diltiazem reduces OSSS and can cause secondary arterial hypotension, it is necessary to monitor blood pressure, in particular, at the beginning of the course treatment, while therapeutic doses are not yet specified.

In case of persistent skin rash, which develop into multiforme erythema and exfoliative dermatitis, diltiazem retard should be stopped.

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 (the patient takes Diltiazem retard).

In elderly patients, the half-life of diltiazem may increase.

Effect on the ability to drive transp. cf. and fur:

To date, it has not been established that the administration of 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:

Capsules of prolonged action, 90 mg and 180 mg.

Packaging:

For 7 capsules (with a dosage of 90 mg) or 10 capsules (with a dosage of 180 mg) in a planar cell pack of a polyvinylchloride film and aluminum foil.

3 contour squares, together with instructions for use, are placed in a cardboard pack.

Storage conditions:

In a dry, the dark place at a temperature of no higher than 25 ° C.

Keep out of the reach of children.

Shelf life:

3 years.

Do not use after the expiration date.

Terms of leave from pharmacies:On prescription

Registration number:LSR-009002/10

Date of registration:31.08.2010

Expiration Date:Unlimited

The owner of the registration certificate:K.O. Ромфарм Компани С.Р.Л.K.O. Ромфарм Компани С.Р.Л. Romania

Manufacturer: & nbsp

S.C. ROMPHARM Company, S.R.L. Romania

Representation: & nbspРомфарма ОООРомфарма ООО

Information update date: & nbsp09.11.2016

Illustrated instructions

Instructions

Diltiazem retard (Diltiazem retard)