Diltiazem retard sustained release capsules 180mg, 30pcs

Composition

Active ingredient:  

diltiazem 180 mg;

Auxiliary substances:  

granulated sugar (sucrose, starch molasses),

copolymer of methyl methacrylate,

trimethylammonioethyl methacrylate and ethyl acrylate (1: 2: 0.1)

a copolymer of methyl methacrylate,

trimethylammonioethyl methacrylate chloride and ethyl acrylate (1: 2: 0.2),

paraffin,

talc

Pharmacological action

Diltiazem is a derivative of benzothiazepines; it has antiarrhythmic, antianginal and hypotensive activity. Slow calcium channel blocker (BMCC), reduces intracellular calcium content in cardiomycytes and smooth muscle cells, expands coronary and peripheral arteries and arterioles, reduces total peripheral vascular resistance (OPSS), smooth muscle tone, increases coronary, cerebral and renal blood flow, reduces heart rate (HR).

The antiarrhythmic effect is due to the suppression of ionized calcium transport in the heart tissues, which leads to an increase in the effective refractory period and lengthening the time spent in the atrioventicular (AV) node (it is of clinical importance in patients with sinus node weakness syndrome, elderly patients in whom calcium channel blockade can interfere with pulse generation in the sinus node and cause sinoatrial (SA) blockade. Normal atrial action potential or intraventricular conduction does not change (normal sinus rhythm is usually not affected), but when the amplitude of atrial contraction decreases, the rate of depolarization and conduction decrease. The anterograde effective refractory period in additional bypass conduction beams may be shortened.

The antianginal effect is due to the expansion of peripheral blood vessels and a decrease in systemic blood pressure (afterload), which leads to a decrease in the tension of the myocardial wall and its oxygen demand. In concentrations that do not lead to a negative inotropic effect, it causes relaxation of the smooth muscles of the coronary vessels and dilation of both large and small arteries.

The antihypertensive effect is due to dilation of resistive vessels and a decrease in OPSS. The degree of reduction in blood pressure (BP) correlates with its initial indicator (in patients with normal blood pressure, there is a minimal effect on blood pressure). Reduces blood pressure both in the “lying” and “standing” positions. Rarely causes postural arterial hypotension and refractive tachycardia. It does not change or slightly reduces the maximum heart rate during exercise. Long-term therapy does not lead to hypercatecholaminemia, an increase in the activity of the renin-angiotensin-aldosterone system (RAAS). Reduces the renal and peripheral effects of angiotensin II. Improves diastolic relaxation of the myocardium in patients with arterial hypertension, coronary heart disease, hypertrophic cardiomyopathy, reduces platelet aggregation.

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

It can cause regression of left ventricular hypertrophy in patients with arterial hypertension. The onset of action when taken orally 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 taken orally, it is rapidly and almost completely absorbed in the gastrointestinal tract (90%). The time to reach the maximum concentration in blood plasma is 6-14 hours. The values of plasma concentrations in individual patients are very different. The relationship 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 of body weight.

After absorption from the gastrointestinal tract, the Active ingredient undergoes intensive metabolism, due to the “first pass” effect mainly through the liver. In the liver, it is metabolized by deacetylation and demethylation (with the participation of SURZA 4, CYP3A5 and CYP3A7 isoenzymes) to form the active metabolite of deacetyldylthiazem, which is determined in blood plasma at 5-10 times lower concentrations than the initial diltiazem, and has 2-4 times less activity.

T1 / 2 when taken orally is biphasic: early – 20-30 minutes, final-3.5 hours (5-8 hours – at high and repeated doses).

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

The pharmacokinetics of diltiazem do not change with prolonged use. Diltiazem does not accumulate or induce its own metabolism.

In patients with angina pectoris and impaired renal function, the pharmacokinetics of diltiazem do not change. In patients with hepatic insufficiency, bioavailability increases and T1 lengthens/2. Diltiazem clearance may also be reduced in the elderly. It is not excreted during hemodialysis and peritoneal dialysis.

Indications

• prevention of paroxysmal supraventricular tachycardia;
• arterial hypertension;
• prevention of angina attacks (including Prinzmetal angina).

Contraindications

• cardiogenic shock,
• sinoatrial and AV-block II and III degree (except in patients with a pacemaker);
• the syndrome Wolff-Parkinson-white –
• syndrome Lawn Ganong-Levin in combination with flutter or atrial fibrillation (except for patients with a pacemaker);
• congestive heart failure (decompensation);
• acute heart failure;
• myocardial infarction with signs of left ventricular failure;
• sick sinus syndrome node without the use of an artificial pacemaker;
• severe hypotension (systolic BP less than 90 mm Hg. St. )
• bradycardia;
• ventricular tachycardia with a wide QRS complex;
• porphyria;
• pregnancy;
• lactation;
• age to 18 years (efficacy and safety not established);
• fructose intolerance and malabsorption syndrome glucose/galactose or sucrase deficiency/isomaltase;
• hypersensitivity to the drug and other derivative benzodiazepine.

With caution:  use in patients with severe liver and kidney dysfunction, severe aortic stenosis, acute phase of myocardial infarction (without signs of left ventricular insufficiency), hypertrophic obstructive cardiomyopathy (HOCMP), arterial hypotension, grade I AV block or prolongation of the PQ interval, when used simultaneously with beta-blockers or digoxin, compensated chronic heart failure, with a tendency to bradycardia, in the elderly.

Side effects

From the cardiovascular system: angina, arrhythmia, bradycardia (less than 50 beats / min) or tachycardia, AV block, bundle branch block, development or aggravation of heart failure, ECG changes, “hot flashes” of blood, marked decrease in blood pressure, palpitation, syncope, ventricular extrasystole.

Nervous system disorders:  sleep disorders, amnesia, depression, gait disorders, hallucinations, insomnia, nervousness, paresthesia, personality changes, drowsiness, tremor.

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

From the side of the skin:  petechiae, photosensitivity, pruritus, urticaria.

Other services:  amblyopia, increased creatine phosphokinase (CPK) activity, shortness of breath, nosebleeds, eye irritation, hyperglycemia, hyperuricemia, impotence, muscle cramps, nasal congestion, nocturia, osteoarticular pain, polyuria, sexual dysfunction, tinnitus.

Post-marketing experience:  allergic reactions, alopecia, angioedema (including facial edema and periorbital edema), erythema multiforme (including Stevens-Johnson syndrome), toxic epidermal necrolysis, extrapyramidal syndrome, gum hyperplasia, hemolytic anemia, prolonged bleeding time, leukopenia, purpura, retinopathy, myopathy, thrombocytopenia, exfoliative dermatitis. There were cases of generalized rash, which in some cases was a manifestation of leukocytoclastic vasculitis; cases of myocardial infarction were reported, which is not always easy to distinguish from the manifestations of the existing disease.

Composition

Pharmacodynamic interaction

With the simultaneous use of diltiazem with antihypertensive agents, an increase in the hypotensive effect is noted.

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

When taken simultaneously with antiarrhythmic drugs, beta-blockers, cardiac glycosides, bradycardia, violation of atrioventricular conduction, and the appearance of symptoms of heart failure may develop.

Concomitant use with adenosine increases the risk of prolonged bradycardia.

Salicylates additionally inhibit the ability to aggregate platelets.

Ethanol: increased hypotensive effect.

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

Inhaled anesthetics (hydrocarbon derivatives), thiazide diuretics, and other blood pressure-lowering agents enhance the hypotensive effect of diltiazem.

Phenytoin reduces the effect of diltiazem.

Antipsychotic drugs (neuroleptics) enhance the hypotensive effect. Simultaneous use of nitrates (including prolonged forms) is possible. Lithium preparations may increase the neurotoxic effects of diltiazem (nausea, vomiting, diarrhea, ataxia, trembling and / or tinnitus).

Indometacin and other nonsteroidal anti-inflammatory drugs (NSAIDs), glucorticosteroids and estrogens, as well as symptomatic medications reduce the hypotensive effect.

Pharmacokinetic properties of

Concomitant use 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 the concentration of theophylline and carbamazepine in blood plasma (40-70%) and increases the risk of adverse reactions, including ataxia, nystagmus, diplopia, headache, vomiting, confusion, as well as increases the concentration of cyclosporine, digoxin (up to 50%), imipramine, lithium and midazolam.

Increased effect of hypoglycemic agents for oral use (for example, chlorpropamide and glipizide).

With the simultaneous use of diltiazem and cyclosporine in patients with a transplanted kidney, intoxication and paresthesia may develop. Therefore, it is necessary to monitor the plasma concentrations of cyclosporine in this group of patients. Food intake increases the absorption and bioavailability of diltiazem by up to 20-30%. May increase the bioavailability of propranolol. Increases the concentration of moracizin in the blood plasma.

Phenobarbital, diazepam, rifampicin reduce the concentration of diltiazem in blood plasma. Increases the concentration of quinidine and valproic acid in the blood (it may be necessary to reduce the dose).

Antiviral agents: ritonavir may increase plasma concentrations of BMCC.

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

BMCC: nifedipine clearance is reduced by diltiazem (increased plasma concentration).

Diltiazem significantly increases the concentration of lovastatin in the blood plasma. It also enhances the effect of simvastatin, so when they are used simultaneously, the dose of simvastatin should be reduced. When diltiazem is co-administered with lovastatin and simvastatin, monitoring of patients is necessary, due to the possibility of developing myositis or rhabdomyolysis.

How to take, course of use and dosage

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

Initial dose of the drug Diltiazem retard is 1 tablet of 90 mg 2 times a day. The average daily dose is 180-240 mg. Correction of the dosage regimen can be carried out only after 2 weeks.

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

Overdose

Symptoms: severe bradycardia, marked decrease in blood pressure, turning into collapse, violation of atrioventricular and sinoatrial conduction, 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, take activated charcoal, further treatment is symptomatic. If necessary, it is recommended to prescribe atropine, isoprenaline, dopamine or dobutamine, and also, with severe conduction disorders, electrocardiostimulation may be used.

Hemodialysis and peritoneal dialysis are ineffective.

Form of production

Capsules

Storage conditions

Store in a dry place, protected from light, at a temperature not exceeding 25 °C.

Active ingredient

Diltiazem

Conditions of release from pharmacies

By prescription

Dosage form

long-acting capsules

Purpose

For adults as directed by your doctor

Indications

Angina, Hypertension, Arrhythmia