Diltiazem retard tablets 90mg, No. 30
Expiration Date: 05/2027
Russian Pharmacy name:
Дилтиазем ретард таблетки 90мг, №30
prevention of paroxysmal supraventricular tachycardia;
arterial hypertension;
prevention of angina attacks (including Prinzmetal's angina).
The tablets should be taken orally, before meals, whole, without chewing or crushing, with a small amount of liquid.
The initial dose of the drug Diltiazem retard is 1 tablet, 90 mg 2 times a day. The average daily dose is 180-240 mg. The dosage regimen can be adjusted only after 2 weeks.
The maximum dose is 360 mg / day (used only in a hospital).
diltiazem - 90 mg
Excipients : sugar grits (sucrose, starch syrup), copolymer of methyl methacrylate, trimethylammonioethyl methacrylate and ethyl acrylate (1: 2: 0.1) copolymer of methyl methacrylate, trimethylammonioethyl methacrylate chloride and ethyl acrylate (1: 2: 0.2), paraffin paraffin.
cardiogenic shock,
sinoatrial and AV-blockade of II and III degrees (except for patients with a pacemaker);
Wolff-Parkinson-White syndrome;
Laun-Ganong-Levin syndrome in combination with atrial flutter or fibrillation (except for patients with a pacemaker);
chronic heart failure (in the stage of decompensation);
acute heart failure;
myocardial infarction with signs of left ventricular failure;
sick sinus syndrome without the use of an artificial pacemaker;
severe arterial hypotension (systolic blood pressure less than 90 mm Hg);
severe bradycardia;
wide-complex ventricular tachycardia;
porphyria;
pregnancy;
lactation period;
age up to 18 years (efficacy and safety have not been established);
fructose intolerance and glucose / galactose malabsorption syndrome or sucrase / isomaltase deficiency;
hypersensitivity to the drug and to other benzothiazepine derivatives.
With caution: use in patients with severe impaired 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 (GOKMP), arterial hypotension, AV blockade of the 1st degree or lengthening of the PQ interval , with simultaneous use with beta-blockers or digoxin, compensated chronic heart failure, with a tendency to bradycardia, in old age.
Clinical and pharmacological group: Calcium channel blocker
Pharmaco-therapeutic group: BMCC
pharmachologic effect
Diltiazem is a benzothiazepine derivative; possesses antiarrhythmic, antianginal and hypotensive activity. A blocker of 'slow' calcium channels (BMCC), reduces the intracellular calcium content in cardiomycytes and smooth muscle cells, expands coronary and peripheral arteries and arterioles, reduces total peripheral vascular resistance (OPSR), smooth muscle tone, increases coronary, cerebral and renal blood flow, slows down the heart rate (HR).
The antiarrhythmic effect is due to the suppression of the transport of ionized calcium in the heart tissues, which leads to an increase in the effective refractory period and lengthening of the conduction time in the atrioventicular (AV) node (it is of clinical importance in patients with sick sinus syndrome, elderly patients in whom calcium channel blockade can interfere with the generation of an impulse in the sinus node and cause sinoatrial (SA) block.Normal atrial action potential or intraventricular conduction does not change (normal sinus rhythm is usually not affected), but with a decrease in the amplitude of atrial contraction, the rate of depolarization and conduction rate decrease.Anterograde effective refractory period in additional bypass beams, conduction can be shortened.
The antianginal effect is due to the expansion of peripheral vessels and a decrease in systemic arterial pressure (afterload), which leads to a decrease in the tension of the myocardial wall and its oxygen demand. At concentrations that do not lead to the appearance of a negative inotropic effect, it causes relaxation of the smooth muscles of the coronary vessels and dilatation of both large and small arteries.
The antihypertensive effect is due to the dilatation of resistive vessels and a decrease in the systemic vascular resistance. The degree of reduction in blood pressure (BP) correlates with its baseline value (in patients with normal BP, there is a minimal effect on BP). Reduces blood pressure both in the 'lying' and 'standing' position. Rarely causes postural arterial hyotension and refractory tachycardia. 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 arterial hypertension, coronary heart disease, hypertrophic cardiomyopathy, reduces platelet aggregation.
Has a minimal effect on the smooth muscles of the gastrointestinal tract (GIT). During long-term (8 months) therapy, tolerance does not develop. Does not affect blood lipid profile.
Able to 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 connection with blood plasma proteins is 70-80% (with albumin - 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 substance 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 isoenzymes CYP3A4, CYP3A5 and CYP3A7) with the formation of an active metabolite of deacetyldylthiazem, which is determined in blood plasma in 5-10 times lower concentration than the original 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 - 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 does not change with prolonged use. Diltiazem does not cumulate or induce its own metabolism.
In patients with angina pectoris and impaired renal function, the pharmacokinetics of diltiazem does not change. In patients with hepatic insufficiency, bioavailability increases and T1 / 2 is lengthened. In old age, clearance of diltiazem may also be reduced. Not excreted during hemodialysis and peritoneal dialysis.
Indications of the drug
prevention of paroxysmal supraventricular tachycardia;
arterial hypertension;
prevention of angina attacks (including Prinzmetal's angina).
Dosage regimen
The tablets should be taken orally, before meals, whole, without chewing or crushing, with a small amount of liquid.
The initial dose of the drug Diltiazem retard is 1 tablet, 90 mg 2 times a day. The average daily dose is 180-240 mg. The dosage regimen can be adjusted only after 2 weeks.
The maximum dose is 360 mg / day (used only in a hospital).
Side effect
The most frequently observed (in many cases, the connection with the drug intake has not been established): peripheral edema (2.4%), headache (2.1%), nausea (1.9%), dizziness (1.5%), skin rash (1.3%), asthenia ( 1.2%).
With a frequency of less than 1%:
From the side of the cardiovascular system : angina pectoris, arrhythmia, bradycardia (less than 50 beats / min) or tachycardia, AV block, bundle branch block, development or worsening of heart failure, ECG changes, blood 'hot flashes', marked decrease in blood pressure , palpitations, fainting, ventricular premature beats.
From the nervous system: sleep disturbance, amnesia, depression, gait disturbance, hallucinations, insomnia, nervousness, paresthesia, personality changes, drowsiness, tremors.
From the digestive system: dryness of the oral mucosa, anorexia, constipation or diarrhea, taste disturbance, dyspepsia, moderate increase in the activity of alkaline phosphatase (ALP), aspartate aminotransferase (ACT), alanine aminotransferase (ALT), lactate dehydrogenase (LDH); thirst, vomiting, weight gain.
On the part of the skin: petechiae, photosensitivity, pruritus, urticaria.
Others: 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 eiidermal necrolysis, extrapyramidal syndrome, gingival hyperplasia, hemolytic anemia, prolonged bleeding, leukopura 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.
Contraindications for use
cardiogenic shock,
sinoatrial and AV-blockade of II and III degrees (except for patients with a pacemaker);
Wolff-Parkinson-White syndrome;
Laun-Ganong-Levin syndrome in combination with atrial flutter or fibrillation (except for patients with a pacemaker);
chronic heart failure (in the stage of decompensation);
acute heart failure;
myocardial infarction with signs of left ventricular failure;
sick sinus syndrome without the use of an artificial pacemaker;
severe arterial hypotension (systolic blood pressure less than 90 mm Hg);
severe bradycardia;
wide-complex ventricular tachycardia;
porphyria;
pregnancy;
lactation period;
age up to 18 years (efficacy and safety have not been established);
fructose intolerance and glucose / galactose malabsorption syndrome or sucrase / isomaltase deficiency;
hypersensitivity to the drug and to other benzothiazepine derivatives.
With caution: use in patients with severe impaired 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 (GOKMP), arterial hypotension, AV blockade of the 1st degree or lengthening of the PQ interval , with simultaneous use with beta-blockers or digoxin, compensated chronic heart failure, with a tendency to bradycardia, in old age.
Application during pregnancy and lactation
Diltiazem retard is contraindicated for use during pregnancy and lactation (diltiazem passes into breast milk).
Women of childbearing age should exclude pregnancy before the appointment of Diltiazem retard.
Application for violations of liver function
Diltiazem retard is prescribed with caution in patients with hepatic impairment; in this group of patients, if necessary, the prescribed dose of the drug should be reduced. In patients with impaired liver function, the daily dose should not exceed 90 mg and it is recommended to regularly monitor liver function.
Application for impaired renal function
Use with caution in patients with severe renal impairment.
Application in children
Contraindicated in children under 18 years of age.
Use in elderly patients
Use with caution in the elderly.
For elderly patients, the dose is selected individually.
special instructions
Diltiazem retard reduces myocardial conductivity, so it should be used with extreme caution in patients with grade I AV block and bradycardia. Caution is also required when used in patients with impaired left ventricular function of the heart.
Diltiazem retard is used with caution in 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 is prescribed with caution in patients with renal or hepatic insufficiency; in this group of patients, if necessary, the prescribed doses of the drug should be reduced and the concentration of urea in urine, creatinine should be monitored.
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.
Since diltiazem reduces the systemic vascular resistance and can cause secondary arterial hypotension, it is necessary to control blood pressure, in particular, at the beginning of the course of treatment, while the therapeutic doses have not yet been clarified.
In case of persistent skin rashes developing into erythema multiforme and exfoliative dermatitis, Diltiazem retard should be discontinued.
If during therapy the patient needs to undergo surgery under general anesthesia, it is necessary to inform the anesthesiologist about the nature of the therapy (the patient is taking Diltiazem retard).
Elderly patients may have an increase in the half-life of diltiazem.
Influence on the ability to drive vehicles and control mechanisms
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 hazardous activities that require increased attention, a quick mental and motor reaction.
Overdose
Symptoms: severe bradycardia, marked decrease in blood pressure, turning into collapse, impaired 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 flush the stomach, take activated charcoal, further treatment is symptomatic. If necessary, it is recommended to prescribe atropine, isoprenaline, dopamine or dobutamine, and, in case of severe conduction disturbances, the use of pacing is possible.
Hemodialysis and peritoneal dialysis are ineffective.
Drug interactions
Pharmacodynamic
With the simultaneous use of diltiazem with antihypertensive drugs, an increase in the antihypertensive effect is noted.
With the simultaneous administration of diltiazem and digoxin, an increase in the concentration of digoxin in the blood is possible.
When taken simultaneously with antiarrhythmic drugs, beta-blockers, cardiac glycosides, it is possible to develop bradycardia, violation of atrioventricular conduction, the appearance of symptoms of heart failure.
With simultaneous use with adenosine, the risk of developing prolonged bradycardia is increased.
Salicylates additionally inhibit the ability to aggregate platelets.
Ethanol: increased antihypertensive effect.
Procainamide, quinidine and other drugs that cause QT prolongation increase the risk of QT prolongation.
—редства дл¤ ингал¤ционной анестезии (производные углеводородов), тиазидные диуретики и другие средства, снижающие ј?, усиливают гипотензивный эффект дилтиазема.
‘енитоин снижает эффект дилтиазема.
јнтипсихотические средства (нейролептики) усиливают гипотензивный эффект. ¬озможно одновременное назначение нитратов (в том числе пролонгированных форм). ѕрепараты лити¤ могут усиливать нейротоксическое действие дилтиазема (тошнота, рвота, диаре¤, атакси¤, дрожание и/или шум в ушах).
»ндометацин и другие нестероидные противовоспалительные препараты (Ќѕ¬ѕ), глюкортикостероиды и эстрогены, а также симтоматические лекарственные средства снижают гипотензивный эффект.
‘армакокинетическое
ќдновременное применение с циметидином приводит к значительному увеличению плазменных концентраций дилтиазема, что в свою очередь может привести к его токсическому действию на сердечно-сосудистую систему.
?илтиазем увеличивает концентрацию теофиллина и карбамазепина в плазме крови (40-70%) и повышает риск возникновени¤ побочных реакций, в т.ч. атаксии, нистагма, диплопии, головной боли, рвоты, спутанности сознани¤, а также увеличивает концентрации циклоспорина, дигоксина (до 50%), имипрамина, лити¤ и мидазолама.
”силение действие гипогликемических средств дл¤ приема внутрь (например, хлорпропамида и глипизида).
ѕри одновременном применении дилтиазема и циклоспорина у больных с пересаженной почкой, возможно развитие интоксикации, парестезии. ѕоэтому необходимо контроль плазменных концентраций циклоспорина у данной группы пациентов. ѕрием пищи увеличивает всасывание и биодоступность дилтиазема до 20-30%. ћожет повышать биодоступность пропранолола. ѕовышает концентрацию морацизина в плазме крови.
‘енобарбитал, диазепам, рифампицин снижают концентрацию дилтиазема в плазме крови. ѕовышает концентрацию в крови хинидина, валъпроевой кислоты (может потребоватьс¤ снижение дозы).
ѕротивовирусные средства: ритонавир может повышать плазменные концентрации Ѕћ .
јнксиолитики и снотворные средства: дилтиазем угнетает метаболизм мидазолама (повышаетс¤ плазменна¤ концентраци¤ с усилением седативного действи¤).
Ѕћ : выведение нифедипина снижаетс¤ дилтиаземом (повышаетс¤ плазменна¤ концентраци¤).
?илтиазем значительно увеличивает концентрацию ловастатина в плазме крови. “акже усиливает действие симвастатина, поэтому при их одновременном применении дозы симвастатина необходимо снизить. ѕри одновременном применении дилтиазема с ловастатином и симвастатином необходим контроль за пациентами, из-за возможности развити¤ миозита или рабдомиолиза.
”слови¤ хранени¤
¬ сухом, защищенном от света месте, при температуре не выше 25?—. ’ранить в недоступном дл¤ детей месте.
—рок годности
—рок годности - 3 года.
”слови¤ реализации
ѕо рецепту.