Diltiazem lannacher - instructions for use. How and When to Take Diltiazem Side Effects of Diltiazem

17.08.2020

Diltiazem hydrochloride (diltiazem)

Composition and form of release of the drug

10 pieces. - cellular contour packings (3) - packs of cardboard.

pharmachologic effect

Selective class III, benzothiazepine derivative. It has antianginal, hypotensive and antiarrhythmic effects. Reduces myocardial contractility, slows down AV conduction, reduces heart rate, reduces myocardial oxygen demand, dilates 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, reduces heart rate, may have a slight negative inotropic effect, increases coronary, cerebral and renal blood flow. In concentrations at which there is no negative inotropic effect, it causes relaxation of the smooth muscles of the coronary vessels and dilatation of both large and small arteries.

The antianginal effect is due to an improvement in myocardial blood supply and a decrease in its oxygen demand as a result of a decrease in peripheral vascular resistance, systemic blood pressure (afterload), a decrease in myocardial tone and an increase in the time of diastolic relaxation of the left ventricle.

The antiarrhythmic effect is due to the suppression of calcium ion transport in the tissues of the heart, which leads to a lengthening of the effective refractory period and a slowdown in conduction in the AV node (in patients with SSS, the elderly, in whom blockade of calcium channels can prevent the generation of an impulse in the sinus node and cause sinoatrial blockade). The normal atrial action potential or intraventricular conduction is not altered (normal sinus rhythm is usually unaffected), but depolarization rate and conduction rate decrease as the amplitude of atrial contraction decreases. The anterograde effective refractory period in additional bypass conduction bundles may be shortened. When administered parenterally, it causes a rapid transition of paroxysmal supraventricular tachycardia (including those associated with additional bypass conduction bundles) to sinus rhythm, as well as a temporary cessation of ventricular tachycardia during flutter or atrial fibrillation.

The hypotensive effect is due to the dilatation of resistive vessels and a decrease in OPSS. The degree of reduction in blood pressure correlates with its initial level (with fluctuations in blood pressure within the normal range, there is a minimal effect on blood pressure). Reduces blood pressure in both horizontal and vertical positions. Rarely causes postural arterial hypotension and reflex tachycardia. Does not change or slightly reduces the maximum heart rate during exercise. Long-term therapy does not lead to hypercatecholaminemia, an increase in RAAS activity. Reduces renal and peripheral effects of angiotensin II. Promotes diastolic relaxation of the myocardium in arterial hypertension, coronary artery disease, hypertrophic obstructive cardiomyopathy, reduces platelet aggregation. Able to cause regression of left ventricular hypertrophy in patients with arterial hypertension.

Slightly affects the smooth muscles of the gastrointestinal tract. During long-term (8 months) therapy, tolerance does not develop. Does not affect the lipid profile of the blood.

The onset and duration of action depends on the dosage form used.

Pharmacokinetics

Protein binding is about 80%. Diltiazem is excreted in breast milk. It is intensively metabolized in the liver with the participation of the cytochrome P 450 enzyme system. One of the metabolites, desacetyldylthiazem, has 25-50% of the activity of the unchanged substance.

T1 / 2 diltiazem is 3-5 hours. Excreted mainly as metabolites in the bile and urine, approximately 2-4% is excreted in the urine unchanged.

Diltiazem is poorly excreted by dialysis.

Indications

Prevention of angina attacks (including Prinzmetal's 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 pectoris, prevention of spasm of the coronary arteries during coronary angiography or coronary artery bypass surgery, paroxysmal ventricular tachycardia, for the relief of frequent ventricular rhythm with atrial fibrillation or flutter (with the exception of WPW syndrome).

Contraindications

Severe bradycardia, AV block II and III degree (except for patients with a pacemaker), SSS, cardiogenic shock, atrial fibrillation in WPW and Laun-Ganog-Levin syndrome, myocardial infarction with pulmonary congestion, arterial hypotension, chronic insufficiency II B Stage III, acute heart failure, hemodynamically significant aortic stenosis, impaired liver and kidney function, pregnancy, lactation, hypersensitivity to benzothiazepine derivatives.

Dosage

When taken orally, the initial dose is 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 used 1-2 times / day, depending on the dose.

Maximum daily dose when taken orally is 360 mg.

With a / in the introduction of a single dose - 300 mcg / kg.

For intravenous drip, the dose is 2.8-14 mcg / kg / min. Maximum daily dose is 300 mg.

Side effects

From the side of the central nervous system and peripheral nervous system: headache, dizziness, fainting, fatigue, asthenia, sleep disturbances, drowsiness, anxiety, extrapyramidal (parkinsonism) disorders (ataxia, mask-like face, shuffling gait, stiffness of the arms or legs, trembling of the hands and fingers, difficulty swallowing), depression ; when used in high doses - paresthesia, tremor, visual impairment (transient loss of vision).

From the side of the cardiovascular system: asymptomatic decrease in blood pressure; rarely - angina pectoris, arrhythmia (including flutter and ventricular fibrillation), bradycardia (less than 50 bpm) or tachycardia, AV block II and III degree up to asystole, development or aggravation of heart failure; when used in high doses and with intravenous administration - angina pectoris, bradycardia, AV blockade, a pronounced decrease in blood pressure, aggravation of chronic heart failure.

From the digestive system: dry mouth, increased appetite, nausea, vomiting, constipation or diarrhea, increased activity of hepatic transaminases, gingival hyperplasia (bleeding, soreness, swelling).

From the hematopoietic system: rarely - thrombocytopenia, agranulocytosis.

Allergic reactions: flushing of the skin of the face, skin rash, arthritis, erythema multiforme exudative (including Stevens-Johnson syndrome).

Others: when used in high doses - pulmonary edema (difficulty breathing, coughing, stridor breathing); peripheral edema (swelling of the lower extremities - ankles, feet, legs), increased serum creatinine; rarely - galactorrhea, weight gain.

drug interaction

With simultaneous use with (including propranolol, atenolol, metoprolol, pindolol, sotalol), an additive cardiodepressive effect is possible along with an increase in the antianginal effect in most patients. Patients with prior left ventricular dysfunction or conduction disturbances are at an increased risk of developing severe and threatening bradycardia.

Diltiazem inhibits the metabolism of propranolol, but not atenolol.

With simultaneous use with amiodarone, the negative inotropic effect, bradycardia, conduction disturbance, and AV blockade increase.

Since diltiazem inhibits the CYP3A4 isoenzyme, which is involved in the metabolism of atorvastatin, lovastatin and simvastatin, drug interactions are theoretically possible due to an increase in plasma concentrations of statins. Cases of rhabdomyolysis have been described.

With simultaneous use with buspirone, the concentration of buspirone in the blood plasma increases, and its therapeutic and side effects increase.

With simultaneous use with vecuronium chloride, an increase in the duration of neuromuscular blockade is possible.

With simultaneous use with digitoxin, it is possible to increase the concentrations of digoxin and digitoxin in the blood plasma.

With simultaneous use with imipramine, the concentration of imipramine in the blood plasma increases and there is a risk of developing unwanted changes on the ECG.

Cases of increased plasma concentrations of trimipramine and nortriptyline have been described with simultaneous use with diltiazem.

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 interacts in the same way with trimipramine and nortriptyline.

When used simultaneously with insulin, a case of a decrease in the effectiveness of insulin is described.

Due to inhibition of the metabolism of anticonvulsants in the liver under the influence of diltiazem and a decrease in their clearance from the body, an increase in plasma concentrations of carbamazepine and phenytoin is possible with the risk of developing a toxic effect.

With simultaneous use with lithium carbonate, 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 increase due to inhibition of the CYP3A4 isoenzyme under the influence of diltiazem, with the participation of which the metabolism of these benzodiazepines is carried out.

With simultaneous use with sodium amidotrizoate, it is possible to enhance the antihypertensive effect of diltiazem.

With simultaneous use with sodium nitroprusside, a significant increase in efficacy in controlled arterial hypotension is possible.

With simultaneous use with nifedipine, the antihypertensive effect is enhanced.

Rifampicin induces the activity of liver enzymes, accelerating the metabolism of diltiazem, which leads to a decrease in its effectiveness.

With simultaneous use with theophylline, a slight decrease in theophylline metabolism in the liver is possible, apparently due to 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 a pronounced prolongation of the QT interval. It is believed that diltiazem inhibits the activity of the CYP3A4 isoenzyme, which leads to an increase in the concentration of cisapride in the blood plasma and, possibly, an increase in its cardiotoxicity.

With simultaneous use, diltiazem inhibits the metabolism of cyclosporine in the liver, which leads to a decrease in its excretion and an increase in plasma concentration. At the same time, a decrease in the manifestations of nephrotoxicity and an increase in the immunosuppressive effect were noted.

With simultaneous use with cimetidine, the concentration of diltiazem in the blood plasma increases due to inhibition of its oxidative metabolism in the liver under the influence of cimetidine. May enhance the effects of diltiazem.

With simultaneous use with enflurane, there have been cases of impaired AV conduction of the myocardium.

special instructions

Use with caution in AV blockade of the I degree, intraventricular conduction disorders, in patients prone to arterial hypotension, chronic heart failure, myocardial infarction with left ventricular failure, ventricular tachycardia with an expansion of the QRS complex, liver failure, renal failure, in elderly patients, in children (efficacy and safety have not been studied).

IV is used only for emergency therapy, but if necessary, it can be administered over several days. With the introduction of diltiazem, careful monitoring of the function of the cardiovascular system is necessary. Against the background of regular intake of beta-blockers, it is necessary to strictly clarify the indications for intravenous administration of diltiazem and use it only after ECG monitoring in the intensive care unit, while taking into account the possible need for the use of a pacemaker.

Sudden withdrawal of diltiazem can lead to the development of an angina attack.

Patients with impaired liver and / or kidney function and the elderly require correction of the dosing regimen.

Pregnancy and lactation

Use in the elderly

Use with caution in elderly patients.

Diltiazem is a drug used to treat diseases of the cardiovascular system.

Release form and composition

Diltiazem is produced in the form of round white tablets, on one side of which there is a risk, in blister packs of 10 pcs.

The composition of one tablet includes 60 or 90 mg of diltiazem chloride and excipients such as:

Gelatin;
colloidal silicon dioxide;
Lactose;
Calcium phosphate dibasic;
magnesium stearate;
Corn starch;
Povidone;
Microcrystalline cellulose;
Talc;
Hydroxypropyl methylcellulose;
Sodium benzoate.

They also produce a dry substance Diltiazem, intended for the preparation of a solution for injection, in transparent vials. One bottle contains 10 or 25 mg of diltiazem chloride.

Indications for use

Diltiazem is prescribed to patients with arterial hypertension and stable angina pectoris.

Contraindications

The use of Diltiazem is contraindicated in case of hypersensitivity to its constituent components, as well as in cases of:

Severe arterial hypotension;
Pregnancy and during the period of breastfeeding;
Severe bradycardia;
Laun-Ganong-Levin syndrome in combination with fibrillation or atrial flutter;
AV block II-III degree;
WPW syndrome;
SA blockade;
Sick sinus syndrome.

With caution, Diltiazem is prescribed for children under 18 years of age and elderly patients, as well as for chronic heart failure, myocardial infarction, AV block I degree, severe aortic stenosis, cardiogenic shock, mild or moderate arterial hypotension, ventricular tachycardia, liver and kidney failure.

Method of application and dosage

Tablets are taken orally before meals with a small amount of water. The dosage of Diltiazem is 30 mg three or four times a day, with a possible gradual increase in dose at intervals of 1-2 days.

Diltiazem solution is administered intravenously. The dose of the drug is determined individually. On average, when stopping supraventricular tachycardia, 0.15-0.25 mg of the solution is administered per 1 kg of body weight for 2 minutes.

Side effects

The instructions for Diltiazem indicate that the drug can cause side effects on the part of some organs and systems of the body, namely:

Dryness of the oral mucosa, thirst, taste disturbance, anorexia, hepatitis, constipation or diarrhea, dyspepsia, vomiting, weight gain, a moderate increase in the activity of alkaline phosphatase, aminotransferases, alanine aminotransferase and lactate dehydrogenase (digestive system);
Arrhythmia, angina pectoris, bundle branch block, bradycardia, palpitations, tachycardia, orthostatic hypotension, AV block, syncope, ECG changes, marked decrease in blood pressure, development or worsening of heart failure, ventricular extrasystole and flushing (cardiovascular system) ;
Itching, urticaria, petechiae, erythema and photosensitivity (skin and skin appendages);
Sleep disturbance, hallucinations, depression, insomnia, personality changes, amnesia, gait disturbance, paresthesia, tremors, nervousness and drowsiness (nervous system).

Diltiazem can cause asthenia, shortness of breath, headache, dizziness, polyuria, nausea, and also:

Increased activity of CPK;
impotence;
Agranulocytosis;
exfoliative dermatitis;
sexual dysfunction;
osteoarticular pain;
allergic reactions;
Nose bleed;
thrombocytopenia;
Extrapyramidal syndrome;
gum hyperplasia;
Prolongation of bleeding time.

Symptoms of an overdose of Diltiazem are chronic heart failure, severe bradycardia, cardiogenic shock, low blood pressure, asystole, and impaired AV conduction.

In such cases, gastric lavage, the appointment of activated charcoal and symptomatic therapy are required.

special instructions

The dosage regimen of Diltiazem for elderly patients with bradycardia should be selected with extreme caution.

In cases of prolonged intravenous administration of the solution, the patient's heart rate, electrocardiography, kidney and liver function, and the patient's blood pressure should be constantly monitored. Infusions lasting more than 1 day or at an infusion rate of 15 mg per hour are not recommended.

If during the period of use of Diltiazem there is a need for surgical intervention, the anesthesiologist should be warned in advance about taking the drug.

The hypotensive effect of Diltiazem is enhanced by hydrocarbon derivatives, thiazide diuretics and other drugs that lower blood pressure.

Simultaneous administration of the drug with quinidine, beta-blockers, cardiac glycosides is potentially dangerous and can lead to the development of heart failure.

Diazepam, phenobarbital and rifampicin reduce the concentration of the drug in the blood, and cimetidine increases it.

The drug can be used simultaneously with nitrates.

Diltiazem increases the blood concentration of carbamazepine, quinidine, cyclosporine, valproic acid, digoxin and theophylline, and also enhances the cardiodepressive effect of general anesthetics.

The drug in the form of a solution is incompatible with furosemide.

Analogues

Synonyms of the drug are Diazem and Cardil. Analogues of Diltiazem include Cortiazem, Amlodak, Tiakem, Isoptin, Nifebene, Amlodak and Breinal.

Terms and conditions of storage

The instructions for Diltiazem indicate that the drug should be stored in a place protected from light, dry and out of the reach of children, at a temperature not exceeding 25 ºС.

From pharmacies, the drug is dispensed by prescription. The shelf life of tablets, subject to the manufacturer's recommendations, is two years, dry matter - five years.

Found a mistake in the text? Select it and press Ctrl + Enter.

Selective calcium antagonists are a promising group of drugs included in the list of first-line drugs of choice for hypertensive patients. One of the popular drugs in this group is Diltiazem, which is used to effectively lower blood pressure and prevent the development of complications of hypertension.

The main active ingredient of the drug is diltiazem hydrochloride. The drug is available in the form of tablets. Auxiliary and formative substances vary depending on the manufacturer.

Diltiazem Lannacher is a drug from an Austrian pharmaceutical company. It is available in two dosages - 90 or 180 mg of the active ingredient in one tablet. Diltiazem Lannacher also contains lactose, talc, titanium dioxide and other excipients. The drug has a prolonged action and is a small light-colored film-coated tablets.

The long-acting drug Diltiazem Lannacher is available in two dosages.

Diltiazem Retard - tablets of prolonged action, which are produced in the Donetsk region and in Romania. Available in three dosages: 60, 90 and 120 mg of the active ingredient in one tablet. The mechanism of slow release of the active substance is carried out thanks to the following auxiliary components:

microcrystalline cellulose;
glycol wax;
lactose monohydrate;
mineral oil;
magnesium stearate.

Diltiazem Retard tablets are packed in blister packs of 12. Medicine is on sale on 1-10 blisters in a pack. Diltiazem Lannacher is available in blister packs of 10 tablets, two blisters per pack.

Diltiazem is a prescription drug, it can be purchased at pharmacies, but you must first get a prescription from your doctor.

What is the difference between different forms of the drug?

Diltiazem Lannacher and Diltiazem Retard are long acting drugs. They differ in a two-stage scheme for the release of the active substance. The drug begins to act a few hours after taking the pill, the peak of its work is noted after 7-8 hours after ingestion, and then the effect slowly declines. This feature allows you to take the medicine only twice a day.

Unlike other long-acting drugs, the effect of Diltiazem lasts not 24, but 12 hours, so the tablets are drunk in the morning and evening.

On the shelves of pharmacies, you can find the drug Diltiazem without any prefixes and explanatory words in the title. This drug works like regular pills. After taking it, the rapid release of the active substance begins, the peak of action occurs after two hours, and then the process of removing the drug from the body begins. Such tablets must be taken several times a day, but in smaller doses than Diltiazem Retard.

As a rule, slow-release tablets are more expensive, but due to the nature of their metabolism, Diltiazem Retard and Diltiazem Lannacher are less likely to cause side effects.

Long-acting drugs are more easily tolerated by the body

Indications for use

Diltiazem is a selective calcium antagonist with a predominant effect on the heart. Diltiazem is indicated for lowering blood pressure while monitoring heart rate.

The main indications for the use of Diltiazem are arterial hypertension of any type with a risk of developing heart complications. According to the doctor's prescription, the drug can be taken for angina pectoris, coronary heart disease, during the recovery period after a heart attack.

The drug reduces the risk of developing heart failure and other myocardial disorders against the background of hypertension.

Diltiazem can be taken with a steady increase in blood pressure, both as an independent agent (monotherapy), and in combination with other antihypertensive drugs.

As the only drug for pressure control, Diltiazem Retard is prescribed for pressure increases in the range of 150 mm Hg. If the tonometer readings are significantly higher, it is necessary to additionally take diuretics or other drugs.

At the initial stage of hypertension, Diltiazem can be prescribed to patients at risk of developing complications and disruption of the heart.

How to take Diltiazem?

Reception of Diltiazem is carried out in the morning and in the evening, at the same time. Instructions for Diltiazem contain a detailed description of all possible regimens. It is recommended to take the drug immediately after a meal. In this case, the tablet must be swallowed, a violation of its integrity leads to a deterioration in the therapeutic effect.

The dosage of the drug is selected individually for each patient. Usually therapy begins with Diltiazem 60 mg twice a day. After a week of therapy, the effectiveness of the drug for the patient's body is evaluated, and the dosage can be increased to Diltiazem 90 mg.

Diltiazem, the indication of which is hypertension, is intended for long-term use. At the same time, if therapy is carried out in high doses, after a few weeks or months they must be reduced in order to minimize the risk of side effects.

Patients with angina pectoris or coronary heart disease should stop taking the drug by gradually reducing the dosage.

Treatment with the drug begins with a minimum dosage

Use in pregnancy, children and the elderly

The drug is not intended for use during the period of bearing a child, since studies of its effect on the fetus have not been conducted. You can start therapy with this medicine only after the exclusion of pregnancy.

The main active substance penetrates into breast milk, and therefore the drug is forbidden to be used during lactation.

The drug is well tolerated, so elderly patients can take the drug in standard dosages.

Diltiazem is not used in pediatric practice and is intended for the treatment of adult patients only.

Side effects

Side effects while taking Diltiazem are observed infrequently. The listed symptoms occurred in one of 10 thousand patients:

nervousness;
sleep disturbance;
confusion;
headache;
dizziness;
tremor;
hot flashes;
photosensitivity of the eyes;
pain and pain in the eyes;
noise in ears;
dyspnea;
nosebleeds;
gynecomastia and impotence in men.

In the first days of taking the drug, hypotension may develop due to high dosages of the drug. Usually, the symptoms of low blood pressure go away as the body gets used to it. If after 3-4 days there is dizziness, loss of strength, pale skin, you should consult your doctor about reducing the amount of the drug taken.

Contraindications

Reception of Diltiazem instructions for use prohibits in the following cases:

hypersensitivity to the active substance;
hypotension;
cardiogenic shock;
bradycardia;
the period of bearing a child and lactation;
childhood;
acute heart failure.

The drug does not affect the functioning of the liver and kidneys, so it can be used for renal and hepatic insufficiency. The action of the drug tablet does not affect drugs to lower blood sugar, so the drug Diltiazem can be prescribed to patients with type 2 diabetes.

special instructions

Patients with renal insufficiency do not need to adjust the dosage of the drug, except in cases of severe renal impairment. It is recommended to consult your doctor about reducing the number of tablets.

In case of liver failure, dosage reduction is not required, except for severe forms of the disorder, while it is advisable to carry out the treatment with the drug at a dosage of 60 mg.

In case of heart failure, the drug should be taken under the supervision of a specialist. It is recommended to regularly monitor changes in myocardial function. The drug is prescribed with caution for bradycardia, left ventricular failure, aortic stenosis.

In heart disease, regular monitoring is required during the period of taking the drug.

Overdose

Taking large doses of the drug (over 1.5 g) leads to the development of severe intoxication. This is manifested by a number of symptoms: irritability, nervousness, loss of strength, respiratory disorders, nausea, decreased pressure. There are cases of cardiac arrest due to an overdose of this drug, which can lead to death.

There is no specific antidote, symptomatic treatment is applied and, if necessary, resuscitation measures. If you suspect an overdose, it is recommended not to wait, but to immediately call an ambulance at home.

drug interaction

Any medication must be taken correctly. Despite seeming safety, Diltiazem can cause adverse reactions when taken with other drugs.

Although diltiazem can be taken with other antihypertensive drugs, the decision to prescribe auxiliary drugs should only be made by a doctor. Self-therapy with several different drugs for hypertension entails a strong decrease in blood pressure, the development of hypotension and bradycardia.
Means that reduce the heart rate are not recommended to be taken together with Diltiazem. Due to the potentiation of their action, the use of Diltiazem tablets with such drugs can lead to cardiac arrhythmias and bradycardia.
Diltiazem increases the toxicity of cyclosporine and carbamazepine. If co-administration is necessary, the dosage of these drugs should be halved.
Diltiazem increases the concentration of buspirone in the blood, which leads to severe side effects from taking the latter.
There have been cases of a decrease in the effect of administered insulin when taking Diltiazem, which must be taken into account in patients with type 1 diabetes mellitus.
Diltiazem should not be taken with lithium preparations, as this combination of drugs can lead to the development of mental disorders and parkinsonism.

It is important to remember that while taking Diltiazem, you should refrain from drinking alcoholic beverages in order to avoid increasing the load on the liver.

Cost and analogues

With the constant use of the drug Diltiazem, the price plays an important role. Everyone can afford the medicine - Diltiazem Lannacher will cost 150 rubles for a pack of 90 mg tablets, or 310 rubles at a dosage of 180 mg.

Ukrainian Diltiazem Retard at a dosage of 60 mg costs about 90 rubles per pack, a Romanian drug with the same name will cost 230 rubles, but already at a dosage of 180 mg.

There are no complete analogues of the drug. To date, only two diltiazem-based long-acting drugs are available in pharmacies. If necessary, a cardiologist will help you choose analogues to replace Diltiazem, but you will have to look for substitutes among drugs based on other active ingredients.

In this article, you can read the instructions for using the drug Diltiazem. Reviews of site visitors - consumers of this medicine, as well as opinions of doctors of specialists on the use of Diltiazem in their practice are presented. A big request to actively add your reviews about the drug: did the medicine help or not help get rid of the disease, what complications and side effects were observed, perhaps not declared by the manufacturer in the annotation. Analogues of Diltiazem in the presence of existing structural analogues. Use to treat hypertension or lower blood pressure and prevent angina attacks in adults, children, and during pregnancy and lactation.

Diltiazem- a selective calcium channel blocker of the 3rd class, a benzothiazepine derivative. It has antianginal, hypotensive and antiarrhythmic effects. Reduces myocardial contractility, slows down AV conduction, reduces heart rate, reduces myocardial oxygen demand, dilates coronary arteries, increases coronary blood flow. Reduces the tone of smooth muscles of peripheral arteries and OPSS.

The antiarrhythmic effect is due to the suppression of the transport of calcium ions in the tissues of the heart, which leads to a lengthening of the effective refractory period and a slowdown in the conduction in the AV node (in patients with sick sinus node syndrome (SSS), elderly people in whom blockade of calcium channels can prevent impulse generation in the sinus node and cause sinoatrial block). The normal atrial action potential or intraventricular conduction is not altered (normal sinus rhythm is usually unaffected), but depolarization rate and conduction rate decrease as the amplitude of atrial contraction decreases. The anterograde effective refractory period in additional bypass conduction bundles may be shortened. When administered parenterally, it causes a rapid transition of paroxysmal supraventricular tachycardia (including those associated with additional bypass conduction bundles) to sinus rhythm, as well as a temporary cessation of ventricular tachycardia during flutter or atrial fibrillation.

The hypotensive effect is due to the dilatation of resistive vessels and a decrease in OPSS. The degree of reduction in blood pressure correlates with its initial level (with fluctuations in blood pressure within the normal range, there is a minimal effect on blood pressure). Reduces blood pressure in both horizontal and vertical positions. Rarely causes postural arterial hypotension and reflex tachycardia. Does not change or slightly reduces the maximum heart rate during exercise. Long-term therapy does not lead to hypercatecholaminemia, an increase in RAAS activity. Reduces the renal and peripheral effects of angiotensin 2. Promotes diastolic relaxation of the myocardium in hypertension, coronary artery disease, hypertrophic obstructive cardiomyopathy, reduces platelet aggregation. Able to cause regression of left ventricular hypertrophy in patients with arterial hypertension.

Slightly affects the smooth muscles of the gastrointestinal tract. During long-term (8 months) therapy, tolerance does not develop. Does not affect the lipid profile of the blood.

The onset and duration of action depends on the dosage form used.

Compound

Diltiazem hydrochloride + excipients.

Pharmacokinetics

After oral administration, diltiazem is almost completely absorbed from the gastrointestinal tract. It undergoes intensive metabolism during the "first pass" through the liver. Bioavailability is about 40%. Plasma concentration is variable. Plasma protein binding is about 80%. Diltiazem is excreted in breast milk. It is intensively metabolized in the liver with the participation of the cytochrome P450 enzyme system. One of the metabolites, desacetyldylthiazem, has 25-50% of the activity of the unchanged substance. It is excreted mainly in the form of metabolites with bile and urine, approximately 2-4% is excreted in the urine unchanged. Diltiazem is poorly excreted by dialysis.

Indications

prevention of angina attacks (including Prinzmetal's angina)
arterial hypertension (lowering pressure)
prevention of supraventricular arrhythmias (paroxysmal supraventricular tachycardia, atrial fibrillation, atrial flutter, extrasystole)
relief of acute attacks of angina pectoris, prevention of spasm of the coronary arteries during coronary angiography or coronary artery bypass surgery, paroxysmal ventricular tachycardia, for the relief of frequent ventricular rhythm with atrial fibrillation or flutter (with the exception of WPW syndrome) - for intravenous administration.

Release form

Tablets 30 mg, 60 mg and 90 mg.

Long-acting film-coated tablets 90 mg and 180 mg (Diltiazem Lannacher).

Long-acting capsules 90 mg, 120 mg and 180 mg (Diltiazem Retard).

Long-acting film-coated tablets 120 mg and 240 mg (Diltiazem Teva).

Instructions for use and dosage

Pills

When taken orally, the initial dose is 60 mg 3 times a day or 90 mg 2 times a day. With insufficient effectiveness, the dose is increased to 180 mg 2 times a day. Prolonged forms are used 1-2 times a day, depending on the dose.

The maximum daily dose for oral administration is 360 mg.

Ampoules

With intravenous administration, a single dose is 300 mcg / kg.

For intravenous drip, the dose is 2.8-14 mcg / kg / min. The maximum daily dose is 300 mg.

Tablets Retard

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 of 90 mg 2 times a day. The 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 per day (used only in a hospital).

Lannacher tablets

The drug is prescribed in a daily dose of 180-360 mg, divided into 2 doses. When switching to long-term maintenance therapy, the dose of the drug can be reduced to 180 mg 1 time per day (in the morning).

Tablets should be taken whole, without chewing and with a small amount of liquid.

Side effect

dry mouth;
nausea, vomiting;
constipation;
flatulence;
heartburn;
increased activity of hepatic transaminases;
arterial hypotension;
violation of AV conduction;
symptoms of heart failure;
bradycardia;
headache;
dizziness;
increased fatigue;
sleep disorders;
nervousness;
skin rash;
exanthema;
swelling of the lower extremities;
hyperplasia of the mucous membrane of the gums.

Contraindications

severe bradycardia;
sick sinus syndrome (SSS);
cardiogenic shock;
AV blockade 2 and 3 degrees (with the exception of patients with a pacemaker);
WPW syndrome;
arterial hypotension;
chronic heart failure stage 2B-3;
acute heart failure;
severe liver dysfunction;
severe renal dysfunction;
pregnancy;
lactation;
children under the age of 18;
hypersensitivity to benzothiazepine derivatives.

Use during pregnancy and lactation

Diltiazem is contraindicated for use during pregnancy and lactation (breastfeeding).

Use in children

The drug is not indicated for use in children and adolescents under the age of 18 years.

special instructions

With caution, the drug should be prescribed to patients prone to arterial hypotension, bradycardia, with intraventricular conduction disorders, elderly patients, patients with impaired liver and kidney function.

During the period of taking the drug, alcohol should be avoided.

Influence on the ability to drive vehicles and control mechanisms

The drug may affect the performance of work that requires the speed of psychomotor reactions (management of mechanisms, vehicles).

drug interaction

With the simultaneous administration of the drug Diltiazem with antihypertensive agents, an increase in the hypotensive effect is noted.

With the simultaneous administration of Diltiazem and digoxin, an increase in the concentration of digoxin in the blood is possible.

With the simultaneous administration of the drug Diltiazem with antiarrhythmic drugs, beta-blockers, cardiac glycosides, bradycardia, impaired AV conduction, and symptoms of heart failure may develop.

Cimetidine weakens the process of biotransformation of diltiazem in the liver, slows down its excretion, increasing the duration of action of the drug Diltiazem.

While taking the drug with carbamazepine, quinidine, cyclosporine and theophylline, it is possible to increase the toxic effect of the latter due to the inhibitory effect of diltiazem on cytochrome P450.

Analogues of the drug Diltiazem

Structural analogues for the active substance:

Altiazem RR;
Blockalcin;
Diacordin 120 Retard;
Diacordin 60;
Diacordin 90 Retard;
Dilcardia;
Diltazem SR;
diltiazem hydrochloride;
Diltiazem Lannacher;
Diltiazem retard;
Diltiazem Teva;
Dilren;
Diltz;
Silden;
Cardil;
Cortiazem;
Tiakem.

Analogues for the pharmacological group (calcium channel blockers):

Adalat;
Amlodipine;
Amlocard Sanovel;
Amlonorm;
Amlorus;
Ancardine;
Vamloset;
Verapamil;
Vertizin;
Dilceren;
Isoptin;
Kalchek;
Ko Dalneva;
Co. Exforge;
Corvadil;
Cordaflex;
Cordipin;
Corinfar;
Lerkamen;
Lercanidipine;
Lomir;
Nebilong;
Nicardia;
Nimotop;
Nifedex;
Nifedipine;
Nifecard;
Norvask;
Normodipin;
Octidipine;
Plendil;
Pozikor;
Prestance;
Procorum;
Stamlo;
Stugeron;
Tenox;
felodipine;
Felotens retard;
Finoptin;
Foridon;
Cinnarizine;
Cinnasan;
Ekvakard;
Equator;
Exforge;
Enanorm.

In the absence of analogues of the drug for the active substance, you can follow the links below to the diseases that the corresponding drug helps with and see the available analogues for the therapeutic effect.

Gross formula

C 22 H 26 N 2 O 4 S

Pharmacological group of the substance Diltiazem

Nosological classification (ICD-10)

CAS code

42399-41-7

Characteristics of the substance Diltiazem

A derivative of benzothiazepine. White or off-white crystalline powder with a bitter taste. Insensitive to light. Soluble in water, methanol, chloroform.

Pharmacology

pharmachologic effect- antianginal, hypotensive, antiarrhythmic.

It blocks voltage-dependent L-type calcium channels and inhibits the entry of calcium ions into the depolarization phase of cardiomyocytes and vascular smooth muscle cells. As a result of inhibition of the slow depolarizing flow of calcium into the cells of excitable tissues, it inhibits the formation of an action potential and uncouples the excitation-contraction process. Reduces myocardial contractility, reduces heart rate and slows down AV conduction. Relaxes vascular smooth muscle, lowers OPSS. It has a dose-dependent antihypertensive effect in mild to moderate hypertension. The degree of reduction in blood pressure correlates with the level of hypertension (in people with normal blood pressure, there is only a minimal decrease in blood pressure). The hypotensive effect is manifested both in the horizontal and in the vertical position. Rarely causes postural hypotension and reflex tachycardia. Does not change or slightly reduces the maximum heart rate during exercise.

Long-term therapy is not accompanied by hypercatecholaminemia, an increase in the activity of the renin-angiotensin-aldosterone system. Reduces renal and peripheral effects of angiotensin II. The antianginal effect is due to a decrease in myocardial oxygen demand, due to a decrease in heart rate and systemic blood pressure, vasodilation of epicardial vessels, and the ability to eliminate coronary spasm. Relaxes the smooth muscles of the coronary vessels at a concentration that does not cause a negative inotropic effect. Efficiency in supraventricular tachycardias is associated with an increase (by 20%) in the effective and functional refractory period of the AV node and a prolongation of the conduction time in the AV node (with a normal heart rate, the effect on the AV node is minimal). Slows ventricular rate in patients with high ventricular rate with atrial fibrillation and flutter. Restores normal sinus rhythm in paroxysmal supraventricular tachycardia, interrupts the circulation of excitation of the re-entry type in nodal tachycardia and tachycardia with reciprocal conduction, incl. WPW syndrome e. Long-term use is accompanied by a slight increase in the sinoatrial PR interval on the ECG. With the syndrome of weakness of the sinus node, it significantly increases the duration of the sinus cycle. With atrial fibrillation and flutter under conditions of bolus administration, it effectively lowers heart rate (by at least 20% in 95% of patients). The action usually occurs within 3 minutes and reaches a maximum within 2-7 minutes. The slowing of the rhythm persists for 1-3 hours. With prolonged infusion, a decrease in heart rate by 20% is observed in 83% of patients and persists after administration for a period of 0.5 hours to 10 hours. Efficiency in restoring sinus rhythm in paroxysmal supraventricular tachycardias is 88 % within 3 min. In patients with severe changes in the myocardium of the left ventricle (heart failure, myocardial infarction, hypertrophic cardiomyopathy), it does not change contractility, final diastolic blood pressure in the left ventricle and pulmonary capillary wedge pressure. It has a minimal effect on the smooth muscles of the gastrointestinal tract. Long-term (8 months) therapy is not accompanied by the development of tolerance and changes in the plasma lipid profile. Able to cause regression of left ventricular hypertrophy in patients with arterial hypertension. In usual therapeutic doses, it does not affect mortality, but in patients with signs of pulmonary congestion, it increased the incidence of cardiovascular complications by 40%. In patients with acute myocardial infarction on the background of thrombolytic therapy with a plasminogen activator, it increased the frequency of hemorrhagic complications by 5 times.

Well (more than 90% of the dose) is absorbed from the gastrointestinal tract. Bioavailability is 40% (pronounced effect of "first pass" through the liver). C max is reached in 2-4 hours (table), 3.9-4.3 hours (caps. 180 mg), 5-7 hours (table. retard), 6-14 hours (caps. prolong.). The volume of distribution is 5.3 l/kg. T 1/2 is 1-3 hours (with intravenous administration), 3-4.5 hours (table), 5-7 hours (table retard), 7.3-14.7 hours (caps. 180 mg). It binds to plasma proteins by 70-80% (40% - with acidic alpha-glycoprotein, 30% - with albumin). The action develops within 3 minutes with a rapid on / in the introduction, after 2-3 hours (caps. prolong.) Or 30-60 minutes (table.) when administered orally. The duration of action when taken orally is 4-8 hours (table) and 12-24 hours (caps. prolong.). Metabolized in the liver by deacetylation, demethylation with the participation of cytochrome P450 (in addition to conjugation). The two main metabolites found in plasma after oral administration are deacetyldylthiazem and desmethyldilthiazem. The deacetylated metabolite has the properties of a coronary vasodilator (plasma concentration is 10-20%, activity - 25-50% of that of diltiazem), is capable of cumulation. With a single intravenous administration, these metabolites are not detected in plasma. It is concentrated in bile and undergoes enterohepatic circulation. Excretion (including metabolites) is carried out mainly through the gastrointestinal tract (65%) and to a lesser extent by the kidneys (35%). In the urine, 5 metabolites and 2-4% of the unchanged drug are determined. Penetrates into breast milk. With prolonged oral administration, bioavailability increases and clearance decreases, which leads to an increase in therapeutic effects and side effects.

According to the results obtained in 21-24-month experiments on rats and mice and in bacterial tests in vitro, does not possess carcinogenic and mutagenic activity. In experiments on rats, mice, rabbits, when using doses 5-10 times higher than the recommended daily doses for humans, it caused the death of embryos and fetuses, a decrease in the survival rate of newborn rats and the development of skeletal anomalies. At doses 20 or more times higher than those recommended for humans, it increased the frequency of stillbirths in experimental animals.

It can be used in transplantology: after kidney transplantation (prevention of graft failure), during immunosuppressive therapy (to reduce the nephrotoxicity of cyclosporine A).

The use of the substance Diltiazem

Angina pectoris (stable, vasospastic); prevention of coronary spasm during coronary angiography or coronary artery bypass surgery; arterial hypertension (monotherapy or in combination with other antihypertensive drugs), incl. after myocardial infarction (mainly retard forms, when beta-blockers are contraindicated), in patients with concomitant angina pectoris (if there are contraindications to the appointment of beta-blockers), in patients with diabetic nephropathy (when ACE inhibitors are contraindicated); paroxysmal supraventricular tachycardia.

Contraindications

Hypersensitivity, severe arterial hypotension (SBP less than 90 mm Hg), cardiogenic shock, left ventricular systolic dysfunction (clinical and radiological signs of congestion in the lungs, left ventricular ejection fraction less than 35-40%), incl. in acute myocardial infarction, sinus bradycardia (less than 55 beats / min), sick sinus syndrome (if no pacemaker is implanted), sinoatrial and AV block II-III degree (without a pacemaker), WPW syndrome and Lown-Ganong syndrome - Levin with paroxysms of atrial fibrillation or flutter (except for patients with a pacemaker), pregnancy, breastfeeding.

Application restrictions

Sinoatrial and AV blockade of the first degree, severe aortic stenosis, intraventricular disturbance of excitation (left or right bundle branch block), chronic heart failure, renal and / or liver failure, old age, children (efficacy and safety of use have not been determined) age .

Use during pregnancy and lactation

Contraindicated in pregnancy.

At the time of treatment should stop breastfeeding.

Side effects of Diltiazem

From the side of the cardiovascular system and blood (hematopoiesis, hemostasis): transient hypotension; bradycardia, conduction disorder I degree, decrease in cardiac output, palpitations, fainting, eosinophilia.

From the nervous system and sensory organs: headache, dizziness, weakness, feeling tired.

From the genitourinary system: peripheral edema, impaired potency (separate cases).

From the digestive tract: dyspeptic phenomena (constipation or diarrhea, nausea, heartburn, etc., more often in elderly patients), hyperplasia of the gum mucosa (rarely).

From the side of the skin: sweating, redness of the skin.

Allergic reactions: skin rash and itching, rarely - exudative erythema multiforme.

Others: increased activity of transaminases (ALT, AST), LDH and alkaline phosphatase, hyperglycemia (separate cases).

Interaction

Increases plasma levels of carbamazepine, theophylline, cyclosporine A, digoxin. May enhance the inhibitory effect of anesthetics on contractility, conduction and automatism of the heart. Weakens the nephrotoxic effects of cyclosporine A. Cimetidine increases the level of diltiazem in plasma, digoxin - potentiates the effectiveness in the tachysystolic form of atrial fibrillation. Antiarrhythmic drugs and beta-blockers contribute to the development of bradycardia, AV conduction disorders, symptoms of heart failure. Antihypertensive drugs enhance the hypotensive effect. Diltiazem solution is incompatible with furosemide solution.

Overdose

Symptoms: bradycardia, hypotension, intracardiac blockade and heart failure.

Treatment: gastric lavage, administration of activated charcoal, plasmapheresis and hemoperfusion using activated charcoal. Antidote properties are calcium preparations (calcium gluconate) when administered intravenously, symptomatic therapy - the introduction of atropine, isoproterenol, dopamine or dobutamine, diuretics, fluid infusion. At high degrees of AV blockade, electrical pacing is possible.

Routes of administration

inside.

Diltiazem Substance Precautions

Against the background of taking dosage forms of prolonged action, it is not recommended to / in the introduction of beta-blockers. It should be used with caution to normalize the heart rhythm in patients with impaired hemodynamics or in conjunction with drugs that reduce OPSS, myocardial contractility and conduction. Parenteral administration is possible with the availability of funds and equipment (including a defibrillator) for emergency care. With prolonged intravenous administration, constant monitoring of the ECG and blood pressure is necessary.