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Diltiazem

Diltiazem
Diltiazem is used for arterial hypertension (monotherapy or in combination with other antihypertensive drugs).

Brand: Diltiazem

Availability: In Stock
Average Delivery Time: 9 Days
Exp. Date: October 2023
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Diltiazem 180 mg
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Diltiazem 120 mg
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Diltiazem 90 mg
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Diltiazem 60 mg
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Diltiazem 30 mg
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Product description

Pharmacological action of Diltiazem 

Buy Diltiazem in Canada

Class III selective calcium channel blocker, benzothiazepine derivative. It has antianginal, hypotensive and antiarrhythmic effects. Reduces myocardial contractility, slows down AV conduction, decreases 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. At 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 systemic 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 the transport of calcium ions in the heart tissues, which leads to a lengthening of the effective refractory period and a slowdown in conduction in the AV node (in patients with SSS, elderly people, in whom blockade of calcium channels can interfere with the generation of an impulse in the sinus node and cause sinoatrial blockade). Normal atrial action potential or intraventricular conduction is unchanged (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. The anterograde effective refractory period in additional bypass conduction bundles can 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 with flutter or atrial fibrillation.

The antihypertensive effect is due to the dilatation of resistive vessels and a decrease in OPSS. The degree of decrease 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 II. Promotes diastolic relaxation of the myocardium in arterial hypertension, ischemic heart 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 blood lipid profile.

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

Pharmacokinetics

After oral administration, diltiazem is almost completely absorbed from the gastrointestinal tract. 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 extensively metabolized in the liver with the participation of the cytochrome Penzyme system450. One of the metabolites, desacetyldylthiazem, has 25-50% activity of the unchanged substance.

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

Diltiazem is poorly eliminated by dialysis.

Indications of the active substances of the drug Diltiazem

Prevention of angina attacks with Diltiazem

Prevention of angina attacks (including Prinzmetal's angina). 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 grafting, paroxysmal ventricular tachycardia, to arrest the rapid rhythm of the ventricles with atrial fibrillation or flutter (except for WPW syndrome).

Dosage regimen of Diltiazem

Diltiazem 30mg and 60mg packaging

For oral administration, 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.

The maximum daily dose for oral administration is 360 mg.

When administered intravenously, a single dose is 300 mcg / kg.

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


Contraindications for use

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

Application during pregnancy and lactation

Contraindicated for use during pregnancy and lactation (breastfeeding).

In experimental studies , the teratogenic effect of diltiazem has been established.

Application for violations of liver function

Contraindicated in violation of liver function. Use with caution in liver failure.

Application for impaired renal function

Contraindicated in impaired renal function. Use with caution in renal failure.

Use in children 

Use with caution in children (efficacy and safety have not been studied).

Use in elderly patients

Use with caution in elderly patients.

Special instructions

Use with caution in AV blockade of the 1st degree, intraventricular conduction disorders, in patients prone to arterial hypotension, chronic heart failure, myocardial infarction with left ventricular failure, ventricular tachycardia with expansion of the QRS complex, liver failure, renal failure, in elderly patients age, in children (efficacy and safety of use have not been studied).

IV is used only for emergency treatment, 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, the indications for intravenous administration of diltiazem should be strictly clarified and used only after ECG monitoring in the intensive care unit, while taking into account the possible need to use a pacemaker.

The simultaneous use of beta-blockers and diltiazem for parenteral administration is not recommended.

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

Patients with impaired liver and / or kidney function and the elderly require dosage adjustment.

Drug interaction

With simultaneous use with beta-blockers (including propranolol, atenolol, metoprolol, pindolol, sotalol), an additive cardiodepressant effect is possible along with an increase in antianginal action in most patients. Patients with preexisting left ventricular dysfunction or conduction abnormalities are at increased risk of severe and threatening bradycardia.

Diltiazem inhibits the metabolism of propranolol, metoprolol, but not atenolol.

With simultaneous use with amiodarone, the negative inotropic effect, bradycardia, conduction disturbances, AV blockade are enhanced.

Since diltiazem inhibits the isoenzyme CYP3A4, 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 the development of rhabdomyolysis are described.

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

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

With simultaneous use with digoxin, digitoxin, an increase in the concentration of digoxin and digitoxin in blood plasma is possible.

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 with simultaneous use with diltiazem have been described.

Diltiazem increases the bioavailability of imipramine by decreasing 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.

With simultaneous use with insulin, a case of a decrease in the effectiveness of insulin has been described.

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

With simultaneous use with lithium carbonate, cases of the development of acute parkinsonism syndrome, psychosis have been described.

With simultaneous use with midazolam, triazolam, the concentration of midazolam and triazolam in the blood plasma increases and their effects are enhanced due to the inhibition of the CYP3A4 isoenzyme under the influence of diltiazem, with the participation of which these benzodiazepines are metabolized.

When used simultaneously with sodium amidotrizoate, the antihypertensive effect of diltiazem may be enhanced.

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

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 the metabolism of theophylline 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 isoenzyme CYP3A4, which leads to an increase in the concentration of cisapride in the blood plasma and, possibly, to an increase in its cardiotoxicity.

With 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. The effects of diltiazem may be enhanced.

With simultaneous use with enflurane, cases of violation of the AV conduction of the myocardium have been noted.

Side effect

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, stiff arms or legs, trembling 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 fibrillation of the ventricles), bradycardia (less than 50 beats / min) or tachycardia, AV block II and III degrees up to asystole, development or aggravation of heart failure; when used in high doses and with intravenous administration - angina pectoris, bradycardia, AV blockade, marked 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 facial skin, skin rash, arthritis, erythema multiforme exudative (including Stevens-Johnson syndrome).

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