Diacordin® [Diltiazem]

Pharmacological properties

Diltiazem is used to prevent angina attacks and reduce hell. the drug reduces myocardial oxygen demand and improves coronary blood supply, which prevents the occurrence of an attack of angina pectoris. diltiazem affects the blood vessels and thus reduces hell.

The mechanism of action of diltiazem is to limit the ingress of calcium into the myocardial cells and into the smooth muscle cells of the vessel walls, which leads to vasodilation, and, consequently, to a decrease in peripheral vascular resistance and a decrease in blood pressure. This drug does not cause reflex tachycardia due to the negative chronotropic effect of diltiazem.

The clinical response is achieved by doses of diltiazem, which cause a minimal negative inotropic effect or do not cause such an effect at all. Diltiazem reduces myocardial oxygen demand. The antianginal effect is noted after taking the initial dose, while the antihypertensive effect is manifested only after about two weeks of continuous use of the drug.

Pharmacokinetics Diltiazem is very rapidly absorbed in the digestive tract and enters the bloodstream several minutes after administration. WITH_max in blood plasma determined after 4.1-7.1 hours after administration. The degree of binding of diltiazem to plasma proteins is 80–85%. Due to the effect of the first pass, the bioavailability of the tablet, which contains 60 mg of diltiazem, is about 40%.

Diacordin 90 and 120 retard: due to the slow release of the active substance, C_max diltiazema in blood plasma is achieved 5-7 hours after administration, the duration of action is 12 hours.

Biological T_½ Diltiazem consists of two phases: the early - 20-30 minutes and the final - about 3.5 hours. Diltiazem is largely metabolized by liver cytochrome P450. The two main circulating metabolites are N-monodesmethyldylthiazem and deacetyldyldiazem. Diltiazem is excreted in the bile (65%) and urine (35%).

Indications

• Stable angina pectoris, vasospastic angina pectoris (prinzmetal angina) vasospastic angina pectoris; ag i and ii stages - both for monotherapy, and in combination with other antihypertensive drugs.

Application

The dose of the drug should be selected individually, depending on the appropriate reaction of the patient. in elderly patients, a possible increased reaction to the drug should be considered. the drug should be taken with food or on an empty stomach. the tablet is swallowed whole, washed down with a sufficient amount of water.

Diacordin 60. Adults are usually prescribed 60 mg (1 tablet) 3-4 times a day. The maximum daily dose for adults is 360 mg (6 tablets). The treatment of elderly people and patients with impaired liver or kidney function can begin with the introduction of the drug in a dose of 60 mg 2 times a day, which is gradually increased in accordance with the therapeutic response.

Diacordin 90 retard. Adults are usually prescribed 90 mg (1 tablet) 2 times a day. With insufficient effectiveness, the dose can be increased to 180 mg (2 tablets) 2 times a day. The maximum daily dose for adults is 360 mg (4 tablets).

Diacordin 120 retard. Adults are usually prescribed 120 mg (1 tablet) 2 times a day. The maximum daily dose for adults is 360 mg (3 tablets).

Contraindications

• Hypersensitivity to diltiazem or excipients that are part of the drug; cardiogenic shock on the background of myocardial infarction or heart failure; severe arterial hypotension (systolic hell 90 mm RT. Art.); decompensated heart failure; acute myocardial infarction with complicated course; ventricular arrhythmia and / or extrasystole; av blockade of degree II or III without pacemaker; atrial flutter or atrial fibrillation with wolf-parkinson-white syndrome or laun-ganong-levin syndrome without an implanted pacemaker; violation of conduction in the sinus-atrial node (sinus node weakness syndrome); bradycardia (heart rate 55 bpm); concomitant use with dantrolene infusion due to the risk of ventricular fibrillation (see interactions); During pregnancy and breastfeeding; children under 15 years old.

Side effects

Classification of the incidence of adverse reactions: very often (1/10); often (1/100 1/10); infrequently (1/1000 1/100); rarely (1/10 000 1/1000); very rarely (1/10 000), including single messages.

On the part of the cardiovascular system: often - AV blockade of I degree, sinus bradycardia; rarely - bradycardia, AV block II – III degree, cessation of sinus node activity, exacerbation of symptoms of angina pectoris, congestive heart failure, arterial hypotension, tachycardia, palpitations, arrhythmia, extrasystole, fainting, hot flashes, peripheral edema, syncope.

From the alimentary canal: often - nausea, constipation, diarrhea, pain in the stomach, dry mouth and throat; rarely - anorexia, dyspepsia, vomiting, weight gain, gingivitis, gingival hyperplasia.

On the part of the skin: often - exanthema, itching, skin rashes; rarely Stevens-Johnson syndrome, angioedema, toxic epidermal necrolysis, exfoliative dermatitis, lupus erythematosus, petechiae, photosensitivity, urticaria, allergic skin reactions, including erythema multiforme, vasculitis, lymphadenopathy, eosinophilia.

From the hepatobiliary system: often - increased levels of aminotransferases; rarely - granulomatous hepatitis, increased levels of alkaline phosphatase, AlAT, AsAT, LDH, hyperglycemia.

From the hematopoietic and lymphatic system: rarely - thrombocytopenia, leukopenia, prolonged bleeding time.

From the psyche: rarely - confusion, amnesia, depression, hallucinations, insomnia, nervousness, personality change, impaired taste and smell.

From the nervous system: often - headache, dizziness; rarely - gait disturbance, paresthesia, drowsiness, tremor, asthenia; frequency unknown - extrapyramidal syndrome.

From the side of the organ of vision: rarely - amblyopia, eye irritation.

On the part of the hearing organ: rarely - tinnitus.

From the musculoskeletal system: rarely - pain in the bones and joints, myalgia.

From the respiratory system: rarely - shortness of breath, nosebleeds, congestion in the nose.

From the urinary system: rarely - nocturia, polyuria, increased creatine kinase levels.

From the reproductive system: rarely - gynecomastia, sexual dysfunctions.

General disorders and reactions at the injection site: infrequently - weakness and fatigue, sweating, general malaise.

special instructions

It is necessary to prescribe the drug with caution to patients with hepatic or renal failure, as well as to patients prone to arterial hypotension or bradycardia (55 beats / min). the drug should be used with caution in patients with acute porphyria.

Diltiazem should be used with caution in patients with left atrial insufficiency, bradycardia, prolonged P-Q interval and aortic stenosis. Caution should also be exercised during the joint use of the drug with β-adrenergic receptor blockers or other drugs that reduce cardiac contractility or AV conduction.

Calcium antagonists can potentiate the effects of anesthetics on the formation of cardiac impulses, affect conduction, contractility and vascular tone.

Calcium antagonists can help reduce male fertility, this should be considered if patients who take calcium antagonists are diagnosed with infertility of unknown etiology. This effect disappears after discontinuation of therapy.

Absorption of diltiazem can be reduced in patients with prolonged depression (for example, with ulcerative colitis or Crohns disease).

Patients with rare inherited disorders such as galactose intolerance, lactase deficiency, or glucose-galactose malabsorption should not take this medication.

During treatment, it is not recommended to drink alcohol.

During pregnancy and breastfeeding. The drug is contraindicated during pregnancy and lactation. If it is necessary to use the drug, breast-feeding should be discontinued.

Children. The drug is not used in children.

The ability to influence the speed of reactions when driving vehicles and working with other mechanisms. At the beginning of treatment, the drug can adversely affect activities that require quick mental and physical reactions, the adoption of quick decisions, so the use of the drug while driving or working with other mechanisms is not recommended.

Interactions

There is evidence that the regular occurrence of ventricular fibrillation, which led to death in animals in which diltiazem was used as a concomitant therapy for dantrolene infusion. therefore, the combination with dantrolene is potentially unsafe (see contraindications).

Possible potentiation of the action of other antihypertensive drugs. The simultaneous use of the drug with β-adrenoreceptor blockers, amiodarone or digoxin, can inhibit AV conduction and increase the risk of developing bradycardia or the occurrence of heart failure. Diltiazem may increase the severity of the inhibitory effect on the heart of halothane and isoflurane. In / in the use of calcium salts reduces the pharmacological response to the use of diltiazem.

Diltiazem is initially metabolized via the cytochrome CYP 3A4 enzyme mechanism. Cimetidine as an inhibitor of the cytochrome CYP 3A4 enzyme can increase the concentration of diltiazem in blood plasma.

It is possible to potentiate the effect of diltiazem while used with macrolides, antifungal drugs, azole derivatives, fluoxetine, tamoxifen, nifedipine and HIV protease inhibitors. With the simultaneous use of drugs that induce cytochrome CYP 3A4, for example, carbamazepine, moricizine, phenobarbital and rifampicin, it is possible to accelerate the metabolism of diltiazem.

Diltiazem inhibits the metabolism of drugs that are metabolized by the enzymes cytochrome CYP 3A4 and P-glycoprotein. Diltiazem is also a substrate for the cytochrome CYP 3A4 enzyme and P-glycoprotein. It is necessary to control the concentration in the blood plasma and the development of side effects when using the following drugs: carbamazepine, phenytoin, cyclosporine, sirolimus, tacrolimus, digoxin, digitoxin, methylprednisolone and theophylline. With the simultaneous use of diltiazem and HMG-CoA reductase inhibitors, which are metabolized using cytochrome CYP 3A4 enzymes, for example, simvastatin, atorvastatin, lovastatin and serivastatin, the doses of the latter should be reduced to prevent the development of rhabdomyolysis and liver damage. The drug does not inhibit the clearance of pravastatin and fluvastatin.

With the simultaneous use of diltiazem and nifedipine, quinidine, propranolol, metoprolol, imipramine, nortriptyline, sildenafil, buspirone, midazolam, triazolam, diazepam, alprazolam, alfentanil and cisapride, the concentration of the latter in the blood plasma may increase.

With the simultaneous use of lithium and diltiazem preparations, neurotoxicity may develop, therefore, it is necessary to carefully monitor the concentration of lithium in the blood serum.

The simultaneous use of disopyramide, procainamide or quinidine (and other similar substances that affect myocardial contraction) with diltiazem may increase the risk of diltiazem-specific side effects (increased negative inotropic effects).

With the simultaneous use of diltiazem with prolonged-action nitrates, an additive effect is manifested during the treatment of angina pectoris.

The drug can potentiate the reduction of contractility, conduction and myocardial automatism and promotes the expansion of blood vessels due to the use of anesthetics.

Overdose

The clinical effects of acute overdose may include bradycardia, high severity av blockade, heart failure, and arterial hypotension. Diltiazem is poorly excreted by dialysis. therapy in case of overdose: rinse the stomach, take activated charcoal, inject iv calcium preparations. with bradycardia and av-blockade, it is advisable to consider the possibility of iv administration of atropine and pacing; with heart failure - iv administration of dopamine and diuretics; with arterial hypotension - in / in the introduction of dopamine and fluid infusion.

With tachycardia in patients with Laun-Ganong-Levine syndrome, impaired cardiac conduction, which leads to an accelerated contraction of the ventricles or atrial fibrillation, cardioversion or iv administration of lidocaine or mesocaine is recommended.

Storage conditions

At a temperature not exceeding 25 ° C.