Diltiazem Lannacher - instructions for use, dose, side effects, contraindications

Excipients: lactose monohydrate 60.0 / 120.0 mg, methyl methacrylate and ethyl acrylate copolymer [2: 1] 4.5 / 9.0 mg, methacrylic acid and ethyl acrylate copolymer (1: 1) 57.75 (79.5 mg, methyl methacrylate, trimethylammonioethyl methacrylate chloride and ethyl acrylate copolymer [1: 2: 0.1] 7.5 / 15.0 mg, hypromellose 5 mPa * s 9.5 / 15.0 mg, magnesium stearate 0.75 / 1.5 mg;

shell: macrogol 6000 2.247 / 2.996 mg, hypromellose 5 mPa * s 1,875 / 2,500 mg, titanium dioxide 1,017 / 1,356 mg, talc 9,303 / 12,404 mg, methyl methacrylate and ethyl acrylate copolymer [2: 1] 0.558 / 0.744 mg.

Description:

Round, biconvex tablets, covered with a film coat of white color, on a cross-section the core of a tablet of white color.

Pharmacotherapeutic group:blocker of "slow" calcium channels

ATX: & nbsp

C.08.D.B.01 Diltiazem

C.05.A.E.03 Diltiazem

Pharmacodynamics:

Diltiazem is a derivative of benzothiazepines; has antiarrhythmic, antianginal and hypotensive activity. The blocker of "slow" calcium channels (BCCC), reduces the intracellular content of calcium ions in cardiomyocytes and smooth muscle cells, expands coronary and peripheral arteries and arterioles, reduces overall peripheral vascular resistance (OPSS), smooth muscle tone, strengthens coronary, cerebral and renal blood flow , reduces the heart rate (heart rate).

Antiarrhythmic action is caused by the suppression of the transport of ionized calcium in the heart tissues, which leads to an increase in the effective refractory period and an extension of the time spent in the atrioventricular (AV) node (has clinical significance in patients with sinus node weakness syndrome, elderly patients in whom blockade of calcium channels can interfere with generation of a pulse in the sinus node and cause a sinoatrial (SA) blockade).The normal atrial action potential or intraventricular conduction does not change (normal sinus rhythm is usually unaffected), but with a decrease in the amplitude of atrial contraction, the rate of depolarization and speed of conduction decrease. Anterograde effective refractory period in additional bypass beams of conduction may be shortened.

Antianginal action is caused by the expansion of peripheral vessels and a decrease in systemic arterial pressure (postload), which leads to a decrease in the stress of the myocardium wall and its oxygen demand. In concentrations that do not lead to the appearance of a negative inotropic effect, it causes the relaxation of the smooth muscles of the coronary vessels and the dilatation of both large and small arteries.

Antihypertensive action is caused by dilatation of resistive vessels and a decrease in OPSS. The degree of decrease in blood pressure (BP) correlates with its baseline level (in "normotonics" there is a minimal effect on blood pressure). Reduces blood pressure in both the "lying" and "standing" positions. Rarely causes postural arterial hypotension and reflex tachycardia.Does not change or slightly reduces the maximum heart rate under the load. Long-term therapy does not lead to hyperkatecholamineemia, an increase in the activity of the renin-angiotensin-aldosterone system. Reduces the renal and peripheral effects of angiotensin I. Improves diastolic relaxation of the myocardium with arterial hypertension, coronary heart disease, hypertrophic obstructive cardiomyopathy, reduces platelet aggregation.

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

It is able to cause regression of left ventricular hypertrophy in patients with arterial hypertension. The onset of action with oral administration is 2-3 hours. The duration of action is 12-14 hours.

The maximum severity of the hypotensive effect is achieved within 2 weeks.

Pharmacokinetics:

After oral administration, it is quickly and almost completely absorbed into the digestive tract. The time to reach the maximum concentration in blood plasma is 6-14 hours. The connection with plasma proteins is 70-80% (with albumins - 35-40%).Intensively metabolized in the liver by de-acetylation and demethylation (with the participation of isoenzymes CYP3A4, CYP3A5 and CYP3A7) with the formation of an active metabolite of deacetylldithiasem, which is determined in plasma 5-10 times less than that of diltiazem, and has 2-4 times less activity. Penetrates into breast milk.

The half-life period of diltiazem when taken orally is two-phase: early - 20-30 minutes, final - 3.5 hours (5-8 hours - at high and repeated doses). The half-life of the drug Diltiazem Lannacher in the form of a sustained-release tablet 90 mg and 180 mg is up to 10 hours. It is excreted through the intestines with bile (65%) and kidneys (35%, including 2-4% unchanged).

The pharmacokinetics of diltiazem for prolonged use does not change. The drug does not cumulate or induce its own metabolism.

In patients with angina and impaired renal function the pharmacokinetics of diltiazem does not change.

In patients with hepatic insufficiency increases bioavailability and lengthens the half-life.

In old age also the clearance of diltiazem can be reduced. It is not excreted in hemodialysis and peritoneal dialysis.

Indications:

- Arterial hypertension;

- Pthe prevention of angina attacks (including Prinzmetal angina pectoris);

- Pthe prevention of attacks of supraventricular arrhythmias (paroxysmal tachycardia, flicker or atrial flutter, extrasystole).

Contraindications:

Hypersensitivity to the drug and to other benzothiazepine derivatives, sinoatrial and atrioventricular blockade of II and III degree (except for patients with pacemaker), pronounced bradycardia, sinus node weakness syndrome without the use of an artificial pacemaker, cardiogenic shock, Wolff-Parkinson-White syndrome, syndrome Launa-Ganong-Levin in combination with flutter or atrial fibrillation (except for patients with a pacemaker), severe arterial hypotension (systolic blood pressure less than 90 mm Hg), acute heart failure, chronic heart failure (in the stage of decompensation), myocardial infarction with signs of left ventricular failure, ventricular tachycardia with a wide complex QRS, pregnancy, lactation, age under 18 (efficacy and safety not established), lactose intolerance, lactase deficiency and glucose-galactose malabsorption.

Carefully:

Carefully It should be used in patients with severe liver and kidney disease, acute porphyria, severe aortic stenosis, in the acute phase of myocardial infarction (without signs of left ventricular failure), hypertrophic obstructive cardiomyopathy, mild to moderate arterial hypotension, atrioventricular block I degree or elongation interval PQ, While the use of beta-blockers or digoxin, compensated chronic heart failure, with a tendency to bradycardia, in the elderly.

Pregnancy and lactation:

Diltiazem Lannacher is contraindicated during pregnancy and lactation.

Women in child-bearing age before the appointment of diltiazem should be excluded from pregnancy.

Dosing and Administration:

The tablets should be taken orally before meals, with liquid squeezed small amount of liquid.

The dosage regimen is set individually.

Initial dose Diltiazem Lannacher is 1 tablet of 90 mg 2 times a day.

Average daily dose is 180-270 mg. Correction of the dosing regimen can be carried out only after 2 weeks.

The maximum daily dose is 360 mg.

With long-term treatment with a good therapeutic effect, a dose reduction is possible.

Side effects:

From the side of the cardiovascular system: bradycardia, ventricular extrasystole, chronic heart failure, sinoauric blockade, atrioventricular blockade up to asystole, marked decrease in blood pressure, syncope, redness of the skin, angina pectoris, arrhythmia (including flutter and fibrillation of the ventricles), tachycardia, dyspnea, peripheral edema. When used in high doses - angina, bradycardia, atrioventricular block.

From the digestive system: dry mouth, increased appetite, vomiting, nausea, heartburn, diarrhea, gipertrophic gingivitis, constipation, hypercreatininaemia, abdominal pain, impaired liver function, intestinal obstruction.

From the central nervous system: headache, general weakness, asthenia, fatigue, anxiety, dizziness, drowsiness, insomnia, depression, a condition of pathological fear, extrapyramidal disorders, parkinsonism (ataxia, "masky" face, "shuffling" gait,stiffness of hands or feet, trembling of hands and fingers, difficulty swallowing).

When used in high doses - paresthesia.

From the sense organs: impaired vision (transitory blindness).

Allergic reactions: increased photosensitivity, itching, skin rash, facial skin flushing, Stevens-Johnson syndrome, polymorphic erythema, exfoliative dermatitis.

Other: taking the drug may lead to an increase in the concentrations of "liver" enzymes in the blood serum, peripheral edema.

When used in high doses - pulmonary edema (difficulty breathing, coughing, stridorous breathing), thrombocytopenia, agranulocytosis, galactorrhea, weight gain. With a sharp withdrawal of the drug can develop a syndrome of "withdrawal" with concomitant tachycardia, hypertension and worsening of the course of angina.

Overdose:

Symptoms: bradycardia, marked decrease in blood pressure, which results in a collapse, atrioventricular and sinoatrial conduction disorder, heart failure, cardiogenic shock, asystole, nausea, vomiting, metabolic acidosis, hyperkalemia.

Treatment: depending on the severity of the overdose.It is necessary to wash the stomach, appoint Activated carbon, further treatment is symptomatic. If necessary, it is recommended that atropine, isoprenaline, dopamine or dobutamine, and also, with pronounced conduction disorders, the use of electrocardiostimulation is possible.

Hemodialysis and peritoneal dialysis are ineffective.

Interaction:

Pharmacodynamic

With the simultaneous administration of diltiazem with antihypertensive drugs, there is an increase in antihypertensive action.

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 diltiazem with antiarrhythmics, beta-adrenoblockers, cardiac glycosides, bradycardia, violation of atrioventricular conduction, the appearance of symptoms of heart failure may develop.

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 lengthening of the interval QT, increase the risk of significant lengthening.

Means for inhalation anesthesia (derivatives of hydrocarbons), thiazide diuretics and other drugs that reduce blood pressure, enhance the hypotensive effect of diltiazem.

Phenytoin reduces the effect of diltiazem.

Antipsychotic drugs (antipsychotics) increase the antihypertensive effect of diltiazem.

The simultaneous administration of nitrates (including prolonged forms) is possible.

Lithium preparations can enhance the neurotoxic effect of diltiazem (nausea, vomiting, diarrhea, ataxia, tremor and / or tinnitus).

Indomethacin and other nonsteroidal anti-inflammatory drugs, glucocorticosteroids and estrogens, as well as sympathetic drugs, reduce the hypotensive effect.

Strengthens the cardiodepressive effect of general anesthetics.

Pharmacokinetic

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

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

Enhances the effect of hypoglycemic agents for oral administration (eg, chlorpropamide and glipizide).

With the simultaneous use of diltiazem and cyclosporine in patients with a transplanted kidney, it is possible to develop intoxication last, paresthesia. Therefore, it is necessary to closely monitor the plasma concentrations of cyclosporine in this group of patients.

The intake of food increases the absorption and bioavailability of diltiazem by 20-30%.

May increase the bioavailability of propranolol. Increases the concentration of moracisin in the blood plasma.

Phenobarbital, diazepam, rifampicin reduce the concentration of diltiazem in the blood plasma.

Increases the concentration in the blood of quinidine, valproic acid (a dose reduction may be required).

Antiviral drugs: ritonavir can increase plasma concentrations of BCC.

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

BCCI: elimination of nifedipine is reduced by diltiazem (plasma concentration is increased).

Diltiazem significantly increases the concentration of lovastatin in blood plasma. It also increases the action of simvastatin, so when using them simultaneously, simvastatin should be lowered. With the simultaneous use of diltiazem with lovastatin and simvastatin, monitoring of patients is necessary, because of the possibility of developing myositis or rhabdomyolysis.

Special instructions:

Diltiazem reduces the conductance of the myocardium, so it is with particular caution prescribed to patients with AV blockade of the 1st degree and with bradycardia. Caution is also needed when used in patients with left ventricular dysfunction.

Diltiazem with caution appoint patients already taking other medications, in particular, beta-blockers. In this group of patients, the treatment process should be carried out under the close supervision of a cardiologist.

Diltiazem with caution appoint to patients with renal or hepatic insufficiency; in this group of patients, if necessary, reduce the prescribed doses of the drug and monitor the urea content in the urine, creatinine.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, because the half-life of diltiazem may increase.

As diltiazem reduces OSSS and can cause secondary arterial hypotension, it is necessary to monitor blood pressure, in particular, at the beginning of the course treatment, while therapeutic doses are not yet specified.

In the case of persistent skin rashes that develop into polymorphic erythema and exfoliative dermatitis, Diltiazem Lannacher should be discontinued.

If during the therapy the patient is required to undergo surgery under general anesthesia, it is necessary to inform the anesthetist about the nature of the therapy (the patient is receiving Diltiazem Lannacher).

During the administration of Diltiazem Lannacher, the use of alcoholic beverages is not recommended.

Effect on the ability to drive transp. cf. and fur:

The use of Diltiazem Lannacher can negatively affect the performance of work,requiring high speed of mental and physical reactions (for example, management of vehicles, mechanisms, work at height, etc.).

Form release / dosage:

Tablets of prolonged action, film-coated, 90 and 180 mg.

Packaging:

For 10 tablets in PVC / Al blister.

2 blisters (for 90 mg tablets) or 3 blisters (for 180 mg tablets) along with instructions for use in a cardboard pack.

Storage conditions:

Store at a temperature not exceeding 30 ° C.

Keep out of the reach of children.

Shelf life:

3 years.

Do not use after expiry date.

Terms of leave from pharmacies:On prescription

Registration number:П N013738 / 01

Date of registration:26.12.2011 / 02.09.2013

Expiration Date:Unlimited

The owner of the registration certificate:VALEANT, LLC VALEANT, LLC Russia

Manufacturer: & nbsp

LANNACHER HEILMITTEL, GmbH Austria

Representation: & nbspVALEANT LLC VALEANT LLC Russia

Information update date: & nbsp09.11.2016

Illustrated instructions

Instructions

Diltiazem Lannacher (Diltiazem Lannacher)