Diltiazem Lannacher (Tablets) Instructions for Use

Marketing Authorization Holder

Bausch Health, LLC (Russia)

Manufactured By

G.L. Pharma, GmbH (Austria)

Contact Information

BAUSH HEALTH LLC (Russia)

ATC Code

C08DB01 (Diltiazem)

Active Substance

Diltiazem (Rec.INN registered by WHO)

Dosage Forms

	Diltiazem Lannacher	Extended-release film-coated tablets, 90 mg: 20 pcs.
		Extended-release film-coated tablets, 180 mg: 30 pcs.

Dosage Form, Packaging, and Composition

Extended-release film-coated tablets white, round, biconvex, with a white core on the cross-section.

Excipients : lactose monohydrate, methyl methacrylate and ethyl acrylate copolymer [2:1], methacrylic acid and ethyl acrylate copolymer [1:1], ethyl acrylate, methyl methacrylate, trimethylammonioethyl methacrylate chloride copolymer [1:2:0.1], hypromellose 5 mPa*s, magnesium stearate; coating: hypromellose 5 mPa*s, macrogol 6000, titanium dioxide, talc, methyl methacrylate and ethyl acrylate copolymer [2:1].

10 pcs. – blisters (2) – cardboard packs.

Extended-release film-coated tablets white, round, biconvex, with a white core on the cross-section.

Excipients : lactose monohydrate, methyl methacrylate and ethyl acrylate copolymer [2:1], methacrylic acid and ethyl acrylate copolymer [1:1], ethyl acrylate, methyl methacrylate, trimethylammonioethyl methacrylate chloride copolymer [1:2:0.1], hypromellose 5 mPa*s, magnesium stearate; coating: hypromellose 5 mPa*s, macrogol 6000, titanium dioxide, talc, methyl methacrylate and ethyl acrylate copolymer [2:1].

10 pcs. – blisters (3) – cardboard packs.

Clinical-Pharmacological Group

Calcium channel blocker

Pharmacotherapeutic Group

“Slow” calcium channel blocker

Pharmacological Action

Diltiazem is a benzothiazepine derivative; it has antiarrhythmic, antianginal, and antihypertensive activity.

A blocker of “slow” calcium channels (BSCC), it reduces the intracellular content of calcium ions in cardiomyocytes and smooth muscle cells, dilates coronary and peripheral arteries and arterioles, reduces total peripheral vascular resistance (TPVR), smooth muscle tone, enhances coronary, cerebral, and renal blood flow, and slows the heart rate (HR).

Antiarrhythmic action is due to the suppression of ionized calcium transport in heart tissues, which leads to an increase in the effective refractory period and prolongation of conduction time in the atrioventricular (AV) node (clinically significant in patients with sick sinus syndrome, elderly patients, in whom calcium channel blockade may impede 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 not affected), but with a decrease in atrial contraction amplitude, the depolarization rate and conduction velocity decrease. The antegrade effective refractory period in accessory bypass tracts may shorten.

Antianginal action is due to the dilation of peripheral vessels and a decrease in systemic BP (afterload), which leads to a reduction in myocardial wall tension and its oxygen demand.

At concentrations not causing a negative inotropic effect, it causes relaxation of the smooth muscles of the coronary vessels and dilation of both large and small arteries.

Antihypertensive action is due to the dilation of resistive vessels and a decrease in TPVR.

The degree of BP reduction correlates with its initial level (minimal effect on BP is noted in “normotensive” individuals).

It reduces BP both in the supine and standing positions.

It rarely causes postural arterial hypotension and reflex tachycardia.

It does not change or slightly reduces the maximum HR during exercise.

Long-term therapy does not lead to hypercatecholaminemia, increased activity of the RAAS.

It reduces the renal and peripheral effects of angiotensin II.

It improves diastolic myocardial relaxation in arterial hypertension, coronary artery disease, hypertrophic obstructive cardiomyopathy, and reduces platelet aggregation.

It has a minimal effect on the smooth muscles of the gastrointestinal tract.

Tolerance does not develop during long-term (8 months) therapy.

It does not affect the blood lipid profile.

It is capable of causing regression of left ventricular hypertrophy in patients with arterial hypertension.

The onset of action after 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

Absorption and Distribution

After oral administration, it is rapidly and almost completely absorbed from the gastrointestinal tract.

The time to reach C_max in blood plasma is 6-14 hours.

Binding to plasma proteins is 70-80% (with albumin – 35-40%).

It penetrates into breast milk.

Metabolism

It is intensively metabolized in the liver by deacetylation and demethylation (with the participation of isoenzymes CYP3A4, CYP3A5, and CYP3A7) to form the active metabolite desacetyldiltiazem, which is detected in plasma at a concentration 5-10 times lower than Diltiazem and has 2-4 times lower activity.

Elimination

The T_1/2 of diltiazem after oral administration is biphasic: early – 20-30 minutes, terminal – 3.5 hours (5-8 hours – with high and repeated doses).

The T_1/2 of the drug Diltiazem Lannacher in the extended-release tablet dosage form of 90 mg and 180 mg is up to 10 hours.

It is excreted through the intestine with bile (65%) and by the kidneys (35%, including 2-4% unchanged).

The pharmacokinetics of diltiazem do not change with long-term use.

The drug does not accumulate and does not induce its own metabolism.

Pharmacokinetics in Special Clinical Cases

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

It is not removed by hemodialysis and peritoneal dialysis.

In patients with hepatic insufficiency, bioavailability increases and T_1/2 is prolonged.

In the elderly, the clearance of diltiazem may also be reduced.

Indications

• Arterial hypertension;
• Prevention of angina attacks (including Prinzmetal’s angina);
• Prevention of supraventricular arrhythmia attacks (paroxysmal tachycardia, atrial fibrillation or flutter, extrasystole).

ICD codes

Dosage Regimen

The drug is taken orally, before meals, without chewing and with a small amount of liquid.

The dosage regimen is set individually.

The initial dose of Diltiazem Lannacher is 1 tab. (90 mg) 2 times/day. The average daily dose is 180-270 mg. The maximum daily dose is 360 mg.

Adjustment of the dosage regimen can be made only after 2 weeks. With long-term treatment and good therapeutic effect, a dose reduction is possible.

Adverse Reactions

From the cardiovascular system bradycardia, ventricular extrasystole, chronic heart failure, sinoauricular block, AV-block up to asystole, pronounced decrease in BP, syncope, skin flushing, angina, arrhythmia (including ventricular flutter and fibrillation), tachycardia, dyspnea, peripheral edema. When used in high doses – angina, bradycardia, AV-block.

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

From the nervous system headache, general weakness, asthenia, increased fatigue, anxiety, dizziness, drowsiness, insomnia, depression, pathological fear state, extrapyramidal disorders, parkinsonism (ataxia, mask-like face, “shuffling” gait, stiffness of arms or legs, trembling of hands and fingers, difficulty swallowing). When used in high doses – paresthesia.

From the organ of vision visual impairment (transient blindness).

Allergic reactions increased photosensitivity, itching, skin rash, facial skin hyperemia, Stevens-Johnson syndrome, erythema multiforme, exfoliative dermatitis.

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

When used in high doses – pulmonary edema (difficulty breathing, cough, stridor breathing), thrombocytopenia, agranulocytosis, galactorrhea, weight gain.

With abrupt withdrawal of the drug, withdrawal syndrome may develop with accompanying tachycardia, arterial hypertension, and worsening of angina.

Contraindications

• Hypersensitivity to the drug and other benzothiazepine derivatives;
• Sinoatrial and AV-block of II and III degree (except for patients with a pacemaker);
• Severe bradycardia;
• Sick sinus syndrome without the use of an artificial pacemaker;
• Cardiogenic shock;
• Wolff-Parkinson-White syndrome;
• Lown-Ganong-Levine syndrome in combination with atrial flutter or fibrillation (except for patients with a pacemaker);
• Severe arterial hypotension (systolic BP 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 wide QRS complex;
• Pregnancy;
• Breastfeeding period;
• Age under 18 years (efficacy and safety not established);
• Lactose intolerance, lactase deficiency, and glucose-galactose malabsorption.

With caution the drug should be used in patients with severe impairment of liver and kidney function, acute porphyria, with severe aortic stenosis, in the acute phase of myocardial infarction (without signs of left ventricular failure), with hypertrophic obstructive cardiomyopathy, mild and moderate arterial hypotension, AV-block I degree or PQ interval prolongation, simultaneous use with beta-blockers or digoxin, compensated chronic heart failure, with a tendency to bradycardia, in the elderly.

Use in Pregnancy and Lactation

Diltiazem Lannacher is contraindicated during pregnancy and breastfeeding.

Women of childbearing age should be excluded from pregnancy before prescribing diltiazem.

Use in Hepatic Impairment

The drug should be used with caution in patients with severe hepatic impairment.

Use in Renal Impairment

The drug should be used with caution in patients with severe renal impairment.

Pediatric Use

The use of the drug is contraindicated under the age of 18 years (efficacy and safety not established).

Geriatric Use

With caution the drug should be used in the elderly.

Special Precautions

Diltiazem reduces myocardial conduction, so it is prescribed with particular caution to patients with AV-block I degree and with bradycardia.

Caution is also necessary when using it in patients with impaired left ventricular function.

Diltiazem is prescribed with caution to patients already taking other medications, in particular, beta-blockers.

In this group of patients, the treatment process should be carried out under the careful supervision of a cardiologist.

Diltiazem is prescribed with caution to patients with renal or hepatic insufficiency; in this group of patients, if necessary, the prescribed doses of the drug should be reduced and the content of urea in the urine and creatinine should be monitored.

In patients with impaired liver function, the daily dose should not exceed 90 mg, and regular monitoring of liver function is recommended.

For elderly patients, the dose is selected individually, because the T_1/2 of diltiazem may increase.

Since Diltiazem reduces TPVR and may cause secondary arterial hypotension, it is necessary to monitor BP, particularly at the beginning of the course of treatment, while therapeutic doses are not yet specified.

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

If during therapy the patient requires surgery under general anesthesia, it is necessary to inform the anesthesiologist about the nature of the therapy being conducted (the patient is taking Diltiazem Lannacher).

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

Effect on the ability to drive vehicles and mechanisms

The use of Diltiazem Lannacher may negatively affect the performance of work requiring high speed of mental and physical reactions (for example, driving vehicles, operating machinery, working at heights).

Overdose

Symptoms bradycardia, pronounced decrease in BP, turning into collapse, impaired atrioventricular and sinoatrial conduction, heart failure, cardiogenic shock, asystole, nausea, vomiting, metabolic acidosis, hyperkalemia.

Treatment depending on the severity of overdose manifestations.

It is necessary to perform gastric lavage, prescribe activated charcoal, further treatment is symptomatic.

If necessary, it is recommended to prescribe atropine, isoprenaline, dopamine or dobutamine, and also, in case of severe conduction disturbances, the use of electrocardiostimulation is possible.

Hemodialysis and peritoneal dialysis are not effective.

Drug Interactions

Pharmacodynamic interaction

With simultaneous use of diltiazem with antihypertensive agents, an enhancement of the antihypertensive effect is noted.

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

With simultaneous use of diltiazem with antiarrhythmic agents, beta-blockers, cardiac glycosides, the development of bradycardia, impaired AV conduction, and the appearance of symptoms of heart failure are possible.

With simultaneous use with adenosine, the risk of prolonged bradycardia is increased.

Salicylates additionally inhibit the ability of platelet aggregation.

Ethanol enhances the antihypertensive effect.

Procainamide, quinidine, and other drugs causing QT interval prolongation increase the risk of its significant prolongation.

Inhalation anesthetics (hydrocarbon derivatives), thiazide diuretics, and other drugs that reduce BP enhance the hypotensive effect of diltiazem.

Phenytoin reduces the effect of diltiazem.

Antipsychotic agents (neuroleptics) enhance the antihypertensive effect of diltiazem.

Simultaneous administration of nitrates (including prolonged forms) is possible.

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

Indomethacin and other NSAIDs, corticosteroids, and estrogens, as well as sympathomimetic drugs reduce the hypotensive effect.

It enhances the cardiodepressant effect of general anesthetics.

Pharmacokinetic interaction

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

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

It enhances the action of oral hypoglycemic agents (for example, chlorpropamide and glipizide).

With simultaneous use of diltiazem and cyclosporine in patients with a kidney transplant, the development of intoxication with the latter, paresthesia, is possible. Therefore, it is necessary to carefully monitor the plasma concentrations of cyclosporine in this group of patients.

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

It may increase the bioavailability of propranolol.

It increases the plasma concentration of moracizine.

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

It increases the blood concentration of quinidine, valproic acid (dose reduction may be required).

Ritonavir may increase the plasma concentrations of BMKK.

Diltiazem inhibits the metabolism of midazolam (plasma concentration increases with enhanced sedative effect).

The elimination of nifedipine is reduced by diltiazem (plasma concentration increases).

Diltiazem significantly increases the plasma concentration of lovastatin. It also enhances the effect of simvastatin, therefore, when used simultaneously, the doses of simvastatin must be reduced. When diltiazem is used concomitantly with lovastatin and simvastatin, patient monitoring is necessary due to the possibility of developing myositis or rhabdomyolysis.

Storage Conditions

The drug should be stored out of the reach of children at a temperature not exceeding 30°C (86°F).

Shelf Life

The shelf life is 3 years. Do not use after the expiration date.

Dispensing Status

The drug is dispensed by prescription.

Important Safety Information

This information is for educational purposes only and does not replace professional medical advice. Always consult your doctor before use. Dosage and side effects may vary. Use only as prescribed.