Amlodigamma (Tablets) Instructions for Use

Marketing Authorization Holder

Woerwag Pharma GmbH & Co. KG (Germany)

Manufactured By

Unichem Laboratories, Ltd. (India)

Packaged By

MAUERMANN ARZNEIMITTEL FRANZ MAUERMANN, OHG (Germany)

ATC Code

C08CA01 (Amlodipine)

Active Substance

Amlodipine (Rec.INN registered by WHO)

Dosage Forms

	Amlodigamma	Tablets 5 mg: 3, 50, 100 or 300 pcs.
		Tablets 10 mg: 3, 50, 100 or 300 pcs.

Dosage Form, Packaging, and Composition

10 pcs. – blisters (3) – carton packs.
10 pcs. – blisters (5) – carton packs.
10 pcs. – blisters (10) – carton packs.
10 pcs. – blisters (30) – carton packs.

10 pcs. – blisters (3) – carton packs.
10 pcs. – blisters (5) – carton packs.
10 pcs. – blisters (10) – carton packs.
10 pcs. – blisters (30) – carton packs.

Clinical-Pharmacological Group

Calcium channel blocker

Pharmacotherapeutic Group

BMCC (Bone Mineral Crystal Complex)

Pharmacological Action

A dihydropyridine derivative – a second-generation slow calcium channel blocker, it has antianginal and antihypertensive effects. By binding to dihydropyridine receptors, it blocks calcium channels, reduces the transmembrane transition of calcium ions into the cell (more so in vascular smooth muscle cells than in cardiomyocytes).

The antianginal effect is due to the dilation of coronary and peripheral arteries and arterioles: in angina, it reduces the severity of myocardial ischemia; by dilating peripheral arterioles, it reduces total peripheral vascular resistance, reduces cardiac preload, and reduces myocardial oxygen demand. By dilating the main coronary arteries and arterioles in unchanged and ischemic areas of the myocardium, it increases oxygen supply to the myocardium (especially in vasospastic angina); prevents the development of coronary artery constriction (including that caused by smoking). In patients with angina, a single daily dose increases exercise tolerance time, slows the development of angina and ischemic ST-segment depression, and reduces the frequency of angina attacks and nitroglycerin consumption.

It has a long-term dose-dependent antihypertensive effect. The antihypertensive effect is due to a direct vasodilatory effect on vascular smooth muscles. In arterial hypertension, a single dose provides a clinically significant reduction in BP over 24 hours (in both supine and standing positions). It does not cause a sharp decrease in BP, a decrease in exercise tolerance, or a decrease in left ventricular ejection fraction. It reduces the degree of left ventricular myocardial hypertrophy, has an antiatherosclerotic and cardioprotective effect in coronary artery disease. It does not affect myocardial contractility and conduction, does not cause a reflex increase in heart rate, inhibits platelet aggregation, increases glomerular filtration rate, and has a weak natriuretic effect. In diabetic nephropathy, it does not increase the severity of microalbuminuria. It has no adverse effects on metabolism and plasma lipids. The onset of action is 2-4 hours, the duration of action is 24 hours.

Pharmacokinetics

After oral administration, Amlodipine is slowly absorbed from the gastrointestinal tract. The mean absolute bioavailability is 64%, C_max in serum is observed after 6-9 hours. Steady-state concentration is reached after 7 days of therapy. Food intake does not affect the absorption of amlodipine. The mean V_d is 21 L/kg of body weight, indicating that most of the drug is in the tissues, and a relatively smaller part is in the blood. Most of the drug in the blood (95%) is bound to plasma proteins. Amlodipine undergoes slow but extensive metabolism (90%) in the liver to form inactive metabolites, has a first-pass effect through the liver. Metabolites do not have significant pharmacological activity. After a single oral dose, T_1/2 ranges from 31 to 48 hours, with repeated administration T_1/2 is approximately 45 hours. About 60% of the orally administered dose is excreted by the kidneys mainly as metabolites, 10% unchanged, and 20-25% through the intestines, and also with breast milk. The total clearance of amlodipine is 0.116 ml/s/kg (7 ml/min/kg, 0.42 L/h/kg). In elderly patients (over 65 years), the elimination of amlodipine is slowed (T_1/2 65 hours) compared to young patients, but this difference is not clinically significant. In patients with hepatic impairment, a prolongation of T_1/2 is expected, and with long-term administration, the accumulation of the drug in the body will be higher (T_1/2 up to 60 hours). Renal impairment does not significantly affect the kinetics of amlodipine. The drug crosses the blood-brain barrier. It is not removed by hemodialysis.

Indications

• Arterial hypertension (monotherapy or in combination with other antihypertensive agents);
• Stable exertional angina, vasospastic angina (Prinzmetal’s angina).

ICD codes

Dosage Regimen

Orally, the initial dose for the treatment of arterial hypertension and angina is 5 mg once/day. The dose can be increased to a maximum of 10 mg once/day.

For arterial hypertension, the maintenance dose is 5 mg/day.

For stable exertional angina and vasospastic angina – 5-10 mg/day, once.

No dose adjustment is required when co-administered with thiazide diuretics, beta-blockers, and angiotensin-converting enzyme inhibitors.

No dose adjustment is required in patients with renal impairment.

Patients with low body weight or short stature, as well as with severe hepatic impairment may require lower doses.

Adverse Reactions

From the cardiovascular system palpitations, dyspnea, marked decrease in BP, syncope, vasculitis, peripheral edema (ankle and foot swelling), flushing; rarely – arrhythmias (bradycardia, ventricular tachycardia, atrial flutter), myocardial infarction, chest pain, orthostatic hypotension; very rarely – development or worsening of heart failure, extrasystole, migraine.

From the CNS headache, dizziness, fatigue, drowsiness, mood lability, convulsions; rarely – loss of consciousness, hypoesthesia, peripheral neuropathy, paresthesia, tremor, vertigo, asthenia, malaise, insomnia, depression, unusual dreams; very rarely – ataxia, apathy, agitation, amnesia.

From the digestive system nausea, vomiting, epigastric pain; rarely – increased activity of liver transaminases and jaundice (due to cholestasis), pancreatitis, dry mouth, thirst, hepatitis, flatulence, gingival hyperplasia, constipation or diarrhea; very rarely – gastritis, increased appetite, anorexia, hyperbilirubinemia.

From the urinary system rarely – pollakiuria, painful urge to urinate, nocturia, sexual dysfunction (including decreased potency); very rarely – dysuria, polyuria.

From the skin very rarely – xeroderma, alopecia, dermatitis, purpura, skin pigmentation disorder.

Allergic reactions skin itching, rash (including erythematous, maculopapular rash, urticaria), angioedema, erythema multiforme.

From the musculoskeletal system rarely – arthralgia, arthrosis, muscle cramps, myalgia (with long-term use); very rarely – myasthenia.

Other rarely – gynecomastia, hyperuricemia, increase/decrease in body weight, thrombocytopenia, leukopenia, hyperglycemia, visual impairment, diplopia, conjunctivitis, eye pain, tinnitus, back pain, dyspnea, epistaxis, increased sweating, thirst; very rarely – cold clammy sweat, cough, rhinitis, parosmia, taste perversion, accommodation disorder, xerophthalmia.

Contraindications

• Severe arterial hypotension;
• Collapse;
• Cardiogenic shock;
• Unstable angina (except for Prinzmetal’s angina);
• Severe aortic stenosis;
• Pregnancy;
• Lactation period;
• Age under 18 years (efficacy and safety not established);
• Hypersensitivity to amlodipine and other dihydropyridine derivatives.

With caution impaired liver function, sick sinus syndrome (severe bradycardia, tachycardia), chronic heart failure in the stage of decompensation, mild or moderate arterial hypotension, aortic stenosis, mitral stenosis, hypertrophic obstructive cardiomyopathy, acute myocardial infarction (and within 1 month after), elderly age, simultaneous use of beta-blockers and digoxin.

Use in Pregnancy and Lactation

Contraindicated during pregnancy and lactation.

Use in Hepatic Impairment

Patients with severe hepatic impairment may require lower doses.

Use with caution impaired liver function

Use in Renal Impairment

No dose adjustment is required in patients with renal impairment.

Pediatric Use

Contraindicated in children under 18 years of age (efficacy and safety not established).

Geriatric Use

Use with caution in the elderly.

The dosage regimen for the elderly is the same as for patients of other age groups. When increasing the dose, careful monitoring of elderly patients is necessary.

Special Precautions

During treatment, monitoring of body weight and sodium intake is necessary, and an appropriate diet should be prescribed.

Maintenance of dental hygiene and frequent visits to the dentist are necessary (to prevent soreness, bleeding, and gingival hyperplasia).

The dosage regimen for the elderly is the same as for patients of other age groups. When increasing the dose, careful monitoring of elderly patients is necessary.

Although there is no withdrawal syndrome with BMCC, it is recommended to gradually reduce the doses before discontinuing treatment.

Amlodipine does not affect plasma concentrations of potassium ions, glucose, triglycerides, total cholesterol, low-density lipoproteins, uric acid, creatinine, and urea nitrogen.

Effect on ability to drive vehicles and operate machinery

There have been no reports of the effect of amlodipine on driving or operating machinery. Nevertheless, some patients, mainly at the beginning of treatment, may experience drowsiness and dizziness. If they occur, the patient should take special precautions when driving and operating machinery.

Overdose

Symptoms marked decrease in BP, tachycardia, excessive peripheral vasodilation (risk of developing severe and persistent arterial hypotension, including shock and fatal outcome).

Treatment gastric lavage, administration of activated charcoal (especially within the first 2 hours after overdose), maintenance of cardiovascular function, monitoring of heart and lung function parameters, elevated position of the limbs, monitoring of circulating blood volume and diuresis. To restore vascular tone – use of vasoconstrictors (if there are no contraindications to their use); to eliminate the consequences of calcium channel blockade – intravenous administration of calcium gluconate. Hemodialysis is not effective.

Drug Interactions

Inhibitors of microsomal oxidation increase the plasma concentration of amlodipine, increasing the risk of side effects, while inducers of liver microsomal enzymes decrease it.

Unlike other BMCCs, no clinically significant interaction with NSAIDs, especially indomethacin, has been noted.

Thiazide and loop diuretics, beta-blockers, verapamil, ACE inhibitors, and nitrates enhance the antianginal and antihypertensive effect.

Amiodarone, quinidine, alpha₁-blockers, antipsychotics (neuroleptics), and BMCCs may enhance the antihypertensive effect.

Amlodipine does not affect the pharmacokinetic parameters of digoxin and warfarin.

Cimetidine does not affect the pharmacokinetics of amlodipine.

When amlodipine is used concomitantly with lithium preparations, manifestations of their neurotoxicity may be enhanced (nausea, vomiting, diarrhea, ataxia, tremor, tinnitus).

Calcium preparations may reduce the effect of BMCCs.

Antiviral agents (ritonavir) increase plasma concentrations of BMCCs, including amlodipine.

Neuroleptics and isoflurane – enhancement of the antihypertensive effect of dihydropyridine derivatives.

Grapefruit juice may reduce the plasma concentration of amlodipine, but this reduction is so small that it does not significantly change the effect of amlodipine.

Storage Conditions

List B. The drug should be stored at a temperature not exceeding 25°C (77°F). Store in places inaccessible to children.

Shelf Life

The shelf life is 3 years. Do not use the drug after the date indicated on the packaging.

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.