Agen (Tablets) Instructions for Use

Marketing Authorization Holder

Zentiva, a.s. (Czech Republic)

ATC Code

C08CA01 (Amlodipine)

Active Substance

Amlodipine (Rec.INN registered by WHO)

Dosage Forms

	Agen	Tablets 5 mg: 10 or 30 pcs.
		Tablets 10 mg: 10 or 30 pcs.

Dosage Form, Packaging, and Composition

Tablets white or almost white, oblong, with a dividing score on one side and an engraving “A” and “10”; on the break – a dense homogeneous mass of white or almost white color.

Excipients : microcrystalline cellulose, calcium hydrogen phosphate dihydrate, sodium carboxymethyl starch type A, magnesium stearate.

10 pcs. – blisters (1) – cardboard packs.
10 pcs. – blisters (3) – cardboard packs.

Tablets white or almost white, oblong, with a dividing score on one side and an engraving “A” and “5”; on the break – a dense homogeneous mass of white or almost white color.

Excipients : microcrystalline cellulose, calcium hydrogen phosphate dihydrate, sodium carboxymethyl starch type A, magnesium stearate.

10 pcs. – blisters (1) – cardboard packs.
10 pcs. – blisters (3) – cardboard packs.

Clinical-Pharmacological Group

Calcium channel blocker

Pharmacotherapeutic Group

BMCC (Bone Mineral Crystal Complex)

Pharmacological Action

Amlodipine is a second-generation slow calcium channel blocker from the group of dihydropyridine derivatives. It has antihypertensive and antianginal action. It blocks the entry of calcium ions through cell membranes into the smooth muscle cells of the myocardium and blood vessels.

The mechanism of the hypotensive action is due to a direct relaxing effect on vascular smooth muscles.

The antianginal effect of the drug is due to its ability to dilate peripheral arterioles, which leads to a decrease in total peripheral vascular resistance. The reduction in cardiac load leads to a decrease in myocardial oxygen demand. Under the action of the drug, due to the expansion of the coronary arteries, the supply of oxygen to the myocardium increases (especially in vasospastic angina).

It does not have an adverse effect on metabolism and blood plasma lipids, has anti-atherosclerotic, antithrombotic activity, increases the glomerular filtration rate, and has a weak natriuretic effect. In diabetic nephropathy, it does not increase the severity of microalbuminuria.

The time to onset of effect is 2-4 hours; duration is 24 hours.

Pharmacokinetics

After oral administration, Amlodipine is absorbed in the gastrointestinal tract, absorption is slow, about 90%, does not depend on food intake, binding to plasma proteins is 90-97%.

C_max in plasma is reached on average after 6-12 hours, C_ss in plasma is reached within 7-8 days of continuous use of the drug. V_d is 21 L/kg. Bioavailability is 64-80%. It penetrates the blood-brain barrier and is excreted in breast milk.

It is metabolized in the liver to form inactive metabolites, T _1/2 is on average about 35 hours, in patients with arterial hypertension – about 48 hours, in hepatic insufficiency – up to 60 hours, in elderly patients it increases to 65 hours, in renal impairment – does not change. It is excreted from the body mainly in the urine both unchanged (up to 10%) and as metabolites (60%), as metabolites – in bile and through the intestine (20-25%).

Indications

• Arterial hypertension;
• Stable angina pectoris;
• Vasospastic angina.

ICD codes

Dosage Regimen

Administer orally, with a sufficient amount of water. Take regardless of meals.

For arterial hypertension and stable angina pectoris, the initial adult dose is 5 mg once daily.

For vasospastic angina, the initial adult dose is 5 mg once daily.

Dose titration may be performed after 7-14 days of therapy based on individual therapeutic response and tolerability.

The dose may be increased to the maximum recommended dose of 10 mg once daily.

Use the lower 2.5 mg initial dose in patients with hepatic impairment or those who are small, fragile, or elderly.

No initial dose adjustment is required for patients with renal impairment.

When co-administering with thiazide diuretics, beta-blockers, or ACE inhibitors, no dose adjustment of amlodipine is required.

Tablets are scored and can be divided for dose titration; however, swallow whole or halved tablets without chewing or crushing.

Initiate therapy at the low end of the dosing range in the elderly due to a higher frequency of decreased hepatic, renal, or cardiac function.

Regular clinical monitoring of blood pressure and angina symptoms is necessary to determine the appropriate maintenance dose.

Discontinuation should be gradual to avoid potential rebound effects, particularly in patients with coronary artery disease.

Adverse Reactions

From the cardiovascular system palpitations, shortness of breath, marked decrease in blood pressure, fainting, vasculitis, edema (swelling of the ankles and feet); rarely – cardiac arrhythmias (bradycardia, ventricular tachycardia, atrial flutter), chest pain, orthostatic hypotension.

From the CNS: dizziness, headache, flushing, drowsiness, increased fatigue; rarely – mood changes, asthenia, muscle cramps, myalgia, visual impairment, paresthesia, tremor, insomnia.

From the digestive system: dyspeptic disorders, nausea, hyperbilirubinemia, abdominal pain; rarely – increased levels of liver transaminases and jaundice (due to cholestasis), pancreatitis, taste perversion, dry mouth, change in bowel habits, gingival hyperplasia; very rarely – gastritis.

From the genitourinary system: rarely – pollakiuria, painful urge to urinate, nocturia, decreased potency; very rarely – dysuria, polyuria.

From the musculoskeletal system: arthralgia, myalgia.

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

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

Other: increase/decrease in body weight, cough, rhinitis, gynecomastia, leukopenia, thrombocytopenia, hyperglycemia.

Contraindications

• Severe arterial hypotension;
• Age under 18 years (efficacy and safety not established);
• Hypersensitivity to amlodipine and other dihydropyridine derivatives.

With caution the drug should be prescribed to patients with impaired liver and/or kidney function, chronic heart failure, sick sinus syndrome (severe bradycardia, tachycardia), aortic and mitral stenosis, hypertrophic obstructive cardiomyopathy, mild or moderate arterial hypotension, acute myocardial infarction (and within 1 month after), diabetes mellitus, impaired lipid profile, elderly patients.

Use in Pregnancy and Lactation

The safety of using Agen during pregnancy has not been established, so it is recommended to use only in cases where the risk associated with the disease itself exceeds the possible harm to the mother and fetus.

If it is necessary to prescribe the drug during lactation, the issue of discontinuing breastfeeding should be decided.

Use in Hepatic Impairment

With caution the drug should be prescribed to patients with impaired liver function.

Use in Renal Impairment

With caution the drug should be prescribed to patients with impaired kidney function.

Pediatric Use

Contraindication: age under 18 years (efficacy and safety not established)

Geriatric Use

With caution the drug should be prescribed to elderly patients.

Special Precautions

No dose reduction is required for patients with impaired renal function, as well as for elderly patients.

During treatment with the drug, body weight control and regular visits to the dentist are necessary (prevention of soreness, bleeding and overgrowth of the gums).

It is not recommended to use the drug Agen simultaneously with other medicines without consulting a doctor.

There is no experience with the use of Agen in children.

Effect on the ability to drive vehicles and mechanisms

Does not affect the ability to drive vehicles and moving mechanisms.

Overdose

Symptoms marked peripheral vasodilation, marked decrease in blood pressure, tachycardia.

Treatment therapy is carried out depending on the severity of the manifestation of intoxication. Gastric lavage, administration of activated charcoal, maintenance of cardiovascular function, monitoring of heart and lung function parameters, elevated position of the limbs, control of circulating blood volume and diuresis, symptomatic and supportive therapy. To restore vascular tone – the use of vasoconstrictor drugs (in the absence of 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 concentration of amlodipine in plasma, increasing the risk of side effects, inducers of liver microsomal enzymes reduce the concentration of amlodipine.

Indomethacin and other NSAIDs (sodium retention and blockade of prostaglandin synthesis by the kidneys), alpha-adrenergic stimulants**,sympathomimetics and estrogens (sodium retention) reduce the hypotensive effect of amlodipine.

Thiazide and “loop” diuretics, beta-blockers, verapamil, ACE inhibitors and nitrates enhance the antianginal and hypotensive effects.

Amiodarone, quinidine, alpha₁-blockers, antipsychotic drugs (neuroleptics) may enhance the hypotensive effect.

With simultaneous use of amlodipine with lithium preparations, it is possible to enhance the manifestation of neurotoxic effects of lithium (nausea, vomiting, diarrhea, ataxia, tinnitus).

Does not affect the pharmacokinetic parameters of digoxin and warfarin.

Cimetidine does not affect the pharmacokinetics of amlodipine.

Calcium preparations may reduce the effect of slow calcium channel blockers.

Procainamide, quinidine and other drugs that cause QT interval prolongation enhance the negative inotropic effect and may increase the risk of significant QT interval prolongation.

Storage Conditions

List B. Store in a dry, light-protected place, out of reach of children, at a temperature up to 25°C (77°F).

Shelf Life

Shelf life – 3 years.

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.