Akridipin^® (Tablets) Instructions for Use

Marketing Authorization Holder

Marvel LifeSciences, Pvt. Ltd. (India)

Trademark Owner

AKRIKHIN Chemical and Pharmaceutical Plant, JSC (Russia)

ATC Code

C08CA01 (Amlodipine)

Active Substance

Amlodipine (Rec.INN registered by WHO)

Dosage Forms

	Akridipin®	Tablets 2.5 mg: 30 pcs.
		Tablets 5 mg: 30 pcs.

Dosage Form, Packaging, and Composition

Tablets light orange in color, round, flat, with beveled edges, with a score on one side.

Excipients: corn starch, dibasic calcium phosphate, purified talc, colloidal silicon dioxide, sodium starch glycolate, magnesium stearate, sunset yellow dye.

10 pcs. – blisters (2) – cardboard packs.
10 pcs. – blisters (3) – cardboard packs.
10 pcs. – strips (2) – cardboard packs.
10 pcs. – strips (3) – cardboard packs.

Tablets white in color, round, flat, with beveled edges, with a score on one side.

Excipients: corn starch, dibasic calcium phosphate, purified talc, colloidal silicon dioxide, sodium starch glycolate, magnesium stearate.

10 pcs. – blisters (2) – cardboard packs.
10 pcs. – blisters (3) – cardboard packs.
10 pcs. – strips (2) – cardboard packs.
10 pcs. – strips (3) – cardboard packs.

Clinical-Pharmacological Group

Calcium channel blocker

Pharmacotherapeutic Group

BMCC (Bone Mineral Crystal Complex)

Pharmacological Action

Amlodipine is a dihydropyridine derivative. 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, firstly, to its ability to dilate peripheral arterioles, which leads to a decrease in total peripheral vascular resistance. The reduction in cardiac workload leads to a decrease in myocardial oxygen demand. Secondly, 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).

Amlodipine 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.

Pharmacokinetics

After oral administration, Amlodipine is slowly absorbed from the gastrointestinal tract (90%) regardless of food intake, C_max of the drug in the blood is observed after 6-12 hours. The steady-state equilibrium concentration of the drug in the blood plasma is reached after 7-8 days of its continuous use. The drug has a high V_d – about 20 L/kg; bioavailability is 60-65%, binding to blood plasma proteins is high – more than 95%. T_1/2 of the drug is 35-45 hours, which allows it to be prescribed once a day. It is metabolized mainly in the liver to form inactive metabolites. Less than 10% of the orally administered dose is excreted unchanged, about 60% is excreted by the kidneys as inactive metabolites; 20-25% is excreted as metabolites in the bile and through the intestine, as well as in breast milk. It penetrates the blood-brain barrier. T_1/2 in patients with arterial hypertension is 48 hours, in elderly patients it increases to 65 hours, in hepatic insufficiency – up to 60 hours, in renal impairment – does not change. It is not removed by hemodialysis.

Indications

• Arterial hypertension (as monotherapy and in combination with thiazide diuretics, ACE inhibitors, and alpha- and beta-blockers);
• Stable and unstable angina (including Prinzmetal’s angina or variant angina).

ICD codes

Dosage Regimen

Initial dose: as an antihypertensive agent – 2.5 mg (especially for thin and elderly patients, patients with impaired liver function, and as part of complex therapy); as an antianginal agent – 5 mg (recommended for elderly patients and patients with impaired liver function).

For arterial hypertension and angina, the dose of Akridipin^® is 5 mg/day. If necessary, the daily dose can be increased to 10 mg/day. The maximum daily dose is 10 mg. No dose adjustment of Akridipin^® is required when used concomitantly with thiazide diuretics, beta-blockers, or ACE inhibitors.

Adverse Reactions

The drug is usually well tolerated by patients, however, in some cases, the following may be observed

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

From the central nervous system: dizziness, headache, hot flushes, drowsiness, increased fatigue; rarely – mood changes, asthenia, muscle cramps, myalgia, visual impairment, paresthesia.

From the digestive system: dyspeptic disorders, nausea, abdominal pain; rarely: increased levels of liver transaminases and jaundice (due to cholestasis), pancreatitis, taste perversion, dry mouth.

From the skin: allergic reactions (skin rash, itching); rarely – multiforme erythema, skin discoloration.

From the genitourinary system: rarely – gynecomastia, impotence, increased frequency of urination.

Other edema, gingival hyperplasia, asthenia, increase/decrease in body weight, thrombocytopenia, leukopenia.

Contraindications

• Arterial hypotension;
• Heart failure of grades II and III;
• Tachycardia;
• Aortic stenosis;
• Hypertrophic cardiomyopathy with obstruction of the left ventricular outflow tract;
• Collapse;
• Vascular and cardiogenic shock;
• Myocardial infarction (first week);
• Hypersensitivity to amlodipine and other dihydropyridine derivatives.

Use in Pregnancy and Lactation

The safety of using Akridipin^® during pregnancy and lactation has not been established, therefore the use of the drug during pregnancy and breastfeeding is recommended only in cases where the risk associated with the disease itself exceeds the possible harm of treatment for 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

Initial dose: as an antihypertensive agent – 2.5 mg (especially for patients with impaired liver function); as an antianginal agent – 5 mg (recommended for patients with impaired liver function).

Pediatric Use

There is no experience with the use of Akridipin^® in children.

Geriatric Use

Initial dose: as an antihypertensive agent – 2.5 mg (especially for elderly patients); as an antianginal agent – 5 mg (recommended for elderly patients).

Special Precautions

During treatment, it is necessary to control body weight and diet, especially sodium intake, maintain dental hygiene and visit the dentist frequently (to prevent soreness, bleeding, and overgrowth of the gums).

Use with caution in patients with impaired liver and kidney function.

There is no experience with the use of Akridipin^® in children.

Effect on the ability to drive vehicles and operate machinery

Akridipin^® does not affect the ability to drive vehicles.

Overdose

Symptoms: pronounced decrease in blood pressure, tachycardia, excessive peripheral vasodilation.

Treatment: support of the cardiovascular system function, monitoring of heart and lung performance indicators, elevated position of the limbs, control of circulating blood volume and diuresis. To restore vascular tone – use of vasoconstrictor drugs (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

Compatible with thiazide diuretics, adrenergic blockers, ACE inhibitors, long-acting and short-acting nitrates, NSAIDs, antibiotics, oral hypoglycemic drugs.

Concomitant use of Amlodipine and digoxin does not change the serum digoxin concentration level and the renal clearance of digoxin.

Concomitant use of Amlodipine and cimetidine does not change the pharmacokinetics of Amlodipine.

Concomitant administration of Amlodipine did not significantly alter the effect of warfarin on prothrombin time in healthy male volunteers.

The hypotensive effect is weakened by NSAIDs, especially indomethacin (sodium retention and blockade of prostaglandin synthesis by the kidneys), sympathomimetics, and estrogens (sodium retention).

Inhalation anesthetics (hydrocarbon derivatives), amiodarone, quinidine, slow calcium channel blockers may enhance the hypotensive effect.

When used concomitantly with lithium preparations, neurotoxicity may occur.

Storage Conditions

List B. Store in a light-protected place, out of the 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.