Amlodipine-Astrapharm tablets 10 mg blister No. 30

Translation of the instructions can be

Instruction

For medical use of the medicinal product

Amlodipine-Astrapharm

(Amlodipine-astrapharm)

Composition:

Active ingredient: amlodipine;

1 tablet contains amlodipine besylate in terms of 100% substance 5 mg or 10 mg;

excipients: calcium hydrogen phosphate, microcrystalline cellulose, magnesium stearate, corn starch.

Dosage form.

Pills.

Main physicochemical properties: white tablets, flat-cylindrical in shape, beveled edges, risk on one side.

Pharmacotherapeutic group.

Selective calcium antagonists with a predominant effect on blood vessels. Dihydropyridine derivative. Amlodipine. ATC code c08c A01.

Pharmacological properties.

Pharmacodynamics.

Amlodipine is a calcium antagonist (dihydropyridine derivative) that blocks the entry of calcium ions into the myocardium and smooth muscle cells.

The mechanism of the hypotensive action of amlodipine is due to a direct relaxing effect on vascular smooth muscle. The exact mechanism of the antianginal effect of amlodipine is not well established, but the following effects play a role:

In patients with arterial hypertension, the use of the drug 1 time per day provides a clinically significant reduction in blood pressure for 24 hours in both the supine and standing positions. Due to the slow onset of action of amlodipine, acute arterial hypotension is usually not observed.

In patients with angina pectoris, a single daily dose of the drug increases the total time of physical exertion, the time to the onset of angina pectoris, and the time to 1 mm of ST-segment depression. The drug reduces the frequency of angina attacks and reduces the need for nitroglycerin.

Amlodipine is not associated with any adverse metabolic effects or changes in plasma lipid levels and can be used in patients with asthma, diabetes mellitus, and gout.

Pharmacokinetics.

Absorption/distribution. After oral administration of therapeutic doses, amlodipine is gradually absorbed into the blood plasma. Simultaneous food intake does not affect the absorption of amlodipine. The absolute bioavailability of the unchanged molecule is approximately 64-80%. Maximum plasma concentrations are achieved within 6-12 hours after administration. The volume of distribution is approximately 21 l/kg; the acid dissociation constant (pKa) of amlodipine is 8.6. In vitro studies have shown that the binding of amlodipine to plasma proteins is approximately 97.5%.

Concomitant food intake does not affect the absorption of amlodipine.

Metabolism/Excretion: The plasma half-life is approximately

35-50 hours. Steady-state plasma concentrations are reached after 7-8 days of continuous administration. Amlodipine is mainly metabolized to inactive metabolites. About 60% of the administered dose is excreted in the urine, of which about 10% is unchanged amlodipine.

Elderly patients. The time to reach steady-state plasma concentrations of amlodipine is similar in elderly patients and in adult patients. The clearance of amlodipine is usually somewhat reduced, which in elderly patients leads to an increase in the area under the concentration-time curve (AUC) and the half-life of the drug.

Patients with renal impairment. Amlodipine is extensively biotransformed to inactive metabolites. 10% of amlodipine is excreted unchanged in the urine. Changes in plasma amlodipine concentrations do not correlate with the degree of renal impairment. Patients with renal impairment can use the usual doses of amlodipine. Amlodipine is not dialysable.

Patients with impaired liver function.

Information on the use of amlodipine in patients with hepatic impairment is very limited. In patients with hepatic insufficiency, clearance of the drug is reduced, resulting in an increase in the half-life and an increase in AUC by approximately 40-60%.

Children. Pharmacokinetic studies were conducted in 74 hypertensive children aged 12 to 17 years (including 34 patients aged 6 to 12 years and 28 patients aged 13 to 17 years) who received amlodipine at doses of 1.25-20 mg/day in 1 or 2 divided doses. The mean oral clearance in children aged 6 to 12 years and 13 to 17 years was 22.5 and 27.4 l/h, respectively, for boys and 16.4 and 21.3 l/h, respectively, for girls. There is considerable inter-patient variability in exposure. Limited information is available in patients under 6 years of age.

Clinical characteristics.

Contraindication.

Interaction with other drugs and other types of interactions.

Effect of other drugs on amlodipine.

CYP3A4 inhibitors.

Concomitant use of amlodipine and strong or moderate CYP3A4 inhibitors (protease inhibitors, azole antifungals, macrolides such as erythromycin or clarithromycin, verapamil or diltiazem) may lead to a significant increase in amlodipine exposure, which increases the risk of hypotension. The clinical significance of such changes may be more pronounced in elderly patients. Clinical monitoring of the patient's condition and dose adjustment may be necessary.

It is not recommended to use amlodipine and grapefruit or grapefruit juice simultaneously, since in some patients the bioavailability of amlodipine may increase, which, in turn, leads to increased hypotensive effect.

CYP3A4 inducers.

There is no information on the effect of CYP3A4 inducers on amlodipine. Concomitant use of amlodipine and substances that are CYP3A4 inducers (e.g. rifampicin, St. John's wort) may lead to a decrease in amlodipine plasma concentrations, therefore such combinations should be used with caution.

Dantrolene (infusion).

Due to the risk of hyperkalemia, it is recommended to avoid the use of calcium channel blockers, such as amlodipine, in patients prone to malignant hyperthermia and in the treatment of malignant hyperthermia.

The effect of amlodipine on other drugs.

The hypotensive effect of amlodipine potentiates the hypotensive effect of other antihypertensive agents.

Tacrolimus.

There is a risk of increased blood levels of tacrolimus when used concomitantly with amlodipine, but the pharmacokinetic mechanism of this interaction has not been fully established. To avoid tacrolimus toxicity, regular monitoring of tacrolimus blood levels and, if necessary, dose adjustment are required when amlodipine is used concomitantly.

Cyclosporine.

No interaction studies of cyclosporine and amlodipine have been conducted in healthy volunteers or other populations, except in renal transplant patients, where variable increases in cyclosporine trough concentrations (mean 0-40%) were observed. Monitoring of cyclosporine concentrations and, if necessary, reduction of the cyclosporine dose are recommended in renal transplant patients receiving amlodipine.

Simvastatin.

Coadministration of multiple doses of amlodipine 10 mg and simvastatin 80 mg resulted in a 77% increase in simvastatin exposure compared to simvastatin alone. For patients taking amlodipine, the dose of simvastatin should be limited to 20 mg daily.

Clinical drug interaction studies have shown that amlodipine does not affect the pharmacokinetics of atorvastatin, digoxin, and warfarin.

Application features.

The safety and efficacy of amlodipine in hypertensive crisis have not been evaluated.

Patients with heart failure. Amlodipine-Astrapharm should be used with caution in this category of patients. Calcium channel blockers, including amlodipine, should be used with caution in patients with congestive heart failure, as they increase the risk of future cardiovascular events and mortality.

Patients with hepatic impairment. The half-life of amlodipine and AUC parameters are higher in patients with hepatic impairment; there are no recommendations for the dosage of the drug. Therefore, this category of patients should start taking the drug with the lowest dose. Caution should be exercised both at the beginning of the drug and when increasing the dose. Patients with severe hepatic insufficiency may require a free dose selection and careful monitoring of the patient's condition.

Elderly patients: Increasing the dose of the drug in this category of patients should be done with caution.

Patients with renal impairment. This category of patients should use the usual doses of the drug. Changes in the concentration of amlodipine in the blood plasma do not correlate with the degree of renal impairment. Amlodipine is not removed by dialysis.

Amlodipine does not affect the results of laboratory tests.

It is not recommended to use amlodipine with grapefruit or grapefruit juice, because in some patients the bioavailability may be increased, leading to an increase in the hypotensive effect of the drug.

Use during pregnancy or breastfeeding.

Pregnancy.

The safety of amlodipine during pregnancy has not been established.

The use of amlodipine during pregnancy is recommended only in cases where the expected benefit to the mother outweighs the potential risk to the fetus.

Reproductive toxicity was observed in animal studies at high doses.

It is not known whether amlodipine is excreted in human milk. A decision must be made whether to continue breastfeeding or to use amlodipine, taking into account the benefit of breastfeeding to the child and the benefit of the drug to the mother.

Fertility: Reversible biochemical changes in the head of sperm have been reported in some patients receiving calcium channel blockers. There is insufficient clinical information regarding the potential effect of amlodipine on fertility.

The ability to influence the reaction speed when driving vehicles or other mechanisms.

Amlodipine may have minor or moderate influence on the ability to drive and use machines. Reaction speed may be reduced in the presence of symptoms such as dizziness, headache, confusion or nausea. Caution should be exercised, especially at the beginning of therapy.

Method of administration and doses.

Adults.

Usually, for the treatment of hypertension and angina pectoris, the recommended initial dose of the drug is 5 mg of amlodipine once a day. Depending on the patient's response to therapy, the dose can be increased to a maximum dose of 10 mg once a day.

In patients with angina pectoris, the drug can be used as monotherapy or in combination with other antianginal drugs in case of resistance to nitrates and/or adequate doses of β-blockers.

There is experience of using the drug in combination with thiazide diuretics, α-blockers, β-blockers or angiotensin-converting enzyme inhibitors in patients with arterial hypertension.

There is no need to adjust the dose of the drug when used simultaneously with thiazide diuretics, β-blockers and angiotensin-converting enzyme inhibitors.

Children from 6 years of age with arterial hypertension.

The recommended initial dose for this category of patients is 2.5 mg once daily. If the desired blood pressure level is not achieved within 4 weeks, the dose can be increased to 5 mg daily. The use of the drug in doses higher than 5 mg in this category of patients has not been studied.

Elderly patients.

There is no need to adjust the dose for this category of patients. Increasing the dose should be done with caution.

Patients with impaired renal function.

It is recommended to use the usual doses of the drug, since changes in the concentration of amlodipine in the blood plasma are not associated with the severity of renal failure. Amlodipine is not excreted by dialysis.

Use in patients with impaired liver function.

The doses of the drug for use in patients with mild to moderate hepatic insufficiency have not been established, therefore dose selection should be carried out with caution and use should be started with the lowest dose (see sections “Special instructions for use” and “Pharmacological properties. Pharmacokinetics”).

Children.

The drug is used in children from 6 years of age.

The effect of amlodipine on blood pressure in patients under 6 years of age is unknown.

Overdose.

Experience with intentional overdose of amlodipine is limited.

Symptoms: Significant overdose will result in excessive peripheral vasodilation and possibly reflex tachycardia. Significant and prolonged systemic hypotension, including shock with fatal outcome, has been reported.

Treatment: Clinically significant hypotension due to amlodipine overdose requires active support of the cardiovascular system, including frequent monitoring of cardiac and respiratory functions, elevation of extremities, monitoring of circulating fluid volume and urine output.

Vasoconstrictors can be used to restore vascular tone and blood pressure, provided there are no contraindications to their use. Intravenous administration of calcium gluconate may be useful in reversing the effects of calcium channel blockade.

Gastric lavage may be useful in some cases. Administration of activated charcoal to healthy volunteers within 2 hours of administration of 10 mg amlodipine significantly reduced its absorption.

Since amlodipine is highly bound to plasma proteins, the effect of dialysis is negligible.

Adverse reactions.

The most commonly reported adverse reactions with amlodipine are: drowsiness, dizziness, headache, palpitations, flushing, abdominal pain, nausea, leg swelling, edema, and fatigue.

From the blood system: leukocytopenia, thrombocytopenia.

On the part of the immune system: allergic reactions.

Metabolic disorders: hyperglycemia.

Psychiatric: depression, mood changes (including anxiety), insomnia, confusion.

Nervous system: drowsiness, dizziness, headache (mainly at the beginning of treatment), tremor, dysgeusia, syncope, hypoesthesia, paresthesia, hypertonicity, peripheral neuropathy.

On the part of the organs of vision: visual disturbances (including diplopia).

On the part of the organs of hearing: ringing in the ears.

Cardiovascular system: palpitations, arrhythmia (including bradycardia, ventricular tachycardia and atrial flutter), myocardial infarction, hot flashes, hypotension, vasculitis.

Gastrointestinal tract: abdominal pain, nausea, dyspepsia, intestinal motility disorders (including diarrhea and constipation), vomiting, dry mouth, pancreatitis, gastritis, gingival hyperplasia.

Hepatobiliary system: hepatitis, jaundice, increased liver enzymes (most often associated with cholestasis).

Skin and subcutaneous tissue disorders: alopecia, purpura, skin discoloration, increased sweating, itching, rash, exanthema, urticaria, angioedema, erythema multiforme, exfoliative dermatitis, Stevens-Johnson syndrome, Quincke's edema, photosensitivity.

Musculoskeletal system: swelling of the lower legs, muscle cramps, joint pain, muscle pain, back pain.

From the urinary system: urinary disorders, nocturia, increased urinary frequency.

From the reproductive system: impotence, gynecomastia.

General disorders: edema, fatigue, asthenia, chest pain, pain, malaise.

Laboratory indicators: weight gain or loss.

Exceptional cases of extrapyramidal syndrome have been reported.

Reporting of suspected adverse reactions.

Reporting suspected adverse reactions after the registration of a medicinal product is of utmost importance. This allows monitoring of the balance between benefits and risks associated with the use of this medicinal product. Physicians should report any suspected adverse reactions in accordance with legal requirements.

Expiration date.

3 years.

Storage conditions.

Store in original packaging at a temperature not exceeding 25 degrees Celsius.

Keep out of reach of children.

Packaging.

10 tablets in a blister; 2, 3, or 10 blisters in a box.

Vacation category.

According to the recipe.

Producer.

"Astrafarm" LLC.

Location of the manufacturer and address of its place of business.

Ukraine, 08132, Kyiv region, Kyiv-Svyatoshyn district, Vyshneve city, Kyivska st., 6.