Amlodipine tablets 10 mg blister No. 90

Translation of the instructions can be

Instruction

For medical use of the medicinal product

Amlodipine

(Amlodipine)

Composition:

Active ingredient: amlodipine besylate;

1 tablet contains amlodipine besylate equivalent to amlodipine 5 mg or 10 mg;

excipients: lactose, microcrystalline cellulose, croscarmellose sodium, hypromellose (hydroxypropylmethylcellulose), povidone 25, magnesium stearate, colloidal anhydrous silicon dioxide, indigo carmine (E 132).

Dosage form.

Pills.

Main physicochemical properties: single-layer round tablets of white or white with a bluish tint, the upper and lower surfaces of which are convex. A relatively homogeneous structure is visible on the fracture under a magnifying glass.

Pharmacotherapeutic group.

Selective calcium antagonists with a predominant effect on blood vessels. Dihydropyridine derivatives. 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:

1. Amlodipine dilates peripheral arterioles and thus reduces peripheral resistance (afterload). Reducing the workload on the heart leads to a decrease in energy consumption and myocardial oxygen demand.

2. Dilation of the main coronary arteries and coronary arterioles may also play a role in the mechanism of action of amlodipine. Such dilation increases myocardial oxygen saturation in patients with coronary artery spasm (Prinzmetal's angina or variant angina).

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 supine and standing positions. Due to the slow onset of action of amlodipine, acute arterial hypotension is not observed.

In patients with angina pectoris, a single daily dose of the drug increases the total time of physical exertion. 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, 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 about 64-80%. Maximum plasma concentration is 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%.

Metabolism/Excretion. The plasma half-life is approximately 35-50 hours. Steady-state plasma concentrations are reached after 7-8 days of continuous dosing. Amlodipine is primarily metabolized to inactive metabolites. Approximately 60% of the administered dose is excreted in the urine, approximately 10% of which is unchanged amlodipine.

Elderly patients. The time to reach steady-state plasma concentrations of amlodipine is similar in the elderly and in adult patients. The clearance of amlodipine is usually slightly 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 be treated with normal doses of amlodipine. Amlodipine is not dialysable.

Patients with hepatic impairment. 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 to 20 mg/day in 1 or 2 divided doses. The mean oral clearance in children aged 6 to 12 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 for patients under 6 years of age.

Clinical characteristics.

Contraindication.

Interaction with other drugs and other types of interactions.

Effect of other drugs on amlodipine.

There is evidence of the safe use of amlodipine with thiazide diuretics, alpha-blockers, beta-blockers, ACE inhibitors, long-acting nitrates, sublingual nitroglycerin, nonsteroidal anti-inflammatory drugs (NSAIDs), antibiotics, and oral hypoglycemic drugs.

Data obtained during in vitro studies with human blood plasma indicate that amlodipine has no effect on the binding of the studied drugs (digoxin, phenytoin, warfarin or indomethacin) to blood proteins.

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 may also lead to an increased risk of hypotension. The clinical significance of such changes may be more pronounced in elderly patients. Clinical monitoring of the patient 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.

Plasma concentrations of amlodipine may be altered following concomitant use of known CYP3A4 inducers. Therefore, blood pressure should be monitored and the dose adjusted to take into account the concomitant use of these medicinal products both during and after concomitant treatment, especially with strong CYP3A4 inducers (e.g. rifampicin, St. John's wort).

Dantrolene (infusion).

Fatal ventricular fibrillation and cardiovascular collapse associated with hyperkalemia have been observed in animals following intravenous administration of verapamil and dantrolene. Because of the risk of hyperkalemia, it is recommended that calcium channel blockers, such as amlodipine, be avoided in patients predisposed 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 co-administered with amlodipine, but the pharmacokinetic mechanism of this interaction has not been fully established. To avoid tacrolimus toxicity when co-administered with amlodipine, regular monitoring of tacrolimus blood levels and, if necessary, dose adjustment are necessary.

mTOR inhibitors (mammalian target of rapamycin).

mTOR inhibitors such as sirolimus, temsirolimus, and everolimus are substrates of CYP3A. Amlodipine is a weak inhibitor of CYP3A. When amlodipine is used concomitantly with mTOR inhibitors, it may potentiate the effects of the latter.

Cyclosporine.

Interaction studies of cyclosporine and amlodipine have not been conducted in healthy volunteers or other populations, except in renal transplant patients, where a variable increase in cyclosporine trough concentrations (mean 0-40%) was observed. For renal transplant patients receiving amlodipine, monitoring of cyclosporine concentrations should be considered and, if necessary, a reduction in the cyclosporine dose.

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.

Sildenafil.

A single dose of 100 mg of sildenafil in patients with essential hypertension did not affect the pharmacokinetics of amlodipine. When amlodipine and sildenafil were used simultaneously as combination therapy, each drug exhibited an independent hypotensive effect.

Ethanol.

Single and multiple doses of 10 mg amlodipine had no significant effect on the pharmacokinetics of ethanol.

Other medicines.

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

Co-administration of amlodipine with cimetidine had no effect on the pharmacokinetics of amlodipine.

Co-administration of aluminum/magnesium preparations (antacids) with a single dose of amlodipine had no significant effect on the pharmacokinetics of amlodipine.

Laboratory tests.

The effect on laboratory test results is unknown.

Application features.

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

This category of patients should use the drug with caution. In a long-term placebo-controlled study in patients with severe heart failure (NYHA class III and IV), the incidence of pulmonary edema was higher with amlodipine compared to placebo. Calcium channel blockers, including amlodipine, should be used with caution in patients with congestive heart failure, as they may increase the risk of future cardiovascular events and mortality.

Patients with impaired liver function.

The half-life of amlodipine and AUC parameters are higher in patients with impaired liver function; there are no recommendations for doses 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 slow 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 failure.

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 dysfunction. 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, as bioavailability may be increased in some patients, leading to increased hypotensive effect of the drug.

Excipients.

This medicine contains lactose. Patients with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption should not take this medicine.

Use during pregnancy or breastfeeding.

The safety of amlodipine for use in women during pregnancy has not been established.

The use of amlodipine during pregnancy is recommended only in cases where there is no safer alternative and the risk associated with the disease itself outweighs the possible harm from treatment for the mother and fetus.

Reproductive toxicity was observed in animal studies at high doses.

Breastfeeding. Amlodipine is excreted in breast milk. The ratio of the dose received by the newborn from the mother in the interquartile range is estimated as 3-7%, maximum 15%. The effect of amlodipine on infants is unknown.

When deciding whether to continue breastfeeding or to use amlodipine, the benefit of breastfeeding for the child and the benefit of the drug for the mother should be assessed.

Fertility.

Reversible biochemical changes in the sperm head 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.

For the treatment of hypertension and angina pectoris, the usual starting dose is 5 mg once daily. Depending on the patient's response to therapy, the dose may be increased to a maximum of 10 mg once daily.

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 beta-blockers.

There is experience in using the drug in combination with thiazide diuretics, alpha-blockers, beta-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, beta-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 for dose adjustment for this category of patients. Increasing the dose should be done with caution.

Patients with renal impairment.

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.

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

The pharmacokinetics of amlodipine have not been studied in patients with severe hepatic impairment. In patients with severe hepatic impairment, amlodipine should be started at the lowest dose and titrated gradually.

The 5 mg tablets are not intended to be divided in half to obtain a 2.5 mg dose.

Children.

The drug can be 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 the drug is limited.

Symptoms of Overdose: Significant overdose will result in excessive peripheral vasodilation and possibly reflex tachycardia. Significant and possibly 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 the lower extremities, monitoring of circulating fluid volume and urine output.

Vasoconstrictors can be used to restore vascular tone and blood pressure, making sure there are no contraindications to their use. Intravenous administration of calcium gluconate may be useful for 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 blood proteins, the effect of dialysis is negligible.

Adverse reactions.

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

Adverse reactions reported with amlodipine are listed below by system organ class and frequency: very common (≥ 1/10), common (≥ 1/100 to < 1/1000),

Blood and lymphatic system disorders: very rare: leukocytopenia, thrombocytopenia.

Immune system disorders: very rare: allergic reactions.

Metabolism and nutrition disorders: very rare: hyperglycemia.

Psychiatric disorders: uncommon: depression, mood changes (including anxiety), insomnia; rare: confusion.

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

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

From the side of the organs of hearing and labyrinth: infrequently: tinnitus.

Cardiac disorders: common: palpitations; uncommon: arrhythmia (including bradycardia, ventricular tachycardia and atrial fibrillation); very rare: myocardial infarction

Vascular disorders: common: hot flushes; uncommon: hypotension; very rare: vasculitis.

Respiratory, thoracic and mediastinal disorders: common: dyspnoea; uncommon: rhinitis, cough.

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

Hepatobiliary disorders: very rare: hepatitis, jaundice, increased liver enzymes (which was very often associated with cholestasis).

Skin and subcutaneous tissue disorders: uncommon: alopecia, purpura, skin discoloration, increased sweating, pruritus, rash, exanthema, urticaria; very rare: angioedema, erythema multiforme, exfoliative dermatitis, Stevens-Johnson syndrome, Quincke's edema, photosensitivity; unknown: toxic epidermal necrolysis.

Musculoskeletal and connective tissue disorders: common: leg swelling, muscle cramps; uncommon: joint pain, muscle pain, back pain.

Renal and urinary disorders: uncommon: urinary disorders, nocturia, increased urinary frequency.

Reproductive system and breast disorders: uncommon: impotence, gynecomastia.

General disorders and administration site conditions Very common: oedema; common: fatigue, asthenia; uncommon: chest pain, pain, malaise.

Investigations: uncommon: weight gain or loss.

Exceptional cases of extrapyramidal syndrome have been reported.

Children.

Most adverse reactions were mild or moderate in severity. Serious adverse reactions (mainly headache) occurred in 7.2% of patients receiving 2.5 mg amlodipine, 4.5% of patients receiving 5 mg amlodipine, and 4.6% of patients receiving placebo. The most common reason for discontinuation was uncontrolled hypertension. No laboratory abnormalities were the reason for discontinuation. No significant changes in heart rate were noted.

Reporting of suspected adverse reactions.

Reporting suspected adverse reactions after a medicinal product has been authorised is essential. This allows for continuous monitoring of the benefit-risk balance of the medicinal product. Physicians should report any suspected adverse reactions as required by law.

Expiration date.

3 years.

Storage conditions.

In original packaging at a temperature not exceeding 30 degrees Celsius.

Keep out of reach of children.

Packaging.

For 5 mg dosage:

10 tablets in a blister; 3 or 6 or 9 blisters in a cardboard pack;

10 tablets in a blister; 100 blisters in a cardboard box;

For a dosage of 10 mg:

10 tablets in a blister; 3 or 6 or 9 blisters in a cardboard pack;

10 tablets in a blister; 90 blisters in a cardboard box.

Vacation category.

According to the recipe.

Producer.

Ciao "technologist".

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

Ukraine, 20300, Cherkasy region, Uman city, Stara Prorizna street, building 8.