Vasotal 5 mg Tablets №20 *

Vasotal (AMLODIPINUM) Instructions for use

Composition

active ingredient : amlodipine besylate;

1 tablet contains amlodipine besylate (based on amlodipine) 5 mg or 10 mg

Auxiliary substances : microcrystalline cellulose, corn starch, magnesium stearate.

Dosage form

Tablets.

Basic physical and chemical properties: round, flat tablets from white to almost white.

Pharmacological group. ATX code.

Selective calcium antagonists with a predominant effect on the vessels. Code АТХ С08С А01.

Pharmacological properties

Pharmacological.

Amlodipine is an antagonist of calcium (a derivative of dihydropyridine), which blocks the flow of calcium ions into the myocardium and into the cells of smooth muscles.

The mechanism of hypotensive action of amlodipine is due to a direct relaxing effect on the smooth muscles of the vessels. The exact mechanism of the antianginal effect of amlodipine is not sufficient, but the following effects play a role.

1. Amlodipine expands peripheral arterioles and thus reduces peripheral resistance (post-load). As the heart rate remains stable, reducing heart load leads to a decrease in energy consumption and oxygen demand in the myocardium.

2. The expansion of major coronary arteries and coronary arterioles (normal and ischemic) may also play a role in the mechanism of action of amlodipine. Such an expansion increases the oxygen saturation in patients with coronary artery spasm (angina pectoris or variant angina pectoris).

In patients with arterial hypertension, the use of the drug once a day provides a clinically meaningful decrease in blood pressure for 24 hours in the lying position and standing. Due to the slow onset of amlodipine, acute arterial hypotension is usually not observed.

In patients with angina pectoris, when one daily dose is administered, the total physical activity time, time to the onset of angina and time to 1 mm depression of the ST segment increase. The drug reduces the frequency of seizures and the need for nitroglycerin.

Amlodipine is not associated with any adverse metabolic actions or changes in the level of lipids in the blood plasma and can be used in patients with asthma, diabetes mellitus and gout.

Pharmacokinetics.

Suction / distribution.

After oral administration of therapeutic doses, amlodipine is gradually absorbed into the blood plasma. The bioavailability of the unmodified molecule is approximately 64-80%. The maximum plasma concentration is reached within 6-12 hours after application. The volume of distribution is about 21 l / kg of dissociation acid (pKa) of amlodipine is 8.6. In vitro studies have shown that binding of amlodipine to plasma proteins is approximately 97.5%.

Simultaneous food intake does not affect the absorption of amlodipine.

Metabolism / Ovody.

The half-life of the plasma is about 35-50 hours. Equilibrium concentration in blood plasma is reached after 7-8 days of continuous use of the preparation. Amlodipine is mainly metabolized to the formation of inactive metabolites. About 60% of the administered dose is excreted in urine, about 10% of which is amlodipine in the unmodified form.

Older patients.

The time to reach the equilibrium concentration of amlodipine in plasma 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 impaired kidney function.

Amlodipine extensively metabolizes to inactive metabolites. 10% amlodipine is excreted unchanged with urine. Changes in the concentration of amlodipine in the blood plasma do not correlate with the degree of renal dysfunction. Patients with impaired renal function may use standard doses of amlodipine. Amlodipine is not removed by dialysis.

Patients with impaired liver function.

Information on the use of amlodipine in patients with impaired liver function is very limited. In patients with hepatic insufficiency, clearance of amlodipine is reduced, which leads to an increase in the half-life and an increase in AUC by about 40-60%.

Where are you.

Usually clearance for oral use for children aged 6 to 12 years and from 13 to 17 years was 22.5 and 27.4 l / hr respectively for boys and 16.4 and 21.3 l / h respectively for girls. There is a significant variation in the exposure of different patients. Information about patients under the age of 6 years is limited.

Indications

• Arterial hypertension.
• Chronic stable angina pectoris.
• Vasospastic angina (stenocardia Printsmetala).

Contraindications

• Hypersensitivity to dihydropyridines, amlodipine or to any other component of the drug
• Arterial hypotension of severe degree.
• Shock (including cardiogenic shock).
• Obstruction of the ventricular tract of the left ventricle (eg aortic stenosis of severe degree).
• Hemodynamically unstable cardiac insufficiency after acute myocardial infarction.

Interaction with other drugs and other types of interactions

Effect of other drugs on amlodipine.

CYP3A4 inhibitors.

Simultaneous administration of amlodipine and potent or moderate CYP3A4 inhibitors (protease inhibitors, azole antifungal agents, macrolides such as erythromycin or clarithromycin, verapamil or diltiazem) may result in a significant increase in amlodipine exposure, which may increase 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 selection may be required.

It is not recommended to use amlodipine and grapefruit or grapefruit juice at the same time, since in some patients the bioavailability of amlodipine may increase, which in turn leads to an increase in hypotensive action.

CYP3A4 inducers.

There is no information on the effect of inducers of CYP3A4 on amlodipine. Simultaneous administration of amlodipine and CYP3A4 inducers (eg rifampicin, St. John's Wort) can lead to a decrease in the concentration of amlodipine in plasma, therefore, such combinations should be used with caution.

Dantrolene (infusion).

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

Effect of amlodipine on other medicines.

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

Tacrolimus

There is a risk of rising levels of tacrolimus in the blood while co-administered with amlodipine, however, the pharmacokinetic mechanism of such interaction is not fully established. In order to avoid the toxicity of tacrolimus in the simultaneous use of amlodipine, regular monitoring of tacrolimus blood levels and, if necessary, dosage correction is required.

Ciclosporin

For patients with transplanted kidney who are taking amlodipine, consideration should be given to monitoring the concentrations of cyclosporine and, if necessary, to reduce the dose of cyclosporin.

Simvastatin

Simultaneous administration of multiple doses of amlodipine 10 mg and simvastatin in a dose of 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 per day.

Amlodipine does not affect the pharmacokinetics of atorvastatin, digoxin and warfarin.

Application features

The safety and efficacy of the use of amlodipine in hypertensive crisis has not been evaluated.

Patients with heart failure.

This category of patients should be used with caution. Patients with congestive heart failure, calcium channel blockers, including amlodipine, should be used with caution as they can increase the risk of cardiovascular events and fatal events in the future.

Patients with impaired liver function.

The half-life of amlodipine and the AUC parameters are higher in patients with impaired liver function. Recommendations for doses of the drug are not available. Therefore, this category of patients should start using a low dose drug. Care should be taken both at the start of the application and when the dose is increased. Patients with severe hepatic insufficiency may require a slow dose selection and careful monitoring of the patient's condition.

Older patients.

Increase the dose of this category of patients should be taken with caution.

Patients with renal insufficiency.

In this category of patients, the usual doses of the drug should be used. Changes in the concentration of amlodipine in the plasma do not correlate with the degree of abnormalities in the function of the kidneys. 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 some patients may have increased bioavailability, which will increase the hypotensive effect of the drug.

Fertility.

Reversible biochemical changes in the sperm head have been reported in some patients with calcium channel blockers.Clinical information on the potential impact of amlodipine on fertility is not enough.

Use during pregnancy or breastfeeding.

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

The use of amlodipine during pregnancy is recommended only when there is no safer alternative and the risk associated with the disease itself exceeds the potential harm from treatment for the mother and the fetus.

Breast feeding period.

It is not known that amlodipine penetrates breast milk. When deciding whether to breast-feed or on the use of amlodipine, it's important to evaluate the benefits of breast-feeding for the baby and the benefit of using the product for the mother.

Ability to influence the speed of reaction when driving motor vehicles or other mechanisms.

Amlodipine may have minor or moderate effects on the ability to drive or operate machinery.

The reaction rate may be reduced if there are symptoms such as dizziness, headache, confusion or nausea.

Care should be taken, especially at the start of therapy.

Method of administration and dose

Adults

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

Patients with angina pectoris may be used as monotherapy or in combination with other antianginal drugs for resistance to nitrates and / or adequate doses of beta-blockers.

There is experience with the use of the drug in combination with thiazide diuretics, alpha-blockers, beta-blockers, or ACE inhibitors in patients with arterial hypertension.

There is no need to select a dose of the drug while co-administered with thiazide diuretics, beta-blockers, and ACE inhibitors.

Children aged 6 years and older with arterial hypertension.

The recommended initial dose of Vasotal for this patient category is 2.5 mg once a day. If the required blood pressure level is not reached within 4 weeks, the dose can be increased to 5 mg per day. The use of a 5 mg dose for this patient category has not been studied.

Older patients.

There is no need to select a dose for this patient category. The dose should be increased with caution.

Patients with impaired kidney 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 related to the severity of renal failure. Amlodipine is not eliminated by dialysis.

Patients with impaired liver function.

The doses of the drug for use in patients with mild to moderate hepatic impairment have not been established, therefore the dose selection should be carried out with caution and the use of a low dose dose in the dose range should be initiated (see Section "Peculiarities of use" and "Pharmacological properties Pharmacokinetics" ) The pharmacokinetics of amlodipine have not been studied in patients with severe hepatic impairment. Patients with severe liver function impairment should start with a low dose of amlodipine and gradually increase it.

Where are you.

The drug is used for children aged 6 years and older.

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

Overdose

The experience of intentional overdose is limited.

Overdose Symptoms : Available information suggests that a significant overdose of Vasotal will lead to excessive peripheral vasodilation and, possibly, reflex tachycardia. A significant and, possibly, prolonged systemic arterial hypotension, including fatal shock, has been reported.

Treatment of clinically significant arterial hypotension due to an overdose of amlodipine requires active support for the cardiovascular system, including frequent monitoring of cardiac and respiratory function, elevation of the lower extremities, monitoring of the volume of circulating fluid and urination.

To restore vascular tone and blood pressure, you can use vasoconstrictor drugs, making sure that there are no contraindications to their use. The use of calcium gluconate intravenously may be useful for leveling the effects of blockade of calcium channels.

In some cases, gastric lavage may be beneficial.

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

Adverse reactions

When amlodipine was used, the most commonly reported side effects were drowsiness, dizziness, headache, increased heart rate, blood flushing, abdominal pain, nausea, edema, swelling and fatigue.

Side effects reported with amlodipine are given below by systems and classes of organs.

From the blood and lymphatic system : leukopenia, thrombocytopenia.

From the immune system: allergic reactions.

Disturbance of metabolism and alimentary disorders: hyperglycemia.

Mental disorders : depression, mood changes (including anxiety), insomnia, confusedness of consciousness.

From the nervous system : drowsiness, dizziness, headache (mainly at the beginning of treatment) tremor, dysgeusia, fainting, hyposesthesia, paresthesia; hypertonus, peripheral neuropathy.

From the organ of vision: visual impairment (including diplopia).

On the part of the hearing and labyrinth: ringing in the ears.

From the heart: tachycardia; arrhythmia (including bradycardia, ventricular tachycardia and atrial fibrillation) myocardial infarction.

From the side of the vessels: inflow; arterial hypotension vasculitis.

Respiratory, thoracic and mediastinal disorders : dyspnea, cough, rhinitis.

From the gastrointestinal tract: abdominal pain, nausea, dyspepsia, peristalsis of the intestine (including diarrhea and constipation); vomiting, dry mouth, pancreatitis, gastritis, gum hyperplasia.

From the digestive system: hepatitis, jaundice, elevated liver enzymes (most often associated with cholestasis).

Skin and subcutaneous tissue : alopecia, purpura, skin discoloration, increased sweating, itching, rash, rash, urticaria angioedema, erythema multiforme, exfoliative dermatitis, Stevens Johnson syndrome, Queen's edema, photosensitization.

On the part of the bone-muscle and connective tissue swelling of the legs, muscle cramps ; arthralgia, myalgia, back pain.

On the part of the kidneys and urinary tract : violation of urination, nicoturia, increased frequency of urination.

From the reproductive system and mammary glands : impotence, gynecomastia.

General disorders and conditions at the injection site : edema fatigability, asthenia, chest pain, pain, malaise.

Study: increase or decrease body weight.

Exceptional cases of extrapyramidal syndrome were reported.

Reporting Suspected Side Effects: Reporting suspected adverse reactions after drug registration is important. This allows continuous monitoring of the relationship between benefit and the risks associated with the use of this drug. Doctors should report any suspected adverse reactions in accordance with the requirements of the law.

Shelf life

3 years.

Storage conditions

Hranyt at temperatures Above 30 ° C out of reach of children and of light from zaschyschennom place.

Packaging

10 tablets in blister, blister in 2 kartonnoy box.

Vacation category

For prescription.