Amlodipine Sandoz - instructions for use, dose, side effects, contraindications

Active substance: amlodipine besylate 6.934 mg (corresponding to 5 mg of amlodipine) / amlodipine besylate 13.868 mg (corresponding to 10 mg of amlodipine).

Excipients: lactose anhydrous 109.866 mg / 219.732 mg, microcrystalline cellulose 66,800 mg / 133,600 mg, corn starch (dry) 13,200 mg / 26,400 mg, talc 1,000 mg / 2,000 mg, silicon dioxide colloidal anhydrous 1,000 mg / 2,000 mg, magnesium stearate 1,200 mg / 2,400 mg.

Description:

Round flat tablets white or white with a yellowish tint of color with a risk on one side and bevel.

Pharmacotherapeutic group:blocker of "slow" calcium channels

ATX: & nbsp

C.08.C.A.01 Amlodipine

Pharmacodynamics:

The dihydropyridine derivative is blockedp "slow" calcium channels, has an antianginal and hypotensive effect. Linking with dihydropyridine receptors blocks calcium channels, reduces the transmembrane transition of calcium ions into the cell (mostly in smooth muscle cells of blood vessels, rather than in cardiomyocytes).

Antianginal effect is due to the expansion of coronary and peripheral arteries and arterioles: with angina decreases the severity of myocardial ischemia; expanding peripheral arterioles, reduces the overall peripheral vascular resistance, reduces preload on the heart, reduces the need for myocardium in oxygen. Expanding the main coronary arteries and arterioles in unchanged and ischemic zones of the myocardium, increases the flow of oxygen into the myocardium (especially with vasospastic angina); prevents the development of constriction of the coronary arteries (including caused by smoking).

In patients with angina, a single daily dose increases the time of exercise, slows the development of angina pectoris and "ischemic" depression of the ST segment, reduces the frequency of angina attacks and consumption of nitroglycerin.Has a long-term dose-dependent hypotensive effect. The hypotensive effect is due to a direct vasodilating effect on smooth muscle vessels. With arterial hypertension, a single dose provides a clinically significant decrease in blood pressure (BP) for 24 hours (in the patient's position "lying" and "standing").

Does not cause a sharp decrease in blood pressure, a decrease in exercise tolerance, a fraction of the ejection of the left ventricle. Reduces the degree of myocardial hypertrophy of the left ventricle, has antiatherosclerotic and cardioprotective effect in coronary heart disease. Does not affect the contractility and conductance of the myocardium, does not cause a reflex increase in the heart rate, inhibits platelet aggregation, increases the rate of glomerular filtration, has a weak natriuretic effect. When diabetic nephropathy does not increase the severity of microalbuminuria. Has no adverse effects on the metabolism and concentration of plasma lipids. The time of onset of the effect is 2-4 hours, the duration of the effect is 24 hours.

Pharmacokinetics:

After oral administration amlodipine is slowly absorbed from the gastrointestinal tract. The average absolute bioavailability is 64-80%, the maximum concentration in the blood plasma is observed after 6-12 hours. A stable equilibrium concentration is achieved after 7-8 days of therapy. Food intake does not affect the absorption of amlodipine. The average volume of distribution is 21 l / kg body weight, indicating that most of the drug is in the tissues, and relatively less in the blood. Most of the drug in the blood (97.5%) binds to blood plasma proteins.

Amlodipine undergoes a slow but extensive metabolism (90%) in the liver with the formation of inactive metabolites, has the effect of "primary passage" through the liver. Metabolites do not have significant pharmacological activity. After a single oral intake, the half-life period (T1 / 2) varies from 35 to 50 hours, with repeated application of T1 / 2 it is approximately 45 hours. About 60% of the dose taken internally is excreted by the kidneys mainly in the form of metabolites, 10% unchanged, and 20-25% through the intestine. Excretion with breast milk is unknown. The total clearance of amlodipine is 0.116 ml / s / kg (7 ml / min / kg, 0.42 l / h / kg).

In elderly patients (over 65 years), amlodipine withdrawal is slowed (T1 / 2 65 h) compared with young patients, but this difference is not clinically significant. In patients with hepatic insufficiency, the half-life of amlodipine increases, recommendations for dosage are not determined, therefore amlodipine this group of patients should be used with caution. In patients with renal failure, the elimination half-life increases to 60 hours. The change in the concentration of amlodipine in the blood plasma does not correlate with the degree of impaired renal function. The drug penetrates the blood-brain barrier. When hemodialysis is not removed.

Indications:

- Arterial hypertension (both in monotherapy, and in combination with other antihypertensive drugs).

- Coronary heart disease: stable exertional angina, vasospastic angina (Prinzmetal angina) (both in monotherapy, and in combination with other antianginal agents).

Contraindications:

- hypersensitivity to amlodipine and other dihydropyridine derivatives, as well as to the auxiliary components of the drug;

- severe arterial hypotension;

- collapse, cardiogenic shock;

- unstable angina (with the exception of Prinzmetal angina);

- hemodynamically unstable heart failure after acute myocardial infarction;

- Obstruction of the outflow tract of the left ventricle (eg, pronounced aortic stenosis);

- rare hereditary forms of lactose intolerance, lactase deficiency or impaired absorption of glucose / galactose (because the composition contains lactose);

- age under 18 years (efficiency and safety not established).

Carefully:

With caution should be used in patients with hepatic insufficiency, chronic heart failure in the stage of decompensation, the elderly, the simultaneous use with inhibitors and inducers of the isoenzyme CYP3A4. As with other BCCC, care should be taken against the background of amlodipine in patients with sinus node weakness syndrome, mitral valve stenosis, hypertrophic obstructive cardiomyopathy, mild to moderate arterial hypotension, and acute myocardial infarction (and within 1 month after it).

Pregnancy and lactation:

Security Sandoz® use of amlodipine during pregnancy and lactation has not been established, therefore, use of the drug is possible only when the intended benefits to the mother outweighs the potential risk to the fetus and newborn.

When using the drug during lactation, the question of stopping breastfeeding should be decided (there is no data on excretion of amlodipine with breast milk).

Dosing and Administration:

Inside, once a day, with a sufficient amount of water (100-200 ml), regardless of food intake. For the treatment of hypertension and prevention of attacks of angina pectoris and vasospastic angina initial daily dose of amlodipine Sandoz® is 5 mg at one time. If necessary, the dose may be increased to a maximum daily dose of 10 mg / day, once.

Use in elderly patients. It is recommended to use in usual doses, dose adjustment is not required.

Use in patients with impaired renal function. Correction of the dose is not required.

Use in patients with impaired liver function. Half-life Amlodipine Sandoz® increases in patients with this pathology, recommendations for dosage are not determined, therefore amlodipine this group of patients should be used with caution. Patients with low body weight or low growth, as well as with severe hepatic insufficiency, may need less doses of the drug. There is no need for dose changes with simultaneous administration with thiazide diuretics, beta-blockers and angiotensin-converting enzyme (ACE) inhibitors.

Side effects:

According to the World Health Organization (WHO), undesirable events are classified according to their frequency of development as follows: often (> 1/100, <1/10), infrequently (> 1/1000, <1/100), rarely (> 1 / 10000, <1/1000) and very rarely (<1/10000), including individual messages.

From the nervous system: often: headache (especially at the beginning of treatment), dizziness, fatigue, drowsiness; infrequently: asthenia, general malaise, hypoesthesia, paresthesia, peripheral neuropathy, tremor, insomnia, mood lability, unusual dreams, increased excitability, depression, anxiety, taste perversion; rarely: convulsions; very rarely: migraine, increased sweating, apathy, ataxia, agitation, amnesia.

From the cardiovascular system: often: a feeling of palpitations, peripheral edema (ankles and feet), a feeling of heat and "tides" of blood to the skin of the face; infrequently: excessive decrease in blood pressure; very rarely: fainting, vasculitis, orthostatic hypotension, increased blood pressure, cardiac rhythm disturbances (ventricular tachycardia, atrial fibrillation), myocardial infarction, worsening of symptoms of heart failure, chest pain.

From the digestive system: often: nausea, abdominal pain; infrequent: vomiting, indigestion, dryness of the oral mucosa, changes in the bowel movement (including diarrhea and constipation), flatulence, thirst; rarely: gingival hyperplasia, increased appetite; very rarely: gastritis, pancreatitis, jaundice (usually cholestatic), hyperbilirubinemia, increased activity of "hepatic" transaminases, hepatitis.

From the genitourinary system: infrequently: frequent urination, painful urination, pollakiuria, nocturia, impotence; very rarely: dysuria, polyuria.

From the musculoskeletal system: infrequently: myalgia, arthralgia, muscle cramps, back pain, arthrosis; rarely: myasthenia gravis.

From the skin: rarely: dermatitis; very rarely: alopecia, xeroderma, "cold sweat," a violation of skin pigmentation.

Allergic reactions: infrequently: skin rash (including erythematous, maculopapular rash, hives), itching; very rarely: polymorphic erythema, exfoliative dermatitis (syndrome Stevens-Johnson), angioedema, photosensitivity.

From the senses: infrequently: visual impairment (including diplopia), accommodation disorder, xerophthalmia, conjunctivitis, pain in the eyes, "ringing" in the ears; very rarely: parosmia (perversion of the sense of smell).

On the part of the respiratory system: infrequently: dyspnea, rhinitis, epistaxis, dyspnoea; very rarely: cough.

On the part of the blood system and lymphatic system: very rarely: thrombocytopenia, leukocytopenia, thrombocytopenic purpura.

From the side of metabolism: infrequently; increase / decrease in body weight (weight), gynecomastia; highly rarely: hyperglycemia.

General disorders and disorders at the injection site: infrequently: chills.

Overdose:

Symptoms: marked decrease in BP with possible development of reflex tachycardia and excessive peripheral vasodilation (there is a probabilitythe appearance of severe and persistent arterial hypotension, including with the development of shock and death).

Treatment: the purpose of activated carbon (in the first 2 hours after an overdose), gastric lavage (in some cases), elevating limbs, monitoring the function of the cardiovascular and respiratory systems, actively maintaining the function of the cardiovascular system, monitoring the volume of circulating blood and diuresis.

To restore the tone of blood vessels and increase blood pressure, if there are no contraindications, it is possible to prescribe vasoconstrictive drugs. Intravenous administration of calcium gluconate is used. Hemodialysis is ineffective because amlodipine largely binds to blood plasma proteins.

Interaction:

When using amlodipine in combination with thiazide and "loop" diuretics, verapamil, ACE inhibitors, beta-adrenoblockers and nitrates may increase the antianginal and hypotensive effect.

The combined use of BCCI and beta-adrenoreceptor blockers in patients with myocardial infarction can lead to its re-emergence and development of severe heart failure.

Aluminum / Magnesium containing antacids: their single administration does not have a significant effect on the pharmacokinetics of amlodipine.

Sildenafil: a single dose of 100 mg of sildenafil in patients with essential hypertension does not affect the pharmacokinetics of amlodipine.

Atorvastatin: repeated use of amlodipine at a dose of 10 mg and atorvastatin at a dose of 80 mg is not accompanied by significant changes in the pharmacokinetics of atorvastatin.

With simultaneous use with amlodipine, the maximum daily dose of simvastatin should not exceed 20 mg.

Digoxin: with simultaneous use of amlodipine with digoxin in healthy volunteers, serum concentrations and renal clearance of digoxin do not change.

Ethanol (alcohol-containing beverages): with a single and repeated application in a dose of 10 mg amlodipine has no significant effect on the pharmacokinetics of ethanol.

Warfarin: amlodipine does not affect the changes in prothrombin time caused by warfarin.

Cyclosporine: amlodipine does not cause significant changes in the pharmacokinetics of cyclosporine.

Unlike other BCCI, there was no clinically significant interaction of amlodipinewhen combined with non-steroidal anti-inflammatory drugs (NSAIDs), especially indomethacin.

Cimetidine does not affect the pharmacokinetics of amlodipine.

Grapefruit juice: simultaneous single intake of 240 ml of grapefruit juice and 10 mg of amlodipine inwards is not accompanied by a significant change in the pharmacokinetics of amlodipine.

Amiodarone, quinidine, alpha1-adrenoblockers, antipsychotic drugs (antipsychotics) and BCCC may enhance the hypotensive effect of amlodipine. With the simultaneous use of amlodipine with antiarrhythmic drugs that cause prolongation of the QT interval (for example, amiodarone and quinidine) may increase the severity of negative inotropic action.

When combined with preparations of lithium may be increased manifestations of neurotoxicity (nausea, vomiting, diarrhea, ataxia, tremor, tinnitus).

Calcium preparations reduce the effect of BCCC.

Inhibitors of the isoenzyme CYP3A4: diltiazem, inhibits the metabolism of amlodipine, increasing its concentration in the blood plasma by 50% and reducing its effectiveness. Therefore, it is possible that other inhibitors of the isoenzyme CYP3A4 - ketoconazole, HIV protease inhibitors (ritonavir), clarithromycin, erythromycinalter the pharmacological properties of amlodipine in a similar manner.

Inductors of the isoenzyme CYP3A4 (dexamethasone, phenobarbital, rifampicin, carbamazepine, rifabutin, phenytoin, nevirapine) can reduce the concentration of amlodipine in the blood plasma.

Special instructions:

Optimal use of the drug Amlodipine Sandoz® every day at the same time. Despite the absence of the "cancellation" syndrome in BCC, before the cessation of treatment a gradual dose reduction is recommended. Amlodipine Sandoz® can be used in combination with thiazide diuretics, alpha and beta adrenoblockers, ACE inhibitors, prolonged-action nitrates, nitroglycerin for oral administration, nonsteroidal anti-inflammatory drugs, antibiotics, oral hypoglycemic agents. Amlodipine Sandoz® does not adversely affect the metabolism and lipids of blood plasma, so it can be used in patients with bronchial asthma, diabetes and gout, as well as in cases where the patient is prone to vasospasm / vasoconstriction.

Patients with low body weight, low growth patients and patients with severe liver dysfunction may need a smaller dose. During treatment, it is necessary to control body weight and monitor the dentist (to prevent soreness, bleeding and gingival hyperplasia). In patients with chronic cardiac insufficiency III-IV functional class according to the NYHA classification, there was an increased incidence of pulmonary edema.

Effect on the ability to drive transp. cf. and fur:

With the use of Amlodipine Sandoz®, there was no adverse effect on the ability to drive a car or other technical means, however, because of the possible excessive decrease in blood pressure, slowing the reaction rate due to dizziness, headache, increased fatigue, etc. side effects, caution should be exercised at the beginning of the course of treatment and with a change in the dosing regimen.

Form release / dosage:

Tablets 5 mg, 10 mg.

Packaging:

Primary packaging

For 10 tablets in Al / Al. blister.

Secondary packaging

By 3, 6 or 9 blisters together with instructions for use in a cardboard box.

Storage conditions:

In a dry, the dark place at a temperature of no higher than 25 ° C. Keep out of the reach of children.

Shelf life:

2 years.

Do not use after expiry date.

Terms of leave from pharmacies:On prescription

Registration number:LSR-005229/09

Date of registration:30.06.2009

The owner of the registration certificate:Sandoz d.Sandoz d. Slovenia

Manufacturer: & nbsp

LEK d.d. Slovenia

Representation: & nbspSANDOZ SANDOZ Switzerland

Information update date: & nbsp04.09.2014

Illustrated instructions

Instructions

Amlodipine Sandoz® (Amlodipine Sandoz® )