Amlodipine, tablets 10 mg 30 pcs

Pharmacotherapeutic group

Slow calcium channel blocker

ATX code: C08CA01

Pharmacodynamics:

The “slow” calcium channel blocker dihydropyridine derivative, a second-generation slow calcium channel blocker (BMCC), has antianginal and hypotensive effects. It blocks calcium channels decreases transmembrane transition of calcium ions into the cell (more in vascular smooth muscle cells than in cardiomyocytes).

The antianginal action is caused by the dilation of coronary and peripheral arteries and arterioles: in angina pectoris it reduces myocardial ischemia; dilation of peripheral arterioles reduces total peripheral vascular resistance (TPR) and decreases postcardiac load which reduces myocardial oxygen demand. By dilating the coronary arteries and arterioles in the unchanged and ischemic areas of the myocardium, it increases the oxygen supply to the myocardium (especially in vasospastic angina); prevents coronary artery spasm (including that caused by smoking). In patients with stable angina a single daily dose increases exercise tolerance increases time to an attack of angina and “coronary” ST-segment depression decreases the frequency of angina attacks and nitroglycerin consumption of other nitrates. It has a long-term dose-dependent hypotensive effect. The hypotensive effect is due to the direct vasodilating effect on the vascular smooth muscles. In arterial hypertension a single dose provides clinically significant reduction of blood pressure (BP) for 24 hours. (in patient’s “lying” and “standing” position). Orthostatic hypotension when prescribing amlodipine is rare. It does not cause decrease in left ventricular ejection fraction. It reduces the degree of left ventricular myocardial hypertrophy. Does not affect myocardial contractility and conduction does not cause reflex increases in heart rate

Inhibits platelet aggregation and increases glomerular filtration rate has a weak natriuretic effect.

In diabetic nephropathy it does not increase the severity of microalbuminuria. There is no adverse effect on metabolism and concentration of blood plasma lipids and it can be used for therapy of patients with bronchial asthma, diabetes mellitus and gout. Significant reduction in BP is observed after 6-10 hours the duration of effect is 24 hours.

. In patients with cardiovascular diseases including coronary atherosclerosis with lesion of one vessel and up to stenosis of 3Atherosclerosis of the carotid arteries with myocardial infarction, percutaneous transluminal angioplasty (TLAP) of the coronary arteries, or patients with angina, amlodipine prevents the development of carotid intima-media thickening and reduces mortality from myocardial infarction and stroke TLAP by coronary artery bypass grafting; leads to lower incidence of unstable angina and progression of chronic heart failure (CHF); reduces the frequency of interventions to restore coronary blood flow.

Does not increase risk of death or complications and lethal outcomes in patients with CHF (functional class III-IV according to NYHA classification) during therapy with digoxin diuretics and antotensin-converting enzyme inhibitors (ACEI). In patients with CHF (functional class III-IV according to NYHA classification) of non-ischemic etiology when using amlodipine there is a possibility of pulmonary edema.

Pharmacokinetics:

After oral administration, amlodipine is slowly absorbed from the gastrointestinal tract (GIT). Mean absolute bioavailability is 64% maximum concentration (Cmax) in blood serum is observed after 6-9 hours. Equilibrium concentrations (CSS) are reached after 7-8 days of therapy.

Eating does not affect absorption of amlodipine. Mean volume of distribution is 21 l/kg body weight which indicates that most of the drug is in tissues and less in blood. Most of the drug in blood (95%) is bound to plasma proteins. Amlodipine undergoes slow but active metabolism in the liver with no significant “first pass” effect. Metabolites have no significant pharmacological activity. After a single dose, the elimination half-life (T1/2) varies from 35 to 50 hours with a repeated use of T1/2 of approximately 45 hours. About 60% of oral dose is excreted by kidneys mainly as metabolites, 10% – unchanged, 20-25% – via intestine with bile. Total clearance of amlodipine is 0116 ml/s/kg (7 ml/min/kg 042 l/h/kg).

Elderly patients (over 65 years) have slower excretion of amlodipine (T1/2 is 65 h) compared to younger patients but this difference has no clinical significance. The prolonged T1/2 in patients with hepatic impairment suggests that long-term use will result in higher cumulation (T1/2- up to 60 h). Renal insufficiency has no significant effect on amlodipine kinetics. In patients with impaired renal function, changes in amlodipine plasma concentrations do not correlate with the degree of renal failure. Slight increase in T1/2 is possible.

Amlodipine penetrates the blood-brain barrier. It is not eliminated by hemodialysis.

Indications

– arterial hypertension.

Stable angina pectoris and vasospastic angina pectoris.

Active ingredient

Composition

1 tablet contains:

The active ingredient:

Amlodipine besylate (amlodipine) -13.888 mg (10.00 mg).

Excipients: Microcrystalline cellulose, calcium hydrophosphate (anhydrous), sodium carboxymethyl starch (type A), magnesium stearate.

How to take, the dosage

Overly once daily with the required amount of water (100 ml).

In case of arterial hypertension and angina pectoris, the initial dose is 5 mg once daily. If there is no therapeutic effect within 2-4 weeks, the drug dose can be increased to 10 mg once daily.

In elderly patients

There is no need for dose adjustment.

In patients with hepatic impairment

Even though the T1/2 of amlodipine, like all BMCCs, is prolonged in patients with hepatic impairment, dosage adjustment is usually not required (see section “Special Precautions”).

In patients with renal impairment

It is recommended that Amlodipine-Teva be used in usual doses (see section “Special Precautions”).

Interaction

Amlodipine may be safely used for therapy of arterial hypertension together with thiazide diuretics alpha-adrenoblockers or ACE inhibitors. In patients with stable angina pectoris, amlodipine may be combined with other antianginal agents such as long-acting or short-acting nitrates.

In contrast to other PBMCs no clinically significant interaction of amlodipine (second generation PBMCs) has been found with anti-inflammatory drugs (NSAIDs) including indomethacin. Increased antianginal and hypotensive effect of PBMCs is possible when used together with thiazide and “loop” diuretics, ACE inhibitors and nitrates as well as increased hypotensive effect when used together with alpha1-adrenoblockers.

Eritromycin when used together increases Cmax of amlodipine by 22% in young patients and by 50% in elderly patients.

Beta-adrenoblockers concomitantly used with amlodipine may aggravate the course of heart failure.

While no negative inotropic effects have generally been seen with amlodipine, some DMARDs can exacerbate the negative inotropic effects of antiarrhythmic agents that prolong the QT interval (e.g., amiodarone and quinidine).

A single use of 100 mg sildenafil in patients with arterial hypertension has no effect on the pharmacokinetic parameters of amlodipine.

Repeated use of amlodipine 10 mg and atorvastatin 80 mg has no significant changes in pharmacokinetic parameters of atorvastatin.

Ethanol (beverages containing alcohol): amlodipine in single and repeated use in dose of 10 mg does not affect the pharmacokinetics of ethanol.

Antiretroviral agents (ritonavir) increase plasma concentrations of PBMCs including amlodipine.

Neuroleptics and isoflurane increase the hypotensive effect of dihydropyridine derivatives.

Calcium preparations may decrease the effect of BMCCs.

The co-administration of amlodipine with lithium preparations may increase the manifestation of neurotoxicity (nausea vomiting diarrhea ataxia tremor tinnitus). Amlodipine does not alter the pharmacokinetics of cyclosporine.

It does not affect the serum concentration of digoxin and its renal clearance.

There is no significant effect on the effect of warfarin (prothrombin time). Cimetidine does not affect the pharmacokinetics of amlodipine.

In in-vitro studies amlodipine does not affect the binding to plasma proteins of digoxin phenytoin warfarin and indomethacin.

Grapefruit juice: Concomitant administration of 240 mg of grapefruit juice and 10 mg of oral amlodipine is not accompanied by significant changes in pharmacokinetics of amlodipine.

Aluminum- or magnesium-containing antacids: their single administration has no significant effect on amlodipine pharmacokinetics.

Special Instructions

During therapy with Amlodipine-Teva it is necessary to control body weight and sodium intake and an appropriate diet is indicated.

Maintenance of oral hygiene and monitoring by a dentist is necessary (to prevent bleeding soreness and gum hyperplasia).

When using Amlodipine-Teva in patients with chronic heart failure of NYHA functional class III and IV, pulmonary edema may develop.

In acute myocardial infarction Amlodipine-Teva is prescribed after hemodynamic stabilization (see section “Contraindications”).

Patients with hepatic impairment should be under medical supervision if Amlodipine-Teva must be taken.

In elderly patients the T1/2 may increase and the drug clearance may decrease. No change in dosage is required, but closer monitoring of patients in this category is necessary.

In patients with impaired renal function, monitoring is necessary. The efficacy and safety of Amlodipine-Teva in hypertensive crisis have not been established.

While there is no withdrawal syndrome in DMARDs, it is advisable to discontinue Amlodipine-Teva gradually reducing the dose of the drug.

While Amlodipine-Teva has not been observed to have any adverse effect on the ability to drive or operate motor vehicles or other complex machines, caution should be exercised in the following situations, especially at initial treatment and with increasing doses, due to the potential for excessive BP decrease and dizziness or other adverse reactions.

Contraindications

– hypersensitivity to amlodipine and other dihydropyridine derivatives and other components of the drug;

– severe arterial hypotension (systolic BP less than 90 mm Hg).);

– cardiogenic shock;

– acute myocardial infarction (within the first 28 days);

– unstable angina (except for Prinzmetal angina);

– left ventricular outflow tract obstruction;

– clinically significant aortic stenosis;

– age less than 18 years (efficacy and safety not established).

Side effects

The frequency of adverse reactions was determined according to the following (classification of the World Health Organization): very common – at least 10%; common – at least 1% but less than 10%; infrequent – at least 01% but less than 1%; rare – at least 001% but less than 01%; very rare – less than 001% including individual reports.

Frequent – headache (especially at the beginning of treatment) dizziness increased fatigue somnolence; infrequent – general malaise hypoesthesia asthenia paresthesia peripheral neuropathy tremor insomnia emotional lability unusual dreams nervousness increased excitability depression anxiety increased sweating; rare – convulsions apathy agitation; very rare – ataxia amnesia migraine.

The digestive system: frequently – nausea abdominal pain; infrequently – vomiting anorexia dry mouth mucosa thirst; rarely – gum hyperplasia increased appetite; very rarely – pancreatitis gastritis jaundice (usually cholestatic) hyperbilirubinemia increased activity of “liver” transaminases hepatitis.

Cardiovascular system disorders: frequent – peripheral edema (ankles and feet) palpitation “rushes” of blood to the skin of the face; infrequent – excessive reduction of BP orthostatic hypotension vasculitis; rare – development or aggravation of the course of CHF; very rare – syncope dyspnea heart rhythm disorders (including bradycardia ventricular tachycardia and atrial fibrillation) myocardial infarction difficult cage pain pulmonary edema.

Hematopoietic and lymphatic system disorders: very rare – thrombocytopenic purpura leukopenia thrombocytopenia.

The urinary system: infrequent – pollakiuria painful urge to urinate nycturia; very rare – dysuria polyuria.

With the reproductive system and mammary glands: infrequent – gynecomastia impotence.

Respiratory system: infrequent dyspnea rhinitis; very rare – cough.

Musculoskeletal system: infrequent – muscle cramps myalgia arthralgia back pain arthrosis; rarely – myasthenia.

Skin: infrequent alopecia; rarely dermatitis; very rare alopecia xeroderma cold clammy sweat disorder of skin pigmentation.

Allergic reactions: rare – skin itching rash (including erythematous maculopapular rash); very rare – urticaria angioedema mulyiform erythema.

Sense organs: infrequent – tinnitus visual impairment diplopia accommodation disorder xerophthalmia conjunctivitis eye pain; very rare – parosmia.

Mechanical disorders: very rarely – hyperglycemia.

Others: infrequent – weight loss weight gain perversion of taste nasal bleeding chills.

Overdose

Symptoms: marked BP decrease with possible development of reflex tachycardia and excessive peripheral vasodilation (risk of severe and persistent arterial hypotension including development of shock and death).

The treatment: gastric lavage administration of activated charcoal (especially in the first 2 hours after overdose) maintenance of cardiovascular function elevation of the lower extremities monitoring of heart and lung function parameters control of circulating blood volume (CBV) and diuresis. To restore vascular tone – the use of vasoconstrictors (if there are no contraindications for their use); to eliminate the effects of calcium channel blockade – intravenous injection of calcium gluconate. Hemodialysis is ineffective.

Pregnancy use

Fetotoxic and embryotoxic effects of the drug have not been established in experimental studies, but use in pregnancy is possible only when the benefit to the mother exceeds the potential risk to the fetus.

There are no data indicating excretion of amlodipine with breast milk. However, other dihydropyridine derivatives are known to be excreted in breast milk. Therefore, if it is necessary to prescribe Amlodipine-Teva during lactation, discontinuation of breastfeeding should be considered.

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