The mechanism of action
A drug blocking III generation Calcium channels, dihydropyridine derivative with prolonged action. It inhibits the inflow of calcium ions to vascular smooth muscle cells and to a lesser extent to myocardial cells. Lowering blood pressure results from a direct reduction of vascular smooth muscle tone. A single daily dose lowers blood pressure in both standing and lying positions, persisting for 24 hours. It does not cause acute hypotension (delayed onset of action) or orthostatic hypotension. The action in angina is the result of: dilation of peripheral arterioles with a decrease in peripheral resistance and subsequent loading (afterload), with reduced myocardial oxygen demand and lower energy consumption; enlargement of arteries and coronary arterioles, both in the normal muscle and in the area of ischaemia, which improves the oxygenation of the myocardium, including in patients with Prinzmetal angina. As a result, it increases the total time to angina pain during exercise, reduces the frequency of angina attacks and Nitroglycerin consumption. There was no effect on the sinus node function or on the conductivity within the atrioventricular junction.
Amlodipine is well absorbed from the gastrointestinal tract, reaching a maximum concentration after 6-12 h. Biological availability is 64-80% and does not change under the influence of food. t1/2 in the final phase of elimination is 35-50 h, therefore it is possible to use the drug 1 × / d. Steady state of therapeutic concentration occurs after 7-8 days of daily administration of the drug. plasma proteins are 97.5% bound. It is metabolized to a large extent in the liver to inactive metabolites. It is excreted in the urine in 60% in the form of inactive metabolites, in 10% unchanged. Renal insufficiency does not significantly affect the pharmacokinetics of the drug. Amlodipine is not removed during dialysis. In the elderly, it is well tolerated, but its clearance, similarly to patients with liver damage, is smaller.
Hypertension in adults (monotherapy or combination therapy with diuretics, β-blockers, ACE inhibitors) and hypertension in children and adolescents 6.-17. years of age.
Stable angina (monotherapy or combination therapy with β-blockers, ACE inhibitors, long-acting nitrates).
Vasospastic angina (Prinzmetal angina) monotherapy or combination with a calcium channel blocker from a different group or with long-acting nitrates.
Hypersensitivity to any of the other ingredients or other dihydropyridines, severe hypotension, shock (including cardiogenic shock), narrowing of the left ventricle outflow pathway (clinically significant aortic stenosis), haemodynamically unstable heart failure after recent myocardial infarction.
Use with caution in people with congestive heart failure.
Caution should be exercised in persons with impaired hepatic function, both during initiation of therapy and during dose escalation; start using the lowest possible dose.
In elderly people, increase the dose with caution.
Fresh heart attack
The efficacy and safety of amlodipine in patients with acute myocardial infarction and within 1 month after the infarction has not been established.
A hypertensive crisis
The safety and efficacy of patients with hypertensive crisis have not been established.
Discontinuation of the drug
It is recommended to gradually reduce the dose before stopping the drug.
Children and youth
The long-term effects of amlodipine on the growth, maturation and overall development of children have not been studied.
Other antihypertensive drugs
Amlodipine may potentiate the effects of other antihypertensive agents (diuretics of the thiazide group, α-blockers, β-blockers, ACE inhibitors), but it can usually be safely used in combination with these medicines.
The drug can also be used in combination with prolonged nitrates and administered nitroglycerineS.L. (caution), digoxin, warfarin, atorvastatin, sildenafil, antacids, NSAIDs, antibiotics, oral hypoglycaemic agents, cimetidine.
The use of amlodipine in combination with β-blockers in high-risk patients may lead to heart failure, hypotension, and myocardial infarction; in addition, the β-blocker may reduce the sympathetic response in case of excessive hemodynamic response.
The use of amlodipine and baclofen may increase the antihypertensive effect; blood pressure and renal function should be monitored and the dose of amlodipine should be adjusted as necessary.
Corticosteroids, tetracosactis and amifostine
Corticosteroids, tetracosactide and amifostine may reduce the antihypertensive effect of amlodipine.
Amlodipine and Sildenafil used in parallel have an independent effect on lowering blood pressure.
Cimetidine does not affect the pharmacokinetics of amlodipine.
Atorvastatin, digoxin, Warfarin and cyclosporin
Amlodipine does not affect the pharmacokinetics of atorvastatin, digoxin, warfarin and cyclosporine.
Often: headaches (especially at the beginning of treatment), edema (including swelling of the ankles), fatigue, drowsiness, nausea, abdominal pain, flushing of the face with a feeling of heat, palpitations, dizziness.
not veryoften: insomnia, mood disorders (including anxiety), depression, tremor, taste disorders, fainting, hypoesthesia, hyperaesthesia, paresthesia, visual disturbances (including double vision), tinnitus, hypotension, dyspnea, rhinitis, vomiting, indigestion, intestinal dysfunction (including diarrhea and constipation), dry mouth, alopecia, purpura, hyperpigmentation, increased sweating, pruritus, rash, rash, joint pain, muscle pain, muscle spasms, back pain, urination disorders , pollakiuria, impotence, gynecomastia, chest pain, asthenia, malaise, weight gain or loss.
Very rarely: leukopenia, thrombocytopenia, allergic reactions (angioneurotic edema, erythema multiforme, exfoliative dermatitis, Stevens and Johnson syndrome, urticaria, Quincke edema, hypersensitivity to light), hyperglycemia, increased muscle tone, peripheral neuropathy, myocardial infarction, arrhythmias (in including tachycardia, ventricular tachycardia and atrial fibrillation), vasculitis, cough, pancreatitis, gastritis, gingival hypertrophy, hepatitis, jaundice, increased liver enzymes. Isolated cases of extrapyramidal syndrome have been reported.
There is no well-documented experience in the management of amlodipine poisoning. As the drug is absorbed slowly, in selected cases, gastric lavage and the administration of activated charcoal may be beneficial. Massive poisoning can cause a significant and long-lasting drop in blood pressure with reflex tachycardia, requiring active maintenance of the cardiovascular system, with intravascular volume control and diuresis. It may be advisable to administer vasokonstriction drugs (if there are no contraindications) and administrationi.v. calcium gluconate. Dialysis is not effective.
Category C. The safety of the medicine has not been established in pregnant women. Do not use during pregnancy unless the benefit of treatment clearly outweighs the potential risk.
It is not known if the drug is excreted in human milk. The decision regarding the use of amlodipine and breastfeeding should be made after considering the benefits and risks.
After., regardless of meals.
Adultsinitially usually 5 mg 1 × / d; if necessary, the dose can be increased to a maximum of 10 mg 1 × / d.
Use with caution in people with hepatic impairment; treatment should start with the lowest possible dose.
In the elderly, dose modification is not generally necessary, but caution should be exercised when increasing the dose.
Impaired renal function
No dosage adjustment is necessary for people with impaired renal function.
Children and youth
In children and adolescents 6.-17. with an initial hypertension of 2.5 mg / d, if necessary after 4 weeks, the dose can be increased to 5 mg / d.