Amlodipine-ALSI, tablets 10 mg 30 pcs

Dihydropyridine derivative is a “slow” calcium channels blocker (BMCC) of II generation, has antianginal and hypotensive effects. By binding to dihydropyridine receptors, it blocks calcium channels, reduces transmembrane transfer of calcium ions into 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), decreases cardiac preload, reduces myocardial oxygen demand.

Dilates main coronary arteries and arterioles in unchanged and ischemic areas of the myocardium, increases the flow of oxygen to the myocardium (especially in vasospastic angina); prevents development of coronary artery spasm (including that caused by smoking). In patients with stable angina a single daily dose increases exercise tolerance, slows down the development of angina and “coronary” ST-segment depression, reduces the frequency of angina attacks and the use of nitroglycerin and other nitrates.

It has a long-term dose-dependent hypotensive effect. The hypotensive effect is due to a direct vasodilatory effect on the vascular smooth muscles. In arterial hypertension, a single dose provides clinically significant reduction of blood pressure (BP) for 24 hours (in the position of the patient “lying” and “standing”). Orthostatic hypotension when prescribing amlodipine is quite rare. It does not cause reduction of exercise tolerance and left ventricular ejection fraction.

Limits the degree of myocardial hypertrophy of the left ventricle, has anti-atherosclerotic and cardioprotective effect in coronary heart disease (CHD). It does not affect myocardial contractility and conduction, does not cause reflex increase in heart rate (HR), inhibits platelet aggregation, increases glomerular filtration rate, has a weak natriuretic effect. In diabetic nephropathy it does not increase the severity of microalbuminuria.

It does not have adverse effects on metabolism and concentration of plasma lipids and can be used for treatment of patients with bronchial asthma, diabetes and gout. Significant decrease in BP is observed after 6-10 hours, the duration of the effect is 24 hours. With prolonged therapy maximum BP reduction occurs 6-12 hours after oral amlodipine administration. If after prolonged treatment amlodipine is stopped, effective BP reduction is maintained for 48 hours after the last dose. Then BP values gradually return to baseline within 5-6 days.

Indications

Active ingredient

Composition

One tablet contains:

as the active ingredient:

amlodipine besylate – 13.8 mg, which corresponds to 10 mg of amlodipine;

excipients:

lactose monohydrate – 171.4 mg,

povidone – 6.4 mg,

crospovidone – 6.4 mg,

calcium stearate – 2.0 mg.

Interaction

Amlodipine may be safely used for the treatment of arterial hypertension together with thiazide diuretics, alpha-adrenoblockers, beta-adrenoblockers or ACE inhibitors. In patients with stable angina pectoris the drug may be combined with other antianginal agents, e.g., long-acting nitrates, beta-adrenoblockers or short-acting nitrates.

Amlodipine may be combined with nonsteroidal anti-inflammatory drugs (NSAIDs) (especially indomethacin), antibacterial agents and oral hypoglycemic agents.

The antianginal and hypotensive effects of DMARDs may be enhanced when combined with thiazide and loop diuretics, verapamil, ACE inhibitors, beta-adrenoblockers and nitrates; and their hypotensive effects may be increased when combined with alpha 1-adrenoblockers and neuroleptics.

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 essential hypertension has no effect on the pharmacokinetic parameters of amlodipine.

The repeated use of amlodipine 10 mg and atorvastatin 80 mg dose is not associated with significant changes in pharmacokinetic parameters of atorvastatin.

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

Antiviral 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 DMARDs.

In co-administration of amlodipine with lithium preparations an increase in neurotoxicity (nausea, vomiting, diarrhea, ataxia, tremor, tinnitus) may occur.

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 blood 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 amlodipine pharmacokinetics.

Directions for use

In the oral route, the initial dose for the treatment of arterial hypertension and angina pectoris is 5 mg of the drug once daily. The maximum daily dose is 10 mg once.

In arterial hypertension, the maintenance dose may be 2.5 to 5 mg (1/2 tablet of 5 mg – 1 tablet of 5 mg) per day.

In angina of tension and vasospastic angina, 5-10 mg once daily. For prophylaxis of angina attacks – 10 mg/day.

Patients with impaired liver function as a hypotensive agent are prescribed with caution, in an initial dose of 2.5 mg (1/2 tablet of 5 mg), as an antianginal agent – 5 mg.

In elderly patients, T1/2 Amlodipine may be increased and creatinine clearance (CK) may decrease. No dose changes are required, but closer monitoring of patients is necessary.

Dose changes are not required when concomitantly administered with thiazide diuretics, beta-adrenoblockers and angiotensin-converting enzyme (ACE) inhibitors.

There is no need to change the dose in patients with renal impairment.

Special Instructions

Body weight and sodium intake should be controlled during treatment with Amlodipine and an appropriate diet should be prescribed. It is necessary to maintain dental hygiene and to see a dentist (to prevent soreness, bleeding and gum hyperplasia).

Patients who are underweight, short in stature, or have significant liver dysfunction may require a lower dose.

In elderly patients the T1/2 and clearance of the drug may be prolonged. No dose changes are required in elderly patients; closer monitoring of patients is necessary if the dose is increased.

In impaired liver function, the T1/2 of the drug may also be prolonged. Therefore, Amlodipine should be prescribed with caution in these patients.

While discontinuation of Amlodipine is not accompanied by development of withdrawal syndrome, it is advisable to discontinue treatment by gradually reducing the dose of the drug.

The efficacy and safety of the drug in hypertensive crisis have not been established.

Impact on the ability to drive and other complex mechanisms: There have been no reports about the effect of Amlodipine on driving or operating machinery. However, drowsiness and dizziness may occur in some patients, mainly at the beginning of treatment. If they occur, the patient should take special precautions when driving a car and working with complex mechanisms.

Synopsis

Features

After oral administration amlodipine is slowly absorbed from the gastrointestinal tract (GIT). Mean absolute bioavailability is 64%, maximum serum concentration (Cmax) is observed after 6-9 hours. Equilibrium serum concentrations (Ссs) are reached 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 that is in the 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 oral dose, the elimination half-life (T1/2) ranges from 31 to 48 hours, with a repeat administration of approximately 45 hours T1/2. About 60% of the oral dose is excreted by the kidneys mainly as metabolites, 10% is excreted unchanged, and 20-25% is excreted through the intestine and with the breast milk. Total clearance of amlodipine is 0.116 ml/kg (7 ml/min/kg, 0.42 l/h/kg).

The excretion of amlodipine is delayed (T1/2 – 65 h) in elderly patients (over 65 years) compared to younger patients, but this difference is not clinically relevant. The prolonged T1/2 in patients with hepatic insufficiency suggests that the drug will cumulate in the body more with long-term administration (T1/2- to 60 h). Renal insufficiency has no significant effect on amlodipine kinetics. The drug penetrates through the blood-brain barrier. It is not eliminated by hemodialysis.

Contraindications

Side effects

World Health Organization (WHO) Frequency Classification of side effects:

very often >1/10

often from >1/100 to <1/10

sometimes from >1/1000 to < 1/100

rarely from >1/10000 to < 1/1000

very rarely from < 1/10000, including individual posts.

Cardiovascular system disorders: frequent – palpitations, peripheral edema (swelling of ankles and feet), “rushes” of blood to the skin of the face; sometimes – excessive reduction of BP; very rare – syncope, dyspnea, vasculitis, orthostatic hypotension, development or worsening of heart failure, cardiac rhythm disturbances (including bradycardia, ventricular tachycardia and atrial fibrillation), myocardial infarction, chest pain.

The central and peripheral nervous system: frequently – headache, dizziness, fatigue, somnolence; sometimes – asthenia, general malaise, hypoesthesia, paresthesia, peripheral neuropathy, tremor, insomnia, mood swings, unusual dreams, nervousness, depression, anxiety, very rarely – migraine, increased sweating, apathy.

Digestive system disorders: often – nausea, abdominal pain; sometimes – vomiting, constipation or diarrhea, flatulence, dyspepsia, anorexia, dry mouth, thirst;
rare – gum hyperplasia, increased appetite; very rare – pancreatitis, gastritis, jaundice (due to cholestasis), hyperbilirubinemia, increased activity of “liver” transaminases, hepatitis.

Hematopoietic organs: very rarely – thrombocytopenic purpura, leukopenia, thrombocytopenia.

Urogenital system disorders: sometimes – frequent urination, painful urination, nicturia, impotence, very rarely – dysuria, polyuria, gynecomastia.

Respiratory system disorders: sometimes – shortness of breath, rhinitis, very rarely – cough.

The skin: rarely – dermatitis, very rarely – alopecia, xeroderma, “cold” sweat, impaired skin pigmentation.

Allergic reactions: skin itching, rash (including erythematous, maculopapular rash, urticaria), angioedema, erythema multiforme.

Musculoskeletal system: sometimes – muscle cramps, myalgia, arthralgia, back pain, arthrosis, rarely – myasthenia.

Others: sometimes – tinnitus, diplopia, accommodation disorder, xerophthalmia, conjunctivitis, eye pain, chills, nasal bleeding, very rare – parosmia, hyperglycemia.

Overdose

Symptoms: excessive peripheral vasodilation with marked and possibly prolonged BP decrease, collapse, shock.

Treatment: gastric lavage, administration of activated charcoal, maintenance of cardiovascular function, control of heart and lung function parameters, elevated, above head level, position of lower extremities, control of circulating blood volume and diuresis. To restore vascular tone – use 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.

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