Amlodipine-Vertex, tablets 10 mg 60 pcs

Pharmacodynamics

Amlodipine is a dihydropyridine derivative – blocker of “slow” calcium channels (BMCC) of II generation, has antianginal and hypotensive effect. 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 due to the dilation of coronary and peripheral arteries and arterioles: in angina pectoris it reduces the severity of myocardial ischemia; by dilation of peripheral arterioles it reduces total peripheral vascular resistance; reduces the preload on the heart, myocardial oxygen demand. Dilates the 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 the development of coronary artery spasm (including that caused by smoking). In patients with angina a single daily dose increases exercise tolerance, delays the development of another angina attack and “coronary” ST-segment depression; reduces the frequency of angina attacks and nitroglycerin consumption.

Amlodipine has a long-term dose-dependent hypotensive effect, which is due to direct vasodilator effect on vascular smooth muscle. In arterial hypertension a single daily dose of amlodipine provides clinically significant reduction of arterial pressure (BP) for 24 hours (in “lying” and “standing” position of the patient).

Limits the degree of left ventricular myocardial hypertrophy, has anti-atherosclerotic and cardioprotective effects in coronary heart disease (CHD). It does not affect myocardial contractility and conduction, inhibits platelet aggregation, increases glomerular filtration rate, has a weak natriuretic effect. In diabetic nephropathy it does not increase the severity of microalbuminuria. It has no adverse effect on metabolism and blood plasma lipid concentration. Time of onset of therapeutic effect is 2-4 hours, duration – 24 hours.

Pharmacokinetics

After oral administration amlodipine is slowly absorbed from the gastrointestinal tract. Food intake has no effect on the absorption of amlodipine. The average absolute bioavailability is 64%. Maximum serum concentration is observed after 6-9 hours. The equilibrium concentration is reached after 7-8 days of therapy. The binding to plasma proteins is 95%. Average volume of distribution is 21 l/kg body weight. Amlodipine undergoes slow but active metabolism (90 to 97%) in the liver with no significant “first pass” effect. Metabolites have no significant pharmacological activity.

The elimination half-life (T1/2) averages 35 hours. T1/2 in patients with arterial hypertension is 48 hours, in elderly patients it is increased up to 65 hours, in hepatic insufficiency – up to 60 hours, similar parameters of increase of T1/2 are observed in severe chronic heart failure, in renal function disorders – it does not change.

About 60% of a dose taken by mouth is excreted by kidneys mainly as metabolites, 10% – as unchanged, 20-25% – in bile and intestine as metabolites, as well as with breast milk.

The total clearance of amlodipine is 0.116 ml/s/kg (7ml/min/kg, 0.42 l/h/kg).

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

Indications

Aarterial hypertension (monotherapy or in combination with other antihypertensive agents);
Stable tension angina and Prinzmetal angina (monotherapy or in combination with other antianginal agents).

Active ingredient

Composition

1 tablet contains
active ingredient:

amlodipine besylate in terms of amlodipine 10 mg;

excipients:

microcrystalline cellulose,

lactose (milk sugar),

croscarmellose sodium (primellose),

calcium stearate (calcium octadecanoate).

How to take, the dosage

Ingestion, regardless of meals.

To treat arterial hypertension and prevent attacks of angina pectoris and vasospastic angina, the initial dose of Amlodipine is 5 mg once daily. If necessary, the daily dose may be increased to a maximum of 10 mg (once daily).

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, the T1/2 may increase 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. No dose modification is required in patients with renal insufficiency.

Interaction

Microsomal oxidation inhibitors may increase the plasma concentration of amlodipine, increasing the risk of side effects, and hepatic microsomal enzyme inducers may decrease this parameter.

Unlike other DMARDs, amlodipine has no clinically significant interactions with nonsteroidal anti-inflammatory drugs, especially indomethacin.

Thiazide and “loop” diuretics, beta-adrenoblockers, verapamil, ACE inhibitors and nitrates enhance the antianginal or hypotensive effects of amlodipine.

Amiodarone, quinidine, alpha1-adrenoblockers, antipsychotics (neuroleptics) and isoflurane may increase the hypotensive effects of amlodipine.

Calcium preparations may decrease the effect of BMCC.

The co-administration of amlodipine with lithium preparations may increase the neurotoxicity of the latter (nausea, vomiting, diarrhea, ataxia, tremor, tinnitus).

Amlodipine has no effect on pharmacokinetic parameters of digoxin and warfarin. Cimetidine has no effect on the pharmacokinetics of amlodipine.

The antiviral agents (ritonavir) contribute to increased plasma concentrations of PBMCs (including amlodipine).

Special Instructions

During treatment with Amlodipine it is necessary to control patients’ body weight and sodium salt intake; an appropriate low-salt diet is prescribed.

Tooth hygiene should be maintained and regular visits to the dentist (to prevent soreness, bleeding and gum hyperplasia).

The dosing regimen of Amlodipine in elderly patients is similar to that in patients of other age groups. Careful monitoring of elderly patients is necessary when increasing the dose.

Although there is no withdrawal syndrome in AMLs, a gradual reduction in doses is recommended before discontinuing treatment.

Amlodipine does not affect plasma concentrations of potassium ions, glucose, triglycerides, total cholesterol, low-density lipoproteins, uric acid, creatinine and urea nitrogen.

An abrupt withdrawal of the drug should be avoided because of the risk of worsening the course of angina pectoris.

Amlodipine tablets are not recommended in hypertensive crisis.

Patients of low body weight, short stature, and patients with significant liver dysfunction may require a lower dose.

The effect on driving and operating machinery
There have been no reports about the effect of Amlodipine on driving or operating machinery. Nevertheless, drowsiness and dizziness may occur in some patients, mainly at the beginning of treatment. If they occur, caution should be exercised while driving motor transport and engaging in potentially dangerous activities requiring high concentration and quick psychomotor reactions.

Contraindications

With caution: impaired liver function, sinus node weakness syndrome (marked bradycardia, tachycardia), chronic heart failure of non-ischemic etiology of NYHA functional class III-IV, aortic stenosis, mitral stenosis, hypertrophic obstructive cardiomyopathy, acute myocardial infarction (and within 1 month after), elderly age.

Side effects

Cardiovascular system: often – palpitations, peripheral edema (edema of ankles and feet), infrequently – excessive reduction of BP, orthostatic hypotension, vasculitis; rarely – development or worsening of chronic heart failure; very rarely – rhythm disturbances (bradycardia, ventricular tachycardia, atrial fibrillation), myocardial infarction, pain in the chest, migraine.

Central nervous system: often – headache, dizziness, fatigue; infrequently. malaise, fainting, asthenia, hypoesthesia, paresthesia, peripheral neuropathy, tremor, insomnia, emotional lability, unusual dreams, nervousness, depression, anxiety; rarely – seizures, apathy, agitation; very rarely – ataxia, amnesia.

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

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

Gastrointestinal tract disorders: frequent – nausea, abdominal pain; infrequent – vomiting, change of defecation mode (including constipation, flatulence), dyspepsia, diarrhea, anorexia, dry oral mucosa, thirst; rare – gum hyperplasia, increased appetite; very rare – gastritis, pancreatitis, hyperbilirubinemia, jaundice (usually cholestatic), increased activity of “liver” transaminases, hepatitis.

Urogenital system disorders: infrequent – pollakiuria, painful urge to urinate, nycturia, impotence; very rarely – dysuria, polyuria.

Skin disorders: rare – increased sweating, very rare – cold sticky sweat, xeroderma, alopecia, dermatitis, purpura, skin discoloration.

Allergic reactions: infrequent – skin itching, rash, very rare – angioedema, erythema multiforme, urticaria.

Musculoskeletal system: infrequent – arthralgia, muscle cramps, arthrosis, myalgia (with long-term use), back pain; rarely – myasthenia.

Others: infrequent – alopecia, tinnitus, gynecomastia, weight gain/decrease, visual disturbance, diplopia, accommodation disturbance, xerophthalmia, conjunctivitis, eye pain, perversion of taste, chills, nosebleed, increased sweating; rare – dermatitis; very rare – cold sticky sweat, parasmia, skin pigmentation disorders, hyperglycemia.

Overdose

Symptoms:

pronounced BP decrease with possible development of reflex tachycardia and excessive peripheral vasodilation (risk of severe and persistent arterial hypotension, including with the development of shock and death).

Treatment:

Gastric lavage, prescription of activated charcoal (especially in the first 2 hours after overdose), maintenance of cardiovascular function, control of heart and lung function parameters, Trendelenburg posture, control of circulating blood volume and diuresis. To restore vascular tone – application 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 not effective.

Pregnancy use

There has been no teratogenicity of amlodipine in animal studies, but there is no clinical experience with its use in pregnancy and lactation.

Therefore, amlodipine should not be administered to pregnant and lactating women or to women of childbearing age unless they use reliable contraception.

Similarities