Kalchek, tablets 10 mg 30 pcs

Pharmacodynamics

Amlodipine is a dihydropyridine derivative. Binding to dihydropyridine receptors, it blocks “slow” calcium channels, inhibits transmembrane calcium transfer in heart and vascular smooth muscle cells (more in vascular smooth muscle cells than in cardiomyocytes). It has hypotensive and antianginal effect.
The mechanism of hypotensive action of amlodipine is due to a direct relaxing effect on vascular smooth muscle.

Amlodipine reduces myocardial ischemia in the following two ways:
1. Dilates the arterioles and thus reduces total peripheral resistance (post-load) while keeping heart rate virtually unchanged, resulting in lower energy consumption and myocardial oxygen demand.
2. dilates coronary and peripheral arteries and arterioles in both normal and ischemic areas of the myocardium, which increases the flow of oxygen to the myocardium in patients with vasospastic angina (Prinzmetal angina) and prevents the development of coronarospasm caused by smoking.
In patients with arterial hypertension, a single daily dose of Kalchek provides reduction of blood pressure (BP) for 24 hours (both “lying” and “standing”). Because of the slow onset of action, amlodipine does not cause a sharp decrease in BP.

In patients with angina a single daily dose of the drug increases exercise time, delays onset of angina attack and ST-segment depression (by 1 mm) with exercise, decreases angina attacks frequency and nitroglycerin consumption.

The use in patients with coronary heart disease (CHD)

In patients with cardiovascular disease (including coronary atherosclerosis with lesion of one vessel and up to stenosis of 3 or more arteries and atherosclerosis of carotid arteries), who have had myocardial infarction, percutaneous transluminal angioplasty of coronary arteries (TPA) or suffering from angina pectoris, the use of Kalchek prevents the development of carotid artery intima-media thickening, stroke, THA, aortocoronary bypass surgery, results in fewer hospitalizations for unstable angina and progression of chronic heart failure (CHF), and reduces the frequency of interventions aimed at restoring coronary flow.

The use in patients with heart failure
Kalchek does not increase the risk of death or development of complications and fatal outcomes in patients with chronic heart failure (CHF) of functional class III-IV (according to NYHA) on the background of therapy with digoxin, diuretics and ACE inhibitors. In patients with CHF of III-IV functional class according to NYHA of non-ischemic etiology, there is a possibility of pulmonary edema when using Kalchek. Kalchek has no adverse effect on metabolism and blood plasma lipid concentration.

Pharmacokinetics

After oral administration, amlodipine is slowly absorbed (about 90%) from the gastrointestinal tract. Absolute bioavailability is 64-80%, the maximum concentration in blood serum is observed after 6-9 hours. Equilibrium concentrations are reached after 7-8 days of therapy. Food intake has no effect on 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 a relatively smaller part of it is in the blood.
Most of the drug that is in the blood (97%) is bound to plasma proteins.

Amlodipine is metabolized in the liver to form inactive metabolites.
After a single oral dose the elimination half-life (T_1/2) is on average 35 hours. About 60% of the dose taken orally is excreted by the kidneys mainly as metabolites, 10% – unchanged, and 20-25% – with the bile through the intestine.
In patients with arterial hypertension T_1/2 is 48 hours, in elderly patients (over 65 years) excretion of amlodipine is delayed (T_1/2 is 65 h) compared to younger patients, but this limit is not clinically relevant.

In patients with hepatic impairment, a prolongation of T_1/2 is expected, and cumulation of the drug in the body will be higher with long-term administration (T_1/2 up to 60 h).

Renal insufficiency has no significant effect on the kinetics of amlodipine.
The drug penetrates the blood-brain barrier. It is not eliminated by hemodialysis.

Indications

Arterial hypertension (in monotherapy or in combination with other antihypertensive agents);
stable angina pectoris, vasospastic angina pectoris (Prinzmetal angina) (in monotherapy or in combination with other antianginal agents).

Active ingredient

Composition

1 tablet contains:

the active ingredient:

amlodipine besylate, which is equivalent to amlodipine 10 mg.

auxiliary substances:

corn starch,

calcium hydrophosphate,

talc,

colloidal silicon dioxide,

sodium carboxymethyl starch,

magnesium stearate.

How to take, the dosage

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 dose can be maximally increased up to 10 mg once daily.

In arterial hypertension, the maintenance dose may be 5 mg daily.

There is no need to change the dose when concomitantly prescribed with thiazide diuretics, beta-adrenoblockers or angiotensin-converting enzyme (ACE) inhibitors.

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

In patients with impaired liver function no dose adjustment is usually required.

In elderly patients, use in an average therapeutic dose is recommended and no dose adjustment is necessary.

Interaction

Liver microsomal enzyme inhibitors can be expected to increase plasma concentrations of amlodipine, increasing the risk of side effects, and hepatic microsomal enzyme inducers can be expected to decrease them.

In contrast to other DMARDs, no clinically significant interactions with nonsteroidal anti-inflammatory drugs, especially indomethacin, have been observed.

Tiazide and “loop” diuretics, beta-adrenoblockers, verapamil, ACE inhibitors and nitrates increase antianginal and hypotensive effect of amlodipine.

Amiodarone, quinidine, agents for inhalation anesthesia (hydrocarbon derivatives), alpha1-adrenoblockers, antipsychotics (neuroleptics) and DMARDs may increase the hypotensive effect.

Amlodipine has no effect on pharmacokinetic parameters of digoxin and warfarin.

Cimetidine: concomitant use of amlodipine with cimetidine does not change pharmacokinetics of amlodipine.
Co-administration of amlodipine with lithium preparations may increase manifestations of their neurotoxicity (nausea, vomiting, diarrhea, ataxia, tremor, tinnitus).

Calcium preparations may decrease the effect of BMCC.

Antiviral agents (ritonavir) increase plasma concentrations of BMCCs, including amlodipine.
Isoflurane – increase the hypotensive effect of dihydropyridine derivatives.

The co-administration of PBMCs with lithium preparations may increase neurotoxicity.

Repeated use of amlodipine 10 mg and atorvastatin 80 mg is not accompanied by significant changes in pharmacokinetics of atorvastatin.

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

Concomitant administration of 100 mg sildenafil in patients with essential hypertension has no effect on amlodipine pharmacokinetic parameters.

Special Instructions

During treatment it is necessary to control body weight and sodium intake, prescribing an appropriate diet.

It is necessary to maintain dental hygiene and frequent visits to the dentist (to prevent soreness, bleeding and hyperplasia of the gums).

The dosing regimen for elderly patients is the same as for patients in other age groups. Careful monitoring of elderly patients is necessary when increasing the dose.

While there is no withdrawal syndrome in BMKs, 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 uric acid nitrogen.

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

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

Influence on driving and operating ability

During the treatment period, caution should be exercised while driving motor transport and engaging in other activities requiring concentration and rapid psychomotor reactions due to the possibility of dizziness and somnolence.

Contraindications

Side effects

Cardiovascular system: palpitations, marked BP decrease, peripheral edema (edema of ankles and feet), rarely – cardiac arrhythmia (bradycardia, ventricular tachycardia, atrial flutter), myocardial infarction, chest pain, orthostatic hypotension, vasculitis, very rarely – development or worsening of heart failure, extrasystole, migraine.

Central nervous system disorders: Headache, dizziness, increased fatigue, feeling of heat and “rushes” of blood to the skin of the face, drowsiness, mood changes, seizures, rarely – loss of consciousness, hypoesthesia, nervousness, paresthesias, Peripheral neuropathy, tremor, vertigo, asthenia, malaise, fainting, insomnia, emotional lability, depression, anxiety, unusual dreams, very rare – ataxia, apathy, agitation, amnesia.

Digestive system disorders: nausea, vomiting, epigastric pain, rarely – increased activity of “liver” transaminases, hyperbilirubinemia, jaundice (due to cholestasis), pancreatitis, dry oral mucosa, thirst, hepatitis, flatulence, gum hyperplasia, constipation, diarrhea, anorexia, very rarely – gastritis, increased appetite.

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

Respiratory system disorders: dyspnea, rhinitis, very rarely – cough.

Urinary system disorders: rarely – pollakiuria, painful urge to urinate, nycturia, sexual dysfunction (including decreased potency); very rarely – dysuria, polyuria.

Skin disorders: very rarely xeroderma, dermatitis, purpura, pigmentation disorders.

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

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

Others: rare – gynecomastia, gyneruricemia, weight gain/decrease, hyperglycemia, visual disturbances, diplopia, conjunctivitis, eye pain, tinnitus, dyspnea, nasal bleeding, increased sweating; very rare – cold sticky sweat, parosmia, taste disturbances, accommodation disorders, xerophthalmia.

Overdose

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

The treatment: gastric lavage, prescription of activated charcoal (especially in the first 2 hours after overdose), maintenance of cardiovascular system function, control of heart and lung function parameters, elevated position of 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.

Pregnancy use

Safety of amlodipine use in pregnancy has not been established, therefore use in pregnancy is possible only when the benefit to the mother exceeds the risk to the fetus.

There are no data indicating excretion of amlodipine with breast milk.

However, other DMARDs, dihydropyridine derivatives, are known to be excreted with breast milk. If it is necessary to prescribe amlodipine during lactation, discontinuation of breastfeeding should be considered.

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