Instructions for use Amlodipine-Darnitsa tablets 5 mg No. 90
Composition
active ingredient: amlodipine;
1 tablet contains amlodipine besylate (as amlodipine) 5 mg or 10 mg;
Excipients: lactose monohydrate, microcrystalline cellulose, corn starch, colloidal anhydrous silica, magnesium stearate, povidone.
Dosage form
Pills.
Main physicochemical properties: tablets of white or white with a yellowish tint, flat-cylindrical shape, with a bevel.
Pharmacotherapeutic group
Selective calcium antagonists with a predominant effect on blood vessels. ATC code C08C A01.
Pharmacological properties
Pharmacodynamics.
Amlodipine is a calcium ion antagonist (slow calcium channel blocker) that blocks the influx of calcium ions through membranes into myocardial and vascular smooth muscle cells. The mechanism of hypotensive action of amlodipine is due to a direct relaxing effect on vascular smooth muscle. The nature of the antianginal effect of amlodipine has not yet been sufficiently studied, but it can be stated that the drug reduces general ischemic disorders in the following two ways:
– dilates peripheral arterioles and thus reduces total peripheral resistance (afterload). Since the heart rate remains almost unchanged, the reduction in the load on the heart leads to a decrease in energy consumption and myocardial oxygen demand;
– promotes dilation of large coronary arteries and coronary arterioles in both intact and ischemic areas of the myocardium. Such dilation increases oxygen supply to the myocardium in patients with vasospastic angina (Prinzmetal's angina or variant angina) and prevents the development of coronary vasoconstriction.
In patients with hypertension, a single dose of amlodipine provides a clinically significant reduction in blood pressure for 24 hours in both the supine and standing positions. Due to its slow onset of action, amlodipine does not cause acute hypotension.
In patients with angina pectoris, amlodipine helps to increase physical performance (extends the time of physical exertion, delays the development of an angina attack and the time of ST segment depression by 1 mm during exertion), reduces the frequency of angina attacks and reduces the need for nitroglycerin tablets.
Hemodynamic studies and controlled clinical trials in patients with heart failure of functional class II-III (according to the NYHA classification) have shown that amlodipine does not cause deterioration of their condition according to criteria such as exercise tolerance, left ventricular ejection fraction and clinical symptoms.
Pharmacokinetics.
After oral administration in therapeutic doses, amlodipine is well absorbed, reaching maximum blood concentrations after 6-12 hours. Absolute bioavailability reaches 64-80%. The volume of distribution is approximately 20 l/kg. Approximately 97.5% of amlodipine is bound to plasma proteins. Food intake does not affect the absorption of amlodipine.
The plasma half-life is approximately 35-50 hours, which allows once-daily dosing. Steady-state plasma concentrations of amlodipine are reached within 7-8 days of regular dosing.
Amlodipine is extensively metabolized in the liver to form inactive metabolites. It is excreted in the urine: 10% of the administered dose is unchanged, 60% is excreted as metabolites.
In elderly patients and patients with congestive heart failure, there was a tendency for amlodipine clearance to decrease, resulting in an increase in the area under the concentration-time curve (AUC) and half-life of the drug.
Indication
- – Arterial hypertension.
- – Chronic stable angina.
- – Vasospastic angina (Prinzmetal's angina).
Contraindication
- Known hypersensitivity to dihydropyridines, amlodipine or any other component of the drug.
- Severe arterial hypotension.
- Shock (including cardiogenic shock).
- Left ventricular outflow tract obstruction (e.g., severe aortic stenosis).
- Hemodynamically unstable heart failure after acute
myocardial infarction.
Interaction with other medicinal products and other types of interactions
Effect of other drugs on amlodipine.
There is no data on the safe use of amlodipine with thiazide diuretics, alpha-blockers, beta-blockers, ACE inhibitors, long-acting nitrates, sublingual nitroglycerin, nonsteroidal anti-inflammatory drugs, antibiotics, and oral hypoglycemic drugs.
Data obtained during in vitro studies with human blood plasma indicate that amlodipine has no effect on the binding of the studied drugs (digoxin, phenytoin, warfarin or indomethacin) to blood proteins.
Concomitant use of amlodipine and strong or moderate CYP3A4 inhibitors (protease inhibitors, azole antifungals, macrolides such as erythromycin or clarithromycin, verapamil or diltiazem) may lead to a significant increase in amlodipine exposure, which may also lead to an increased risk of hypotension. The clinical significance of such changes may be more pronounced in elderly patients. Clinical monitoring of the patient and dose adjustment may be necessary.
When using amlodipine, it is not recommended to consume grapefruit or grapefruit juice at the same time, since in some patients the bioavailability of amlodipine may increase, which in turn leads to increased hypotensive effect.
CYP3A4 inducers.
There is no information on the effect of CYP3A4 inducers on amlodipine. Concomitant use of amlodipine and substances that are CYP3A4 inducers (e.g. rifampicin, St. John's wort) may lead to a decrease in amlodipine plasma concentrations, therefore such combinations should be used with caution.
Dantrolene (infusion).
Fatal ventricular fibrillation and cardiovascular collapse associated with hyperkalemia have been observed in animals following intravenous administration of verapamil and dantrolene. Due to the risk of hyperkalemia, it is recommended that calcium channel blockers such as amlodipine be avoided in patients predisposed to malignant hyperthermia and in the treatment of malignant hyperthermia.
The effect of amlodipine on other drugs.
The hypotensive effect of amlodipine potentiates the hypotensive effect of other antihypertensive agents.
Tacrolimus.
There is a risk of increased blood levels of tacrolimus when co-administered with amlodipine, but the pharmacokinetic mechanism of this interaction is not fully established. To avoid tacrolimus toxicity when co-administered with amlodipine, patients should have their blood levels of tacrolimus monitored regularly and the dose of tacrolimus adjusted if necessary.
Cyclosporine.
No interaction studies have been conducted with ciclosporin and amlodipine in healthy volunteers or other populations, except in renal transplant patients, where a variable increase in ciclosporin trough concentrations (mean 0-40%) was observed. In renal transplant patients receiving amlodipine, monitoring of ciclosporin concentrations should be considered and, if necessary, a reduction in the ciclosporin dose should be considered.
Simvastatin.
Co-administration of multiple doses of amlodipine 10 mg and simvastatin 80 mg resulted in a 77% increase in simvastatin exposure compared to simvastatin alone. For patients taking amlodipine, the dose of simvastatin should be limited to 20 mg daily.
Sildenafil.
A single dose of 100 mg of sildenafil in patients with essential hypertension did not affect the pharmacokinetics of amlodipine. When amlodipine and sildenafil were used simultaneously as combination therapy, each drug had an independent hypotensive effect.
Other medicines.
Clinical drug interaction studies have shown that amlodipine does not affect the pharmacokinetics of atorvastatin, digoxin, or warfarin.
Ethanol (alcohol).
Single and multiple doses of 10 mg amlodipine had no significant effect on the pharmacokinetics of ethanol.
Co-administration of amlodipine with cimetidine did not affect the pharmacokinetics of amlodipine.
Co-administration of aluminum/magnesium preparations (antacids) with a single dose of amlodipine had no significant effect on the pharmacokinetics of amlodipine.
Laboratory tests.
The effect on laboratory test results is unknown.
Application features
The safety and efficacy of amlodipine in hypertensive crisis have not been evaluated.
Use for the treatment of patients with heart failure.
An increased incidence of pulmonary edema has been reported in patients with NYHA class III-IV heart failure. Calcium channel blockers, including amlodipine, should be used with caution in patients with congestive heart failure as they may increase the risk of future cardiovascular events and mortality.
Use in patients with impaired liver function.
In patients with impaired liver function, amlodipine should be started at the lowest dose. Caution should be exercised both when starting the drug and when increasing the dose. In patients with severe liver failure, slow dose titration and careful monitoring of the patient's condition may be necessary.
Use for the treatment of patients with renal failure.
For the treatment of such patients, amlodipine should be used in normal doses. Changes in plasma concentrations of amlodipine do not correlate with the degree of renal insufficiency. Amlodipine is not dialysable, so it should be administered with caution to patients undergoing hemodialysis.
Application for the treatment of elderly patients.
It is recommended to prescribe the drug in normal doses, caution should be exercised when increasing the dose.
Reversible biochemical changes in the sperm head have been reported in some patients receiving calcium channel blockers. There is insufficient clinical information on the potential effect of amlodipine on fertility.
Amlodipine does not affect the results of laboratory tests.
When using amlodipine, it is not recommended to consume grapefruit or grapefruit juice at the same time, since in some patients the bioavailability may be increased, which will lead to an increase in the hypotensive effect of the drug.
Use during pregnancy or breastfeeding
In animal studies with amlodipine, reproductive toxicity was observed at high doses.
The safety of amlodipine for use in women during pregnancy has not been established.
The use of amlodipine during pregnancy is recommended only in cases where there is no safer alternative and the risk associated with the disease itself outweighs the possible risk of treatment for the mother/fetus.
It is not known whether amlodipine is excreted in human milk. A decision on whether to continue breastfeeding or to use amlodipine should be made taking into account the benefit/risk of breastfeeding to the child and the use of the drug to the mother.
Ability to influence reaction speed when driving vehicles or other mechanisms
Amlodipine - Darnitsa may have minor or moderate influence on the ability to drive and use machines.
Reaction speed may be reduced if symptoms such as dizziness, headache, confusion or nausea are present. In such cases, you should refrain from driving or operating other mechanisms.
Method of administration and doses
Adults: The usual recommended starting dose for the treatment of hypertension and angina pectoris is 5 mg amlodipine once daily. Depending on the patient's response to therapy, the dose may be increased to a maximum of 10 mg once daily.
Children aged 6 years and older with arterial hypertension. The recommended initial dose of amlodipine for this category of patients is 2.5 mg once a day. Amlodipine ˗ Darnitsa 5 mg tablets are not intended to be divided in half to obtain a dose of 2.5 mg, therefore it is necessary to use amlodipine tablets of the appropriate dosage.
If the desired blood pressure level is not achieved within 4 weeks, the dose may be increased to 5 mg per day. The use of the drug in doses above 5 mg for this category of patients has not been studied.
Elderly patients: No dose adjustment is necessary for this category of patients. Dose increases should be made with caution.
Patients with renal impairment: No dose adjustment is necessary for this category of patients.
Patients with hepatic impairment: Doses of the medicinal product for use in this category of patients have not been established (see section "Special warnings and precautions for use").
Patients with liver dysfunction.
Doses for patients with mild to moderate hepatic impairment have not been established, therefore dose selection should be carried out with caution and the drug should be started at the lowest dose in the dose range (see section "Special instructions"). The pharmacokinetics of amlodipine have not been studied in patients with severe hepatic impairment. For patients with severe hepatic impairment, amlodipine should be started at the lowest dose and titrated gradually.
Children.
Amlodipine - Darnitsa should be used in children over 6 years of age.
The effect of amlodipine on blood pressure in patients under 6 years of age is unknown.
Overdose
Symptoms: Significant overdose (> 100 mg) may lead to excessive peripheral vasodilation and possible reflex tachycardia. Cases of significant and possibly prolonged systemic hypotension, including shock with fatal outcome, have been described.
Non-cardiogenic pulmonary edema has been reported rarely following amlodipine overdose, which may have a delayed onset (24-48 hours after ingestion) and may require mechanical ventilation. Factors contributing to the development of non-cardiogenic pulmonary edema may include early resuscitation measures (including fluid overload) to maintain perfusion and cardiac output.
Clinically significant hypotension caused by amlodipine overdose requires active measures to support cardiovascular function, including monitoring of cardiac and pulmonary function, elevation of the legs, control of circulating blood volume, and diuresis. Vasoconstrictors may be useful to restore vascular tone and blood pressure, unless contraindicated. Intravenous calcium gluconate may be useful to reverse the effects of calcium channel blockade. Since amlodipine is highly protein bound, dialysis is unlikely to be effective.
Adverse reactions
On the part of the organs of vision: visual disturbances (including diplopia).
From the side of the organs of hearing and vestibular apparatus: ringing in the ears.
Respiratory, thoracic and mediastinal disorders: dyspnea, rhinitis, cough.
Gastrointestinal: abdominal pain, nausea, loss of appetite, change in taste, vomiting, dyspepsia, intestinal motility disorders (including constipation and diarrhea), flatulence, dry mouth, sore throat, pancreatitis, gastritis, gingival hyperplasia.
Liver and biliary tract: hepatitis, jaundice, increased liver enzymes (most often associated with cholestasis).
Renal and urinary disorders: urinary incontinence, nocturia, frequent urination.
From the side of metabolism: increase or decrease in body weight, hyperglycemia.
Nervous system: fatigue, asthenia, malaise, drowsiness, dizziness, headache (at the beginning of treatment), tremor, dysgeusia, hypoesthesia, paresthesia, insomnia, mood changes (including anxiety), depression, confusion, hypertonia, peripheral neuropathy, syncope, extrapyramidal disorders.
Cardiovascular system: hot flashes, hypotension, palpitations, chest pain, myocardial infarction, arrhythmia (including bradycardia, ventricular tachycardia and atrial fibrillation), vasculitis.
Blood and lymphatic system disorders: leukocytopenia, thrombocytopenia.
On the part of the immune system: allergic reactions.
Skin and subcutaneous tissue disorders: alopecia, purpura, skin discoloration, increased sweating, itching, rash, exanthema, angioedema, erythema multiforme, urticaria, exfoliative dermatitis, Stevens-Johnson syndrome, angioedema, photosensitivity.
Musculoskeletal and connective tissue disorders: swelling of the lower extremities, arthralgia, myalgia, muscle cramps, back pain.
From the reproductive system and mammary gland function: impotence, gynecomastia.
General disorders: edema.
Other reactions: increased sweating, nonspecific pain of various localization.
After discontinuation of the drug, adverse reactions in most cases completely disappeared.
Expiration date
3 years.
Storage conditions
Store in the original packaging at a temperature not exceeding 25 °C.
Keep out of reach of children.
Packaging
10 tablets in a contour blister pack; 2, 3 or 9 contour blister packs in a pack.
Vacation category
According to the recipe.
Producer
PrJSC "Pharmaceutical Company "Darnitsa".
Location of the manufacturer and its business address.
Ukraine, 02093, Kyiv, Boryspilska St., 13.
