Emlodin

Emlodin is a selective calcium antagonist that acts on the vascular system.

Indications Emlodina

It is used for the following disorders:

• increased blood pressure;
• stable form of angina of a chronic nature;
• variant angina.

Release form

The drug is released in tablets, 10 pieces inside a blister plate. The box contains 3 such plates.

Pharmacodynamics

The element amlodipine is a calcium antagonist (a derivative of dihydropyridine) that blocks the penetration of Ca ions into the myocardium and smooth muscle cells.

The mechanism of the antihypertensive effect of the substance is associated with its direct relaxing effect on the smooth muscles of the vessels. The mechanism of the antianginal effect of the drug has not been fully studied, but it is known that the following factors play an important role in this:

• dilation of peripheral arterioles, resulting in a decrease in afterload (peripheral resistance). Since the heart rate remains stable, due to the decrease in the load exerted on the heart, there is also a decrease in energy consumption, as well as the myocardium's need for oxygen;
• dilation affecting the main coronary arteries, as well as coronary arterioles (both normal and ischemic), probably also plays an important role in the medicinal effect of the substance. Due to this dilation, the volume of oxygen received by the myocardium increases in people with spasms in the area of the coronary arteries (variant angina).

In people with elevated blood pressure, a single use of the drug per day leads to a clinically significant decrease in these indicators for a period of 24 hours (the patient can remain in either a lying or standing position during this entire period). Due to the slow onset of the drug effect, a sharp decrease in blood pressure is often not observed.

In people with angina, when using a single daily dose, the total period of physical activity increases, as well as the interval before the onset of an angina attack and the interval up to 1 mm of ST-segment depression. The drug reduces the frequency of angina attacks, as well as the need for nitroglycerin.

Amlodipine does not have any negative effects on metabolism, and does not cause changes in lipid levels in blood plasma. It is approved for use by people with diabetes, asthma, and gout.

Pharmacokinetics

Absorption.

When therapeutic doses of the drug are taken orally, the active element is gradually absorbed into the blood plasma. The bioavailability level of the unchanged molecule is approximately 64-80%. Peak values in the blood plasma are noted after 6-12 hours after taking the drug. Combination of the drug with food does not affect the absorption of amlodipine.

Distribution.

The distribution volume is approximately 21 L/kg and the pKa value of the active substance is 8.6. In vitro tests have shown that plasma protein synthesis of the drug is approximately 97.5%.

Metabolic processes and excretion.

The half-life of the component from plasma is approximately 35-50 hours. The drug reaches equilibrium values in the blood plasma after 7-8 days of continuous administration. In this case, amlodipine is mainly subject to metabolism, as a result of which inactive decay products are formed. About 60% of the consumed portion is excreted in the urine (approximately 10% of this is unchanged amlodipine).

People with liver disorders.

There is limited information on the use of the drug in people with liver dysfunction. In people with liver failure, the clearance rate of amlodipine is reduced, which increases the half-life of the substance and the AUC (by approximately 40-60%).

Dosing and administration

Adults.

To reduce elevated blood pressure values, as well as to treat angina, a single daily dose of the initial dose of the drug, amounting to 5 mg, is required. Taking into account the patient's response to such treatment, the daily single dose of the drug can be subsequently increased to a maximum of 10 mg.

People with angina can use the drug as monotherapy or in combination with other antianginal drugs if they are resistant to nitrates or standard doses of β-blockers.

There are data on the use of the drug together with thiazide-type diuretics, β- and α-blockers or ACE inhibitors in people with elevated blood pressure. There is no need to select a dose of the drug in case of combination with these medications.

Children over 6 years of age with elevated blood pressure.

The recommended initial dose of Emlodin for this group of patients is 2.5 mg, taken once a day. If the desired result is not achieved (achievement of the desired blood pressure values) after 1 month of therapy, the daily dosage may be increased to 5 mg. However, it should be taken into account that the use of the drug in a 5 mg dose has not been studied in this group of patients.

Persons with liver dysfunction.

The dosage sizes of the drug for people with mild to moderate liver problems are not defined, so the dosage should be selected carefully, starting with the lowest dose. People with severe liver problems should start using the drug with the lowest dose, then gradually increase it.

To obtain a dosage of 2.5 mg, a 5 mg tablet should be divided in half.

[ 1 ]

Use Emlodina during pregnancy

There is no data on the safety of amlodipine use in pregnant women. During this period, Emlodin can be used only in situations where it is not possible to take an alternative drug with a safer effect, and the risk associated with the pathology is higher than the likelihood of complications for the woman and the fetus.

In animal tests, reproductive toxicity was observed when high doses were used.

There is no information on whether amlodipine is excreted in human milk. Before deciding whether to continue breastfeeding or to use the drug, the risks and benefits of taking it for the mother and infant should be assessed.

Contraindications

Main contraindications:

• the presence of intolerance to dihydropyridines, as well as amlodipine and other components of the therapeutic agent;
• extremely low blood pressure;
• shock state (this includes cardiogenic shock);
• obstruction in the area of the outflow tract in the left ventricle (for example, severe aortic stenosis);
• heart failure that is hemodynamically unstable and develops in connection with acute myocardial infarction.

Side effects Emlodina

As a result of using the medication, negative effects such as dizziness, tachycardia, a feeling of drowsiness, hot flashes, headaches, nausea, severe fatigue, abdominal pain and swelling (including in the shins) often developed.

Taking the pills may also cause the following side effects:

• disorders associated with lymph and systemic blood flow: leukopenia or thrombocytopenia appear occasionally;
• immune disorders: signs of allergy are observed sporadically;
• problems affecting metabolic processes, as well as alimentary disorders: hyperglycemia develops occasionally;
• Mental disorders: mood swings (including anxiety), depression and insomnia may sometimes occur. A feeling of confusion is occasionally noted;
• disorders affecting the function of the nervous system: dizziness, drowsiness and headaches are often observed (mainly at the beginning of therapy). Fainting, paresthesia, dysgeusia and hypesthesia sometimes occur. Polyneuropathy or hypertonia are rare;
• visual disturbances: problems with visual function are often noted (this includes diplopia);
• problems affecting the labyrinth and auditory organs: sometimes tinnitus appears;
• cardiac dysfunction: increased heart rate is often observed. Sometimes arrhythmia develops (this includes ventricular tachycardia, bradycardia, and atrial fibrillation). Myocardial infarction occurs occasionally;
• vascular disorders: hot flashes often occur. Sometimes blood pressure decreases. Vasculitis occurs occasionally;
• thoracic, respiratory and mediastinal disorders: dyspnea often occurs. Sometimes a runny nose or cough is observed;
• problems with the gastrointestinal tract: nausea, abdominal pain, dyspeptic symptoms often appear, and in addition, intestinal peristalsis disorders develop (including constipation and diarrhea). Dryness of the oral mucosa and vomiting are sometimes noted. Gastritis, pancreatitis, and in addition, gingival hyperplasia develop occasionally;
• disorders of hepatobiliary function: jaundice, hepatitis and increased liver enzyme levels (often associated with cholestasis) are occasionally observed;
• lesions in the subcutaneous layer and skin surface: sometimes purpura, itching, urticaria, rashes, alopecia, hyperhidrosis occur, and in addition, skin tone changes. Polyform erythema, Quincke's edema, exfoliative dermatitis, photosensitivity and Stevens-Johnson syndrome appear sporadically;
• dysfunction of connective and musculoskeletal tissues: swelling in the shins and muscle cramps are often observed. Sometimes there is pain in the back, myalgia or arthralgia;
• lesions affecting the urinary system and kidneys: sometimes nocturia, urinary disorder, and increased frequency of urination occur;
• disorders of the mammary glands and reproductive organs: sometimes gynecomastia or impotence is observed;
• systemic disorders: edema often develops. Asthenia and a feeling of extreme fatigue also often appear. Sometimes there is malaise and pain (particularly in the sternum area);
• Test results: weight gain or loss is sometimes noted. Extrapyramidal syndrome has been reported sporadically.

Overdose

There is only limited information regarding intentional overdose of the drug.

Manifestations of intoxication: Based on the available data, it can be assumed that significant intoxication with Emlodin will cause severe vasodilation of a peripheral nature, and also, possibly, the development of reflex tachycardia. There is information about a significant and probably prolonged systemic decrease in blood pressure values (this includes a state of shock with a fatal outcome).

When treating a clinically significant decrease in blood pressure caused by amlodipine poisoning, it is necessary to qualitatively support the function of the cardiovascular system - constantly monitor the work of the respiratory system and heart, raise the patient's legs, and also monitor the volume of fluid circulating in the body along with urination processes.

To restore vascular tone and blood pressure, vasoconstrictor agents should be used, after making sure that there are no contraindications to their use. Intravenous administration of calcium gluconate can also help - to eliminate symptoms caused by blockade of Ca channels.

Sometimes gastric lavage may be required. After a volunteer took activated carbon, its absorption was significantly reduced for 2 hours after taking 10 mg of the drug.

Because a significant portion of amlodipine is synthesized with protein, the dialysis procedure will be ineffective.

Interactions with other drugs

Drugs that inhibit the activity of the CYP3A4 element.

Combination of the drug with substances that inhibit the CYP3A4 component, having a moderate or strong effect (drugs that inhibit proteases, azole antifungals and macrolides (eg, erythromycin with clarithromycin, as well as diltiazem with verapamil)), may cause a significant increase in drug exposure, which may increase the likelihood of a decrease in blood pressure. The medicinal significance of such changes may be more pronounced in the elderly. Clinical monitoring of the patient's condition and selection of the dose size may be necessary.

It is forbidden to combine the drug with grapefruit or juice from this fruit, because in some people this increases the bioavailability of amlodipine, as a result of which its antihypertensive effect is enhanced.

Medicines that induce the activity of the CYP3A4 element.

The combination of the drug with drugs that induce the CYP3A4 component (such as St. John's wort or rifampicin) can cause a decrease in plasma levels of amlodipine, which is why such drugs should be combined with caution.

Dantrolene infusions.

Ventricular fibrillation with subsequent death, as well as collapse of the cardiovascular system function, have been observed in animals (associated with hyperkalemia) as a result of using dantrolene with verapamil. Due to the high probability of hyperkalemia, people with a tendency to develop malignant hyperthermia, as well as during its treatment, should refrain from using drugs that block Ca channels.

Effect of drugs on other medications.

The antihypertensive effect of amlodipine enhances the similar effect of other antihypertensive drugs.

Tacrolimus.

There is a possibility of increased tacrolimus levels in the blood when combined with Emlodin, but the pharmacokinetic scheme of this interaction could not be fully established. In order to avoid the development of toxic effects of tacrolimus when combined with amlodipine, the former's levels in the blood should be constantly monitored and, if necessary, the doses should be adjusted.

Cyclosporine.

The drug has not been tested in combination with cyclosporine, except in kidney transplant recipients, who have shown variable increases in cyclosporine trough levels (mean 0-40%). Kidney transplant recipients using Emlodin should consider monitoring cyclosporine levels and reducing the dose as needed.

Simvastatin.

Concomitant administration of multiple doses of amlodipine (10 mg) with simvastatin in a dose of 80 mg causes an increase in the exposure of the latter by 77% (compared to the use of simvastatin alone). The use of simvastatin when using Emlodin should be limited to a dosage of 20 mg per day.

[ 2 ], [ 3 ]

Storage conditions

Emlodin should be kept in a dark place, out of reach of children. Temperature – no more than 25°C.

[ 4 ]

Shelf life

Emlodin can be used for 5 years from the date of release of the drug.

Application for children

It is prohibited to prescribe Emlodin to children under 6 years of age, because there is no data on the effect of amlodipine on blood pressure in this age group.

Analogues

The analogs of the drug are Azomex with Amlong, Amlo and Amlodipine-Farmak, Amlodipine-Norton, Amlopril-Darnitsa and Equator, as well as Amlodipine-Health, Normodipine and Stamlo.