Agrelid

Agrelide is known in medical practice as a drug from the group of antiplatelet agents with the international name Anagrelide. According to the generally accepted pharmaceutical classification, this agent refers to antiplastic and immunomodulating drugs, in particular antitumor agents. As a result Agregled is encrypted under the code L01XX35. One capsule contains 0.5 mg of the main active substance, which is anagrelide hydrochloride monohydrate, and several additional components.

This drug is widely used in oncology practice. Its use is due to the high content of platelets in the human bloodstream. As a result, changes in the rheological characteristics of the blood are observed with an increase in its viscosity. This contributes to an increase in the likelihood of thrombus formation. Agrelide can be used by adults and children over 7 years old. However, it is necessary to take into account the presence of adverse reactions and strictly adhere to the scheme of taking the medicine. It is necessary to adhere to a certain scheme of increasing and decreasing the dosage.

Indications of the agrelida

Indications for the use of Agrelid are based on its main action, which manifests itself in a decrease in the number of platelets in the bloodstream. This effect is used both for treatment and prevention of increased thrombus formation.

This drug is needed to treat thrombocytosis in diseases whose pathogenesis is the proliferation of myeloid tissue. As a result of such processes, there is an increase in the level of platelets in the blood.

In addition to the main effect Agreglide reduces the number of leukocytes and red blood cells, but with the observance of dosages, these parameters do not change significantly.

Indications Agreglide also includes symptomatic therapy, when certain diseases are accompanied by clinical manifestations in the form of thrombohemorrhagic reactions. In most cases, such pathological conditions are characterized by chronic course, and therefore require careful selection of dosage.

Elevated levels of platelets in the blood significantly changes its rheological parameters, which consist in increasing the viscosity and increasing thrombogenesis.

Release form

The form of release of the drug ensures the delivery of the main active substance to the site of its cleavage and absorption. The form of Agrelide is a capsule. Thanks to it, the agent is not exposed to enzymes ahead of time and enters the stomach unchanged. Capsules are contained in vials of 50 pieces in each.

The main active substance, which provides characteristic therapeutic effects, is anagrelide. One capsule contains a certain amount of anagrelide, which corresponds to a single dosage. Thus, the capsule of the medicament contains 0.5 mg of anagrelide, which is hydrochloride monohydrate.

In addition, the drug has ancillary components such as magnesium stearate, lactose monohydrate, microcrystalline cellulose, povidone, anhydrous lactose and crospovidone.

The capsule consists of gelatin, silicon dioxide, purified water, titanium dioxide (E 171) and sodium lauryl sulfate. Thanks to a similar composition, the drug with the main active substance is protected by a capsule from the action of the active media of the organism until the right moment.

The capsule is externally an opaque shell of gelatin with a white or slightly creamy hue. Size # 4, and the inscription on each capsule is represented by a dosage of "0.5 mg". In addition, these data are also written on the cap of the vial. Capsule fillings are practically white granules.

Pharmacodynamics

 Provides a reduction in the total number of platelets in the bloodstream. With oral administration of this drug, a dose-dependent decrease in platelet levels in the peripheral parts of the circulatory system is observed.

Clinical studies showed inhibition of anagrelide by the overgrowth of megakaryocytes. This effect is dose-dependent. In the blood of healthy people who took Agrelid, there were violations of the postmitotic stage of development of megakaryocytes. In addition, there was a decrease in their size.

Therapeutic doses of Agrelide contribute not only to a significant decrease in the level of platelets, but also to minor leukopenia and anemia.

 Causes inhibition of phosphodiesterase III of cyclic AMP. These inhibitors can provoke a decrease in the adhesion of platelets. A more pronounced therapeutic effect is observed when taking high doses of the drug.

Agreglide has no significant effect on the parameters of the blood clotting system, the length of the life cycle of platelets and the morphological features of the bone marrow. This drug does not affect systemic blood pressure, rhythm and heart rate, as well as urine and ECG.         

Pharmacokinetics

Pharmacokinetics Agrelid causes a rapid cleavage of anagrelide in the stomach and intestines, because more than 75% of the capsule is absorbed precisely in the intestine. After oral administration of the drug with a dosage of 0.5 mg to 2.0 mg, the pharmacokinetics of Agrelyde are characterized by typical reactions for the drug.

Admission of this drug to an empty stomach at a dose of 0.5 mg causes its half-elimination for more than an hour. Based on these features, the Agrelide can be taken 2 to 4 times a day. In addition, the main active substance does not have a cumulative effect.

After oral administration of the drug, its metabolism quickly occurs, as a result of which the major part is excreted by urinary organs throughout the day. In addition, no more than 1% is allocated unchanged.

It should be borne in mind that the simultaneous reception of Agrelid with food slows its absorption, as a result of which its active substance is longer in the bloodstream. The intake of anagrelide at a dosage of 0.5 mg after a meal is characterized by a slight decrease in bioavailability by 15%, in parallel, the elimination half-life increases to almost 2 hours.

Pharmacokinetics in a single dose of 1 mg does not change in severe form of renal failure with creatinine clearance less than 30 ml / min. In people with moderate hepatic insufficiency, the half-life is prolonged 8-fold.

Dosing and administration

The method of administration and dose are determined by the form of release and the quantitative composition of one capsule. In this regard, the drug is taken internally with a single dose of 0.5 mg (1 capsule). At the initial stage of Agreglide therapy, it is necessary to monitor a person's condition for correction of dosage and prevention of complications.

Start therapy should have a dose not higher than 2 mg / day, divided into several doses. Further within a week should maintain this dosage. If the effect is insufficient, gradually increase the dose to a minimum effective. This means that you need to select the minimum dose that would have the desired effect.

To determine the results of treatment, it is necessary to monitor the level of platelets, which at first should not exceed 600 × 109 / L, and in the course of time be in the range from 150 to 400 × 109 / L.

The way of application and dose should be selected individually. In the absence of the desired effect, the dose should be increased by 0.5 mg / day throughout the week. A single dose should not exceed 2.5 mg, and a daily intake should not exceed 10 mg / day.

In the first week of therapy, the platelet count must be checked every 2 days. Further, when choosing the dosage - it is enough to check their quantity once a week. The first significant shift toward decreasing platelets should be expected no earlier than 2-3 weeks after the start of treatment. The maintenance dose in most cases is 1-3 mg / day.

As for children from 7 to 14 years, it is rational to start with a single dose of 0.5 mg of anagrelide and gradually increase to 0.5 mg 4 times a day. To select the minimum effective dose, you must follow the same scheme as for adults.

In the elderly, there is no need to revise the dosage in the absence of contraindications. People with hepatic and renal insufficiency should analyze the benefits and risks of developing side effects from anagrelide.

[1]

Use of the agrelida during pregnancy

Studies that would have proved the effectiveness of this drug on the body of a pregnant woman were not carried out. In this regard, the use of the drug is not desirable due to the lack of reliable data on its use.

In addition, this applies to women who breastfeed, because the penetration of the main active substance into the milk is not known. In the case when a woman becomes pregnant during the reception of Agreglida, she should be aware of the side effects of his actions and the impact on the development of the fetus.

To avoid such a situation, it is necessary to additionally use contraception during the application of this medication. These can be oral contraceptives or a barrier method of protection.

Both use of the drug during pregnancy and during the lactation period should be discussed with the doctor. This is due to the lack of information about the effects of anagrelide on the fetus, as well as the already born baby. Thus, during the reception of the drug should stop breastfeeding.

Contraindications

Contraindications to the use of Agrelid include individual features of the body and the presence of concomitant pathology. The intolerance of Agreglide may be due to the genetic reaction of the body to certain constituent substances. Side effects can develop on the main active substance - anagrelide or any other auxiliary component. Also, the use of the drug in children under 7 years of age is prohibited.

Contraindications to the use of Agrelid in the form of concomitant pathology may prevent the use of this medication over an extended period of time.

Such conditions include hepatic insufficiency heavier than mild. The indicator of the severity of the disease is an increase in the content of liver enzymes more than 5 times. To control the functioning of the liver, it is necessary to take into account the level of ALT and AST.

It is also necessary to take into account the severity of the course of renal failure in the selection of dosages for the long-term use of Agrelyd. To determine the degree of dysfunction, as well as to control the work of the kidneys, the creatinine filtration index should be taken into account.

Despite the fact that the main active substance of the drug contributes to a decrease in the number of platelets in the blood, nevertheless Agreglide is not a drug of choice for the treatment of life-threatening conditions from complications of thrombocytosis. 

Side effects of the agrelida

Side effects Agreglide is generally not very pronounced and rapidly passing without specific treatment. At observance of dosages and frequency of reception they can at all be absent.

In the presence of myeloproliferative diseases, the frequency and severity of side effects practically does not change with the duration of therapy. In exceptional cases, it is possible to develop serious conditions in the form of congestive events in heart failure, cardiomyopathy, pericarditis, myocardial infarction, increase in heart size, complete blockade of cardiac muscle pulse and atrial flutter. There is also a violation of cerebral circulation, the appearance of infiltration in the lungs, pneumofibrosis, pulmonary hypertension, inflammation of the stomach mucosa, pancreas, the formation of ulcerative defects in the stomach and intestines, as well as convulsive attacks.

 When the dosage is increased, side effects of Agrelide are observed in a greater intensity and frequency. Most often, headaches, a feeling of rapid heartbeat, arrhythmias, signs of heart failure, lowering blood pressure, loss of consciousness, dyspeptic manifestations, symptoms of pancreatitis and bleeding from the digestive tract, impaired intestinal function, in particular diarrhea, bloating, nausea, vomiting and pain syndrome.

Dizziness, sensitivity changes, dyspnea, cough, chest pain, peripheral puffiness and various rashes are also possible.

Common manifestations may include weakness, increased fatigue, a decrease in the number of red blood cells and platelets in the blood, bleeding and thrombosis.

It is often possible the appearance of pain along the spine, in the joints, muscles and bones. The nervous system can provoke insomnia, impaired consciousness, hallucinations and increased irritability.

Overdose

Overdose may occur in case of failure to follow the recommendations for used dosages, as well as long-term administration of this drug without control. On an overdose, the cardiovascular and digestive system is the first to react, since the drug is taken orally.

So, it is necessary to revise the dosage when nausea, vomiting and rhythm disturbances and pulse conduction occur on the heart muscle. Anagrelide does not have its specific antidote. When the first symptoms of an overdose appear, you should immediately consult a doctor and be under control during a difficult period.

Overdosing threatens with such a condition as hemorrhagic manifestations due to a decrease in the number of platelets in the blood. It is necessary to cancel the drug and regularly monitor the level of platelets. The use of Agrelide can be resumed only after the normalization of the platelet level.

If the recommended dosages of anagrelide are exceeded, a reduction in systemic arterial pressure with periodic hypotonic conditions, loss of consciousness and collapse can occur. These symptoms can develop after taking 5 mg of anagrelide.

Interactions with other drugs

Interaction Agrelide with other drugs is due to its ability to inhibit phosphodiesterase III, so the simultaneous use of drugs with a similar mechanism of action is contraindicated. These drugs include cilostazol, milrinone, amrinone, enoximone and olprinone.

Omeprazole, sucralfate and fluvoxamine may have a negative effect on the absorption of the main active ingredient. Agreglide may enhance the therapeutic effect of other agents that increase platelet levels in the blood, for example, acetylsalicylic acid. As a result, the risk of developing massive bleeding increases, so it is necessary to regularly monitor their level.

Interaction Agrelide with other drugs, such as warfarin, digoxin, acetaminophen, ranitidine, furosemide, hydroxyurea, iron preparations and allopurinol, does not provoke any negative effects.

Complex treatment with anagrelide in conjunction with phlebotomy showed good results, as with combination of anagrelide with aspirin, alkylating agents, hydroxyurea and interferon.

[2], [3]

Storage conditions

Storage conditions Agrelid implies the implementation of certain recommendations for compliance with temperature, humidity and storage space. This drug requires maintaining the temperature at a level no higher than 25 degrees.

The place where further storage is expected should not be influenced by direct sunlight. It is also necessary to take care of the inaccessibility of children to this medication. Agreglide is contraindicated for use in infants whose age does not exceed 7 years. However, if they have access to the drug, an overdose or blockage of the upper respiratory tract capsule is possible.

Agrelide storage conditions ensure the preservation of the indicated therapeutic properties of the medicinal product during the shelf life. Subject to non-compliance with storage requirements, Agreglide may lose its characteristic effects and, after administration, cause side reactions.

It is not recommended to take this pharmaceutical product when it is stored in unfavorable conditions in order to avoid the development of adverse reactions, both known and spontaneous.

[4]

Shelf life

Shelf life is characterized by a period of time during which the drug retains its therapeutic properties and causes harm. However, compliance with storage conditions is a necessary requirement. In the absence of implementation of recommendations, anagrelide may lose its proven properties and negatively affect the body.

Shelf life of this medication is 5 years. Agrelide is not allowed to use if the packaging in which the drug is stored is damaged. Each package contains 50 capsules in a vial, if damaged, it is possible not to observe the storage conditions of the preparation.

The expiration date is calculated taking into account the safety of the main active substance and auxiliary components. As soon as the last period of taking the medicine expires, it is necessary to stop using it.

Agrelide is an effective drug for its use as an integrated treatment for many diseases, the basis of which is the increase in platelet levels with a change in the rheological characteristics of blood and increased thrombosis.