Agrelide

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 drug belongs to antiplastic and immunomodulatory drugs, in particular antitumor agents. As a result, Agrelide is encrypted under the code L01XX35. One of its capsules contains 0.5 mg of the main active substance, which is anagrelide hydrochloride monohydrate, and several additional components.

This medicine 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 of age. However, it is necessary to take into account the presence of side effects and strictly adhere to the regimen of taking the drug. It is necessary to adhere to a certain scheme of increasing and decreasing the dosage.

Indications Agrelida

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

This drug is necessary for the treatment of thrombocytosis in diseases, the pathogenesis of which lies in the proliferation of myeloid tissue. As a result of such processes, an increase in the level of platelets in the blood is observed.

In addition to the main effect, Agrelide reduces the number of leukocytes and erythrocytes, but when the dosage is observed, these indicators do not change significantly.

Indications for use Agrelide also include 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 a chronic course, therefore, they require careful selection of dosage.

An increased level of platelets in the blood significantly changes its rheological parameters, which consist of an increase in viscosity and increased thrombus formation.

Release form

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

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

In addition, this drug contains auxiliary 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. Due to this composition, the medicine with the main active substance is protected by the capsule from the effects of the body's active environment until the right moment.

The capsule is externally an opaque shell made of gelatin of white or slightly cream shade. Size No. 4, and the inscription on each capsule is represented by the dosage "0.5 mg". In addition, this data is also written on the cap of the bottle. The filling of the capsule is almost white granules.

Pharmacodynamics

Provides a reduction in the total number of platelets in the bloodstream. When this drug is taken orally, a dose-dependent reduction in the level of platelets in the peripheral parts of the circulatory system is observed.

Clinical studies have shown that anagrelide inhibits megakaryocyte over-maturity. This effect is dose-dependent. In the blood of healthy people who took Agrelide, there were violations of the postmitotic stage of megakaryocyte development. In addition, there was a decrease in their size.

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

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

Agrelide does not have a significant effect on the parameters of the blood coagulation system, the duration of the platelet life cycle and the morphological features of the bone marrow. This drug does not affect systemic arterial pressure, heart rhythm and frequency, as well as urine and ECG parameters.

Pharmacokinetics

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

Taking this drug on an empty stomach at a dose of 0.5 mg causes its half-life to be more than an hour. Based on these features, 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 occurs quickly, as a result of which the main part is excreted by the urinary organs within 24 hours. In addition, no more than 1% is excreted unchanged.

It should be taken into account that taking Agrelide with food slows down its absorption, as a result of which its active substance is in the bloodstream longer. Taking anagrelide at a dosage of 0.5 mg after a meal is characterized by a slight decrease in bioavailability by 15%, in parallel with this, the half-life increases to almost 2 hours.

The pharmacokinetics of a single 1 mg dose are not altered in severe renal impairment with creatinine clearance less than 30 ml/min. In individuals with moderate hepatic impairment, the half-life is prolonged by 8 times.

Dosing and administration

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

The initial therapy should have a dose of no more than 2 mg/day, divided into several doses. Then, for a week, this dosage should be maintained. If the effect is insufficient, it is necessary to gradually increase the dose to the minimum effective one. This means that it is necessary to select the minimum dose that would have the desired effect.

To determine the results of treatment, it is necessary to monitor the platelet level, which initially should not exceed 600×109/l, and over time should be in the range of 150 to 400×109/l.

The method of administration and doses should be selected individually. In the absence of the desired effect, the dose should be increased by 0.5 mg/day over the course of a week. A single dose should not exceed 2.5 mg, and the daily dose should not exceed 10 mg/day.

During the first week of therapy, the platelet level should be monitored every 2 days. Then, when selecting the dosage, it is enough to check their number once a week. The first significant shift towards a decrease in 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 aged 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 need to adhere to the same scheme as for adults.

In the elderly, there is no need to revise the dosage in the absence of contraindications. In people with liver and kidney failure, the benefits and risks of developing side effects from anagrelide should be analyzed.

[ 1 ]

Use Agrelida during pregnancy

There are no studies that would prove the effectiveness of this drug on the body of a pregnant woman. In this regard, the use of the drug is not advisable due to the lack of reliable data on its use.

In addition, this applies to women who are breastfeeding, because the penetration of the main active substance into milk is unknown. If a woman becomes pregnant while taking Agrelide, she should be aware of its side effects and the impact on fetal development.

To avoid such a situation, it is necessary to additionally use contraception during the use of this drug. This may be oral contraceptives or a barrier method of protection.

Both the use of the drug during pregnancy and during the lactation period should be discussed with a doctor. This is due to the lack of information about the effect of anagrelide on the fetus, as well as the already born baby. Therefore, breastfeeding should be stopped while taking the drug.

Contraindications

Contraindications to the use of Agrelide include individual characteristics of the body and the presence of concomitant pathology. Intolerance to Agrelide may be due to the body's genetic reaction to some of the components. Side effects may develop on the main active substance - anagrelide or any other auxiliary component. It is also prohibited to use the drug in children under 7 years of age.

Contraindications to the use of Agrelide in the form of concomitant pathology may prevent the use of this drug over a long period of time.

These conditions include liver failure of a more severe than mild degree. An indicator of the severity of the disease is an increase in the content of liver enzymes by more than 5 times. To monitor 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 renal failure when selecting dosages for long-term use of Agrelide. To determine the degree of dysfunction, as well as to monitor kidney function, the creatinine filtration rate should be taken into account.

Despite the fact that the main active ingredient of the drug helps to reduce the number of platelets in the blood, Agrelide is still not the drug of choice for the treatment of life-threatening conditions from complications of thrombocytosis.

Side effects Agrelida

Side effects of Agrelide are generally not very pronounced and quickly pass without specific treatment. If the dosage and frequency of administration are observed, they may be absent altogether.

In the presence of myeloproliferative diseases, the frequency and severity of side effects practically do not change with the duration of therapy. In exceptional cases, serious conditions may develop in the form of congestive heart failure, cardiomyopathy, pericarditis, myocardial infarction, enlargement of the heart, complete blockade of impulse conduction through the heart muscle and atrial fibrillation. Also observed are cerebrovascular accident, the appearance of infiltration in the lungs, pneumofibrosis, pulmonary hypertension, inflammation of the gastric mucosa, pancreas, the formation of ulcerative defects in the stomach and intestines, as well as seizures.

With increasing dosage, side effects of Agrelide are observed in greater intensity and frequency. Most often, headaches, a feeling of increased heart rate, arrhythmia, signs of heart failure, decreased blood pressure, loss of consciousness, dyspeptic manifestations, symptoms of pancreatitis and bleeding from the digestive tract, intestinal dysfunction, in particular, diarrhea, bloating, nausea, vomiting and pain syndrome can be observed.

Dizziness, changes in sensitivity, shortness of breath, cough, chest pain, peripheral edema and various rashes are also possible.

General manifestations may include weakness, increased fatigue, decreased red blood cell and platelet counts, bleeding and thrombosis.

Often, pain may appear 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 if the dosage recommendations are not followed, as well as if the drug is taken for a long time without supervision. The cardiovascular and digestive systems are the first to react to an overdose, since the drug is taken orally.

Thus, it is necessary to review the dosage if nausea, vomiting, and disturbances in the rhythm and conduction of the impulse through the heart muscle occur. Anagrelide does not have its own specific antidote. If the first symptoms of overdose appear, it is necessary to immediately consult a doctor and be under supervision throughout the severe period.

Overdose may result in hemorrhagic manifestations due to a decrease in the number of platelets in the blood. It is necessary to stop taking the drug and regularly monitor the platelet level. Agrelide can be resumed only after the platelet level has returned to normal.

When the recommended dosages of anagrelide are exceeded, a decrease in systemic arterial pressure with periodic hypotonic states, loss of consciousness and collapse is possible. These symptoms can develop after taking 5 mg of anagrelide.

Interactions with other drugs

Agrelide's interaction 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. Such drugs include cilostazol, milrinone, amrinone, enoximone and olprinone.

Omeprazole, sucralfate and fluvoxamine may have a negative effect on the absorption of the main active substance. Agrelide may enhance the therapeutic effect of other agents that increase the level of platelets in the blood, such as acetylsalicylic acid. As a result, the risk of developing massive bleeding increases, so it is necessary to regularly monitor their level.

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

Combination treatment with anagrelide and phlebotomy has shown good results, as has the combination of anagrelide with aspirin, alkylating agents, hydroxyurea and interferon.

[ 2 ], [ 3 ]

Storage conditions

Storage conditions of Agrelid imply the implementation of certain recommendations on maintaining the temperature regime, humidity and storage location. This drug requires maintaining the temperature at a level not exceeding 25 degrees.

The place where further storage is supposed to take place should not be exposed to direct sunlight. It is also necessary to ensure that children do not have access to this medicine. Agrelide is contraindicated for use in children under 7 years of age. However, if they have access to the drug, an overdose or blockage of the upper respiratory tract by the capsule is possible.

The storage conditions of Agrelide ensure the preservation of the therapeutic properties of the drug specified in the instructions throughout the shelf life. If the storage requirements are not met, Agrelide may lose its characteristic effects and cause adverse reactions after administration.

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

[ 4 ]

Shelf life

The shelf life is characterized by the period of time during which the drug retains its therapeutic properties and does not cause harm. However, compliance with storage conditions is a necessary requirement. If recommendations are not followed, anagrelide may lose its properties proven by the manufacturer and negatively affect the body.

The shelf life of this drug is 5 years. Agrelide must not be used if the packaging in which the drug is stored is damaged. Each package contains 50 capsules in a bottle, if the bottle is damaged, the storage conditions of the drug may not be observed.

The expiration date is calculated taking into account the preservation 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 a complex treatment for many diseases, the development of which is based on an increase in the level of platelets with a change in the rheological characteristics of the blood and increased thrombus formation.