Anagrelide

2024 Author: Rachel Wainwright | [email protected]. Last modified: 2023-12-15 07:39

Anagrelide: instructions for use and reviews

1. Release form and composition
2. Pharmacological properties
3. Indications for use
4. Contraindications
5. Method of application and dosage
6. Side effects
7. Overdose
8. Special instructions
9. Application during pregnancy and lactation
10. Use in childhood
11. In case of impaired renal function
12. For violations of liver function
13. Use in the elderly
14. Drug interactions
15. Analogs
16. Terms and conditions of storage
17. Terms of dispensing from pharmacies
18. Reviews
19. Price in pharmacies

Latin name: Anagrelide

ATX code: L01XX35

Active ingredient: anagrelide (Anagrelide)

Manufacturer: Peoples' Friendship University of Russia (RUDN) (Russia)

Description and photo update: 2020-28-05

Anagrelide is a drug for the treatment of essential thrombocythemia.

Release form and composition

Dosage form - capsules: No. 4, hard gelatinous, red-brown cap and body; capsule filler - powder from white to almost white color (100 pcs. in white opaque high-density polyethylene bottles, sealed with white opaque screw caps made of polypropylene, equipped with a control ring of the first opening and desiccant-silica gel in a white polyethylene capsule, sealed with a dense sheet paper; in a cardboard box 1 bottle and a leaflet with instructions for the use of Anagrelide).

Composition for 1 capsule:

active substance: anagrelide - 0.5 mg (in the form of anagrelide hydrochloride monohydrate - 0.61 mg);
auxiliary ingredients: lactose - 65.76 mg; lactose monohydrate - 53.74 mg; crospovidone - 3 mg; povidone K30 - 3.75 mg; magnesium stearate - 0.75 mg; MCC (microcrystalline cellulose Vivapur 102) - 22.5 mg;
capsule body and cap: gelatin - 37.3033 mg; titanium dioxide (E171) - 0.1267 mg; iron dye red oxide (E172) - 0.57 mg.

Pharmacological properties

Pharmacodynamics

Anagrelide causes a selective, dose-dependent and reversible decrease in platelet levels in humans, but the exact mechanism of its action is currently unknown. It has been found that in cell culture it inhibits the expression of transcription factors, including GATA-1 (erythroid transcription factor) and FOG-1 (coactivator protein), involved in the process of megakaryocytopoiesis, which ultimately leads to a decrease in platelet production.

In the course of an in vitro study of the process of human megakaryocytopoiesis, it was revealed that inhibition of platelet production occurs due to a slowdown in maturation, a decrease in size, and a decrease in the ploidy of megakaryocytes. In vivo, similar effects are found in the study of bone marrow biopsies of patients receiving anagrelide.

Anagrelide is an inhibitor of cyclic adenosine monophosphate phosphodiesterase III (PDE III cAMP).

Efficiency and safety

The clinical efficacy and safety of anagrelide, used to reduce platelet counts, has been evaluated in four open, uncontrolled studies involving more than 4,000 patients with myeloproliferative hemoblastosis.

In patients with ET (essential thrombocythemia), a complete response was considered to be a decrease in the number of platelets below 600 × 10 ⁹ / L or more than 50% of the initial number, while this level of platelets should have been maintained for at least 4 weeks. In clinical trials, the period to development of a complete response varied over a wide range of 4-12 weeks.

Effect on heart rate (heart rate) and QTc interval

The effect of anagrelide on heart rate and QTc interval was studied in a double-blind, placebo- and actively controlled, randomized, crossover clinical study of healthy female and male volunteers. The effect of two different doses of 0.5 and 2.5 mg was observed.

A dose-dependent increase in heart rate was observed during the first 12 hours. At the same time, the time to reach the maximum value of this indicator approximately corresponded to the time to reach the maximum concentration (C _max) of anagrelide in blood plasma and was equal to 2 hours. The maximum increase in heart rate 2 hours after taking the drug in doses of 0, 5 and 2.5 mg, respectively, were + 7.8 and + 29.1 beats per minute.

An obvious transient increase in the QTc interval was noted after taking the drug in both doses, simultaneously with an increase in heart rate. The maximum change in the QTc interval, corrected by the Fridericia formula (QTcF), 2 hours after taking 0.5 mg was + 5 msec, 1 hour after taking 2.5 mg - + 10 msec. Evidence suggests that an increase in the QTc interval may be due to the physiological effect of increased heart rate and QT-RR hysteresis, rather than a direct effect of anagrelide on repolarization.

Application in pediatrics

According to the results of an open clinical study in 8 children and 10 adolescents (including those who had not previously received therapy with anagrelide and who had taken this drug for the previous 5 years), after a 12-week course, there was a decrease in the average number of platelets to a controlled level.

According to a study included in the register of clinical trials in children, while taking anagrelide, the average platelet count decreased from the time of diagnosis verification and was maintained at a stable level until 18 months in 14 pediatric patients with ET, including 4 children and 10 adolescents. In an earlier open-label clinical study, a decrease in mean platelet counts was observed in 7 children and 9 adolescents who received anagrelide for a period ranging from 3 months to 6.5 years. The drug should be prescribed with caution for the treatment of children, since the experience of its use in this age group is limited due to the rare occurrence of the disease.

In all clinical trials, the average daily therapeutic dose of anagrelide used in children varied widely. Despite this, the generalized data confirm that for the treatment of adolescents, anagrelide is effective at initial and maintenance doses similar to those for adult patients. For the treatment of children over the age of 6 years, the drug is recommended to be used in a lower initial dose than in adults, namely 0.5 mg per day.

The optimal dose of anagrelide for use in pediatric practice requires careful individual selection.

Pharmacokinetics

The main pharmacokinetic characteristics of anagrelide:

absorption: after oral administration, up to 70% of the substance is absorbed in the gastrointestinal tract (gastrointestinal tract); the time to reach the maximum concentration (T _Cmax) in the blood plasma when taking the drug on an empty stomach is about 1 hour. According to the study of the pharmacokinetics of anagrelide in healthy volunteers, the simultaneous intake of the substance at a dose of 1 mg with food reduces its maximum concentration (C _max) in plasma by 14 %, but increases the area under the concentration-time pharmacokinetic curve (AUC) by 20%, while the C _{max of} its active metabolite, 3-hydroxy-anagrelide, decreases by 29%, while its AUC does not change;
metabolism: anagrelide is metabolized in the liver mainly by the isoenzyme of the cytochrome P ₄₅₀ CYP1A2 system to 3-hydroxy-anagrelide and 2-amino-5,6-dichloro-3,4-dihydroquinazoline, the average content of the latter in urine varies from 18 to 35% of taken dose of the drug;
excretion: anagrelide has a short T _1/2 (half-life) from blood plasma, which is ~ 1.3 hours, and therefore, the accumulation of the drug in the body is not expected. Less than 1% of the dose taken is excreted unchanged by renal elimination, in the form of 3-hydroxyanagrelide and RL603, approximately 3% and 16–20%, respectively. As part of the study with the participation of healthy volunteers, it was found that after oral administration of ¹⁴ C-labeled anagrelide, isotope excretion within 24 hours reached 61%, within 72 hours (3 days) - 90%, within 168 hours (7 days) - 100%. Excretion of ¹⁴ C-anagrelide in urine was 79%, with feces - 21%.

Anagrelide demonstrates a linear dependence of the variability of pharmacokinetic parameters on the dose taken, provided that it is used in a daily dose of 0.5 to 2 mg.

Pharmacokinetics of anagrelide in special patient groups:

children and adolescents: data from studies of the use of anagrelide on an empty stomach in patients with ET aged 7 to 16 years confirm that the C _max and AUC values of the substance, reduced to normal body weight, are higher in children and adolescents than in adults. In addition, a tendency was found to increase the exposure values of its active metabolite;
elderly patients (65–75 years old): data from studies of the use of anagrelide on an empty stomach in elderly patients with ET, in comparison with those in younger patients (22–50 years old), confirm that in the former, the C _max level of anagrelide in blood plasma was higher by 36%, and AUC - by 61%, while for the active metabolite, 3-hydroxy-anagrelide, the values of C _max and AUC were lower by 42% and 37%, respectively, which is probably due to a decrease in the rate of presystemic metabolism of anagrelide to 3-hydroxyanagrelide;
patients with hepatic impairment: the main route of anagrelide clearance is hepatic metabolism. The use of the drug in severe hepatic impairment has not been studied. According to studies of the use of anagrelide in moderate hepatic insufficiency (from 7 to 9 points on the Child-Pugh scale), after a single dose of 1 mg, an increase in the average values of C _max and AUC was recorded by 2 and 8 times, respectively, compared with those in healthy volunteers. The mean C _{max of the} active metabolite, 3-hydroxy-anagrelide, decreased by 24%, and the mean AUC increased by 77% in comparison with healthy volunteers;
patients with renal failure: according to studies of the use of anagrelide in severe renal impairment, with creatinine clearance (CC) less than 30 ml / min, after a single dose of 1 mg, no changes in the pharmacokinetic properties of anagrelide were observed. At the same time, in 3-hydroxy-anagrelide, the exposure value AUC _{0 – ∞} was approximately 50% higher than in healthy patients; there were no differences in plasma C _max values between the groups.

Indications for use

Anagrelide is used in patients with increased platelet count in ET patients with a high risk of complications who do not tolerate current therapy or when it does not lead to a decrease in platelet concentration to an acceptable level.

Conditions related to a high risk of complications (one or more of the following): age over 60 years, platelet counts above 1000 × 10 ⁹ / L, history of data on thrombohemorrhagic complications.

Contraindications

Absolute:

severe liver dysfunction;
severe renal dysfunction (CC less than 30 ml / min);
pregnancy and the period of breastfeeding;
children under 6 years of age;
congenital lactase deficiency, glucose-galactose malabsorption, lactose intolerance;
increased individual sensitivity to anagrelide or any of the auxiliary components in the capsule.

With caution, Anagrelide capsules are prescribed for mild and moderate hepatic / renal insufficiency, diseases of the cardiovascular system, simultaneously with acetylsalicylic acid, in combination with inhibitors of the cytochrome P ₄₅₀ isoenzyme CYP1A2 (fluvoxamine, ciprofloxacin), patients with known QT risk factors for lengthening (hypokalemia, congenital long QT interval syndrome, a history of acquired prolongation of the QTc interval, when taken with drugs that cause prolongation of the QTc interval), children and adolescents aged 6 to 17 years.

Anagrelide, instructions for use: method and dosage

Anagrelide capsules are intended for oral administration. They should be swallowed whole, do not crush or dissolve the contents of the capsules in liquid.

A physician with experience in treating ET patients should begin drug therapy.

Recommended dosage regimen:

adults and elderly patients: initial dose - 1 mg (2 capsules) per day, divided into 2 doses of 0.5 mg (1 capsule);
children and adolescents: initial dose - 0.5 mg (1 capsule) per day.

Anagrelide in the initial dose should be taken for at least 1 week. Then, if necessary, the dose of the drug can be gradually increased, taking into account the individual characteristics and the patient's response to therapy. The dose increase for any week of treatment should not exceed 0.5 mg.

Maximum doses: daily - 10 mg, single - 2.5 mg.

Dose titration:

adults and elderly patients: the dose is adjusted until the minimum effective is achieved, providing a decrease and / or maintenance of platelet concentration to / at a level below 600 × 10 ⁹ / l (optimal platelet count is 150–400 × 10 ⁹ / l);
children and adolescents: the doctor determines the target platelet count individually.

In the absence of a satisfactory response to therapy in children after 3 months of taking the drug, it is necessary to consider discontinuing anagrelide.

It is required to regularly monitor the patient's condition and evaluate the effectiveness of Anagrelide. When treatment is started with a dose exceeding 1 mg per day, platelet count is determined every two days during the first week of the course. Further studies are carried out at least once a week, until the selection of a maintenance dose that ensures the stability of the target platelet level. As a rule, a decrease in the number of platelets can be achieved 7-21 days from the beginning of the course. For most patients, the optimal therapeutic and maintenance dose is in the range of 1 to 3 mg per day.

A break in taking the drug or cessation of treatment causes a temporary increase in the number of platelets as a result of the phenomenon of negative aftereffect (withdrawal syndrome), which is characterized by significant variability. This indicator rises, as a rule, within the first 4 days after discontinuation of anagrelide, and returns to the initial level within 1–2 weeks. At the same time, an increase in the number of platelets above the initial value is likely, which requires careful frequent monitoring of their content.

If the patient is unresponsive to anagrelide, alternative therapies should be considered.

Side effects

Clinical scientific studies to assess the safety of anagrelide were carried out in four open groups, in three of which 942 patients took anagrelide at an average dose of about 2 mg / day, in 22 of them the duration of taking the drug reached 4 years. In the fourth group, including 3660 patients, in the framework of a clinical study, anagrelide was taken on average approximately 2 mg / day, including 34 subjects over 5 years. According to the results of these studies, it was determined that the most frequent adverse reactions when taking Anagrelide were: headache - 14%, palpitations - 9%, nausea - 6%, fluid retention in the body - 6%, diarrhea - 5%. Being, in all likelihood, a consequence of the pharmacological effectiveness of anagrelide, these actions were, as a rule, weakly expressed and took place on their own,or were warned by a slow transition from initial doses to higher ones.

Adverse drug reactions of anagrelide, registered both in clinical trials and in the post-marketing period (frequency scale according to systemic organ classes: very often - not less than 10%; often - from 1 to 10%; infrequently - from 0, 1 to 1%; rarely - from 0.01 to 0.1%; frequency unknown - according to the available data, it is impossible to estimate the frequency of occurrence):

blood and lymphatic system: often - anemia; infrequently - pancytopenia, thrombocytopenia, bleeding, ecchymosis;
metabolism and nutrition: often - fluid retention; infrequently - weight loss, edema; rarely - increased body weight;
nervous system: very often - headache; often - vertigo (dizziness); infrequently - insomnia, paresthesia, depression, hypesthesia, confusion, nervousness, xerostomia (dry mouth), amnesia; rarely - drowsiness, coordination disorders, migraine, dysarthria;
organ of vision: rarely - impaired visual perception, diplopia;
organ of hearing and labyrinthine disorders: rarely - tinnitus (tinnitus);
cardiovascular system: often - palpitations, tachycardia; infrequently - arrhythmia, CHF (chronic heart failure), increased blood pressure (blood pressure), fainting, supraventricular tachycardia, atrial fibrillation, ventricular tachycardia; rarely - angina pectoris, myocardial infarction, cardiomegaly, cardiomyopathy, pericardial effusion, vasodilation, orthostatic hypotension; frequency unknown - polymorphic ventricular tachycardia of the "pirouette" type;
respiratory system, chest and mediastinal organs: infrequently - epistaxis, shortness of breath, pleural effusion, pulmonary hypertension, pneumonia; rarely - infiltrates in the lungs; frequency unknown - interstitial lung disease, including allergic alveolitis and pneumonitis;
digestive tract: often - abdominal pain, nausea, diarrhea, vomiting, flatulence; infrequently - anorexia, dyspepsia, pancreatitis, gastrointestinal upset, gastrointestinal bleeding, constipation; rarely - gastritis, colitis, bleeding gums;
hepatobiliary system: infrequently - increased activity of hepatic enzymes; frequency unknown - hepatitis;
skin and subcutaneous tissue: often - skin rash; infrequently - discoloration of the skin, alopecia, itching; rarely - dry skin;
musculoskeletal and connective tissue: infrequently - arthralgia, myalgia, back pain;
genitourinary system: infrequently - impotence; rarely - renal failure, bedwetting; frequency unknown - tubulointerstitial nephritis;
general disorders and disorders at the injection site: often - fatigue; infrequently - weakness, chest pain, chills, fever, malaise; rarely - pain, asthenia, flu-like syndrome;
data from laboratory and instrumental studies: rarely - an increase in the level of creatinine in the blood.

In clinical trials / special programs for the use of anagrelide in pediatrics, a group of 48 patients aged 6 to 17 years was observed (among whom there were 19 children and 29 adolescents). They received the drug for a long time, up to 6.5 years. The observed safety profile was predominantly consistent with that of adult patients. Despite this, there are insufficient data for a full comparative analysis that would allow assessing the safety of anagrelide use in children.

Overdose

There is little information about episodes of deliberate overdose of anagrelide. The patients noted the development of sinus tachycardia and vomiting, which were successfully stopped by symptomatic therapy.

Anagrelide, when taken in doses exceeding the recommended ones, lowers blood pressure up to the development of arterial hypotension. A single dose of 5 mg of anagrelide can lead to a decrease in blood pressure and dizziness. Due to the fact that the decrease in the concentration of platelets is dose-dependent, the development of thrombocytopenia, potentially capable of provoking hemorrhagic complications, can also be attributed to the symptoms of an overdose.

The specific antidote for anagrelide is unknown. In case of drug intoxication, the patient needs to ensure careful monitoring of the clinical condition, including taking a blood test for platelets to diagnose thrombocytopenia. Depending on the patient's condition, the drug is canceled or the dose is reduced until the platelet level is restored.

special instructions

In patients with impaired renal and hepatic function of mild / moderate severity, before starting the course, an assessment of the ratio of the potential risk and the expected benefit of treatment with anagrelide should be carried out. In the course of therapy, they need to ensure careful monitoring of the clinical condition, including a complete blood count (hemoglobin, leukocyte and platelet levels), an assessment of liver function [the activity of the liver enzymes ALT (alanine aminotransferase) and AST (aspartate aminotransferase)], an assessment of renal function (concentration of creatinine in the blood and urea, the content of electrolytes - potassium, magnesium and calcium). In addition, frequent diagnosis of hepatic function is required, especially at the start of treatment. It is not recommended to use anagrelide for moderate and severe hepatic insufficiency.

Usually, after discontinuation of therapy, the platelet count in the blood begins to increase within 4 days, the indicators return to the initial value after 10-14 days and are even able to exceed it. In this regard, at the end of the course, frequent monitoring of the platelet concentration is necessary.

Regardless of age, with confirmed heart disease, or in case of suspicion of such, patients should take the drug with caution. Since Anagrelide is a PDE III cAMP inhibitor, it exhibits positive inotropic and chronotropic effects. In addition, serious cardiovascular adverse reactions have also been reported in patients with no history of cardiac disease with normal cardiovascular function in pre-treatment studies.

Before starting therapy, all patients are advised to undergo a cardiovascular examination, including echocardiography (EchoCG) and electrocardiography (ECG) of the heart. In the course of treatment, it is necessary to control the appearance of cardiovascular pathologies (for example, an ECG or EchoCG), based on the results of which a decision is made on the need for additional examination.

In the presence of risk factors for prolongation of the QT interval (hypokalemia, congenital prolongation of the QT interval, a history of acquired QTc prolongation, the use of drugs that can cause prolongation of the QTc interval), Anagrelide should be used with caution. Before starting the course, hypokalemia and hypomagnesemia must be excluded, and during treatment, the content of potassium and magnesium must be checked periodically. It is recommended to constantly monitor the QTc interval.

There is reliable evidence of serious undesirable effects developing when taking anagrelide on the part of the cardiovascular system, such as polymorphic ventricular tachycardia of the "pirouette" type, cardiomyopathy, ventricular tachycardia, cardiomegaly and heart failure.

Caution should be exercised when prescribing the drug at probable high plasma C _max values of anagrelide and 3-hydroxy-anagrelide, for example, in patients with hepatic insufficiency or taking inhibitors of the cytochrome CYP1A2 isoenzyme.

Anagrelide is used only when the potential benefits of therapy outweigh the potential risks.

Cases of the development of pulmonary hypertension during therapy have been described, as a result of which, before and during the use of the drug, the signs and symptoms of concomitant heart and lung diseases are assessed.

With the simultaneous use of anagrelide and acetylsalicylic acid, it is possible to develop a clinically significant pharmacological interaction associated with severe bleeding. In the course of studying this interaction in healthy volunteers, it was found that with repeated administration of anagrelide once a day at a dose of 1 mg and acetylsalicylic acid once a day at a dose of 75 mg, an increase in the inhibition of platelet aggregation caused by these drugs, exceeding that which develops with taking only acetylsalicylic acid. There is evidence of severe bleeding resulting from the use of this combination of drugs. If it is necessary to prescribe such a combination of drugs, a thorough assessment of the possible risks should be carried out, especially in patients with a high probability of developing bleeding.

It is important to take into account that the first time the drug is taken, such side effects of anagrelide as headache, nausea, palpitations, fluid retention in the body, diarrhea are often manifested. They usually go away on their own in a few weeks. But the development of these negative reactions can be prevented by slow titration of the dose upward, carried out after the appointment of the initial dose.

If one or more doses are missed, the drug is continued in accordance with the established dosing regimen.

Special instructions for use in pediatrics

Due to the limited experience of using the drug for the treatment of children and adolescents, anagrelide in this age group of patients should be used with caution.

Since there are no specific prescriptions for children and adolescents, the diagnostic criteria for ET, according to the WHO (World Health Organization), for the treatment of adult patients are regarded as applicable in pediatric practice. It is required to strictly follow the guidelines for the diagnosis of ET; in unclear cases, the diagnosis should be periodically verified using all methods of differential diagnosis of congenital or secondary thrombocytosis, up to genetic analysis and bone marrow biopsy.

Cytoreductive therapy is generally considered for use in high-risk children. Anagrelide is taken only in case of signs of disease progression or with the development of thrombosis. At the beginning of the course, a regular assessment of the balance of benefits and risks is necessary, and the need to continue this treatment should also be periodically confirmed.

As in adults, before starting treatment and regularly during therapy, children perform a detailed blood test, an assessment of the functions of the liver, kidneys and heart. There is a possibility of progression of the disease with the development of myelofibrosis or acute myeloid leukemia. The frequency of this course of the disease is unknown, but since pediatric patients are characterized by a longer duration of ET, the risk of malignant transformation is higher in them than in adults. In this regard, it is necessary to regularly monitor the condition of children in order to detect the progression of the disease in accordance with good clinical practice, namely, conduct a physical examination, evaluate the appropriate markers of pathology and do a bone marrow biopsy. It is necessary to ensure a timely assessment of all pathological changes in order to take measures that may, incl.include dose reduction and temporary or complete cessation of the course.

Influence on the ability to drive vehicles and complex mechanisms

With the development of dizziness after taking Anagrelide, one should refrain from driving a car or working with complex machinery, machine tools and production equipment until the ability to concentrate and psychomotor speed is fully restored.

Application during pregnancy and lactation

Anagrelide is not indicated for the treatment of women who are pregnant or breastfeeding.

There are insufficient data on the effect of anagrelide on pregnancy in humans. According to the results of studies on animals, the reproductive toxicity of the substance was revealed.

If it is necessary to use the drug during pregnancy or when it develops during treatment, the patient needs to be warned about the risk to the fetus.

Against the background of therapy with anagrelide, women of reproductive age need to use reliable measures to prevent pregnancy.

It has not been reliably established whether anagrelide is excreted in human breast milk. According to the results of animal studies, the excretion of the main substance and its metabolites with breast milk was revealed. Since it is impossible to exclude the possibility of developing undesirable side effects of the drug in a newborn or breastfed baby, breastfeeding should be discontinued during the therapy period.

Pediatric use

In pediatric practice, it is contraindicated to use Anagrelide for the treatment of children under the age of 6 years due to the lack of clinical data on the safety and efficacy of the drug in this age category.

Children over 6 years of age are recommended to prescribe the drug at an initial dose of 0.5 mg per day.

The selection of a therapeutic dose of the drug should be carried out taking into account the individual characteristics of the course of the disease in children.

With impaired renal function

In patients with mild / moderate renal impairment, an assessment of the possible risks and benefits of therapy should be carried out before starting treatment.

Severe renal failure (CC less than 30 ml / min) is an absolute contraindication for the use of the drug.

In case of impaired renal function, dose adjustment of anagrelide is not required.

For violations of liver function

In patients with mild / moderate hepatic impairment, an assessment of the possible risks and benefits should be carried out before starting treatment and during therapy.

With moderate impairment of hepatic function, the initial dose of anagrelide should be 0.5 mg per day.

Severe hepatic impairment is an absolute contraindication for the use of the drug.

Use in the elderly

The existing difference in the pharmacokinetic parameters of anagrelide in elderly and younger patients with ET does not require correction of the initial dose and changing the titration algorithm until the individual optimal maintenance dose is reached.

According to the results of clinical studies, in which about half of the patients were aged 60 years and older, it was found that the dose adjustment of anagrelide depending on age was not required. But the development of serious adverse events (primarily disorders of the cardiovascular system) in elderly patients was observed twice as often.

Drug interactions

Currently, there is not enough information on the kinetics and dynamics of the pharmacological interaction of anagrelide when it is used with other drugs.

Known effects of drugs / drugs on anagrelide:

inhibitors of the cytochrome P ₄₅₀ isoenzyme CYP1A2, for example, fluvoxamine and ciprofloxacin: since anagrelide is mainly metabolized with the participation of this isoenzyme, drugs that suppress the activity of CYP1A2 are theoretically able to reduce the clearance of anagrelide;
inducers of the cytochrome P ₄₅₀ isoenzyme CYP1A2, for example, omeprazole: probably a decrease in the exposure of anagrelide; such a combination may require dose titration of the latter to compensate for the decrease in its exposure;
digoxin and warfarin: in vivo studies of their interaction with anagrelide in humans showed no mutual pharmacokinetic action.

Known effects of anagrelide on other drugs / drugs:

theophylline and other drugs with similar clearance: being a weak inhibitor of the CYP1A2 isoenzyme, anagrelide is theoretically able to interact with these drugs;
inotropic drugs (amrinone, milrinone, olprinone, enoximone, cilostazol): as a PDE III inhibitor, anagrelide can enhance the effect of these drugs with similar efficacy;
other drugs that inhibit or alter platelet function (acetylsalicylic acid): anagrelide, used in therapeutic doses recommended for ET therapy, can enhance their effects;
oral hormonal contraceptives: due to the fact that anagrelide causes intestinal dysfunction in some patients, this can lead to a decrease in the absorption of contraceptives and reduce their effectiveness.

Taking anagrelide simultaneously with food slows down its absorption, but does not have a clinically significant effect on its systemic exposure and bioavailability.

Anagrelide drug interaction study was conducted only in adult patients.

Analogs

Anagrelide analogs are Agrilin, Busulfan, Trombonorm, Hydrea, Thromboreductin.

Terms and conditions of storage

Store at temperatures up to 25 ° C in a place protected from light. Keep out of the reach of children.

The shelf life is 3 years.

Terms of dispensing from pharmacies

Dispensed by prescription.

Reviews about Anagrelide

Perhaps due to the fact that ET is one of the orphan (rare) diseases affecting a small part of the population, there are no reviews from patients about Anagrelide.

A case is described when a patient regularly took a drug for the treatment of ET for 12 years. Immediately after a 2-week break in therapy, her condition deteriorated significantly.

The price of Anagrelide in pharmacies

Since the drug is currently not available in pharmacies, the price of Anagrelide is unknown. The approximate cost of an analogue for the active ingredient, Thromboreductin, 5 mg capsules, 100 pcs. in the package is 51,150 rubles.

Maria Kulkes Medical journalist About the author

Education: First Moscow State Medical University named after I. M. Sechenov, specialty "General Medicine".

Information about the drug is generalized, provided for informational purposes only and does not replace the official instructions. Self-medication is hazardous to health!