akr-501 and Thrombocytopenia

akr-501 has been researched along with Thrombocytopenia* in 28 studies

Reviews

10 review(s) available for akr-501 and Thrombocytopenia

ArticleYear
Efficacy and Incidence of Treatment-Related Adverse Events of Thrombopoietin Receptor Agonists in Adults with Immune Thrombocytopenia: A Systematic Review and Network Meta-Analysis of Randomized Controlled Study.
    Acta haematologica, 2023, Volume: 146, Issue:3

    The aim of the study was to conduct a network meta-analysis to assess the efficacy and incidence of treatment-related adverse events (TRAEs) of eltrombopag, romiplostim, avatrombopag, recombinant human thrombopoietin (rhTPO), and hetrombopag for adult immune thrombocytopenia (ITP).. Randomized controlled trials (RCTs) of the five therapies from inception to June 1, 2022, were included. The efficacy outcome was the rate of platelet response, defined as the achievement of platelet counts above 50 × 109/L. Pairwise odds ratios (ORs) and 95% confidence intervals (CIs) were calculated. The surface under the cumulative ranking (SUCRA) was used to rank the included therapies for each outcome.. In total, 1,360 participants were analyzed in 14 eligible RCTs. All of the therapies showed a significantly better platelet response than the placebo, and avatrombopag (OR, 7.42; 95% CI: 1.74-31.69) and rhTPO (OR, 3.86; 95% CI: 1.62-9.18) were better than eltrombopag. Regarding TRAEs, no significant differences were found between patients receiving eltrombopag, romiplostim, and avatrombopag. Avatrombopag carried the highest platelet response rate with SUCRA value of 87.5, and carried the least TRAEs risk with SUCRA value of 37.0.. These findings indicated that avatrombopag appeared to be the optimal choice as the second-line therapy for adult ITP.

    Topics: Adult; Benzoates; Humans; Hydrazines; Incidence; Network Meta-Analysis; Purpura, Thrombocytopenic, Idiopathic; Randomized Controlled Trials as Topic; Receptors, Fc; Receptors, Thrombopoietin; Recombinant Fusion Proteins; Thrombocytopenia; Thrombopoietin

2023
Avatrombopag: A Review in Thrombocytopenia.
    Drugs, 2021, Volume: 81, Issue:16

    Avatrombopag (Doptelet

    Topics: Adult; Animals; Chronic Disease; Humans; Liver Diseases; Purpura, Thrombocytopenic, Idiopathic; Receptors, Thrombopoietin; Thiazoles; Thiophenes; Thrombocytopenia

2021
Avatrombopag for the management of thrombocytopenia in patients with chronic liver disease.
    Revista espanola de enfermedades digestivas, 2021, Volume: 113, Issue:2

    Severe thrombocytopenia (platelet count < 50 x 109/l) is the most frequent hematological disorder in patients with chronic liver disease, affecting 64-84 % of individuals with cirrhosis. The pathophysiological mechanisms that underlie thrombocytopenia are complex, but the reduction of thrombopoietin levels is considered to play a key role. Until recently, there was a continuous debate about the optimal management of patients with chronic liver disease and whether low platelet counts require a scheduled invasive procedure. Transfusion of platelet concentrates is considered to be the standard treatment, but has major limitations such as its short lifespan, limited efficacy and relevant adverse effects. Avatrombopag is an oral thrombopoietin receptor agonist that induces megakaryocytic proliferation and differentiation and platelet production. It has been approved by the Spanish Agency of Medicines and Health Products for the treatment of severe thrombocytopenia in adult patients with chronic liver disease before scheduled procedures, to decrease the risk of bleeding. Randomized trials have demonstrated that this agent is effective in maintaining platelet counts above 50 × 109/l over a period of more than two weeks, with a similar safety profile to the placebo. In this article, we review avatrombopag in the treatment of thrombocytopenia in patients with chronic liver disease. Furthermore, the main differences of this intervention in comparison to the previous standard of care therapy are discussed.

    Topics: Adult; Chronic Disease; Humans; Liver Diseases; Thiazoles; Thiophenes; Thrombocytopenia

2021
Thrombopoietin Receptor Agonists (TPO-RAs): Drug Class Considerations for Pharmacists.
    Drugs, 2021, Volume: 81, Issue:11

    The thrombopoietin receptor agonists (TPO-RAs) romiplostim, eltrombopag, avatrombopag, and lusutrombopag carry unique US Food and Drug Administration (US FDA)- and European Medicines Agency (EMA)-approved indications and may be used to increase platelet counts in a variety of conditions. Current indications for available TPO-RAs include treatment of chronic immune thrombocytopenia (ITP) in cases of insufficient response to prior treatment (avatrombopag, eltrombopag, romiplostim), management of thrombocytopenia in adult patients with chronic liver disease who are scheduled to undergo a procedure (avatrombopag, lusutrombopag), management of severe aplastic anemia (eltrombopag), and management of thrombocytopenia associated with interferon-based therapy for hepatitis C (eltrombopag). Across current indications, pharmacists can assist in stabilizing platelet counts and help to reduce large undulations commonly seen when starting, stopping, or transitioning between these agents. If therapy modifications may benefit the patient, pharmacists should discuss possible changes with the patient's treatment team or treating physician. When used for ITP, romiplostim, eltrombopag, and avatrombopag stimulate TPO receptors on hematopoietic stem cells (also known as c-Mpl, or CD110) to promote platelet production; however, romiplostim is the only TPO-RA that binds at the same site as endogenous TPO. These subtle mechanistic differences may explain why switching TPO-RA may be clinically advantageous in some situations. As pharmacists are called to counsel patients on TPO-RA use, a deep understanding of potential adverse events and management strategies, as well as appropriate monitoring, will increase the likelihood that patients meet their goals of therapy in the shortest timeframe. Other uses of TPO-RAs are also discussed in this review, including use following hematopoietic stem cell transplant, use in myelodysplastic syndrome, and use in chemotherapy-induced thrombocytopenia.

    Topics: Benzoates; Cinnamates; Dose-Response Relationship, Drug; Drug Monitoring; Health Knowledge, Attitudes, Practice; Humans; Hydrazines; Pharmacists; Platelet Count; Pyrazoles; Receptors, Fc; Receptors, Thrombopoietin; Recombinant Fusion Proteins; Thiazoles; Thiophenes; Thrombocytopenia; Thrombopoietin

2021
Thrombocytopenia in Chronic Liver Disease: New Management Strategies.
    Clinics in liver disease, 2020, Volume: 24, Issue:3

    Thrombocytopenia is common in advanced liver disease, and such patients frequently need invasive procedures. Numerous mechanisms for thrombocytopenia exist, including splenic sequestration and reduction of levels of the platelet growth factor thrombopoietin. Traditionally, platelet transfusions have been used to increase platelet counts before elective procedures, usually to a threshold of greater than or equal to 50,000/μL, but levels vary by provider, procedure, and specific patient. Recently, the thrombopoietin receptor agonists avatrombopag and lusutrombopag were studied and found efficacious for increasing platelet count in the outpatient setting for select patients with advanced liver disease who need a procedure.

    Topics: Chronic Disease; Cinnamates; Hemorrhage; Humans; Liver Diseases; Platelet Count; Platelet Transfusion; Receptors, Thrombopoietin; Risk Factors; Surgical Procedures, Operative; Thiazoles; Thiophenes; Thrombocytopenia; Thrombopoiesis

2020
Avatrombopag and lusutrombopag for thrombocytopenia in people with chronic liver disease needing an elective procedure: a systematic review and cost-effectiveness analysis.
    Health technology assessment (Winchester, England), 2020, Volume: 24, Issue:51

    There have been no licensed treatment options in the UK for treating thrombocytopenia in people with chronic liver disease requiring surgery. Established management largely involves platelet transfusion prior to the procedure or as rescue therapy for bleeding due to the procedure.. To assess the clinical effectiveness and cost-effectiveness of two thrombopoietin receptor agonists, avatrombopag (Doptelet. Systematic review and cost-effectiveness analysis.. Secondary care.. Severe thrombocytopenia (platelet count of < 50,000/µl) in people with chronic liver disease requiring surgery.. Lusutrombopag 3 mg and avatrombopag (60 mg if the baseline platelet count is < 40,000/µl and 40 mg if it is 40,000-< 50,000/µl).. Risk of platelet transfusion and rescue therapy or risk of rescue therapy only.. Systematic review including meta-analysis. English-language and non-English-language articles were obtained from several databases including MEDLINE, EMBASE and Cochrane Central Register of Controlled Trials, all searched from inception to 29 May 2019.. Model-based cost-effectiveness analysis.. From a comprehensive search retrieving 11,305 records, six studies were included. Analysis showed that avatrombopag and lusutrombopag were superior to no thrombopoietin receptor agonist in avoiding both platelet transfusion and rescue therapy or rescue therapy only, and mostly with a statistically significant difference (i.e. 95% confidence intervals not overlapping the point of no difference). However, only avatrombopag seemed to be superior to no thrombopoietin receptor agonist in reducing the risk of rescue therapy, although far fewer patients in the lusutrombopag trials than in the avatrombopag trials received rescue therapy. When assessing the cost-effectiveness of lusutrombopag and avatrombopag, it was found that, despite the success of these in avoiding platelet transfusions prior to surgery, the additional long-term gain in quality-adjusted life-years was very small. No thrombopoietin receptor agonist was clearly cheaper than both lusutrombopag and avatrombopag, as the cost savings from avoiding platelet transfusions were more than offset by the drug cost. The probabilistic sensitivity analysis showed that, for all thresholds below £100,000, no thrombopoietin receptor agonist had 100% probability of being cost-effective.. Some of the rescue therapy data for lusutrombopag were not available. There were inconsistencies in the avatrombopag data. From the cost-effectiveness point of view, there were several additional important gaps in the evidence required, including the lack of a price for avatrombopag.. Avatrombopag and lusutrombopag were superior to no thrombopoietin receptor agonist in avoiding both platelet transfusion and rescue therapy, but they were not cost-effective given the lack of benefit and increase in cost.. A head-to-head trial is warranted.. This study is registered as PROSPERO CRD42019125311.. This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in

    Topics: Bayes Theorem; Cinnamates; Clinical Trials as Topic; Cost-Benefit Analysis; End Stage Liver Disease; Humans; Models, Economic; Platelet Transfusion; Quality-Adjusted Life Years; Receptors, Thrombopoietin; Secondary Care; Technology Assessment, Biomedical; Thiazoles; Thiophenes; Thrombocytopenia

2020
New Small Molecule Drugs for Thrombocytopenia: Chemical, Pharmacological, and Therapeutic Use Considerations.
    International journal of molecular sciences, 2019, Jun-20, Volume: 20, Issue:12

    This review provides details about three small molecules that were recently approved by the FDA for the treatment of thrombocytopenia. The new treatments include lusutrombopag, avatrombopag, and fostamatinib. The first two drugs are orally active thrombopoietin receptor (TPO-R) agonists which are FDA-approved for the treatment of thrombocytopenia in adult patients with chronic liver disease who are scheduled to undergo a procedure. Fostamatinib is orally active prodrug that, after activation, becomes spleen tyrosine kinase (SYK) inhibitor. Fostamatinib is currently used to treat chronic and refractory immune thrombocytopenia in patients who have had insufficient response to previous treatment. Chemical structures, available dosage forms, recommended dosing, pharmacokinetics, results of toxicity studies in animals, most frequent adverse effects, significant outcomes of the corresponding clinical trials, and their use in specific patient populations are thoroughly described. Described also is a comparative summary of the different aspects of five currently available therapies targeting TPO-R or SYK for the treatment of thrombocytopenia.

    Topics: Aminopyridines; Animals; Cinnamates; Drug Development; Humans; Morpholines; Oxazines; Pyridines; Pyrimidines; Receptors, Thrombopoietin; Small Molecule Libraries; Syk Kinase; Thiazoles; Thiophenes; Thrombocytopenia

2019
Avatrombopag: First Global Approval.
    Drugs, 2018, Volume: 78, Issue:11

    Avatrombopag (Doptelet

    Topics: Chronic Disease; Drug Approval; Humans; Liver Diseases; Receptors, Thrombopoietin; Thiazoles; Thiophenes; Thrombocytopenia; United States; United States Food and Drug Administration

2018
Avatrombopag maleate for the treatment of periprocedural thrombocytopenia in patients with chronic liver disease.
    Drugs of today (Barcelona, Spain : 1998), 2018, Volume: 54, Issue:11

    Avatrombopag maleate (Doptelet; Dova Pharmaceuticals) is an oral, small-molecule second-generation thrombopoietin (TPO) receptor agonist under development for the treatment of thrombocytopenia. Recently approved by the U.S. Food and Drug Administration (FDA) for the treatment of periprocedural thrombocytopenia in patients with chronic liver disease on the basis of the results of two phase III trials, it is currently under investigation for treatment of immune thrombocytopenia (two randomized trials demonstrating efficacy have already been completed), chemotherapy-induced thrombocytopenia and perioperative thrombocytopenia in patients undergoing major surgical procedures. This review will evaluate the preclinical pharmacology, pharmacokinetics, clinical studies, safety, indications and drug interactions of avatrombopag, with a focus on its use for the treatment of periprocedural thrombocytopenia in patients with chronic liver disease.

    Topics: Animals; Chronic Disease; Drug Interactions; Hematologic Agents; Humans; Liver Diseases; Perioperative Period; Thiazoles; Thiophenes; Thrombocytopenia; Treatment Outcome

2018
Management of Thrombocytopenia in Chronic Liver Disease: Focus on Pharmacotherapeutic Strategies.
    Drugs, 2015, Volume: 75, Issue:17

    Thrombocytopenia (platelet count <150 × 10(9)/L) often complicates chronic liver disease, impeding optimal management of these patients. The prevalence of this manifestation ranges from 6% among non-cirrhotic patients with chronic liver disease to 70% among patients with liver cirrhosis. It has also been shown that the severity of liver disease is associated with both prevalence and level of thrombocytopenia. Its development is often multifactorial, although thrombopoietin is thought to be a major factor. The discovery of and ability to clone thrombopoietin led to new treatment opportunities for this clinical manifestation. This review discusses data on the three most important thrombopoietin receptor agonists: eltrombopag, avatrombopag, and romiplostim. Currently, only eltrombopag is approved for usage among patients with thrombocytopenia and chronic hepatitis C virus infection in order to initiate and maintain interferon-based antiviral treatment. Nevertheless, the optimal management of hematologic abnormalities among patients with chronic liver disease, and its risk for bleeding complications, is still a matter of discussion. Thrombocytopenia definitely contributes to hemostatic defects but is often counterbalanced by the enhanced presence of procoagulant factors. Therefore, a thorough assessment of the patient's risk for thrombotic events is essential when the use of thrombopoietin receptor agonists is considered among patients with chronic liver disease and thrombocytopenia.

    Topics: Benzoates; Chronic Disease; Disease Management; Hepatitis C, Chronic; Humans; Hydrazines; Liver Diseases; Pyrazoles; Receptors, Fc; Receptors, Thrombopoietin; Recombinant Fusion Proteins; Thiazoles; Thiophenes; Thrombocytopenia; Thrombopoietin

2015

Trials

6 trial(s) available for akr-501 and Thrombocytopenia

ArticleYear
Plasma gastric biomarker evaluation with avatrombopag dosing in patients with chronic immune thrombocytopenia in phase 3 trials.
    British journal of haematology, 2023, Volume: 202, Issue:4

    Topics: Humans; Platelet Count; Purpura, Thrombocytopenic, Idiopathic; Thiazoles; Thrombocytopenia

2023
Real-world use of avatrombopag in patients with chronic liver disease and thrombocytopenia undergoing a procedure.
    Medicine, 2023, Oct-06, Volume: 102, Issue:40

    The phase 4 observational cohort study assessed the effectiveness and safety of the thrombopoietin receptor agonist avatrombopag in patients with chronic liver disease (CLD) and thrombocytopenia undergoing a procedure. Patients with CLD may have thrombocytopenia, increasing the risk of periprocedural bleeding. Prophylactic platelet transfusions used to reduce this risk have limitations including lack of efficacy and transfusion-associated reactions. Prophylactic thrombopoietin receptor agonists have been shown to increase platelet counts and decrease platelet transfusions. Effectiveness was assessed by change from baseline in platelet count and proportion of patients needing a platelet transfusion. Safety was assessed by monitoring adverse events (AEs). Of 50 patients enrolled, 48 were unique patients and 2 patients were enrolled twice for separate procedures. The mean (standard deviation) change in platelet count from baseline to procedure day was 41.1 × 109/L (33.29 × 109/L, n = 38), returning to near baseline at the post-procedure visit (change from baseline -1.9 × 109/L [15.03 × 109/L], n = 11). The proportion of patients not requiring a platelet transfusion after baseline and up to 7 days following the procedure was 98% (n = 49). Serious AEs were infrequent (n = 2 [4%]). No treatment-emergent AEs were considered related to avatrombopag. There were 2 mild bleeding events, no thromboembolic events or deaths, and no patients received rescue procedures (excluding transfusions). This study found that in a real-world setting, treatment with avatrombopag was well tolerated, increased the mean platelet count by procedure day, and reduced the need for intraoperative platelet transfusions in patients with CLD and thrombocytopenia.

    Topics: Anemia; Humans; Liver Diseases; Platelet Count; Receptors, Thrombopoietin; Thrombocytopenia

2023
Avatrombopag for chemotherapy-induced thrombocytopenia in patients with non-haematological malignancies: an international, randomised, double-blind, placebo-controlled, phase 3 trial.
    The Lancet. Haematology, 2022, Volume: 9, Issue:3

    Chemotherapy-induced thrombocytopenia is common and causes chemotherapy dose reductions or treatment delays, bleeding, and suboptimal oncological outcomes. We aimed to evaluate avatrombopag, a thrombopoietin receptor agonist that increases platelet counts, in patients with non-haematological cancer and platelet counts lower than 50 ×10. In this randomised, double-blind, placebo-controlled, phase 3 study, patients aged 18 years or older at 71 hospitals or cancer treatment centres in China, Hungary, Poland, Russia, Serbia, Ukraine, and the USA and with ovarian, bladder, or lung cancer receiving chemotherapy who had severe thrombocytopenia were randomly assigned (2:1) to oral avatrombopag 60 mg or oral placebo once daily given 5 days before and after chemotherapy, with randomisation stratified by number of chemotherapy drugs used. Patients, investigators, and data collectors were masked to group allocation. Eligibility required two previous lines of chemotherapy or fewer, an ECOG performance status of 2 or less, and no previous history of chemotherapy-induced thrombocytopenia. The composite primary endpoint was the proportion of responders not requiring platelet transfusion or either a 15% or more chemotherapy dose reduction or a 4-day or more chemotherapy delay due to thrombocytopenia following study treatment until the start of the subsequent cycle. Analyses were done on the intention-to-treat and per protocol populations. Safety was analysed in all patients who received at least one dose of avatrombopag. The trial is registered with ClinicalTrials.gov, NCT03471078, and has been completed.. Between Oct 12, 2018, and June 28, 2020, 122 patients were enrolled and randomly assigned to receive avatrombopag (n=82) or placebo (n=40). Median follow-up was 31 days (IQR 22-61). Similar proportions of patients reached the primary endpoint in the avatrombopag and placebo groups (intention-to-treat: 57 [70%, 95% CI 58-79] of 82 vs 29 [73%, 95% CI 56-85] of 40; difference -3·0% (95% CI -21·6 to 15·6); p=0·72; per protocol: 51 [85%, 95% CI 73-93] of 60 vs 27 [84%, 95% CI 67-95] of 32; 0·6% (95% CI -20·8 to 22·1); p=0·96). 15 (18%) of 82 patients had serious adverse events in the avatrombopag group and eight (20%) of 40 in the placebo group, of which thrombocytopenia was most common (4 [5%] of 82 and 4 [10%] of 40 patients). Common grade 3-4 treatment-emergent adverse events were neutropenia (22 [27%] of 82 and 16 [40%] of 40 patients), leukopenia (19 [23%] of 82 and 5 [13%] of 40), anaemia (16 [20%] of 82 and 9 [23%] of 40), and thrombocytopenia (16 [20%] of 82 and 14 [35%] of 40). Most adverse events were considered unrelated to study drug. No treatment-related deaths were reported.. In this population of patients with non-haematological malignancies who are relatively chemotherapy naive, chemotherapy-induced thrombocytopenia treatment outcomes were similar between the avatrombopag and placebo groups. Given its safety and ability to augment platelet counts in patients with chemotherapy-induced thrombocytopenia, evaluation of avatrombopag in populations with more persistent chemotherapy-induced thrombocytopenia is warranted.. Dova Pharmaceuticals, a Sobi company.

    Topics: Adolescent; Anemia; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Double-Blind Method; Humans; Neutropenia; Thiazoles; Thiophenes; Thrombocytopenia; Treatment Outcome

2022
Avatrombopag, an oral thrombopoietin receptor agonist: results of two double-blind, dose-rising, placebo-controlled Phase 1 studies.
    British journal of haematology, 2018, Volume: 183, Issue:3

    Topics: Adolescent; Adult; Aged; Double-Blind Method; Female; Humans; Male; Middle Aged; Receptors, Thrombopoietin; Thiazoles; Thiophenes; Thrombocytopenia

2018
Avatrombopag increases platelet count but not platelet activation in patients with thrombocytopenia resulting from liver disease.
    Journal of thrombosis and haemostasis : JTH, 2018, Volume: 16, Issue:12

    Essentials Thrombopoietin (TPO) lowers the threshold for platelet activation. TPO receptor agonists (RAs) may therefore also lead to platelet activation. Patients with chronic liver disease and thrombocytopenia participated in a randomized trial. The TPO-RA avatrombopag did not increase platelet activation in vivo or reactivity in vitro.. The thrombopoietin (TPO) receptor agonist (TPO-RA) avatrombopag has recently been Food and Drug Administration-approved for the treatment of thrombocytopenia in patients with chronic liver disease (CLD) scheduled for a procedure. The TPO receptor c-mpl is expressed on the platelet surface, and TPO lowers the threshold for platelet activation. TPO-RAs may therefore also lead to platelet activation.. To evaluate the effects of avatrombopag on platelet activation.. CLD patients with thrombocytopenia participated in a randomized, double-blind, placebo-controlled, parallel-group study. No patient received a platelet transfusion within 10 days of study blood draws. Platelet activation was evaluated with whole blood flow cytometry (which, unlike other methods, is accurate in thrombocytopenic samples).. Avatrombopag, but not placebo, increased platelet counts. As measured by platelet surface P-selectin and activated glycoprotein IIb-IIIa: (i) the numbers of circulating activated platelets were not increased in avatrombopag-treated patients as compared with placebo-treated patients; and (ii) platelet reactivity to low and high concentrations of ADP and thrombin receptor-activating peptide was not increased in avatrombopag-treated patients as compared with placebo-treated patients.. In this randomized, double-blind, placebo-controlled, parallel-group study of CLD patients with thrombocytopenia, avatrombopag increased platelet counts but did not increase platelet activation in vivo or platelet reactivity in vitro.

    Topics: Blood Platelets; Chronic Disease; Double-Blind Method; Hematologic Agents; Humans; Liver Diseases; Platelet Activation; Platelet Count; Thiazoles; Thiophenes; Thrombocytopenia; Thrombopoiesis; Time Factors; Treatment Outcome; United States

2018
Phase II study of avatrombopag in thrombocytopenic patients with cirrhosis undergoing an elective procedure.
    Journal of hepatology, 2014, Volume: 61, Issue:6

    This is a phase II multicentre study to investigate the efficacy and safety of avatrombopag (E5501), an investigational second-generation thrombopoietin receptor agonist, administered one week prior to elective procedures in patients with thrombocytopenia secondary to cirrhosis.. Adults with cirrhosis and platelet counts ⩾10 to ⩽58×10(9)/L were randomized to placebo or avatrombopag in two sequential cohorts. Cohort A: placebo vs. one of 3 different doses (100mg loading dose followed by 20, 40, or 80 mg/day on days 2-7) of a first-generation avatrombopag formulation. Cohort B: placebo vs. one of 2 different doses (80 mg loading dose followed by 10 mg/day for days 2-7, or 20mg/day for days 2-4) of a second-generation avatrombopag formulation. Primary end point was achievement of a platelet increase of ⩾20×10(9)/L from baseline and >50×10(9)/L at least once during days 4-8.. A total of 130 patients were randomized: 93 patients (51, cohort A; 42, cohort B) to avatrombopag and 37 (16, cohort A; 21 cohort B) to placebo. The primary end point was achieved by 49.0% of treated patients in cohort A and 47.6% in cohort B compared to 6.3% and 9.5% of controls; a dose response was seen. Each avatrombopag regimen had a higher proportion of responders compared with their respective cohort placebo arms (p<0.01), except for the 100/40 mg group in cohort A (p=0.17). The most common adverse events were nausea, fatigue, and headache. One patient in the (100/80) avatrombopag group, without a Doppler assessment at screening was diagnosed with portal vein thrombosis during post-treatment follow-up.. In this study avatrombopag was generally well-tolerated and increased platelet counts in patients with cirrhosis undergoing elective invasive procedures.

    Topics: Blood Platelets; Dose-Response Relationship, Drug; Double-Blind Method; Elective Surgical Procedures; Fatigue; Female; Headache; Humans; Incidence; Liver Cirrhosis; Male; Middle Aged; Nausea; Platelet Count; Receptors, Thrombopoietin; Risk Factors; Thiazoles; Thiophenes; Thrombocytopenia

2014

Other Studies

12 other study(ies) available for akr-501 and Thrombocytopenia

ArticleYear
Additional efficacy analysis of avatrombopag phase III data for the treatment of adults with immune thrombocytopenia.
    Platelets, 2023, Volume: 34, Issue:1

    Topics: Adult; Humans; Platelet Count; Purpura, Thrombocytopenic, Idiopathic; Receptors, Thrombopoietin; Recombinant Fusion Proteins; Thrombocytopenia; Thrombopoietin

2023
Efficacy and safety of avatrombopag for thrombocytopenia following allogeneic hematopoietic stem cell transplantation: A real-world data evaluation on 14 cases.
    Zhong nan da xue xue bao. Yi xue ban = Journal of Central South University. Medical sciences, 2023, Mar-28, Volume: 48, Issue:3

    Thrombocytopenia following allogeneic hematopoietic stem cell transplantation (allo-HSCT) is a common and serious complication that leads to an increased risk of bleeding and poor prognosis. Traditional strategies consist of platelet transfusion, glucocorticoid therapy, intravenous human immunoglobulin, recombinant human thrombopoietin injection, and CD34. Fourteen patients with thrombocytopenia after allo-HSCT underwent avatrom-bopag treatment from September 2020 to September 2021 were retrospectively studied. Of these patients, 8 patients had delayed platelet engraftment (DPE) and 6 cases had secondary failure of platelet recovery (SFPR). The efficacy and safety of the treatment and the survival of the patients were assessed.. The median treatment time of avatrombopag was 34 days, and no patients stopped treatment due to adverse reactions or drug intolerance. Compared with the treatment before, the levels of platelet count, megakaryocytes, and hemoglobin in patients were significantly increased (. Avatrombopag is effective on increasing platelet counts in patients with thrombocytopenia after allo-HSCT, with a good safety profile. It is a suitable therapeutic option for thrombocytopenia after allo-HSCT.

    Topics: Blood Platelets; Hematopoietic Stem Cell Transplantation; Humans; Retrospective Studies; Thrombocytopenia

2023
Avatrombopag increased platelet count in a patient with chronic immune thrombocytopenia refractory to multiple lines of treatment.
    Blood coagulation & fibrinolysis : an international journal in haemostasis and thrombosis, 2023, Jul-01, Volume: 34, Issue:5

    We present a case of a 30-year-old man suffering from chronic refractory immune thrombocytopenia (ITP) from early childhood. The patient was treated with all the therapeutic methods available in Poland, without platelet response: corticosteroids, intravenous immunoglobulins, splenectomy, cyclophosphamide, vinblastine, azathioprine, mycophenolate mofetil, rituximab, ciclosporin A, romiplostim, and eltrombopag. He continued to function persistently with deep thrombocytopenia, symptoms of hemorrhagic diathesis, and one episode of spontaneous subarachnoid bleeding. In April 2022, at the age of 29, the patient received avatrombopag. Within 4 weeks of starting avatrombopag 20 mg daily for 2 weeks and then 40 mg daily, he reached a platelet (PLT) count of 67 x 10 9 /l. In the next month, platelets fell below 30 x 10 9 /l, but subsequently the count increased to 47 x 10 9 /l, then to 52 x 10 9 /l, and remained stable. The symptoms of cutaneous hemorrhage diathesis have resolved completely since avatrombopag was introduced and did not reappear despite the decrease in PLT count.

    Topics: Adult; Child, Preschool; Humans; Male; Platelet Count; Purpura, Thrombocytopenic, Idiopathic; Thiazoles; Thrombocytopenia

2023
Avatrombopag improves thrombocytopenia in MYH9-related disorder following eltrombopag treatment failure.
    Platelets, 2022, Nov-17, Volume: 33, Issue:8

    MYH9-related disorder (MYH9-RD) is autosomal dominant thrombocytopenia caused by mutations in the

    Topics: Benzoates; Hearing Loss, Sensorineural; Humans; Hydrazines; Male; Molecular Motor Proteins; Mutation; Myosin Heavy Chains; Pyrazoles; Thiazoles; Thiophenes; Thrombocytopenia; Treatment Failure

2022
An evaluation of avatrombopag for the treatment of thrombocytopenia.
    Expert opinion on pharmacotherapy, 2021, Volume: 22, Issue:3

    Topics: Humans; Liver Diseases; Purpura, Thrombocytopenic, Idiopathic; Thiazoles; Thiophenes; Thrombocytopenia

2021
Second-generation thrombopoietin receptor agonists: New players in the management of cirrhotic patients undergoing therapeutic endoscopy?
    Digestive and liver disease : official journal of the Italian Society of Gastroenterology and the Italian Association for the Study of the Liver, 2021, Volume: 53, Issue:10

    Topics: Cinnamates; Endoscopy; Humans; Liver Cirrhosis; Receptors, Thrombopoietin; Surveys and Questionnaires; Thiazoles; Thiophenes; Thrombocytopenia

2021
Clinical outcomes in eight patients with immune thrombocytopenia each treated with the three approved thrombopoietin receptor agonists.
    American journal of hematology, 2021, 10-01, Volume: 96, Issue:10

    Topics: Adult; Aged; Benzoates; Female; Humans; Hydrazines; Male; Middle Aged; Pyrazoles; Receptors, Fc; Receptors, Thrombopoietin; Recombinant Fusion Proteins; Thiazoles; Thiophenes; Thrombocytopenia; Thrombopoietin; Treatment Outcome

2021
Avatrombopag Optimizes Response to Niraparib by Managing Thrombocytopenia Associated with Poly-ADP Ribose Polymerase (PARP) Inhibition in Ovarian Cancer and Breast Cancer: A Case Series.
    The American journal of case reports, 2020, Nov-16, Volume: 21

    BACKGROUND Thrombocytopenia is a potentially treatment-limiting adverse event of particular interest with the PARP inhibitor niraparib. This adverse event may necessitate niraparib dose reduction or treatment discontinuation, resulting in suboptimal treatment outcomes. Here, we report on niraparib dose optimization in 2 patients with breast cancer and 4 patients with ovarian cancer through concurrent administration of the thrombopoietin receptor stimulating agent avatrombopag to mitigate thrombocytopenia, enabling niraparib reescalation and improved clinical response. CASE REPORT Three of 6 patients received niraparib 300 mg daily, the highest recommended dose, for a sustained period. Avatrombopag therapy enabled niraparib dose escalation that led to reductions in biomarkers associated with disease progression. Before initiation of avatrombopag, increases in CA-125 levels, a marker for ovarian cancer, were observed in association with niraparib dose interruption, and in 2 patients with ovarian cancer CA-125 levels fell in response to niraparib dose escalation enabled by concurrent avatrombopag therapy. Further, in 2 patients with metastatic breast cancer, intracranial response was observed in association with avatrombopag-enabled niraparib therapy. In 1 patient with metastatic breast cancer, niraparib induced an intracranial response, while previous use of talazoparib had not, confirming preclinical findings of superior blood-brain-barrier penetrance with niraparib. CONCLUSIONS Avatrombopag is currently approved for use in chronic immune thrombocytopenia and thrombocytopenia associated with chronic liver disease in patients undergoing a surgical procedure. A clinical trial of avatrombopag for chemotherapy-induced thrombocytopenia is ongoing. Preliminary results in these 6 patient cases demonstrate the need for a confirmatory trial of avatrombopag for optimizing the dose of niraparib.

    Topics: Adenosine Diphosphate Ribose; Breast Neoplasms; Female; Humans; Indazoles; Ovarian Neoplasms; Piperidines; Poly(ADP-ribose) Polymerase Inhibitors; Poly(ADP-ribose) Polymerases; Thiazoles; Thiophenes; Thrombocytopenia

2020
What Did We Learn From the ADAPT Trials?
    Gastroenterology, 2019, Volume: 156, Issue:3

    Topics: Humans; Liver Diseases; Platelet Transfusion; Thiazoles; Thiophenes; Thrombocytopenia

2019
Population Pharmacokinetic/Pharmacodynamic Analyses of Avatrombopag in Patients With Chronic Liver Disease and Optimal Dose Adjustment Guide With Concomitantly Administered CYP3A and CYP2C9 Inhibitors.
    Journal of clinical pharmacology, 2018, Volume: 58, Issue:12

    Topics: Adolescent; Adult; Aged; Aged, 80 and over; Computer Simulation; Cytochrome P-450 CYP2C9 Inhibitors; Cytochrome P-450 CYP3A Inhibitors; Dose-Response Relationship, Drug; Drug Interactions; End Stage Liver Disease; Female; Humans; Male; Middle Aged; Models, Biological; Thiazoles; Thiophenes; Thrombocytopenia; Young Adult

2018
First Drug Approved to Reduce Bleeding Risk During Medical Procedures in Patients with Chronic Liver Disease.
    The American journal of nursing, 2018, Volume: 118, Issue:9

    Topics: Drug Approval; End Stage Liver Disease; Humans; Receptors, Thrombopoietin; Thiazoles; Thiophenes; Thrombocytopenia

2018
AKR-501 (YM477) in combination with thrombopoietin enhances human megakaryocytopoiesis.
    Experimental hematology, 2008, Volume: 36, Issue:10

    AKR-501 (YM477) is an orally active thrombopoietin (TPO) receptor agonist that mimics the biological effect of TPO in vitro and in vivo. Here, we report that AKR-501 in combination with TPO has additive effect on megakaryocytopoiesis.. Granulocyte colony-stimulating factor-mobilized human peripheral blood CD34+ cells were cultured with AKR-501, TPO, or a combination of the two in serum-free liquid culture system. The numbers of hematopoietic progenitor cells, megakaryocytic progenitor cells, and megakaryocytes were measured using flow cytometry. Further, the effect of AKR-501 on TPO binding to TPO receptor was examined.. Both AKR-501 and TPO alone increased the number of megakaryocytes, and the maximum activities of AKR-501 and TPO were similar. Interestingly, in the presence of TPO concentrations producing maximal stimulation, the addition of AKR-501 increased the number of megakaryocytes to about 200% of that generated with TPO only. In the time course experiment, the combination of AKR-501 and TPO augmented the numbers of hematopoietic progenitor cells and colony-forming unit in culture in the early stages. Thus, the combination of AKR-501 and TPO enhanced not only the differentiation into megakaryocytes, but also the expansion of human hematopoietic progenitor cells. Further, AKR-501 did not inhibit TPO binding to the TPO receptor. This result indicated the possibility that AKR-501 and TPO may act simultaneously on the TPO receptor, and this could be responsible for their additive effect of on megakaryocytopoiesis.. This study suggests that AKR-501 would be useful for the treatment of thrombocytopenia even at high plasma levels of endogenous TPO following chemotherapy.

    Topics: Antigens, CD; Antigens, CD34; Blood Platelets; Cells, Cultured; Colony-Forming Units Assay; Flow Cytometry; Humans; Piperidines; Receptors, Thrombopoietin; Thiazoles; Thiophenes; Thrombocytopenia; Thrombopoiesis; Thrombopoietin

2008