Use our structured and evidence-based datasets to unlock new insights and accelerate drug research. Clin Gastroenterol Hepatol. Avatrombopag mimics the biological activities of TPO. In the phase III ADAPT studies, a short course of avatrombopag was superior to placebo in increasing the proportion of patients who did not require a platelet transfusion or rescue procedure for bleeding (Sect. Consider reducing the dosage of P-gp substrates, where minimal concentration changes may lead to serious or life-threatening toxicities.Serious - Use Alternative (1)tucatinib will increase the level or effect of avatrombopag by affecting hepatic/intestinal enzyme CYP3A4 metabolism. The above information is provided for general 14 CLINICAL STUDIES . They include a summary of their mechanisms of action and clinical trial results. 2013;98(1):1023. commonly, these are "non-preferred" brand drugs. Avoid concomitant use of tucatinib with CYP3A substrates, where minimal concentration changes may lead to serious or life-threatening toxicities. The excretion of Acamprosate can be decreased when combined with Avatrombopag. Avatrombopag is metabolized primarily by cytochrome P450 (CYP) 2C9 and CYP3A, with unchanged drug and metabolites excreted mostly in faeces (88%), and no metabolites detected in plasma. Pharmacokinetic/pharmacodynamic drugdrug interactions of avatrombopag when coadministered with dual or selective CYP2C9 and CYP3A interacting drugs. For 2 weeks after abametapir application, avoid taking drugs that are CYP3A4 substrates. Use Caution/Monitor. Coadministration of avatrombopag with a moderate or strong dual CYP2C9/3A4 inhibitor requires a decreased avatrombopag starting dose to 20 mg PO TID. If you log out, you will be required to enter your username and password the next time you visit. Avatrombopag has an estimated mean volume of distribution (%CV) of 180 L (25%) Label. Refer to drug monograph for specific recommendations. 2006;23(8):105565. Obtain platelet count weekly for 4 weeks following discontinuation of therapy. Monitor Closely (1)cenobamate will decrease the level or effect of avatrombopag by affecting hepatic/intestinal enzyme CYP3A4 metabolism. sotorasib will decrease the level or effect of avatrombopag by P-glycoprotein (MDR1) efflux transporter. Coadministration may increase risk for adverse effects of CYP3A4 substrates. For 2 weeks after abametapir application, avoid taking drugs that are CYP3A4 substrates. Complete all 5 days of dosing if treating chronic liver disease-associated thrombocytopenia. Avatrombopag maleate increases platelet production by activating the intracellular signaling system, and promotes production of platelets and megakaryocytes from hemopoietic precursor cells. Use Caution/Monitor. Doptelet (avatrombopag): US prescribing information. Avatrombopag (Doptelet) is an orally administered second generation thrombopoietin receptor agonist (TPO-RA) approved for the treatment of primary chronic immune thrombocytopenia (ITP) in adult patients who are refractory or have an unsatisfactory response to other treatments, as well as for the treatment of thrombocytopenia in adult patients with chronic liver disease (CLD) scheduled to undergo an invasive procedure. 2009;82(4):24754. Istradefylline 40 mg/day increased peak levels and AUC of CYP3A4 substrates in clinical trials. The mean (%CV) of the clearance of avatrombopag is estimated to be 6.9 L/hr (29%) Label. This information is not specific medical advice and does not replace information you receive from the healthcare provider. Increased Megakaryocte Cell Production. If unable to avoid coadministration of belzutifan with sensitive CYP3A4 substrates, consider increasing the sensitive CYP3A4 substrate dose in accordance with its prescribing information. commonly, these are generic drugs. Modify Therapy/Monitor Closely. The studies suggest 25 that CYP2C is a predominant enzyme in the metabolism of avatrombopag, and based on this knowledge, dose adjustment is advised with concomitant use of fluconazole. 2018;93(7):92130. Wojciechowski P, Wilson K, Pochopien M, et al. Article Review article: thrombocytopenia in chronic liver disease and pharmacologic treatment options. In vitro, avatrombopag induced proliferation of human thrombopoietin receptor-expressing murine Ba/F3 cells in a concentration-dependent manner (EC50 3.3nmol/L), with maximal activity similar to that of recombinant human thrombopoietin (rhTPO). The excretion of Allopurinol can be decreased when combined with Avatrombopag. When treating ITP, reduce starting dose of avatrombopag to 20 mg PO 3 times weekly when used concomitantly with mifepristone; in patients starting mifepristone while receiving avatrombopag, monitor platelet counts and adjust avatrombopag dose as necessary; coadministration of avatrombopag with a moderate or strong dual CYP2C9/3A4 inhibitor requires a decreased avatrombopag starting dose. Refer to drug monograph for specific recommendations. The incidence of treatment-emergent adverse events considered to be treatment-related was 11.3% in the avatrombopag 60mg/day cohort versus 17.6% with placebo, and 7.0% in the avatrombopag 40mg/day cohort versus 6.2% with placebo. Management: Management of this interaction varies based on avatrombopag indication. Wait 2 weeks to assess the effects of this regimen and any subsequent dose adjustments. Accessed 17 Sep 2021. Slichter SJ, Davis K, Enright H, et al. [Google Scholar] 22. Tell your doctor if any of these symptoms are severe or do not go away: extreme tiredness headache nosebleeds or gum bleeding joint pain Some side effects can be serious. This material is provided for educational purposes only and is not intended for medical advice, diagnosis, or treatment. Avatrombopag is an orally bioavailable, small molecule TPO receptor agonist that stimulates proliferation and differentiation of megakaryocytes from bone marrow progenitor cells, resulting in an increased production of platelets. Afdhal N, McHutchison J, Brown R, et al. This effect was not observed with istradefylline 20 mg/day. When treating ITP, coadministration of avatrombopag with a moderate or strong dual CYP2C9/3A4 inducer requires an increased avatrombopag starting dose. Massoud OI, Zein NN. Blood. American Society of Hematology 2019 guidelines for immune thrombocytopenia. Refer to drug monograph for specific recommendations. Avoid or Use Alternate Drug. If use is unavoidable, refer to the prescribing information of the P-gp substrate for dosage modifications. Avatrombopag was superior to placebo in terms of the cumulative mean number of weeks of platelet response (defined as a platelet count 50109/L) without needing rescue therapy (primary endpoint; 12 weeks vs 0.1 weeks [p<0.0001]). 6,9. Article Use Caution/Monitor. Avoid or Use Alternate Drug. Mechanism of action Avatrombopag is an orally bioavailable, small molecule thrombopoietin (TPO) receptor agonist that stimulates proliferation and differentiation of megakaryocytes from bone marrow progenitor cells resulting in an increased production of platelets. Sub-analysis of data from patients participating in ADAPT-1 and 2 found that the efficacy of avatrombopag was not affected by bleeding risk when procedures were divided according to low (paracentesis, endoscopy, colonoscopy), moderate (liver biopsy, ethanol ablation, chemoembolization for HCC) or high (dental, transjugular intrahepatic portosystemic shunt [TIPS], laparoscopy, radio-ablation, vascular catheterization) risk of bleeding. All authors contributed to the review and are responsible for the article content. J Hepatol. Accessed 17 Sep 2021. Avatrombopag is a substrate of cytochrome P450 (CYP) 2C9 and CYP3A. Chronic liver disease-associated thrombocytopenia: Treatment of thrombocytopenia in adult patients with chronic liver disease who are scheduled to undergo a procedure. All patients: Monitor for signs/symptoms of thromboembolism. In the double-blind, placebo-controlled, phase 3 trial, investigators set out to examine the safety and efficacy of avatrombopag in patients with chemotherapy-induced thrombocytopenia who are. It is administered orally as avatrombopag maleate, its salt form 11. Avoid concomitant use of tucatinib with CYP3A substrates, where minimal concentration changes may lead to serious or life-threatening toxicities. The serum concentration of Avatrombopag can be increased when it is combined with Abrocitinib. In a pooled pharmacogenomic analysis, when compared to subjects wild-type for CYP2C9 (normal metabolizers), subjects heterozygous for CYP2C9 loss-of-function polymorphisms (intermediate metabolizers) experienced ~1.4-fold higher exposure, and subjects homozygous for CYP2C9 loss-of-function polymorphisms (poor metabolizers) had ~2-fold higher exposure. Phase II study of avatrombopag in thrombocytopenic patients with cirrhosis undergoing an elective procedure. When treating ITP, coadministration of avatrombopag with a moderate or strong dual CYP2C9/3A4 inducer requires an increased avatrombopag starting dose. After a stable platelet count has been achieved, platelet counts should be obtained at least monthly. If you experience any of these symptoms call your doctor immediately: swollen, painful, red, or tender leg The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. 4.1), with a second phase III study comparing avatrombopag to eltrombopag unfortunately terminated before any meaningful conclusions could be drawn. 2014;123(25):388794. Adjust dosage of CYP2C9 substrates, if clinically indicated. If concomitant use unavoidable, reduce the P-gp substrate dosage if recommended in its approved product labeling. Monitor Closely (1)mifepristone will increase the level or effect of avatrombopag by affecting hepatic/intestinal enzyme CYP3A4 metabolism. In vivo in nonobese diabetic/severe combined immunodeficiency mice transplanted with human fetal liver CD34+ cells, oral administration of avatrombopag produced a dosedependent increase in human platelet count [10]. We review the mechanism of action, safety and efficacy of fostmatinib in 2 randomized controlled trials in North America, Australia and Europe (FIT1 . 5.2). Chronic treatment with fostamatinib has demonstrated efficacy in studies in patients who had nearly all received 23 previous therapies [24] but its role as second-line treatment has not been fully established [2]. Platelet count >400,000/mm3: Withhold avatrombopag and increase platelet monitoring to twice per week; when platelet count is <150,000/mm3, reinitiate avatrombopag with the dose decreased one dose level. Monitor Closely (1)belzutifan will decrease the level or effect of avatrombopag by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Management: Management of this interaction varies based on avatrombopag indication. Avoid or Use Alternate Drug. Share cases and questions with Physicians on Medscape consult. Al-Samkari H, Jiang D, Gernsheimer T, et al. ribociclib will increase the level or effect of avatrombopag by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Descriptions. + 46 733 666 599. paula.treutiger@sobi.com. PubMed Refer to drug monograph for specific recommendations. [5] It is a thrombopoietin receptor agonist. 2020. https://www.nice.org.uk/guidance/ta626. Swedish Orphan Biovitrum. When treating ITP, coadministration of avatrombopag with a moderate or strong dual CYP2C9/3A4 inducer requires an increased avatrombopag starting dose. Management of thrombocytopenia in advanced liver disease. Adverse reactions occurring in more than one patient that required discontinuation of avatrombopag included headache, occurring in two patients (1.6%) [7]. Avoid coadministration with sensitive CYP3A4 substrates with a narrow therapeutic index. Qamar AA, Grace ND, Groszmann RJ, et al. World J Radiol. 2019;3(22):3780817. The onset of the platelet count increase was noted within 3 to 5 days of the start of a 5-day treatment course, with the highest level of effect measured after 10 to 13 days. Refer to drug monograph for specific recommendations. 2022 Springer Nature Switzerland AG. Other side effects of this drug: Talk with your doctor right away if you have any of these signs of: Note: This is not a comprehensive list of all side effects. EU summary of the risk management plan for Doptelet. Diclofenac inhibits cyclooxygenase-1 and -2, the enzymes responsible for production of prostaglandin (PG) G 2 which is the precursor to other PGs. Bussel JB, Kuter DJ, Aledort LM, et al. Fukushima-Shintani M, Suzuki K, Iwatsuki Y, et al. Blood Adv. stomach (abdominal) pain or tenderness. Monitor Closely (1)fosphenytoin will decrease the level or effect of avatrombopag by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Available data indicate the risk of bleeding in patients with platelet counts 50109/L undergoing invasive procedures is minimal; however, the risk of bleeding in patients with more severe thrombocytopenia (platelet count 20109/L) is unclear. The effect of transjugular intrahepatic portosystemic shunt on platelet counts in patients with liver cirrhosis. Terrault N, Chen YC, Izumi N, et al. Arterial and venous thrombotic events have occurred in patients with chronic immune thrombocytopenia. Modify Therapy/Monitor Closely. Coadministration of avatrombopag with a moderate or strong dual CYP2C9/3A4 inhibitor requires a decreased avatrombopag starting dose to 20 mg PO TID. Avatrombopag also promoted megakaryocyte differentiation from human cord blood CD34+ cells in a concentration-dependent manner (EC50 25.0nmol/L), with maximum activity similar to that of rhTPO. Modify Therapy/Monitor Closely. Treatment for ITP should aim to improve platelet count such that the risk of bleeding is reduced with minimal treatment-related adverse events [5]. Refer to manufacturer recommendations. Monitor or titrate P-gp substrate dose if coadministered. Epub 2014 May 6. The content offered on Treatable.org is intended for informational purposes only and not as medical advice. Partial splenic artery embolization in cirrhotic patients. Incidence, prevalence, and clinical significance of abnormal hematologic indices in compensated cirrhosis. Refer to drug monograph for specific recommendations. Add these foods to your everyday eating plan. 2018;58(12):162938. Epub 2016 Oct 9. Splenectomy is effective but is an invasive procedure associated with a life-long risk of complications. In the phase III study, the overall incidence of treatment-emergent adverse events was 96.9% (31 of 32 patients) in avatrombopag recipients compared to 58.8% (10 of 17 patients) with placebo; however, no clinically important difference was observed when incidence rates were adjusted for exposure (4.3% per patient-week with avatrombopag vs 6.6% per patient-week with placebo) [15]. J Clin Pharmacol. Patients who had a durable response in the double-blind phase had response at 60.1% of the extension phase visits. shortness of breath. rifapentine will decrease the level or effect of avatrombopag by affecting hepatic/intestinal enzyme CYP3A4 metabolism. voxelotor will increase the level or effect of avatrombopag by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Dosage adjustment for concomitant therapy with moderate or strong dual inhibitors of CYP2C9 and CYP3A4 in chronic immune thrombocytopenia: Initial: 20 mg 3 times per week. NCT01433978. The mean plasma elimination half-life (%CV) of Avalet 20 mg is approximately 19 hours (19%). Gangireddy VG, Kanneganti PC, Sridhar S, et al. View avatrombopag information, including dose, uses, side-effects, pregnancy, breast feeding, monitoring requirements and drug action. Davis Drug Guide PDF. Coadministration of a single 20mg dose of avatrombopag with the dual CYP2C9 and CYP3A inducer rifampin was associated with a 0.5-fold decrease in AUC and an approximate halving of t, although this did not have a clinically relevant effect on platelet count [14]. Lm, et al on Treatable.org is intended for informational purposes only not. Aa, Grace ND, Groszmann RJ, et al hemopoietic precursor cells by P-glycoprotein ( MDR1 ) efflux...., diagnosis, or treatment effective but is an invasive procedure associated a! 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Not replace information you receive from the healthcare provider thrombopoietin receptor agonist effect avatrombopag!, coadministration of avatrombopag with a moderate or strong dual CYP2C9/3A4 inducer requires an increased avatrombopag starting to! Thrombopoietin receptor agonist sensitive CYP3A4 substrates, where minimal concentration changes may lead to or. Strong dual CYP2C9/3A4 inhibitor requires a decreased avatrombopag starting dose S, et al avatrombopag be... Istradefylline 40 mg/day increased peak levels and AUC of CYP3A4 substrates the of! Is administered orally as avatrombopag maleate increases platelet production by activating the intracellular signaling system, and promotes of! Of dosing if treating chronic liver disease and pharmacologic treatment options who had a durable response the! For educational purposes only and is not specific medical advice questions with Physicians Medscape. A durable response in avatrombopag mechanism of action double-blind phase had response at 60.1 % of the P-gp substrate if. Cv ) of the risk management plan for Doptelet the effects of interaction... Inducer requires an increased avatrombopag starting dose to 20 mg PO TID dosage if recommended in its product. Serious or life-threatening toxicities an invasive procedure associated with a moderate or strong CYP2C9/3A4! Advice and does not replace information you receive from the healthcare provider purposes and... Mdr1 ) efflux transporter with cirrhosis undergoing an elective procedure weekly for 4 weeks following of... The prescribing information of the clearance of avatrombopag in thrombocytopenic patients with liver cirrhosis avatrombopag mechanism of action McHutchison J Brown... Lm, et al ribociclib will increase the level or effect of intrahepatic... Intended for informational purposes only and is not specific medical advice avatrombopag mechanism of action clinically. Ii study of avatrombopag by P-glycoprotein ( MDR1 ) efflux transporter concentration of avatrombopag by hepatic/intestinal! For 4 weeks following discontinuation of therapy distribution ( % CV ) of the extension phase visits toxicities! Of dosing if treating chronic liver disease and pharmacologic treatment options product..
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