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Doptelet is a brand name for Avatrombopag. The medicine, its uses, side effects and dosage are the same regardless of brand.
Used for: Doptelet is indicated for the treatment of severe thrombocytopenia in adult patients with chronic liver disease who are scheduled to undergo an invasive procedure. Doptelet is indicated for the treatment of primary chronic immune thrombocytopenia (ITP) in adult patients who are refractory to other treatments (e.g.,…
Verbatim from this product's EMA label. Tap a section to expand.
Posology Treatment should be initiated by and remain under the supervision of a physician who is experienced in the treatment of haematological diseases. , in the morning or evening) with food, including when taking the dose less frequently than once daily.
5. The recommended daily dose of avatrombopag is based on the patient’s platelet count (see Table 1). Dosing should begin 10 to 13 days prior to the planned procedure. The patient should undergo their procedure 5 to 8 days after the last dose of avatrombopag.
3 Table 1: Daily dose recommendation for avatrombopag Platelet count (×109/L) Once-daily dose Duration of dosing < 40 60 mg (Three 20 mg tablets) 5 days ≥ 40 to < 50 40 mg (Two 20 mg tablets) 5 days Duration of treatment Due to limited information, avatrombopag should not be taken for more than 5 days.
Missed doses If a dose is missed, it should be taken as soon as it is remembered. Two doses should not be taken at one time to make up for a missed dose. The next dose should be taken at the usual time the next day. Chronic immune thrombocytopenia Use the lowest dose of Doptelet needed to achieve and maintain a platelet count ≥ 50 × 109/L as necessary to reduce the risk for bleeding.
Do not use avatrombopag to normalise platelet counts. In clinical trials, platelet counts generally increased within 1 week after starting avatrombopag and decreased within 1 to 2 weeks after discontinuation. Initial dose regimen The recommended starting dose of Doptelet is 20 mg (1 tablet) once daily with food.
Monitoring and dose adjustment After initiating therapy, assess platelet counts at least once weekly until a stable platelet count ≥ 50 × 109/L and ≤ 150 × 109/L has been achieved. Twice weekly platelet count monitoring should be conducted during the first weeks of therapy in patients receiving avatrombopag only once or twice weekly.
Twice weekly monitoring should also be conducted after dose adjustments during the treatment. Due to the potential risk of platelet counts above 400 × 109/L within the first weeks of treatment patients should be carefully monitored for any signs or symptoms of thrombocytosis.
After a stable platelet count has been achieved, obtain platelet counts at least monthly. After discontinuation of avatrombopag, platelet counts should be obtained weekly for at least 4 weeks. Dose adjustments (see Table 2 and Table 3) are based on the platelet count response.
Summary of the safety profile Chronic liver disease The safety of avatrombopag was evaluated in two randomised, double-blind, placebo-controlled trials, ADAPT-1 and ADAPT-2, in which 430 patients with chronic liver disease and thrombocytopenia received either avatrombopag (n = 274) or placebo (n = 156), and had 1 post-dose safety assessment.
10 Chronic immune thrombocytopenia The safety of avatrombopag in adult patients was evaluated in three controlled trials and one uncontrolled trial which enrolled 161 patients with chronic immune thrombocytopenia. The pooled safety data from these four trials includes 128 patients who were exposed to avatrombopag for a median duration of 29 weeks.
The safety of avatrombopag in paediatric patients ≥ 1 to < 18 years of age with persistent or chronic thrombocytopenia was evaluated in a randomized, placebo-controlled trial with a 12-week double- blind Core Phase followed by an optional open-label Extension Phase in which patients could receive avatrombopag for up to 2 years.
The safety data from the Core Phase includes 54 patients who were exposed to avatrombopag for a median duration of 12 weeks. The overall safety profile in paediatric patients treated with avatrombopag is comparable to that in adult patients.
Tabulated list of adverse reactions Adverse reactions are classified by Preferred Term and System Organ Class, and by frequency. Frequencies are defined as: very common (≥ 1/10); common (≥ 1/100 to < 1/10); uncommon (≥ 1/1 000 to < 1/100); rare (≥ 1/10 000 to < 1/1 000); very rare (< 1/10 000); not known (cannot be estimated from the available data).
1. 1. ** In the clinical trial in paediatric patients, thrombocytosis was reported in one patient during the Core Phase of the study and in one patient during the open-label Extension Phase. Description of selected adverse reactions Thromboembolic events In the ADAPT-1 and ADAPT-2 clinical trials in patients with thrombocytopenia and chronic liver disease, there was 1 treatment-emergent event of portal vein thrombosis in a patient (n = 1/274 of patients receiving avatrombopag) which was reported 14 days after treatment with Doptelet ended.
Thrombotic/thromboembolic events Patients with chronic liver disease are known to be at increased risk for thromboembolic events. 8). 8). Doptelet was not studied in patients with prior thromboembolic events. g. g. antiphospholipid syndrome), advanced age, patients with prolonged periods of immobilisation, malignancies, contraceptives and hormone replacement therapy, surgery/trauma, obesity and smoking.
Doptelet should not be administered to patients with chronic liver disease or chronic immune thrombocytopenia in an attempt to normalise platelet counts. QTc prolongation with concomitant medicinal products At exposures similar to that achieved at the 40 mg and 60 mg dose, Doptelet did not prolong the QT interval to any clinically relevant extent.
Mean QTc prolongation effects > 20 ms are not anticipated with the highest recommended therapeutic dosing regimen based on analysis of data from the pooled clinical trials in patients with chronic liver disease. However, caution must be exercised when Doptelet is co-administered with moderate or strong dual CYP3A4/5 and CYP2C9 inhibitors, or with moderate or strong CYP2C9 inhibitors, as these medicinal products can increase avatrombopag exposures.
Caution must also be exercised in patients with loss-of-function polymorphisms of CYP2C9, as these can increase avatrombopag exposure. Reoccurrence of thrombocytopenia and bleeding after cessation of treatment in patients with chronic immune thrombocytopenia Thrombocytopenia is likely to reoccur in ITP patients upon discontinuation of treatment with avatrombopag.
Following discontinuation of avatrombopag, platelet counts return to baseline levels within 2 weeks in the majority of patients, which increases the bleeding risk and in some cases may lead to bleeding. There is an increased risk of bleeding if avatrombopag treatment is discontinued in the presence of anticoagulants or anti-platelet agents.
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Do not exceed a daily dose of 40 mg (2 tablets). 4 Table 2: Avatrombopag dose adjustments for patients with primary chronic immune thrombocytopenia Platelet count (× 109/L) Dose adjustment or action < 50 after at least 2 weeks of avatrombopag treatment • Increase One Dose Level per Table 3.
• Wait 2 weeks to assess the effects of this regimen and any subsequent dose adjustments. > 150 and ≤ 250 • Decrease One Dose Level per Table 3. • Wait 2 weeks to assess the effects of this regimen and any subsequent dose adjustments.
> 250 • Stop avatrombopag. • Increase platelet monitoring to twice weekly. • When platelet count is less than 100 × 109/L, decrease One Dose Level per Table 3 and reinitiate therapy. < 50 after 4 weeks of avatrombopag 40 mg once daily • Discontinue avatrombopag.
> 250 after 2 weeks of avatrombopag 20 mg weekly • Discontinue avatrombopag.
Table 3:
Avatrombopag dose levels for titration in patients with primary chronic immune thrombocytopenia *Initial dose regimen for all patients except those taking moderate or strong dual inducers or moderate or strong dual inhibitors of CYP2C9 and CYP3A4/5, or of CYP2C9 alone.
≠ Patients taking avatrombopag less frequently than once daily should take the medicinal product in a consistent manner from week to week. g. g. g. Monday In the case of a missed dose, patients should take the missed dose of avatrombopag as soon as they remember.
Patients should not take two doses at one time to make up for a missed dose, and should take the next dose per the current regimen. Avatrombopag can be administered in addition to other ITP medicinal products. Platelet counts should be monitored when combining avatrombopag with other medicinal products for the treatment of primary ITP in order to avoid platelet counts outside of the recommended range, and to determine whether the dose of either medicinal product should be reduced.
Dose≠ Dose Level 40 mg once daily 6 40 mg three times a week AND 20 mg on the four remaining days of each week 5 20 mg once daily* 4 20 mg three times a week 3 20 mg twice a week OR 40 mg once weekly 2 20 mg once weekly 1 5 Discontinuation Discontinue avatrombopag if the platelet count does not increase to ≥ 50 × 109/L after 4 weeks of dosing at the maximum dose of 40 mg once daily.
Discontinue Doptelet if the platelet count is greater than 250 × 109/L after 2 weeks of dosing at 20 mg once weekly. Recommended dose with concomitant moderate or strong dual inducers or inhibitors of CYP2C9 and CYP3A4/5, or of CYP2C9 alone, in patients with chronic immune thrombocytopenia The recommended starting doses of avatrombopag in patients with chronic immune thrombocytopenia receiving concomitant medicinal products are summarised in Table 4.
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This adverse reaction was assessed as non-serious. In the four pooled clinical trials in adult patients with chronic immune thrombocytopenia, thromboembolic events were observed in 7% (9/128) of patients. The only thromboembolic event which occurred in […]
Patients should be closely monitored for a decrease in platelet count and medically managed to avoid bleeding upon discontinuation of treatment with avatrombopag. It is recommended that, if treatment with avatrombopag is discontinued, ITP treatment be restarted according to current treatment guidelines.
Additional medical management may 7 include cessation of anticoagulant and/or antiplatelet therapy, reversal of anticoagulation, or platelet support. Increased bone marrow reticulin Increased bone marrow reticulin is believed to be a result of TPO receptor stimulation, leading to an increased number of megakaryocytes in the bone marrow, which may subsequently release cytokines.
Increased reticulin may be suggested by morphological changes in the peripheral blood cells and can be detected through bone marrow biopsy. Therefore, examinations for cellular morphological abnormalities using peripheral blood smear and complete blood count (CBC) prior to and during treatment with avatrombopag are recommended.
If a loss of efficacy and abnormal peripheral blood smear are observed in patients, administration of avatrombopag should be discontinued, a physical examination should be performed, and a bone marrow biopsy with appropriate staining for reticulin should be considered.
If available, comparison to a prior bone marrow biopsy should be made. If efficacy is maintained and abnormal peripheral blood smear is observed in patients, the physician should follow appropriate clinical judgment, including consideration of a bone marrow biopsy, and the risk-benefit of avatrombopag and alternative ITP treatment options should be re-assessed.
Progression of existing myelodysplastic syndrome (MDS) The effectiveness and safety of Doptelet have not been established for the treatment of thrombocytopenia due to MDS. Doptelet should not be used outside of clinical trials for the treatment of thrombocytopenia due to MDS.
There is a theoretical concern that TPO-R agonists may stimulate the progression of existing haematological malignancies such as MDS. TPO-R agonists are growth factors that lead to thrombopoietic progenitor cell expansion, differentiation and platelet production.
The TPO-R is predominantly expressed on the surface of cells of the myeloid lineage. The diagnosis of ITP in adults and elderly patients should have been confirmed by the exclusion of other clinical entities presenting with thrombocytopenia, in particular the diagnosis of MDS must be excluded.
Consideration should be given to performing a bone marrow aspirate and biopsy over the course of the disease and treatment, particularly in patients over 60 years of age, for those with systemic symptoms or abnormal signs such as increased peripheral blast cells.
Severe hepatic impairment There is limited information on the use of avatrombopag in patients with severe (Child-Pugh class C, MELD score > 24) hepatic impairment. 2). Patients with severe hepatic impairment should be supported in line with clinical practice by close monitoring for early signs of worsening or new onset hepatic encephalopathy, ascites, and thrombotic or bleeding tendency, through monitoring of liver function tests, tests used for assessing clotting status and through imaging of portal vasculature […]