Doptelet (avatrombopag) - 2 indications

Scroll down for information on each indication:

• for the treatment of thrombocytopenia in adults with chronic liver disease scheduled to undergo a procedure; approved May 2018
• for patients with chronic immune thrombocytopenia who have had an insufficient prior response to treatment; approved June 2019 

General Information

Doptelet (avatrombopag) is a thrombopoietin receptor agonist. 

Doptelet is specifically indicated for the following:

• for the treatment of thrombocytopenia in adult patients with chronic liver disease who are scheduled to undergo a procedure
• for the treatment of thrombocytopenia in adult patients with chronic immune thrombocytopenia who have had an insufficient response to a previous treatment

Doptelet is supplied as a tablet for oral administration. Scroll down for recommended dosing/administration for each indication.

Mechanism of Action

Doptelet (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. Avatrombopag does not compete with TPO for binding to the TPO receptor and has an additive effect with TPO on platelet production. 

Side Effects

Adverse effects associated with the use of Doptelet may include, but are not limited to, the following:

• pyrexia
• abdominal pain
• nausea
• headache
• fatigue
• edema peripheral

Indication 1 - for the treatment of thrombocytopenia in adults with chronic liver disease scheduled to undergo a procedure

approved May 2018

Dosing/Administration

Begin Doptelet dosing 10-13 days prior to the scheduled procedure. The recommended daily dose of Doptelet is based on the patient’s platelet count prior to the scheduled procedure (see below). Patients should undergo their procedure 5 to 8 days after the last dose of Doptelet. Doptelet should be taken orally once daily for 5 consecutive days with food. In the case of a missed dose, patients should take the next dose of Doptelet 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 at the usual time the next day; all five days of dosing should be completed. 

Recommended Dose and Duration:

Platelet Count (x109/L): Less than 40 Once Daily Dose: 60 mg (3 tablets) for 5 days

Platelet Count (x109/L): 40 to less than 50 Once Daily Dose: 40 mg (2 tablets) for 5 days

Clinical Results

The FDA approval of Doptelet was based on two trials, (ADAPT-1 and ADAPT-2) involving 435 patients with chronic liver disease and severe thrombocytopenia who were scheduled to undergo a procedure that would typically require platelet transfusion. The trials investigated two dose levels of Doptelet administered orally over five days as compared to placebo. The trial results showed that for both dose levels of Doptelet, a higher proportion of patients had increased platelet counts and did not require platelet transfusion or any rescue therapy on the day of the procedure and up to seven days following the procedure as compared to those treated with placebo. Percentage of Responders: ADAPT-1: 66% vs. 23% and ADAPT-2: 69% vs. 35%. 

Indication 2 - for patients with chronic immune thrombocytopenia who have had an insufficient prior response to treatment

approved June 2019 

Dosing/Administration

Initiate Doptelet at 20 mg (1 tablet) once daily. Adjust the dose or frequency of dosing to maintain platelet count greater than or equal to 50×109 /L. Do not exceed 40 mg per day.

Clinical Trial Results

FDA approval was based on data from a phase 3, double blind, placebo controlled trial evaluating the efficacy of Doptelet in adult patients (N=49) with chronic ITP who previously received ≥1 ITP therapy (ie, corticosteroids, immunoglobulins, azathioprine, danazol, cyclophosphamide and/or rituximab). The primary outcome measure was the cumulative number of weeks in which the platelet count was ≥50 x109/L during the 6 month treatment period in the absence of rescue therapy. Results showed that patients treated with Doptelet had a longer duration of platelet counts ≥50 x109/L in the absence of rescue therapy compared with those who received placebo (median 12.4 [0, 25] vs [0, 2] weeks, respectively. In addition, a larger proportion of patients in the Doptelet arm had platelet counts ≥50 x109/L at Day 8 compared with placebo (21/32; 66% vs 0/17; 0.0%).