DOPTELET SIDE EFFECTS
- Generic Name: avatrombopag tablets
- Brand Name: Doptelet
SIDE EFFECTS
The following clinically significant adverse reactions are discussed in detail in other sections of the labeling:
- Thrombotic/Thromboembolic Complications.
Clinical Trial Experience
Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.
Patients With Chronic Liver Disease
The safety of DOPTELET was evaluated in two international, identically designed, randomized, double-blind, placebo-controlled trials, ADAPT-1 and ADAPT-2, in which 430 patients with chronic liver disease and thrombocytopenia received either DOPTELET (n=274) or placebo (n=156) daily for 5 days prior to a scheduled procedure, and had one post-dose safety assessment. Patients were divided into two groups based on their mean platelet count at baseline:
- Low Baseline Platelet Count Cohort (less than 40×109/L) who received DOPTELET 60 mg once daily for 5 days
- High Baseline Platelet Count Cohort (40 to less than 50×109/L) who received DOPTELET 40 mg once daily for 5 days
The majority of patients were males (65%) and median subject age was 58 years (ranging from 19-86 years of age). The racial and ethnic distribution was White (60%), Asian (33%), Black (3%) and Other (3%).
The most common adverse reactions (those occurring in ≥3% of patients) in the DOPTELET-treated groups (60 mg or 40 mg) across the pooled data from the two trials are summarized in Table 1.
Table 1: Adverse Reactions with a Frequency ≥3% in Patients with Chronic Liver Disease Treated with DOPTELET – Pooled Data ADAPT-1 and ADAPT-2
Adverse Reactions | Low Baseline Platelet Count Cohort (<40×109/L) |
High Baseline Platelet Count Cohort (≥40 to <50×109/L) |
Combined Baseline Platelet Count Cohorts (<50×109/L) |
|||
DOPTELET 60 mg (N=159) % |
Placebo (N=91) % |
DOPTELET 40 mg (N=115) % |
Placebo (N=65) % |
Total DOPTELET (N=274) % |
Total Placebo (N=156) % |
|
Pyrexia | 11 | 9 | 8 | 9 | 10 | 9 |
Abdominal Pain | 6 | 7 | 7 | 6 | 7 | 6 |
Nausea | 6 | 8 | 7 | 6 | 7 | 7 |
Headache | 4 | 8 | 7 | 5 | 6 | 6 |
Fatigue | 4 | 4 | 3 | 2 | 4 | 3 |
Edema Peripheral | 3 | 2 | 4 | 2 | 3 | 2 |
For the Low Baseline Platelet Count Cohort, the incidence of serious adverse reactions was 7% (11/159) in the 60 mg DOPTELET treatment group. For the High Baseline Platelet Count Cohort, the incidence of serious adverse reactions was 8% (9/115) in the 40 mg DOPTELET treatment group. The most common serious adverse reaction reported with DOPTELET was hyponatremia. Two DOPTELET-treated patients (0.7%) developed hyponatremia.
Adverse reactions resulting in discontinuation of DOPTELET were anemia, pyrexia, and myalgia; each was reported in a single (0.4%) patient in the DOPTELET (60 mg) treatment group.
Patients With Chronic Immune Thrombocytopenia
The safety of DOPTELET was evaluated in four clinical trials in patients with chronic immune thrombocytopenia: two Phase 3 trials (one randomized, double-blind, placebo-controlled trial, and one randomized, double-blind, active-controlled trial) and two Phase 2 trials (one randomized, double-blind, placebo-controlled, dose-ranging, trial, and one open-label extension trial) in 161 patients with chronic immune thrombocytopenia in both the double-blind and open-label extension phases.
The pooled safety data from these four clinical trials includes 128 patients who received 2.5 to 40 mg of DOPTELET once daily for a median duration of exposure of 29.1 weeks and had 1 post-dose safety assessment. The majority of patients were female (63%) and median subject age was 50.5 years (ranging from 18-88 years of age). The racial and ethnic distribution was White (84%), Black (6%), Asian (6%) and Other (6%).
The most common adverse reactions (those occurring in ≥10% of patients) in the DOPTELET-treated patients across the pooled safety data from the four trials are summarized in Table 2.
Table 2: Adverse Reactions with a Frequency ≥10% in Patients with Chronic Immune Thrombocytopenia Treated with DOPTELET – Pooled Data from Clinical Trials
Adverse Reactions | DOPTELET (N=128) % | Placebo (N= 22) % |
Headache | 31 | 14 |
Fatigue | 28 | 9 |
Contusion | 26 | 18 |
Epistaxis | 19 | 18 |
Upper Respiratory Tract Infection | 15 | 5 |
Arthralgia | 13 | 0 |
Gingival Bleeding | 13 | 0 |
Petechiae | 11 | 9 |
Nasopharyngitis | 10 | 0 |
The incidence of serious adverse reactions was 9% (12/128) in the DOPTELET treatment group. Serious adverse reactions reported in more than 1 individual DOPTELET-treated patient included headache, occurring in 1.6% (2/128).
Adverse reactions resulting in discontinuation of DOPTELET that were reported in more than 1 patient included headache, occurring in 1.6% (2/128).
Postmarketing Experience
The following adverse reactions have been identified during post approval use of DOPTELET. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.
Immune System Disorders
Hypersensitivity reactions including pruritus, rash, choking sensation, erythema, pharyngeal edema, pruritus generalized, rash macular, swelling face, and swollen tongue.
SRC: NLM .