Avatrombopag
Avatrombopag Uses, Dosage, Side Effects, Food Interaction and all others data.
Avatrombopag (Doptelet), is an orally administered, small-molecule thrombopoietin receptor (c-Mpl) agonist which increases platelet number, but not platelet activation , . This decreases the need for blood transfusions .
Patients with thrombocytopenia and chronic liver disease (leading to thrombocytopenia) often require platelet transfusions before surgical procedures to decrease the risk of bleeding . Thrombocytopenia (or decreased numbers of platelets) is a common complication in patients suffering from chronic liver disease, either as an immediate result of liver disease or a consequence of interferon-based antiviral therapy .
Avatrombopag was approved by the FDA on May 21, 2018 for thrombocytopenia (low platelets) in adults with chronic liver disease who are scheduled to undergo a procedure . It is administered orally as avatrombopag maleate, its salt form .
| Trade Name | Avatrombopag |
| Availability | Prescription only |
| Generic | Avatrombopag |
| Avatrombopag Other Names | Avatrombopag |
| Related Drugs | Promacta, prednisone, dexamethasone, triamcinolone, Decadron, Deltasone, Nplate |
| Weight | 20mg |
| Type | Oral tablet |
| Formula | C29H34Cl2N6O3S2 |
| Weight | Average: 649.65 Monoisotopic: 648.1510867 |
| Protein binding | Avatrombopag is greater than 96% bound to human plasma proteins . |
| Groups | Approved, Investigational |
| Therapeutic Class | |
| Manufacturer | |
| Available Country | United States |
| Last Updated: | September 19, 2023 at 7:00 am |
Uses
Avatrombopag is a thrombopoietin receptor agonist used to treat thrombocytopenia in patients with chronic liver disease who are scheduled to undergo a procedure.
Indicated for the treatment of thrombocytopenia in adult patients with chronic liver disease who are scheduled to undergo a procedure .
Avatrombopag is also used to associated treatment for these conditions: Thrombocytopenia
How Avatrombopag works
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. Avatrombopag is not competitive with thrombopoietin for binding to the TPO receptor and has an additive pharmacological effect with TPO on platelet production .
Avatrombopag is a thrombopoietin receptor (TPOR; MPL) agonist, with possible megakaryopoiesis stimulating activity. After administration, avatrombopag binds to and stimulates the platelet thrombopoeitin receptor (TPOR), which can lead to the proliferation and differentiation of megakaryocytes from bone marrow progenitor cells. This process increases the production of platelets and may serve to prevent chemotherapy-induced thrombocytopenia (CIT). TPOR is classified as a cytokine receptor and as a member of the hematopoietin receptor superfamily .
Toxicity
The most common adverse reactions reported in at least 3% of patients were pyrexia, abdominal pain, nausea, headache, fatigue, and peripheral edema , . Hyponatremia was also a rare serious adverse effect of this drug, seen in only 2 patients in the treatment group . Adverse reactions resulting in discontinuation of this drug have been anemia, pyrexia, and myalgia .
Atrombopag is a thrombopoietin (TPO) receptor agonist, and TPO receptor agonists have been associated with thrombotic and thromboembolic complications in patients with chronic liver disease. Portal venous thrombosis occurrence has been reported in patients with chronic liver disease who are treated with TPO receptor agonists . Patients should be monitored carefully .
Food Interaction
- Take with food.
[Moderate] ADJUST DOSING INTERVAL: Food reduces the variability in oral absorption and bioavailability of avatrombopag.
According to the product labeling, avatrombopag peak plasma concentration (Cmax) and systemic exposure (AUC) were not affected when administered with either a low-fat (500 calories; 3 g fat, 15 g proteins, 108 g carbohydrates) or high-fat (918 calories; 59 g fat, 39 g proteins, 59 g carbohydrates) meal.
However, the variability of avatrombopag exposure was reduced by 40% to 60% with food, and the time to reach Cmax was delayed by 0 to 2 hours relative to the fasted state.
MANAGEMENT: To ensure consistent absorption and plasma drug levels, avatrombopag should be taken with food.
Avatrombopag Disease Interaction
Moderate: severe renal dysfunction, thrombotic / thromboembolic complications
Volume of Distribution
Avatrombopag has an estimated mean volume of distribution (%CV) of 180 L (25%) .
Elimination Route
Following single dosing under fasted and fed conditions, mean peak concentrations occurred at 5-8 hours and declined with a half-life of 16-18 hours in Japanese and white subjects. Administration with food did not have an effect on the rate or extent of avatrombopag absorption, however, significantly reduced pharmacokinetic variability relative to the fasting state .
Avatrombopag showed dose-proportional pharmacokinetics after single doses from 10 mg (0.25-times the lowest approved dosage) to 80 mg (1.3-times the highest recommended dosage). Healthy subjects administered 40 mg of avatrombopag showed a geometric mean (%CV) maximal concentration (Cmax) of 166 (84%) ng/mL and area under the time-concentration curve, extrapolated to infinity (AUC0-inf) of 4198 (83%) ng.hr/mL. The pharmacokinetics of avatrombopag are similar in both healthy subjects and the chronic liver disease population .
Half Life
The mean plasma elimination half-life (%CV) of avatrombopag is approximately 19 hours (19%) .
Clearance
The mean (%CV) of the clearance of avatrombopag is estimated to be 6.9 L/hr (29%) .
Elimination Route
Fecal excretion accounted for 88% of the administered dose, with 34% of the dose excreted as unchanged avatrombopag. Only 6% of the administered dose was found in urine .
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