Avatrombopag

Avatrombopag is an oral thrombopoietin receptor agonist used before elective procedures in adults with chronic liver disease and thrombocytopenia, and in chronic immune thrombocytopenia.

Classification. Thrombopoietin receptor agonist.

Mechanism. Binds the thrombopoietin receptor at a site distinct from thrombopoietin, stimulating megakaryocyte production without competing with endogenous thrombopoietin.

Pharmacokinetics. Absorption is improved by food. It is more than 96% protein bound and metabolised by CYP2C9 and CYP3A4. Half-life is about 19 hours. Platelets rise from day 3 to 5 and peak at day 10 to 13.

Thrombocytopenia in chronic liver disease before a procedure (adults).

• Dose, by pre-treatment platelet count: under 40 × 10⁹/L, 60 mg orally once daily for 5 days; 40 to under 50 × 10⁹/L, 40 mg once daily for 5 days.
• Timing: start 10 to 13 days before the procedure, with the procedure 5 to 8 days after the last dose.
• Maximum: 60 mg daily. Loading dose: none. Titration: none.

Chronic immune thrombocytopenia (adults).

• Dose: 20 mg orally once daily with food.
• Titration: adjust within 20 to 40 mg daily to keep platelets at 50 to 150 × 10⁹/L. Reduce the dose if platelets exceed 200 × 10⁹/L; hold above 400 × 10⁹/L and restart at a lower dose when under 150 × 10⁹/L.
• Maximum: 40 mg daily. Stop after 4 weeks at maximum dose if there is no response.

Interaction adjustments. With drugs that strongly or moderately inhibit both CYP2C9 and CYP3A4 (for example fluconazole), use a lower dose: 20 mg three times weekly in immune thrombocytopenia, and 40 mg (platelets under 40 × 10⁹/L) or 20 mg (40 to under 50 × 10⁹/L) for 5 days in liver disease. With dual strong inducers such as rifampicin, higher doses are required; follow the label.

Adjustments. Kidney: no adjustment. Liver: none for chronic liver disease; use is established in Child-Pugh A and B.

Contraindications. Hypersensitivity.

Warnings. Thrombotic and thromboembolic complications, including portal vein thrombosis, in chronic liver disease, especially with platelets above 200 × 10⁹/L; do not use to normalise platelets.

Adverse effects. Fatigue, headache, fever, oedema, abdominal pain, nausea, thrombosis.

Interactions. Fluconazole and other dual inhibitors raise exposure. Rifampicin and other dual inducers reduce exposure, which is relevant for patients on tuberculosis therapy.

Pregnancy and breastfeeding. Avoid in pregnancy; avoid breastfeeding during treatment and for 2 weeks after the last dose.

Common errors. Taking without food in immune thrombocytopenia; stopping before the procedure; using for planned procedures with platelets of 50 × 10⁹/L or more.

Administration. Oral, with food. Procedure-based courses are 5 days; immune thrombocytopenia is long-term.

Baseline. Full blood count, liver function, review of interacting drugs.

Monitoring. Platelet count before starting and on the day of the procedure; weekly during immune thrombocytopenia titration, then monthly; report any limb swelling or abdominal pain.

Referral and escalation. Refer thrombosis, unresponsive immune thrombocytopenia or bleeding to haematology.