avatrombopag

Absorption: 66–69% absorbed following oral administration.

Distribution: Widely distributed to tissues.

Protein Binding: >96%.

Metabolism/Excretion: Primarily metabolized by CYP2C9 and CYP3A4 isoenzymes; the CYP2C9 enzyme system exhibits genetic polymorphism (intermediate or poor metabolizers may have significantly ↑ avatrombopag concentrations and an ↑ risk of adverse effects). Primarily eliminated in feces (34% as unchanged drug).

Half-Life: 19 hr.

Time/Action Profile ⬆ ⬇

(effect on platelet count)

ROUTE	ONSET	PEAK	DURATION
PO	3–5 days	10–13 days	2 wk

Contraind./Precautions ⬆ ⬇

Contraindicated in:

OB: Pregnancy (may cause fetal harm);
Lactation: Lactation.

Use Cautiously in:

Factor V Leiden, prothrombin 20210A, antithrombin deficiency, protein C or S deficiency, or antiphospholipid syndrome (↑ risk for thromboembolism);
Pedi: Safety and effectiveness not established in children.

Adv. Reactions/Side Effects ⬆ ⬇

CV: peripheral edema, THROMBOEMBOLISM

F and E: hyponatremia

GI: abdominal pain, nausea

Hemat: anemia

MS: myalgia

Neuro: fatigue, headache

Misc: fever, HYPERSENSITIVITY REACTIONS (INCLUDING TONGUE SWELLING AND LARYNGEAL EDEMA)

Interactions ⬆ ⬇

Drug-drug:

Moderate or strong dual inhibitors of CYP2C9 and CYP3A4, including fluconazole, may ↑ levels and risk of toxicity; ↓ starting dose of avatrombopag.
Moderate or strong dual inducers of CYP2C9 and CYP3A4, including rifampin, may ↓ levels and effectiveness; ↑ starting dose of avatrombopag.

Route/Dosage ⬆ ⬇

Patients with Chronic Liver Disease

PO (Adults ): Platelet count <40 × 10⁹/L: 60 mg once daily for 5 days (should be initiated 10–13 days prior to scheduled procedure; procedure should be performed 5–8 days after last dose); Platelet count 40–<50 × 10⁹/L: 40 mg once daily for 5 days (should be initiated 10–13 days prior to scheduled procedure; procedure should be performed 5–8 days after last dose.

Patients with Chronic Immune Thrombocytopenia

PO (Adults ): Dose levels recommended for titration of therapy based on platelet counts: Dose Level 1: 20 mg once weekly; Dose Level 2: 20 mg twice weekly OR 40 mg once weekly; Dose Level 3: 20 mg 3 times weekly; Dose Level 4: 20 mg once daily; Dose Level 5: 40 mg 3 times weekly AND20 mg the remaining 4 days of the wk; Dose Level 6: 40 mg once daily; initiate therapy at Dose Level 4 (20 mg once daily); if platelet count <50 × 10⁹/L after 2 wk of therapy, ↑ one Dose Level; if platelet count 50–200 × 10⁹/L after 2 wk of therapy, continue current Dose Level; if platelet count 200–400 × 10⁹/L after 2 wk of therapy, ↓ one Dose Level; if platelet count >400 × 10⁹/L, discontinue avatrombopag and restart therapy (↓ one Dose Level) once platelet count <150 × 10⁹/L. Concurrent use of moderate or strong dual inhibitors of CYP3A4 and CYP2C9: Initiate therapy at Dose Level 3 (20 mg 3 times weekly). Concurrent use of moderate or strong dual inducers of CYP3A4 and CYP2C9: Initiate therapy at Dose Level 6 (40 mg once daily).

Availability ⬆ ⬇

Assessment ⬆ ⬇

Monitor for signs and symptoms of thromboembolism (leg swelling, pain, or tenderness; tachycardia; dyspnea; abdominal pain or tenderness; chest pain) during and following therapy.
Monitor for hypersensitivity reactions (pruritus, rash, choking sensation, erythema, pharyngeal edema, swelling face, and swollen tongue).

Lab Test Considerations:

Chronic Liver Disease: Obtain platelet count before starting therapy and on day of procedure to make sure platelet count is adequate.
- Chronic Immune Thrombocytopenia Assess platelet count weekly until stable at ≥50 × 10⁹/L achieved; obtain platelet counts monthly thereafter. Obtain platelet counts weekly for ≥4 wk following discontinuation of therapy. If platelet count <50 × 10⁹/L after ≥2 wk of therapy: ↑one dose level. Wait 2 wk to assess effects of ↑ in dose. If platelet count 200–400 × 10⁹/L: ↓one dose level. Wait 2 wk to assess effects of ↓ in dose. If platelet count >400 × 10⁹/L: stop avatrombopag. ↑ platelet monitoring to twice weekly. When platelet count <150 × 10⁹/L, ↓ one dose level and reinitiate therapy. If platelet count <50 after 4 wk of avatrombopag 40 mg once daily or >400 after 2 wk of avatrombopag 20 mg weekly: discontinue therapy.

Implementation ⬆ ⬇

Patients with Chronic Liver Disease: Begin dosing 10–13 days prior to procedure. Schedule procedure for 5–8 days after last dose.
PO: Administer daily for 5 days with food.
Patients with Chronic Immune Thrombocytopenia : Use lowest dose needed to achieve and maintain a platelet count ≥50 × 10⁹/L to ↓ risk of bleeding.
PO: Administer once daily with food.

Patient/Family Teaching ⬆ ⬇

Explain purpose and side effects of medication to patient. Advise patient to read Patient Information before starting therapy.
Advise patient to notify health care professional of all Rx or OTC medications, vitamins, or herbal products being taken and to consult health care professional before taking other medications.
Instruct patient to take avatrombopag as directed. Take missed dose as soon as remembered; do not take two doses in the same day.
Advise patient to notify health care professional immediately if signs and symptoms of blood clots or hypersensitivity reactions occur.
Rep: May cause fetal harm. Advise women of reproductive potential to use effective contraception during therapy and to avoid breastfeeding during therapy and for 2 wk after last dose. Advise patient to notify health care professional immediately if pregnancy is suspected.

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Pronunciation ⬇

Classifications ⬆ ⬇

Indications ⬆ ⬇

Action ⬆ ⬇

Pharmacokinetics ⬆ ⬇