avatrombopag (Rx)

Brand and Other Names:Doptelet
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Dosing & Uses

AdultPediatric

Dosage Forms & Strengths

tablet

  • 20mg

Thrombocytopenia

Patients with chronic liver disease

  • Indicated for thrombocytopenia in adults with chronic liver disease who are scheduled to undergo a procedure
  • Taken orally once daily for 5 consecutive days with food
  • Initiate dosing 10-13 days prior to the scheduled procedure
  • Patients should undergo their procedure 5-8 days after the last dose
  • Dose based on preprocedure platelet count
    • Platelet count <40 x10^9/L: 60 mg PO qDay x 5 days
    • Platelet count 40 to <50 x10^9/L: 40 mg PO qDay x 5 days

Patients with chronic immune thrombocytopenia

  • Indicated for thrombocytopenia in adults with chronic immune thrombocytopenia (ITP) who have had an insufficient response to a previous treatment
  • Use lowest dose needed to achieve and maintain a platelet count ≥50 x10^9/L as necessary to reduce the risk for bleeding
  • Initial dose: 20 mg PO qDay
  • Dose adjustments by platelet count for chronic ITP
    • Platelet count <50 x10^9/L after ≥2 weeks: Increase by 1 dose level; wait 2 wk to assess effects before further adjustment
    • Platelet count 200-400 x10^9/L: Decrease 1 dose level; wait 2 wk to assess effects before further adjustment
    • Platelet count >400 x10^9/L: Stop avatrombopag and increase platelet monitoring to twice weekly; may reinitiated by decreasing 1 dose level when platelets <150 x10^9/L
    • Platelet count <50 x10^9/L after 4 weeks at 40 mg/day: Discontinue avatrombopag
    • Platelet count >400 x10^9/L after 2 weeks at 20 mg/week: Discontinue avatrombopag
  • Dose levels for titration in ITP
    • Dose level 6: 40 mg/day
    • Dose level 5: 40 mg 3x/week AND 20 mg on the 4 remaining days each week
    • Dose level 4: 20 mg/day
    • Dose level 3: 20 mg 3x/week
    • Dose level 2: 20 mg 2x/week OR 40 mg qWeek
    • Dose level 1: 20 mg qWeek

Dosage Modifications

Renal impairment

  • Mild-to-moderate (CrCl ≥30 mL/min): No dose adjustment required; minimally excreted by the kidneys
  • Severe (CrCl <30 mL/min) or hemodialysis: Unknown

Hepatic impairment

  • Child-Turcotte-Pugh grades A, B, or C or MELD score 4-23: No clinically meaningful effects on the pharmacokinetics

Recommended starting dose based on concomitant medications (chronic ITP)

  • Moderate or strong dual inhibitors of CYP2C9 and CYP3A4: Start avatrombopag 20 mg 3x/week
  • Moderate or strong dual inducers of CYP2C9 and CYP3A4: Start avatrombopag 40 mg qDay

Dosing Considerations

Do not administer in an attempt to normalize platelet counts

Chronic liver disease

  • Obtain a platelet count before initiating therapy and on the day of a procedure to ensure an adequate increase in platelet count
  • Investigated only as a single 5-day once-daily dosing regimen in clinical trials in patients with chronic liver disease

Chronic ITP

  • After initiating, assess platelet counts weekly until stable platelet ≥50 x10^9/L achieved, and then obtain platelet counts monthly thereafter
  • Obtain platelet counts weekly for at least 4 weeks following discontinuation

Safety and efficacy not established

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Adverse Effects

>10%

Pyrexia (8-11%)

1-10%

Abdominal pain (6-7%)

Nausea (6-7%)

Headache (4-7%)

Fatigue (3-4%)

Peripheral edema (3-4%)

<1%

Hyponatremia (0.7%)

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Warnings

Contraindications

None

Cautions

Thrombotic/thromboembolic complications

  • Thrombopoietin (TPO) receptor agonists associated with thrombotic and thromboembolic complications in patients with chronic liver disease or chronic ITP
  • Portal vein thrombosis reported with chronic liver disease in patients treated with thrombopoietin (TPO) receptor agonists (ADAPT-1 and ADAPT-2 clinical trials)
  • Consider the potential increased thrombotic risk when administering to patients with known risk factors for thromboembolism, including genetic prothrombotic conditions (eg, factor V Leiden, prothrombin 20210A, antithrombin deficiency, or protein C or S deficiency)
  • Not to be administered to patients with chronic liver disease or chronic immune thrombocytopenia in an attempt to normalize platelet counts; thromboembolic events (arterial or venous) reported
  • Follow dosing guidelines to achieve target platelet counts; monitor patients receiving therapy for signs and symptoms of thromboembolic events and institute treatment promptly
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Pregnancy

Pregnancy

Based on findings from animal reproduction studies, may cause fetal harm when administered to pregnant women

In animal reproduction studies, administration resulted in adverse developmental outcomes when administered during organogenesis in rabbits and during organogenesis and the lactation period in rats

However, these findings were observed at exposures based on AUC substantially higher than the AUC observed in patients at the recommended dose of 60 mg once daily

Advise pregnant women of the potential risk to a fetus

Lactation

No data are available regarding the presence of the drug in human milk, the effects on the breastfed child, or the effects on milk production

In studies, avatrombopag was present in the milk of lactating rats; when a drug is present in animal milk, it is likely the drug will be present in human milk

Owing to the potential for serious adverse reactions in a breastfed child, breastfeeding is not recommended during treatment and for at least 2 weeks after the last dose

Pregnancy Categories

A:Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.

B:May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.

C:Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.

D:Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.

X:Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.

NA:Information not available.

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Pharmacology

Mechanism of Action

Second-generation orally administered thrombopoietin receptor agonist (TPO-RA)

Stimulates proliferation and differentiation of megakaryocytes from bone marrow progenitor cells, resulting in an increased production of platelets

Does not compete with TPO for binding to the TPO receptor and has an additive effect with TPO on platelet production

Absorption

Peak plasma time: 5-6 hr

Peak plasma concentration: 166 ng/mL

AUC: 4198 ng·hr/mL

Systemic exposure variability reduced by 40-60% when administered with food

Distribution

Protein bound: >96%

Vd: 180 L

Metabolism

Metabolized primarily by CYP2C9 and CYP3A4

Elimination

Half-life: 19 hr

Clearance: 6.9 L/hr

Excretion: 88% feces (34% unchanged); 6% urine

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Administration

Oral Administration

Take with food

Missed dose

  • In the case of a missed dose, administer next dose as soon as possible
  • Do not take 2 doses at one time to make up for a missed dose and should take the next dose at the usual time the next day

Storage

Store at room temperature of 20-25°C (68-77°F); excursions permitted to 15-30°C (59-86°F)

Store tablets in original package

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Formulary

FormularyPatient Discounts

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The above information is provided for general informational and educational purposes only. Individual plans may vary and formulary information changes. Contact the applicable plan provider for the most current information.

Tier Description
1 This drug is available at the lowest co-pay. Most commonly, these are generic drugs.
2 This drug is available at a middle level co-pay. Most commonly, these are "preferred" (on formulary) brand drugs.
3 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs.
4 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
5 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
6 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
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Code Definition
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Drugs that require prior authorization. This restriction requires that specific clinical criteria be met prior to the approval of the prescription.
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Drugs that have step therapy associated with each prescription. This restriction typically requires that certain criteria be met prior to approval for the prescription.
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Medscape prescription drug monographs are based on FDA-approved labeling information, unless otherwise noted, combined with additional data derived from primary medical literature.