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Avatrombopag

Class: Hematopoietic Agents
Chemical Name: 1-[3-chloro-5-[[4-(4-chlorothiophen-2-yl)-5-(4-cyclohexylpiperazin-1-yl)-1,3-thiazol-2-yl]carbamoyl]pyridin-2-yl]piperidine-4-carboxylic acid
Molecular Formula: C29H34Cl2N6O3S2•C4H4O4
CAS Number: 677007-74-8
Brands: Doptelet

Medically reviewed by Drugs.com. Last updated on May 25, 2020.

Introduction

Avatrombopag maleate is a hematopoietic agent.

Uses for Avatrombopag

Avatrombopag maleate has the following uses:

Avatrombopag maleate is a thrombopoietin receptor agonist indicated for the treatment of thrombocytopenia in adult patients with chronic liver disease who are scheduled to undergo a procedure.1

Avatrombopag Dosage and Administration

General

Avatrombopag maleate is available in the following dosage form(s) and strength(s):

  • Tablet: 20 mg.1

Dosage

It is essential that the manufacturer's labeling be consulted for more detailed information on dosage and administration of this drug. Dosage summary:

Adults

Dosage & Administration Section
  • Begin dosing avatrombopag maleate 10 to 13 days prior to a scheduled procedure.1

  • Patients should undergo their procedure within 5 to 8 days after the last dose.1

  • Avatrombopag maleate should be taken orally with food once daily for 5 consecutive days.1

  • The recommended dose of avatrombopag maleate is based on a patient’s platelet count prior to a scheduled procedure.1

  • Recommended Dose and Duration:1

Platelet Count (x109/L)

Once Daily Dose

Duration

Less than 40

60 mg (3 tablets)

5 days

40 to less than 50

40 mg (2 tablets)

5 days

Cautions for Avatrombopag

Contraindications

None.1

Warnings/Precautions

Thrombotic/Thromboembolic Complications

Avatrombopag maleate 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 vein thrombosis has been reported in patients with chronic liver disease treated with TPO receptor agonists. In the ADAPT-1 and ADAPT-2 clinical trials, there was 1 treatment-emergent event of portal vein thrombosis in a patient (n=1/430) with chronic liver disease and thrombocytopenia treated with avatrombopag maleate. Consider the potential increased thrombotic risk when administering avatrombopag maleate to patients with known risk factors for thromboembolism, including genetic prothrombotic conditions (factor V Leiden, prothrombin 20210A, antithrombin deficiency, or protein C or S deficiency).1

Avatrombopag maleate should not be administered to patients with chronic liver disease in an attempt to normalize platelet counts.1

Specific Populations

Pregnancy

Risk Summary: Based on findings from animal reproduction studies, avatrombopag maleate may cause fetal harm when administered to a pregnant woman. The available data on avatrombopag maleate in pregnant women are insufficient to inform a drug-associated risk of adverse developmental outcomes. In animal reproduction studies, oral administration of avatrombopag 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 dosage of 60 mg once daily. Advise pregnant women of the potential risk to a fetus. 1

The estimated background risk of major birth defects and miscarriage for the indicated population is unknown. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. In the U.S. general population, the estimated background risk of major birth defects and of miscarriage in clinically recognized pregnancies is 2-4% and 15-20%, respectively.1

Animal Data: In embryo-fetal development studies, avatrombopag was administered during organogenesis at doses of 100, 300, and 1000 mg/kg/day in rats and doses of 100, 300, and 600 mg/kg/day in rabbits. Minimal decreases in fetal weights were observed in rats at the maternally toxic dose of 1000 mg/kg/day with exposures 190 times the human exposure based on AUC. Spontaneous abortions were observed at all doses tested in rabbits and were associated with decreased body weights and food consumption at 300 and 600 mg/kg/day; exposures at the lowest dose of 100 mg/kg/day were 10 times the AUC in patients at the recommended dose of 60 mg once daily. There were no embryo-fetal effects in rats administered avatrombopag at doses up to 100 mg/kg/day (53 times the human exposure based on AUC) or rabbits administered avatrombopag at doses up to 600 mg/kg (35 times the human exposure based on AUC).1

In pre- and postnatal development studies in rats, avatrombopag was administered during both the organogenesis and lactation periods at doses ranging from 5 to 600 mg/kg/day. Doses of 100, 300, and 600 mg/kg/day caused maternal toxicity leading to total litter losses, decreased body weight in pups, and increased pup mortality, with the majority of the pup mortality occurring between postnatal days 14 to 21. At a dose of 50 mg/kg/day that did not produce clear maternal toxicity, avatrombopag caused increased pup mortality from postnatal days 4 to 21, and mortality continued through postnatal day 25. The 50 mg/kg/day dose also decreased body weight gain in the pups, resulting in a delay in sexual maturation. There were no effects on behavioral or reproductive functions in the offspring. The 50 mg/kg/day dose resulted in maternal exposures 43 times and pup exposures approximately 3 times the AUC observed in patients at the recommended dose of 60 mg once daily.1

Lactation

There is no information regarding the presence of avatrombopag in human milk, the effects on the breast-fed child, or the effects on milk production. 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. Due to the potential for serious adverse reactions in a breast-fed child from avatrombopag maleate, breast-feeding is not recommended during treatment with avatrombopag maleate and for at least 2 weeks after the last dose.1

A lactating woman should interrupt breast-feeding and pump and discard breast milk during treatment and for two weeks after the last dose of avatrombopag maleate in order to minimize exposure to a breast-fed child.1

Pediatric Use

Safety and effectiveness in pediatric patients have not been established.1

Geriatric Use

Clinical studies of avatrombopag maleate did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects. Other reported clinical experience has not identified differences in responses between the elderly and younger patients.1

Common Adverse Effects

Most common adverse reactions (≥3%) are pyrexia, abdominal pain, nausea, headache, fatigue, and peripheral edema.1

Drug Interactions

Specific Drugs

It is essential that the manufacturer's labeling be consulted for more detailed information on interactions with this drug, including possible dosage adjustments. Interaction highlights:

Please see product labeling for drug interaction information.

Actions

Avatrombopag is an orally bioavailable, small molecule TPO receptor agonist that stimulates proliferation and differentiation of megakaryocytes from bone marrow progenitor cells, resulting in an increased production of platelets. Avatrombopag does not compete with TPO for binding to the TPO receptor and has an additive effect with TPO on platelet production.1

Advice to Patients

Advise the patient or caregiver to read the FDA-approved patient labeling.1

Prior to treatment, patients should fully understand and be informed of the following risks and considerations for avatrombopag maleate:1

Thrombotic/Thromboembolic Complications

Avatrombopag maleate is a TPO receptor agonist, and TPO receptor agonists have been associated with thrombotic and thromboembolic complications in patients with chronic liver disease. Portal vein thrombosis has been reported in patients with chronic liver disease treated with TPO receptor agonists.1

Pregnancy

Advise pregnant women of the potential risk to a fetus. Advise females of reproductive potential to inform their prescriber of a known or suspected pregnancy.1

Lactation

Advise women not to breast-feed during treatment with avatrombopag maleate and for at least 2 weeks after the final dose.1

Additional Information

AHFSfirstRelease. For additional information until a more detailed monograph is developed and published, the manufacturer's labeling should be consulted. It is essential that the manufacturer's labeling be consulted for more detailed information on usual uses, dosage and administration, cautions, precautions, contraindications, potential drug interactions, laboratory test interferences, and acute toxicity.

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.

Avatrombopag Maleate

Routes

Dosage Forms

Strengths

Brand Names

Manufacturer

Oral

Tablet, Film Coated

20 mg

Doptelet

AkaRx Inc.

AHFS Drug Information. © Copyright 2021, Selected Revisions June 4, 2018. American Society of Health-System Pharmacists, Inc., 4500 East-West Highway, Suite 900, Bethesda, Maryland 20814.

References

1. AkaRx, Inc.. DOPTELET (avatrombopag maleate) ORAL prescribing information. 2018 May http://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=e2d5960d-6c18-46cc-86bd-089222b09852

Frequently asked questions