Avatrombopag

Avatrombopag is a prescription medication used for the treatment of:

• thrombocytopenia in adults with chronic liver disease (CLD) who are scheduled to undergo a procedure
• thrombocytopenia in adults with chronic immune thrombocytopenia (ITP) who have had an insufficient response to a previous treatment
• thrombocytopenia in children 1 year and older with persistent or chronic ITP who have had an insufficient response to previous treatment

Avatrombopag is available under the following different brand names: Doptelet, Doptelet Sprinkle

Common side effects of Avatrombopag include:

• fever
• easy bruising
• unusual bleeding (nosebleeds, bleeding gums)
• purple or red spots on the skin
• upper respiratory tract infection
• swelling of the hands or feet
• tiredness
• headache
• joint pain
• runny or stuffy nose
• sneezing
• sore throat
• nausea
• stomach pain
• swelling in the hands or feet
• viral infection
• cough
• pain in the mouth or throat

Serious side effects of Avatrombopag include:

• increased risk of blood clots

Rare side effects of Avatrombopag include:

• None 

Seek medical care or call 911 at once if you have the following serious side effects:

• Severe headache, confusion, slurred speech, arm or leg weakness, trouble walking, loss of coordination, feeling unsteady, very stiff muscles, high fever, profuse sweating, or tremors;
• Serious eye symptoms such as sudden vision loss, blurred vision, tunnel vision, eye pain or swelling, or seeing halos around lights;
• Serious heart symptoms include fast, irregular, or pounding heartbeats; fluttering in the chest; shortness of breath; sudden dizziness, lightheadedness, or passing out. 

This is not a complete list of side effects and other serious side effects or health problems that may occur because of the use of this drug. Call your doctor for medical advice about serious side effects or adverse reactions. You may report side effects or health problems to FDA at 1-800-FDA-1088.

 Adult and pediatric dosage

Tablet

• 20 mg

Capsule, oral granules

• 10mg

Thrombocytopenia

Adult dosage

• Patients with chronic liver disease
  • Initiate 10-13 days before the scheduled procedure.
• Patients should undergo their procedure 5-8 days after the last dose.
• Dose based on pre-procedure platelet count.
  • Platelet count less than 40 x10^9/L: 60 mg orally once a day for 5 days
  • Platelet count 40 to less than 50 x10^9/L: 40 mg orally once a day for 5 days
• Patients with chronic immune thrombocytopenia
  • Use the lowest dose needed to achieve and maintain a platelet count of 50 x109/L and more to reduce the risk of bleeding.
  • Initial dose: 20 mg orally once a day; not to exceed 40 mg orally once a day.
• Dose adjustments by platelet count
  • Platelet count less than 50x 10^9/L after 2 weeks and more: Increase by 1 dose level; wait 2 wk to assess effects before further adjustment
  • Platelet count between 200 and 400x 10^9/L: Decrease 1 dose level; wait 2 wk to assess effects before further adjustment
  • Platelet count greater than 400x 10^9/L: Stop treatment and increase platelet monitoring to twice weekly; may restart by decreasing 1 dose level when platelets is less than 150x 10^9/L
  • Platelet count less than 5 x 10^9/L after 4 weeks at 40 mg/day: Discontinue treatment
  • Platelet count greater than 400x 10^9/L after 2 weeks at 20 mg/week: Discontinue treatment
• Dose levels for titration
  • Dose level 6: 40 mg daily
  • Dose level 5: 40 mg 3x/week and 20 mg on the 4 remaining days each week
  • Dose level 4: 20 mg daily
  • Dose level 3: 20 mg 3x/week
  • Dose level 2: 20 mg 2x/week or 40 mg once weekly
  • Dose level 1: 20 mg once weekly
    • Discontinue treatment
• Platelet count does not increase 50x 10^9/L and more after 4 weeks at 40 mg daily (maximum dose)
• Platelet count is is greater than 400x 10^9/L after 2 weeks at 20 mg once weekly

Pediatric dosage

• Children aged below 1 year: Safety and efficacy not established
• Children aged 6 years and older (tablet)
• Initial: 20 mg orally daily
• Dose adjustments according to platelet count
  • Platelet count less than 50x 10^9/L: Increase 1 dose level; wait 2 weeks to assess effect and any subsequent dose adjustments
  • Platelet count between 200 and 400x 10^9/L: Decrease 1 dose level; wait 2 weeks to assess effect and any subsequent dose adjustments
  • Platelet count greater than 400x 10^9/L: Stop avatrombopag and increase platelet monitoring to 2x/week; when platelet count is less than 150x 10^9/L, decrease by 1 dose level and reinitiate therapy
  • Platelet count less than 50x 10^9/L after 4 weeks of 40 mg/day: Discontinue
  • Platelet count greater than 400x 10^9/L after 2 weeks of 20 mg/week: Discontinue
• Dose levels for titration
  • Dose level 6: 40 mg daily
  • Dose level 5: 40 mg 3x/week and 20 mg on 4 remaining days each week
  • Dose level 4: 20 mg daily
  • Dose level 3: 20 mg 3x/week
  • Dose level 2: 20 mg 2x/week or 40 mg once weekly
  • Dose level 1: 20 mg once weekly
• Coadministration of dual CYP2C9 and CYP3A4 inhibitors or inducers
• Moderate or strong dual inhibitors of CYP2C9 and CYP3A4: Initiate at 20 mg 3x/week
• Moderate or strong dual inducers of CYP2C9 and CYP3A4: Initiate at 40 mg daily
• Children aged 1 year to less than 6 years (oral granules)
  • Initial: 10 mg orally daily
  • Dose adjustments according to platelet count
    • Platelet count less than 50x10^9/L: Increase 1 dose level; wait 2 weeks to assess effect and any subsequent dose adjustments
    • Platelet count between 200 and 400x 10^9/L: Decrease 1 dose level; wait 2 weeks to assess effect and any subsequent dose adjustments
    • Platelet count greater than 400x 10^9/L: Stop avatrombopag and increase platelet monitoring to 2x/week; when platelet count is less than 150x 10^9/L, decrease by 1 dose level and reinitiate therapy
    • Platelet count less than 50x 10^9/L after 4 weeks of 20 mg/day: Discontinue
    • Platelet count greater than 400x 10^9/L after 2 weeks of 10 mg/week: Discontinue
• Dose levels for titration
  • Dose level 6: 20 mg daily
  • Dose level 5: 20 mg 3x/week and 10 mg on 4 remaining days each week
  • Dose level 4: 10 mg daily
  • Dose level 3: 10 mg 3x/week
  • Dose level 2: 10 mg 2x/week or 20 mg once weekly
  • Dose level 1: 10 mg once weekly
  • Coadministration of dual CYP2C9 and CYP3A4 inhibitors or inducers
  • Moderate or strong dual inhibitors of CYP2C9 and CYP3A4: Initiate at 10 mg 3x/week
  • Moderate or strong dual inducers of CYP2C9 and CYP3A4: Initiate at 20 mg daily

If your doctor has directed you to use this medication, your doctor or pharmacist may already be aware of any possible drug interactions and may be monitoring you for them. Do not start, stop, or change the dosage of any medicine before checking with your doctor, health care provider, or pharmacist first.
Drug interaction overview

• Avatrombopag is a CYP2C9 and CYP3A4 substrate; it inhibits organic anion transporter (OAT) 3 and breast cancer resistance protein (BCRP)
• Moderate or strong dual CYP2C9 and CYP3A4 inhibitors
• Coadministration with a moderate or strong dual CYP2C9 and CYP3A4 inhibitor increases avatrombopag AUC, which may increase the risk of avatrombopag toxicities.
• If starting a moderate or strong dual CYP2C9 and CYP3A4 inhibitor during treatment, monitor platelet counts and adjust the avatrombopag dose as necessary.
• Moderate or strong dual CYP2C9 and CYP3A4 inducers
• Coadministration with a moderate or strong dual CYP2C9 and CYP3A4 inducers decreases avatrombopag AUC, which may reduce the efficacy of avatrombopag.
• If starting a moderate or strong dual CYP2C9 and CYP3A4 inducer during treatment, monitor platelet counts and adjust the avatrombopag dose as necessary.

Contraindications

• None

Effects of drug abuse

• None

Short-Term Effects

• See “What Are Side Effects Associated with Using Avatrombopag?”

Long-Term Effects

• See “What Are Side Effects Associated with Using Avatrombopag?”

Cautions

• Thrombotic/thromboembolic complications
  • Thrombopoietin (TPO) receptor agonists are 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 (.g, 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.
  • Monitor platelet counts and follow dosing guidelines to achieve target platelet counts; monitor patients receiving therapy for signs and symptoms of thromboembolic events and institute treatment promptly.
• Drug interaction overview
  • Avatrombopag is a CYP2C9 and CYP3A4 substrate; it inhibits organic anion transporter (OAT) 3 and breast cancer resistance protein (BCRP)
  • Moderate or strong dual CYP2C9 and CYP3A4 inhibitors
  • Coadministration with a moderate or strong dual CYP2C9 and CYP3A4 inhibitor increases avatrombopag AUC, which may increase the risk of avatrombopag toxicities.
  • If starting a moderate or strong dual CYP2C9 and CYP3A4 inhibitor during treatment, monitor platelet counts and adjust the avatrombopag dose as necessary.
• Moderate or strong dual CYP2C9 and CYP3A4 inducers
  • Coadministration with a moderate or strong dual CYP2C9 and CYP3A4 inducers decreases avatrombopag AUC, which may reduce the efficacy of avatrombopag.
  • If starting a moderate or strong dual CYP2C9 and CYP3A4 inducer during treatment, monitor platelet counts and adjust the avatrombopag dose as necessary.

Pregnancy and Lactation

• Based on findings from animal reproduction studies, may cause fetal harm when administered to pregnant women
• 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
• Clinical considerations
  • Interrupt breastfeeding and pump and discard breast milk in lactating women receiving avatrombopag for brief periods (. g, before an invasive procedure) during treatment and for 2 weeks after the last dose to minimize exposure to a breastfed child.