Doptelet (avatrombopag)

Doptelet is a prescription medicine used to treat low blood platelet counts in adults with:

• long-lasting (chronic) liver disease (CLD) who are scheduled to have a medical or dental procedure.
• chronic immune thrombocytopenia (ITP) when other treatments have not worked well enough.

Doptelet is not used to make platelet counts normal in adults with chronic liver disease or chronic immune thrombocytopenia.

It is not known if Doptelet is safe and effective in children.

Doptelet may cause serious side effects, including:

Blood clots. People with chronic liver disease or chronic immune thrombocytopenia and people with certain blood clotting conditions may have an increased risk of developing blood clots. Tell your healthcare provider right away if you have signs and symptoms of a blood clot, including:

• swelling, pain, or tenderness in your legs
• fast heartbeat
• shortness of breath
• stomach (abdominal) pain or tenderness
• chest pain
• severe headache
• slurred speech, facial droop, arm or leg weakness, or severe dizziness

The most common side effects of Doptelet when used to treat low blood platelet counts in adults with chronic liver disease (CLD) who are scheduled to have a medical or dental procedure are:

• fever
• headache
• stomach (abdominal) pain
• tiredness
• nausea
• swelling of hands or feet

The most common side effects of Doptelet when used to treat low blood platelet counts in adults with chronic immune thrombocytopenia (ITP) are:

• headache
• joint pain
• tiredness
• bleeding gums
• bruising
• purple or red spots on your skin
• nosebleed
• runny nose
• upper respiratory tract infection

These are not all of the possible side effects of Doptelet.

Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

Recommended Dosage For Patients With Chronic Liver Disease

Begin Doptelet dosing 10 to 13 days prior to the scheduled procedure. The recommended daily dose of Doptelet is based on the patient’s platelet count prior to the scheduled procedure (see Table 1). Patients should undergo their procedure 5 to 8 days after the last dose of Doptelet.

Doptelet should be taken orally once daily for 5 consecutive days with food. In the case of a missed dose, patients should take the next dose of Doptelet as soon as they remember. Patients should not take two doses at one time to make up for a missed dose, and should take the next dose at the usual time the next day; all 5 days of dosing should be completed.

Table 1: Recommended Dose and Duration in Patients with Chronic Liver Disease Scheduled to Undergo a Procedure

Doptelet has been investigated only as a single 5-day once daily dosing regimen in clinical trials in patients with chronic liver disease. Doptelet should not be administered to patients with chronic liver disease in an attempt to normalize platelet counts.

Monitoring

Obtain a platelet count prior to administration of Doptelet therapy and on the day of a procedure to ensure an adequate increase in platelet count.

Recommended Dosage For Patients With Chronic Immune Thrombocytopenia

Use the lowest dose of Doptelet needed to achieve and maintain a platelet count greater than or equal to 50×10⁹/L as necessary to reduce the risk for bleeding. Dose adjustments are based on platelet count response. Do not use Doptelet to normalize platelet counts.

Initial Dose Regimen

Begin Doptelet at a starting dose of 20 mg (1 tablet) once daily with food.

Monitoring

After initiating therapy with Doptelet, assess platelet counts weekly until a stable platelet count greater than or equal to 50×10⁹/L has been achieved, and then obtain platelet counts monthly thereafter. Obtain platelet counts weekly for at least 4 weeks following discontinuation of Doptelet.

Dose adjustments (see Table 2 and Table 3) are based on the platelet count response. Do not exceed a daily dose of 40 mg (2 tablets).

Table 2: Doptelet Dose Adjustments for Patients with Chronic Immune Thrombocytopenia

Table 3: Doptelet Dose Levels for Titration in Patients with Chronic Immune Thrombocytopenia

In the case of a missed dose, patients should take the missed dose of Doptelet as soon as they remember. Patients should not take two doses at one time to make up for a missed dose, and should take the next dose per the current regimen.

Discontinuation

Discontinue Doptelet if the platelet count does not increase to greater than or equal to 50×10⁹ /L after 4 weeks of dosing at the maximum dose of 40 mg once daily. Discontinue Doptelet if the platelet count is greater than 400×10⁹ /L after 2 weeks of dosing at 20 mg once weekly.

Recommended Dosage With Concomitant Moderate Or Strong Dual Inducers Or Inhibitors Of CYP2C9 And CYP3A4 In Patients With Chronic Immune Thrombocytopenia

The recommended starting doses of Doptelet in patients with chronic immune thrombocytopenia receiving concomitant medications are summarized in Table 4.

Table 4:Doptelet Recommended Starting Dose for Patients with Chronic Immune Thrombocytopenia Based on Concomitant Medications

Effect Of Other Drugs On Doptelet In Patients With Chronic Immune Thrombocytopenia

Moderate Or Strong Dual Inhibitors Of CYP2C9 And CYP3A4

• Concomitant use with a moderate or strong dual inhibitor of CYP2C9 and CYP3A4 increases avatrombopag AUC, which may increase the risk of Doptelet toxicities. Reduce the starting dosage of Doptelet when used concomitantly with a moderate or strong dual inhibitor of CYP2C9 and CYP3A4 (see Table 4).
• In patients starting moderate or strong dual inhibitors of CYP2C9 and CYP3A4 while receiving Doptelet, monitor platelet counts and adjust Doptelet dose as necessary (see Table 3).

Moderate Or Strong Dual Inducers Of CYP2C9 And CYP3A4

• Concomitant use with a moderate or strong dual inducer of CYP2C9 and CYP3A4 decreases avatrombopag AUC which may reduce Doptelet efficacy. Increase the recommended starting dosage of Doptelet when used concomitantly with a moderate or strong dual inducer of CYP2C9 and CYP3A4 (see Table 4).
• In patients starting moderate or strong dual inducers of CYP2C9 and CYP3A4 while receiving Doptelet, monitor platelet counts and adjust Doptelet dose as necessary (see Table 3).

Patients with Chronic Liver Disease

• No dosage adjustments are required for patients with chronic liver disease.

• Based on findings from animal reproduction studies, Doptelet may cause fetal harm when administered to a pregnant woman. The available data on Doptelet in pregnant women are insufficient to inform a drug-associated risk of adverse developmental outcomes.
• There is no information regarding the presence of avatrombopag in human milk, the effects on the breastfed 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 breastfed child from Doptelet, breastfeeding is not recommended during treatment with Doptelet and for at least 2 weeks after the last dose