Is Avalet safe for long-term use?

jnspharma

Avalet, whose active ingredient is avatrombopag, is a medication primarily used to treat thrombocytopenia (low platelet count) in adults with:

Chronic Liver Disease (CLD) who are scheduled to undergo a procedure.
Chronic Immune Thrombocytopenia (ITP) who have had an insufficient response to a previous treatment.
The question of whether Avalet is safe for long-term use is complex and depends on the specific condition being treated, individual patient factors, and careful medical monitoring. Here's a breakdown of the considerations:

How Avalet Works:

Avatrombopag is a thrombopoietin (TPO) receptor agonist. It stimulates the proliferation and differentiation of megakaryocytes (cells in the bone marrow that produce platelets), leading to an increased production of platelets. This helps to reduce the risk of bleeding in patients with low platelet counts.

Long-Term Use in Chronic Immune Thrombocytopenia (ITP):

For patients with chronic ITP, Avalet 20 mg (Avatrombopag) is often used as a long-term treatment to maintain adequate platelet levels and prevent bleeding. Studies have shown that avatrombopag can achieve rapid and sustained platelet responses in ITP patients, including in long-term use. A recent real-world observational study on Chinese children with primary ITP demonstrated sustained response at 24 and 48 weeks without significant or new adverse events. Another study on adults who switched to avatrombopag from other TPO-RAs also showed sustained effectiveness and improved treatment satisfaction over 90 days.

Long-Term Use in Chronic Liver Disease (CLD):

In CLD, Avalet is typically used for a shorter duration, specifically before procedures to increase platelet counts and minimize bleeding risk. The clinical trials for CLD patients focused on a single 5-day once-daily dosing regimen prior to a procedure. Therefore, long-term continuous use in CLD specifically for platelet count management outside of procedural preparation is not as well-established or recommended as a standard approach. However, real-world data in liver cancer patients with severe thrombocytopenia (with or without CLD) suggested that avatrombopag was safe and effective in ensuring successful implementation of anticancer treatment, with no thrombosis or hemorrhagic events observed.

Potential Side Effects and Risks (Relevant for Long-Term Use):

While generally considered safe when used as directed, Avalet, like all medications, carries potential side effects and risks, which can be particularly relevant for long-term use:

Thrombotic/Thromboembolic Complications: As a TPO receptor agonist, Avalet stimulates platelet production. An excessive increase in platelet count (thrombocytosis) can increase the risk of blood clots (thrombosis). This is a significant concern, especially in patients with pre-existing risk factors for blood clots or conditions that can exacerbate clotting. Regular platelet monitoring is crucial to manage this risk, and dose adjustments are made to keep platelet counts within a safe range (typically not aiming to normalize platelet counts, but rather to keep them above a threshold to reduce bleeding risk, e.g., ≥50×10
9
/L).

Liver Function: While used in patients with liver disease, Avalet is metabolized by the liver (CYP2C9 and CYP3A4). Liver function should be monitored before starting treatment and regularly thereafter. Patients with severe liver disease or active liver disease may require dose adjustments or may not be suitable candidates for Avalet.

Common Side Effects: Many side effects are generally mild and may decrease over time. These can include:

Headache
Fatigue
Nausea
Abdominal pain
Peripheral edema (swelling of extremities)
Joint pain (arthralgia)
Muscle pain
Indigestion
Urinary tract infection
Abnormal liver function tests

Less Common/Serious Side Effects: Patients should be monitored for:

Signs of blood clots (e.g., chest pain, shortness of breath, sudden numbness or weakness, severe headache, leg pain/swelling).
Signs of liver problems (e.g., unusual dark urine, yellowing of skin or eyes, severe stomach pain).

Allergic reactions (rash, hives, swelling of face/lips/tongue).

Pregnancy and Breastfeeding: Avalet is considered unsafe during pregnancy and breastfeeding due to potential harm to the developing baby. Women of reproductive potential should be advised of the risks and to inform their doctor if they are pregnant or suspect pregnancy. Breastfeeding should be avoided during treatment and for at least two weeks after the final dose.

Diabetes: Diabetic patients should monitor their blood sugar levels closely, as Avalet may cause an increase in blood sugar.
Important Considerations for Long-Term Safety:

Individualized Treatment: The decision for long-term use of Avalet must always be made by a qualified healthcare professional who considers the patient's specific medical condition, overall health, other medications, and potential risks versus benefits.

Regular Monitoring: Close and regular monitoring of platelet counts, liver function, and general health is essential for patients on long-term Avalet therapy to detect and manage potential adverse effects promptly.

Adherence to Dosage: Patients should adhere strictly to the prescribed dosage and not discontinue the medication or adjust the dose without consulting their doctor.

Drug Interactions: Avalet can interact with other medications, particularly moderate or strong dual inhibitors of CYP2C9 and CYP3A4. Patients should inform their doctor about all medications, supplements, and herbal products they are taking.

Conclusion:

For patients with chronic immune thrombocytopenia (ITP), Avalet (avatrombopag) is generally considered safe and effective for long-term use when administered under careful medical supervision and with regular monitoring to prevent thrombotic complications and manage other potential side effects. The goal is to maintain platelet counts at a level that reduces bleeding risk without increasing the risk of clots.

For patients with chronic liver disease (CLD) requiring a procedure, Avalet is indicated for short-term use to elevate platelet counts. Its long-term continuous use in CLD for general platelet management is not the primary indication and would require careful consideration and monitoring beyond established protocols.

Ultimately, the safety of Avalet for long-term use hinges on appropriate patient selection, strict adherence to prescribed dosage, and continuous monitoring by a healthcare provider who can assess the ongoing benefit-risk profile for the individual patient.