The FDA has finally approved WAYRILZ™ (rilzabrutinib) in 2025, making it one of the newest targeted therapies for adults living with persistent or chronic immune thrombocytopenia (ITP) who have not responded adequately to previous treatments.

As ITP management continues to evolve from steroids and IVIG toward targeted immunomodulators, WAYRILZ brings a unique mechanism and a promising clinical profile.

What Exactly Is WAYRILZ?

WAYRILZ is a Bruton’s Tyrosine Kinase (BTK) inhibitor—but unlike older BTK inhibitors used in CLL or lymphomas, rilzabrutinib is highly selective and designed to modulate the immune attack on platelets without causing broad immunosuppression.

In simpler terms:

👉 It reduces the autoimmune destruction of platelets

👉 Without significantly suppressing the entire immune system

👉 Making it safer than many older agents

Who Should Receive WAYRILZ? (FDA-Approved Use)

WAYRILZ is indicated for:

✔ Adults with persistent or chronic ITP

✔ Who had an insufficient response to at least one previous therapy

This includes patients who failed or did not tolerate:

• Corticosteroids
• IVIG
• Thrombopoietin receptor agonists (TPO-RAs: eltrombopag, romiplostim, avatrombopag)
• Rituximab
• Immunosuppressants
• Splenectomy candidates or those refusing splenectomy

Where Does WAYRILZ Fit in the ITP Treatment Algorithm?

WAYRILZ is best considered in:

1. Steroid-refractory ITP

When patients relapse after prednisone or dexamethasone pulses.

2. Patients who did not tolerate TPO-RAs

Ideal for those who could not use:

• Eltrombopag (liver issues, food restrictions)
• Romiplostim (injectable, expensive)
• Avatrombopag

BTK inhibitors can work synergistically or as an alternative.

3. Patients looking for an oral, non-immunosuppressive option

Especially those unwilling to take rituximab or azathioprine.

4. Pre-splenectomy

A trial of WAYRILZ may avoid the need for surgery.

5. Elderly ITP patients

Because BTK inhibitors generally have better tolerability than strong immunosuppressants.

Dosing and How to Take WAYRILZ

FDA-recommended dose:

➡️ 400 mg orally twice daily (800 mg/day total)

Administration details:

• Take with or without food
• Swallow tablets whole
• Do NOT cut, crush, or chew (affects bioavailability)
• Use plain water—avoid acidic beverages around dosing
• Maintain consistent timing every day

Important Drug Interactions

WAYRILZ is metabolized via CYP3A, so interactions matter.

Avoid:

🚫 Strong or moderate CYP3A inhibitors

e.g., ketoconazole, clarithromycin, grapefruit

🚫 Strong or moderate CYP3A inducers

e.g., rifampin, carbamazepine, phenytoin

🚫 Proton Pump Inhibitors (PPIs)

e.g., omeprazole, esomeprazole

(They reduce absorption)

If needed:

• Take WAYRILZ 2 hours before antacids or H2 blockers.

Side Effects – What Clinicians Should Watch For

Overall, WAYRILZ was well tolerated in trials, with mostly low-grade GI and viral symptoms.

Most Common Side Effects (≥10%):

Serious but Less Common Side Effects

1. Serious Infections

Although WAYRILZ is highly selective, infections can occur.

• Monitor for fever, cough, urinary symptoms
• Avoid use in uncontrolled infections
• Counsel patients on early reporting

2. Hepatotoxicity & Drug-Induced Liver Injury

FDA warns of potential liver enzyme elevation.

Monitoring plan:

• Baseline LFTs (bilirubin, AST, ALT)
• Repeat as clinically indicated
• Hold drug if significant increase is noted

3. Embryo-Fetal Toxicity

Early animal data suggests potential fetal harm.

Advice:

• Avoid in pregnancy
• Use effective contraception during treatment
• Do not breastfeed

4. Renal & Hepatic Impairment

Avoid use in:

• Moderate to severe hepatic impairment
• Severe renal impairment

Why WAYRILZ Matters in ITP

ITP treatment has traditionally relied on steroids, IVIG, and immunosuppressants—many of which come with significant toxicity.

WAYRILZ offers:

✔ A targeted, once-daily oral therapy

✔ Good tolerability

✔ Lower immunosuppression

✔ A new mechanism for patients who fail existing options

As more data emerges from real-world use, WAYRILZ may become a routine second-line option, especially in patients wanting effective but gentler therapies.

Bottom Line for Clinicians

WAYRILZ is a promising new entry into the ITP landscape. While not a first-line therapy, it is an excellent choice after inadequate response to steroids or TPO-RAs—particularly in patients wanting an oral, selective, and relatively safer option