Rilzabrutinib

Rilzabrutinib is a prescription medication indicated for the treatment of adult patients with persistent or chronic immune thrombocytopenia (ITP) who have had an insufficient response to a previous treatment.

• Rilzabrutinib is available under the following different brand names: Wayrilz.

Common side effects of Rilzabrutinib include:

• diarrhea
• nausea
• headache
• abdominal pain
• COVID-19 

Serious side effects of Rilzabrutinib include:

• increased risk of serious infections 
• hepatotoxicity, including drug-induced liver injury 

Rare side effects of Rilzabrutinib 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, coordination loss, 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 dosage

Tablet, film-coated

• 400 mg

Immune Thrombocytopenia (ITP)

Adult dosage

• 400 mg orally two times a day

Dosage Considerations – Should be Given as Follows: 

• See "Dosages"

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, healthcare provider, or pharmacist first.

Drug interaction overview

• Rilzabrutinib is a sensitive CYP3A substrate and a moderate CYP3A inhibitor
• Strong or moderate CYP3A inhibitors
• Avoid coadministration
  • If concomitant use is unavoidable and the CYP3A inhibitor is for short-term use only (e.g., less than 7 days of antibiotics), hold rilzabrutinib therapy
  • Coadministration may increase rilzabrutinib exposure and increase the risk of adverse events
• Avoid concomitant use with grapefruit, starfruit, and Seville oranges
• Strong or moderate CYP3A inducers
  • Avoid coadministration
  • Coadministration may decrease rilzabrutinib exposure, which may result in reduced efficacy
• CYP3A substrates
  • Follow CYP3A substrate recommendations for use with moderate CYP3A inhibitors
  • Coadministration may increase the exposure of CYP3A substrates and increase the risk of adverse events
• P-gp, BCRP, and OATP1B substrates
  • Follow P-gp, BCRP, and OATP1B substrate recommendations for use with P-gp, BCRP, and OATP1B inhibitors
  • In a drug interaction study, concurrent use with a P-gp substrate increased the P-gp substrate’s exposure by 13%
  • BCRP and OATP1B substrates may be inhibited at clinically relevant rilzabrutinib concentrations based on in vitro data
  • Coadministration may increase exposure of P-gp, BCRP, and OATP1B substrates and increase the risk of adverse events
• Gastric acid-reducing agents

Rilzabrutinib exhibits pH-dependent solubility

• Avoid coadministration with proton pump inhibitors (PPIs)
• Take Rilzabrutinib dose at least 2 hours before antacids or histamine-2 (H2)-receptor antagonists
• Gastric acid-reducing agents decrease rilzabrutinib exposure, which may reduce efficacy

Contraindications

• None

Effects of drug abuse

• None

Short-Term Effects

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

Long-Term Effects

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

Cautions

• Infection
  • Serious infections reported, including 1 case of fatal pneumonia
  • Monitor for signs and symptoms of infection and treat appropriately
• Hepatotoxicity
  • BTK inhibitors can cause severe, life-threatening, and potentially fatal cases of DILI
  • Transaminase elevations reported, most cases mild to moderate in severity
  • Obtain liver function test (LFT) at baseline and as clinically indicated during treatment
  • If liver test abnormalities occur, increase LFT monitoring and evaluate for clinical signs and symptoms of hepatotoxicity
  • Hold therapy if DILI suspected; discontinue therapy if DILI confirmed
• Embryo-fetal toxicity
  • May cause fetal harm when administered during pregnancy
  • Advise pregnant patients of potential fetal risk
  • Effective contraception is recommended during and after therapy in females of reproductive potential

Pregnancy and Lactation

• May cause fetal harm when administered during pregnancy, based on findings from animal studies
• There are no available data on use in pregnant patients to inform drug-associated risk of major birth defects, miscarriage, or other adverse maternal or fetal outcomes
• Advise pregnant patients of potential fetal risk
• Verify pregnancy status before starting therapy in females of reproductive potential
• Contraception requirements
  • Females of reproductive potential: Use effective contraception during therapy and for 1 week after the last dose
• Lactation
  • No data on the presence of rilzabrutinib in human milk or effects on breastfed children or on milk production
  • Due to the potential for serious adverse reactions in breastfed children, avoid breastfeeding during therapy and for 1 week after the last dose