LuciRip (Ripretinib)

About Ripretinib

Ripretinib is a type of targeted medicine, Ripretinib inhibits the activity of the kinases KIT and PDGFRA, which helps keep cancer cells from growing.

Ripretinib is a medication for the treatment of adults with advanced gastrointestinal stromal tumor (GIST), a type of tumor that originates in the gastrointestinal tract.

Gastrointestinal Stromal Tumors

Indicated for advanced gastrointestinal stromal tumor (GIST) in adults previously treated with 3 or more kinase inhibitors, including imatinib

150 mg PO daily until disease progression or unacceptable toxicity

Dosage Modifications

Dose reduction recommendations

• Reduce to 100 mg PO daily
• Unable to tolerate 100 mg/day: Permanently discontinue

Left ventricular systolic dysfunction

• Grade 3 or 4: Permanently discontinue

Palmoplantar erythrodysesthesia syndrome (PPES)

• Grade 2

  • Withhold until Grade ≤1 or baseline; resume at the same dose if resolved within 7 days; otherwise, resume at reduced dose
  • Consider re-escalating dose if maintained at Grade ≤1 or baseline for at least 28 days
  • If PPES recurs, withhold until Grade ≤1 or baseline and then resume at a reduced dose regardless of time to improvement

• Grade 3

  • Withhold for at least 7 days or until Grade ≤1or baseline (maximum 28 days) and then resume at reduced dose
  • Consider re-escalating dose if maintained at Grade ≤1 for at least 28 days

Hypertension

• Grade 3

  • Symptomatic: Withhold until symptoms resolve and blood pressure (BP) is controlled; resume at the same dose if BP is controlled to Grade ≤1 or baseline; otherwise, resume at reduced dose
  • Grade 3 hypertension recurs: Withhold until symptoms resolve and BP is controlled; resume at reduced dose

• Grade 4

  • Permanently discontinue

Arthralgia or myalgia

• Grade 2

  • Withhold until Grade ≤1 or baseline; resume at the same dose if resolved within 7 days; otherwise, resume at reduced dose
  • Consider re-escalating dose if maintained at Grade ≤1 or baseline for at least 28 days
  • If arthralgia or myalgia recurs, withhold until Grade ≤1 or baseline and then resume at a reduced dose regardless of time to improvement

• Grade 3

  • Withhold for at least 7 days or until Grade ≤1 or baseline (maximum 28 days) and then resume at reduced dose
  • Consider re-escalating dose if maintained at Grade ≤1 or baseline for at least 28 days

Other adverse reactions

• Grade 3 or 4

  • Withhold for at least 7 days or until Grade ≤1 or baseline (maximum 28 days) and then resume at reduced dose; otherwise permanently discontinue
  • Consider re-escalating dose if maintained at Grade ≤1 for at least 28 days
  • If Grade 3 or 4 recurs, permanently discontinue

Renal impairment

• Mild-to-moderate (CrCl 30 to <90 mL/min): No clinically significant differences in the pharmacokinetics of ripretinib were observed
• Severe (CrCl 15 to 29 mL/min): Pharmacokinetics of ripretinib have not been studied

Hepatic impairment

• Mild, moderate, or severe (Child-Pugh A, B, or C): No dose adjustment necessary

CYP3A inducers

• Strong CYP3A inducers: Avoid
• Moderate CYP3A inducers: Avoid; if unavoidable, increased dose frequency to 150 mg BID during coadministration