Ripretinib

Ripretinib is a prescription medicine used for the treatment of advanced gastrointestinal stromal tumor (GIST) in adults previously treated with 3 or more kinase inhibitors, including imatinib. 

• Ripretinib is available under the following different brand names: Qinlock.

Common side effects of Ripretinib include:

• hair loss
• fatigue
• nausea
• abdominal pain
• constipation
• muscle pain
• diarrhea
• decreased appetite
• hand-foot syndrome, also called palmar-plantar erythrodysesthesia (PPES)
• vomiting
• increased level of lipase
• decreased phosphate level

Serious side effects of Ripretinib include:

• redness, pain, blisters, bleeding, or swelling on hands or feet
• rash
• new warts
• changes in skin appearance
• skin sores or red bumps that bleed or do not heal
• change in size or color of a mole
• tiredness
• swelling of stomach, legs, or ankles
• shortness of breath or neck veins sticking out

Rare side effects of Ripretinib 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

• 50 mg

Gastrointestinal stromal tumors

Adult dosage

• 150 mg orally once a day
• Continue until disease progression or unacceptable toxicity

Dosage Considerations – Should be Given as Follows:

• See “Dosages”

If your medical doctor is using this medicine to treat your pain, 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.

• Ripretinib has severe interactions with no other drugs.
• Ripretinib has serious interactions with at least 21 other drugs.
• Ripretinib has moderate interactions with at least 32 other drugs.
• Ripretinib has minor interactions with no other drugs.

This information does not contain all possible interactions or adverse effects. Visit the RxList Drug Interaction Checker for any drug interactions. Therefore, before using this product, tell your doctor or pharmacist about all the products you use. Keep a list of all your medications with you and share this information with your doctor and pharmacist. Check with your healthcare professional or doctor for additional medical advice, health questions, or concerns.

Contraindications

• None

Effects of drug abuse

• None

Short-Term Effects

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

Long-Term Effects

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

Cautions

• PPES reported
  • Fetal harm may occur when administered to pregnant women
  • Therapy may cause photosensitivity reactions; advise patients to limit direct ultraviolet exposure during treatment for at least one week after discontinuation of treatment
• Wound healing complications
  • Impaired wound healing complications can occur in patients who receive drugs that inhibit the vascular endothelial growth factor (VEGF) signaling pathway; use may adversely affect wound healing
  • Withhold for at least 1 week before elective surgery; do not administer for at least 2 weeks following major surgery and until adequate wound healing
  • Safety of resumption after resolution of wound healing complications has not been established
• Primary cutaneous malignancies H4
  • Cutaneous squamous cell carcinoma was reported with a median time to event of 4.6 months. 
  • Melanoma and keratoacanthoma were also reported
  • Perform dermatologic evaluations when initiating and routinely during tre atment
  • Manage suspicious skin lesions with excision and dermatopathology evaluation; continue treatment at the same dose
• Cardiac dysfunction
  • Cardiac dysfunction (including cardiac failure, acute left ventricular failure, diastolic dysfunction, and ventricular hypertrophy) occurred
  • Grade 3 decreased ejection fraction (EF) reported
  • Safety has not been assessed in patients with a baseline EF below 50%
  • Assess EF by echocardiogram or multigated acquisition scan before initiating and during treatment, as clinically indicated
• Drug interaction overview
• Ripretinib and DP-5439 (active metabolite) inhibit CYP2C8, P-glycoprotein (P-gp), and breast cancer resistance protein (BCRP)
• DP-5439 is a substrate of P-gp and BCRP
  • DP-5439 inhibits MATE1 (multidrug and toxin extrusion protein 1)
• Strong CYP3A inhibitors
  • Coadministration with a strong CYP3A inhibitor increases Ripretinib and DP-5439 systemic exposure, which may increase the risk for adverse reactions
  • Closely monitor for adverse reactions
  • Moderate or strong CYP3A inducers
    • Avoid coadministration
    • Coadministration with a moderate or strong CYP3A inducer may decrease Ripretinib and DP-5439 systemic exposure, which may decrease antitumor activity
    • If coadministration with a moderate CYP3A inducer cannot be avoided, increase dosing frequency from the recommended dose of 150 mg once daily to 150 mg twice daily during the coadministration period; monitor for clinical response and tolerability

Pregnancy and Lactation

• Based on findings from animal studies and the drug’s mechanism of action, fetal harm may occur when administered to pregnant women
• No data is available on use in pregnant women to inform a drug-associated risk
• Verify the pregnancy status of women of reproductive potential before initiation
• Contraception
  • Women of reproductive potential: Use effective contraception during treatment and for at least 1 week after the final dose
  • Male with female partners of reproductive potential: Use effective contraception during treatment and for at least 1 week after the final dose
• Infertility
  • Based on findings from animal studies, fertility may be impaired in men of reproductive potential
• Lactation
  • No data available
  • Advise women not to breastfeed during treatment and for at least 1 week after the final dose