ripretinib (Rx)

Brand and Other Names:Qinlock
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Dosing & Uses

AdultPediatric

Dosage Forms & Strengths

tablet

  • 50mg

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 qDay

Continue until disease progression or unacceptable toxicity

Dosage Modifications

Dose reduction recommendations

  • Reduce to 100 mg qDay
  • 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 (total bilirubin [TB] ≤ULN and AST >ULN or TB 1-1.5x ULN and any AST): No dose adjustment necessary
  • Moderate or severe: Recommended dosage has not been established

Dosing Considerations

Verify pregnancy status of females of reproductive potential before initiating

Safety and efficacy not established

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Interactions

Interaction Checker

and ripretinib

No Results

     activity indicator 
    No Interactions Found
    Interactions Found

    Contraindicated

      Serious - Use Alternative

        Significant - Monitor Closely

          Minor

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            Adverse Effects

            >10%

            All grades

            • Alopecia (52%)
            • Fatigue (42%)
            • Nausea (39%)
            • Abdominal pain (36%)
            • Increased aPTT (35%)
            • Constipation (34%)
            • Myalgia (32%)
            • Increased lipase (32%)
            • Diarrhea (28%)
            • Decreased appetite (27%)
            • Decreased phosphate (26%)
            • Increased triglycerides (26%)
            • Decreased calcium (23%)
            • Increased blood bilirubin (22%)
            • PPES (21%)
            • Increased CPK (21%)
            • Increased INR (21%)
            • Vomiting (21%)
            • Decreased weight (19%)
            • Headache (19%)
            • Arthralgia (18%)
            • Decreased sodium (17%)
            • Peripheral edema (17%)
            • Increased creatinine (16%)
            • Muscle spasms (15%)
            • Hypertension (14%)
            • Dyspnea (13%)
            • Increased serum amylase (13%)
            • Dry skin (13%)
            • Asthenia (13%)
            • Increased ALT (12%)
            • Stomatitis (11%)
            • Pruritus (11%)

            1-10%

            All grades

            • Decreased neutrophil count (10%)

            Grade 3-4

            • Abdominal pain (7%)
            • Hypertension (7%)
            • Increased lipase (7%)
            • Decreased phosphate (4.9%)
            • Increased INR (3.8%)
            • Fatigue (3.5%)
            • Nausea (3.5%)
            • Vomiting (3.5%)
            • Decreased sodium (2.4%)
            • Increased triglycerides (2.4%)
            • Peripheral edema (1.2%)
            • Asthenia (1.2%)
            • Constipation (1.2%)
            • Diarrhea (1.2%)
            • Decreased appetite (1.2%)
            • Myalgia (1.2%)
            • Increased serum amylase (1.2%)
            • Increased ALT (1.2%)
            • Increased CPK (1.2%)
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            Warnings

            Contraindications

            None

            Cautions

            PPES reported

            Fetal harm may occur when administered to pregnant females

            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 occurred with a median time to event of 4.6 months
            • Melanoma and keratoacanthoma also reported
            • Perform dermatologic evaluations when initiating and routinely during treatment
            • Manage suspicious skin lesions with excision and dermatopathologic evaluation; continue 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 <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-gp (P-glycoprotein), and BCRP (breast cancer resistance protein)
            • 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 risk of adverse reactions
              • Closely monitor for adverse reactions
            • Strong CYP3A inducers
              • Avoid coadministration
              • Coadministration with a strong CYP3A inducer may decrease ripretinib and DP-5439 systemic exposure, which may decrease antitumor activity
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            Pregnancy & Lactation

            Pregnancy

            Based on findings from animal studies and its mechanism of action, fetal harm may occur when administered to pregnant females

            No data available on use in pregnant females to inform a drug-associated risk

            Verify pregnancy status of females of reproductive potential before initiation

            Animal data

            • Administration to pregnant rats and rabbits during organogenesis resulted in malformations primarily associated with the cardiovascular and skeletal systems, anatomic variations, reduced fetal body weight, and increased postimplantation loss at maternal exposures that were approximately equal to 150 mg
            • Advise pregnant females of the potential risk to a fetus

            Contraception

            • Females of reproductive potential: Use effective contraception during treatment and for at least 1 week after the final dose
            • Males 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 males of reproductive potential

            Lactation

            No data available

            Advise females not to breastfeed during treatment and for at least 1 week after the final dose

            Pregnancy Categories

            A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.

            B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.

            C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.

            D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.

            X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.

            NA: Information not available.

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            Pharmacology

            Mechanism of Action

            Broad-spectrum inhibitor or proto-oncogene receptor tyrosine kinase (KIT) and platelet derived growth factor receptor-A (PDGFRA), including wild type, primary, and secondary mutations

            Also, inhibits other kinases in vitro (eg, PDGFRB, TIE2, VEGFR2, BRAF)

            Absorption

            Steady-state achieved in 14 days

            Peak plasma concentration

            • Ripretinib: 761 ng/mL
            • DP-5439 (active metabolite): 804 ng/mL

            Peak plasma time

            • Ripretinib: 4 hr
            • DP-5439: 15.6 hr

            AUC H4

            • Ripretinib: 5678 ng·hr/mL
            • DP-5439: 7138 ng·hr/mL

            Distribution

            Vd (steady-state)

            • Ripretinib: 307 L
            • DP-5439: 507 L

            Protein bound

            • Human serum albumin
              • Ripretinib: 99.8%
              • DP-5439: 99.7%
            • Alpha-1 acid glycoprotein
              • Ripretinib: 99.4%
              • DP-5439: >99.8%

            Metabolism

            Major pathway: CYP3A4 (ripretinib and DP-5439 [active metabolite])

            Minor pathway

            • Ripretinib: CYP2C8 and CYP2D6
            • DP-5439: CYP2C8, CYP2E1, and CYP2D6

            Elimination

            Excretion

            • Ripretinib: Feces (34%); urine (0.02%)
            • DP-5439: Feces (6%); urine (0.1%)
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            Administration

            Oral Administration

            May take with or without food at the same time each day

            Swallow tablets whole

            Missed dose <8 hr passed since missed scheduled dose: May take missed dose

            Vomited dose: Do not to take an additional dose and continue with next scheduled dose

            Storage

            Dispense in original container only

            Store in the original container with the desiccant to protect from moisture and light

            Replace cap securely each time after opening; do not discard desiccant

            Store at 20-25ºC (68-77ºF); excursion permitted to 15-30ºC (59-86ºF)

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            Formulary

            FormularyPatient Discounts

            Adding plans allows you to compare formulary status to other drugs in the same class.

            To view formulary information first create a list of plans. Your list will be saved and can be edited at any time.

            Adding plans allows you to:

            • View the formulary and any restrictions for each plan.
            • Manage and view all your plans together – even plans in different states.
            • Compare formulary status to other drugs in the same class.
            • Access your plan list on any device – mobile or desktop.

            The above information is provided for general informational and educational purposes only. Individual plans may vary and formulary information changes. Contact the applicable plan provider for the most current information.

            Tier Description
            1 This drug is available at the lowest co-pay. Most commonly, these are generic drugs.
            2 This drug is available at a middle level co-pay. Most commonly, these are "preferred" (on formulary) brand drugs.
            3 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs.
            4 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
            5 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
            6 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
            NC NOT COVERED – Drugs that are not covered by the plan.
            Code Definition
            PA Prior Authorization
            Drugs that require prior authorization. This restriction requires that specific clinical criteria be met prior to the approval of the prescription.
            QL Quantity Limits
            Drugs that have quantity limits associated with each prescription. This restriction typically limits the quantity of the drug that will be covered.
            ST Step Therapy
            Drugs that have step therapy associated with each prescription. This restriction typically requires that certain criteria be met prior to approval for the prescription.
            OR Other Restrictions
            Drugs that have restrictions other than prior authorization, quantity limits, and step therapy associated with each prescription.
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            Medscape prescription drug monographs are based on FDA-approved labeling information, unless otherwise noted, combined with additional data derived from primary medical literature.