QINLOCK
Clinical safety rating: caution
Comprehensive clinical and safety monograph for QINLOCK (QINLOCK).
Ripretinib is a switch-control tyrosine kinase inhibitor that inhibits KIT proto-oncogene receptor tyrosine kinase (KIT) and platelet-derived growth factor receptor alpha (PDGFRA) kinase signaling. It binds to both the switch pocket and the activation loop of KIT and PDGFRA, preventing kinase activation and inhibiting downstream signaling pathways involved in tumor cell proliferation and survival.
| Metabolism | Primarily metabolized by CYP3A4, with minor contributions from CYP2C8 and CYP2D6. |
| Excretion | Primarily hepatic metabolism, with <1% excreted unchanged in urine. Fecal excretion accounts for approximately 80% of the administered dose, with renal excretion of unchanged drug being minimal (<1%). |
| Half-life | Terminal elimination half-life is approximately 15 hours (range 11–20 hours) in patients with advanced GIST. This supports twice-daily dosing. |
| Protein binding | Approximately 94% bound to plasma proteins, primarily albumin. |
| Volume of Distribution | Apparent volume of distribution (Vd/F) is approximately 2,100 L (range 1,400–3,100 L), indicating extensive tissue distribution. |
| Bioavailability | Oral bioavailability is approximately 70% (range 50–90%) under fasting conditions. Absorption is reduced by high-fat meals (AUC decreased by about 30%). |
| Onset of Action | Clinical response (e.g., symptom improvement, tumor response) may be observed within 2–4 weeks of initiating therapy at the recommended dose. |
| Duration of Action | Continuous therapy is required to maintain disease control. Treatment duration is variable and based on individual patient tolerability and clinical response; median treatment duration in clinical trials was approximately 6 months. |
| Molecular Weight | 559.7 |
150 mg orally once daily with food, until disease progression or unacceptable toxicity.
| Dosage form | TABLET |
| Renal impairment | No dose adjustment required for mild to moderate renal impairment (CrCl ≥30 mL/min). Not studied in severe renal impairment (CrCl <30 mL/min) or end-stage renal disease. |
| Liver impairment | Mild hepatic impairment (Child-Pugh A): no adjustment. Moderate (Child-Pugh B): reduce dose to 100 mg orally once daily. Severe (Child-Pugh C): not recommended. |
| Pediatric use | Safety and efficacy not established in pediatric patients. |
| Geriatric use | No specific dose adjustment; no overall differences in safety or efficacy observed in patients aged ≥65 years compared to younger adults. |
| 1st trimester | Limited human data; animal studies show embryotoxicity and teratogenicity. Avoid use during first trimester unless benefit outweighs risk. |
| 2nd trimester | Limited human data; potential for fetal harm. Use only if clearly needed and after careful risk-benefit assessment. |
| 3rd trimester | Limited human data; potential for fetal harm. Use only if clearly needed and after careful risk-benefit assessment. |
Clinical note
Comprehensive clinical and safety monograph for QINLOCK (QINLOCK).
| Placental transfer | Expected to cross placenta due to molecular weight; no specific data available. |
| Breastfeeding | No data on presence in human milk; however, due to molecular weight and potential for serious adverse effects, breastfeeding is not recommended during therapy and for at least 2 weeks after last dose. |
■ FDA Black Box Warning
None.
| Serious Effects |
Hypersensitivity to ripretinib or any excipients
| Precautions | Palmar-plantar erythrodysesthesia (hand-foot skin reaction), Hypertension, Cardiac dysfunction (including left ventricular ejection fraction reduction), Hemorrhage and gastrointestinal perforation, Wound healing complications, Hepatotoxicity, Embryo-fetal toxicity |
| Food/Dietary | Avoid grapefruit and grapefruit juice as they may increase ripretinib concentrations. No other food restrictions known. Take with or without food. |
| Clinical Pearls |
Loading safety data…
| Lactation Rating |
| L5 - Contraindicated |
| Teratogenic Risk | QINLOCK (ripretinib) is a kinase inhibitor. Based on its mechanism of action and animal studies, it may cause fetal harm when administered to pregnant women. There are no adequate and well-controlled studies in pregnant women. In animal reproduction studies, ripretinib caused embryo-fetal toxicity including reduced fetal body weights and skeletal abnormalities at maternal exposures below the recommended human dose. Therefore, it is contraindicated in pregnancy. Women of childbearing potential should use effective contraception during treatment and for at least 2 weeks after the last dose. |
| Fetal Monitoring | Monitor pregnant women exposed to QINLOCK for fetal toxicity. Perform pregnancy testing prior to initiation of therapy in women of childbearing potential. Use effective contraception during treatment and for at least 2 weeks post-treatment. No specific fetal monitoring guidelines established; consider ultrasound and fetal assessment if exposure occurs. |
| Fertility Effects | Based on animal studies, ripretinib may impair fertility in males and females of reproductive potential. In female rats, ripretinib caused decreased fertility and early embryo loss at clinically relevant exposures. In male rats, impaired spermatogenesis and reduced testicular weight were observed. The reversibility of these effects is unknown. |
| QINLOCK (ripretinib) is a switch-control tyrosine kinase inhibitor approved for advanced gastrointestinal stromal tumor (GIST) after prior treatment with imatinib, sunitinib, and regorafenib. Monitor for palmar-plantar erythrodysesthesia syndrome, hypertension, fatigue, and alopecia. ECG monitoring for QTc prolongation is recommended, especially in patients with electrolyte abnormalities or on QTc-prolonging drugs. Dose modifications are required for moderate to severe hepatic impairment. |
| Patient Advice | Take QINLOCK exactly as prescribed, with or without food, at the same time each day. · Do not crush, chew, or split tablets; swallow whole. · Report new or worsening skin reactions on palms or soles, severe fatigue, or muscle spasms. · Avoid grapefruit and grapefruit juice during treatment. · Use effective contraception during treatment and for at least 1 week after the last dose. · Inform your doctor of all medications, including over-the-counter drugs and supplements. · Do not drive or operate machinery if you experience dizziness or fatigue. |