Ripretinib
Ripretinib Uses, Dosage, Side Effects, Food Interaction and all others data.
Ripretinib is a kinase inhibitor used for the treatment of advanced gastrointestinal stromal tumor (GIST) that has not adequately responded to other kinase inhibitors such as sunitinib and imatinib. Ripretinib, also known as Qinlock, is manufactured by Deciphera Pharmaceuticals and was initially approved by the FDA on May 15, 2020.
It is the first drug approved as a fourth-line therapy in the specific setting of prior treatment with a minimum of 3 other kinase inhibitors.
As a broad-spectrum kinase inhibitor, ripretinib inhibits various gene mutations, increasing progression-free survival in patients with advanced gastrointestinal stromal tumors (GIST). It is effective in treating mutations that are resistant to chemotherapy with other kinase inhibitors, such as imatinib.
| Trade Name | Ripretinib |
| Availability | Prescription only |
| Generic | Ripretinib |
| Ripretinib Other Names | Ripretinib |
| Related Drugs | imatinib, Gleevec, sunitinib, Sutent, Stivarga, avapritinib |
| Weight | 50mg |
| Type | Oral tablet |
| Formula | C24H21BrFN5O2 |
| Weight | Average: 510.367 Monoisotopic: 509.086266 |
| Protein binding | Ripretinib is over 99% bound to albumin and alpha-1 acid glycoprotein. |
| Groups | Approved |
| Therapeutic Class | |
| Manufacturer | |
| Available Country | United States |
| Last Updated: | September 19, 2023 at 7:00 am |
Uses
Ripretinib is a kinase inhibitor used to treat advanced gastrointestinal stromal tumor (GIST).
Ripretinib is indicated to treat adults diagnosed with advanced gastrointestinal stromal tumor (GIST) who have had prior therapy with at least 3 kinase inhibitors, including the imatinib.
Ripretinib is also used to associated treatment for these conditions: Advanced Gastrointestinal Stromal Tumor (GIST)
How Ripretinib works
Protein kinases play important roles in cellular function, and their dysregulation can lead to carcinogenesis. Ripretinib inhibits protein kinases including wild type and mutant platelet-derived growth factor receptor A (PDGFRA) and KIT that cause the majority of gastrointestinal stromal tumor (GIST). In vitro, ripretinib has been shown to inhibit PDGFRB, BRAF, VEGF, and TIE2 genes.
Ripretinib binds to KIT and PDGFRA receptors with mutations on the exons 9, 11, 13, 14, 17 and 18 (for KIT mutations), and exons 12, 14 and 18 (for PDGFRA mutations). The “switch pocket” of a protein kinase is normally bound to the activation loop, acting as an “on-off switch” of a kinase. Ripretinib boasts a unique dual mechanism of action of binding to the kinase switch pocket as well as the activation loop, thereby turning off the kinase and its ability to cause dysregulated cell growth.
Toxicity
There is limited information in the literature regarding an overdose with ripretinib, and LD50 information is not readily available. Like other kinase inhibitors, an overdose with ripretinib likely results in hematological toxicity, skin toxicity, as well as muscle, liver, and gastrointestinal toxicity.
Food Interaction
- Take with or without food.
[Moderate] MONITOR: Grapefruit juice may increase the plasma concentrations of orally administered drugs that are substrates of the CYP450 3A4 isoenzyme.
The proposed mechanism is inhibition of CYP450 3A4-mediated first-pass metabolism in the gut wall by certain compounds present in grapefruit.
Because grapefruit juice inhibits primarily intestinal rather than hepatic CYP450 3A4, the magnitude of interaction is greatest for those drugs that undergo significant presystemic metabolism by CYP450 3A4 (i.e., drugs with low oral bioavailability).
In general, the effect of grapefruit juice is concentration-, dose- and preparation-dependent, and can vary widely among brands.
Certain preparations of grapefruit juice (e.g., high dose, double strength) have sometimes demonstrated potent inhibition of CYP450 3A4, while other preparations (e.g., low dose, single strength) have typically demonstrated moderate inhibition.
Pharmacokinetic interactions involving grapefruit juice are also subject to a high degree of interpatient variability, thus the extent to which a given patient may be affected is difficult to predict.
MANAGEMENT: Patients who regularly consume grapefruit or grapefruit juice should be monitored for adverse effects and altered plasma concentrations of drugs that undergo significant presystemic metabolism by CYP450 3A4.
Grapefruit and grapefruit juice should be avoided if an interaction is suspected.
Orange juice is not expected to interact with these drugs.
Ripretinib Hypertension interaction
[Moderate] Ripretinib may cause hypertension.
It is recommended to control blood pressure prior to initiating therapy and monitor blood pressure as clinically indicated during treatment.
Based on severity, withhold treatment with ripretinib and resume at the same or reduced dose or permanently discontinue.
Do not initiate ripretinib in patients with uncontrolled hypertension.
Ripretinib Drug Interaction
Moderate: amlodipineUnknown: tamsulosin, meloxicam, paroxetine, omeprazole
Ripretinib Disease Interaction
Volume of Distribution
The mean volume of distribution of ripretinib is 307 L.
Elimination Route
Ripretinib is absorbed in the gastrointestinal tract and Tmax is achieved in 4 hours, with steady-state concentrations reached within 14 days.
Half Life
The average half-life of ripretinib is 14.8 hours.
Clearance
The mean apparent clearance of ripretinib is 15.3 L/hour.
Elimination Route
Ripretinib is 34% excreted in the feces and 0.2% excreted in the urine.
Innovators Monograph
You find simplified version here Ripretinib
