Dosing & Uses
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, 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
Dosing Considerations
Verify pregnancy status of females of reproductive potential before initiating
Safety and efficacy not established
Interactions
Interaction Checker
No Results
Contraindicated
Serious - Use Alternative
Significant - Monitor Closely
Minor
Contraindicated (0)
Serious - Use Alternative (22)
- amobarbital
amobarbital will decrease the level or effect of ripretinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Coadministration with a strong CYP3A inhibitor will decrease systemic exposure to ripretinib and its active metabolite (DP-5439), which may decrease risk of adverse reactions.
- apalutamide
apalutamide will decrease the level or effect of ripretinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Coadministration with a strong CYP3A inhibitor will decrease systemic exposure to ripretinib and its active metabolite (DP-5439), which may decrease risk of adverse reactions.
- bosentan
bosentan will decrease the level or effect of ripretinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Coadministration with a strong CYP3A inhibitor will decrease systemic exposure to ripretinib and its active metabolite (DP-5439), which may decrease risk of adverse reactions.
- carbamazepine
carbamazepine will decrease the level or effect of ripretinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Coadministration with a strong CYP3A inhibitor will decrease systemic exposure to ripretinib and its active metabolite (DP-5439), which may decrease risk of adverse reactions.
- dabrafenib
dabrafenib will decrease the level or effect of ripretinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Coadministration with a strong CYP3A inhibitor will decrease systemic exposure to ripretinib and its active metabolite (DP-5439), which may decrease risk of adverse reactions.
- efavirenz
efavirenz will decrease the level or effect of ripretinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Coadministration with a strong CYP3A inhibitor will decrease systemic exposure to ripretinib and its active metabolite (DP-5439), which may decrease risk of adverse reactions.
- enzalutamide
enzalutamide will decrease the level or effect of ripretinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Coadministration with a strong CYP3A inhibitor will decrease systemic exposure to ripretinib and its active metabolite (DP-5439), which may decrease risk of adverse reactions.
- etrasimod
etrasimod, ripretinib. Either increases effects of the other by immunosuppressive effects; risk of infection. Avoid or Use Alternate Drug. Risk of additive immune system effects with etrasimod has not been studied in combination with antineoplastic, immune-modulating, or noncorticosteroid immunosuppressive therapies. Avoid coadministration during and in the weeks following administration of etrasimod. .
- etravirine
etravirine will decrease the level or effect of ripretinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Coadministration with a strong CYP3A inhibitor will decrease systemic exposure to ripretinib and its active metabolite (DP-5439), which may decrease risk of adverse reactions.
- fosphenytoin
fosphenytoin will decrease the level or effect of ripretinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Coadministration with a strong CYP3A inhibitor will decrease systemic exposure to ripretinib and its active metabolite (DP-5439), which may decrease risk of adverse reactions.
- lumacaftor/ivacaftor
lumacaftor/ivacaftor will decrease the level or effect of ripretinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Coadministration with a strong CYP3A inhibitor will decrease systemic exposure to ripretinib and its active metabolite (DP-5439), which may decrease risk of adverse reactions.
- mitotane
mitotane will decrease the level or effect of ripretinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Coadministration with a strong CYP3A inhibitor will decrease systemic exposure to ripretinib and its active metabolite (DP-5439), which may decrease risk of adverse reactions.
- nafcillin
nafcillin will decrease the level or effect of ripretinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Coadministration with a strong CYP3A inhibitor will decrease systemic exposure to ripretinib and its active metabolite (DP-5439), which may decrease risk of adverse reactions.
- pentobarbital
pentobarbital will decrease the level or effect of ripretinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Coadministration with a strong CYP3A inhibitor will decrease systemic exposure to ripretinib and its active metabolite (DP-5439), which may decrease risk of adverse reactions.
- phenobarbital
phenobarbital will decrease the level or effect of ripretinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Coadministration with a strong CYP3A inhibitor will decrease systemic exposure to ripretinib and its active metabolite (DP-5439), which may decrease risk of adverse reactions.
- phenytoin
phenytoin will decrease the level or effect of ripretinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Coadministration with a strong CYP3A inhibitor will decrease systemic exposure to ripretinib and its active metabolite (DP-5439), which may decrease risk of adverse reactions.
- primidone
primidone will decrease the level or effect of ripretinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Coadministration with a strong CYP3A inhibitor will decrease systemic exposure to ripretinib and its active metabolite (DP-5439), which may decrease risk of adverse reactions.
- rifabutin
rifabutin will decrease the level or effect of ripretinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Coadministration with a strong CYP3A inhibitor will decrease systemic exposure to ripretinib and its active metabolite (DP-5439), which may decrease risk of adverse reactions.
- rifampin
rifampin will decrease the level or effect of ripretinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Coadministration with a strong CYP3A inhibitor will decrease systemic exposure to ripretinib and its active metabolite (DP-5439), which may decrease risk of adverse reactions.
- rifapentine
rifapentine will decrease the level or effect of ripretinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Coadministration with a strong CYP3A inhibitor will decrease systemic exposure to ripretinib and its active metabolite (DP-5439), which may decrease risk of adverse reactions.
- secobarbital
secobarbital will decrease the level or effect of ripretinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Coadministration with a strong CYP3A inhibitor will decrease systemic exposure to ripretinib and its active metabolite (DP-5439), which may decrease risk of adverse reactions.
- St John's Wort
St John's Wort will decrease the level or effect of ripretinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Coadministration with a strong CYP3A inhibitor will decrease systemic exposure to ripretinib and its active metabolite (DP-5439), which may decrease risk of adverse reactions.
Monitor Closely (32)
- armodafinil
armodafinil will decrease the level or effect of ripretinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. If coadministration cannot be avoided, increase dosing frequency from recommended dose of 150 mg once daily to 150 mg twice daily during co-administration period; monitor for clinical response and tolerability
- atazanavir
atazanavir will increase the level or effect of ripretinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Coadministration with a strong CYP3A inhibitor will increase systemic exposure to ripretinib and its active metabolite (DP-5439), which may increase risk of adverse reactions.
- bexarotene
bexarotene will decrease the level or effect of ripretinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. If coadministration cannot be avoided, increase dosing frequency from recommended dose of 150 mg once daily to 150 mg twice daily during co-administration period; monitor for clinical response and tolerability
- brigatinib
brigatinib will decrease the level or effect of ripretinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. If coadministration cannot be avoided, increase dosing frequency from recommended dose of 150 mg once daily to 150 mg twice daily during co-administration period; monitor for clinical response and tolerability
- chloramphenicol
chloramphenicol will increase the level or effect of ripretinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Coadministration with a strong CYP3A inhibitor will increase systemic exposure to ripretinib and its active metabolite (DP-5439), which may increase risk of adverse reactions.
- clarithromycin
clarithromycin will increase the level or effect of ripretinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Coadministration with a strong CYP3A inhibitor will increase systemic exposure to ripretinib and its active metabolite (DP-5439), which may increase risk of adverse reactions.
- clobazam
clobazam will decrease the level or effect of ripretinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. If coadministration cannot be avoided, increase dosing frequency from recommended dose of 150 mg once daily to 150 mg twice daily during co-administration period; monitor for clinical response and tolerability
- cobicistat
cobicistat will increase the level or effect of ripretinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Coadministration with a strong CYP3A inhibitor will increase systemic exposure to ripretinib and its active metabolite (DP-5439), which may increase risk of adverse reactions.
- conivaptan
conivaptan will increase the level or effect of ripretinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Coadministration with a strong CYP3A inhibitor will increase systemic exposure to ripretinib and its active metabolite (DP-5439), which may increase risk of adverse reactions.
- darunavir
darunavir will increase the level or effect of ripretinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Coadministration with a strong CYP3A inhibitor will increase systemic exposure to ripretinib and its active metabolite (DP-5439), which may increase risk of adverse reactions.
- elagolix
elagolix will decrease the level or effect of ripretinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. If coadministration cannot be avoided, increase dosing frequency from recommended dose of 150 mg once daily to 150 mg twice daily during co-administration period; monitor for clinical response and tolerability
- encorafenib
encorafenib will decrease the level or effect of ripretinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. If coadministration cannot be avoided, increase dosing frequency from recommended dose of 150 mg once daily to 150 mg twice daily during co-administration period; monitor for clinical response and tolerability
- eslicarbazepine acetate
eslicarbazepine acetate will decrease the level or effect of ripretinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. If coadministration cannot be avoided, increase dosing frequency from recommended dose of 150 mg once daily to 150 mg twice daily during co-administration period; monitor for clinical response and tolerability
- grapefruit
grapefruit will increase the level or effect of ripretinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Coadministration with a strong CYP3A inhibitor will increase systemic exposure to ripretinib and its active metabolite (DP-5439), which may increase risk of adverse reactions.
- idelalisib
idelalisib will increase the level or effect of ripretinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Coadministration with a strong CYP3A inhibitor will increase systemic exposure to ripretinib and its active metabolite (DP-5439), which may increase risk of adverse reactions.
- indinavir
indinavir will increase the level or effect of ripretinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Coadministration with a strong CYP3A inhibitor will increase systemic exposure to ripretinib and its active metabolite (DP-5439), which may increase risk of adverse reactions.
- isoniazid
isoniazid will increase the level or effect of ripretinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Coadministration with a strong CYP3A inhibitor will increase systemic exposure to ripretinib and its active metabolite (DP-5439), which may increase risk of adverse reactions.
- itraconazole
itraconazole will increase the level or effect of ripretinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Coadministration with a strong CYP3A inhibitor will increase systemic exposure to ripretinib and its active metabolite (DP-5439), which may increase risk of adverse reactions.
- ketoconazole
ketoconazole will increase the level or effect of ripretinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Coadministration with a strong CYP3A inhibitor will increase systemic exposure to ripretinib and its active metabolite (DP-5439), which may increase risk of adverse reactions.
- levoketoconazole
levoketoconazole will increase the level or effect of ripretinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Coadministration with a strong CYP3A inhibitor will increase systemic exposure to ripretinib and its active metabolite (DP-5439), which may increase risk of adverse reactions.
- lorlatinib
lorlatinib will decrease the level or effect of ripretinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. If coadministration cannot be avoided, increase dosing frequency from recommended dose of 150 mg once daily to 150 mg twice daily during co-administration period; monitor for clinical response and tolerability
- mifepristone
mifepristone will increase the level or effect of ripretinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Coadministration with a strong CYP3A inhibitor will increase systemic exposure to ripretinib and its active metabolite (DP-5439), which may increase risk of adverse reactions.
- nefazodone
nefazodone will increase the level or effect of ripretinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Coadministration with a strong CYP3A inhibitor will increase systemic exposure to ripretinib and its active metabolite (DP-5439), which may increase risk of adverse reactions.
- nelfinavir
nelfinavir will increase the level or effect of ripretinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Coadministration with a strong CYP3A inhibitor will increase systemic exposure to ripretinib and its active metabolite (DP-5439), which may increase risk of adverse reactions.
- posaconazole
posaconazole will increase the level or effect of ripretinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Coadministration with a strong CYP3A inhibitor will increase systemic exposure to ripretinib and its active metabolite (DP-5439), which may increase risk of adverse reactions.
- ritonavir
ritonavir will increase the level or effect of ripretinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Coadministration with a strong CYP3A inhibitor will increase systemic exposure to ripretinib and its active metabolite (DP-5439), which may increase risk of adverse reactions.
- saquinavir
saquinavir will increase the level or effect of ripretinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Coadministration with a strong CYP3A inhibitor will increase systemic exposure to ripretinib and its active metabolite (DP-5439), which may increase risk of adverse reactions.
- sotorasib
sotorasib will decrease the level or effect of ripretinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. If coadministration cannot be avoided, increase dosing frequency from recommended dose of 150 mg once daily to 150 mg twice daily during co-administration period; monitor for clinical response and tolerability
- stiripentol
stiripentol will increase the level or effect of ripretinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Coadministration with a strong CYP3A inhibitor will increase systemic exposure to ripretinib and its active metabolite (DP-5439), which may increase risk of adverse reactions.
- telotristat ethyl
telotristat ethyl will decrease the level or effect of ripretinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. If coadministration cannot be avoided, increase dosing frequency from recommended dose of 150 mg once daily to 150 mg twice daily during co-administration period; monitor for clinical response and tolerability
- tipranavir
tipranavir will increase the level or effect of ripretinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Coadministration with a strong CYP3A inhibitor will increase systemic exposure to ripretinib and its active metabolite (DP-5439), which may increase risk of adverse reactions.
- voriconazole
voriconazole will increase the level or effect of ripretinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Coadministration with a strong CYP3A inhibitor will increase systemic exposure to ripretinib and its active metabolite (DP-5439), which may increase risk of adverse reactions.
Minor (0)
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%)
Postmarketing Reports
Photosensitivity
Peripheral sensory neuropathy
Dermatitis acneiform
Rash
Warnings
Contraindications
None
Cautions
PPES reported
Fetal harm may occur when administered to pregnant females
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 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
-
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 recommended dose of 150 mg once daily to 150 mg twice daily during co-administration period; monitor for clinical response and tolerability
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.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%)
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)
Images
Formulary
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