Dosing & Uses
Dosage Forms & Strengths
tablet
- 150mg
- 200mg
Non-Small Cell Lung Cancer
Indicated for metastatic non-small cell lung cancer (NSCLC) in adults whose tumors have a mutation that leads to mesenchymal-epithelial transition (MET) exon 14 skipping
400 mg PO BID
Continue until disease progression or unacceptable toxicity
Dosage Modifications
Dose reductions for adverse reactions
- First occurrence: Restart at 300 mg PO BID
- Second occurrence: Restart at 200 mg PO BID
- Unable to tolerate 200 mg PO BID: Permanently discontinue
Interstitial lung disease (ILD)/pneumonitis
- Any grade: Permanently discontinue
Liver function test abnormalities
- ALT and/or AST >3x ULN with total bilirubin >2x ULN: Permanently discontinue
-
Increased ALT and/or AST without increased total bilirubin
- Grade 3: Withhold until recovery to baseline ALT/AST; if recovered to baseline within 7 days, then resume at the same dose; otherwise, resume at reduced dose
- Grade 4: Permanently discontinue
-
Increased total bilirubin without concurrent increased ALT and/or AST
- Grade 2: Withhold until recovery to baseline ALT/AST; if recovered to baseline within 7 days, then resume at the same dose; otherwise, resume at reduced dose
- Grade 3: Withhold until recovery to baseline ALT/AST; if recovered to baseline within 7 days, then resume at reduced dose; otherwise, permanently discontinue
- Grade 4: Permanently discontinue
Other adverse reactions
- Grade 2: Maintain dose level; if intolerable, consider withholding until resolved, then resume at reduced dose
- Grade 3: Withhold until resolved, then resume at reduced dose
- Grade 4: Permanently discontinue
Renal impairment
- Mild-to-moderate (CrCl 30-89 mL/min): No dosage adjustment necessary
- Severe (CrCl 15 to <30 mL/min): Not studied
Dosing Considerations
Patient selection
- Select patients for treatment based on the presence of mutation that leads to MET exon 14 skipping in tumor specimens
- Information on FDA-approved tests is available at: http://www.fda.gov/CompanionDiagnostics
Safety and efficacy not established
Interactions
Interaction Checker
No Results
Contraindicated
Serious - Use Alternative
Significant - Monitor Closely
Minor
Contraindicated (0)
Serious - Use Alternative (22)
- abametapir
abametapir will increase the level or effect of capmatinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
- amobarbital
amobarbital will decrease the level or effect of capmatinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
- apalutamide
apalutamide will decrease the level or effect of capmatinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
- bosentan
bosentan will decrease the level or effect of capmatinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
- carbamazepine
carbamazepine will decrease the level or effect of capmatinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
- conivaptan
conivaptan will increase the level or effect of capmatinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
- dabrafenib
dabrafenib will decrease the level or effect of capmatinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
- efavirenz
efavirenz will decrease the level or effect of capmatinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
- enzalutamide
enzalutamide will decrease the level or effect of capmatinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
- fosphenytoin
fosphenytoin will decrease the level or effect of capmatinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
- lorlatinib
lorlatinib will decrease the level or effect of capmatinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
- mifepristone
mifepristone will increase the level or effect of capmatinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
- mitotane
mitotane will decrease the level or effect of capmatinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
- nafcillin
nafcillin will decrease the level or effect of capmatinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
- phenobarbital
phenobarbital will decrease the level or effect of capmatinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
- phenytoin
phenytoin will decrease the level or effect of capmatinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
- primidone
primidone will decrease the level or effect of capmatinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
- rifabutin
rifabutin will decrease the level or effect of capmatinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
- rifampin
rifampin will decrease the level or effect of capmatinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
- rifapentine
rifapentine will decrease the level or effect of capmatinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
- ritonavir
ritonavir will increase the level or effect of capmatinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
- secobarbital
secobarbital will decrease the level or effect of capmatinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
Monitor Closely (23)
- atazanavir
atazanavir will increase the level or effect of capmatinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
- berotralstat
capmatinib increases levels of berotralstat by Other (see comment). Modify Therapy/Monitor Closely. Comment: Reduced dose of berotralstat (a BCRP substrate) to 110 mg/day when coadministered with BCRP inhibitors.
- ceritinib
ceritinib will increase the level or effect of capmatinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
- chloramphenicol
chloramphenicol will increase the level or effect of capmatinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely.
- clarithromycin
clarithromycin will increase the level or effect of capmatinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
- cobicistat
cobicistat will increase the level or effect of capmatinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
- darunavir
darunavir will increase the level or effect of capmatinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
- etravirine
etravirine will decrease the level or effect of capmatinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
- idelalisib
idelalisib will increase the level or effect of capmatinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
- indinavir
indinavir will increase the level or effect of capmatinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
- itraconazole
itraconazole will increase the level or effect of capmatinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
- ivosidenib
ivosidenib will decrease the level or effect of capmatinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
- ketoconazole
ketoconazole will increase the level or effect of capmatinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
- levoketoconazole
levoketoconazole will increase the level or effect of capmatinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
- lopinavir
lopinavir will increase the level or effect of capmatinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
- nefazodone
nefazodone will increase the level or effect of capmatinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
- nelfinavir
nelfinavir will increase the level or effect of capmatinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
- posaconazole
posaconazole will increase the level or effect of capmatinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
- ribociclib
ribociclib will increase the level or effect of capmatinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
- saquinavir
saquinavir will increase the level or effect of capmatinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
- selexipag
capmatinib will increase the level or effect of selexipag by Other (see comment). Use Caution/Monitor. Selexipag is a ABCG2 (BCRP) substrate. Monitor selexipag for increased pharmacologic or adverse effects when coadministered with ABCG2 (BCRP) inhibitors.
- tipranavir
tipranavir will increase the level or effect of capmatinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
- voriconazole
voriconazole will increase the level or effect of capmatinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
Minor (4)
- acetazolamide
acetazolamide will increase the level or effect of capmatinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.
- anastrozole
anastrozole will increase the level or effect of capmatinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.
- cyclophosphamide
cyclophosphamide will increase the level or effect of capmatinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.
- larotrectinib
larotrectinib will increase the level or effect of capmatinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.
Adverse Effects
>10%
All grades
- Decreased albumin (68%)
- Increased creatinine (62%)
- Peripheral edema (52%)
- Nausea (44%)
- Decreased lymphocytes (44%)
- Increased ALT (37%)
- Increased alkaline phosphatase (32%)
- Fatigue (32%)
- Increased amylase (31%)
- Increased gamma-glutamyltransferase (GGT) (29%)
- Vomiting (28%)
- Increased lipase (26%)
- Increased AST (25%)
- Dyspnea (24%)
- Decreased hemoglobin (24%)
- Decreased sodium (23%)
- Decreased phosphate (23%)
- Increased potassium (23%)
- Decreased leukocytes (23%)
- Decreased glucose (21%)
- Decreased appetite (21%)
- Constipation (18%)
- Diarrhea (18%)
- Cough (16%)
- Noncardiac chest pain (15%)
- Back pain (14%)
- Pyrexia (14%)
Grade 3 to 4
- Decreased lymphocytes (14%)
1-10%
All grades
- Decreased weight (10%)
-
<10%
- Pruritus (allergic and generalized)
- ILD/pneumonitis
- Cellulitis
- Acute kidney injury (including renal failure)
- Urticaria
- Acute pancreatitis
Grade 3 to 4
- Peripheral edema (9%)
- Fatigue (8%)
- Increased ALT (8%)
- Increased GGT (7%)
- Increased lipase (7%)
- Dyspnea (7%)
- Decreased sodium (6%)
- Increased AST (4.9%)
- Increased amylase (4.4%)
- Increased potassium (3.1%)
- Decreased hemoglobin (2.8%)
- Nausea (2.7%)
- Vomiting (2.4%)
- Noncardiac chest pain (2.1%)
- Decreased albumin (1.8%)
<1%
Grade 3 to 4
- Back pain (0.9%)
- Constipation (0.9%)
- Decreased appetite (0.9%)
- Decreased leukocytes (0.9%)
- Pyrexia (0.6%)
- Decreased weight (0.6%)
- Cough (0.6%)
- Diarrhea (0.3%)
- Decreased glucose (0.3%)
- Increased alkaline phosphatase (0.3%)
- Increased creatinine (0.3%)
Postmarketing Reports
Hypersensitivity reactions
Warnings
Contraindications
None
Cautions
ILD/pneumonitis, which can be fatal, occurred during clinical trials; monitor for new or worsening pulmonary symptoms indicative of ILD/pneumonitis
Hepatotoxicity occurred; monitor liver function tests (including ALT, AST, and total bilirubin) before initiation, every 2 weeks during the first 3 months of treatment, and then once monthly or as clinically indicated, with more frequent testing in patients who develop increased transaminases or bilirubin
Elevations in amylase and lipase levels occurred in patients receiving therapy; monitor amylase and lipase at baseline and regularly during treatment; based on severity of adverse drug reaction, temporarily withhold, dose reduce, or permanently discontinue therapy
Serious hypersensitivity reactions reported with use; signs and symptoms of hypersensitivity included pyrexia, chills, pruritus, rash, decreased blood pressure, nausea, and vomiting; based on severity of adverse reaction, temporarily withhold or permanently discontinue therapy
May cause photosensitivity reactions; advise patients to limit direct ultraviolet exposure; limit direct ultraviolet exposure by using sunscreen or protective clothing during treatment
Fetal harm may occur
Drug interaction overview
- Capmatinib is a CYP3A4 substrate and inhibits CYP1A2, P-glycoprotein (P-gp), breast cancer resistance protein (BCRP), MATE 1, and MATE2K
-
Strong CYP3A Inhibitors
- Coadministration with a strong CYP3A inhibitor increased capmatinib exposure, which may increase the incidence and severity of adverse reactions of capmatinib
- Closely monitor for adverse reactions
-
Strong and moderate CYP3A inducers
- Avoid coadministration
- Concomitant use with capmatinib a strong or moderate CYP3A inducer decreased capmatinib exposure and efficacy
-
Substrates of CYP1A2, P-gp, BCRP, MATE1 or MATE2K
- Coadministration with CYP1A2, P-gp, BCRP, MATE1 or MATE2K substrates increased the exposure and adverse reactions of these substrates
- If coadministration unavoidable, reduce dose of CYP1A2, P-gp, BCRP, MATE1 or MATE2K substrate in accordance with the approved prescribing information
Pregnancy & Lactation
Pregnancy
Based on animal studies and its mechanism of action, fetal harm may occur when administered to pregnant females
No available data on use in pregnant females
Verify pregnancy status for females of reproductive potential before starting treatment
Contraception
- Females of reproductive potential: Use effective contraception during treatment and for 1 week after final dose
- Males with female partners of reproductive potential: Use effective contraception during treatment and for 1 week after final dose
Animal data
- Oral administration to pregnant rats and rabbits during organogenesis resulted in malformations at maternal exposures less than the human exposure based on AUC at the 400 mg BID clinical dose
Lactation
No data available on the presence of capmatinib or its metabolites in either human or animal milk or its effects on breastfeeding, or on milk production
Advise females not to breastfeed during treatment and for 1 week after 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
MET tyrosine kinase stimulates cell scattering, invasion, protection from apoptosis, and angiogenesis; a variety of cancers (eg, lung, gastric) are associated when MET becomes dysregulated owing to MET amplifications and exon 14 skipping mutations
Absorption
Peak plasma time: 1-2 hr
Steady-state reached by day 3 following BID dosing
Absorption: >70%
Distribution
Protein bound: 96%
Vd (steady-state): 164 L
Metabolism
Primarily metabolized by CYP3A4 and aldehyde oxidase
Elimination
Half-life: 6.5 hr
Clearance: 24 L/hr
Excretion: Feces (42%, unchanged); urine (22%, unchanged)
Administration
Oral Administration
May take with or without food
Swallow tablets whole; do not break, crush, or chew
Missed or vomited dose: Do not make up dose; take next dose at its scheduled time
Storage
Dispense in the original package with the desiccant cartridge
Store at 20-25ºC (68-77ºF), excursions permitted to 15-30ºC (59-86ºF)
Protect from moisture
Discard any remaining drug after 6 weeks of first opening the bottle
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Formulary
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