Note: Select patients for treatment based on the presence of a mutation that leads to MET exon 14 skipping in tumor or plasma specimens (if not detected in plasma, test tumor tissue if feasible).
Non–small cell lung cancer, metastatic, with MET exon 14 skipping mutation: Oral: 400 mg twice daily (Ref); continue until disease progression or unacceptable toxicity.
Missed dose: If a dose is missed or vomited, administer the next dose at its scheduled time. Do not make up the missed dose.
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
Note: Renal function estimated using the Cockcroft-Gault formula.
CrCl ≥30 mL/minute: No dosage adjustment is necessary.
CrCl <30 mL/minute: There are no dosage adjustments provided in the manufacturer's labeling (has not been studied).
Preexisting impairment:
Child-Pugh classes A, B, or C: There are no dosage adjustments provided in the manufacturer's labeling; however, no clinically significant effects on pharmacokinetic parameters were observed.
Hepatotoxicity during treatment:
Adverse reaction |
Severity |
Dose modificationa |
---|---|---|
aSee recommended capmatinib dosage level reductions in "Dosing Adjustment for Toxicity". | ||
Increased ALT and/or AST without increased total bilirubin |
Grade 3 |
Withhold capmatinib until recovery to baseline ALT/AST. If recovered to baseline within 7 days, resume capmatinib at the same dose. If not recovered to baseline within 7 days, resume capmatinib at a lower dose. |
Grade 4 |
Permanently discontinue capmatinib. | |
Increased ALT and/or AST with increased total bilirubin in the absence of cholestasis or hemolysis |
ALT and/or AST >3 times ULN with total bilirubin >2 times ULN |
Permanently discontinue capmatinib. |
Increased total bilirubin without concurrent increased ALT and/or AST |
Grade 2 |
Withhold capmatinib until recovery to baseline bilirubin. If recovered to baseline within 7 days, resume capmatinib at the same dose. If not recovered to baseline within 7 days, resume capmatinib at a lower dose. |
Grade 3 |
Withhold capmatinib until recovery to baseline bilirubin. If recovered to baseline within 7 days, resume capmatinib at a reduced dose. If not recovered to baseline within 7 days, permanently discontinue capmatinib. | |
Grade 4 |
Permanently discontinue capmatinib. |
Recommended Capmatinib Dosage Level Reductions for Adverse Reactions | ||
---|---|---|
Initial dose is 400 mg twice daily. | ||
Dose reduction |
Dose and schedule | |
First |
300 mg twice daily | |
Second |
200 mg twice daily | |
If unable to tolerate 200 mg twice daily |
Permanently discontinue capmatinib. | |
Recommended Capmatinib Dosage Modifications for Adverse Reactions | ||
Adverse reaction |
Severity |
Dose modification |
Hypersensitivity |
Any grade |
Withhold capmatinib until resolution if hypersensitivity is suspected (based on clinical judgement). Permanently discontinue capmatinib if hypersensitivity reaction is severe. |
Interstitial lung disease/pneumonitis |
Suspected |
Immediately withhold capmatinib. |
Any grade |
Permanently discontinue capmatinib. | |
Lipase or amylase increase |
Grade 3 |
Withhold capmatinib until recovered to ≤ grade 2 or baseline. If recovered to baseline or ≤ grade 2 within 14 days, resume capmatinib at a reduced dose. Otherwise permanently discontinue capmatinib. |
Grade 4 |
Permanently discontinue capmatinib. | |
Pancreatitis |
Grade 3 or 4 |
Permanently discontinue capmatinib. |
Other adverse reactions |
Grade 2 |
Maintain current capmatinib dose. If toxicity is intolerable, consider withholding capmatinib until resolved, then resume at a reduced dose. |
Grade 3 |
Withhold capmatinib until resolved, then resume at a reduced dose. | |
Grade 4 |
Permanently discontinue capmatinib. |
Refer to adult dosing.
Hepatoxicity, including severe acute hepatotoxicity, increased serum alanine aminotransferase (ALT), increased serum alkaline phosphatase, and increased serum aspartate aminotransferase (AST), has been reported(Ref) . Therapy interruption and/or dose modification or discontinuation may be warranted, depending on severity (Ref).
Onset: Varied; median time to onset of grade ≥3 elevated ALT/AST was 1.8 months (range: 0.5 to 46.4 months) (Ref).
Pancreatic toxicity, including acute pancreatitis, increased serum amylase, and increased serum lipase, has been reported. Therapy interruption and/or dose modification or discontinuation may be warranted, depending on severity.
Onset: Varied; median time to onset of grade ≥3 elevated amylase and lipase was 2 months (range: 0.03 to 31.2 months).
Dyspnea has been reported with capmatinib and may be severe (grade ≥3) (Ref). Potentially life-threatening interstitial lung disease (ILD)/pneumonitis have occurred. ILD/pneumonitis typically presents as cough, dyspnea, and fever.
Onset: Varied; median time to onset of grade ≥3 ILD/pneumonitis was 1.8 months (range: 0.2 months to 1.7 years).
The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified. Reported adverse reactions are for adults.
>10%:
Cardiovascular: Edema (59%; including facial edema, genital edema, peripheral edema; severe edema [2%])
Dermatologic: Skin rash (13%; including acneiform eruption, bullous rash, dermatitis, eczema, erythema multiforme, maculopapular rash, pustular rash, vesicular eruption)
Endocrine & metabolic: Decreased serum albumin (72%), decreased serum glucose (23%), decreased serum phosphate (26%), decreased serum sodium (24%), increased serum potassium (25%), weight loss (11%)
Gastrointestinal: Constipation (19%), decreased appetite (21%), diarrhea (19%; grades 3/4: <1%), increased serum amylase (34%), increased serum lipase (29%), nausea (46%; grades 3/4: 2%), vomiting (28%; grades 3/4: 2%)
Hematologic & oncologic: Decreased hemoglobin (24%; grades 3/4: 3%), leukopenia (25%; grades 3/4: 2%), lymphocytopenia (45%; grades 3/4: 14%)
Hepatic: Increased gamma-glutamyl transferase (30%), increased serum alanine aminotransferase (39%), increased serum alkaline phosphatase (32%), increased serum aspartate aminotransferase (28%)
Nervous system: Dizziness (13%; including vertigo), fatigue (34%; including asthenia)
Neuromuscular & skeletal: Musculoskeletal pain (40%; including arthralgia, back pain, jaw pain, limb pain, musculoskeletal chest pain, myalgia, neck pain, noncardiac chest pain, ostealgia)
Renal: Increased serum creatinine (65%)
Respiratory: Cough (21%), dyspnea (25%; grades 3/4: 7% [Dhillon 2020]), pneumonia (13%)
Miscellaneous: Fever (14%)
1% to 10%:
Dermatologic: Cellulitis (<10%), pruritus (<10%), urticaria (<10%)
Renal: Acute kidney injury (<10%; including kidney failure)
Respiratory: Interstitial lung disease (≤5%), pleural effusion (4%), pneumonitis (≤5%)
<1%: Gastrointestinal: Pancreatitis (grade 3)
Frequency not defined: Hepatic: Hepatotoxicity
Postmarketing:
Hematologic & oncologic: Thrombocytopenia
Hepatic: Acute hepatotoxicity (severe) (Valencia Soto 2023), increased serum bilirubin (Valencia Soto 2023)
Hypersensitivity: Hypersensitivity reaction
There are no contraindications listed in the manufacturer's US labeling.
Canadian labeling: Hypersensitivity to capmatinib or any component of the formulation.
Concerns related to adverse effects:
• Hypersensitivity reactions: Severe hypersensitivity reactions (eg, chills, fever, hypotension, nausea, pruritus, rash, vomiting) have been reported with capmatinib therapy.
• Photosensitivity: Capmatinib may cause photosensitivity reactions. In a clinical trial, it was recommended that patients take precautions against ultraviolet exposure through the use of sunscreen or protective clothing during capmatinib therapy. Patients should limit direct ultraviolet exposure during treatment with capmatinib.
Other warnings/precautions:
• Appropriate use: Select patients for treatment based on the presence of a mutation that leads to MET exon 14 skipping in tumor or plasma specimens (if not detected in plasma, test tumor tissue if feasible). Information on approved tests is available at http://www.fda.gov/CompanionDiagnostics.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Tablet, Oral, as hydrochloride:
Tabrecta: 150 mg, 200 mg
No
Tablets (Tabrecta Oral)
150 mg (per each): $250.00
200 mg (per each): $250.00
Disclaimer: A representative AWP (Average Wholesale Price) price or price range is provided as reference price only. A range is provided when more than one manufacturer's AWP price is available and uses the low and high price reported by the manufacturers to determine the range. The pricing data should be used for benchmarking purposes only, and as such should not be used alone to set or adjudicate any prices for reimbursement or purchasing functions or considered to be an exact price for a single product and/or manufacturer. Medi-Span expressly disclaims all warranties of any kind or nature, whether express or implied, and assumes no liability with respect to accuracy of price or price range data published in its solutions. In no event shall Medi-Span be liable for special, indirect, incidental, or consequential damages arising from use of price or price range data. Pricing data is updated monthly.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Tablet, Oral:
Tabrecta: 150 mg, 200 mg
Oral: Administer with or without food. Swallow tablets whole; do not break, crush, or chew.
This medication is not on the NIOSH (2024) list; however, it may meet the criteria for a hazardous drug. Capmatinib may cause teratogenicity.
Use appropriate precautions for receiving, handling, storage, preparation, dispensing, transporting, administration, and disposal. Follow NIOSH and USP 800 recommendations and institution-specific policies/procedures for appropriate containment strategy (NIOSH 2023; NIOSH 2024; USP-NF 2020).
Note: Facilities may perform risk assessment of some hazardous drugs to determine if appropriate for alternative handling and containment strategies (USP-NF 2020). Refer to institution-specific handling policies/procedures.
Non–small cell lung cancer, metastatic: Treatment of metastatic non–small cell lung cancer in adults whose tumors have a mutation that leads to MET exon 14 skipping as detected by an approved test.
Capmatinib may be confused with cabozantinib, capecitabine, Capmist, Caprelsa, ceritinib, cobimetinib, crizotinib, imatinib, tepotinib.
The Institute for Safe Medication Practices (ISMP) includes this medication among its list of drug classes (chemotherapeutic agent, parenteral and oral) which have a heightened risk of causing significant patient harm when used in error (High-Alert Medications in Acute Care, Community/Ambulatory Care, and Long-Term Care Settings).
Substrate of CYP3A4 (Major), P-glycoprotein (Minor); Note: Assignment of Major/Minor substrate status based on clinically relevant drug interaction potential; Inhibits BCRP, CYP1A2 (Moderate), P-glycoprotein;
Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the drug interactions program by clicking on the “Launch drug interactions program” link above.
Afatinib: P-glycoprotein/ABCB1 Inhibitors may increase serum concentration of Afatinib. Management: If combined, administer the P-gp inhibitor simultaneously with, or after, the dose of afatinib. Monitor closely for signs and symptoms of afatinib toxicity and if the combination is not tolerated, reduce the afatinib dose by 10 mg. Risk D: Consider Therapy Modification
Agomelatine: CYP1A2 Inhibitors (Moderate) may increase serum concentration of Agomelatine. Risk C: Monitor
Aliskiren: P-glycoprotein/ABCB1 Inhibitors may increase serum concentration of Aliskiren. Risk C: Monitor
Alosetron: CYP1A2 Inhibitors (Moderate) may increase serum concentration of Alosetron. Management: Avoid concomitant use of alosetron and moderate CYP1A2 inhibitors whenever possible. If combined use is necessary, monitor for increased alosetron effects/toxicities. Risk D: Consider Therapy Modification
Alpelisib: BCRP/ABCG2 Inhibitors may increase serum concentration of Alpelisib. Management: Avoid coadministration of BCRP/ABCG2 inhibitors and alpelisib due to the potential for increased alpelisib concentrations and toxicities. If coadministration cannot be avoided, closely monitor for increased alpelisib adverse reactions. Risk D: Consider Therapy Modification
Anagrelide: CYP1A2 Inhibitors (Moderate) may increase serum concentration of Anagrelide. CYP1A2 Inhibitors (Moderate) may increase active metabolite exposure of Anagrelide. Risk C: Monitor
Bendamustine: CYP1A2 Inhibitors (Moderate) may increase serum concentration of Bendamustine. Management: Consider alternatives to moderate CYP1A2 inhibitors during therapy with bendamustine due to the potential for increased bendamustine plasma concentrations and increased bendamustine toxicity. Risk D: Consider Therapy Modification
Beta-Acetyldigoxin: P-glycoprotein/ABCB1 Inhibitors may increase serum concentration of Beta-Acetyldigoxin. Risk C: Monitor
Bilastine: P-glycoprotein/ABCB1 Inhibitors may increase serum concentration of Bilastine. Risk X: Avoid
Caffeine and Caffeine Containing Products: CYP1A2 Inhibitors (Moderate) may increase serum concentration of Caffeine and Caffeine Containing Products. Risk C: Monitor
Celiprolol: P-glycoprotein/ABCB1 Inhibitors may increase serum concentration of Celiprolol. Risk C: Monitor
Cladribine: BCRP/ABCG2 Inhibitors may increase serum concentration of Cladribine. Management: Avoid concomitant use of BCRP inhibitors during the 4 to 5 day oral cladribine treatment cycles whenever possible. If combined, consider dose reduction of the BCRP inhibitor and separation in the timing of administration. Risk D: Consider Therapy Modification
Clofazimine: May increase serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Risk C: Monitor
ClomiPRAMINE: CYP1A2 Inhibitors (Moderate) may increase serum concentration of ClomiPRAMINE. Risk C: Monitor
CloZAPine: CYP1A2 Inhibitors (Moderate) may increase serum concentration of CloZAPine. Risk C: Monitor
Colchicine: P-glycoprotein/ABCB1 Inhibitors may increase serum concentration of Colchicine. Colchicine distribution into certain tissues (e.g., brain) may also be increased. Management: This combination is often contraindicated, but combined use may be permitted with dose adjustment and monitoring. Recommendations vary based on brand, indication, use of CYP3A4 inhibitors, and hepatic/renal function. See interaction monograph for details. Risk D: Consider Therapy Modification
CycloSPORINE (Systemic): P-glycoprotein/ABCB1 Inhibitors may increase serum concentration of CycloSPORINE (Systemic). Risk C: Monitor
CYP3A4 Inducers (Moderate): May decrease serum concentration of Capmatinib. Risk X: Avoid
CYP3A4 Inducers (Strong): May decrease serum concentration of Capmatinib. Risk X: Avoid
CYP3A4 Inhibitors (Strong): May increase serum concentration of Capmatinib. Risk C: Monitor
Dabigatran Etexilate: P-glycoprotein/ABCB1 Inhibitors may increase active metabolite exposure of Dabigatran Etexilate. Risk C: Monitor
Diazoxide Choline: CYP1A2 Inhibitors (Moderate) may increase serum concentration of Diazoxide Choline. Risk C: Monitor
Digitoxin: P-glycoprotein/ABCB1 Inhibitors may increase serum concentration of Digitoxin. Risk C: Monitor
Digoxin: P-glycoprotein/ABCB1 Inhibitors may increase serum concentration of Digoxin. Management: Measure digoxin serum concentrations before initiating treatment with these P-glycoprotein (P-gp) inhibitors. Reduce digoxin concentrations by either reducing the digoxin dose by 15% to 30% or by modifying the dosing frequency. Risk D: Consider Therapy Modification
DOXOrubicin (Conventional): P-glycoprotein/ABCB1 Inhibitors may increase serum concentration of DOXOrubicin (Conventional). Risk X: Avoid
DOXOrubicin (Liposomal): P-glycoprotein/ABCB1 Inhibitors may increase serum concentration of DOXOrubicin (Liposomal). Risk C: Monitor
DULoxetine: CYP1A2 Inhibitors (Moderate) may increase serum concentration of DULoxetine. Risk C: Monitor
Edoxaban: P-glycoprotein/ABCB1 Inhibitors may increase serum concentration of Edoxaban. Risk C: Monitor
Ensartinib: P-glycoprotein/ABCB1 Inhibitors may increase serum concentration of Ensartinib. Risk X: Avoid
Etoposide Phosphate: P-glycoprotein/ABCB1 Inhibitors may increase serum concentration of Etoposide Phosphate. Risk C: Monitor
Etoposide: P-glycoprotein/ABCB1 Inhibitors may increase serum concentration of Etoposide. Risk C: Monitor
Everolimus: P-glycoprotein/ABCB1 Inhibitors may increase serum concentration of Everolimus. Risk C: Monitor
Fezolinetant: CYP1A2 Inhibitors (Moderate) may increase serum concentration of Fezolinetant. Risk X: Avoid
Fusidic Acid (Systemic): May increase serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Management: Consider avoiding this combination if possible. If required, monitor patients closely for increased adverse effects of the CYP3A4 substrate. Risk D: Consider Therapy Modification
Glecaprevir and Pibrentasvir: P-glycoprotein/ABCB1 Inhibitors may increase serum concentration of Glecaprevir and Pibrentasvir. Risk C: Monitor
Lapatinib: P-glycoprotein/ABCB1 Inhibitors may increase serum concentration of Lapatinib. Risk C: Monitor
Larotrectinib: P-glycoprotein/ABCB1 Inhibitors may increase serum concentration of Larotrectinib. Risk C: Monitor
Lefamulin: P-glycoprotein/ABCB1 Inhibitors may increase serum concentration of Lefamulin. Management: Avoid concomitant use of lefamulin tablets with P-glycoprotein/ABCB1 inhibitors. If concomitant use is required, monitor for lefamulin adverse effects. Risk D: Consider Therapy Modification
Mavorixafor: P-glycoprotein/ABCB1 Inhibitors may increase serum concentration of Mavorixafor. Risk C: Monitor
Melatonin: CYP1A2 Inhibitors (Moderate) may increase serum concentration of Melatonin. Risk C: Monitor
Morphine (Systemic): P-glycoprotein/ABCB1 Inhibitors may increase serum concentration of Morphine (Systemic). Risk C: Monitor
Nadolol: P-glycoprotein/ABCB1 Inhibitors may increase serum concentration of Nadolol. Risk C: Monitor
Naldemedine: P-glycoprotein/ABCB1 Inhibitors may increase serum concentration of Naldemedine. Risk C: Monitor
Naloxegol: P-glycoprotein/ABCB1 Inhibitors may increase serum concentration of Naloxegol. Risk C: Monitor
OLANZapine: CYP1A2 Inhibitors (Moderate) may increase serum concentration of OLANZapine. Risk C: Monitor
PAZOPanib: P-glycoprotein/ABCB1 Inhibitors may increase serum concentration of PAZOPanib. Risk X: Avoid
Pentoxifylline: CYP1A2 Inhibitors (Moderate) may increase serum concentration of Pentoxifylline. Risk C: Monitor
Pirfenidone: CYP1A2 Inhibitors (Moderate) may increase serum concentration of Pirfenidone. Management: Avoid concomitant use of pirfenidone and moderate CYP1A2 inhibitors whenever possible. If combined, decrease the pirfenidone dose to 1,602 mg per day (534 mg three times daily) and monitor for increased pirfenidone toxicities. Risk D: Consider Therapy Modification
Pomalidomide: CYP1A2 Inhibitors (Moderate) may increase serum concentration of Pomalidomide. Risk C: Monitor
Pralsetinib: P-glycoprotein/ABCB1 Inhibitors may increase serum concentration of Pralsetinib. Management: If this combo cannot be avoided, decrease pralsetinib dose from 400 mg daily to 300 mg daily; from 300 mg daily to 200 mg daily; and from 200 mg daily to 100 mg daily. Risk D: Consider Therapy Modification
Propranolol: CYP1A2 Inhibitors (Moderate) may increase serum concentration of Propranolol. Risk C: Monitor
Ramelteon: CYP1A2 Inhibitors (Moderate) may increase serum concentration of Ramelteon. Risk C: Monitor
Ramosetron: CYP1A2 Inhibitors (Moderate) may increase serum concentration of Ramosetron. Risk C: Monitor
Ranolazine: P-glycoprotein/ABCB1 Inhibitors may increase serum concentration of Ranolazine. Risk C: Monitor
Rasagiline: CYP1A2 Inhibitors (Moderate) may increase serum concentration of Rasagiline. Management: Limit rasagiline dose to 0.5 mg once daily in patients taking moderate CYP1A2 inhibitors. Risk D: Consider Therapy Modification
Relugolix, Estradiol, and Norethindrone: P-glycoprotein/ABCB1 Inhibitors may increase serum concentration of Relugolix, Estradiol, and Norethindrone. Management: Avoid use of relugolix/estradiol/norethindrone with P-glycoprotein (P-gp) inhibitors. If concomitant use is unavoidable, relugolix/estradiol/norethindrone should be administered at least 6 hours before the P-gp inhibitor. Risk D: Consider Therapy Modification
Relugolix: P-glycoprotein/ABCB1 Inhibitors may increase serum concentration of Relugolix. Management: Avoid coadministration of relugolix with oral P-gp inhibitors whenever possible. If combined, take relugolix at least 6 hours prior to the P-gp inhibitor and monitor patients more frequently for adverse reactions. Risk D: Consider Therapy Modification
Repotrectinib: P-glycoprotein/ABCB1 Inhibitors may increase serum concentration of Repotrectinib. Risk X: Avoid
RifAXIMin: P-glycoprotein/ABCB1 Inhibitors may increase serum concentration of RifAXIMin. Risk C: Monitor
Rimegepant: P-glycoprotein/ABCB1 Inhibitors may increase serum concentration of Rimegepant. Management: Avoid administration of another dose of rimegepant within 48 hours if given concomitantly with a P-glycoprotein (P-gp) inhibitor. Risk D: Consider Therapy Modification
RisperiDONE: P-glycoprotein/ABCB1 Inhibitors may increase serum concentration of RisperiDONE. Risk C: Monitor
RomiDEPsin: P-glycoprotein/ABCB1 Inhibitors may increase serum concentration of RomiDEPsin. Risk C: Monitor
ROPINIRole: CYP1A2 Inhibitors (Moderate) may increase serum concentration of ROPINIRole. Risk C: Monitor
ROPivacaine: CYP1A2 Inhibitors (Moderate) may increase serum concentration of ROPivacaine. Risk C: Monitor
Rosuvastatin: Capmatinib may increase serum concentration of Rosuvastatin. Management: Limit the dose of rosuvastatin to 10 mg daily or rosuvastatin/ezetimibe 10 mg/10 mg daily when combined with capmatinib. Monitor closely for increased rosuvastatin effects/toxicities (eg, myalgias, rhabdomyolysis) when these agents are combined. Risk D: Consider Therapy Modification
Saquinavir: P-glycoprotein/ABCB1 Inhibitors may increase serum concentration of Saquinavir. Risk C: Monitor
Seladelpar: BCRP/ABCG2 Inhibitors may increase serum concentration of Seladelpar. Risk C: Monitor
Silodosin: P-glycoprotein/ABCB1 Inhibitors may increase serum concentration of Silodosin. Risk C: Monitor
Sirolimus (Conventional): P-glycoprotein/ABCB1 Inhibitors may increase serum concentration of Sirolimus (Conventional). Management: Avoid concurrent use of sirolimus with P-glycoprotein (P-gp) inhibitors when possible and alternative agents with lesser interaction potential with sirolimus should be considered. Monitor for increased sirolimus concentrations/toxicity if combined. Risk D: Consider Therapy Modification
Sirolimus (Protein Bound): P-glycoprotein/ABCB1 Inhibitors may increase serum concentration of Sirolimus (Protein Bound). Risk X: Avoid
Tacrolimus (Systemic): P-glycoprotein/ABCB1 Inhibitors may increase serum concentration of Tacrolimus (Systemic). Risk C: Monitor
Talazoparib: BCRP/ABCG2 Inhibitors may increase serum concentration of Talazoparib. Risk C: Monitor
Talazoparib: P-glycoprotein/ABCB1 Inhibitors may increase serum concentration of Talazoparib. Risk C: Monitor
Tasimelteon: CYP1A2 Inhibitors (Moderate) may increase serum concentration of Tasimelteon. Risk C: Monitor
Teniposide: P-glycoprotein/ABCB1 Inhibitors may increase serum concentration of Teniposide. Risk C: Monitor
Tenofovir Disoproxil Fumarate: P-glycoprotein/ABCB1 Inhibitors may increase serum concentration of Tenofovir Disoproxil Fumarate. Risk C: Monitor
Theophylline Derivatives: CYP1A2 Inhibitors (Moderate) may increase serum concentration of Theophylline Derivatives. Management: Consider avoidance of this combination. If coadministration is necessary, monitor for increased theophylline serum concentrations and toxicities when combined. Theophylline dose reductions will likely be required. Risk D: Consider Therapy Modification
TiZANidine: CYP1A2 Inhibitors (Moderate) may increase serum concentration of TiZANidine. Management: Avoid the use of tizanidine with moderate CYP1A2 inhibitors when possible. If combined, monitor closely for increased tizanidine toxicities (eg, hypotension, bradycardia, drowsiness). Tizanidine dose reduction or discontinuation may be necessary. Risk D: Consider Therapy Modification
Topotecan: BCRP/ABCG2 Inhibitors may increase serum concentration of Topotecan. Risk X: Avoid
Topotecan: P-glycoprotein/ABCB1 Inhibitors may increase serum concentration of Topotecan. Risk X: Avoid
Ubrogepant: BCRP/ABCG2 Inhibitors may increase serum concentration of Ubrogepant. Management: Use an initial ubrogepant dose of 50 mg and second dose (at least 2 hours later if needed) of 50 mg when used with a BCRP inhibitor. Risk D: Consider Therapy Modification
Ubrogepant: P-glycoprotein/ABCB1 Inhibitors may increase serum concentration of Ubrogepant. Management: Use an initial ubrogepant dose of 50 mg and second dose (at least 2 hours later if needed) of 50 mg when used with a P-gp inhibitor. Risk D: Consider Therapy Modification
Venetoclax: P-glycoprotein/ABCB1 Inhibitors may increase serum concentration of Venetoclax. Management: Reduce the venetoclax dose by at least 50% in patients requiring concomitant treatment with P-glycoprotein (P-gp) inhibitors. Resume the previous venetoclax dose 2 to 3 days after discontinuation of a P-gp inhibitor. Risk D: Consider Therapy Modification
VinCRIStine: P-glycoprotein/ABCB1 Inhibitors may increase serum concentration of VinCRIStine. Risk X: Avoid
Vorasidenib: CYP1A2 Inhibitors (Moderate) may increase serum concentration of Vorasidenib. Management: Avoid concurrent use with moderate CYP1A2 inhibitors when possible. If combined use cannot be avoided, monitor for evidence of adverse effects and adjust vorasidenib dose accordingly if necessary. Risk D: Consider Therapy Modification
Evaluate pregnancy status prior to use in patients who could become pregnant.
Patients who could become pregnant should use effective contraception during therapy and for 1 week after the last capmatinib dose. Patients with partners who could become pregnant should use effective contraception during therapy and for 1 week after the last capmatinib dose.
Based on the mechanism of action and data from animal reproduction studies, in utero exposure to capmatinib may cause fetal harm.
It is not known if capmatinib is present in breast milk.
Due to the potential for serious adverse reactions in the breastfed infant, breastfeeding is not recommended by the manufacturer during therapy and for 1 week after the last capmatinib dose.
MET exon 14 skipping mutation status (in tumor or plasma specimens). Monitor LFTs (including ALT, AST, and total bilirubin) prior to treatment initiation, every 2 weeks during the first 3 months of therapy, then once monthly or as clinically necessary (monitor more frequently in patients who develop elevated LFTs). Monitor amylase and lipase prior to treatment initiation and regularly during treatment. Evaluate pregnancy status prior to use in patients who could become pregnant. Monitor for new or worsening pulmonary symptoms indicative of interstitial lung disease/pneumonitis (eg, dyspnea, cough, fever); monitor for signs/symptoms of hepatoxicity, hypersensitivity (eg, fever, chills, pruritus, rash, hypotension, nausea and/or vomiting), pancreatitis, and photosensitivity reactions. Monitor adherence.
The American Society of Clinical Oncology hepatitis B virus (HBV) screening and management provisional clinical opinion (ASCO [Hwang 2020]) recommends HBV screening with hepatitis B surface antigen, hepatitis B core antibody, total Ig or IgG, and antibody to hepatitis B surface antigen prior to beginning (or at the beginning of) systemic anticancer therapy; do not delay treatment for screening/results. Detection of chronic or past HBV infection requires a risk assessment to determine antiviral prophylaxis requirements, monitoring, and follow-up.
Capmatinib is a potent and highly-selective inhibitor of MET, including the mutant variant produced by exon 14 skipping. MET exon 14 skipping results in increased downstream MET signaling. Through MET inhibition, capmatinib decreases cancer cell growth. Capmatinib inhibits MET phosphorylation triggered by binding of c-MET (also known as hepatocyte growth factor) or by MET amplification, as well as MET-mediated phosphorylation of downstream signaling proteins.
Absorption: >70%.
Distribution: Vdss: 164 L.
Protein binding: 96%.
Metabolism: Primarily hepatic via CYP3A4 and aldehyde oxidase.
Half-life elimination: 6.5 hours.
Time to peak: ~1 to 2 hours.
Excretion: Feces: 78% (42% as unchanged drug); urine: 22% (primarily as metabolites).
Clearance: 24 L/hour.