Capmatinib: Drug information

(For additional information see "Capmatinib: Patient drug information")

For abbreviations, symbols, and age group definitions used in Lexicomp (show table)

Brand Names: US

Tabrecta

Brand Names: Canada

Tabrecta

Pharmacologic Category

Antineoplastic Agent, MET Inhibitor;
Antineoplastic Agent, Tyrosine Kinase Inhibitor

Dosing: Adult

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

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.

Dosing: Kidney Impairment: Adult

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).

Dosing: Hepatic Impairment: Adult

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:

Recommended Capmatinib Dosage Modifications for Hepatotoxicity
Adverse reaction	Severity	Dose modification^a
^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.
Increased ALT and/or AST without increased total bilirubin	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.

Dosing: Adjustment for Toxicity: Adult

**Recommended Capmatinib Dosage Reductions/Modifications for Adverse Reactions**
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.
Interstitial lung disease/pneumonitis	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.
Lipase or amylase increase	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.

Dosing: Older Adult

Refer to adult dosing.

Adverse Reactions (Significant): Considerations

Hepatotoxicity

Hepatoxicity, including increased serum alanine aminotransferase (ALT), increased serum alkaline phosphatase, and increased serum aspartate aminotransferase (AST), 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 ALT/AST was 1.8 months (range: 0.5 to 46.4 months).

Pancreatic toxicity

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).

Pulmonary toxicity

Dyspnea is common 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).

Adverse Reactions

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, and 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, and 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 renal failure syndrome)

Respiratory: Interstitial lung disease (≤5%), pleural effusion (4%), pneumonitis (≤5%)

<1%: Gastrointestinal: Pancreatitis (grade 3)

Frequency not defined: Hepatic: Hepatotoxicity, increased serum bilirubin

Postmarketing: Hypersensitivity: Hypersensitivity reaction

Contraindications

There are no contraindications listed in the manufacturer's US labeling.

Canadian labeling: Hypersensitivity to capmatinib or any component of the formulation.

Warnings/Precautions

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.

Dosage Forms: US

Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Tablet, Oral, as hydrochloride:

Tabrecta: 150 mg, 200 mg

Generic Equivalent Available: US

Pricing: US

Tablets (Tabrecta Oral)

150 mg (per each): $243.90

200 mg (per each): $243.90

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.

Dosage Forms: Canada

Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Tablet, Oral:

Tabrecta: 150 mg, 200 mg

Administration: Adult

Oral: Administer with or without food. Swallow tablets whole; do not break, crush, or chew.

Hazardous Drugs Handling Considerations

This medication is not on the NIOSH (2016) 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 2016; 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.

Use: Labeled Indications

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.

Medication Safety Issues

Sound-alike/look-alike issues:

Capmatinib may be confused with cabozantinib, capecitabine, Capmist, Caprelsa, ceritinib, cobimetinib, crizotinib, imatinib, tepotinib.

High alert medication:

This medication is in a class the Institute for Safe Medication Practices (ISMP) includes among its lists of drug classes that have a heightened risk of causing significant patient harm when used in error.

Metabolism/Transport Effects

Substrate of CYP3A4 (major), P-glycoprotein/ABCB1 (minor); Note: Assignment of Major/Minor substrate status based on clinically relevant drug interaction potential; Inhibits BCRP/ABCG2, CYP1A2 (moderate), P-glycoprotein/ABCB1

Drug Interactions

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 Lexicomp drug interactions program by clicking on the “Launch drug interactions program” link above.

Afatinib: P-glycoprotein/ABCB1 Inhibitors may increase the 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 the serum concentration of Agomelatine. Risk C: Monitor therapy

Aliskiren: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Aliskiren. Risk C: Monitor therapy

Alosetron: CYP1A2 Inhibitors (Moderate) may increase the 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 the 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 concentrations of the active metabolite(s) of Anagrelide. CYP1A2 Inhibitors (Moderate) may increase the serum concentration of Anagrelide. Risk C: Monitor therapy

Bendamustine: CYP1A2 Inhibitors (Moderate) may increase the 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

Berotralstat: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Berotralstat. Management: Decrease the berotralstat dose to 110 mg daily when combined with P-glycoprotein (P-gp) inhibitors. Risk D: Consider therapy modification

Bilastine: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Bilastine. Risk X: Avoid combination

Bromazepam: CYP1A2 Inhibitors (Moderate) may increase the serum concentration of Bromazepam. Risk C: Monitor therapy

Caffeine and Caffeine Containing Products: CYP1A2 Inhibitors (Moderate) may increase the serum concentration of Caffeine and Caffeine Containing Products. Risk C: Monitor therapy

Celiprolol: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Celiprolol. Risk C: Monitor therapy

Cladribine: BCRP/ABCG2 Inhibitors may increase the 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 the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Risk C: Monitor therapy

ClomiPRAMINE: CYP1A2 Inhibitors (Moderate) may increase the serum concentration of ClomiPRAMINE. Risk C: Monitor therapy

CloZAPine: CYP1A2 Inhibitors (Moderate) may increase the serum concentration of CloZAPine. Risk C: Monitor therapy

Colchicine: P-glycoprotein/ABCB1 Inhibitors may increase the 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 the serum concentration of CycloSPORINE (Systemic). Risk C: Monitor therapy

CYP3A4 Inducers (Moderate): May decrease the serum concentration of Capmatinib. Risk X: Avoid combination

CYP3A4 Inducers (Strong): May decrease the serum concentration of Capmatinib. Risk X: Avoid combination

CYP3A4 Inhibitors (Strong): May increase the serum concentration of Capmatinib. Risk C: Monitor therapy

Dabigatran Etexilate: P-glycoprotein/ABCB1 Inhibitors may increase serum concentrations of the active metabolite(s) of Dabigatran Etexilate. Risk C: Monitor therapy

Digoxin: P-glycoprotein/ABCB1 Inhibitors may increase the 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 the serum concentration of DOXOrubicin (Conventional). Risk X: Avoid combination

DOXOrubicin (Liposomal): P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of DOXOrubicin (Liposomal). Risk C: Monitor therapy

DULoxetine: CYP1A2 Inhibitors (Moderate) may increase the serum concentration of DULoxetine. Risk C: Monitor therapy

Edoxaban: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Edoxaban. Risk C: Monitor therapy

Etoposide: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Etoposide. Risk C: Monitor therapy

Etoposide Phosphate: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Etoposide Phosphate. Risk C: Monitor therapy

Everolimus: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Everolimus. Risk C: Monitor therapy

Fexinidazole: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Risk X: Avoid combination

Fezolinetant: CYP1A2 Inhibitors (Moderate) may increase the serum concentration of Fezolinetant. Risk X: Avoid combination

Fusidic Acid (Systemic): May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Risk X: Avoid combination

Glecaprevir and Pibrentasvir: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Glecaprevir and Pibrentasvir. Risk C: Monitor therapy

Lapatinib: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Lapatinib. Risk C: Monitor therapy

Larotrectinib: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Larotrectinib. Risk C: Monitor therapy

Lefamulin: P-glycoprotein/ABCB1 Inhibitors may increase the 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

Melatonin: CYP1A2 Inhibitors (Moderate) may increase the serum concentration of Melatonin. Risk C: Monitor therapy

Morphine (Systemic): P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Morphine (Systemic). Risk C: Monitor therapy

Nadolol: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Nadolol. Risk C: Monitor therapy

Naldemedine: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Naldemedine. Risk C: Monitor therapy

Naloxegol: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Naloxegol. Risk C: Monitor therapy

OLANZapine: CYP1A2 Inhibitors (Moderate) may increase the serum concentration of OLANZapine. Risk C: Monitor therapy

PAZOPanib: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of PAZOPanib. Risk X: Avoid combination

PAZOPanib: BCRP/ABCG2 Inhibitors may increase the serum concentration of PAZOPanib. Risk X: Avoid combination

Pentoxifylline: CYP1A2 Inhibitors (Moderate) may increase the serum concentration of Pentoxifylline. Risk C: Monitor therapy

Pirfenidone: CYP1A2 Inhibitors (Moderate) may increase the 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 the serum concentration of Pomalidomide. Risk C: Monitor therapy

Pralsetinib: P-glycoprotein/ABCB1 Inhibitors may increase the 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 the serum concentration of Propranolol. Risk C: Monitor therapy

Ramelteon: CYP1A2 Inhibitors (Moderate) may increase the serum concentration of Ramelteon. Risk C: Monitor therapy

Ramosetron: CYP1A2 Inhibitors (Moderate) may increase the serum concentration of Ramosetron. Risk C: Monitor therapy

Ranolazine: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Ranolazine. Risk C: Monitor therapy

Rasagiline: CYP1A2 Inhibitors (Moderate) may increase the 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: P-glycoprotein/ABCB1 Inhibitors may increase the 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

Relugolix, Estradiol, and Norethindrone: P-glycoprotein/ABCB1 Inhibitors may increase the 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

Repotrectinib: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Repotrectinib. Risk X: Avoid combination

RifAXIMin: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of RifAXIMin. Risk C: Monitor therapy

Rimegepant: P-glycoprotein/ABCB1 Inhibitors may increase the 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 the serum concentration of RisperiDONE. Risk C: Monitor therapy

RomiDEPsin: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of RomiDEPsin. Risk C: Monitor therapy

ROPINIRole: CYP1A2 Inhibitors (Moderate) may increase the serum concentration of ROPINIRole. Risk C: Monitor therapy

ROPivacaine: CYP1A2 Inhibitors (Moderate) may increase the serum concentration of ROPivacaine. Risk C: Monitor therapy

Rosuvastatin: Capmatinib may increase the serum concentration of Rosuvastatin. Management: Limit the dose of rosuvastatin to 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 the serum concentration of Saquinavir. Risk C: Monitor therapy

Silodosin: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Silodosin. Risk C: Monitor therapy

Sirolimus (Conventional): P-glycoprotein/ABCB1 Inhibitors may increase the 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 the serum concentration of Sirolimus (Protein Bound). Risk X: Avoid combination

Tacrolimus (Systemic): P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Tacrolimus (Systemic). Risk C: Monitor therapy

Talazoparib: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Talazoparib. Risk C: Monitor therapy

Talazoparib: BCRP/ABCG2 Inhibitors may increase the serum concentration of Talazoparib. Risk C: Monitor therapy

Tasimelteon: CYP1A2 Inhibitors (Moderate) may increase the serum concentration of Tasimelteon. Risk C: Monitor therapy

Tegaserod (Withdrawn from US Market): P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Tegaserod (Withdrawn from US Market). Risk C: Monitor therapy

Teniposide: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Teniposide. Risk C: Monitor therapy

Tenofovir Disoproxil Fumarate: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Tenofovir Disoproxil Fumarate. Risk C: Monitor therapy

Theophylline Derivatives: CYP1A2 Inhibitors (Moderate) may increase the 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 the serum concentration of TiZANidine. Management: If combined use cannot be avoided, initiate tizanidine in adults at 2 mg and increase in 2 to 4 mg increments based on patient response. Monitor for increased effects of tizanidine, including adverse reactions. Risk D: Consider therapy modification

Topotecan: BCRP/ABCG2 Inhibitors may increase the serum concentration of Topotecan. Risk X: Avoid combination

Topotecan: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Topotecan. Risk X: Avoid combination

Ubrogepant: BCRP/ABCG2 Inhibitors may increase the 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 the 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 the 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 (Liposomal): P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of VinCRIStine (Liposomal). Risk X: Avoid combination

Reproductive Considerations

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.

Pregnancy Considerations

Based on the mechanism of action and data from animal reproduction studies, in utero exposure to capmatinib may cause fetal harm.

Breastfeeding Considerations

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.

Monitoring Parameters

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.

Mechanism of Action

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.

Pharmacokinetics (Adult Data Unless Noted)

Absorption: >70%.

Distribution: V_dss: 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.

Brand Names: International

International Brand Names by Country

For country code abbreviations (show table)

(AT) Austria: Tabrecta;
(BR) Brazil: Tabrecta;
(CH) Switzerland: Tabrecta;
(CZ) Czech Republic: Tabrecta;
(FI) Finland: Tabrecta;
(FR) France: Capmatinib nph;
(HK) Hong Kong: Tabrecta;
(MY) Malaysia: Rahika;
(NL) Netherlands: Tabrecta;
(NO) Norway: Tabrecta;
(PL) Poland: Tabrecta;
(PR) Puerto Rico: Tabrecta;
(PT) Portugal: Tabrecta;
(SE) Sweden: Tabrecta;
(SG) Singapore: Tabrecta;
(SK) Slovakia: Tabrecta;
(TH) Thailand: Tabrecta;
(TW) Taiwan: Tabrecta

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Dhillon S. Capmatinib: First approval. Drugs. 2020;80(11):1125-1131. doi:10.1007/s40265-020-01347-3 [PubMed 32557339]
Hwang JP, Feld JJ, Hammond SP, et al. Hepatitis B virus screening and management for patients with cancer prior to therapy: ASCO provisional clinical opinion update. J Clin Oncol. 2020;38(31):3698-3715. doi:10.1200/JCO.20.01757 [PubMed 32716741]
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Tabrecta (capmatinib) [product monograph]. Montreal, Quebec, Canada: Novartis Pharmaceuticals Canada Inc; June 2023.
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Capmatinib: Drug information