Version July 2025
Non–small cell lung cancer, locally advanced or metastatic, ROS1 positive: Note: Select patients for treatment with repotrectinib based on the presence of ROS1 rearrangement(s) in tumor specimens.
Oral: 160 mg once daily for 14 days, then increase dose to 160 mg twice daily; continue until disease progression or unacceptable toxicity (Ref).
Solid tumors, NTRK gene fusion positive: Note: Select patients for treatment with repotrectinib based on the presence of NTRK1/2/3 rearrangements in tumor specimens. In patients with secretory breast cancer or mammary analogue secretory cancer, consider repotrectinib treatment without confirmation of NTRK rearrangement in tumor specimens.
Oral: 160 mg once daily for 14 days, then increase dose to 160 mg twice daily; continue until disease progression or unacceptable toxicity (Ref).
Missed doses: If dose of repotrectinib is missed or if vomiting occurs following administration, skip dose and resume with next scheduled dose.
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
eGFR ≥30 mL/minute: No dosage adjustment is necessary.
eGFR <30 mL/minute: There are no dosage adjustments provided in the manufacturer's labeling (has not been studied).
End-stage kidney disease on hemodialysis: There are no dosage adjustments provided in the manufacturer's labeling (has not been studied).
Hepatic impairment prior to treatment initiation:
Mild (total bilirubin >1 to 1.5 × ULN or AST > ULN) impairment: No dosage adjustment is necessary.
Moderate (total bilirubin >1.5 to 3 × ULN with any AST) or severe (total bilirubin >3 × ULN with any AST) impairment: There are no dosage adjustments provided in the manufacturer's labeling (has not been studied).
Acute hepatotoxicity during treatment:
Grade 3: Withhold repotrectinib until toxicity resolves to ≤ grade 1 or baseline. Resume repotrectinib at the same dose if resolution occurs within 4 weeks of interruption.
Grade 3, recurrent: Withhold repotrectinib until toxicity resolves to ≤ grade 1 or baseline. Resume repotrectinib at a reduced dose for recurrent toxicity that resolves within 4 weeks.
Grade 4: Withhold repotrectinib until toxicity resolves to ≤ grade 1 or baseline. Resume repotrectinib at a reduced dose. Permanently discontinue if resolution does not occur within 4 weeks of interruption.
Grade 4, recurrent: Permanently discontinue repotrectinib.
ALT or AST >3 times ULN with concurrent total bilirubin >1.5 times ULN (in the absence of cholestasis or hemolysis): Permanently discontinue repotrectinib.
|
Dosage reduction level |
Recommended repotrectinib dosage and schedule | |
|---|---|---|
|
Initial (usual) dosage |
160 mg once daily |
160 mg twice daily |
|
First dosage reduction |
120 mg once daily |
120 mg twice daily |
|
Second dosage reduction |
80 mg once daily |
80 mg twice daily |
|
Adverse reaction |
Severity |
Repotrectinib dosage modification |
|---|---|---|
|
CNS toxicity |
Intolerable grade 2 |
Withhold repotrectinib until toxicity resolves to ≤ grade 1 or baseline; resume repotrectinib at the same or reduced dose as clinically appropriate. |
|
Grade 3 |
Withhold repotrectinib until toxicity resolves to ≤ grade 1 or baseline; resume repotrectinib at a reduced dose. | |
|
Grade 4 |
Permanently discontinue repotrectinib. | |
|
Creatine phosphokinase (CPK) elevation |
Initiate supportive care as clinically indicated. | |
|
CPK >5 × ULN (first occurrence) |
Withhold repotrectinib until CPK recovers to baseline or to ≤2.5 × ULN; resume repotrectinib at the same dose. | |
|
CPK >5 × ULN (second occurrence) or CPK >10 × ULN |
Withhold repotrectinib until CPK recovers to baseline or to ≤2.5 × ULN; resume repotrectinib at a reduced dose. | |
|
Fracture signs or symptoms |
Pain, changes in mobility, deformity |
Evaluate promptly (may require treatment interruption). There are no data on the effects of repotrectinib on healing of known fractures or the risk of future fractures. |
|
Hyperuricemia |
Grade 3 or 4 |
Initiate treatment with urate-lowering medications as clinically indicated. Withhold repotrectinib until improvement of signs or symptoms; resume repotrectinib at the same or reduced dose. |
|
Pulmonary toxicity |
Suspected interstitial lung disease/pneumonitis |
Withhold repotrectinib. |
|
Confirmed interstitial lung disease/pneumonitis |
Permanently discontinue repotrectinib. | |
|
Other toxicity (clinically relevant) |
Intolerable grade 2 or Grade 3 or Grade 4 |
Withhold repotrectinib until toxicity resolves to ≤ grade 1 or baseline. Resolution of toxicity within 4 weeks of interruption: Resume repotrectinib at the same or reduced dose. Toxicity does not resolve within 4 weeks of interruption: Permanently discontinue repotrectinib. |
|
Recurrent grade 4 |
Permanently discontinue repotrectinib. | |
Refer to adult dosing.
(For additional information see "Repotrectinib: Pediatric drug information")
Solid tumors, NTRK gene fusion positive: Note: Select patients for treatment of solid tumors with repotrectinib based on the presence of NTRK1/2/3 rearrangements in tumor specimens.
Children ≥12 years and Adolescents: Oral: Initial: 160 mg once daily for 14 days, then increase to 160 mg twice daily; continue until disease progression or unacceptable toxicity.
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
Dosing adjustment for toxicity:
Dose reduction levels:
|
Dosage reduction level |
Repotrectinib dosage and schedule | |
|---|---|---|
|
Usual dose |
160 mg once daily |
160 mg twice daily |
|
First dose reduction |
120 mg once daily |
120 mg twice daily |
|
Second dose reduction |
80 mg once daily |
80 mg twice daily |
Dosage adjustments:
|
Adverse reaction |
Description/severity |
Repotrectinib dosage modification |
|---|---|---|
|
CNS toxicity |
Grade 2 (intolerable) |
Withhold repotrectinib until toxicity resolves to ≤ grade 1 or baseline; resume repotrectinib at the same or reduced dose as clinically appropriate. |
|
Grade 3 |
Withhold repotrectinib until toxicity resolves to ≤ grade 1 or baseline; resume repotrectinib at a reduced dose. | |
|
Grade 4 |
Permanently discontinue repotrectinib. | |
|
Creatine phosphokinase (CPK) elevation |
CPK >5 × ULN (first occurrence) |
Initiate supportive care as clinically indicated and withhold repotrectinib until CPK recovers to baseline or to ≤2.5 × ULN; resume repotrectinib at the same dose. |
|
CPK >5 × ULN (second occurrence) or CPK >10 × ULN |
Initiate supportive care as clinically indicated and withhold repotrectinib until CPK recovers to baseline or to ≤2.5 × ULN; resume repotrectinib at a reduced dose. | |
|
Hyperuricemia |
Grade 3 or 4 |
Initiate treatment with urate-lowering medications as clinically indicated. Withhold repotrectinib until improvement of signs or symptoms; resume repotrectinib at the same or reduced dose. |
|
Interstitial lung disease/pneumonitis |
Any grade |
Withhold repotrectinib for suspected; permanently discontinue if confirmed. |
|
Other toxicity (clinically relevant) |
Grade 2 (intolerable) or Grade 3 or Grade 4 (first occurrence) |
Withhold repotrectinib until toxicity resolves to ≤ grade 1 or baseline. Resolution of toxicity within 4 weeks of interruption: Resume repotrectinib at the same or reduced dose. Toxicity does not resolve within 4 weeks of interruption: Permanently discontinue repotrectinib. |
|
Grade 4 (recurrent) |
Permanently discontinue repotrectinib. |
Children ≥12 years and Adolescents: Oral:
eGFR ≥30 mL/minute: No dosage adjustment is necessary.
eGFR <30 mL/minute: There are no dosage adjustments provided in the manufacturer's labeling (has not been studied).
End-stage kidney disease on hemodialysis: There are no dosage adjustments provided in the manufacturer's labeling (has not been studied).
Children ≥12 years and Adolescents: Oral:
Baseline liver impairment:
Mild impairment (total bilirubin >1 to 1.5 × ULN or AST > ULN): No dosage adjustment is necessary.
Moderate impairment (total bilirubin >1.5 to 3 × ULN with any AST) or severe impairment (total bilirubin >3 × ULN with any AST): There are no dosage adjustments provided in the manufacturer's labeling (has not been studied).
Acute liver toxicity during treatment:
|
Adverse reaction |
Description/severity |
Repotrectinib dosage modification |
|---|---|---|
|
Acute liver toxicity |
Grade 3 (first occurrence) |
Withhold repotrectinib until toxicity resolves to ≤ grade 1 or baseline; resume repotrectinib at the same dose if resolution occurs within 4 weeks of interruption. |
|
Grade 3 (recurrent) |
Withhold repotrectinib until toxicity resolves to ≤ grade 1 or baseline. Resume repotrectinib at a reduced dose based on dosage reduction level tables for recurrent toxicity that resolves within 4 weeks. | |
|
Grade 4 (first occurrence) |
Withhold repotrectinib until toxicity resolves to ≤ grade 1 or baseline. Resume repotrectinib at a reduced dose based on dosage reduction level tables. Permanently discontinue if resolution does not occur within 4 weeks of interruption. | |
|
Grade 4 (recurrent) |
Permanently discontinue repotrectinib. | |
|
ALT or AST >3 × ULN with concurrent total bilirubin >1.5 × ULN (in the absence of cholestasis or hemolysis) |
Permanently discontinue repotrectinib. |
The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified. Reported adverse reactions are for adults.
>10%:
Cardiovascular: Edema (15%)
Endocrine & metabolic: Decreased serum glucose (20%), decreased serum phosphate (22%), increased serum glucose (26%), increased serum potassium (22%), increased serum sodium (33%), weight gain (16%)
Gastrointestinal: Constipation (38%), decreased appetite (11%), diarrhea (14%; grades 3/4: <1%), dysgeusia (54%), nausea (20%; grades 3/4: <1%), vomiting (12%; grades 3/4: 1%)
Hematologic & oncologic: Decreased hemoglobin (79%; grades 3/4: 8%), decreased neutrophils (34%; grades 3/4: 9%), increased INR (24%), lymphocytopenia (43%; grades 3/4: 10%), prolonged prothrombin time (26%; grades 3/4: <1%)
Hepatic: Increased gamma-glutamyl transferase (50%), increased serum alanine aminotransferase (38%), increased serum alkaline phosphatase (29%), increased serum aspartate aminotransferase (41%)
Nervous system: Central nervous system dysfunction (77%; including ataxia [28%], cognitive dysfunction [25%; including amnesia, aphasia, confusion: 2%, delirium, delusion, disturbance in attention: 12%, hallucination, impaired consciousness, memory impairment: 15%], dizziness [65%; including vertigo]), fatigue (30%), headache (19%), myasthenia (20%), peripheral neuropathy (49%; grades 3/4: 1%), sleep disturbance (18%; including drowsiness [9%], hypersomnia [2%], insomnia [6%])
Neuromuscular & skeletal: Increased creatine phosphokinase in blood specimen (61%), myalgia (13%)
Ophthalmic: Visual disturbance (12%)
Respiratory: Cough (18%), dyspnea (30%), pneumonia (11%)
1% to 10%:
Endocrine and metabolic: Hyperuricemia (5%)
Nervous system: Falling (4%), mood disorder (6%; including anxiety [3%], mania [grade 4: <1%])
Neuromuscular & skeletal: Bone fracture (2%)
Respiratory: Hypoxia (serious: 3%), pleural effusion (serious: 3%), pneumonitis (3%)
Miscellaneous: Fever (9%)
<1%: Respiratory: Interstitial pneumonitis
Frequency not defined: Hepatic: Hyperbilirubinemia
There are no contraindications listed in the manufacturer's labeling.
Concerns related to adverse effects:
• CNS effects: Ataxia, cognitive disorders, dizziness, mood disorders, and sleep disturbances have been reported with repotrectinib; approximately three-quarters of repotrectinib-treated patients experienced CNS toxicity; grade 3 or 4 reactions have been observed. Ataxia, including gait disturbance and balance disorder, occurred in nearly one-third of patents. Grade 3 ataxia occurred in a small number of patients; dose modification was necessary in <10% of patients due to ataxia. The median time to onset of ataxia was 15 days (range: 1 day to 1.4 years). Cognitive disorders including memory impairment, disturbance in attention, and confused state have occurred with repotrectinib; grade 3 cognitive disorders occurred in <1% of patients; dose modification secondary to cognitive disorders was required in some repotrectinib-treated patients. The median time to onset of cognitive disorders was 37 days (range: 1 day to 1.4 years). Dizziness, including vertigo, occurred in nearly two-thirds of patients (grade 3 dizziness also occurred); some patients required dose modification due to dizziness. The median time to onset of dizziness was 7 days (range: 1 day to 1.4 years). Mood disorders occurring in >1% of patients treated with repotrectinib included anxiety; grade 4 mood disorders (mania) also occurred. Dose modification was required in some patients due to mood disorders. Sleep disorders have occurred in repotrectinib-treated patients and included somnolence, insomnia, and hypersomnia. Dose modification due to sleep disorders occurred in a small number of repotrectinib-treated patients. The incidence of CNS toxicity observed was similar in patients with and without CNS metastases. Caution patients about performing tasks that require mental alertness (eg, operating machinery or driving).
• Hepatotoxicity: Increased AST and ALT occurred in 41% and 38% of patients, respectively; grade 3 and 4 transaminase elevations have also been reported. The median time to onset of increased ALT or AST was 15 days (range: 1 day to 1.9 years). Increased ALT or AST and hyperbilirubinemia leading to dose interruptions or reductions occurred in a small number of patients treated with repotrectinib.
• Hyperuricemia: Repotrectinib can cause hyperuricemia, including grade 3 or 4 events. One patient without preexisting gout required initiation of urate-lowering therapy.
• Myalgia/creatine phosphokinase elevation: Repotrectinib may cause myalgia (including grade 3 events); myalgia may occur with or without creatine phosphokinase (CPK) elevation. Median time to onset of myalgia was 19 days (range: 1 day to 2 years). Advise patients to report any unexplained muscle pain, tenderness, or weakness.
• Pulmonary toxicity: Interstitial lung disease/pneumonitis, including grade 3 events, have occurred with repotrectinib. The median time to onset was 45 days (range: 19 days to 0.9 years). Dose modification due to pulmonary toxicity was required in a small number of patients.
• Skeletal fractures: The risk of skeletal fractures is increased with repotrectinib therapy; a small number of patients required treatment interruption. In repotrectinib-treated patients, fractures involving the ribs, feet, spine, acetabulum, sternum, and ankles occurred; some fractures occurred at sites of disease and prior radiation therapy. The median time to fracture was 71 days (range: 31 days to 1.4 years). Promptly evaluate for signs/symptoms of fractures, such as pain, changes in mobility, or deformity; may require repotrectinib treatment interruption. No data is available on repotrectinib effects on healing of confirmed fractures and risk of future fractures.
Other warnings/precautions:
• Appropriate use: Select patients for treatment of locally advanced or metastatic non-small cell lung cancer based on the presence of ROS1 rearrangement(s) in tumor specimens. Select patients for treatment of solid tumors based on the presence of NTRK1/2/3 rearrangements in tumor specimens; consider repotrectinib treatment without confirmation of NTRK rearrangement in patients with secretory breast cancer or mammary analogue secretory cancer.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Capsule, Oral:
Augtyro: 40 mg
Augtyro: 160 mg [contains fd&c blue #1 (brilliant blue)]
No
Capsules (Augtyro Oral)
40 mg (per each): $153.70
160 mg (per each): $614.80
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.
Repotrectinib is available through specialty distributors and specialty pharmacies. Access information from the manufacturer may be found at https://www.augtyrohcp.com/assets/commercial/us/augtyrohcp/en/pdf/Authorized-Distributors-for-AUGTYRO.pdf.
Oral: Administer repotrectinib with or without food at approximately the same time each day. Swallow capsules whole; do not open, chew, crush, or dissolve capsules. Do not administer broken, cracked, or damaged capsules.
Oral: Administer repotrectinib without regard to food at approximately the same time each day. Swallow capsules whole; do not open, chew, crush, or dissolve capsules. Do not administer broken, cracked, or damaged capsules. If vomiting occurs following administration, skip dose; do not repeat.
Missed doses: If dose of repotrectinib is missed, skip dose and resume with next scheduled dose.
This medication is not on the NIOSH (2024) list; however, it may meet the criteria for a hazardous drug. Repotrectinib may cause teratogenicity and genotoxicity.
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, locally advanced or metastatic, ROS1 positive: Treatment of locally advanced or metastatic ROS1-positive non–small cell lung cancer in adults.
Solid tumors, NTRK gene fusion–positive: Treatment of solid tumors in adult and pediatric patients ≥12 years of age that have a neurotrophic tyrosine receptor kinase (NTRK) gene fusion, are locally advanced or metastatic or where surgical resection is likely to result in severe morbidity, and have progressed following treatment or have no satisfactory alternative therapy.
Augtyro may be confused with Aubagio
Repotrectinib may be confused with entrectinib, larotrectinib, regorafenib, ripretinib, rucaparib.
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 (Major with inhibitors), P-glycoprotein (Minor with inducers); Note: Assignment of Major/Minor substrate status based on clinically relevant drug interaction potential; Induces CYP3A4 (Moderate);
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.
Abemaciclib: CYP3A4 Inducers (Moderate) may decrease serum concentration of Abemaciclib. Risk X: Avoid
Abiraterone Acetate: CYP3A4 Inducers (Moderate) may decrease serum concentration of Abiraterone Acetate. Risk C: Monitor
Acalabrutinib: CYP3A4 Inducers (Moderate) may decrease serum concentration of Acalabrutinib. Risk C: Monitor
ALfentanil: CYP3A4 Inducers (Moderate) may decrease serum concentration of ALfentanil. Management: If concomitant use of alfentanil and moderate CYP3A4 inducers is necessary, consider dosage increase of alfentanil until stable drug effects are achieved. Monitor patients for signs of opioid withdrawal. Risk D: Consider Therapy Modification
Alpelisib: CYP3A4 Inducers (Moderate) may decrease serum concentration of Alpelisib. Risk C: Monitor
ALPRAZolam: CYP3A4 Inducers (Moderate) may decrease serum concentration of ALPRAZolam. Risk C: Monitor
AmLODIPine: CYP3A4 Inducers (Moderate) may decrease serum concentration of AmLODIPine. Risk C: Monitor
Apremilast: CYP3A4 Inducers (Moderate) may decrease serum concentration of Apremilast. Risk C: Monitor
ARIPiprazole Lauroxil: CYP3A4 Inducers (Moderate) may decrease serum concentration of ARIPiprazole Lauroxil. Risk C: Monitor
ARIPiprazole: CYP3A4 Inducers (Moderate) may decrease serum concentration of ARIPiprazole. Risk C: Monitor
Artemether and Lumefantrine: CYP3A4 Inducers (Moderate) may decrease serum concentration of Artemether and Lumefantrine. CYP3A4 Inducers (Moderate) may decrease active metabolite exposure of Artemether and Lumefantrine. Specifically, concentrations of dihydroartemisinin (DHA), the active metabolite of artemether may be decreased. Risk C: Monitor
Asciminib: May increase serum concentration of P-glycoprotein/ABCB1 Substrates (Narrow Therapeutic Index/Sensitive with Inhibitors). Risk C: Monitor
Atogepant: CYP3A4 Inducers (Moderate) may decrease serum concentration of Atogepant. Management: For treatment of episodic migraine, the recommended dose of atogepant is 30 mg once daily or 60 mg once daily when combined with CYP3A4 inducers. When used for treatment of chronic migraine, use of atogepant with CYP3A4 inducers should be avoided. Risk D: Consider Therapy Modification
Atorvastatin: CYP3A4 Inducers (Moderate) may decrease serum concentration of Atorvastatin. Risk C: Monitor
Atrasentan: CYP3A4 Inducers (Moderate) may decrease serum concentration of Atrasentan. Risk X: Avoid
Avacopan: Repotrectinib may decrease serum concentration of Avacopan. Avacopan may increase serum concentration of Repotrectinib. Risk X: Avoid
Avanafil: CYP3A4 Inducers (Moderate) may decrease serum concentration of Avanafil. Risk X: Avoid
Avapritinib: CYP3A4 Inducers (Moderate) may decrease serum concentration of Avapritinib. Risk X: Avoid
Axitinib: CYP3A4 Inducers (Moderate) may decrease serum concentration of Axitinib. Management: Concurrent use of axitinib with a moderate CYP3A4 inducer should be avoided when possible. If any such combination is necessary, monitor for reduced axitinib efficacy. Risk D: Consider Therapy Modification
Bedaquiline: CYP3A4 Inducers (Moderate) may decrease serum concentration of Bedaquiline. CYP3A4 Inducers (Moderate) may increase active metabolite exposure of Bedaquiline. Risk X: Avoid
Benzhydrocodone: CYP3A4 Inducers (Moderate) may decrease serum concentration of Benzhydrocodone. Specifically, the serum concentrations of hydrocodone may be reduced. Risk C: Monitor
Bortezomib: CYP3A4 Inducers (Moderate) may decrease serum concentration of Bortezomib. Risk C: Monitor
Bosutinib: CYP3A4 Inducers (Moderate) may decrease serum concentration of Bosutinib. Risk C: Monitor
Brexpiprazole: CYP3A4 Inducers (Moderate) may decrease serum concentration of Brexpiprazole. Risk C: Monitor
Brigatinib: CYP3A4 Inducers (Moderate) may decrease serum concentration of Brigatinib. Management: Avoid concurrent use of brigatinib with moderate CYP3A4 inducers when possible. If combined, increase the daily dose of brigatinib in 30 mg increments after 7 days of treatment with the current brigatinib dose, up to maximum of twice the dose. Risk D: Consider Therapy Modification
Buprenorphine: CYP3A4 Inducers (Moderate) may decrease serum concentration of Buprenorphine. Risk C: Monitor
BusPIRone: CYP3A4 Inducers (Moderate) may decrease serum concentration of BusPIRone. Risk C: Monitor
Cabozantinib: CYP3A4 Inducers (Moderate) may decrease serum concentration of Cabozantinib. Management: For cabozantinib tablets (Cabometyx), avoid combined use if possible. If combined, increase cabozantinib by 20 mg from previous dose, max 80 mg daily. For cabozantinib capsules (Cometriq), monitor for reduced cabozantinib efficacy if combined. Risk D: Consider Therapy Modification
Calcifediol: CYP3A4 Inducers (Moderate) may decrease serum concentration of Calcifediol. Risk C: Monitor
Calcitriol (Systemic): CYP3A4 Inducers (Moderate) may decrease serum concentration of Calcitriol (Systemic). Risk C: Monitor
Cannabis: CYP3A4 Inducers (Moderate) may decrease serum concentration of Cannabis. More specifically, tetrahydrocannabinol and cannabidiol serum concentrations may be decreased. Risk C: Monitor
Capivasertib: CYP3A4 Inducers (Moderate) may decrease serum concentration of Capivasertib. Risk X: Avoid
Capmatinib: CYP3A4 Inducers (Moderate) may decrease serum concentration of Capmatinib. Risk X: Avoid
Cariprazine: CYP3A4 Inducers (Moderate) may decrease serum concentration of Cariprazine. Risk X: Avoid
Clindamycin (Systemic): CYP3A4 Inducers (Moderate) may decrease serum concentration of Clindamycin (Systemic). Risk C: Monitor
Clofazimine: May increase serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Risk C: Monitor
CloZAPine: CYP3A4 Inducers (Moderate) may decrease serum concentration of CloZAPine. Risk C: Monitor
Cobimetinib: CYP3A4 Inducers (Moderate) may decrease serum concentration of Cobimetinib. Risk X: Avoid
Codeine: CYP3A4 Inducers (Moderate) may decrease active metabolite exposure of Codeine. Risk C: Monitor
Copanlisib: CYP3A4 Inducers (Moderate) may decrease serum concentration of Copanlisib. Risk C: Monitor
Crinecerfont: CYP3A4 Inducers (Moderate) may decrease serum concentration of Crinecerfont. Management: Double the evening dose of crinecerfont and continue the morning dose unchanged during coadministration with moderate CYP3A4 inducers. See full interaction monograph for details. Risk D: Consider Therapy Modification
CYP3A4 Inducers (Moderate): May decrease serum concentration of Repotrectinib. Risk X: Avoid
CYP3A4 Inducers (Strong): May decrease serum concentration of Repotrectinib. Risk X: Avoid
CYP3A4 Inhibitors (Moderate): May increase serum concentration of Repotrectinib. Risk X: Avoid
CYP3A4 Inhibitors (Strong): May increase serum concentration of Repotrectinib. Risk X: Avoid
Dapsone (Systemic): CYP3A4 Inducers (Moderate) may decrease serum concentration of Dapsone (Systemic). Risk C: Monitor
Daridorexant: CYP3A4 Inducers (Moderate) may decrease serum concentration of Daridorexant. Risk X: Avoid
Dasabuvir: CYP3A4 Inducers (Moderate) may decrease serum concentration of Dasabuvir. Risk X: Avoid
Dasatinib: CYP3A4 Inducers (Moderate) may increase serum concentration of Dasatinib. Risk C: Monitor
Deflazacort: CYP3A4 Inducers (Moderate) may decrease active metabolite exposure of Deflazacort. Risk X: Avoid
DexAMETHasone (Systemic): CYP3A4 Inducers (Moderate) may decrease serum concentration of DexAMETHasone (Systemic). Risk C: Monitor
DiazePAM: CYP3A4 Inducers (Moderate) may decrease serum concentration of DiazePAM. Risk C: Monitor
Dienogest: CYP3A4 Inducers (Moderate) may decrease serum concentration of Dienogest. Risk C: Monitor
Disopyramide: CYP3A4 Inducers (Moderate) may decrease serum concentration of Disopyramide. Risk C: Monitor
Doravirine: CYP3A4 Inducers (Moderate) may decrease serum concentration of Doravirine. Risk C: Monitor
DOXOrubicin (Conventional): CYP3A4 Inducers (Moderate) may decrease serum concentration of DOXOrubicin (Conventional). Risk X: Avoid
DroNABinol: CYP3A4 Inducers (Moderate) may decrease serum concentration of DroNABinol. Risk C: Monitor
Dydrogesterone: CYP3A4 Inducers (Moderate) may decrease serum concentration of Dydrogesterone. Risk C: Monitor
Elacestrant: CYP3A4 Inducers (Moderate) may decrease serum concentration of Elacestrant. Risk X: Avoid
Elbasvir and Grazoprevir: CYP3A4 Inducers (Moderate) may decrease serum concentration of Elbasvir and Grazoprevir. Risk X: Avoid
Ensartinib: CYP3A4 Inducers (Moderate) may decrease serum concentration of Ensartinib. Risk X: Avoid
Entrectinib: CYP3A4 Inducers (Moderate) may decrease serum concentration of Entrectinib. Risk X: Avoid
Erdafitinib: CYP3A4 Inducers (Moderate) may decrease serum concentration of Erdafitinib. Management: If a moderate CYP3A4 inducer must be used at the start of erdafitinib, administer erdafitinib at a dose of 9 mg daily. If a moderate CYP3A4 inducer is discontinued, continue erdafitinib at the same dose unless there is evidence of drug toxicity. Risk D: Consider Therapy Modification
Erdafitinib: May increase serum concentration of P-glycoprotein/ABCB1 Substrates (Narrow Therapeutic Index/Sensitive with Inhibitors). Management: If coadministration with these narrow therapeutic index/sensitive P-gp substrates is unavoidable, separate erdafitinib administration by at least 6 hours before or after administration of these P-gp substrates. Risk D: Consider Therapy Modification
Erlotinib: CYP3A4 Inducers (Moderate) may decrease serum concentration of Erlotinib. Management: Avoid the combination of erlotinib and strong CYP3A4 inducers whenever possible. If this combination must be used, increase erlotinib dose by 50 mg increments every 2 weeks as tolerated, to a maximum of 450 mg/day. Risk D: Consider Therapy Modification
Estrogen Derivatives: CYP3A4 Inducers (Moderate) may decrease serum concentration of Estrogen Derivatives. Risk C: Monitor
Etoposide Phosphate: CYP3A4 Inducers (Moderate) may decrease serum concentration of Etoposide Phosphate. Risk C: Monitor
Etoposide: CYP3A4 Inducers (Moderate) may decrease serum concentration of Etoposide. Risk C: Monitor
Everolimus: CYP3A4 Inducers (Moderate) may decrease serum concentration of Everolimus. Risk C: Monitor
Exemestane: CYP3A4 Inducers (Moderate) may decrease serum concentration of Exemestane. Risk C: Monitor
Fedratinib: CYP3A4 Inducers (Moderate) may decrease serum concentration of Fedratinib. Risk X: Avoid
Felodipine: CYP3A4 Inducers (Moderate) may decrease serum concentration of Felodipine. Risk C: Monitor
FentaNYL: CYP3A4 Inducers (Moderate) may decrease serum concentration of FentaNYL. Risk C: Monitor
Finerenone: CYP3A4 Inducers (Moderate) may decrease serum concentration of Finerenone. Risk X: Avoid
Flibanserin: CYP3A4 Inducers (Moderate) may decrease serum concentration of Flibanserin. Risk X: Avoid
Fosaprepitant: CYP3A4 Inducers (Moderate) may decrease serum concentration of Fosaprepitant. Specifically, CYP3A4 Inducers (Moderate) may decrease serum concentrations of the active metabolite aprepitant. Risk C: Monitor
Fruquintinib: CYP3A4 Inducers (Moderate) may decrease serum concentration of Fruquintinib. Management: Avoid this combination when possible. If combined, continue the same fruquintinib dose, but monitor for reduced fruquintinib efficacy. Risk D: Consider Therapy Modification
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
Futibatinib: May increase serum concentration of P-glycoprotein/ABCB1 Substrates (Narrow Therapeutic Index/Sensitive with Inhibitors). Risk C: Monitor
Ganaxolone: CYP3A4 Inducers (Moderate) may decrease serum concentration of Ganaxolone. Management: Avoid concomitant use of ganaxolone and moderate CYP3A4 inducers whenever possible. If combined, consider increasing the dose of ganaxolone, but do not exceed the maximum recommended daily dose. Risk D: Consider Therapy Modification
Gefitinib: CYP3A4 Inducers (Moderate) may decrease serum concentration of Gefitinib. Risk C: Monitor
Gemigliptin: CYP3A4 Inducers (Moderate) may decrease serum concentration of Gemigliptin. CYP3A4 Inducers (Moderate) may decrease active metabolite exposure of Gemigliptin. Risk C: Monitor
Gepirone: CYP3A4 Inducers (Moderate) may decrease serum concentration of Gepirone. Risk C: Monitor
Gepotidacin: CYP3A4 Inducers (Moderate) may decrease serum concentration of Gepotidacin. Risk C: Monitor
Gilteritinib: May increase serum concentration of P-glycoprotein/ABCB1 Substrates (Narrow Therapeutic Index/Sensitive with Inhibitors). Risk C: Monitor
Glasdegib: CYP3A4 Inducers (Moderate) may decrease serum concentration of Glasdegib. Management: Avoid use of glasdegib and moderate CYP3A4 inducers whenever possible. If combined, increase glasdegib dose from 100 mg daily to 200 mg daily or from 50 mg daily to 100 mg daily. Resume previous glasdegib dose 7 days after discontinuation of the inducer. Risk D: Consider Therapy Modification
Grapefruit Juice: May increase serum concentration of Repotrectinib. Risk X: Avoid
GuanFACINE: CYP3A4 Inducers (Moderate) may decrease serum concentration of GuanFACINE. Management: Increase extended-release guanfacine dose by up to double when initiating guanfacine in patients taking CYP3A4 inducers or if initiating a CYP3A4 inducer in a patient already taking extended-release guanfacine. Monitor for reduced guanfacine efficacy. Risk D: Consider Therapy Modification
Hormonal Contraceptives: Repotrectinib may decrease serum concentration of Hormonal Contraceptives. Risk X: Avoid
HYDROcodone: CYP3A4 Inducers (Moderate) may decrease serum concentration of HYDROcodone. Risk C: Monitor
Hydrocortisone (Systemic): CYP3A4 Inducers (Moderate) may decrease serum concentration of Hydrocortisone (Systemic). Risk C: Monitor
Ibrexafungerp: CYP3A4 Inducers (Moderate) may decrease serum concentration of Ibrexafungerp. Risk X: Avoid
Ibrutinib: CYP3A4 Inducers (Moderate) may decrease serum concentration of Ibrutinib. Risk C: Monitor
Ifosfamide: CYP3A4 Inducers (Moderate) may decrease active metabolite exposure of Ifosfamide. CYP3A4 Inducers (Moderate) may increase active metabolite exposure of Ifosfamide. Risk C: Monitor
Irinotecan Products: CYP3A4 Inducers (Moderate) may decrease active metabolite exposure of Irinotecan Products. Specifically, concentrations of SN-38 may be reduced. Risk C: Monitor
Isradipine: CYP3A4 Inducers (Moderate) may decrease serum concentration of Isradipine. Risk C: Monitor
Istradefylline: CYP3A4 Inducers (Moderate) may decrease serum concentration of Istradefylline. Risk C: Monitor
Ivabradine: CYP3A4 Inducers (Moderate) may decrease serum concentration of Ivabradine. Risk X: Avoid
Ixabepilone: CYP3A4 Inducers (Moderate) may decrease serum concentration of Ixabepilone. Risk C: Monitor
Ixazomib: CYP3A4 Inducers (Moderate) may decrease serum concentration of Ixazomib. Risk C: Monitor
Ketamine: CYP3A4 Inducers (Moderate) may decrease serum concentration of Ketamine. Risk C: Monitor
Larotrectinib: CYP3A4 Inducers (Moderate) may decrease serum concentration of Larotrectinib. Management: Double the larotrectinib dose if used together with a moderate CYP3A4 inducer. Following discontinuation of the moderate CYP3A4 inducer, resume the previous dose of larotrectinib after a period of 3 to 5 times the inducer's half-life. Risk D: Consider Therapy Modification
Lasmiditan: May increase serum concentration of P-glycoprotein/ABCB1 Substrates (Narrow Therapeutic Index/Sensitive with Inhibitors). Risk X: Avoid
Lazertinib: CYP3A4 Inducers (Moderate) may decrease serum concentration of Lazertinib. Risk X: Avoid
Lefamulin (Intravenous): CYP3A4 Inducers (Moderate) may decrease serum concentration of Lefamulin (Intravenous). Management: Avoid concomitant use of lefamulin (intravenous) with moderate CYP3A4 inducers unless the benefits outweigh the risks. Risk D: Consider Therapy Modification
Lemborexant: CYP3A4 Inducers (Moderate) may decrease serum concentration of Lemborexant. Risk X: Avoid
Lenacapavir: CYP3A4 Inducers (Moderate) may decrease serum concentration of Lenacapavir. Risk X: Avoid
Leniolisib: CYP3A4 Inducers (Moderate) may decrease serum concentration of Leniolisib. Risk X: Avoid
Lercanidipine: CYP3A4 Inducers (Moderate) may decrease serum concentration of Lercanidipine. Risk C: Monitor
Levacetylleucine: May increase serum concentration of P-glycoprotein/ABCB1 Substrates (Narrow Therapeutic Index/Sensitive with Inhibitors). Risk C: Monitor
Levamlodipine: CYP3A4 Inducers (Moderate) may decrease serum concentration of Levamlodipine. Risk C: Monitor
Levomethadone: CYP3A4 Inducers (Moderate) may decrease serum concentration of Levomethadone. Risk C: Monitor
LinaGLIPtin: CYP3A4 Inducers (Moderate) may decrease serum concentration of LinaGLIPtin. Risk C: Monitor
Lonafarnib: CYP3A4 Inducers (Moderate) may decrease serum concentration of Lonafarnib. Risk X: Avoid
Lovastatin: CYP3A4 Inducers (Moderate) may decrease serum concentration of Lovastatin. Risk C: Monitor
Lumateperone: CYP3A4 Inducers (Moderate) may decrease serum concentration of Lumateperone. Risk X: Avoid
Lurasidone: CYP3A4 Inducers (Moderate) may decrease serum concentration of Lurasidone. Management: After chronic treatment (7 days or more) with a moderate CYP3A4 inducer, lurasidone dose increases may be needed. Monitor closely for decreased lurasidone effects and increase the lurasidone dose as needed. Risk D: Consider Therapy Modification
Macitentan: CYP3A4 Inducers (Moderate) may decrease serum concentration of Macitentan. Risk C: Monitor
Maraviroc: CYP3A4 Inducers (Moderate) may decrease serum concentration of Maraviroc. Management: Increase maraviroc adult dose to 600 mg twice/day, but only if not receiving a strong CYP3A4 inhibitor. Not recommended for pediatric patients not also receiving a strong CYP3A4 inhibitor. Contraindicated in patients with CrCl less than 30 mL/min. Risk D: Consider Therapy Modification
Maribavir: CYP3A4 Inducers (Moderate) may decrease serum concentration of Maribavir. Risk C: Monitor
Mavacamten: CYP3A4 Inducers (Moderate) may decrease serum concentration of Mavacamten. Risk X: Avoid
Mefloquine: CYP3A4 Inducers (Moderate) may decrease serum concentration of Mefloquine. Risk C: Monitor
Meperidine: CYP3A4 Inducers (Moderate) may decrease serum concentration of Meperidine. CYP3A4 Inducers (Moderate) may increase active metabolite exposure of Meperidine. Specifically, concentrations of normeperidine, the CNS stimulating metabolite, may be increased. Risk C: Monitor
Methadone: CYP3A4 Inducers (Moderate) may decrease serum concentration of Methadone. Risk C: Monitor
MethylPREDNISolone: CYP3A4 Inducers (Moderate) may decrease serum concentration of MethylPREDNISolone. Risk C: Monitor
Mianserin: CYP3A4 Inducers (Moderate) may decrease serum concentration of Mianserin. Risk C: Monitor
Midazolam: CYP3A4 Inducers (Moderate) may decrease serum concentration of Midazolam. Risk C: Monitor
Midostaurin: CYP3A4 Inducers (Moderate) may decrease serum concentration of Midostaurin. Risk C: Monitor
Mirodenafil: CYP3A4 Inducers (Moderate) may decrease serum concentration of Mirodenafil. Risk C: Monitor
Mobocertinib: CYP3A4 Inducers (Moderate) may decrease serum concentration of Mobocertinib. CYP3A4 Inducers (Moderate) may decrease active metabolite exposure of Mobocertinib. Risk X: Avoid
Montelukast: CYP3A4 Inducers (Moderate) may decrease serum concentration of Montelukast. Risk C: Monitor
Naldemedine: CYP3A4 Inducers (Moderate) may decrease serum concentration of Naldemedine. Risk C: Monitor
Naloxegol: CYP3A4 Inducers (Moderate) may decrease serum concentration of Naloxegol. Risk C: Monitor
Neratinib: CYP3A4 Inducers (Moderate) may decrease serum concentration of Neratinib. Risk X: Avoid
Nevirapine: CYP3A4 Inducers (Moderate) may decrease serum concentration of Nevirapine. Risk C: Monitor
NIFEdipine: CYP3A4 Inducers (Moderate) may decrease serum concentration of NIFEdipine. Risk C: Monitor
Nilvadipine: CYP3A4 Inducers (Moderate) may decrease serum concentration of Nilvadipine. Risk C: Monitor
NiMODipine: CYP3A4 Inducers (Moderate) may decrease serum concentration of NiMODipine. Risk C: Monitor
Nirogacestat: CYP3A4 Inducers (Moderate) may decrease serum concentration of Nirogacestat. Risk X: Avoid
Nisoldipine: CYP3A4 Inducers (Moderate) may decrease serum concentration of Nisoldipine. Risk X: Avoid
Olaparib: CYP3A4 Inducers (Moderate) may decrease serum concentration of Olaparib. Risk X: Avoid
Oliceridine: CYP3A4 Inducers (Moderate) may decrease serum concentration of Oliceridine. Risk C: Monitor
Olmutinib: CYP3A4 Inducers (Moderate) may decrease serum concentration of Olmutinib. Risk C: Monitor
Olutasidenib: CYP3A4 Inducers (Moderate) may decrease serum concentration of Olutasidenib. Risk X: Avoid
Omaveloxolone: CYP3A4 Inducers (Moderate) may decrease serum concentration of Omaveloxolone. Risk X: Avoid
OxyCODONE: CYP3A4 Inducers (Moderate) may decrease serum concentration of OxyCODONE. Risk C: Monitor
P-glycoprotein/ABCB1 Inhibitors: May increase serum concentration of Repotrectinib. Risk X: Avoid
PACLitaxel (Conventional): CYP3A4 Inducers (Moderate) may decrease serum concentration of PACLitaxel (Conventional). Risk C: Monitor
PACLitaxel (Protein Bound): CYP3A4 Inducers (Moderate) may decrease serum concentration of PACLitaxel (Protein Bound). Risk C: Monitor
Palbociclib: CYP3A4 Inducers (Moderate) may decrease serum concentration of Palbociclib. Risk C: Monitor
Paliperidone: CYP3A4 Inducers (Moderate) may decrease serum concentration of Paliperidone. Risk C: Monitor
Palovarotene: CYP3A4 Inducers (Moderate) may decrease serum concentration of Palovarotene. Risk X: Avoid
PAZOPanib: CYP3A4 Inducers (Moderate) may decrease serum concentration of PAZOPanib. Risk C: Monitor
Pemigatinib: CYP3A4 Inducers (Moderate) may decrease serum concentration of Pemigatinib. Risk X: Avoid
Perampanel: CYP3A4 Inducers (Moderate) may decrease serum concentration of Perampanel. Management: Increase perampanel starting dose to 4 mg/day if used with moderate CYP3A4 inducers. Increase perampanel dose by 2 mg/day no more than once weekly based on response and tolerability. Dose adjustments may be needed if the inducer is discontinued. Risk D: Consider Therapy Modification
Pimavanserin: CYP3A4 Inducers (Moderate) may decrease serum concentration of Pimavanserin. Risk X: Avoid
Piperaquine: CYP3A4 Inducers (Moderate) may decrease serum concentration of Piperaquine. Risk C: Monitor
PONATinib: CYP3A4 Inducers (Moderate) may decrease serum concentration of PONATinib. Risk C: Monitor
Pralsetinib: CYP3A4 Inducers (Moderate) may decrease serum concentration of Pralsetinib. Management: If this combo cannot be avoided, increase pralsetinib dose from 400 mg daily to 600 mg daily; from 300 mg daily to 500 mg daily; and from 200 mg daily to 300 mg daily. Risk D: Consider Therapy Modification
Praziquantel: CYP3A4 Inducers (Moderate) may decrease serum concentration of Praziquantel. Management: Consider alternatives to this combination whenever possible. If combined, monitor closely for reduced praziquantel efficacy. If possible, stop the moderate CYP3A4 inducer 2 to 4 weeks before praziquantel initiation. Risk D: Consider Therapy Modification
PrednisoLONE (Systemic): CYP3A4 Inducers (Moderate) may decrease serum concentration of PrednisoLONE (Systemic). Risk C: Monitor
PredniSONE: CYP3A4 Inducers (Moderate) may decrease serum concentration of PredniSONE. Risk C: Monitor
Pretomanid: CYP3A4 Inducers (Moderate) may decrease serum concentration of Pretomanid. Risk X: Avoid
Primaquine: May increase serum concentration of P-glycoprotein/ABCB1 Substrates (Narrow Therapeutic Index/Sensitive with Inhibitors). Risk C: Monitor
QUEtiapine: CYP3A4 Inducers (Moderate) may decrease serum concentration of QUEtiapine. Risk C: Monitor
Quizartinib: CYP3A4 Inducers (Moderate) may decrease serum concentration of Quizartinib. Risk X: Avoid
Ranolazine: CYP3A4 Inducers (Moderate) may decrease serum concentration of Ranolazine. Risk X: Avoid
Regorafenib: CYP3A4 Inducers (Moderate) may decrease serum concentration of Regorafenib. CYP3A4 Inducers (Moderate) may increase active metabolite exposure of Regorafenib. Risk C: Monitor
Repaglinide: CYP3A4 Inducers (Moderate) may decrease serum concentration of Repaglinide. Risk C: Monitor
Revumenib: CYP3A4 Inducers (Moderate) may decrease serum concentration of Revumenib. Risk X: Avoid
Rilpivirine: CYP3A4 Inducers (Moderate) may decrease serum concentration of Rilpivirine. Risk C: Monitor
Rimegepant: CYP3A4 Inducers (Moderate) may decrease serum concentration of Rimegepant. Risk X: Avoid
Ripretinib: CYP3A4 Inducers (Moderate) may decrease serum concentration of Ripretinib. Management: Avoid this combination if possible. If concomitant use is required, increase ripretinib to 150 mg twice daily. Decrease ripretinib to 150 mg once daily 14 days after stopping a moderate CYP3A4 inducer. Monitor patients for ripretinib response and toxicity Risk D: Consider Therapy Modification
RisperiDONE: CYP3A4 Inducers (Moderate) may decrease serum concentration of RisperiDONE. CYP3A4 Inducers (Moderate) may decrease active metabolite exposure of RisperiDONE. Risk C: Monitor
Ritlecitinib: CYP3A4 Inducers (Moderate) may decrease serum concentration of Ritlecitinib. Risk C: Monitor
Roflumilast (Systemic): CYP3A4 Inducers (Moderate) may decrease serum concentration of Roflumilast (Systemic). CYP3A4 Inducers (Moderate) may decrease active metabolite exposure of Roflumilast (Systemic). Risk C: Monitor
Samidorphan: CYP3A4 Inducers (Moderate) may decrease serum concentration of Samidorphan. Risk C: Monitor
Selpercatinib: CYP3A4 Inducers (Moderate) may decrease serum concentration of Selpercatinib. Risk X: Avoid
Selumetinib: CYP3A4 Inducers (Moderate) may decrease serum concentration of Selumetinib. Risk X: Avoid
Sertraline: CYP3A4 Inducers (Moderate) may decrease serum concentration of Sertraline. Risk C: Monitor
Sildenafil: CYP3A4 Inducers (Moderate) may decrease serum concentration of Sildenafil. Risk C: Monitor
Simeprevir: CYP3A4 Inducers (Moderate) may decrease serum concentration of Simeprevir. Risk X: Avoid
Simvastatin: CYP3A4 Inducers (Moderate) may decrease serum concentration of Simvastatin. Risk C: Monitor
Sirolimus (Conventional): CYP3A4 Inducers (Moderate) may decrease serum concentration of Sirolimus (Conventional). Risk C: Monitor
Sirolimus (Protein Bound): CYP3A4 Inducers (Moderate) may decrease serum concentration of Sirolimus (Protein Bound). Risk C: Monitor
Sonidegib: CYP3A4 Inducers (Moderate) may decrease serum concentration of Sonidegib. Risk X: Avoid
SORAfenib: CYP3A4 Inducers (Moderate) may decrease serum concentration of SORAfenib. Risk C: Monitor
Sparsentan: May increase serum concentration of P-glycoprotein/ABCB1 Substrates (Narrow Therapeutic Index/Sensitive with Inhibitors). Risk X: Avoid
SUFentanil: CYP3A4 Inducers (Moderate) may decrease serum concentration of SUFentanil. Risk C: Monitor
SUNItinib: CYP3A4 Inducers (Moderate) may decrease serum concentration of SUNItinib. Risk C: Monitor
Suvorexant: CYP3A4 Inducers (Moderate) may decrease serum concentration of Suvorexant. Risk C: Monitor
Suzetrigine: CYP3A4 Inducers (Moderate) may decrease serum concentration of Suzetrigine. Risk X: Avoid
Tacrolimus (Systemic): CYP3A4 Inducers (Moderate) may decrease serum concentration of Tacrolimus (Systemic). Risk C: Monitor
Tadalafil: CYP3A4 Inducers (Moderate) may decrease serum concentration of Tadalafil. Risk C: Monitor
Tamoxifen: CYP3A4 Inducers (Moderate) may decrease serum concentration of Tamoxifen. CYP3A4 Inducers (Moderate) may decrease active metabolite exposure of Tamoxifen. Risk C: Monitor
Tasimelteon: CYP3A4 Inducers (Moderate) may decrease serum concentration of Tasimelteon. Risk C: Monitor
Taurursodiol: May increase serum concentration of P-glycoprotein/ABCB1 Substrates (Narrow Therapeutic Index/Sensitive with Inhibitors). Risk X: Avoid
Tazemetostat: CYP3A4 Inducers (Moderate) may decrease serum concentration of Tazemetostat. Risk X: Avoid
Temsirolimus: CYP3A4 Inducers (Moderate) may decrease serum concentration of Temsirolimus. CYP3A4 Inducers (Moderate) may decrease active metabolite exposure of Temsirolimus. Specifically, sirolimus concentrations may be decreased. Risk C: Monitor
Teniposide: CYP3A4 Inducers (Moderate) may decrease serum concentration of Teniposide. Risk C: Monitor
Tetrahydrocannabinol and Cannabidiol: CYP3A4 Inducers (Moderate) may decrease serum concentration of Tetrahydrocannabinol and Cannabidiol. Risk C: Monitor
Tetrahydrocannabinol: CYP3A4 Inducers (Moderate) may decrease serum concentration of Tetrahydrocannabinol. Risk C: Monitor
Thiotepa: CYP3A4 Inducers (Moderate) may increase active metabolite exposure of Thiotepa. CYP3A4 Inducers (Moderate) may decrease serum concentration of Thiotepa. Risk C: Monitor
Ticagrelor: CYP3A4 Inducers (Moderate) may decrease serum concentration of Ticagrelor. CYP3A4 Inducers (Moderate) may decrease active metabolite exposure of Ticagrelor. Risk C: Monitor
Tivozanib: CYP3A4 Inducers (Moderate) may decrease serum concentration of Tivozanib. Risk C: Monitor
Tofacitinib: CYP3A4 Inducers (Moderate) may decrease serum concentration of Tofacitinib. Risk C: Monitor
Tolvaptan: CYP3A4 Inducers (Moderate) may decrease serum concentration of Tolvaptan. Risk C: Monitor
Toremifene: CYP3A4 Inducers (Moderate) may decrease serum concentration of Toremifene. CYP3A4 Inducers (Moderate) may decrease active metabolite exposure of Toremifene. Risk C: Monitor
Trabectedin: CYP3A4 Inducers (Moderate) may decrease serum concentration of Trabectedin. Risk C: Monitor
TraMADol: CYP3A4 Inducers (Moderate) may decrease serum concentration of TraMADol. Risk C: Monitor
TraZODone: CYP3A4 Inducers (Moderate) may decrease serum concentration of TraZODone. Risk C: Monitor
Tretinoin (Systemic): CYP3A4 Inducers (Moderate) may decrease serum concentration of Tretinoin (Systemic). Risk C: Monitor
Triazolam: CYP3A4 Inducers (Moderate) may decrease serum concentration of Triazolam. Risk C: Monitor
Ubrogepant: CYP3A4 Inducers (Moderate) may decrease serum concentration of Ubrogepant. Management: Use an initial ubrogepant dose of 100 mg and second dose (if needed) of 100 mg when used with a moderate CYP3A4 inducer. Risk D: Consider Therapy Modification
Ulipristal: CYP3A4 Inducers (Moderate) may decrease serum concentration of Ulipristal. Risk X: Avoid
Upadacitinib: CYP3A4 Inducers (Moderate) may decrease serum concentration of Upadacitinib. Risk C: Monitor
Valbenazine: CYP3A4 Inducers (Moderate) may decrease serum concentration of Valbenazine. CYP3A4 Inducers (Moderate) may decrease active metabolite exposure of Valbenazine. Risk C: Monitor
Vandetanib: CYP3A4 Inducers (Moderate) may increase active metabolite exposure of Vandetanib. CYP3A4 Inducers (Moderate) may decrease serum concentration of Vandetanib. Risk C: Monitor
Vanzacaftor, Tezacaftor, and Deutivacaftor: CYP3A4 Inducers (Moderate) may decrease serum concentration of Vanzacaftor, Tezacaftor, and Deutivacaftor. Risk X: Avoid
Velpatasvir: CYP3A4 Inducers (Moderate) may decrease serum concentration of Velpatasvir. Risk X: Avoid
Venetoclax: CYP3A4 Inducers (Moderate) may decrease serum concentration of Venetoclax. Risk X: Avoid
Vilazodone: CYP3A4 Inducers (Moderate) may decrease serum concentration of Vilazodone. Risk C: Monitor
Vimseltinib: May increase serum concentration of P-glycoprotein/ABCB1 Substrates (High risk with Inhibitors). Management: Avoid concomitant use of vimseltinib and P-gp substrates when possible. If combined, administer vimseltinib at least 4 hours before the P-gp substrate. Risk D: Consider Therapy Modification
VinCRIStine: CYP3A4 Inducers (Moderate) may decrease serum concentration of VinCRIStine. Risk C: Monitor
Voclosporin: CYP3A4 Inducers (Moderate) may decrease serum concentration of Voclosporin. Risk X: Avoid
Vonoprazan: CYP3A4 Inducers (Moderate) may decrease serum concentration of Vonoprazan. Risk X: Avoid
Vorapaxar: CYP3A4 Inducers (Moderate) may decrease serum concentration of Vorapaxar. Risk X: Avoid
Vortioxetine: CYP3A4 Inducers (Moderate) may decrease serum concentration of Vortioxetine. Risk C: Monitor
Voxelotor: CYP3A4 Inducers (Moderate) may decrease serum concentration of Voxelotor. Management: Avoid concomitant use of voxelotor and moderate CYP3A4 inducers. If unavoidable, increase the voxelotor dose to 2,000 mg once daily. For children ages 4 to less than 12 years, weight-based dose adjustments are required. See full monograph for details. Risk D: Consider Therapy Modification
Voxilaprevir: CYP3A4 Inducers (Moderate) may decrease serum concentration of Voxilaprevir. Risk X: Avoid
Xanomeline: May increase serum concentration of P-glycoprotein/ABCB1 Substrates (Narrow Therapeutic Index/Sensitive with Inhibitors). Risk C: Monitor
Zaleplon: CYP3A4 Inducers (Moderate) may decrease serum concentration of Zaleplon. Risk C: Monitor
Zanubrutinib: CYP3A4 Inducers (Moderate) may decrease serum concentration of Zanubrutinib. Management: Avoid this combination if possible. If coadministration of zanubrutinib and a moderate CYP3A4 inducer is required, increase the zanubrutinib dose to 320 mg twice daily. Risk D: Consider Therapy Modification
Zolpidem: CYP3A4 Inducers (Moderate) may decrease serum concentration of Zolpidem. Risk C: Monitor
Zopiclone: CYP3A4 Inducers (Moderate) may decrease serum concentration of Zopiclone. Risk C: Monitor
Zuranolone: CYP3A4 Inducers (Moderate) may decrease serum concentration of Zuranolone. Risk X: Avoid
Verify pregnancy status prior to use. Patients who could become pregnant should use effective nonhormonal contraception during therapy and for 2 months after the last dose of repotrectinib. Patients with partners who could become pregnant should also use effective contraception during therapy and for 4 months after the last repotrectinib dose.
Repotrectinib may cause some hormonal contraceptives to be ineffective. Consult drug interactions database for more detailed information specific to use of repotrectinib and specific contraceptives.
Based on the mechanism of action, animal reproduction studies, and data from humans with congenital mutations causing tropomyosin receptor tyrosine kinase (TRK) signaling changes, in utero exposure to repotrectinib may cause fetal harm. Repotrectinib inhibits tropomyosin receptor tyrosine kinase. Congenital mutations that cause decreased TRK signaling are associated with anhidrosis, cognitive impairment, developmental delay, obesity, and insensitivity to pain.
It is not known if repotrectinib 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 treatment and for 10 days after the last repotrectinib dose.
For NSCLC, assess ROS1 rearrangement status in tumor specimen prior to treatment initiation. For solid tumors, assess NTRK1/2/3 rearrangements in tumor specimens (consider repotrectinib treatment without confirmation of NTRK rearrangement for secretory breast cancer or mammary analogue secretory cancer).
Monitor liver function tests (AST, ALT, and total bilirubin) at baseline, every 2 weeks during the first month of treatment, then monthly thereafter, and as clinically indicated; creatine phosphokinase (CPK) levels every 2 weeks in during the first month of treatment, then as needed (in patients with unexplained muscle pain, tenderness, or weakness); uric acid at baseline and periodically during treatment. Verify pregnancy status in patients who could become pregnant.
Monitor for signs/symptoms of CNS toxicity (dizziness, vertigo, ataxia, cognitive disorders [memory impairment and attention disturbance], mood disorders, and sleep disorders), hyperuricemia, myalgia with CPK elevation (unexplained muscle pain, tenderness, or weakness), pulmonary toxicity (new or worsening pulmonary symptoms), skeletal fracture (eg, pain, change in mobility, deformity). Monitor adherence.
The American Society of Clinical Oncology hepatitis B virus (HBV) screening and management provisional clinical opinion (Ref) 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.
Repotrectinib is a multikinase/tyrosine kinase inhibitor of proto-oncogene ROS1, in addition to tropomyosin receptor tyrosine kinases TRKA, TRKB, and TRKC. ROS1 and TRK fusion proteins can produce hyperactivation of downstream signaling pathways, leading to cell proliferation and tumorigenic potential.
Distribution: Vd: 432 L.
Protein binding: 95.4%.
Metabolism: Hepatic; primarily via CYP3A4 followed by secondary glucuronidation.
Bioavailability: 45.7%.
Half-life elimination: ~61 hours (following a single dose); ~40 hours (at steady state).
Time to peak: ~2 to 3 hours.
Excretion: Urine: 4.84% (0.56% as unchanged drug); feces: 88.8% (50.6% as unchanged drug).
Clearance: 15.9 L/hour.
