Entrectinib
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From MedlinePlus, U.S. National Library of Medicine
Specialty pharmacy: therapy management checklist, storage and cold chain, dosing calendar, Medicare Part D coverage.
Dosing in kidney impairment
Renal Impairment No dose adjustment is recommended for patients with mild or moderate renal impairment (CLcr 30 to < 90 mL/min calculated by Cockcroft-Gault equation). ROZLYTREK has not been studied in patients with severe renal impairment (CLcr < 30 mL/min) [see Clinical Pharmacology ].
Dosing in liver impairment
Hepatic Impairment The effect of moderate hepatic impairment (total bilirubin > 1.5 – 3.0 times ULN with any aspartate aminotransferase) or severe hepatic impairment (total bilirubin >3.0 times ULN with any aspartate aminotransferase) on the safety of ROZLYTREK at the recommended dosage is unknown. Consider the risk-benefit profile of ROZLYTREK prior to determining whether to administer ROZLYTREK to patients with moderate to severe hepatic impairment.
Monitor for ROZLYTREK adverse reactions in patients with hepatic impairment more frequently since these patients may be at increased risk for adverse reactions [see Clinical Pharmacology ].
Preparation and administration
ROZLYTREK Administration Overview Administer ROZLYTREK capsules, capsules prepared as a suspension, or pellets once daily, with or without food. If a dose of ROZYTREK is missed, make up that dose unless the next dose is due within 12 hours. If vomiting occurs immediately after taking a dose of ROZLYTREK, repeat that dose.
ROZLYTREK Preparation and Administration Instructions ROZLYTREK Capsules Swallow capsules whole. Do not crush or chew the capsules. ROZLYTREK Capsules Prepared as a Suspension for Oral or Enteral Tube Administration It is recommended that a healthcare provider discuss with the patient or caregiver, the volume of water or milk to be added and oral suspension to withdraw, prior to administration of the first dose (see Table 6 ).
Table 6 provides the ROZLYTREK dose and volume of room temperature drinking water or milk required to prepare an oral suspension. Instruct patients or caregivers to carefully open capsule(s) and pour the contents into room temperature drinking water or milk to prepare an oral suspension. Let sit for 15 minutes. [See table below.] 30 mL Administer ROZLYTREK oral suspension immediately after preparation.
Discard any unused suspension if not used within 2 hours. Instruct patients to drink water after taking the oral suspension to ensure ROZLYTREK has been completely swallowed. Enteral Tube Administration If enteral administration (e.g., gastric or nasogastric tube) is required, administer the oral suspension via the tube.
Use an enteral tube that is 8 FR or higher to administer dosing volumes of 3 mL or higher. Instruct patients to divide dosing volumes of 3 mL or higher into at least two aliquots and flush the tube after each administration. Flush the tube with a volume of water or milk that is equal to the aliquot administered. For a dose volume of 30 mL, divide into at least three (10 mL) aliquots.
The tube should be flushed with water or milk after delivering each aliquot of ROZLYTREK. Refer to the Instructions for Use for detailed instructions on preparation and administration of ROZLYTREK capsules as an oral suspension via an enteral tube. ROZLYTREK Oral Pellets Sprinkle pellets on one or more spoonfuls of a soft food (e.g., applesauce, yogurt, or pudding) and take within 20 minutes of preparation.
Do not crush or chew to avoid a bitter taste. The patient should drink water after taking the pellets to ensure the drug has been completely swallowed. Do not attempt to use partial quantities of pellets from 50 mg pellet packets to prepare a dose. Do not use the pellet formulation for enteral tube administration as the pellets may clog the tube.
Refer to the Instructions for Use for detailed instructions on preparation and administration of ROZLYTREK oral pellets.
| Dose of ROZLYTREK to be administered | Dose needed for suspension (using 100 mg or 200 mg capsules, as appropriate) | Volume of water or milk to be added | Volume of oral suspension to withdraw and administer |
|---|---|---|---|
| 20 mg | 100 mg | 5 mL | 1 mL |
| 30 mg | 100 mg | 5 mL | 1.5 mL |
| 40 mg | 100 mg | 5 mL | 2 mL |
| 50 mg | 100 mg | 5 mL | 2.5 mL |
| 60 mg | 100 mg | 5 mL | 3 mL |
| 70 mg | 100 mg | 5 mL | 3.5 mL |
| 80 mg | 100 mg | 5 mL | 4 mL |
| 90 mg | 100 mg | 5 mL | 4.5 mL |
| 100 mg | 100 mg | 5 mL | 5 mL |
| 110 mg | 200 mg | 10 mL | 5.5 mL |
| 120 mg | 200 mg | 10 mL | 6 mL |
| 130 mg | 200 mg | 10 mL | 6.5 mL |
| 140 mg | 200 mg | 10 mL | 7 mL |
| 150 mg | 200 mg | 10 mL | 7.5 mL |
| 200 mg | 200 mg | 10 mL | 10 mL |
| 300 mg | 300 mg | 15 mL | 15 mL |
| 400 mg | 400 mg | 20 mL | 20 mL |
| 600 mg | 600 mg | 30 mL | 30 mL |
Drug interactions
Check interactions
Add the patient's other drugs. Matches come from both FDA labels: by name, drug class, and enzyme or transporter pathway.
- Entrectinib
Label text (4 paragraphs)
Moderate and Strong CYP3A Inhibitors : For adult and pediatric patients 2 years and older, reduce the dose of ROZLYTREK if coadministration of moderate or strong CYP3A inhibitors cannot be avoided. ( 2.8 , 7.1 ) For pediatric patients less than 2 years, avoid coadministration with ROZLYTREK. ( 7.1 ) Moderate and Strong CYP3A Inducers : Avoid coadministration with ROZLYTREK. ( 7.1 ) Drugs That Prolong QTc Interval : Avoid concomitant use with ROZLYTREK. ( 7.2 )
7.1 Effect of Other Drugs on ROZLYTREK Moderate and Strong CYP3A Inhibitors Adults and Pediatric Patients 2 Years and Older Coadministration of ROZLYTREK with a strong or moderate CYP3A inhibitor increases entrectinib plasma concentrations [see Clinical Pharmacology (12.3) ], which could increase the frequency or severity of adverse reactions. Avoid coadministration of strong or moderate CYP3A inhibitors with ROZLYTREK. If coadministration is unavoidable, reduce the ROZLYTREK dose [see Dosage and Administration (2.8) , Clinical Pharmacology (12.3) ].
Pediatric Patients less than 2 Years Avoid coadministration of ROZLYTREK with moderate or strong CYP3A inhibitors [see Clinical Pharmacology (12.3) ] . Avoid grapefruit products during treatment with ROZLYTREK, as they contain inhibitors of CYP3A. Moderate and Strong CYP3A Inducers Coadministration of ROZLYTREK with a strong or moderate CYP3A inducer decreases entrectinib plasma concentrations [see Clinical Pharmacology (12.3) ], which may reduce ROZLYTREK efficacy. Avoid coadministration of strong and moderate CYP3A inducers with ROZLYTREK .
7.2 Drugs That Prolong QTc Interval QTc interval prolongation can occur with ROZLYTREK. Avoid coadministration of ROZLYTREK with other products with a known potential to prolong QT/QTc interval [see Warnings and Precautions (5.6) , Clinical Pharmacology (12.2) ] .
Contraindications
None. None. ( 4 )
Safety data
Reported adverse events (FAERS)
Liver injury (LiverTox)
E*Likelihood score E*: Unproven but suspect rare cause of clinically apparent liver injury.
Entrectinib is an oral selective inhibitor of the neurotrophic T receptor kinase (NTRK) and ROS1 that is used to treat solid tumors with NTRK gene fusion and non-small cell lung cancer with ROS1 mutations. Serum aminotransferase elevations are common during therapy but clinically apparent liver injury is rare, although it has been reported.
ABCDEA: well known cause; E: unlikely cause. [HD]: high doses only.
Pregnancy and lactation
Pregnancy
8.1 Pregnancy Risk Summary Based on literature reports in humans with congenital mutations leading to changes in TRK signaling, findings from animal studies, and its mechanism of action [see Clinical Pharmacology (12.1) ] , ROZLYTREK can cause fetal harm when administered to a pregnant woman. There are no available data on ROZLYTREK use in pregnant women. Administration of entrectinib to pregnant rats during the period of organogenesis resulted in malformations at maternal exposures approximately 2.7 times the human exposure at the 600 mg dose (see Data ) . Advise pregnant women of the potential risk to a fetus. In the U.S.
general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively. Data Human Data Published reports of individuals with congenital mutations in TRK pathway proteins suggest that decreases in TRK-mediated signaling are correlated with obesity, developmental delays, cognitive impairment, insensitivity to pain, and anhidrosis.
Animal Data Entrectinib administration to pregnant rats during the period of organogenesis at a dose of 200 mg/kg [resulting in exposures up to 2.7 times the human exposure (AUC) at the 600 mg dose] resulted in maternal toxicity and fetal malformations including body closure defects (omphalocele and gastroschisis) and malformations of the vertebrae, ribs, and limbs (micromelia and adactyly), but not embryolethality. Lower fetal weights and reduced skeletal ossification occurred at doses ≥ 12.5 and 50 mg/kg [approximately 0.2 and 0.9 times the human exposure (AUC) at the 600 mg dose], respectively.
Breastfeeding (LactMed)
No information is available on the clinical use of entrectinib during breastfeeding. Because entrectinib and its active metabolite are >99% bound to plasma proteins, the amount in milk is likely to be low. However, because of its potential toxicity in the breastfed infant, the manufacturer recommends that breastfeeding be discontinued during entrectinib therapy and for 7 days after the last dose.
Supply and cost
Drug shortage status
Recalls (last 24 months)
Therapeutic equivalence (Orange Book)
Price ladder
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