Jideytro®
Zidesamtimib, a kinase inhibitor, is an antineoplastic agent.1
Zidesamtimib has the following uses:
Zidesamtimib is indicated for the treatment of adult patients with locally advanced or metastatic ROS1 -positive non-small cell lung cancer (NSCLC) who received a prior ROS1 kinase inhibitor.1
Zidesamtimib is available in the following dosage form(s) and strength(s):
Tablets: 25 mg and 100 mg.1
It is essential that the manufacturer's labeling be consulted for more detailed information on dosage and administration of this drug. Dosage summary:
Zidesamtimib can cause adverse CNS effects.1
In the pooled safety population, a broad spectrum of CNS adverse reactions, including dizziness, ataxia, cognitive and psychiatric disorders, occurred in 25% of patients who received zidesamtimib; of these, 2.5% were Grade 3 or 4.1 One patient (0.2%) with brain metastases experienced a Grade 3 seizure.1
Dizziness, including vertigo, presyncope and positional dizziness occurred in 12% of patients who received zidesamtimib; of these 0.2% were Grade 3.1 The median time to onset of dizziness was 22 days (range: 1 day to 9 months).1 Dosage interruption of zidesamtimib for dizziness was required in 0.4% of patients, and 0.7% of patients required dose reduction.1
Ataxia, including gait disturbance and balance disorder, occurred in 2% of patients who received zidesamtimib and were all Grade 1 or 2.1 The median time to onset of ataxia was 64 days (range: 6 days to 2.5 years).1
Cognitive impairment occurred in 9% of patients who received zidesamtimib, of these 1.6% were Grade 3 or 4.1 Cognitive impairment included memory impairment (3.1%), cognitive disorder (1.6%), hallucination (1.1%), delirium (1.1%), aphasia (0.9%), amnesia (0.7%), confusional state (0.7%), anterograde amnesia (0.2%), disturbance in attention (0.4%), slow speech (0.2%).1 The median time to onset of cognitive impairment was 43 days (range: 4 days to 1.9 years).1 Dose interruption of zidesamtimib for cognitive impairment was required in 1.3% of patients.1
Psychiatric disorders occurred in 6% of patients who received zidesamtimib, of these 0.7% were Grade 3 or 4.1 Psychiatric disorders included anxiety (3.1%), depression (1.3%), agitation (0.7%), affect lability (0.4%), irritability (0.4%), abnormal behavior (0.2%), depressed mood (0.2%), personality change (0.2%), psychotic disorder (0.2%), and suicidal ideation (0.2%).1 The median time to onset of psychiatric disorders was 57 days (range: 1 day to 10 months).1 Dosage interruption of zidesamtimib for psychiatric disorders was required in 0.9% of patients.1 Advise patients and caregivers of the risk of CNS adverse reactions with zidesamtimib.1 Advise patients to avoid engaging in hazardous tasks requiring mental alertness and motor coordination such as operating machinery or driving a motor vehicle if they are experiencing CNS reactions.1 Monitor patients for CNS adverse reactions and suicidal thoughts and behaviors during treatment with zidesamtimib.1 Withhold and then resume at the same or reduced dose upon improvement or permanently discontinue zidesamtimib based on severity.1
Zidesamtimib can cause QTc interval prolongation, which can increase the risk for ventricular tachyarrhythmias (e.g., torsades de pointes) or sudden death.1 Zidesamtimib has not been studied in patients with a history of QTcF >450 msec on more than one assessment prior to initiation.1
In the pooled safety population, of the 435 patients who underwent at least one post baseline electrocardiogram (ECG) assessment, 2% experienced an increase in QTcF of >60 msec compared to baseline after receiving zidesamtimib and 0.2% increase in QTcF to >500 msec.1 The median time from the first dose of zidesamtimib to the onset of QTc prolongation was 15 days (range: 1 day to approximately 1 month).1 QTc prolongation led to dose interruption in 0.4% of patients who received zidesamtimib.1
Evaluate ECGs and electrolytes prior to administration of zidesamtimib and monitor periodically during treatment.1 Adjust the frequency of monitoring based on risk factors such as known long QT syndromes, clinically significant bradyarrhythmias, severe or uncontrolled heart failure, and concomitant medications associated with QTc interval prolongation.1 Withhold, then resume at the same or reduced dose, or permanently discontinue zidesamtimib based on severity.1
Interstitial Lung Disease/Pneumonitis
Zidesamtimib can cause severe or life-threatening interstitial lung disease (ILD) or pneumonitis.1
In the pooled safety population, interstitial lung disease (ILD)/pneumonitis occurred in 1.8% of patients treated with zidesamtimib, including Grade 3 or 4 in 0.4%.1 The median time to first onset of ILD/pneumonitis was 4.5 months (range: 8 days to 11 months).1
ILD/pneumonitis led to dose interruption of zidesamtimib in 0.7% of patients.1 ILD/pneumonitis required dose reduction in 0.2% of patients and permanent discontinuation of zidesamtimib in 0.4% of patients.1
Monitor patients for new or worsening pulmonary symptoms indicative of ILD/pneumonitis.1 Immediately withhold zidesamtimib in patients with suspected ILD/pneumonitis, then upon recovery resume at the same or reduced dose or permanently discontinue based on severity. 1
Zidesamtimib can increase the risk of skeletal fractures.1
In the pooled safety population, 5 patients (1.1%) experienced skeletal fractures, and Grade 3 ankle fractures occurred in two patients (0.4%) who received zidesamtimib.1 Some fractures occurred in the setting of an accidental fall or other predisposing factors such as osteoporosis, bone metastasis, and age-related degenerative conditions.1 The median time to fracture was 48 days (range: 32 days to approximately 6 months).1 Zidesamtimib was interrupted in 0.4% of patients for fractures.1
Myalgia with Creatine Phosphokinase Elevation
Zidesamtimib can cause myalgia with creatine phosphokinase (CPK) elevation.1
In the pooled safety population, myalgia occurred in 13% of patients who received zidesamtimib.1 Based on laboratory values, concurrent myalgia with increased CPK occurred in 2.1% of patients.1 The median time to onset of myalgia for these patients with CPK elevation was 2 months (range: 8 days to 6 months). 1
Advise patients to report unexplained muscle pain or tenderness.1 Monitor serum CPK levels prior to administration of zidesamtimib and every 2 weeks during the first month of treatment and then every 1 to 2 months and as clinically indicated in patients reporting unexplained muscle pain or tenderness.1 Withhold, then resume at the same or reduced dose, or permanently discontinue zidesamtimib based on severity. 1
Zidesamtimib can cause pancreatic toxicity.1
In the pooled safety population, among the subgroup of patients who underwent pancreatic lab testing, increased amylase occurred in 22% and increased lipase occurred in 25% of patients treated with zidesamtimib.1 Grade 3 increased lipase occurred in 8% of these patients.1 Grade 3 lipase elevation resulted in zidesamtimib dose reduction in one patient.1 The median time-to-onset of Grade 3 increased lipase was 143 days (range: 28 to 249 days).1 In the pooled safety population, grade 3 pancreatitis occurred in one patient (0.2%) treated with zidesamtimib.1
Evaluate amylase and lipase prior to administration of zidesamtimib and monitor periodically during treatment.1 Based on the severity of the adverse reaction, temporarily withhold, reduce the dose, or permanently discontinue zidesamtimib.1
Based on literature reports in humans with congenital mutations leading to changes in tropomyosin receptor kinase (TRK) signaling, findings from animal studies and its mechanism of action, zidesamtimib can cause fetal harm when administered to a pregnant woman.1
In an animal reproduction study, oral administration of zidesamtinib to pregnant rats during the period of organogenesis resulted in embryo-fetal mortality, alterations to growth, and structural abnormalities at maternal exposures approximately equivalent to the human exposure at the recommended dose based on AUC. 1
Advise pregnant women and females of reproductive potential of the potential risk to a fetus.1 Advise females of reproductive potential to use effective contraception during treatment with zidesamtimib and for 6 months after the last dose.1 Advise male patients with female partners of reproductive potential to use effective contraception during treatment with zidesamtimib and for 3 months after the last dose.1
Based on literature reports in humans with congenital mutations leading to changes in TRK signaling, findings from animal studies and its mechanism of action, zidesamtimib can cause fetal harm when administered to a pregnant woman.1 There are no available data on zidesamtimib use in pregnant women to inform a drug-associated risk.1 Oral administration of zidesamtinib to pregnant rats during the period of organogenesis resulted in embryo-fetal mortality, alterations to growth, and structural abnormalities at maternal exposures approximately equivalent to the human exposure at the recommended dose based on AUC.1 Advise pregnant women of the potential risk to a fetus.1
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.1
There are no data on the presence of zidesamtimib in human milk or the effects of the drug on either a breastfed child or on milk production.1 Because of the potential for serious adverse reactions in breastfed children, advise women not to breastfeed during treatment with zidesamtimib and for 1 week after the last dose.1
Females and Males of Reproductive Potential
Zidesamtimib can cause fetal harm when administered to a pregnant woman.1
Verify the pregnancy status of females of reproductive potential prior to initiating zidesamtimib. 1
Advise females of reproductive potential to use effective contraception during treatment with zidesamtimib and for 6 months after the last dose.1
Advise male patients with female partners of reproductive potential to use effective contraception during treatment with zidesamtimib and for 3 months after the last dose.1
Based on findings from animal studies, zidesamtimib may impair fertility in males and females.1 The effects on male fertility were reversible.1 The reversibility of the effect on fertility in females is unknown.1
The safety and effectiveness of zidesamtimib in pediatric patients have not been established.1
Daily oral administration of zidesamtinib to juvenile rats from postnatal day 7 to 28 (approximately equal to a human pediatric age of a neonate to child) resulted in ocular toxicity, including hemorrhage, corneal ulcers, rupture, and vision loss at 8 mg/kg/day (approximately 2.4 times the human exposure based on AUC at the recommended dose).1
Of the 446 patients who received zidesamtimib in the principal clinical study, 21.5% were 65 to 74 years of age, and 8% were 75 years of age or older.1 There were no clinically meaningful differences in safety and efficacy between patients younger than 65 years of age and patients 65 years of age or older.1
The effect of severe renal impairment (eGFR <30 mL/min) or dialysis on zidesamtinib pharmacokinetics is unknown.1
No dosage modification is recommended for patients with eGFR 30 to 90 mL/min.1
The effect of severe hepatic impairment (total bilirubin >3 times ULN with any AST) on the zidesamtinib pharmacokinetics is unknown.1
No dosage modification is recommended for patients with mild (total bilirubin >1 to 1.5 times ULN or AST > ULN) or moderate (total bilirubin >1.5 to 3 times ULN with any AST) hepatic impairment.1
Most common adverse reactions (≥15%) were: edema, peripheral neuropathy, constipation, fatigue, and dyspnea.1
Most common Grade 3 or 4 laboratory abnormalities (≥2%) were: increased CPK, increased triglycerides, decreased lymphocytes and decreased hemoglobin.1
It is essential that the manufacturer's labeling be consulted for more detailed information on interactions with this drug, including possible dosage adjustments. Interaction highlights:
Zidesamtinib is an inhibitor of tyrosine kinase ROS1, including ROS1 resistance mutations.1 In a biochemical assay, zidesamtinib inhibited ROS1 (IC50 = 0.7 nM) and also showed inhibitory effects on ALK (IC50 = 3 nM) and tropomyosin receptor kinases (TRKs), TRKB (IC50 = 54 nM), TRKC (IC50 = 193 nM) and TRKA (IC50 = 258 nM).1
In vitro, zidesamtinib inhibited the viability of cultured cells expressing ROS1 fusion genes and resistance mutations (G2032R, S1986F, F2004C/V, L2026M, D2033N, and G2101A).1 In mice subcutaneously implanted with tumors harboring ROS1 fusions, including the G2032R mutation, administration of zidesamtinib resulted in tumor growth inhibition.1 Zidesamtinib had antitumor activity in an intracranial NSCLC xenograft model harboring a ROS1 fusion.
Additional Information
AHFS first Release™. For additional information until a more detailed monograph is developed and published, the manufacturer's labeling should be consulted. It is essential that the manufacturer's labeling be consulted for more detailed information on usual uses, dosage and administration, cautions, precautions, contraindications, potential drug interactions, laboratory test interferences, and acute toxicity.
Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.
Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.
Routes | Dosage Forms | Strengths | Brand Names | Manufacturer |
|---|---|---|---|---|
Oral | Tablets, film-coated | 25 mg | Jideytro® | Nuvalent |
100 mg | Jideytro® | Nuvalent |
AHFS® Drug Information. © Copyright, 1959-2026, Selected Revisions September 10, 2026. American Society of Health-System Pharmacists, Inc., 4500 East-West Highway, Suite 900, Bethesda, MD 20814.