Augtyro (Repotrectinib)

Next-generation ROS1 and TRK inhibitor for advanced cancer

Rx – Prescription Only ATC: L01EX26 TKI – ROS1/TRK Inhibitor
Active Ingredient
Repotrectinib
Dosage Forms
Hard capsules (40 mg, 160 mg)
Manufacturer
Bristol-Myers Squibb
Administration
Oral
Medically reviewed by iMedic Medical Team
Evidence Level 1A

Augtyro (repotrectinib) is a next-generation tyrosine kinase inhibitor specifically designed to treat ROS1-positive non-small cell lung cancer (NSCLC) and NTRK gene fusion-positive solid tumors. As a highly selective ROS1 and TRK inhibitor, it was engineered to retain potency against resistance mutations that can emerge during treatment with earlier-generation inhibitors. Augtyro is taken orally as a capsule and is approved for use in adults and adolescents aged 12 years and older.

Quick Facts

Active Ingredient
Repotrectinib
Drug Class
TKI (ROS1/TRK)
ATC Code
L01EX26
Common Uses
ROS1+ NSCLC, NTRK+ Tumors
Available Forms
Capsules 40 mg, 160 mg
Prescription Status
Rx Only

Key Takeaways

  • Augtyro is a next-generation tyrosine kinase inhibitor that targets both ROS1 and NTRK (TRK) fusion-driven cancers, including forms resistant to first-generation inhibitors.
  • The standard dosing begins with 160 mg once daily for 14 days, followed by 160 mg twice daily, taken orally with or without food.
  • Common side effects include dizziness, ataxia, cognitive disturbances, nausea, fatigue, and visual changes – central nervous system effects are characteristic of this medication.
  • Strong CYP3A4 inhibitors and inducers must be avoided, and grapefruit consumption is contraindicated during treatment.
  • Effective contraception is mandatory for both men and women during treatment and for a period after discontinuation due to potential harm to an unborn child.

What Is Augtyro and What Is It Used For?

Quick Answer: Augtyro (repotrectinib) is a targeted cancer medication that blocks abnormal ROS1 and TRK proteins caused by gene fusions. It is used to treat advanced ROS1-positive non-small cell lung cancer in adults, and NTRK gene fusion-positive solid tumors in adults and children from 12 years of age.

Augtyro belongs to a class of drugs known as tyrosine kinase inhibitors (TKIs). It contains the active substance repotrectinib, which was specifically designed to overcome limitations of earlier-generation ROS1 and TRK inhibitors. Cancer cells sometimes develop gene fusions – abnormal rearrangements of genetic material – that produce overactive signaling proteins. When these fusions involve the ROS1 or NTRK genes, the resulting aberrant proteins continuously stimulate cell growth and survival, driving cancer progression.

Repotrectinib acts by selectively binding to and inhibiting these abnormal ROS1 and TRK (TRKA, TRKB, and TRKC) fusion proteins. Its compact molecular structure allows it to fit into the active site of these kinases even when resistance mutations have altered the binding pocket – a key advantage over first-generation inhibitors such as crizotinib or entrectinib. By blocking the signaling cascades driven by these fusion proteins, Augtyro can slow or stop cancer cell proliferation and may cause tumors to shrink.

ROS1-Positive Non-Small Cell Lung Cancer (NSCLC)

Augtyro is indicated for the treatment of adults with advanced (locally advanced or metastatic) non-small cell lung cancer that has been shown, by a validated test, to harbour a ROS1 gene rearrangement. ROS1 fusions are found in approximately 1–2% of all NSCLC cases, making this a relatively uncommon but clinically important molecular subtype. Despite the low prevalence, identifying ROS1-positive NSCLC is critical because these tumors are highly sensitive to targeted therapy.

In the pivotal TRIDENT-1 clinical trial (NCT03093116), repotrectinib demonstrated robust and durable responses in both treatment-naive patients and those who had previously received a ROS1-targeted tyrosine kinase inhibitor. For patients who had not previously received a ROS1 TKI, objective response rates exceeded 79%, with a median duration of response of approximately 34 months. Even in patients who had been previously treated with one ROS1 TKI, meaningful responses were observed, including in patients with the particularly challenging ROS1 G2032R solvent-front resistance mutation.

The ability to provide effective treatment across the spectrum of ROS1-positive disease – from first-line through to post-resistance settings – distinguishes Augtyro from earlier agents and represents a significant advance in the management of this molecular subtype of lung cancer.

NTRK Gene Fusion-Positive Solid Tumors

Augtyro is also approved for the treatment of adults and children aged 12 years and older with solid tumors that harbour an NTRK gene fusion. NTRK gene fusions can occur in a wide variety of tumor types, including (but not limited to) lung cancer, thyroid cancer, salivary gland tumors, soft tissue sarcomas, and brain tumors. The NTRK genes (NTRK1, NTRK2, and NTRK3) encode TRK proteins (TRKA, TRKB, and TRKC), and when fused with other genes, they produce constitutively active kinases that drive tumor growth.

Augtyro may be used when the cancer has spread within the affected organ or to other parts of the body, or when surgical removal of the tumor would likely cause serious complications. It is approved both for patients who have previously received treatment with NTRK inhibitors (such as larotrectinib or entrectinib) and for patients who have not received NTRK-targeted therapy when other suitable treatments are not available.

A key clinical advantage of repotrectinib in the NTRK fusion setting is its activity against acquired TRK resistance mutations, particularly solvent-front mutations (e.g., TRKA G595R, TRKC G623R) and xDFG mutations, which are the most common mechanisms of resistance to first-generation TRK inhibitors. This makes Augtyro a valuable treatment option for patients whose tumors have progressed on prior TRK-directed therapy.

Conditional Marketing Authorization

Augtyro has been granted conditional marketing authorization by the European Medicines Agency (EMA). This means that additional evidence about the medicine is awaited, and the EMA will review new information annually and update the authorization as necessary. The US Food and Drug Administration (FDA) granted accelerated approval for repotrectinib in November 2023 based on overall response rate and duration of response data from the TRIDENT-1 trial.

What Should You Know Before Taking Augtyro?

Quick Answer: Do not take Augtyro if you are allergic to repotrectinib or any of its ingredients. Inform your doctor if you have experienced dizziness, cognitive changes, lung problems, a history of fractures, or liver disease. Avoid grapefruit and Seville oranges during treatment, and use effective contraception.

Contraindications

There is one absolute contraindication to taking Augtyro: known hypersensitivity (allergy) to repotrectinib or to any of the excipients in the capsule formulation. If you have previously experienced an allergic reaction to any component of Augtyro, you must not take this medication. If you are unsure whether you may be allergic, consult your doctor, pharmacist, or nurse before starting treatment.

Warnings and Precautions

Before starting treatment with Augtyro, your doctor should be informed about your complete medical history. Several important warnings and precautions apply to this medication, and careful monitoring may be required throughout therapy.

Tell your doctor before taking Augtyro if any of the following apply to you:

  • Recent neurological symptoms: If you have recently experienced dizziness, memory loss, confusion, hallucinations, changes in mental status, loss of muscle coordination, or uncoordinated or unsteady walking, your doctor may need to perform additional assessments before starting treatment.
  • Lung problems: Augtyro can cause interstitial lung disease (ILD) and pneumonitis, which are serious conditions involving inflammation and scarring of the lungs. Tell your doctor immediately if you develop any new or worsening respiratory symptoms, including shortness of breath, cough, or fever.
  • History of fractures or bone conditions: Skeletal fractures have been reported in patients treated with Augtyro. If you have previously had bone fractures or have conditions that may increase your risk of fractures (such as osteoporosis), discuss this with your doctor before starting treatment.
  • Liver problems: If you have pre-existing liver disease or impairment, your doctor may need to monitor your liver function more closely during treatment, as Augtyro is metabolized primarily by the liver.

Your doctor will perform regular assessments including blood tests to monitor your liver function, blood cell counts, and other parameters throughout your course of treatment. Dose adjustments, temporary treatment interruptions, or permanent discontinuation may be necessary depending on the severity of any side effects you experience.

Pregnancy and Breastfeeding

Augtyro should not be used during pregnancy because it may cause harm to the developing baby. Based on its mechanism of action and preclinical data, repotrectinib is expected to have the potential to cause birth defects or harm fetal development.

Women of childbearing potential: If you are a woman who could become pregnant, your doctor will ensure that a pregnancy test is performed before starting Augtyro. You must use highly effective contraception during treatment and for at least 2 months after the last dose. Because repotrectinib may reduce the effectiveness of hormonal contraceptives (including oral contraceptive pills and hormonal implants), you must also use a reliable non-hormonal barrier method (such as a condom) in addition to any hormonal contraception.

Male patients: If your female partner could become pregnant, you should use condoms during treatment with Augtyro and for at least 4 months after the last dose to avoid the risk of fathering a child who could be harmed by exposure to the drug.

Breastfeeding: Do not breastfeed while taking Augtyro. It is not known whether repotrectinib passes into breast milk, and a risk to the breastfed infant cannot be excluded.

If you become pregnant or suspect pregnancy during treatment, contact your doctor immediately.

Driving and Operating Machinery

Augtyro may significantly impair your ability to drive or operate machinery. The drug can cause dizziness, impaired balance or coordination, fainting (loss of consciousness), fatigue, changes in mental status, confusion, visual disturbances, and hallucinations. If you experience any of these symptoms, do not drive, cycle, or operate machinery until the symptoms have resolved. Discuss with your doctor or pharmacist whether it is safe for you to drive.

Important Information About Ingredients

Augtyro contains less than 1 mmol (23 mg) of sodium per capsule, meaning it is essentially sodium-free. This is relevant information for patients on a sodium-restricted diet.

How Does Augtyro Interact with Other Drugs?

Quick Answer: Augtyro interacts significantly with strong CYP3A4 inhibitors (e.g., ketoconazole, ritonavir) which increase drug levels, and strong CYP3A4 inducers (e.g., rifampicin, carbamazepine, St. John’s Wort) which decrease effectiveness. Grapefruit and Seville oranges must be avoided. Hormonal contraceptives may be less effective.

Repotrectinib is primarily metabolized by the cytochrome P450 3A4 (CYP3A4) enzyme system. Any medication that significantly inhibits or induces CYP3A4 can alter repotrectinib blood levels, potentially leading to increased toxicity or reduced therapeutic efficacy. Additionally, repotrectinib itself can affect the metabolism and transport of certain other drugs. It is essential to tell your doctor about all medications, herbal supplements, and over-the-counter products you are taking or have recently taken.

Major Interactions

Major Drug Interactions with Augtyro (Repotrectinib)
Interacting Drug Effect Clinical Significance
Ketoconazole, itraconazole, voriconazole, posaconazole (strong CYP3A4 inhibitors) Significantly increased repotrectinib plasma levels, greater risk of toxicity Avoid combination; if unavoidable, dose reduction and close monitoring required
Ritonavir, saquinavir (HIV protease inhibitors / CYP3A4 inhibitors) Markedly increased repotrectinib exposure due to potent CYP3A4 inhibition Avoid combination; seek alternative antiretroviral regimen if possible
Rifampicin (strong CYP3A4 inducer) Significantly decreased repotrectinib plasma levels, reduced anticancer efficacy Avoid combination; treatment may become ineffective
Carbamazepine, phenytoin (strong CYP3A4 inducers / antiepileptics) Reduced repotrectinib exposure due to enhanced hepatic metabolism Avoid combination; consider alternative antiepileptic agents
St. John’s Wort (Hypericum perforatum) Decreased repotrectinib levels via CYP3A4 induction Absolutely contraindicated during Augtyro treatment
Grapefruit / Seville oranges Increased repotrectinib levels via CYP3A4 inhibition in the gut Must be completely avoided throughout treatment

Minor Interactions

Other Drug Interactions with Augtyro (Repotrectinib)
Interacting Drug Effect Clinical Significance
Efavirenz (moderate CYP3A4 inducer) Moderately decreased repotrectinib levels Use with caution; consider alternative if available
Fluvoxamine, bupropion (antidepressants) Possible modest increase in repotrectinib exposure via CYP inhibition Monitor for increased side effects
Warfarin (anticoagulant) Repotrectinib may alter warfarin metabolism; INR changes possible Monitor INR closely; dose adjustment may be needed
Hormonal contraceptives (oral pills, implants) Possible reduced efficacy of hormonal contraception Add a barrier method (e.g., condom) in addition to hormonal contraception
Repaglinide, tolbutamid, metformin (antidiabetics) Repotrectinib may affect drug transporter activity, altering their levels Monitor blood glucose; dose adjustment may be needed
Digoxin, dabigatran, edoxaban (P-gp substrates) Repotrectinib may affect P-glycoprotein transport, altering substrate levels Monitor for signs of toxicity or reduced efficacy of these drugs
Simvastatin, lovastatin, rosuvastatin (statins) Possible altered statin levels via transporter or enzyme interaction Monitor for signs of myopathy; consider dose adjustment

The interaction profile of Augtyro is complex due to its metabolism by CYP3A4 and its effects on various drug transporters, including P-glycoprotein (P-gp), BCRP, MATE1, MATE2-K, OATP1B1, OATP1B3, OAT1, OAT3, and OCT1. Patients taking multiple medications should have their entire drug regimen carefully reviewed by their oncologist and pharmacist before starting treatment. Regular monitoring of concomitant medication levels (such as warfarin INR or blood glucose with antidiabetics) is advisable throughout therapy.

Always inform your doctor if you start or stop any medication, supplement, or herbal product during treatment with Augtyro. Even seemingly minor changes in your medication regimen could have clinically significant effects on repotrectinib levels or the effectiveness of other therapies.

What Is the Correct Dosage of Augtyro?

Quick Answer: The recommended dose is 160 mg once daily for the first 14 days, then 160 mg twice daily thereafter. Capsules are taken orally, with or without food, swallowed whole. Dose reductions to 120 mg or 80 mg may be made based on tolerability.

Always take Augtyro exactly as your doctor or pharmacist has instructed. Do not change your dose or stop taking Augtyro without consulting your doctor first. The capsules should be taken by mouth, with or without food. Swallow each capsule whole – do not open, crush, chew, or dissolve the contents of the capsules, as this can alter the drug’s absorption profile and potentially increase the risk of side effects.

Adults

Standard Dosing Regimen (Lead-in Phase)

Dose: 160 mg once daily

Duration: First 14 days of treatment

Administration: Take four 40 mg capsules or one 160 mg capsule by mouth, once daily at approximately the same time each day

This initial lead-in period at a lower frequency allows the body to gradually adjust to the medication and may help reduce the incidence and severity of early side effects, particularly central nervous system effects such as dizziness and ataxia.

Standard Dosing Regimen (Maintenance Phase)

Dose: 160 mg twice daily (total daily dose: 320 mg)

Duration: From day 15 onwards, until your doctor advises otherwise

Administration: Take 160 mg approximately every 12 hours. Continue for as long as you are benefiting from treatment and tolerating it

The twice-daily maintenance dose provides sustained drug exposure throughout the day, which is important for maintaining continuous inhibition of the target kinases and preventing cancer cell regrowth between doses.

Dose Reductions

Depending on how you respond to treatment and any side effects you experience, your doctor may recommend reducing your dose or temporarily interrupting treatment. The available dose reduction levels are:

Augtyro Dose Reduction Schedule
Dose Level Daily Dose How to Take
Standard dose 160 mg twice daily (320 mg/day) Four 40 mg capsules or one 160 mg capsule, twice daily
First reduction 120 mg twice daily (240 mg/day) Three 40 mg capsules, twice daily
Second reduction 80 mg twice daily (160 mg/day) Two 40 mg capsules, twice daily

Children and Adolescents (12 Years and Older)

Augtyro is approved for use in adolescents aged 12 years and older with NTRK gene fusion-positive solid tumors. The dosing regimen in adolescents follows the same schedule as for adults: 160 mg once daily for the first 14 days, followed by 160 mg twice daily from day 15 onwards. Dose adjustments follow the same reduction schedule as described above. The safety and efficacy of Augtyro in children under 12 years of age have not been established.

Missed Dose

If you miss a dose of Augtyro or if you vomit after taking a dose, take your next scheduled dose at the regular time. Do not take a double dose to make up for a missed dose, as this increases the risk of side effects without providing additional therapeutic benefit.

Overdose

If you have taken more Augtyro than prescribed, contact your doctor or go to the nearest hospital emergency department immediately. Bring the medicine packaging and this information with you. There is no specific antidote for repotrectinib overdose, and treatment would be supportive based on the symptoms experienced.

Do Not Stop Without Medical Advice

Do not stop taking Augtyro without first consulting your doctor. It is important to take Augtyro every day for as long as your doctor has prescribed it. Premature discontinuation of targeted cancer therapy can allow the disease to progress. If you have any questions about your treatment schedule, contact your doctor, pharmacist, or nurse.

What Are the Side Effects of Augtyro?

Quick Answer: The most common side effects of Augtyro include dizziness, ataxia (loss of coordination), cognitive disturbances, nausea, constipation, fatigue, joint and muscle pain, and visual changes. Serious side effects include interstitial lung disease/pneumonitis and skeletal fractures. CNS effects are particularly characteristic of this medication.

Like all medicines, Augtyro can cause side effects, although not everyone will experience them. Some side effects can be serious and may require immediate medical attention. Others are more common and may be manageable with supportive care or dose adjustments. The side effect profile of repotrectinib is characteristic of its mechanism of action – because TRK and ROS1 signaling play a role in the normal nervous system, CNS effects are a notable feature of this drug class.

Side Effects in Adults

Very Common

May affect more than 1 in 10 people
  • Lung infections (pneumonia)
  • Anemia (decreased red blood cells)
  • Dizziness
  • Ataxia (loss of coordination, unsteady walking)
  • Cognitive disturbances (changes in thinking, memory, mental status)
  • Paraesthesia (numbness, tingling)
  • Peripheral sensory neuropathy (nerve damage causing numbness, tingling, burning)
  • Sleep disturbances
  • Headache
  • Taste changes (dysgeusia)
  • Visual disturbances (light flashes, blurred vision, light sensitivity, floaters, double vision)
  • Shortness of breath (dyspnea)
  • Cough
  • Nausea
  • Vomiting
  • Constipation
  • Diarrhea
  • Muscle weakness
  • Pain in arms and/or legs
  • Joint pain (arthralgia)
  • Muscle pain (myalgia)
  • Back pain
  • Fever
  • Fatigue
  • Decreased appetite
  • Swollen ankles, feet, and hands (edema)
  • Elevated creatine phosphokinase (muscle enzyme) in blood
  • Weight gain
  • Elevated liver enzymes (AST or ALT)

Common

May affect up to 1 in 10 people
  • Hyperuricemia (elevated uric acid levels in blood)
  • Interstitial lung disease / pneumonitis (inflammation and scarring in the lungs)
  • Pleural effusion (fluid around the lungs)
  • Abdominal pain
  • Skeletal fractures
  • Elevated gamma-GT or alkaline phosphatase (liver enzymes)
  • Lymphopenia (decreased lymphocytes, a type of white blood cell)
  • Leukopenia (decreased white blood cells)
  • Neutropenia (decreased neutrophils, a type of white blood cell)
  • Increased risk of falls

Side Effects in Patients 18 Years or Younger

The side effect profile in adolescents (aged 12–18 years) is broadly similar to that in adults, with some notable differences. The following effects have been reported at different frequencies compared to the adult population:

Very Common in Adolescents

May affect more than 1 in 10 people
  • Anemia
  • Increased appetite
  • High potassium levels in the blood (hyperkalemia)
  • Hyperuricemia (elevated uric acid)
  • Dizziness, ataxia, cognitive disturbances
  • Paraesthesia (numbness, tingling)
  • Sleep disturbances, headache, taste changes
  • Visual disturbances
  • Shortness of breath, cough
  • Nausea, vomiting, constipation, diarrhea
  • Abdominal pain
  • Skeletal fractures
  • Joint pain (arthralgia)
  • Fever, fatigue
  • Elevated creatine phosphokinase
  • Weight gain
  • Lymphopenia, leukopenia, neutropenia
  • Elevated liver enzymes (AST or alkaline phosphatase)

Common in Adolescents

May affect up to 1 in 10 people
  • Lung infections
  • Peripheral sensory neuropathy
  • Pleural effusion
  • Oral paraesthesia (numbness and tingling of lips, tongue, or mouth)
  • Muscle pain (myalgia)
  • Muscle weakness
  • Increased risk of falls

Adolescent patients may experience some side effects at different frequencies than adults. Notably, increased appetite, hyperkalemia, and skeletal fractures were more frequently reported in the younger population, while peripheral sensory neuropathy was less commonly observed. These differences likely reflect age-related physiological factors, including ongoing skeletal development.

Reporting Side Effects

It is important to report suspected side effects after the medicine has been authorized. This allows continuous monitoring of the benefit–risk balance of the medication. Healthcare professionals and patients are encouraged to report suspected adverse reactions through their national pharmacovigilance system (e.g., the FDA MedWatch program in the US, the Yellow Card Scheme in the UK, or the national medicines agency in your country).

How Should You Store Augtyro?

Quick Answer: Store Augtyro out of the sight and reach of children. Do not use after the expiry date on the packaging. There are no special storage conditions – store at room temperature. Do not dispose of medicines in wastewater or household waste.

Proper storage of Augtyro is essential to maintain the medication’s effectiveness and safety throughout the treatment course. Store this medicine out of the sight and reach of children at all times.

Do not use Augtyro after the expiry date printed on the carton, bottle, or blister pack after “EXP.” The expiry date refers to the last day of the stated month. Once the expiry date has passed, the chemical stability and potency of the drug can no longer be guaranteed.

Augtyro has no special storage requirements. It should be kept at room temperature and protected from extremes of heat and humidity. There is no need for refrigeration. Keep the capsules in their original packaging (bottle or blister pack) to protect them from light and moisture until you are ready to take them.

Do not dispose of medicines by flushing them down the toilet or throwing them in household waste. Ask your pharmacist how to properly dispose of medicines that are no longer needed. These measures help protect the environment and prevent accidental exposure to others.

What Does Augtyro Contain?

Quick Answer: Augtyro capsules contain the active substance repotrectinib (40 mg or 160 mg per capsule). The 40 mg capsules are white with “REP 40” printed in blue; the 160 mg capsules are blue with “REP 160” printed in white.

Active Ingredient

The active substance in Augtyro is repotrectinib. Each hard capsule contains either 40 mg or 160 mg of repotrectinib, depending on the capsule strength.

Other Ingredients

In addition to the active substance, the capsules contain the following inactive excipients:

  • Capsule content: Microcrystalline cellulose, sodium lauryl sulfate, croscarmellose sodium, colloidal anhydrous silica, and magnesium stearate (160 mg hard capsules only).
  • Capsule shell (40 mg): Gelatin, titanium dioxide (E171).
  • Capsule shell (160 mg): Gelatin, titanium dioxide (E171), brilliant blue FCF (E133).
  • Printing ink (40 mg capsules): Shellac (E904) and indigo carmine (E132).
  • Printing ink (160 mg capsules): Shellac and titanium dioxide.

Appearance and Pack Sizes

Augtyro 40 mg hard capsules are opaque, white capsules imprinted with “REP 40” in blue ink. They are supplied in cartons containing one bottle with either 60 or 120 hard capsules.

Augtyro 160 mg hard capsules are opaque, blue capsules imprinted with “REP 160” in white ink. They are supplied in blister packs containing 10 hard capsules. Each carton contains either 20 or 60 hard capsules.

Not all pack sizes may be marketed in every country. Augtyro is manufactured by Bristol-Myers Squibb and is marketed under conditional marketing authorization in the European Union.

Frequently Asked Questions About Augtyro

Augtyro (repotrectinib) is used to treat two types of cancer driven by specific gene fusions. It is approved for adults with advanced ROS1-positive non-small cell lung cancer (NSCLC) that has spread or cannot be surgically removed, and for adults and adolescents aged 12 and older with NTRK gene fusion-positive solid tumors. Augtyro works by blocking the abnormal ROS1 and TRK proteins that cause these cancer cells to grow uncontrollably.

Augtyro was specifically designed as a next-generation inhibitor with a compact molecular structure that allows it to bind to and inhibit both native and resistance-mutant forms of ROS1 and TRK kinases. Earlier-generation inhibitors like crizotinib, entrectinib, and larotrectinib can be effective initially, but cancers often develop resistance mutations (especially solvent-front mutations like ROS1 G2032R) that prevent these drugs from binding effectively. Repotrectinib retains activity against these resistance mutations, making it an important option both as a first-line treatment and after failure of prior targeted therapy.

The 14-day lead-in period, during which Augtyro is taken at 160 mg once daily instead of the full twice-daily dose, is designed to allow your body to gradually adjust to the medication. This stepped approach helps reduce the incidence and severity of central nervous system side effects such as dizziness and loss of coordination (ataxia), which tend to be most pronounced in the early weeks of treatment. After 14 days, the body has typically developed some tolerance to these effects, and the dose is increased to 160 mg twice daily for optimal cancer-fighting activity.

No, you must completely avoid grapefruit juice, grapefruit, and Seville (bitter) oranges throughout your treatment with Augtyro. These fruits contain compounds that inhibit the CYP3A4 enzyme in your gut and liver, which is responsible for metabolizing repotrectinib. Consuming these foods can cause repotrectinib levels in your blood to rise to potentially harmful concentrations, increasing the risk and severity of side effects. Regular oranges, lemons, and limes are generally safe to consume.

Dizziness is one of the most common side effects of Augtyro and is related to its mechanism of action on the nervous system. If you feel dizzy, do not drive, cycle, or operate machinery. Take precautions to prevent falls, such as getting up slowly from sitting or lying positions and using support when walking. Contact your doctor to report the symptom – they may recommend dose adjustments or supportive measures. The dizziness often improves over time as your body adjusts to the medication, particularly after the initial lead-in period.

Augtyro should not be used during pregnancy as it may harm the developing baby. Women who could become pregnant must use highly effective contraception during treatment and for at least 2 months after the last dose, including a non-hormonal barrier method since Augtyro may reduce the effectiveness of hormonal contraceptives. Male patients should use condoms during treatment and for 4 months after. Breastfeeding must also be avoided during treatment. Pregnancy testing is required before starting therapy.

References

  1. European Medicines Agency (EMA). Augtyro (repotrectinib) – Summary of Product Characteristics (SmPC). Last updated January 2026. EMA Product Information
  2. Drilon A, et al. Repotrectinib in ROS1 fusion-positive non-small-cell lung cancer. New England Journal of Medicine. 2024;390(2):118–131. doi:10.1056/NEJMoa2302299
  3. US Food and Drug Administration (FDA). AUGTYRO (repotrectinib) prescribing information. Approved November 2023. FDA Label
  4. National Comprehensive Cancer Network (NCCN). Clinical Practice Guidelines in Oncology: Non-Small Cell Lung Cancer. Version 3.2025. NCCN Guidelines
  5. Yun MR, et al. Repotrectinib exhibits potent antitumor activity in treatment-naive and solvent front-mutant ROS1-rearranged non-small cell lung cancer. Clinical Cancer Research. 2020;26(13):3287–3295. doi:10.1158/1078-0432.CCR-19-2777
  6. Solomon BJ, et al. Updated efficacy and safety from the phase 1/2 TRIDENT-1 trial of repotrectinib in ROS1+ advanced NSCLC. Journal of Clinical Oncology. 2023;41(suppl 16):9074. doi:10.1200/JCO.2023.41.16_suppl.9074
  7. European Society for Medical Oncology (ESMO). Metastatic non-small-cell lung cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Annals of Oncology. 2023;34(4):358–376.
  8. World Health Organization (WHO). Model List of Essential Medicines. 23rd List (2023). Geneva: WHO; 2023.

Editorial Team

This article has been written and reviewed by the iMedic Medical Editorial Team, which includes board-certified physicians with specialization in oncology, thoracic medicine, and clinical pharmacology. Our team follows the GRADE evidence framework and adheres to international guidelines from WHO, EMA, FDA, NCCN, and ESMO.

Medical Writing

iMedic Medical Editorial Team – Specialists in oncology, pharmacology, and evidence-based medicine. All medical claims are supported by peer-reviewed references and international clinical guidelines.

Medical Review

iMedic Medical Review Board – Independent panel of medical experts who verify clinical accuracy, completeness, and adherence to current international treatment guidelines before publication.

Conflict of Interest: The iMedic editorial team declares no conflicts of interest. This content is produced independently with no pharmaceutical company sponsorship, advertising, or commercial funding of any kind.