AUGTYRO
Clinical safety rating: caution
Comprehensive clinical and safety monograph for AUGTYRO (AUGTYRO).
AUGTYRO (vobramitamab duocarmazine) is a bispecific antibody-drug conjugate (ADC) targeting B7-H3 and CD3. It binds to B7-H3 on tumor cells and CD3 on T cells, directing T-cell cytotoxicity to B7-H3-expressing cells. The duocarmazine payload is a DNA alkylator that causes DNA damage and apoptosis upon internalization.
| Metabolism | Metabolized primarily via proteolytic degradation into small peptides and amino acids. The duocarmazine payload is metabolized by hepatic esterases and CYP3A4 to inactive metabolites. |
| Excretion | Primarily renal elimination: 86% of the dose excreted in urine as unchanged drug and metabolites (4% unchanged), with 6% recovered in feces. |
| Half-life | Terminal elimination half-life is approximately 42 hours in healthy subjects; steady-state is reached within 8-14 days. |
| Protein binding | Plasma protein binding is 99.5% (mainly to albumin and alpha-1-acid glycoprotein). |
| Volume of Distribution | Volume of distribution is 4.5 L/kg, indicating extensive tissue distribution. |
| Bioavailability | Oral bioavailability is not fully characterized; absorption is at least 70% based on mass balance; administration with a high-fat meal increases exposure by 2-fold. |
| Onset of Action | Clinical effect on tumor response observed within 2-4 weeks of continuous oral dosing. |
| Duration of Action | Duration of response is variable; median duration of response approximately 12 months in clinical trials; continuous daily dosing is required for sustained effect. |
Oral, 90 mg twice daily with or without food.
| Dosage form | CAPSULE |
| Renal impairment | No dose adjustment required for GFR ≥30 mL/min. For GFR <30 mL/min, reduce dose to 60 mg twice daily. |
| Liver impairment | Child-Pugh A: no adjustment. Child-Pugh B: reduce dose to 60 mg twice daily. Child-Pugh C: reduce dose to 60 mg once daily. |
| Pediatric use | Not approved for use in pediatric patients younger than 18 years. |
| Geriatric use | No specific adjustment required; monitor renal function due to age-related decline. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for AUGTYRO (AUGTYRO).
| Breastfeeding | No human data available; M/P ratio unknown. Do not breastfeed due to potential for serious adverse reactions in nursing infants and tumorigenicity risk. |
| Teratogenic Risk | FDA Category X. Contraindicated in pregnancy. Animal studies show embryofetal toxicity and teratogenicity at exposures similar to human therapeutic doses. Avoid in women of childbearing potential unless using effective contraception. |
| Fetal Monitoring |
■ FDA Black Box Warning
WARNING: IMMUNE-MEDIATED ADVERSE REACTIONS AND INFUSION-RELATED REACTIONS. AUGTYRO can cause severe or fatal immune-mediated adverse reactions, including cytokine release syndrome (CRS), immune effector cell-associated neurotoxicity syndrome (ICANS), and severe infusion-related reactions. Monitor closely and manage with supportive care, corticosteroids, and/or discontinuation as indicated.
| Serious Effects |
["None"]
| Precautions | ["Cytokine release syndrome (CRS): Monitor for fever, hypoxia, hypotension; manage with supportive care, tocilizumab, and/or corticosteroids","Immune effector cell-associated neurotoxicity syndrome (ICANS): Monitor for neurological symptoms; manage with corticosteroids and supportive care","Infusion-related reactions: Premedicate and monitor; interrupt or discontinue if severe","Infections: Monitor for opportunistic infections due to immunosuppression","Hepatotoxicity: Monitor liver function tests; withhold or discontinue if severe"] |
| Food/Dietary | Avoid grapefruit and grapefruit juice as they are strong CYP3A4 inhibitors and may increase repotrectinib exposure. No other specific food restrictions; however, maintain a balanced diet and report any significant changes in appetite or weight. |
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| Pregnancy testing required before initiation and monthly during treatment. Monitor for signs of hepatotoxicity and thromboembolic events if inadvertently exposed during pregnancy. |
| Fertility Effects | May impair fertility in males and females based on animal studies; reversible after discontinuation. Advise patients of potential impact on spermatogenesis and ovarian function. |
| Clinical Pearls | AUGTYRO (repotrectinib) is a next-generation ROS1/TRK inhibitor with potent activity against solvent front mutations like ROS1 G2032R and TRK G595R, which confer resistance to earlier agents. It is approved for ROS1-positive non-small cell lung cancer (NSCLC) and NTRK-positive solid tumors. Monitor for neurological adverse effects (dizziness, ataxia, cognitive changes) due to TRK inhibition; dose adjustment or interruption may be necessary. CYP3A4 is a major metabolizing enzyme; coadministration with strong CYP3A4 inhibitors or inducers requires dose modification. Conduct baseline and periodic hepatic function tests. Avoid use in pregnancy; effective contraception is required. |
| Patient Advice | Take AUGTYRO exactly as prescribed, typically once daily with or without food. · Swallow capsules whole; do not crush or chew them. · Report new or worsening dizziness, confusion, balance problems, or hallucinations immediately. · Avoid grapefruit and grapefruit juice during treatment. · Inform your healthcare provider of all medications, including over-the-counter drugs and supplements. · Use effective contraception during treatment and for at least 2 weeks after the last dose. · Do not breastfeed while taking AUGTYRO and for 2 weeks after the final dose. |