Pancreatic, thyroid, and other endocrine cancers:
Indications for: GAVRETO
Advanced or metastatic RET-mutant medullary thyroid cancer (MTC) in patients who require systemic therapy. Advanced or metastatic RET fusion-positive thyroid cancer in patients who require systemic therapy and who are radioactive iodine-refractory (if radioactive iodine is appropriate).
Adult Dosage:
Confirm presence of a RET gene fusion or mutation. Take on an empty stomach. ≥12yrs: 400mg once daily. Continue until disease progression or until unacceptable toxicity. Concomitant use with combined P-gp and strong CYP3A inhibitors (if unavoidable): reduce to 200mg once daily if current dose is 300mg or 400mg once daily; reduce dose to 100mg once daily if current dose is 200mg once daily. Concomitant use with strong CYP3A inducers (if unavoidable): increase initial dose to double the current Gavreto dosage starting on Day 7 of concomitant use. Dose modifications for adverse reactions: see full labeling.
Children Dosage:
<12yrs: not established.
GAVRETO Warnings/Precautions:
Monitor for pulmonary symptoms indicative of ILD/pneumonitis; withhold therapy and evaluate if occurs. Uncontrolled hypertension: do not initiate. Optimize BP prior to initiation; monitor after 1 week, then at least monthly thereafter and as clinically indicated. Hepatotoxicity. Monitor AST/ALT prior to initiation, every 2 weeks during 1st 3 months, then monthly thereafter and as clinically indicated. Permanently discontinue if severe or life-threatening hemorrhagic events occur. Risk of tumor lysis syndrome in those with MTC (esp. with rapidly growing tumors, high tumor burden, renal dysfunction, dehydration); monitor. Risk of impaired wound healing: withhold for ≥5 days prior to elective surgery; do not give for ≥2 weeks after major surgery and until adequate healing. Moderate (total bilirubin >1.5–3.0×ULN and any AST) or severe (total bilirubin >3.0×ULN and any AST) hepatic impairment. Embryo-fetal toxicity. Advise to use effective non-hormonal contraception during and for 2 weeks (females of reproductive potential) or 1 week (males w. female partners) after the last dose. Pregnancy: exclude status prior to initiation. Nursing mothers: not recommended (during and for 1 week after the last dose).
GAVRETO Classification:
Kinase inhibitor.
GAVRETO Interactions:
See Adults. Potentiated by strong CYP3A inhibitors. Avoid concomitant combined P-gp and strong CYP3A inhibitors; if unavoidable, reduce Gavreto dose. Antagonized by strong CYP3A inducers; avoid concomitant use; if unavoidable, increase Gavreto dose. May antagonist hormonal contraceptives.
Adverse Reactions:
Constipation, hypertension, fatigue, musculoskeletal pain, diarrhea; laboratory abnormalities (decreased lymphocytes, decreased neutrophils, decreased hemoglobin, decreased phosphate, decreased sodium, decreased calcium [corrected], increased ALT/AST/alkaline phosphatase, decreased platelets), pneumonia, pneumonitis, sepsis, UTI, pyrexia.
Generic Drug Availability:
NO
How Supplied:
Caps—60, 90, 120
Respiratory and thoracic cancers:
Indications for: GAVRETO
Metastatic RET fusion-positive non-small cell lung cancer (NSCLC) as detected by an FDA approved test.
Adult Dosage:
Confirm presence of a RET gene fusion. Take on an empty stomach. 400mg once daily. Continue until disease progression or until unacceptable toxicity. Concomitant use with combined P-gp and strong CYP3A inhibitors (if unavoidable): reduce to 200mg once daily if current dose is 300mg or 400mg once daily; reduce dose to 100mg once daily if current dose is 200mg once daily. Concomitant use with strong CYP3A inducers (if unavoidable): increase initial dose to double the current Gavreto dosage starting on Day 7 of concomitant use. Dose modifications for adverse reactions: see full labeling.
Children Dosage:
Not established.
GAVRETO Warnings/Precautions:
Monitor for pulmonary symptoms indicative of ILD/pneumonitis; withhold therapy and evaluate if occurs. Uncontrolled hypertension: do not initiate. Optimize BP prior to initiation; monitor after 1 week, then at least monthly thereafter and as clinically indicated. Hepatotoxicity. Monitor AST/ALT prior to initiation, every 2 weeks during 1st 3 months, then monthly thereafter and as clinically indicated. Permanently discontinue if severe or life-threatening hemorrhagic events occur. Risk of tumor lysis syndrome in those with MTC (esp. with rapidly growing tumors, high tumor burden, renal dysfunction, dehydration); monitor. Risk of impaired wound healing: withhold for ≥5 days prior to elective surgery; do not give for ≥2 weeks after major surgery and until adequate healing. Moderate (total bilirubin >1.5–3.0×ULN and any AST) or severe (total bilirubin >3.0×ULN and any AST) hepatic impairment. Embryo-fetal toxicity. Advise to use effective non-hormonal contraception during and for 2 weeks (females of reproductive potential) or 1 week (males w. female partners) after the last dose. Pregnancy: exclude status prior to initiation. Nursing mothers: not recommended (during and for 1 week after the last dose).
GAVRETO Classification:
Kinase inhibitor.
GAVRETO Interactions:
See Adults. Potentiated by strong CYP3A inhibitors. Avoid concomitant combined P-gp and strong CYP3A inhibitors; if unavoidable, reduce Gavreto dose. Antagonized by strong CYP3A inducers; avoid concomitant use; if unavoidable, increase Gavreto dose. May antagonist hormonal contraceptives.
Adverse Reactions:
Constipation, hypertension, fatigue, musculoskeletal pain, diarrhea; laboratory abnormalities (decreased lymphocytes, decreased neutrophils, decreased hemoglobin, decreased phosphate, decreased sodium, decreased calcium [corrected], increased ALT/AST/alkaline phosphatase, decreased platelets), pneumonia, pneumonitis, sepsis, UTI, pyrexia.
Generic Drug Availability:
NO
How Supplied:
Caps—60, 90, 120
