Version July 2025
Dosage guidance:
Clinical considerations: Select patients for pralsetinib treatment based on the presence of a RET gene fusion. Withhold pralsetinib for at least 5 days prior to elective surgery; do not administer for at least 2 weeks following major surgery and until adequate wound healing has occurred.
Thyroid cancer, advanced or metastatic, RET fusion positive: Children ≥12 years and Adolescents: Oral: 400 mg once daily until disease progression or unacceptable toxicity.
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose adjustment or avoidance. Consult drug interactions database for more information.
Dosing adjustment for toxicity:
Children ≥12 years and Adolescents: Oral:
|
Dose reduction level |
Recommended dosage |
|---|---|
|
Usual (initial dose) |
400 mg once daily |
|
First dose reduction level |
300 mg once daily |
|
Second dose reduction level |
200 mg once daily |
|
Third dose reduction level |
100 mg once daily |
|
Permanently discontinue pralsetinib if unable to tolerate 100 mg once daily. | |
|
Toxicity |
Severity |
Pralsetinib dose modification |
|---|---|---|
|
Hemorrhagic events |
Grade 3 or 4 |
Withhold pralsetinib until recovery to baseline or grade 0 or 1. Permanently discontinue pralsetinib for severe or life-threatening hemorrhagic events. |
|
Hypertension |
Grade 3 |
Initiate or optimize antihypertensive therapy. Withhold pralsetinib for grade 3 hypertension that persists despite management with optimal antihypertensive therapy. Resume pralsetinib at a reduced dose when hypertension is controlled. |
|
Grade 4 |
Discontinue pralsetinib. | |
|
Pulmonary toxicity (interstitial lung disease [ILD]/pneumonitis) |
Grade 1 or 2 |
Withhold pralsetinib until resolution, then resume pralsetinib at a reduced dose. Permanently discontinue pralsetinib for recurrent ILD/pneumonitis. |
|
Grade 3 or 4 |
Permanently discontinue pralsetinib for confirmed ILD/pneumonitis. | |
|
Other adverse reactions |
Grade 3 or 4 |
Withhold pralsetinib until improvement to ≤ grade 2, then resume pralsetinib at a reduced dose. Permanently discontinue pralsetinib for recurrent grade 4 adverse reactions. |
Children ≥12 years and Adolescents: Oral:
CrCl ≥30 mL/minute: There are no dosage adjustments provided in the manufacturer's labeling; however, based on adult data, CrCl 30 to 89 mL/minute had no effect on pralsetinib exposure.
CrCl 15 to 30 mL/minute: There are no dosage adjustments provided in the manufacturer's labeling.
CrCl <15 mL/minute: There are no dosage adjustments provided in the manufacturer's labeling (has not been studied).
Children ≥12 years and Adolescents: Oral:
Baseline hepatic impairment:
Mild (total bilirubin ≤ ULN with AST > ULN or total bilirubin >1 to 1.5 times ULN with any AST) impairment: No dosage adjustment is required.
Moderate (total bilirubin >1.5 to 3 times ULN and any AST) impairment: No dosage adjustment is required.
Severe (total bilirubin >3 times ULN and any AST) impairment: No dosage adjustment is required.
Hepatotoxicity during treatment: Grade 3 or 4: Withhold pralsetinib and monitor AST and ALT once weekly until resolves to grade 1 or baseline. Resume pralsetinib at a reduced dose. If ≥ grade 3 hepatotoxicity recurs, discontinue pralsetinib. See recommended pralsetinib dosage reduction levels.
(For additional information see "Pralsetinib: Drug information")
Dosage guidance:
Safety: Optimize BP prior to initiating treatment; do not initiate pralsetinib in patients with uncontrolled hypertension. Withhold pralsetinib for at least 5 days prior to elective surgery; do not administer for at least 2 weeks following major surgery and until adequate wound healing has occurred.
Clinical considerations: Select patients for pralsetinib treatment based on the presence of a RET gene fusion.
Non–small cell lung cancer, metastatic, RET fusion positive: Oral: 400 mg once daily until disease progression or unacceptable toxicity.
Thyroid cancer, advanced or metastatic, RET fusion positive: Oral: 400 mg once daily until disease progression or unacceptable toxicity.
Missed dose: If a dose is missed, administer as soon as possible on the same day; resume the regular daily pralsetinib dose schedule the following day. If vomiting occurs after pralsetinib administration, do not take an additional dose and continue to the next scheduled time for the next dose.
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
CrCl ≥30 mL/minute: There are no dosage adjustments provided in the manufacturer's labeling; however, CrCl 30 to 89 mL/minute had no effect on pralsetinib exposure.
CrCl 15 to 30 mL/minute: There are no dosage adjustments provided in the manufacturer's labeling.
CrCl <15 mL/minute: There are no dosage adjustments provided in the manufacturer's labeling (has not been studied).
Hepatic impairment at treatment initiation:
Mild (total bilirubin ≤ ULN with AST > ULN or total bilirubin >1 to 1.5 times ULN with any AST), moderate (total bilirubin >1.5 to 3 times ULN and any AST), or severe (total bilirubin >3 times ULN and any AST) impairment: No dosage adjustment is required.
Hepatotoxicity during treatment: Grade 3 or 4: Withhold pralsetinib and monitor AST and ALT once weekly until resolves to grade 1 or baseline. Resume pralsetinib at a reduced dose. If ≥ grade 3 hepatotoxicity recurs, discontinue pralsetinib. See recommended pralsetinib dosage reduction levels in "Dosing - Adjustment for Toxicity."
Hepatotoxicity, including grade 3 or 4 increased serum alanine aminotransferase (ALT) and increased serum aspartate aminotransferase (AST), have been reported; increased serum alkaline phosphatase and increased serum bilirubin have also been reported. Some patients required treatment interruption, dose reduction, and/or permanent discontinuation, depending on severity of hepatoxicity.
Onset: Varied; median time to first onset of elevated AST was 15 days (range: 5 days to 2.5 years); the median time to first onset of elevated ALT was 24 days (range: 7 days to 3.7 years).
Hypertension has been observed with use, including grade 3 hypertension. Although antihypertensive medication was the most common method used to manage treatment-emergent hypertension, some patients required treatment interruption, dose reduction, and/or permanent discontinuation, depending on severity.
Mechanism: Dose-related; exact mechanism is not established.
Risk factors:
• Preexisting uncontrolled hypertension
Severe, life-threatening, and potentially fatal interstitial lung disease (ILD)/pneumonitis may occur with pralsetinib. Pneumonitis has been reported, including grade 3 and 4 events; fatal pneumonitis has also been reported. Withhold therapy and promptly evaluate patients with symptoms indicative of ILD. Therapy interruption, dose reduction, and/or permanent pralsetinib discontinuation may be necessary based on the severity of confirmed ILD.
Cases of tumor lysis syndrome have been reported in patients treated with pralsetinib.
Risk factors:
• Presence of rapidly growing tumors
• High tumor burden
• Kidney dysfunction
• Dehydration
Pralsetinib may have the potential to adversely affect wound healing. Due to this concern, recommendations regarding withholding therapy prior to elective surgery and/or after major surgery exist.
Mechanism: Exact mechanism is unknown; vascular endothelial growth factor receptor inhibitors are associated with impaired wound healing.
Risk factors:
• Major surgery
The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified. Reported adverse reactions are for adults.
>10%:
Cardiovascular: Edema (29% to 44%), hypertension (35% to 40%)
Dermatologic: Skin rash (17% to 24%)
Endocrine & metabolic: Decreased serum albumin (41% to 52%), decreased serum calcium (corrected: 50% to 70%), decreased serum magnesium (25% to 27%), decreased serum phosphate (28% to 50%), decreased serum potassium (27%), decreased serum sodium (28% to 42%), hypermagnesemia (14%), increased serum phosphate (40%), increased serum potassium (26% to 27%)
Gastrointestinal: Abdominal pain (14% to 17%), constipation (41% to 45%), decreased appetite (15% to 18%), diarrhea (30% to 34%; grades 3/4: 3% to 5%, including colitis), dysgeusia (17%), nausea (17% to 19%; grade 3: <1%), stomatitis (6% to 17%; grade 3: <1%), vomiting (14%), xerostomia (17%)
Genitourinary: Urinary tract infection (16%)
Hematologic & oncologic: Decreased hemoglobin (63% to 78%; grades 3/4: 13% to 18%), decreased neutrophils (59% to 70%; grades 3/4: 16% to 21%), decreased platelet count (31% to 33%; grades 3/4: 3% to 5%), leukopenia (79%; grades 3/4: 11%), lymphocytopenia (67% to 73%; grades 3/4: 27% to 32%), tumor lysis syndrome (<15%)
Hepatic: Increased serum alanine aminotransferase (37% to 58%), increased serum alkaline phosphatase (22% to 43%), increased serum aspartate aminotransferase (49% to 80%), increased serum bilirubin (20% to 24%)
Nervous system: Dizziness (19%), fatigue (38% to 42%; including asthenia), headache (15% to 24%), peripheral neuropathy (20%)
Neuromuscular & skeletal: Increased creatine phosphokinase in blood specimen (≤19%), musculoskeletal pain (42% to 44%)
Renal: Increased serum creatinine (41% to 45%)
Respiratory: Cough (27% to 36%), dyspnea (21% to 22%), pneumonia (24%), pneumonitis (12% to 14%)
Miscellaneous: Fever (22% to 29%)
1% to 10%:
Cardiovascular: Pulmonary embolism (≥2%)
Hematologic & oncologic: Hemorrhage (grades ≥3: 4%)
Hepatic: Ascites (≥2%), hepatotoxicity (severe: 2%)
Infection: Sepsis (≥2%)
Nervous system: Seizure (≥2%)
Frequency not defined: Cardiovascular: Syncope
Postmarketing: Cardiovascular: Heart failure (Papaila 2021), pleural effusion (Papaila 2021)
There are no contraindications listed in the manufacturer's US labeling.
Canadian labeling: Hypersensitivity to pralsetinib or any component of the formulation.
Concerns related to adverse effects:
• Infection: As a proposed result of off-target effects on the Janus kinase/signal transducer and activator of transcription protein pathway, pralsetinib may predispose patients to severe or fatal viral, bacterial, and fungal infections (including opportunistic infections); time to first infection ranged from 1 to 9 months (Poumeaud 2024). Pneumonia secondary to opportunistic pathogens has been reported with pralsetinib for the treatment of non–small cell lung cancer; the median time to onset was ~2 months after pralsetinib initiation (Gao 2023).
• Tumor lysis syndrome: Cases of tumor lysis syndrome (TLS) have been reported with pralsetinib in patients with medullary thyroid cancer. The risk for TLS is increased in patients with rapidly growing tumors, a high tumor burden, kidney dysfunction, or dehydration. Assess risk for TLS; consider appropriate prophylaxis (including hydration) and manage as clinically indicated.
Dosage form specific issues:
• Propylene glycol: Some dosage forms may contain propylene glycol; large amounts are potentially toxic and have been associated with hyperosmolality, lactic acidosis, seizures, and respiratory depression; use caution (AAP 1997; Zar 2007). See manufacturer’s labeling.
Other warnings/precautions:
• Immunizations: Ensure patients are current on vaccinations according to local immunization guidelines (Rojkjaer 2024).
• RET gene status: Select patients for pralsetinib treatment based on the presence of a RET gene fusion. Information on approved tests is available at http://www.fda.gov/CompanionDiagnostics.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Capsule, Oral:
Gavreto: 100 mg [contains fd&c blue #1 (brilliant blue)]
No
Capsules (Gavreto Oral)
100 mg (per each): $236.24
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Excipient information presented when available (limited, particularly for generics); consult specific product labeling. [DSC] = Discontinued product
Capsule, Oral:
Gavreto: 100 mg [DSC] [contains fd&c blue #1 (brilliant blue)]
Pralsetinib is available through a specialty pharmacy network and specialty distributors; information may be found at https://gavreto.com/.
Oral: Administer on an empty stomach; no food or meal at least 2 hours before dose and at least 1 hour after. If vomiting occurs after pralsetinib administration, do not take an additional dose; continue to the next scheduled time for the next dose.
Missed dose: If a dose is missed, administer as soon as possible on the same day; resume the regular daily pralsetinib dose schedule the following day.
Oral: Administer on an empty stomach at least 1 hour before and at least 2 hours after a meal or food.
This medication is not on the NIOSH (2024) list; however, it may meet the criteria for a hazardous drug. Pralsetinib may cause reproductive toxicity and teratogenicity.
Use appropriate precautions for receiving, handling, storage, preparation, dispensing, transporting, administration, and disposal. Follow NIOSH and USP 800 recommendations and institution-specific policies/procedures for appropriate containment strategy (NIOSH 2023; NIOSH 2024; USP-NF 2020).
Note: Facilities may perform risk assessment of some hazardous drugs to determine if appropriate for alternative handling and containment strategies (USP-NF 2020). Refer to institution-specific handling policies/procedures.
Store at 20°C to 25°C (68°F to 77°F); excursions permitted between 15°C and 30°C (59°F to 86°F). Protect from moisture.
Treatment of 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) (FDA approved in ages ≥12 years and adults); treatment of metastatic RET fusion-positive non-small cell lung cancer (NSCLC) as detected by an approved test (FDA approved in adults).
Pralsetinib may be confused with pacritinib, pazopanib, pemigatinib, pexidartinib, pirtobrutinib, ponatinib, pralatrexate, ripretinib, selpercatinib.
The Institute for Safe Medication Practices (ISMP) includes this medication among its list of drug classes (chemotherapeutic agent, parenteral and oral) which have a heightened risk of causing significant patient harm when used in error (High-Alert Medications in Acute Care, Community/Ambulatory Care, and Long-Term Care Settings).
Substrate of BCRP, CYP1A2 (Minor), CYP2D6 (Minor), CYP3A4 (Major with inducers), CYP3A4 (Minor with inhibitors), P-glycoprotein (Minor); Note: Assignment of Major/Minor substrate status based on clinically relevant drug interaction potential;
Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the drug interactions program by clicking on the “Launch drug interactions program” link above.
Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the drug interactions program
Androgens: Hypertension-Associated Agents may increase hypertensive effects of Androgens. Risk C: Monitor
Asciminib: May increase serum concentration of P-glycoprotein/ABCB1 Substrates (Narrow Therapeutic Index/Sensitive with Inhibitors). Risk C: Monitor
CYP3A4 Inducers (Moderate): May decrease serum concentration of Pralsetinib. Management: If this combo cannot be avoided, increase pralsetinib dose from 400 mg daily to 600 mg daily; from 300 mg daily to 500 mg daily; and from 200 mg daily to 300 mg daily. Risk D: Consider Therapy Modification
CYP3A4 Inducers (Strong): May decrease serum concentration of Pralsetinib. Management: Avoid concomitant use of pralsetinib with strong CYP3A4 inducers when possible. If combined, increase the starting dose of pralsetinib to double the current pralsetinib dosage starting on day 7 of coadministration. Risk D: Consider Therapy Modification
CYP3A4 Inhibitors (Moderate): May increase serum concentration of Pralsetinib. Management: If this combo cannot be avoided, decrease pralsetinib dose from 400 mg daily to 300 mg daily; from 300 mg daily to 200 mg daily; and from 200 mg daily to 100 mg daily. Risk D: Consider Therapy Modification
CYP3A4 Inhibitors (Strong): May increase serum concentration of Pralsetinib. Management: If this combo cannot be avoided, decrease pralsetinib dose from 400 mg daily to 300 mg daily; from 300 mg daily to 200 mg daily; and from 200 mg daily to 100 mg daily. Risk D: Consider Therapy Modification
Elacestrant: May increase serum concentration of P-glycoprotein/ABCB1 Substrates (Narrow Therapeutic Index/Sensitive with Inhibitors). Risk C: Monitor
Erdafitinib: May increase serum concentration of P-glycoprotein/ABCB1 Substrates (Narrow Therapeutic Index/Sensitive with Inhibitors). Management: If coadministration with these narrow therapeutic index/sensitive P-gp substrates is unavoidable, separate erdafitinib administration by at least 6 hours before or after administration of these P-gp substrates. Risk D: Consider Therapy Modification
Futibatinib: May increase serum concentration of P-glycoprotein/ABCB1 Substrates (Narrow Therapeutic Index/Sensitive with Inhibitors). Risk C: Monitor
Gilteritinib: May increase serum concentration of P-glycoprotein/ABCB1 Substrates (Narrow Therapeutic Index/Sensitive with Inhibitors). Risk C: Monitor
Grapefruit Juice: May increase serum concentration of Pralsetinib. Management: Avoid consumption of grapefruit juice, a moderate CYP3A4 inhibitor, with pralsetinib whenever possible. Because grapefruit juice consumption is highly variable, typical dose adjustments associated with moderate CYP3A4 inhibitors are not likely feasible. Risk D: Consider Therapy Modification
Inhibitors of CYP3A4 (Moderate) and P-glycoprotein: May increase serum concentration of Pralsetinib. Management: If this combo cannot be avoided, decrease pralsetinib dose from 400 mg daily to 300 mg daily; from 300 mg daily to 200 mg daily; and from 200 mg daily to 100 mg daily. Risk D: Consider Therapy Modification
Inhibitors of CYP3A4 (Strong) and P-glycoprotein: May increase serum concentration of Pralsetinib. Management: Avoid concomitant use if possible. If combined, reduce the pralsetinib dose. If taking 400 mg or 300 mg once daily, reduce to 200 mg once daily. If taking 200 mg once daily, reduce to 100 mg once daily. Risk D: Consider Therapy Modification
Lasmiditan: May increase serum concentration of P-glycoprotein/ABCB1 Substrates (Narrow Therapeutic Index/Sensitive with Inhibitors). Risk X: Avoid
Levacetylleucine: May increase serum concentration of P-glycoprotein/ABCB1 Substrates (Narrow Therapeutic Index/Sensitive with Inhibitors). Risk C: Monitor
P-glycoprotein/ABCB1 Inhibitors: May increase serum concentration of Pralsetinib. Management: If this combo cannot be avoided, decrease pralsetinib dose from 400 mg daily to 300 mg daily; from 300 mg daily to 200 mg daily; and from 200 mg daily to 100 mg daily. Risk D: Consider Therapy Modification
Pretomanid: May increase serum concentration of P-glycoprotein/ABCB1 Substrates (Narrow Therapeutic Index/Sensitive with Inhibitors). Risk C: Monitor
Primaquine: May increase serum concentration of P-glycoprotein/ABCB1 Substrates (Narrow Therapeutic Index/Sensitive with Inhibitors). Risk C: Monitor
Solriamfetol: May increase hypertensive effects of Hypertension-Associated Agents. Risk C: Monitor
Sotorasib: May increase serum concentration of P-glycoprotein/ABCB1 Substrates (Narrow Therapeutic Index/Sensitive with Inhibitors). Management: Consider avoiding use of sotorasib and narrow therapeutic index/sensitive P-gp substrates. If combined use is unavoidable, monitor for increased toxicities of the substrate and consider a decrease in the substrate dosage. Risk D: Consider Therapy Modification
Sparsentan: May increase serum concentration of P-glycoprotein/ABCB1 Substrates (Narrow Therapeutic Index/Sensitive with Inhibitors). Risk X: Avoid
Taurursodiol: May increase serum concentration of P-glycoprotein/ABCB1 Substrates (Narrow Therapeutic Index/Sensitive with Inhibitors). Risk X: Avoid
Venetoclax: May increase serum concentration of P-glycoprotein/ABCB1 Substrates (Narrow Therapeutic Index/Sensitive with Inhibitors). Management: Avoid concomitant use of venetoclax and oral p-glycoprotein (P-gp) substrates if possible. If combined use is unavoidable, administer the P-gp substrate at least 6 hours before venetoclax to minimize the potential for an interaction. Risk D: Consider Therapy Modification
Xanomeline: May increase serum concentration of P-glycoprotein/ABCB1 Substrates (Narrow Therapeutic Index/Sensitive with Inhibitors). Risk C: Monitor
Following administration of a single 200 mg pralsetinib dose with a high-fat meal (~800 to 1,000 calories with 50% to 60% of calories from fat), the mean Cmax and AUC0-inf were increased by 2-fold and 2.2-fold, respectively, compared to the fasting state; the median Tmax was delayed from 4 to 8.5 hours. Management: Administer pralsetinib on an empty stomach at least 1 hour before and at least 2 hours after a meal or food.
Evaluate pregnancy status prior to use in patients who could become pregnant.
Patients who could become pregnant should use effective nonhormonal contraception during therapy and for 2 weeks after the last pralsetinib dose. Patients with partners who could become pregnant should also use effective contraception during therapy and for 1 week after the last dose of pralsetinib.
Based on the mechanism of action and data from animal reproduction studies, in utero exposure to pralsetinib may cause fetal harm.
Monitor ALT and AST at baseline, every 2 weeks during the first 3 months of therapy, then monthly thereafter, and as clinically indicated. Hepatitis B virus screening with hepatitis B surface antigen (HBsAg), hepatitis B core antibody (anti-HBc), total Ig or IgG, and antibody to hepatitis B surface antigen (anti-HBs) prior to beginning systemic anticancer therapy (ASCO [Hwang 2020]). Evaluate pregnancy status prior to use in patients who may become pregnant. Monitor BP at baseline, after 1 week, at least monthly thereafter, and as clinically indicated. Monitor for signs/symptoms of interstitial lung disease/pneumonitis, hemorrhage, and impaired wound healing. Monitor adherence. Monitor growth plates in adolescent patients with open growth plates.
Pralsetinib inhibits wild-type RET (REarranged during Transfection), oncogenic RET fusions (CCDC6-RET) and RET mutations (RET V804L, RET V804M, and RET M918T); in enzyme assays, pralsetinib also inhibited DDR1, TRKC, FLT3, JAK1-2, TRKA, VEGFR2, PDGFRb, and FGFR1. Certain activating point mutations in RET or chromosomal rearrangements involving in-frame fusions of RET can result in constitutively activated chimeric RET fusion proteins, which may act as oncogenic drivers, promoting tumor cell line proliferation. Pralsetinib has demonstrated antitumor activity in cells harboring oncogenic RET fusions or mutations including CCDC6-RET, KIF5B-RET, RET M918T, RET C634W, RET V804L, and RET V804M.
Note: Pharmacokinetic data in pediatric patients ≥12 years was shown to be similar to adult patients.
Distribution: Adults: Vd/F: 303 L.
Protein binding: 97%.
Metabolism: Predominantly via CYP3A4 and to a lesser extent by CYP2D6 and CYP1A2.
Half-life elimination: Adults: Single dose: 16 hours; multiple doses: 20 hours.
Time to peak: Adults: 2 to 4 hours.
Excretion: Adults: Feces: ~73% (66% as unchanged drug); urine: ~6% (~5% as unchanged drug).
Clearance: Adults: 11 L/hour.
