Pralsetinib
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From MedlinePlus, U.S. National Library of Medicine
Boxed warning
WARNING: SERIOUS INFECTIONS, INCLUDING OPPORTUNISTIC INFECTIONS GAVRETO may increase the risk for serious infections, including bacterial, fungal, viral and opportunistic infections, which can lead to hospitalization or death. Withhold, reduce the dose or permanently discontinue GAVRETO based on severity [see Dosage and Administration (2.3) , Warnings and Precautions (5.1) ] . WARNING: SERIOUS INFECTIONS, INCLUDING OPPORTUNISTIC INFECTIONS See full prescribing information for complete boxed warning. GAVRETO may increase the risk for serious infections, including bacterial, fungal, viral and opportunistic infections, which can lead to hospitalization or death.
Withhold, reduce the dose or permanently discontinue GAVRETO based on severity. ( 2.3 , 5.1 )
Kinase Inhibitor
Dosing in kidney impairment
Patients may be at risk of TLS if they have rapidly growing tumors, a high tumor burden, renal dysfunction, or dehydration. Closely monitor patients at risk, consider appropriate prophylaxis including hydration, and treat as clinically indicated. 5.7 Risk of Impaired Wound Healing Impaired wound healing can occur in patients who receive drugs that inhibit the vascular endothelial growth factor (VEGF) signaling pathway.
Dosing in liver impairment
Hepatic Impairment No dose adjustment is required for patients with mild (total bilirubin ≤ ULN and AST > ULN or total bilirubin > 1 to 1.5 × ULN and any AST), moderate (total bilirubin > 1.5 to 3 × ULN and any AST) or severe (total bilirubin > 3 × ULN and any AST) hepatic impairment .
Preparation and administration
Dose Modification for Use with CYP3A and/or P-glycoprotein (P-gp) Inhibitors Avoid coadministration of GAVRETO with any of the following: Strong CYP3A inhibitors Moderate CYP3A inhibitors P-gp inhibitors Combined P-gp and strong CYP3A inhibitors Combined P-gp and moderate CYP3A inhibitors If coadministration with any of the above inhibitors cannot be avoided, reduce the current dose of GAVRETO as recommended in Table 3 .
After the inhibitor has been discontinued for 3 to 5 elimination half-lives, resume GAVRETO at the dose taken prior to initiating the inhibitor [see Drug Interactions , Clinical Pharmacology ] . [See table below.] 100 mg orally once daily
Dose Modification for Use with CYP3A Inducers Avoid coadministration of GAVRETO with any of the following: Strong CYP3A inducers Moderate CYP3A inducers If coadministration with any of the above inducers cannot be avoided, increase the starting dose of GAVRETO as recommended in Table 4 starting on Day 7 of coadministration of GAVRETO with the inducer.
After the inducer has been discontinued for at least 14 days, resume GAVRETO at the dose taken prior to initiating the inducer [see Drug Interactions , Clinical Pharmacology ] . [See table below.] 600 mg orally once daily 500 mg orally once daily 200 mg orally once daily 400 mg orally once daily 300 mg orally once daily
Drug interactions
Check pralsetinib against a medication listLabel text (3 paragraphs)
Strong or moderate CYP3A inhibitors and/or P-gp inhibitors : Avoid coadministration. If coadministration cannot be avoided, reduce the dose of GAVRETO. ( 2.4 , 7.1 , 12.3 ) Strong or moderate CYP3A inducers : Avoid coadministration. If coadministration cannot be avoided, increase the dose of GAVRETO. ( 2.5 , 7.1 , 12.3 )
7.1 Effects of Other Drugs on GAVRETO Strong or Moderate CYP3A and/or P-gp Inhibitors Concomitant use with a strong or moderate CYP3A inhibitor and/or a P-gp inhibitor increases pralsetinib exposure [ Clinical Pharmacology (12.3) ] , which may increase the risk of adverse reactions related to GAVRETO. Avoid coadministration of GAVRETO with a strong or moderate CYP3A and/or P-gp inhibitor. If coadministration with any of the above inhibitors cannot be avoided, reduce the GAVRETO dose [see Dosage and Administration (2.4) ].
Strong or Moderate CYP3A Inducers Concomitant use with a strong CYP3A inducer decreases pralsetinib exposure [see Clinical Pharmacology (12.3) ], which may decrease efficacy of GAVRETO. Avoid concomitant use of GAVRETO with strong or moderate CYP3A inducers. If coadministration of GAVRETO with strong or moderate CYP3A inducers cannot be avoided, increase the GAVRETO dose [see Dosage and Administration (2.5) ]
Contraindications
None. None. ( 4 )
Pregnancy and lactation
Pregnancy
8.1 Pregnancy Risk Summary Based on findings from animal studies and its mechanism of action, GAVRETO can cause fetal harm when administered to a pregnant woman [see Clinical Pharmacology (12.1) ]. There are no available data on GAVRETO use in pregnant women to inform drug-associated risk. Oral administration of pralsetinib to pregnant rats during the period of organogenesis resulted in malformations and embryolethality at maternal exposures below the human exposure at the clinical dose of 400 mg once daily (see Data ). Advise pregnant women of the potential risk to a fetus. In the U.S.
general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2-4% and 15-20%, respectively. Data Animal Data In an embryo-fetal development study, once daily oral administration of pralsetinib to pregnant rats during the period of organogenesis resulted in 100% post-implantation loss at dose levels ≥ 20 mg/kg (approximately 1.8 times the human exposure based on area under the curve [AUC] at the clinical dose of 400 mg). Post-implantation loss also occurred at the 10 mg/kg dose level (approximately 0.6 times the human exposure based on AUC at the clinical dose of 400 mg).
Once daily oral administration of pralsetinib at dose levels ≥ 5 mg/kg (approximately 0.2 times the human AUC at the clinical dose of 400 mg) resulted in an increase in visceral malformations and variations (absent or small kidney and ureter, absent uterine horn, malpositioned kidney or testis, retroesophageal aortic arch) and skeletal malformations and variations (vertebral and rib anomalies and reduced ossification).
For breastfeeding, also see LactMed (National Library of Medicine), which summarizes milk levels and infant effects.
Supply and cost
Drug shortage status
Recalls (last 24 months)
Therapeutic equivalence (Orange Book)
Price ladder
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