Pralsetinib is an oral kinase inhibitor of wild-type rearranged during transfection (RET) and oncogenic RET fusions and mutations. It is indicated for the treatment of adult patients with metastatic RET fusion-positive non-small cell lung cancer and adult/pediatric patients 12 years of age and older with advanced or metastatic RET fusion-positive thyroid cancer who require systemic therapy and who are radioactive iodine-refractory (if radioactive iodine is appropriate). Pralsetinib may cause hepatotoxicity, hypertension, and tumor lysis syndrome; monitoring is recommended. Pralsetinib may also impair wound healing and should be avoided for at least 5 days prior to elective surgery, for 2 weeks after major surgery, and until wounds have adequately healed after any surgery.
General Administration Information
For storage information, see the specific product information within the How Supplied section.
Route-Specific Administration
Oral Administration
-Pralsetinib should be taken on an empty stomach, at least 1 hour before or 2 hours after food.
-If a dose is missed, it can be taken as soon as possible on the same day; resume the regular daily schedule the following day. Do not take an additional dose if vomiting occurs.
In a pooled safety population (n = 540), interstitial lung disease (ILD)/pneumonitis occurred in 12% (grade 3 or 4, 3.3%; grade 5, 0.2%) of patients with RET fusion-positive NSCLC or RET-altered thyroid cancer who received pralsetinib. Monitor for signs and symptoms of ILD/pneumonitis. Hold treatment and promptly investigate for ILD in any patient presenting with acute or worsening respiratory symptoms. An interruption of therapy, dose reduction, or discontinuation of therapy may be necessary based on the severity of confirmed ILD. Cough (27% to 36%; grade 3 or 4, 0.4% to 1.4%) and dyspnea (21% to 22%; grade 3 or 4, 2.1% to 2.2%) were also reported in patients treated with pralsetinib.
In a pooled safety population (n = 540), hypertension occurred in 35% (grade 3, 18%) of patients with RET fusion-positive NSCLC or RET-altered thyroid cancer who received pralsetinib. Do not initiate pralsetinib therapy in patients with uncontrolled hypertension; optimize blood pressure prior to initiating therapy. Monitor blood pressure after 1 week, at least monthly thereafter, and as clinically indicated. Initiate or adjust antihypertensive therapy as appropriate. An interruption of therapy, dose reduction, or discontinuation of therapy may be necessary for patients who develop hypertension, based upon the severity.
In a pooled safety population (n = 540), serious hepatotoxicity (1.5%) and elevated hepatic enzymes including increased AST (49%; grade 3 or 4, 7%) and ALT (37%; grade 3 or 4, 4.8%) levels occurred in patients with RET fusion-positive NSCLC or RET-altered thyroid cancer who received pralsetinib. The median time to the first onset of increased AST/ALT levels was 15 to 24 days. Monitor AST/ALT prior to initiation of therapy, every 2 weeks during the first 3 months of therapy, and then monthly and as clinically indicated thereafter. An interruption of therapy, dose reduction, or discontinuation of therapy may be necessary for patients who develop hepatotoxicity. Increased AST (69% to 80%; grade 3 or 4, 3.2% to 4.3%), increased ALT (43% to 58%; grade 3 or 4, 3.6% to 3.9%), increased alkaline phosphatase (22% to 43%; grade 3 or 4, 1.4% to 2.5%), increased bilirubin/hyperbilirubinemia (20% to 24%; grade 3 or 4, 1.4% to 1.8%), and decreased albumin levels/hypoalbuminemia (41% to 52%; grade 3 or 4, 1.5% or less) were reported in the cohorts of patients with RET fusion-positive NSCLC and RET-altered thyroid cancer who received pralsetinib in a multicohort trial. Severe cases of ascites occurred in at least 2% of patients from the thyroid cancer cohort.
In a pooled safety population (n = 540), grade 3 or higher bleeding events occurred in 4.1% of patients with RET fusion-positive NSCLC or RET-altered thyroid cancer who received pralsetinib; 1 patient had a fatal hemorrhagic event. An interruption of therapy or permanent discontinuation of therapy may be necessary for patients who develop grade 3 or 4 bleeding.
Fatigue (including asthenia) occurred in 42% (grade 3, 2.5%) of patients with RET fusion-positive NSCLC (n = 281) and 38% (grade 3, 6%) of patients with RET-altered thyroid cancer (n = 138) who received pralsetinib in a multicohort trial.
Edema occurred in 44% of patients with RET fusion-positive NSCLC (n = 281) and in 29% of patients with RET-altered thyroid cancer (n = 138) who received pralsetinib in a multicohort trial. The term edema included peripheral edema, facial edema, periorbital edema, swelling, and blepharedema (eyelid edema).
Constipation (41% to 45%; grade 3 or 4, 0.7%), diarrhea including colitis (30% to 34%; grade 3 or 4, 2.5% to 5%), nausea (17% to 19%; grade 3 or 4, 0.7% or less), decreased appetite/anorexia (15% to 18%; grade 3 or 4, 1.1% or less), and abdominal pain (14% to 17%; grade 3 or 4, 0.7% or less) were reported in patients RET fusion-positive NSCLC (n = 281) or RET-altered thyroid cancer (n = 183) treated with pralsetinib in a multicohort trial; vomiting was reported in 14% of patients in the NSCLC cohort.
Xerostomia occurred in 17% of patients with RET fusion-positive NSCLC (n = 281) or RET-altered thyroid cancer (n = 183) treated with pralsetinib in a multicohort trial. Additionally, stomatitis (including mucosal inflammation and tongue/oral ulceration) was reported in 6% to 17% of pralsetinib-treated patients in these cohorts (grade 3 or 4, 0.7% or less).
Musculoskeletal pain occurred in 42% to 44% (grade 3 or 4, 0.7% to 2.5%) of patients with RET fusion-positive NSCLC (n = 281) or RET-altered thyroid cancer (n = 138) who received pralsetinib in a multicohort trial; additionally, increased creatine phosphokinase level was reported in 19% or fewer of these patients. The term musculoskeletal pain included back pain, myalgia, arthralgia, extremity pain, neck pain, musculoskeletal chest pain, bone pain, muscle stiffness, arthritis, and spinal pain.
Serious infection including coronavirus infection, pneumonia, sepsis, and urinary tract infection occurred in at least 2% of patients with RET fusion-positive NSCLC (n = 281) or RET-altered thyroid cancer (n = 138) who received pralsetinib in a multicohort trial. Pneumonia (24%; grade 3 or 4, 13%) and urinary tract infection (16%; grade 3 or 4, 3.6%) were individually reported in the cohort of patients with RET fusion-positive NSCLC.
Fever was reported in 22% to 29% (grade 3 or 4, 0.7% to 2.2%) of patients with RET fusion-positive NSCLC (n = 281) or RET-altered thyroid cancer (n = 138) who received pralsetinib in a multicohort trial.
Electrolyte abnormalities including hyperkalemia, hypermagnesemia, hyperphosphatemia, hypocalcemia, hypokalemia, hypomagnesemia, hyponatremia, and hypophosphatemia occurred in patients with RET fusion-positive NSCLC (n = 281) or RET-altered thyroid cancer (n = 183) who received pralsetinib in a multicohort trial. Decreases from baseline in corrected calcium (50% to 70%; grade 3 or 4, 1.8% to 9%), phosphate (28% to 50%; grade 3 or 4, 8% to 17%), sodium (28% to 42%; grade 3 or 4, 2.2% to 10%), and magnesium (25% to 27%; grade 3 or 4, 0.7% or less), and potassium (27% or less; grade 3 or 4, 4.6%) or less) were reported in pralsetinib-treated patients; additionally, increases from baseline in phosphate (40% or less), potassium (26% to 27%; grade 3 or 4, 1.4% to 1.8%), and magnesium (14% or less) were also reported. An increase from baseline in serum creatinine was reported in 33% to 45% (grade 3 or 4, 0.5% to 1.4%) of patients who received pralsetinib.
Hematologic abnormalities including anemia, leukopenia, lymphopenia, neutropenia, and thrombocytopenia occurred in patients with RET fusion-positive NSCLC (n = 281) or RET-altered thyroid cancer (n = 183) who received pralsetinib in a multicohort trial. Decreases from baseline in leukocytes (79% or less; grade 3 or 4, 11% or less), hemoglobin (63% to 78%; grade 3 or 4, 13% to 18%), lymphocytes (67% to 73%; grade 3 or 4, 27% to 32%), neutrophils (59% to 70%; grade 3 or 4, 16% to 21%), and platelets (31% to 33%; grade 3 or 4, 2.9% to 5%) were reported in patients in these cohorts who received pralsetinib.
Cases of tumor lysis syndrome (TLS) have been reported in patients with RET-mutant medullary thyroid carcinoma who received pralsetinib therapy. In patients who are at risk for developing TLS, closely monitor for signs and symptoms of TLS and consider TLS prophylaxis (e.g., hydration); treat as clinically indicated.
Rash occurred in 17% of patients with RET fusion-positive NSCLC (n = 281) who received pralsetinib in one cohort of a multicohort trial, including maculopapular rash, acneiform rash, and erythema.
Headache including migraine (15% to 24%; grade 3 or 4, 1.1% or less) and dysgeusia including ageusia (17%) were reported in patients with RET fusion-positive NSCLC (n = 281) or RET-altered thyroid cancer (n = 183) who received pralsetinib in a multicohort trial. Peripheral neuropathy (20%), and dizziness including vertigo (19%; grade 3, 0.7%) were also reported in the RET-altered thyroid cancer cohort; the term peripheral neuropathy included dysesthesia, hyperesthesia, hypoesthesia, neuralgia, paresthesias, and polyneuropathy.
Use pralsetinib with caution in patients with a history of chronic lung disease (CLD); severe, life-threatening, and fatal interstitial lung disease (ILD)/pneumonitis can occur in patients treated with pralsetinib. Monitor for signs and symptoms of ILD/pneumonitis. Hold treatment and promptly investigate for ILD in any patient presenting with acute or worsening respiratory symptoms (e.g., dyspnea, cough, and fever). An interruption of therapy, dose reduction, or discontinuation of therapy may be necessary based on the severity of confirmed ILD.
Do not initiate pralsetinib therapy in patients with uncontrolled hypertension as treatment has been associated with increased blood pressure; optimize blood pressure prior to initiating therapy. Monitor blood pressure after 1 week, at least monthly thereafter, and as clinically indicated. Initiate or adjust antihypertensive therapy as appropriate. An interruption of therapy, dose reduction, or discontinuation of therapy may be necessary for patients who develop hypertension, based upon the severity.
Use pralsetinib with caution in patients with a history of hepatic disease; hepatotoxicity has been reported in patients treated with pralsetinib. Monitor AST and ALT prior to initiation of therapy, every 2 weeks during the first 3 months of therapy, and then monthly and as clinically indicated thereafter. An interruption of therapy, dose reduction, or discontinuation of therapy may be necessary for patients who develop hepatotoxicity.
Impaired wound healing can occur in patients treated with vascular endothelial growth factor (VEGF) inhibitors such as pralsetinib. Discontinue pralsetinib at least 5 days prior to elective surgery; do not administer pralsetinib for at least 2 weeks following major surgery and until adequate wound healing. The safety of resuming pralsetinib after resolution of wound healing complications has not been established.
Tumor lysis syndrome (TLS) has been reported in patients with medullary thyroid carcinoma (MTC) who received pralsetinib therapy. Patients with rapidly growing tumors, a high tumor burden renal impairment, or dehydration may be at increased risk for developing TLS. In patients who are at risk for developing TLS, closely monitor for signs and symptoms of TLS and consider TLS prophylaxis (e.g., hydration); treat as clinically indicated.
Bone and cartilage abnormalities have been observed in animals who received pralsetinib at doses resulting in exposures similar to the human exposure (AUC) at the clinical dose of 400 mg. Children and adolescents with open growth plates may be at risk for growth inhibition; monitor growth plates in these patients. Perform an individual risk-benefit assessment; consider interrupting or discontinuing pralsetinib therapy based on the severity of growth plate abnormalities. The safety and efficacy of pralsetinib have not been established in pediatric patients with RET fusion-positive NSCLC or in pediatric patients younger than 12 years old with RET-mutant medullary thyroid cancer or RET-fusion thyroid cancer.
Pregnancy should be avoided by females of reproductive potential during pralsetinib treatment and for at least 2 weeks after the last dose. Although there are no adequately controlled studies in pregnant women, pralsetinib can cause fetal harm or death when administered during pregnancy based on its mechanism of action and animal studies. Women who are pregnant or who become pregnant while receiving pralsetinib should be apprised of the potential hazard to the fetus. In an embryo-fetal development study, administration of pralsetinib to pregnant rats during organogenesis resulted in 100% post-implantation loss at dose levels approximating 1.5 to 2.2 times the human exposure based on AUC at the clinical dose of 400 mg; post-implantation loss also occurred at approximately 0.5 times the human AUC at the clinical 400-mg dose. Increased visceral malformations and variations (absent or small kidney and ureter, absent uterine horn, malpositioned kidney or testis, retroesophageal aortic arch) and skeletal malformations/variations (vertebral and rib anomalies and reduced ossification) occurred at exposures of approximately 0.2 times the human AUC at the clinical 400-mg dose.
Counsel patients about the reproductive risk and contraception requirements during pralsetinib treatment. Pralsetinib can be teratogenic if taken by the mother during pregnancy. Females should avoid pregnancy and use effective non-hormonal contraception during and for at least 2 weeks after treatment with pralsetinib. Due to the risk of male-mediated teratogenicity, males with female partners of reproductive potential should also use effective contraception during treatment and for 1 week after the last dose. Females of reproductive potential should undergo pregnancy testing prior to initiation of pralsetinib. Women who become pregnant while receiving pralsetinib should be apprised of the potential hazard to the fetus. Although there are no data regarding the effect of pralsetinib on human fertility, male and female infertility has been observed in animal studies.
Due to the potential for serious adverse reactions in nursing infants from pralsetinib, advise women to discontinue breast-feeding during treatment and for 1 week after the final dose. It is not known whether pralsetinib is present in human milk, although many drugs are excreted in human milk.
For the treatment of non-small cell lung cancer (NSCLC):
NOTE: Pralsetinib is designated as an orphan drug by the FDA for the treatment of RET-rearranged NSCLC, JAK1/2-positive NSCLC, or TRKC-positive NSCLC.
-for the treatment of metastatic RET fusion-positive non-small cell lung cancer (NSCLC):
NOTE: Select patients based on the presence of a RET gene fusion. Information on FDA-approved tests is available at www.fda.gov/CompanionDiagnostics.
Oral dosage:
Adults: 400 mg PO once daily on an empty stomach until disease progression or unacceptable toxicity. Coadministration of certain drugs may need to be avoided or dosage adjustments may be necessary; review drug interactions. Patients with metastatic RET fusion-positive NSCLC who had been previously treated with platinum-based chemotherapy had an overall response rate (ORR) of 63% (complete response [CR], 6%) in one cohort of a nonrandomized, open-label, multicohort clinical trial (the ARROW trial); the response rate was similar (59%) in patients who had previously received an anti-PD-1 or anti-PD-L1 therapy. The median duration of response was 38.8 months, and was at least 12 months in 66% of patients. Patients with treatment-naive RET fusion-positive NSCLC had an ORR of 78% (CR, 7%) for a median duration of 13.4 months; 45% of patients had a duration of response of 12 months or longer.
For the treatment of thyroid cancer:
NOTE: Pralsetinib is designated by the FDA as an orphan drug for RET-fusion, RET-mutation, and TRKC-positive poorly differentiated thyroid cancer, undifferentiated or anaplastic thyroid cancer, medullary thyroid cancer, and locally advanced or metastatic follicular or papillary thyroid cancer.
-for the treatment of advanced or metastatic RET fusion-positive thyroid cancer in patients who require systemic therapy and are refractory to radioactive iodine, if appropriate:
NOTE: Patients should be selected based on the presence of a RET gene fusion. There is no FDA-approved test for the detection of RET gene fusion in thyroid cancer.
Oral dosage:
Adults: 400 mg PO once daily on an empty stomach until disease progression or unacceptable toxicity. Coadministration of certain drugs may need to be avoided or dosage adjustments may be necessary; review drug interactions. Treatment with pralsetinib resulted in an overall response rate (ORR) of 89% (all partial responses) in patients with metastatic RET fusion-positive papillary thyroid cancer who had disease progression following radioactive iodine (n = 9; median age, 61 years; range, 46 to 74 years) in one cohort of a multicenter, noncomparative trial. All responding patients had a response that lasted 6 months or longer. Patients in this cohort had received a median of 2 (range, 1 to 8) prior therapies; 56% of patients had previously received sorafenib and/or lenvatinib.
Adolescents and Children aged 12 years: 400 mg PO once daily on an empty stomach until disease progression or unacceptable toxicity. Coadministration of certain drugs may need to be avoided or dosage adjustments may be necessary; review drug interactions. Evidence of the efficacy of pralsetinib in pediatric patients aged 12 years and older is extrapolated from thyroid cancer studies and population pharmacokinetic data in adult patients.
-for the treatment of advanced or metastatic RET-mutant medullary thyroid cancer (MTC) in patients who require systemic therapy*:
NOTE: FDA approval was removed for this indication in July 2023 after initial accelerated approval due to challenges associated with fulfilling the confirmatory phase 3 AcceleRET-MTC trial.
Oral dosage:
Adults: Dosage not available.
Therapeutic Drug Monitoring:
Dosage Adjustments for Treatment-Related Toxicities
Interrupt pralsetinib therapy per specific instructions below. Restart pralsetinib as appropriate at the following reduced doses:
-First dose reduction: 300 mg PO once daily.
-Second dose reduction: 200 mg PO once daily.
-Third dose reduction: 100 mg PO once daily.
-Subsequent dose reduction: Permanently discontinue pralsetinib therapy in patients unable to tolerate a daily dose of 100 mg.
Hemorrhagic Events
-Grade 3 or 4: Hold pralsetinib therapy. Upon recovery to baseline or grade 1 or less, treatment may be resumed. Discontinue pralsetinib treatment for severe or life-threatening hemorrhagic events.
Hypertension
-Grade 3 hypertension that persists despite optimal antihypertensive therapy: Hold pralsetinib therapy. When hypertension is controlled, treatment may be resumed at a reduced dose.
-Grade 4: Discontinue pralsetinib therapy.
Interstitial Lung Disease (ILD) / Pneumonitis
-Grade 1 or 2: Hold pralsetinib therapy. Upon resolution, treatment may be resumed at a reduced dose. Permanently discontinue pralsetinib treatment if recurrent ILD/pneumonitis occurs.
-Grade 3 or 4: Permanently discontinue pralsetinib therapy for confirmed ILD/pneumonitis.
Other Adverse Reactions
-Grade 3 or 4: Hold pralsetinib therapy. Upon improvement to grade 2 or less, treatment may be resumed at a reduced dose. Permanently discontinue pralsetinib treatment if recurrent grade 4 adverse reactions occur.
Maximum Dosage Limits:
-Adults
400 mg/day PO.
-Geriatric
400 mg/day PO.
-Adolescents
400 mg/day PO.
-Children
12 years: 400 mg/day PO.
11 years or younger: Safety and efficacy not established.
-Infants
Safety and efficacy not established.
Patients with Hepatic Impairment Dosing
Baseline Hepatic Impairment
-Mild, moderate, or severe hepatic impairment: Dosage adjustments are not required.
Treatment-Related Hepatotoxicity
-Grade 3 or 4: Hold pralsetinib therapy and monitor AST/ALT once weekly. Upon resolution to grade 1 or baseline, treatment may be resumed at a reduced dose. Discontinue pralsetinib treatment if hepatotoxicity recurs at grade 3 or higher.
Patients with Renal Impairment Dosing
Baseline Renal Impairment
-Mild to moderate renal impairment (CrCl 30 to 89 mL/min): No dose adjustment is required.
-Severe renal impairment (CrCl less than 15 mL/min): Pralsetinib has not been studied in this population.
*non-FDA-approved indication
Abrocitinib: (Major) Avoid concomitant use of abrocitinib with pralsetinib due to the risk of increased pralsetinib exposure which may increase the risk of adverse reactions. If concomitant use is necessary, reduce the daily dose of pralsetinib by 100 mg. Pralsetinib is a P-gp substrate and abrocitinib is a P-gp inhibitor. Coadministration with another P-gp inhibitor increased the overall exposure of pralsetinib by 81%.
Adagrasib: (Major) Avoid concomitant use of adagrasib and pralsetinib due to the risk of increased pralsetinib exposure which may increase the risk of adverse reactions. If concomitant use is necessary, reduce the dose of pralsetinib to 200 mg once daily for patients taking a daily dose of 400 mg or 300 mg, and to 100 mg once daily for patients taking a daily dose of 200 mg. Pralsetinib is a CYP3A and P-gp substrate and adagrasib is a combined strong CYP3A and P-gp inhibitor. Coadministration with a combined strong CYP3A and P-gp inhibitor is predicted to increase the overall exposure of pralsetinib by 251%.
Amiodarone: (Major) Avoid concomitant use of amiodarone with pralsetinib due to the risk of increased pralsetinib exposure which may increase the risk of adverse reactions. If concomitant use is necessary, reduce the daily dose of pralsetinib by 100 mg. Pralsetinib is a P-gp substrate and amiodarone is a P-gp inhibitor. Coadministration with another P-gp inhibitor increased the overall exposure of pralsetinib by 81%.
Amoxicillin; Clarithromycin; Omeprazole: (Major) Avoid concomitant use of clarithromycin and pralsetinib due to the risk of increased pralsetinib exposure which may increase the risk of adverse reactions. If concomitant use is necessary, reduce the dose of pralsetinib to 200 mg once daily for patients taking a daily dose of 400 mg or 300 mg, and to 100 mg once daily for patients taking a daily dose of 200 mg. Pralsetinib is a CYP3A and P-gp substrate and clarithromycin is a combined strong CYP3A and P-gp inhibitor. Coadministration with a combined strong CYP3A and P-gp inhibitor is predicted to increase the overall exposure of pralsetinib by 251%.
Apalutamide: (Major) Avoid coadministration of apalutamide with pralsetinib due to the risk of decreased pralsetinib exposure which may reduce its efficacy. If concomitant use is unavoidable, double the current dose of pralsetinib starting on day 7 of coadministration. After apalutamide has been discontinued for at least 14 days, resume the pralsetinib dose taken prior to initiating apalutamide. Pralsetinib is a CYP3A substrate and apalutamide is a strong CYP3A inducer. Coadministration with another strong CYP3A inducer decreased the pralsetinib AUC by 68%.
Aprepitant, Fosaprepitant: (Major) Avoid concomitant use of aprepitant/fosaprepitant with pralsetinib due to the risk of increased pralsetinib exposure which may increase the risk of adverse reactions. If concomitant use is necessary, reduce the daily dose of pralsetinib by 100 mg. Pralsetinib is a CYP3A substrate and aprepitant/fosaprepitant is a moderate CYP3A inhibitor. Coadministration with a moderate CYP3A inhibitor is predicted to increase the overall exposure of pralsetinib by 71%.
Asciminib: (Major) Avoid concomitant use of asciminib with pralsetinib due to the risk of increased pralsetinib exposure which may increase the risk of adverse reactions. If concomitant use is necessary, reduce the daily dose of pralsetinib by 100 mg. Pralsetinib is a P-gp substrate and asciminib is a P-gp inhibitor. Coadministration with another P-gp inhibitor increased the overall exposure of pralsetinib by 81%.
Atazanavir: (Major) Avoid concomitant use of atazanavir with pralsetinib due to the risk of increased pralsetinib exposure which may increase the risk of adverse reactions. If concomitant use is necessary, reduce the daily dose of pralsetinib by 100 mg. Pralsetinib is a CYP3A substrate and atazanavir is a strong CYP3A inhibitor. Coadministration with a strong CYP3A inhibitor is predicted to increase the overall exposure of pralsetinib by 122%.
Atazanavir; Cobicistat: (Major) Avoid concomitant use of atazanavir with pralsetinib due to the risk of increased pralsetinib exposure which may increase the risk of adverse reactions. If concomitant use is necessary, reduce the daily dose of pralsetinib by 100 mg. Pralsetinib is a CYP3A substrate and atazanavir is a strong CYP3A inhibitor. Coadministration with a strong CYP3A inhibitor is predicted to increase the overall exposure of pralsetinib by 122%. (Major) Avoid concomitant use of cobicistat and pralsetinib due to the risk of increased pralsetinib exposure which may increase the risk of adverse reactions. If concomitant use is necessary, reduce the dose of pralsetinib to 200 mg once daily for patients taking a daily dose of 400 mg or 300 mg, and to 100 mg once daily for patients taking a daily dose of 200 mg. Pralsetinib is a CYP3A and P-gp substrate and cobicistat is a combined strong CYP3A and P-gp inhibitor. Coadministration with a combined strong CYP3A and P-gp inhibitor is predicted to increase the overall exposure of pralsetinib by 251%.
Belumosudil: (Major) Avoid concomitant use of belumosudil with pralsetinib due to the risk of increased pralsetinib exposure which may increase the risk of adverse reactions. If concomitant use is necessary, reduce the daily dose of pralsetinib by 100 mg. Pralsetinib is a P-gp substrate and belumosudil is a P-gp inhibitor. Coadministration with another P-gp inhibitor increased the overall exposure of pralsetinib by 1.8-fold.
Berotralstat: (Major) Avoid concomitant use of berotralstat with pralsetinib due to the risk of increased pralsetinib exposure which may increase the risk of adverse reactions. If concomitant use is necessary, reduce the daily dose of pralsetinib by 100 mg. Pralsetinib is a CYP3A substrate and berotralstat is a moderate CYP3A inhibitor. Coadministration with a moderate CYP3A inhibitor is predicted to increase the overall exposure of pralsetinib by 71%.
Bexarotene: (Major) Avoid concurrent use of bexarotene and pralsetinib due to the risk of decreased pralsetinib exposure which may reduce its efficacy. If concomitant use is necessary, increase the current dose of pralsetinib (400 mg to 600 mg; 300 mg to 500 mg; 200 mg to 300 mg) starting on day 7 of coadministration. Pralsetinib is a CYP3A substrate and bexarotene is a moderate CYP3A inducer. Coadministration with another moderate CYP3A inducer decreased the pralsetinib overall exposure by 45%.
Bosentan: (Major) Avoid concurrent use of bosentan and pralsetinib due to the risk of decreased pralsetinib exposure which may reduce its efficacy. If concomitant use is necessary, increase the current dose of pralsetinib (400 mg to 600 mg; 300 mg to 500 mg; 200 mg to 300 mg) starting on day 7 of coadministration. Pralsetinib is a CYP3A substrate and bosentan is a moderate CYP3A inducer. Coadministration with another moderate CYP3A inducer decreased the pralsetinib overall exposure by 45%.
Brigatinib: (Major) Avoid concomitant use of brigatinib with pralsetinib due to the risk of increased pralsetinib exposure which may increase the risk of adverse reactions. If concomitant use is necessary, reduce the daily dose of pralsetinib by 100 mg. Pralsetinib is a P-gp substrate and brigatinib is a P-gp inhibitor. Coadministration with another P-gp inhibitor increased the overall exposure of pralsetinib by 81%.
Cabozantinib: (Major) Avoid concomitant use of cabozantinib with pralsetinib due to the risk of increased pralsetinib exposure which may increase the risk of adverse reactions. If concomitant use is necessary, reduce the daily dose of pralsetinib by 100 mg. Pralsetinib is a P-gp substrate and cabozantinib is a P-gp inhibitor. Coadministration with another P-gp inhibitor increased the overall exposure of pralsetinib by 81%.
Cannabidiol: (Major) Avoid concomitant use of cannabidiol with pralsetinib due to the risk of increased pralsetinib exposure which may increase the risk of adverse reactions. If concomitant use is necessary, reduce the daily dose of pralsetinib by 100 mg. Pralsetinib is a P-gp substrate and cannabidiol is a P-gp inhibitor. Coadministration with another P-gp inhibitor increased the overall exposure of pralsetinib by 81%.
Capmatinib: (Major) Avoid concomitant use of capmatinib with pralsetinib due to the risk of increased pralsetinib exposure which may increase the risk of adverse reactions. If concomitant use is necessary, reduce the daily dose of pralsetinib by 100 mg. Pralsetinib is a P-gp substrate and capmatinib is a P-gp inhibitor. Coadministration with another P-gp inhibitor increased the overall exposure of pralsetinib by 81%.
Carbamazepine: (Major) Avoid coadministration of carbamazepine with pralsetinib due to the risk of decreased pralsetinib exposure which may reduce its efficacy. If concomitant use is unavoidable, double the current dose of pralsetinib starting on day 7 of coadministration. After carbamazepine has been discontinued for at least 14 days, resume the pralsetinib dose taken prior to initiating carbamazepine. Pralsetinib is a CYP3A substrate and carbamazepine is a strong CYP3A inducer. Coadministration with another strong CYP3A inducer decreased the pralsetinib AUC by 68%.
Carvedilol: (Major) Avoid concomitant use of carvedilol with pralsetinib due to the risk of increased pralsetinib exposure which may increase the risk of adverse reactions. If concomitant use is necessary, reduce the daily dose of pralsetinib by 100 mg. Pralsetinib is a P-gp substrate and carvedilol is a P-gp inhibitor. Coadministration with another P-gp inhibitor increased the overall exposure of pralsetinib by 81%.
Cenobamate: (Major) Avoid concurrent use of cenobamate and pralsetinib due to the risk of decreased pralsetinib exposure which may reduce its efficacy. If concomitant use is necessary, increase the current dose of pralsetinib (400 mg to 600 mg; 300 mg to 500 mg; 200 mg to 300 mg) starting on day 7 of coadministration. Pralsetinib is a CYP3A substrate and cenobamate is a moderate CYP3A inducer. Coadministration with another moderate CYP3A inducer decreased the pralsetinib overall exposure by 45%.
Ceritinib: (Major) Avoid concomitant use of ceritinib with pralsetinib due to the risk of increased pralsetinib exposure which may increase the risk of adverse reactions. If concomitant use is necessary, reduce the daily dose of pralsetinib by 100 mg. Pralsetinib is a CYP3A substrate and ceritinib is a strong CYP3A inhibitor. Coadministration with a strong CYP3A inhibitor is predicted to increase the overall exposure of pralsetinib by 122%.
Chloramphenicol: (Major) Avoid concomitant use of chloramphenicol with pralsetinib due to the risk of increased pralsetinib exposure which may increase the risk of adverse reactions. If concomitant use is necessary, reduce the daily dose of pralsetinib by 100 mg. Pralsetinib is a CYP3A substrate and chloramphenicol is a strong CYP3A inhibitor. Coadministration with a strong CYP3A inhibitor is predicted to increase the overall exposure of pralsetinib by 122%.
Cholera Vaccine: (Moderate) Patients receiving immunosuppressant medications may have a diminished response to the live cholera vaccine. When feasible, administer indicated vaccines prior to initiating immunosuppressant medications. Counsel patients receiving immunosuppressant medications about the possibility of a diminished vaccine response and to continue to follow precautions to avoid exposure to cholera bacteria after receiving the vaccine.
Ciprofloxacin: (Major) Avoid concomitant use of ciprofloxacin with pralsetinib due to the risk of increased pralsetinib exposure which may increase the risk of adverse reactions. If concomitant use is necessary, reduce the daily dose of pralsetinib by 100 mg. Pralsetinib is a CYP3A substrate and ciprofloxacin is a moderate CYP3A inhibitor. Coadministration with a moderate CYP3A inhibitor is predicted to increase the overall exposure of pralsetinib by 71%.
Clarithromycin: (Major) Avoid concomitant use of clarithromycin and pralsetinib due to the risk of increased pralsetinib exposure which may increase the risk of adverse reactions. If concomitant use is necessary, reduce the dose of pralsetinib to 200 mg once daily for patients taking a daily dose of 400 mg or 300 mg, and to 100 mg once daily for patients taking a daily dose of 200 mg. Pralsetinib is a CYP3A and P-gp substrate and clarithromycin is a combined strong CYP3A and P-gp inhibitor. Coadministration with a combined strong CYP3A and P-gp inhibitor is predicted to increase the overall exposure of pralsetinib by 251%.
Cobicistat: (Major) Avoid concomitant use of cobicistat and pralsetinib due to the risk of increased pralsetinib exposure which may increase the risk of adverse reactions. If concomitant use is necessary, reduce the dose of pralsetinib to 200 mg once daily for patients taking a daily dose of 400 mg or 300 mg, and to 100 mg once daily for patients taking a daily dose of 200 mg. Pralsetinib is a CYP3A and P-gp substrate and cobicistat is a combined strong CYP3A and P-gp inhibitor. Coadministration with a combined strong CYP3A and P-gp inhibitor is predicted to increase the overall exposure of pralsetinib by 251%.
Conivaptan: (Major) Avoid concomitant use of conivaptan with pralsetinib due to the risk of increased pralsetinib exposure which may increase the risk of adverse reactions. If concomitant use is necessary, reduce the daily dose of pralsetinib by 100 mg. Pralsetinib is a CYP3A and P-gp substrate and conivaptan is a combined moderate CYP3A and P-gp inhibitor. Coadministration with another combined moderate CYP3A and P-gp inhibitor increased the overall exposure of pralsetinib by 108%.
Crizotinib: (Major) Avoid concomitant use of crizotinib with pralsetinib due to the risk of increased pralsetinib exposure which may increase the risk of adverse reactions. If concomitant use is necessary, reduce the daily dose of pralsetinib by 100 mg. Pralsetinib is a CYP3A substrate and crizotinib is a moderate CYP3A inhibitor. Coadministration with a moderate CYP3A inhibitor is predicted to increase the overall exposure of pralsetinib by 71%.
Cyclosporine: (Major) Avoid concomitant use of cyclosporine with pralsetinib due to the risk of increased pralsetinib exposure which may increase the risk of adverse reactions. If concomitant use is necessary, reduce the daily dose of pralsetinib by 100 mg. Pralsetinib is a CYP3A and P-gp substrate and cyclosporine is a combined moderate CYP3A and P-gp inhibitor. Coadministration increased the overall exposure of pralsetinib by 81%.
Dabrafenib: (Major) Avoid concurrent use of dabrafenib and pralsetinib due to the risk of decreased pralsetinib exposure which may reduce its efficacy. If concomitant use is necessary, increase the current dose of pralsetinib (400 mg to 600 mg; 300 mg to 500 mg; 200 mg to 300 mg) starting on day 7 of coadministration. Pralsetinib is a CYP3A substrate and dabrafenib is a moderate CYP3A inducer. Coadministration with another moderate CYP3A inducer decreased the pralsetinib overall exposure by 45%.
Danazol: (Major) Avoid concomitant use of danazol with pralsetinib due to the risk of increased pralsetinib exposure which may increase the risk of adverse reactions. If concomitant use is necessary, reduce the daily dose of pralsetinib by 100 mg. Pralsetinib is a CYP3A substrate and danazol is a moderate CYP3A inhibitor. Coadministration with a moderate CYP3A inhibitor is predicted to increase the overall exposure of pralsetinib by 71%.
Danicopan: (Major) Avoid concomitant use of danicopan with pralsetinib due to the risk of increased pralsetinib exposure which may increase the risk of adverse reactions. If concomitant use is necessary, reduce the daily dose of pralsetinib by 100 mg. Pralsetinib is a P-gp substrate and danicopan is a P-gp inhibitor. Coadministration with another P-gp inhibitor increased the overall exposure of pralsetinib by 1.8-fold.
Daridorexant: (Major) Avoid concomitant use of daridorexant with pralsetinib due to the risk of increased pralsetinib exposure which may increase the risk of adverse reactions. If concomitant use is necessary, reduce the daily dose of pralsetinib by 100 mg. Pralsetinib is a P-gp substrate and daridorexant is a P-gp inhibitor. Coadministration with another P-gp inhibitor increased the overall exposure of pralsetinib by 81%.
Darunavir: (Major) Avoid concomitant use of darunavir with pralsetinib due to the risk of increased pralsetinib exposure which may increase the risk of adverse reactions. If concomitant use is necessary, reduce the daily dose of pralsetinib by 100 mg. Pralsetinib is a CYP3A substrate and darunavir is a strong CYP3A inhibitor. Coadministration with a strong CYP3A inhibitor is predicted to increase the overall exposure of pralsetinib by 122%.
Darunavir; Cobicistat: (Major) Avoid concomitant use of cobicistat and pralsetinib due to the risk of increased pralsetinib exposure which may increase the risk of adverse reactions. If concomitant use is necessary, reduce the dose of pralsetinib to 200 mg once daily for patients taking a daily dose of 400 mg or 300 mg, and to 100 mg once daily for patients taking a daily dose of 200 mg. Pralsetinib is a CYP3A and P-gp substrate and cobicistat is a combined strong CYP3A and P-gp inhibitor. Coadministration with a combined strong CYP3A and P-gp inhibitor is predicted to increase the overall exposure of pralsetinib by 251%. (Major) Avoid concomitant use of darunavir with pralsetinib due to the risk of increased pralsetinib exposure which may increase the risk of adverse reactions. If concomitant use is necessary, reduce the daily dose of pralsetinib by 100 mg. Pralsetinib is a CYP3A substrate and darunavir is a strong CYP3A inhibitor. Coadministration with a strong CYP3A inhibitor is predicted to increase the overall exposure of pralsetinib by 122%.
Darunavir; Cobicistat; Emtricitabine; Tenofovir alafenamide: (Major) Avoid concomitant use of cobicistat and pralsetinib due to the risk of increased pralsetinib exposure which may increase the risk of adverse reactions. If concomitant use is necessary, reduce the dose of pralsetinib to 200 mg once daily for patients taking a daily dose of 400 mg or 300 mg, and to 100 mg once daily for patients taking a daily dose of 200 mg. Pralsetinib is a CYP3A and P-gp substrate and cobicistat is a combined strong CYP3A and P-gp inhibitor. Coadministration with a combined strong CYP3A and P-gp inhibitor is predicted to increase the overall exposure of pralsetinib by 251%. (Major) Avoid concomitant use of darunavir with pralsetinib due to the risk of increased pralsetinib exposure which may increase the risk of adverse reactions. If concomitant use is necessary, reduce the daily dose of pralsetinib by 100 mg. Pralsetinib is a CYP3A substrate and darunavir is a strong CYP3A inhibitor. Coadministration with a strong CYP3A inhibitor is predicted to increase the overall exposure of pralsetinib by 122%.
Delavirdine: (Major) Avoid concomitant use of delavirdine with pralsetinib due to the risk of increased pralsetinib exposure which may increase the risk of adverse reactions. If concomitant use is necessary, reduce the daily dose of pralsetinib by 100 mg. Pralsetinib is a CYP3A substrate and delavirdine is a strong CYP3A inhibitor. Coadministration with a strong CYP3A inhibitor is predicted to increase the overall exposure of pralsetinib by 122%.
Dengue Tetravalent Vaccine, Live: (Moderate) Patients receiving immunosuppressant medications may have a diminished response to the dengue virus vaccine. When feasible, administer indicated vaccines at least 2 weeks prior to initiating immunosuppressant medications. If vaccine administration is necessary, consider revaccination following restoration of immune competence. Counsel patients receiving immunosuppressant medications about the possibility of a diminished vaccine response and to continue to follow precautions to avoid exposure after receiving the vaccine.
Dextromethorphan; Quinidine: (Major) Avoid concomitant use of quinidine with pralsetinib due to the risk of increased pralsetinib exposure which may increase the risk of adverse reactions. If concomitant use is necessary, reduce the daily dose of pralsetinib by 100 mg. Pralsetinib is a P-gp substrate and quinidine is a P-gp inhibitor. Coadministration with another P-gp inhibitor increased the overall exposure of pralsetinib by 81%.
Diltiazem: (Major) Avoid concomitant use of diltiazem with pralsetinib due to the risk of increased pralsetinib exposure which may increase the risk of adverse reactions. If concomitant use is necessary, reduce the daily dose of pralsetinib by 100 mg. Pralsetinib is a CYP3A substrate and diltiazem is a moderate CYP3A inhibitor. Coadministration with a moderate CYP3A inhibitor is predicted to increase the overall exposure of pralsetinib by 71%.
Dronedarone: (Major) Avoid concomitant use of dronedarone with pralsetinib due to the risk of increased pralsetinib exposure which may increase the risk of adverse reactions. If concomitant use is necessary, reduce the daily dose of pralsetinib by 100 mg. Pralsetinib is a CYP3A and P-gp substrate and dronedarone is a combined moderate CYP3A and P-gp inhibitor. Coadministration with another combined moderate CYP3A and P-gp inhibitor increased the overall exposure of pralsetinib by 108%.
Duvelisib: (Major) Avoid concomitant use of duvelisib with pralsetinib due to the risk of increased pralsetinib exposure which may increase the risk of adverse reactions. If concomitant use is necessary, reduce the daily dose of pralsetinib by 100 mg. Pralsetinib is a CYP3A substrate and duvelisib is a moderate CYP3A inhibitor. Coadministration with a moderate CYP3A inhibitor is predicted to increase the overall exposure of pralsetinib by 71%.
Efavirenz: (Major) Avoid concurrent use of efavirenz and pralsetinib due to the risk of decreased pralsetinib exposure which may reduce its efficacy. If concomitant use is necessary, increase the current dose of pralsetinib (400 mg to 600 mg; 300 mg to 500 mg; 200 mg to 300 mg) starting on day 7 of coadministration. Pralsetinib is a CYP3A substrate and efavirenz is a moderate CYP3A inducer. Coadministration decreased pralsetinib overall exposure by 45%.
Efavirenz; Emtricitabine; Tenofovir Disoproxil Fumarate: (Major) Avoid concurrent use of efavirenz and pralsetinib due to the risk of decreased pralsetinib exposure which may reduce its efficacy. If concomitant use is necessary, increase the current dose of pralsetinib (400 mg to 600 mg; 300 mg to 500 mg; 200 mg to 300 mg) starting on day 7 of coadministration. Pralsetinib is a CYP3A substrate and efavirenz is a moderate CYP3A inducer. Coadministration decreased pralsetinib overall exposure by 45%.
Efavirenz; Lamivudine; Tenofovir Disoproxil Fumarate: (Major) Avoid concurrent use of efavirenz and pralsetinib due to the risk of decreased pralsetinib exposure which may reduce its efficacy. If concomitant use is necessary, increase the current dose of pralsetinib (400 mg to 600 mg; 300 mg to 500 mg; 200 mg to 300 mg) starting on day 7 of coadministration. Pralsetinib is a CYP3A substrate and efavirenz is a moderate CYP3A inducer. Coadministration decreased pralsetinib overall exposure by 45%.
Elacestrant: (Major) Avoid concomitant use of elacestrant with pralsetinib due to the risk of increased pralsetinib exposure which may increase the risk of adverse reactions. If concomitant use is necessary, reduce the daily dose of pralsetinib by 100 mg. Pralsetinib is a P-gp substrate and elacestrant is a P-gp inhibitor. Coadministration with another P-gp inhibitor increased the overall exposure of pralsetinib by 81%.
Elagolix: (Major) Avoid concomitant use of elagolix with pralsetinib due to the risk of altered pralsetinib exposure which may reduce its efficacy or increase the risk of adverse reactions. Pralsetinib is a CYP3A and P-gp substrate and elagolix is a moderate CYP3A inducer and P-gp inhibitor. Coadministration with another moderate CYP3A inducer decreased the pralsetinib overall exposure by 45% and coadministration with another P-gp inhibitor increased the overall exposure of pralsetinib by 81%.
Elagolix; Estradiol; Norethindrone acetate: (Major) Avoid concomitant use of elagolix with pralsetinib due to the risk of altered pralsetinib exposure which may reduce its efficacy or increase the risk of adverse reactions. Pralsetinib is a CYP3A and P-gp substrate and elagolix is a moderate CYP3A inducer and P-gp inhibitor. Coadministration with another moderate CYP3A inducer decreased the pralsetinib overall exposure by 45% and coadministration with another P-gp inhibitor increased the overall exposure of pralsetinib by 81%.
Elexacaftor; tezacaftor; ivacaftor: (Major) Avoid concomitant use of ivacaftor with pralsetinib due to the risk of increased pralsetinib exposure which may increase the risk of adverse reactions. If concomitant use is necessary, reduce the daily dose of pralsetinib by 100 mg. Pralsetinib is a P-gp substrate and ivacaftor is a P-gp inhibitor. Coadministration with another P-gp inhibitor increased the overall exposure of pralsetinib by 81%.
Eliglustat: (Major) Avoid concomitant use of eliglustat with pralsetinib due to the risk of increased pralsetinib exposure which may increase the risk of adverse reactions. If concomitant use is necessary, reduce the daily dose of pralsetinib by 100 mg. Pralsetinib is a P-gp substrate and eliglustat is a P-gp inhibitor. Coadministration with another P-gp inhibitor increased the overall exposure of pralsetinib by 81%.
Elvitegravir; Cobicistat; Emtricitabine; Tenofovir Alafenamide: (Major) Avoid concomitant use of cobicistat and pralsetinib due to the risk of increased pralsetinib exposure which may increase the risk of adverse reactions. If concomitant use is necessary, reduce the dose of pralsetinib to 200 mg once daily for patients taking a daily dose of 400 mg or 300 mg, and to 100 mg once daily for patients taking a daily dose of 200 mg. Pralsetinib is a CYP3A and P-gp substrate and cobicistat is a combined strong CYP3A and P-gp inhibitor. Coadministration with a combined strong CYP3A and P-gp inhibitor is predicted to increase the overall exposure of pralsetinib by 251%.
Elvitegravir; Cobicistat; Emtricitabine; Tenofovir Disoproxil Fumarate: (Major) Avoid concomitant use of cobicistat and pralsetinib due to the risk of increased pralsetinib exposure which may increase the risk of adverse reactions. If concomitant use is necessary, reduce the dose of pralsetinib to 200 mg once daily for patients taking a daily dose of 400 mg or 300 mg, and to 100 mg once daily for patients taking a daily dose of 200 mg. Pralsetinib is a CYP3A and P-gp substrate and cobicistat is a combined strong CYP3A and P-gp inhibitor. Coadministration with a combined strong CYP3A and P-gp inhibitor is predicted to increase the overall exposure of pralsetinib by 251%.
Enasidenib: (Major) Avoid concomitant use of enasidenib with pralsetinib due to the risk of increased pralsetinib exposure which may increase the risk of adverse reactions. If concomitant use is necessary, reduce the daily dose of pralsetinib by 100 mg. Pralsetinib is a P-gp substrate and enasidenib is a P-gp inhibitor. Coadministration with another P-gp inhibitor increased the overall exposure of pralsetinib by 81%.
Encorafenib: (Major) Avoid concurrent use of encorafenib and pralsetinib due to the risk of decreased pralsetinib exposure which may reduce its efficacy. If concomitant use is necessary, double the current dose of pralsetinib starting on day 7 of coadministration. After encorafenib has been discontinued for at least 14 days, resume the pralsetinib dose taken prior to initiating encorafenib. Pralsetinib is a CYP3A substrate and encorafenib is a strong CYP3A inducer. Coadministration with another strong CYP3A inducer decreased the pralsetinib AUC by 68%.
Enzalutamide: (Major) Avoid coadministration of enzalutamide with pralsetinib due to the risk of decreased pralsetinib exposure which may reduce its efficacy. If concomitant use is unavoidable, double the current dose of pralsetinib starting on day 7 of coadministration. After enzalutamide has been discontinued for at least 14 days, resume the pralsetinib dose taken prior to initiating enzalutamide. Pralsetinib is a CYP3A substrate and enzalutamide is a strong CYP3A inducer. Coadministration with another strong CYP3A inducer decreased the pralsetinib AUC by 68%.
Erdafitinib: (Major) Avoid concomitant use of erdafitinib with pralsetinib due to the risk of increased pralsetinib exposure which may increase the risk of adverse reactions. If concomitant use is necessary, reduce the daily dose of pralsetinib by 100 mg. Pralsetinib is a P-gp substrate and erdafitinib is a P-gp inhibitor. Coadministration with another P-gp inhibitor increased the overall exposure of pralsetinib by 81%.
Erythromycin: (Major) Avoid concomitant use of erythromycin with pralsetinib due to the risk of increased pralsetinib exposure which may increase the risk of adverse reactions. If concomitant use is necessary, reduce the daily dose of pralsetinib by 100 mg. Pralsetinib is a CYP3A and P-gp substrate and erythromycin is a combined moderate CYP3A and P-gp inhibitor. Coadministration with another combined moderate CYP3A and P-gp inhibitor increased the overall exposure of pralsetinib by 108%.
Eslicarbazepine: (Major) Avoid concurrent use of eslicarbazepine and pralsetinib due to the risk of decreased pralsetinib exposure which may reduce its efficacy. If concomitant use is necessary, increase the current dose of pralsetinib (400 mg to 600 mg; 300 mg to 500 mg; 200 mg to 300 mg) starting on day 7 of coadministration. Pralsetinib is a CYP3A substrate and eslicarbazepine is a moderate CYP3A inducer. Coadministration with another moderate CYP3A inducer decreased the pralsetinib overall exposure by 45%.
Etravirine: (Major) Avoid concomitant use of etravirine with pralsetinib due to the risk of altered pralsetinib exposure which may reduce its efficacy or increase the risk of adverse reactions. Pralsetinib is a CYP3A and P-gp substrate and etravirine is a moderate CYP3A inducer and P-gp inhibitor. Coadministration with another moderate CYP3A inducer decreased the pralsetinib overall exposure by 45% and coadministration with another P-gp inhibitor increased the overall exposure of pralsetinib by 81%.
Fedratinib: (Major) Avoid concomitant use of fedratinib with pralsetinib due to the risk of increased pralsetinib exposure which may increase the risk of adverse reactions. If concomitant use is necessary, reduce the daily dose of pralsetinib by 100 mg. Pralsetinib is a CYP3A substrate and fedratinib is a moderate CYP3A inhibitor. Coadministration with a moderate CYP3A inhibitor is predicted to increase the overall exposure of pralsetinib by 71%.
Flibanserin: (Major) Avoid concomitant use of flibanserin with pralsetinib due to the risk of increased pralsetinib exposure which may increase the risk of adverse reactions. If concomitant use is necessary, reduce the daily dose of pralsetinib by 100 mg. Pralsetinib is a P-gp substrate and flibanserin is a P-gp inhibitor. Coadministration with another P-gp inhibitor increased the overall exposure of pralsetinib by 81%.
Fluconazole: (Major) Avoid concomitant use of fluconazole with pralsetinib due to the risk of increased pralsetinib exposure which may increase the risk of adverse reactions. If concomitant use is necessary, reduce the daily dose of pralsetinib by 100 mg. Pralsetinib is a CYP3A substrate and fluconazole is a moderate CYP3A inhibitor. Coadministration is predicted to increase the overall exposure of pralsetinib by 71%.
Fluvoxamine: (Major) Avoid concomitant use of fluvoxamine with pralsetinib due to the risk of increased pralsetinib exposure which may increase the risk of adverse reactions. If concomitant use is necessary, reduce the daily dose of pralsetinib by 100 mg. Pralsetinib is a CYP3A substrate and fluvoxamine is a moderate CYP3A inhibitor. Coadministration with a moderate CYP3A inhibitor is predicted to increase the overall exposure of pralsetinib by 71%.
Fosamprenavir: (Major) Avoid concomitant use of fosamprenavir with pralsetinib due to the risk of increased pralsetinib exposure which may increase the risk of adverse reactions. If concomitant use is necessary, reduce the daily dose of pralsetinib by 100 mg. Pralsetinib is a CYP3A substrate and fosamprenavir is a moderate CYP3A inhibitor. Coadministration with a moderate CYP3A inhibitor is predicted to increase the overall exposure of pralsetinib by 71%.
Fosphenytoin: (Major) Avoid coadministration of fosphenytoin with pralsetinib due to the risk of decreased pralsetinib exposure which may reduce its efficacy. If concomitant use is unavoidable, double the current dose of pralsetinib starting on day 7 of coadministration. After fosphenytoin has been discontinued for at least 14 days, resume the pralsetinib dose taken prior to initiating fosphenytoin. Pralsetinib is a CYP3A substrate and fosphenytoin is a strong CYP3A inducer. Coadministration with another strong CYP3A inducer decreased the pralsetinib AUC by 68%.
Fostamatinib: (Major) Avoid concomitant use of fostamatinib with pralsetinib due to the risk of increased pralsetinib exposure which may increase the risk of adverse reactions. If concomitant use is necessary, reduce the daily dose of pralsetinib by 100 mg. Pralsetinib is a P-gp substrate and fostamatinib is a P-gp inhibitor. Coadministration with another P-gp inhibitor increased the overall exposure of pralsetinib by 81%.
Futibatinib: (Major) Avoid concomitant use of futibatinib with pralsetinib due to the risk of increased pralsetinib exposure which may increase the risk of adverse reactions. If concomitant use is necessary, reduce the daily dose of pralsetinib by 100 mg. Pralsetinib is a P-gp substrate and futibatinib is a P-gp inhibitor. Coadministration with another P-gp inhibitor increased the overall exposure of pralsetinib by 81%.
Gilteritinib: (Major) Avoid concomitant use of gilteritinib with pralsetinib due to the risk of increased pralsetinib exposure which may increase the risk of adverse reactions. If concomitant use is necessary, reduce the daily dose of pralsetinib by 100 mg. Pralsetinib is a P-gp substrate and gilteritinib is a P-gp inhibitor. Coadministration with another P-gp inhibitor increased the overall exposure of pralsetinib by 81%.
Glecaprevir; Pibrentasvir: (Major) Avoid concomitant use of glecaprevir with pralsetinib due to the risk of increased pralsetinib exposure which may increase the risk of adverse reactions. If concomitant use is necessary, reduce the daily dose of pralsetinib by 100 mg. Pralsetinib is a P-gp substrate and glecaprevir is a P-gp inhibitor. Coadministration with another P-gp inhibitor increased the overall exposure of pralsetinib by 81%. (Major) Avoid concomitant use of pibrentasvir with pralsetinib due to the risk of increased pralsetinib exposure which may increase the risk of adverse reactions. If concomitant use is necessary, reduce the daily dose of pralsetinib by 100 mg. Pralsetinib is a P-gp substrate and pibrentasvir is a P-gp inhibitor. Coadministration with another P-gp inhibitor increased the overall exposure of pralsetinib by 81%.
Grapefruit juice: (Major) Have patients avoid grapefruit or grapefruit juice during pralsetinib treatment due to an increased risk of neratinib-related toxicity. Pralsetinib is a CYP3A and P-glycoprotein (P-gp) substrate and grapefruit juice is a combined P-gp and strong CYP3A inhibitor. Coadministration with another combined P-gp and strong CYP3A inhibitor increased the AUC of pralsetinib by 251%.
Ibrutinib: (Major) Avoid concomitant use of ibrutinib with pralsetinib due to the risk of increased pralsetinib exposure which may increase the risk of adverse reactions. If concomitant use is necessary, reduce the daily dose of pralsetinib by 100 mg. Pralsetinib is a P-gp substrate and ibrutinib is a P-gp inhibitor. Coadministration with another P-gp inhibitor increased the overall exposure of pralsetinib by 81%.
Idelalisib: (Major) Avoid concomitant use of idelalisib with pralsetinib due to the risk of increased pralsetinib exposure which may increase the risk of adverse reactions. If concomitant use is necessary, reduce the daily dose of pralsetinib by 100 mg. Pralsetinib is a CYP3A substrate and idelalisib is a strong CYP3A inhibitor. Coadministration with a strong CYP3A inhibitor is predicted to increase the overall exposure of pralsetinib by 122%.
Imatinib: (Major) Avoid concomitant use of imatinib with pralsetinib due to the risk of increased pralsetinib exposure which may increase the risk of adverse reactions. If concomitant use is necessary, reduce the daily dose of pralsetinib by 100 mg. Pralsetinib is a CYP3A substrate and imatinib is a moderate CYP3A inhibitor. Coadministration with a moderate CYP3A inhibitor is predicted to increase the overall exposure of pralsetinib by 71%.
Indinavir: (Major) Avoid concomitant use of indinavir with pralsetinib due to the risk of increased pralsetinib exposure which may increase the risk of adverse reactions. If concomitant use is necessary, reduce the daily dose of pralsetinib by 100 mg. Pralsetinib is a CYP3A substrate and indinavir is a strong CYP3A inhibitor. Coadministration with a strong CYP3A inhibitor is predicted to increase the overall exposure of pralsetinib by 122%.
Isavuconazonium: (Major) Avoid concomitant use of isavuconazonium with pralsetinib due to the risk of increased pralsetinib exposure which may increase the risk of adverse reactions. If concomitant use is necessary, reduce the daily dose of pralsetinib by 100 mg. Pralsetinib is a CYP3A and P-gp substrate and isavuconazonium is a combined moderate CYP3A and P-gp inhibitor. Coadministration with another combined moderate CYP3A and P-gp inhibitor increased the overall exposure of pralsetinib by 108%.
Isoniazid, INH; Pyrazinamide, PZA; Rifampin: (Major) Avoid coadministration of rifampin with pralsetinib due to the risk of decreased pralsetinib exposure which may reduce its efficacy. If concomitant use is unavoidable, double the current dose of pralsetinib starting on day 7 of coadministration. After rifampin has been discontinued for at least 14 days, resume the pralsetinib dose taken prior to initiating rifampin. Pralsetinib is a CYP3A substrate and rifampin is a strong CYP3A inducer. Coadministration with rifampin decreased the pralsetinib AUC by 68%.
Isoniazid, INH; Rifampin: (Major) Avoid coadministration of rifampin with pralsetinib due to the risk of decreased pralsetinib exposure which may reduce its efficacy. If concomitant use is unavoidable, double the current dose of pralsetinib starting on day 7 of coadministration. After rifampin has been discontinued for at least 14 days, resume the pralsetinib dose taken prior to initiating rifampin. Pralsetinib is a CYP3A substrate and rifampin is a strong CYP3A inducer. Coadministration with rifampin decreased the pralsetinib AUC by 68%.
Istradefylline: (Major) Avoid concomitant use of istradefylline with pralsetinib due to the risk of increased pralsetinib exposure which may increase the risk of adverse reactions. If concomitant use is necessary, reduce the daily dose of pralsetinib by 100 mg. Pralsetinib is a P-gp substrate and istradefylline is a P-gp inhibitor. Coadministration with another P-gp inhibitor increased the overall exposure of pralsetinib by 81%.
Itraconazole: (Major) Avoid concomitant use of itraconazole and pralsetinib due to the risk of increased pralsetinib exposure which may increase the risk of adverse reactions. If concomitant use is necessary, reduce the dose of pralsetinib to 200 mg once daily for patients taking a daily dose of 400 mg or 300 mg, and to 100 mg once daily for patients taking a daily dose of 200 mg. Pralsetinib is a CYP3A and P-gp substrate and itraconazole is a combined strong CYP3A and P-gp inhibitor. Coadministration is predicted to increase the overall exposure of pralsetinib by 251%.
Ivacaftor: (Major) Avoid concomitant use of ivacaftor with pralsetinib due to the risk of increased pralsetinib exposure which may increase the risk of adverse reactions. If concomitant use is necessary, reduce the daily dose of pralsetinib by 100 mg. Pralsetinib is a P-gp substrate and ivacaftor is a P-gp inhibitor. Coadministration with another P-gp inhibitor increased the overall exposure of pralsetinib by 81%.
Ketoconazole: (Major) Avoid concomitant use of ketoconazole and pralsetinib due to the risk of increased pralsetinib exposure which may increase the risk of adverse reactions. If concomitant use is necessary, reduce the dose of pralsetinib to 200 mg once daily for patients taking a daily dose of 400 mg or 300 mg, and to 100 mg once daily for patients taking a daily dose of 200 mg. Pralsetinib is a CYP3A and P-gp substrate and ketoconazole is a combined strong CYP3A and P-gp inhibitor. Coadministration with a combined strong CYP3A and P-gp inhibitor is predicted to increase the overall exposure of pralsetinib by 251%.
Lansoprazole; Amoxicillin; Clarithromycin: (Major) Avoid concomitant use of clarithromycin and pralsetinib due to the risk of increased pralsetinib exposure which may increase the risk of adverse reactions. If concomitant use is necessary, reduce the dose of pralsetinib to 200 mg once daily for patients taking a daily dose of 400 mg or 300 mg, and to 100 mg once daily for patients taking a daily dose of 200 mg. Pralsetinib is a CYP3A and P-gp substrate and clarithromycin is a combined strong CYP3A and P-gp inhibitor. Coadministration with a combined strong CYP3A and P-gp inhibitor is predicted to increase the overall exposure of pralsetinib by 251%.
Lapatinib: (Major) Avoid concomitant use of lapatinib with pralsetinib due to the risk of increased pralsetinib exposure which may increase the risk of adverse reactions. If concomitant use is necessary, reduce the daily dose of pralsetinib by 100 mg. Pralsetinib is a P-gp substrate and lapatinib is a P-gp inhibitor. Coadministration with another P-gp inhibitor increased the overall exposure of pralsetinib by 81%.
Lasmiditan: (Major) Avoid concomitant use of lasmiditan with pralsetinib due to the risk of increased pralsetinib exposure which may increase the risk of adverse reactions. If concomitant use is necessary, reduce the daily dose of pralsetinib by 100 mg. Pralsetinib is a P-gp substrate and lasmiditan is a P-gp inhibitor. Coadministration with another P-gp inhibitor increased the overall exposure of pralsetinib by 81%.
Ledipasvir; Sofosbuvir: (Major) Avoid concomitant use of ledipasvir with pralsetinib due to the risk of increased pralsetinib exposure which may increase the risk of adverse reactions. If concomitant use is necessary, reduce the daily dose of pralsetinib by 100 mg. Pralsetinib is a P-gp substrate and ledipasvir is a P-gp inhibitor. Coadministration with another P-gp inhibitor increased the overall exposure of pralsetinib by 81%.
Lefamulin: (Major) Avoid concomitant use of oral lefamulin with pralsetinib due to the risk of increased pralsetinib exposure which may increase the risk of adverse reactions. If concomitant use is necessary, reduce the daily dose of pralsetinib by 100 mg. Pralsetinib is a CYP3A substrate and oral lefamulin is a moderate CYP3A inhibitor; an interaction is not expected with injectable forms of lefamulin. Coadministration with a moderate CYP3A inhibitor is predicted to increase the overall exposure of pralsetinib by 71%.
Lenacapavir: (Major) Avoid concomitant use of lenacapavir with pralsetinib due to the risk of increased pralsetinib exposure which may increase the risk of adverse reactions. If concomitant use is necessary, reduce the daily dose of pralsetinib by 100 mg. Pralsetinib is a CYP3A and P-gp substrate and lenacapavir is a combined moderate CYP3A and P-gp inhibitor. Coadministration with another combined moderate CYP3A and P-gp inhibitor increased the overall exposure of pralsetinib by 108%.
Letermovir: (Major) Avoid concomitant use of letermovir with pralsetinib due to the risk of increased pralsetinib exposure which may increase the risk of adverse reactions. If concomitant use is necessary, reduce the daily dose of pralsetinib by 100 mg. Pralsetinib is a CYP3A substrate and letermovir is a moderate CYP3A inhibitor. Coadministration with a moderate CYP3A inhibitor is predicted to increase the overall exposure of pralsetinib by 71%.
Levoketoconazole: (Major) Avoid concomitant use of ketoconazole and pralsetinib due to the risk of increased pralsetinib exposure which may increase the risk of adverse reactions. If concomitant use is necessary, reduce the dose of pralsetinib to 200 mg once daily for patients taking a daily dose of 400 mg or 300 mg, and to 100 mg once daily for patients taking a daily dose of 200 mg. Pralsetinib is a CYP3A and P-gp substrate and ketoconazole is a combined strong CYP3A and P-gp inhibitor. Coadministration with a combined strong CYP3A and P-gp inhibitor is predicted to increase the overall exposure of pralsetinib by 251%.
Lomitapide: (Major) Avoid concomitant use of lomitapide with pralsetinib due to the risk of increased pralsetinib exposure which may increase the risk of adverse reactions. If concomitant use is necessary, reduce the daily dose of pralsetinib by 100 mg. Pralsetinib is a P-gp substrate and lomitapide is a P-gp inhibitor. Coadministration with another P-gp inhibitor increased the overall exposure of pralsetinib by 81%.
Lonafarnib: (Major) Avoid concomitant use of lonafarnib and pralsetinib due to the risk of increased pralsetinib exposure which may increase the risk of adverse reactions. If concomitant use is necessary, reduce the dose of pralsetinib to 200 mg once daily for patients taking a daily dose of 400 mg or 300 mg, and to 100 mg once daily for patients taking a daily dose of 200 mg. Pralsetinib is a CYP3A and P-gp substrate and lonafarnib is a combined strong CYP3A and P-gp inhibitor. Coadministration with a combined strong CYP3A and P-gp inhibitor is predicted to increase the overall exposure of pralsetinib by 251%.
Lopinavir; Ritonavir: (Major) Avoid concomitant use of ritonavir and pralsetinib due to the risk of increased pralsetinib exposure which may increase the risk of adverse reactions. If concomitant use is necessary, reduce the dose of pralsetinib to 200 mg once daily for patients taking a daily dose of 400 mg or 300 mg, and to 100 mg once daily for patients taking a daily dose of 200 mg. Pralsetinib is a CYP3A and P-gp substrate and ritonavir is a combined strong CYP3A and P-gp inhibitor. Coadministration with a combined strong CYP3A and P-gp inhibitor is predicted to increase the overall exposure of pralsetinib by 251%.
Lorlatinib: (Major) Avoid concurrent use of lorlatinib and pralsetinib due to the risk of decreased pralsetinib exposure which may reduce its efficacy. If concomitant use is necessary, increase the current dose of pralsetinib (400 mg to 600 mg; 300 mg to 500 mg; 200 mg to 300 mg) starting on day 7 of coadministration. Pralsetinib is a CYP3A substrate and lorlatinib is a moderate CYP3A inducer. Coadministration with another moderate CYP3A inducer decreased the pralsetinib overall exposure by 45%.
Lumacaftor; Ivacaftor: (Major) Avoid coadministration of lumacaftor; ivacaftor with pralsetinib due to the risk of decreased pralsetinib exposure which may reduce its efficacy. If concomitant use is unavoidable, double the current dose of pralsetinib starting on day 7 of coadministration. After lumacaftor; ivacaftor has been discontinued for at least 14 days, resume the pralsetinib dose taken prior to initiating lumacaftor; ivacaftor. Pralsetinib is a CYP3A substrate and lumacaftor; ivacaftor is a strong CYP3A inducer. Coadministration with another strong CYP3A inducer decreased the pralsetinib AUC by 68%. (Major) Avoid concomitant use of ivacaftor with pralsetinib due to the risk of increased pralsetinib exposure which may increase the risk of adverse reactions. If concomitant use is necessary, reduce the daily dose of pralsetinib by 100 mg. Pralsetinib is a P-gp substrate and ivacaftor is a P-gp inhibitor. Coadministration with another P-gp inhibitor increased the overall exposure of pralsetinib by 81%.
Lumacaftor; Ivacaftor: (Major) Avoid coadministration of lumacaftor; ivacaftor with pralsetinib due to the risk of decreased pralsetinib exposure which may reduce its efficacy. If concomitant use is unavoidable, double the current dose of pralsetinib starting on day 7 of coadministration. After lumacaftor; ivacaftor has been discontinued for at least 14 days, resume the pralsetinib dose taken prior to initiating lumacaftor; ivacaftor. Pralsetinib is a CYP3A substrate and lumacaftor; ivacaftor is a strong CYP3A inducer. Coadministration with another strong CYP3A inducer decreased the pralsetinib AUC by 68%.
Maribavir: (Major) Avoid concomitant use of maribavir with pralsetinib due to the risk of increased pralsetinib exposure which may increase the risk of adverse reactions. If concomitant use is necessary, reduce the daily dose of pralsetinib by 100 mg. Pralsetinib is a P-gp substrate and maribavir is a P-gp inhibitor. Coadministration with another P-gp inhibitor increased the overall exposure of pralsetinib by 81%.
Mavacamten: (Major) Avoid concurrent use of mavacamten and pralsetinib due to the risk of decreased pralsetinib exposure which may reduce its efficacy. If concomitant use is necessary, increase the current dose of pralsetinib (400 mg to 600 mg; 300 mg to 500 mg; 200 mg to 300 mg) starting on day 7 of coadministration. Pralsetinib is a CYP3A substrate and mavacamten is a moderate CYP3A inducer. Coadministration with another moderate CYP3A inducer decreased the pralsetinib overall exposure by 45%.
Mefloquine: (Major) Avoid concomitant use of mefloquine with pralsetinib due to the risk of increased pralsetinib exposure which may increase the risk of adverse reactions. If concomitant use is necessary, reduce the daily dose of pralsetinib by 100 mg. Pralsetinib is a P-gp substrate and mefloquine is a P-gp inhibitor. Coadministration with another P-gp inhibitor increased the overall exposure of pralsetinib by 81%.
Mifepristone: (Major) Avoid concomitant use of mifepristone with pralsetinib due to the risk of increased pralsetinib exposure which may increase the risk of adverse reactions. If concomitant use is necessary, reduce the daily dose of pralsetinib by 100 mg. Pralsetinib is a CYP3A substrate and mifepristone is a strong CYP3A inhibitor. Coadministration with a strong CYP3A inhibitor is predicted to increase the overall exposure of pralsetinib by 122%.
Mitapivat: (Major) Avoid concomitant use of mitapivat with pralsetinib due to the risk of increased pralsetinib exposure which may increase the risk of adverse reactions. If concomitant use is necessary, reduce the daily dose of pralsetinib by 100 mg. Pralsetinib is a P-gp substrate and mitapivat is a P-gp inhibitor. Coadministration with another P-gp inhibitor increased the overall exposure of pralsetinib by 81%.
Mitotane: (Major) Avoid coadministration of mitotane with pralsetinib due to the risk of decreased pralsetinib exposure which may reduce its efficacy. If concomitant use is unavoidable, double the current dose of pralsetinib starting on day 7 of coadministration. After mitotane has been discontinued for at least 14 days, resume the pralsetinib dose taken prior to initiating mitotane. Pralsetinib is a CYP3A substrate and mitotane is a strong CYP3A inducer. Coadministration with another strong CYP3A inducer decreased the pralsetinib AUC by 68%.
Nafcillin: (Major) Avoid concurrent use of nafcillin and pralsetinib due to the risk of decreased pralsetinib exposure which may reduce its efficacy. If concomitant use is necessary, increase the current dose of pralsetinib (400 mg to 600 mg; 300 mg to 500 mg; 200 mg to 300 mg) starting on day 7 of coadministration. Pralsetinib is a CYP3A substrate and nafcillin is a moderate CYP3A inducer. Coadministration with another moderate CYP3A inducer decreased the pralsetinib overall exposure by 45%.
Nefazodone: (Major) Avoid concomitant use of nefazodone with pralsetinib due to the risk of increased pralsetinib exposure which may increase the risk of adverse reactions. If concomitant use is necessary, reduce the daily dose of pralsetinib by 100 mg. Pralsetinib is a CYP3A substrate and nefazodone is a strong CYP3A inhibitor. Coadministration with a strong CYP3A inhibitor is predicted to increase the overall exposure of pralsetinib by 122%.
Nelfinavir: (Major) Avoid concomitant use of nelfinavir and pralsetinib due to the risk of increased pralsetinib exposure which may increase the risk of adverse reactions. If concomitant use is necessary, reduce the dose of pralsetinib to 200 mg once daily for patients taking a daily dose of 400 mg or 300 mg, and to 100 mg once daily for patients taking a daily dose of 200 mg. Pralsetinib is a CYP3A and P-gp substrate and nelfinavir is a combined strong CYP3A and P-gp inhibitor. Coadministration with a combined strong CYP3A and P-gp inhibitor is predicted to increase the overall exposure of pralsetinib by 251%.
Neratinib: (Major) Avoid concomitant use of neratinib with pralsetinib due to the risk of increased pralsetinib exposure which may increase the risk of adverse reactions. If concomitant use is necessary, reduce the daily dose of pralsetinib by 100 mg. Pralsetinib is a P-gp substrate and neratinib is a P-gp inhibitor. Coadministration with another P-gp inhibitor increased the overall exposure of pralsetinib by 81%.
Netupitant, Fosnetupitant; Palonosetron: (Major) Avoid concomitant use of netupitant with pralsetinib due to the risk of increased pralsetinib exposure which may increase the risk of adverse reactions. If concomitant use is necessary, reduce the daily dose of pralsetinib by 100 mg. Pralsetinib is a CYP3A substrate and netupitant is a moderate CYP3A inhibitor. Coadministration with a moderate CYP3A inhibitor is predicted to increase the overall exposure of pralsetinib by 71%.
Nilotinib: (Major) Avoid concomitant use of nilotinib with pralsetinib due to the risk of increased pralsetinib exposure which may increase the risk of adverse reactions. If concomitant use is necessary, reduce the daily dose of pralsetinib by 100 mg. Pralsetinib is a CYP3A substrate and nilotinib is a moderate CYP3A inhibitor. Coadministration with a moderate CYP3A inhibitor is predicted to increase the overall exposure of pralsetinib by 71%.
Nirmatrelvir; Ritonavir: (Major) Avoid concomitant use of ritonavir and pralsetinib due to the risk of increased pralsetinib exposure which may increase the risk of adverse reactions. If concomitant use is necessary, reduce the dose of pralsetinib to 200 mg once daily for patients taking a daily dose of 400 mg or 300 mg, and to 100 mg once daily for patients taking a daily dose of 200 mg. Pralsetinib is a CYP3A and P-gp substrate and ritonavir is a combined strong CYP3A and P-gp inhibitor. Coadministration with a combined strong CYP3A and P-gp inhibitor is predicted to increase the overall exposure of pralsetinib by 251%.
Nirogacestat: (Major) Avoid concomitant use of nirogacestat with pralsetinib due to the risk of increased pralsetinib exposure which may increase the risk of adverse reactions. If concomitant use is necessary, reduce the daily dose of pralsetinib by 100 mg. Pralsetinib is a CYP3A substrate and nirogacestat is a moderate CYP3A inhibitor. Coadministration with a moderate CYP3A inhibitor is predicted to increase the overall exposure of pralsetinib by 71%.
Omeprazole; Amoxicillin; Rifabutin: (Major) Avoid concurrent use of rifabutin and pralsetinib due to the risk of decreased pralsetinib exposure which may reduce its efficacy. If concomitant use is necessary, increase the current dose of pralsetinib (400 mg to 600 mg; 300 mg to 500 mg; 200 mg to 300 mg) starting on day 7 of coadministration. Pralsetinib is a CYP3A substrate and rifabutin is a moderate CYP3A inducer. Coadministration with another moderate CYP3A inducer decreased the pralsetinib overall exposure by 45%.
Osimertinib: (Major) Avoid concomitant use of osimertinib with pralsetinib due to the risk of increased pralsetinib exposure which may increase the risk of adverse reactions. If concomitant use is necessary, reduce the daily dose of pralsetinib by 100 mg. Pralsetinib is a P-gp substrate and osimertinib is a P-gp inhibitor. Coadministration with another P-gp inhibitor increased the overall exposure of pralsetinib by 81%.
Pacritinib: (Major) Avoid concomitant use of pacritinib with pralsetinib due to the risk of increased pralsetinib exposure which may increase the risk of adverse reactions. If concomitant use is necessary, reduce the daily dose of pralsetinib by 100 mg. Pralsetinib is a P-gp substrate and pacritinib is a P-gp inhibitor. Coadministration with another P-gp inhibitor increased the overall exposure of pralsetinib by 81%.
Pexidartinib: (Major) Avoid concurrent use of pexidartinib and pralsetinib due to the risk of decreased pralsetinib exposure which may reduce its efficacy. If concomitant use is necessary, increase the current dose of pralsetinib (400 mg to 600 mg; 300 mg to 500 mg; 200 mg to 300 mg) starting on day 7 of coadministration. Pralsetinib is a CYP3A substrate and pexidartinib is a moderate CYP3A inducer. Coadministration with another moderate CYP3A inducer decreased the pralsetinib overall exposure by 45%.
Phenobarbital: (Major) Avoid coadministration of phenobarbital with pralsetinib due to the risk of decreased pralsetinib exposure which may reduce its efficacy. If concomitant use is unavoidable, double the current dose of pralsetinib starting on day 7 of coadministration. After phenobarbital has been discontinued for at least 14 days, resume the pralsetinib dose taken prior to initiating phenobarbital. Pralsetinib is a CYP3A substrate and phenobarbital is a strong CYP3A inducer. Coadministration with another strong CYP3A inducer decreased the pralsetinib AUC by 68%.
Phenobarbital; Hyoscyamine; Atropine; Scopolamine: (Major) Avoid coadministration of phenobarbital with pralsetinib due to the risk of decreased pralsetinib exposure which may reduce its efficacy. If concomitant use is unavoidable, double the current dose of pralsetinib starting on day 7 of coadministration. After phenobarbital has been discontinued for at least 14 days, resume the pralsetinib dose taken prior to initiating phenobarbital. Pralsetinib is a CYP3A substrate and phenobarbital is a strong CYP3A inducer. Coadministration with another strong CYP3A inducer decreased the pralsetinib AUC by 68%.
Phenytoin: (Major) Avoid coadministration of phenytoin with pralsetinib due to the risk of decreased pralsetinib exposure which may reduce its efficacy. If concomitant use is unavoidable, double the current dose of pralsetinib starting on day 7 of coadministration. After phenytoin has been discontinued for at least 14 days, resume the pralsetinib dose taken prior to initiating phenytoin. Pralsetinib is a CYP3A substrate and phenytoin is a strong CYP3A inducer. Coadministration with another strong CYP3A inducer decreased the pralsetinib AUC by 68%.
Pirtobrutinib: (Major) Avoid concomitant use of pirtobrutinib with pralsetinib due to the risk of increased pralsetinib exposure which may increase the risk of adverse reactions. If concomitant use is necessary, reduce the daily dose of pralsetinib by 100 mg. Pralsetinib is a P-gp substrate and pirtobrutinib is a P-gp inhibitor. Coadministration with another P-gp inhibitor increased the overall exposure of pralsetinib by 81%.
Posaconazole: (Major) Avoid concomitant use of posaconazole and pralsetinib due to the risk of increased pralsetinib exposure which may increase the risk of adverse reactions. If concomitant use is necessary, reduce the dose of pralsetinib to 200 mg once daily for patients taking a daily dose of 400 mg or 300 mg, and to 100 mg once daily for patients taking a daily dose of 200 mg. Pralsetinib is a CYP3A and P-gp substrate and posaconazole is a combined strong CYP3A and P-gp inhibitor. Coadministration with a combined strong CYP3A and P-gp inhibitor is predicted to increase the overall exposure of pralsetinib by 251%.
Pretomanid: (Major) Avoid concomitant use of pretomanid with pralsetinib due to the risk of increased pralsetinib exposure which may increase the risk of adverse reactions. If concomitant use is necessary, reduce the daily dose of pralsetinib by 100 mg. Pralsetinib is a P-gp substrate and pretomanid is a P-gp inhibitor. Coadministration with another P-gp inhibitor increased the overall exposure of pralsetinib by 81%.
Primidone: (Major) Avoid coadministration of primidone with pralsetinib due to the risk of decreased pralsetinib exposure which may reduce its efficacy. If concomitant use is unavoidable, double the current dose of pralsetinib starting on day 7 of coadministration. After primidone has been discontinued for at least 14 days, resume the pralsetinib dose taken prior to initiating primidone. Pralsetinib is a CYP3A substrate and primidone is a strong CYP3A inducer. Coadministration with another strong CYP3A inducer decreased the pralsetinib AUC by 68%.
Propafenone: (Major) Avoid concomitant use of propafenone with pralsetinib due to the risk of increased pralsetinib exposure which may increase the risk of adverse reactions. If concomitant use is necessary, reduce the daily dose of pralsetinib by 100 mg. Pralsetinib is a P-gp substrate and propafenone is a P-gp inhibitor. Coadministration with another P-gp inhibitor increased the overall exposure of pralsetinib by 81%.
Quinidine: (Major) Avoid concomitant use of quinidine with pralsetinib due to the risk of increased pralsetinib exposure which may increase the risk of adverse reactions. If concomitant use is necessary, reduce the daily dose of pralsetinib by 100 mg. Pralsetinib is a P-gp substrate and quinidine is a P-gp inhibitor. Coadministration with another P-gp inhibitor increased the overall exposure of pralsetinib by 81%.
Quinine: (Major) Avoid concomitant use of quinine with pralsetinib due to the risk of increased pralsetinib exposure which may increase the risk of adverse reactions. If concomitant use is necessary, reduce the daily dose of pralsetinib by 100 mg. Pralsetinib is a P-gp substrate and quinine is a P-gp inhibitor. Coadministration with another P-gp inhibitor increased the overall exposure of pralsetinib by 81%.
Ranolazine: (Major) Avoid concomitant use of ranolazine with pralsetinib due to the risk of increased pralsetinib exposure which may increase the risk of adverse reactions. If concomitant use is necessary, reduce the daily dose of pralsetinib by 100 mg. Pralsetinib is a P-gp substrate and ranolazine is a P-gp inhibitor. Coadministration with another P-gp inhibitor increased the overall exposure of pralsetinib by 81%.
Repotrectinib: (Major) Avoid concurrent use of repotrectinib and pralsetinib due to the risk of decreased pralsetinib exposure which may reduce its efficacy. If concomitant use is necessary, increase the current dose of pralsetinib (400 mg to 600 mg; 300 mg to 500 mg; 200 mg to 300 mg) starting on day 7 of coadministration. Pralsetinib is a CYP3A substrate and repotrectinib is a moderate CYP3A inducer. Coadministration with another moderate CYP3A inducer decreased the pralsetinib overall exposure by 45%.
Ribociclib: (Major) Avoid concomitant use of ribociclib with pralsetinib due to the risk of increased pralsetinib exposure which may increase the risk of adverse reactions. If concomitant use is necessary, reduce the daily dose of pralsetinib by 100 mg. Pralsetinib is a CYP3A substrate and ribociclib is a strong CYP3A inhibitor. Coadministration with a strong CYP3A inhibitor is predicted to increase the overall exposure of pralsetinib by 122%.
Ribociclib; Letrozole: (Major) Avoid concomitant use of ribociclib with pralsetinib due to the risk of increased pralsetinib exposure which may increase the risk of adverse reactions. If concomitant use is necessary, reduce the daily dose of pralsetinib by 100 mg. Pralsetinib is a CYP3A substrate and ribociclib is a strong CYP3A inhibitor. Coadministration with a strong CYP3A inhibitor is predicted to increase the overall exposure of pralsetinib by 122%.
Rifabutin: (Major) Avoid concurrent use of rifabutin and pralsetinib due to the risk of decreased pralsetinib exposure which may reduce its efficacy. If concomitant use is necessary, increase the current dose of pralsetinib (400 mg to 600 mg; 300 mg to 500 mg; 200 mg to 300 mg) starting on day 7 of coadministration. Pralsetinib is a CYP3A substrate and rifabutin is a moderate CYP3A inducer. Coadministration with another moderate CYP3A inducer decreased the pralsetinib overall exposure by 45%.
Rifampin: (Major) Avoid coadministration of rifampin with pralsetinib due to the risk of decreased pralsetinib exposure which may reduce its efficacy. If concomitant use is unavoidable, double the current dose of pralsetinib starting on day 7 of coadministration. After rifampin has been discontinued for at least 14 days, resume the pralsetinib dose taken prior to initiating rifampin. Pralsetinib is a CYP3A substrate and rifampin is a strong CYP3A inducer. Coadministration with rifampin decreased the pralsetinib AUC by 68%.
Rifapentine: (Major) Avoid coadministration of rifapentine with pralsetinib due to the risk of decreased pralsetinib exposure which may reduce its efficacy. If concomitant use is unavoidable, double the current dose of pralsetinib starting on day 7 of coadministration. After rifapentine has been discontinued for at least 14 days, resume the pralsetinib dose taken prior to initiating rifapentine. Pralsetinib is a CYP3A substrate and rifapentine is a strong CYP3A inducer. Coadministration with another strong CYP3A inducer decreased the pralsetinib AUC by 68%.
Ritlecitinib: (Major) Avoid concomitant use of ritlecitinib with pralsetinib due to the risk of increased pralsetinib exposure which may increase the risk of adverse reactions. If concomitant use is necessary, reduce the daily dose of pralsetinib by 100 mg. Pralsetinib is a CYP3A substrate and ritlecitinib is a moderate CYP3A inhibitor. Coadministration with a moderate CYP3A inhibitor is predicted to increase the overall exposure of pralsetinib by 71%.
Ritonavir: (Major) Avoid concomitant use of ritonavir and pralsetinib due to the risk of increased pralsetinib exposure which may increase the risk of adverse reactions. If concomitant use is necessary, reduce the dose of pralsetinib to 200 mg once daily for patients taking a daily dose of 400 mg or 300 mg, and to 100 mg once daily for patients taking a daily dose of 200 mg. Pralsetinib is a CYP3A and P-gp substrate and ritonavir is a combined strong CYP3A and P-gp inhibitor. Coadministration with a combined strong CYP3A and P-gp inhibitor is predicted to increase the overall exposure of pralsetinib by 251%.
Rolapitant: (Major) Avoid concomitant use of rolapitant with pralsetinib due to the risk of increased pralsetinib exposure which may increase the risk of adverse reactions. If concomitant use is necessary, reduce the daily dose of pralsetinib by 100 mg. Pralsetinib is a P-gp substrate and rolapitant is a P-gp inhibitor. Coadministration with another P-gp inhibitor increased the overall exposure of pralsetinib by 81%.
Saquinavir: (Major) Avoid concomitant use of saquinavir and pralsetinib due to the risk of increased pralsetinib exposure which may increase the risk of adverse reactions. If concomitant use is necessary, reduce the dose of pralsetinib to 200 mg once daily for patients taking a daily dose of 400 mg or 300 mg, and to 100 mg once daily for patients taking a daily dose of 200 mg. Pralsetinib is a CYP3A and P-gp substrate and saquinavir is a combined strong CYP3A and P-gp inhibitor. Coadministration with a combined strong CYP3A and P-gp inhibitor is predicted to increase the overall exposure of pralsetinib by 251%.
Sarecycline: (Major) Avoid concomitant use of sarecycline with pralsetinib due to the risk of increased pralsetinib exposure which may increase the risk of adverse reactions. If concomitant use is necessary, reduce the daily dose of pralsetinib by 100 mg. Pralsetinib is a P-gp substrate and sarecycline is a P-gp inhibitor. Coadministration with another P-gp inhibitor increased the overall exposure of pralsetinib by 81%.
SARS-CoV-2 (COVID-19) vaccines: (Moderate) Patients receiving immunosuppressant medications may have a diminished response to the SARS-CoV-2 virus vaccine. When feasible, administer indicated vaccines prior to initiating immunosuppressant medications. Counsel patients receiving immunosuppressant medications about the possibility of a diminished vaccine response and to continue to follow precautions to avoid exposure to SARS-CoV-2 virus after receiving the vaccine.
SARS-CoV-2 Virus (COVID-19) Adenovirus Vector Vaccine: (Moderate) Patients receiving immunosuppressant medications may have a diminished response to the SARS-CoV-2 virus vaccine. When feasible, administer indicated vaccines prior to initiating immunosuppressant medications. Counsel patients receiving immunosuppressant medications about the possibility of a diminished vaccine response and to continue to follow precautions to avoid exposure to SARS-CoV-2 virus after receiving the vaccine.
SARS-CoV-2 Virus (COVID-19) mRNA Vaccine: (Moderate) Patients receiving immunosuppressant medications may have a diminished response to the SARS-CoV-2 virus vaccine. When feasible, administer indicated vaccines prior to initiating immunosuppressant medications. Counsel patients receiving immunosuppressant medications about the possibility of a diminished vaccine response and to continue to follow precautions to avoid exposure to SARS-CoV-2 virus after receiving the vaccine.
SARS-CoV-2 Virus (COVID-19) Recombinant Spike Protein Nanoparticle Vaccine: (Moderate) Patients receiving immunosuppressant medications may have a diminished response to the SARS-CoV-2 virus vaccine. When feasible, administer indicated vaccines prior to initiating immunosuppressant medications. Counsel patients receiving immunosuppressant medications about the possibility of a diminished vaccine response and to continue to follow precautions to avoid exposure to SARS-CoV-2 virus after receiving the vaccine.
Selpercatinib: (Major) Avoid concomitant use of selpercatinib with pralsetinib due to the risk of increased pralsetinib exposure which may increase the risk of adverse reactions. If concomitant use is necessary, reduce the daily dose of pralsetinib by 100 mg. Pralsetinib is a P-gp substrate and selpercatinib is a P-gp inhibitor. Coadministration with another P-gp inhibitor increased the overall exposure of pralsetinib by 81%.
Sodium Phenylbutyrate; Taurursodiol: (Major) Avoid concomitant use of taurursodiol with pralsetinib due to the risk of increased pralsetinib exposure which may increase the risk of adverse reactions. If concomitant use is necessary, reduce the daily dose of pralsetinib by 100 mg. Pralsetinib is a P-gp substrate and taurursodiol is a P-gp inhibitor. Coadministration with another P-gp inhibitor increased the overall exposure of pralsetinib by 81%.
Sofosbuvir; Velpatasvir: (Major) Avoid concomitant use of velpatasvir with pralsetinib due to the risk of increased pralsetinib exposure which may increase the risk of adverse reactions. If concomitant use is necessary, reduce the daily dose of pralsetinib by 100 mg. Pralsetinib is a P-gp substrate and velpatasvir is a P-gp inhibitor. Coadministration with another P-gp inhibitor increased the overall exposure of pralsetinib by 81%.
Sofosbuvir; Velpatasvir; Voxilaprevir: (Major) Avoid concomitant use of velpatasvir with pralsetinib due to the risk of increased pralsetinib exposure which may increase the risk of adverse reactions. If concomitant use is necessary, reduce the daily dose of pralsetinib by 100 mg. Pralsetinib is a P-gp substrate and velpatasvir is a P-gp inhibitor. Coadministration with another P-gp inhibitor increased the overall exposure of pralsetinib by 81%. (Major) Avoid concomitant use of voxilaprevir with pralsetinib due to the risk of increased pralsetinib exposure which may increase the risk of adverse reactions. If concomitant use is necessary, reduce the daily dose of pralsetinib by 100 mg. Pralsetinib is a P-gp substrate and voxilaprevir is a P-gp inhibitor. Coadministration with another P-gp inhibitor increased the overall exposure of pralsetinib by 81%.
Sorafenib: (Major) Avoid concomitant use of sorafenib with pralsetinib due to the risk of increased pralsetinib exposure which may increase the risk of adverse reactions. If concomitant use is necessary, reduce the daily dose of pralsetinib by 100 mg. Pralsetinib is a P-gp substrate and sorafenib is a P-gp inhibitor. Coadministration with another P-gp inhibitor increased the overall exposure of pralsetinib by 81%.
Sotorasib: (Major) Avoid concomitant use of sotorasib with pralsetinib due to the risk of altered pralsetinib exposure which may reduce its efficacy or increase the risk of adverse reactions. Pralsetinib is a CYP3A and P-gp substrate and sotorasib is a moderate CYP3A inducer and P-gp inhibitor. Coadministration with another moderate CYP3A inducer decreased the pralsetinib overall exposure by 45% and coadministration with another P-gp inhibitor increased the overall exposure of pralsetinib by 81%.
Sparsentan: (Major) Avoid concomitant use of sparsentan with pralsetinib due to the risk of increased pralsetinib exposure which may increase the risk of adverse reactions. If concomitant use is necessary, reduce the daily dose of pralsetinib by 100 mg. Pralsetinib is a P-gp substrate and sparsentan is a P-gp inhibitor. Coadministration with another P-gp inhibitor increased the overall exposure of pralsetinib by 81%.
St. John's Wort, Hypericum perforatum: (Major) Avoid coadministration of St. Johns wort with pralsetinib due to the risk of decreased pralsetinib exposure which may reduce its efficacy. If concomitant use is unavoidable, double the current dose of pralsetinib starting on day 7 of coadministration. After St. Johns wort has been discontinued for at least 14 days, resume the pralsetinib dose taken prior to initiating St. Johns wort. Pralsetinib is a CYP3A substrate and St. Johns wort is a strong CYP3A inducer. Coadministration with another strong CYP3A inducer decreased the pralsetinib AUC by 68%.
Stiripentol: (Major) Avoid concomitant use of stiripentol with pralsetinib due to the risk of increased pralsetinib exposure which may increase the risk of adverse reactions. If concomitant use is necessary, reduce the daily dose of pralsetinib by 100 mg. Pralsetinib is a P-gp substrate and stiripentol is a P-gp inhibitor. Coadministration with another P-gp inhibitor increased the overall exposure of pralsetinib by 81%.
Temsirolimus: (Major) Avoid concomitant use of temsirolimus with pralsetinib due to the risk of increased pralsetinib exposure which may increase the risk of adverse reactions. If concomitant use is necessary, reduce the daily dose of pralsetinib by 100 mg. Pralsetinib is a P-gp substrate and temsirolimus is a P-gp inhibitor. Coadministration with another P-gp inhibitor increased the overall exposure of pralsetinib by 81%.
Tepotinib: (Major) Avoid concomitant use of tepotinib with pralsetinib due to the risk of increased pralsetinib exposure which may increase the risk of adverse reactions. If concomitant use is necessary, reduce the daily dose of pralsetinib by 100 mg. Pralsetinib is a P-gp substrate and tepotinib is a P-gp inhibitor. Coadministration with another P-gp inhibitor increased the overall exposure of pralsetinib by 81%.
Tezacaftor; Ivacaftor: (Major) Avoid concomitant use of ivacaftor with pralsetinib due to the risk of increased pralsetinib exposure which may increase the risk of adverse reactions. If concomitant use is necessary, reduce the daily dose of pralsetinib by 100 mg. Pralsetinib is a P-gp substrate and ivacaftor is a P-gp inhibitor. Coadministration with another P-gp inhibitor increased the overall exposure of pralsetinib by 81%.
Ticagrelor: (Major) Avoid concomitant use of ticagrelor with pralsetinib due to the risk of increased pralsetinib exposure which may increase the risk of adverse reactions. If concomitant use is necessary, reduce the daily dose of pralsetinib by 100 mg. Pralsetinib is a P-gp substrate and ticagrelor is a P-gp inhibitor. Coadministration with another P-gp inhibitor increased the overall exposure of pralsetinib by 81%.
Tipranavir: (Major) Avoid concomitant use of tipranavir and pralsetinib due to the risk of increased pralsetinib exposure which may increase the risk of adverse reactions. If concomitant use is necessary, reduce the dose of pralsetinib to 200 mg once daily for patients taking a daily dose of 400 mg or 300 mg, and to 100 mg once daily for patients taking a daily dose of 200 mg. Pralsetinib is a CYP3A and P-gp substrate and tipranavir is a combined strong CYP3A and P-gp inhibitor. Coadministration with a combined strong CYP3A and P-gp inhibitor is predicted to increase the overall exposure of pralsetinib by 251%.
Trandolapril; Verapamil: (Major) Avoid concomitant use of verapamil with pralsetinib due to the risk of increased pralsetinib exposure which may increase the risk of adverse reactions. If concomitant use is necessary, reduce the daily dose of pralsetinib by 100 mg. Pralsetinib is a CYP3A and P-gp substrate and verapamil is a combined moderate CYP3A and P-gp inhibitor. Coadministration increased the overall exposure of pralsetinib by 108%.
Tucatinib: (Major) Avoid concomitant use of tucatinib and pralsetinib due to the risk of increased pralsetinib exposure which may increase the risk of adverse reactions. If concomitant use is necessary, reduce the dose of pralsetinib to 200 mg once daily for patients taking a daily dose of 400 mg or 300 mg, and to 100 mg once daily for patients taking a daily dose of 200 mg. Pralsetinib is a CYP3A and P-gp substrate and tucatinib is a combined strong CYP3A and P-gp inhibitor. Coadministration with a combined strong CYP3A and P-gp inhibitor is predicted to increase the overall exposure of pralsetinib by 251%.
Vemurafenib: (Major) Avoid concomitant use of vemurafenib with pralsetinib due to the risk of increased pralsetinib exposure which may increase the risk of adverse reactions. If concomitant use is necessary, reduce the daily dose of pralsetinib by 100 mg. Pralsetinib is a P-gp substrate and vemurafenib is a P-gp inhibitor. Coadministration with another P-gp inhibitor increased the overall exposure of pralsetinib by 81%.
Venetoclax: (Major) Avoid concomitant use of venetoclax with pralsetinib due to the risk of increased pralsetinib exposure which may increase the risk of adverse reactions. If concomitant use is necessary, reduce the daily dose of pralsetinib by 100 mg. Pralsetinib is a P-gp substrate and venetoclax is a P-gp inhibitor. Coadministration with another P-gp inhibitor increased the overall exposure of pralsetinib by 81%.
Verapamil: (Major) Avoid concomitant use of verapamil with pralsetinib due to the risk of increased pralsetinib exposure which may increase the risk of adverse reactions. If concomitant use is necessary, reduce the daily dose of pralsetinib by 100 mg. Pralsetinib is a CYP3A and P-gp substrate and verapamil is a combined moderate CYP3A and P-gp inhibitor. Coadministration increased the overall exposure of pralsetinib by 108%.
Voclosporin: (Major) Avoid concomitant use of voclosporin with pralsetinib due to the risk of increased pralsetinib exposure which may increase the risk of adverse reactions. If concomitant use is necessary, reduce the daily dose of pralsetinib by 100 mg. Pralsetinib is a P-gp substrate and voclosporin is a P-gp inhibitor. Coadministration with another P-gp inhibitor increased the overall exposure of pralsetinib by 81%.
Vonoprazan; Amoxicillin; Clarithromycin: (Major) Avoid concomitant use of clarithromycin and pralsetinib due to the risk of increased pralsetinib exposure which may increase the risk of adverse reactions. If concomitant use is necessary, reduce the dose of pralsetinib to 200 mg once daily for patients taking a daily dose of 400 mg or 300 mg, and to 100 mg once daily for patients taking a daily dose of 200 mg. Pralsetinib is a CYP3A and P-gp substrate and clarithromycin is a combined strong CYP3A and P-gp inhibitor. Coadministration with a combined strong CYP3A and P-gp inhibitor is predicted to increase the overall exposure of pralsetinib by 251%.
Voriconazole: (Major) Avoid concomitant use of voriconazole with pralsetinib due to the risk of increased pralsetinib exposure which may increase the risk of adverse reactions. If concomitant use is necessary, reduce the daily dose of pralsetinib by 100 mg. Pralsetinib is a CYP3A substrate and voriconazole is a strong CYP3A inhibitor. Coadministration is predicted to increase the overall exposure of pralsetinib by 122%.
Voxelotor: (Major) Avoid concomitant use of voxelotor with pralsetinib due to the risk of increased pralsetinib exposure which may increase the risk of adverse reactions. If concomitant use is necessary, reduce the daily dose of pralsetinib by 100 mg. Pralsetinib is a CYP3A substrate and voxelotor is a moderate CYP3A inhibitor. Coadministration with a moderate CYP3A inhibitor is predicted to increase the overall exposure of pralsetinib by 71%.
Zonisamide: (Major) Avoid concomitant use of zonisamide with pralsetinib due to the risk of increased pralsetinib exposure which may increase the risk of adverse reactions. If concomitant use is necessary, reduce the daily dose of pralsetinib by 100 mg. Pralsetinib is a P-gp substrate and zonisamide is a P-gp inhibitor. Coadministration with another P-gp inhibitor increased the overall exposure of pralsetinib by 81%.
Pralsetinib is an oral tyrosine kinase inhibitor of wild-type RET and oncogenic RET fusions (CCDC6-RET) and mutations (RET V804L, RET V804M, and RET M918T) with half-maximal inhibitory concentrations (IC50s) less than 0.5 nanoMolar. Certain RET fusion proteins and activating point mutations can drive tumorigenic potential through hyperactivation of downstream signaling pathways leading to uncontrolled cell proliferation. Pralsetinib exhibited anti-tumor activity in cultured cells and animal tumor implantation models harboring oncogenic RET fusions or mutations including KIF5B-RET, CCDC6-RET, RET M918T, RET C634W, RET V804E, RET V804L, and RET V804M. Pralsetinib also prolonged survival in mice implanted intracranially with tumor models expressing KIF5B-RET or CCDC6-RET.
In purified enzyme assays, pralsetinib inhibited DDR1, TRKC, FLT3, JAK1-2, TRKA, VEGFR2, PDGFRb, and FGFR1 at higher concentrations that were still clinically achievable at Cmax. In cellular assays, pralsetinib inhibited RET at approximately 14-, 40-, and 12-fold lower concentrations than VEGFR2, FGFR2, and JAK2, respectively.
Pralsetinib is administered orally. It is 97% protein-bound, independent of concentration. The blood-to-plasma ratio is 0.6 to 0.7. The mean apparent volume of distribution (Vd/F) of pralsetinib is 303 liters (CV, 68%). The mean plasma elimination half-life of pralsetinib is 16 hours (+/- 10 hours) after single doses and 20 hours (+/- 12 hours) following multiple doses. The mean apparent oral clearance (CL/F) is 11 liters/hour (CV, 66%) at steady-state. Approximately 73% of the total administered radioactive dose of pralsetinib was recovered in feces (66% as unchanged drug); 6% was recovered in the urine (4.8% as unchanged drug).
Affected cytochrome (CYP) 450 isoenzymes and transporters: CYP3A4, CYP2D6, CYP1A2, P-gp
Pralsetinib is primarily metabolized by CYP3A4 and to a lesser extent by CYP2D6 and CYP1A2 in vitro. After a single radiolabeled dose to healthy subjects, pralsetinib metabolites from oxidation and glucuronidation were detected as 5% or less. In vitro, pralsetinib is also a substrate of P-gp and BCRP. Pralsetinib is a time-dependent inhibitor of CYP3A and is also an inhibitor of CYP2C8 and CYP2C9 at clinically relevant concentrations in vitro; it also inhibits P-gp, BCRP, OATP1B1, OATP1B3, OAT1, MATE1, MATE2-K, and bile salt efflux pump (BSEP) in vitro. Pralsetinib induces CYP2C8, CYP2C9, and CYP3A at clinically relevant concentrations in vitro.
-Route-Specific Pharmacokinetics
Oral Route
Under fasting conditions, the steady-state mean Cmax of pralsetinib at the recommended 400 mg once daily dose was 2,470 ng/mL (CV, 55%) and the AUC was 36,700 hours x ng/mL (CV, 66%); the Cmax and AUC increased inconsistently over the dose range of 60 mg to 600 mg once daily (0.15 to 1.5 times the recommended dose). The mean time to peak concentration (Tmax) ranged from 2 to 4 hours after single pralsetinib doses of 60 mg to 600 mg. Steady-state concentrations were reached by 3 to 5 days. The mean accumulation ratio was about 2-fold after once-daily repeated oral administration.
Effects of Food: After administration of a single 200-mg dose of pralsetinib with a high-fat meal (approximately 800 to 1,000 calories; 50% to 60% fat), the mean Cmax increased by 2-fold and the mean AUC increased by 2.2-fold. The median Tmax was delayed from 4 hours to 8.5 hours compared to the fasted state. There were no clinically significant differences in the pharmacokinetics of pralsetinib when coadministered with gastric acid-reducing agents.
-Special Populations
Renal Impairment
Mild and moderate renal impairment (CrCl 30 to 89 mL/min) had no effect on pralsetinib exposure. Pralsetinib has not been studied in patients with severe renal impairment (CrCl less than 15 mL/min).
Geriatric
Age (19 to 87 years) did not have a clinically significant effect on the pharmacokinetics of pralsetinib.
Gender Differences
Sex did not have a clinically significant effect on the pharmacokinetics of pralsetinib.
Ethnic Differences
Race (White, Black, or Asian) did not have a clinically significant effect on the pharmacokinetics of pralsetinib.
Obesity
Body weight (32 kg to 128 kg) did not have a clinically significant effect on the pharmacokinetics of pralsetinib.