Interactions between Pralsetinib and Sorafenib
1 drug interaction and 12 additional warnings found for the following 2 drugs:
- pralsetinib
- sorafenib
Drug interactions
Moderate drug interactions
Moderate:
SORAfenib pralsetinib
Applies to: sorafenib and pralsetinib
Monitor
Pralsetinib can cause prolongation of the QT interval. Theoretically, coadministration with other agents that can prolong the QT interval may result in additive effects and increased risk of ventricular arrhythmias including torsade de pointes and sudden death. In clinical trials, QT prolongation occurred in 5.1% of 528 patients with non-small cell lung cancer (NSCLC) or other solid tumors. Two patients (0.4%) experienced grade 3 QT prolongation, which resolved in each case. There was no life-threatening or fatal QT prolongation. The QT interval prolongation potential of pralsetinib was assessed in 34 patients with rearranged during transfection (RET) altered solid tumors administered 400 mg once daily, and no mean increase in the corrected QT interval (QTc) greater than 20 ms was detected. In general, the risk of an individual agent or a combination of agents causing ventricular arrhythmia in association with QT prolongation is largely unpredictable but may be increased by certain underlying risk factors such as congenital long QT syndrome, cardiac disease, and electrolyte disturbances (e.g., hypokalemia, hypomagnesemia, hypocalcemia). Moreover, the extent of drug-induced QT prolongation is dependent on the particular drug(s) involved and dosage(s) of the drug(s).
Management
Some authorities recommend caution if pralsetinib is coadministered with other agents known to prolong the QT interval. Patients should be advised to seek prompt medical attention if they experience symptoms that could indicate the occurrence of torsade de pointes such as dizziness, lightheadedness, fainting, palpitation, irregular heart rhythm, shortness of breath, or syncope.
References (4)
- (2023) "Product Information. Gavreto (pralsetinib)." Roche Products Pty Ltd, GAVRETO 20230406
- (2024) "Product Information. Gavreto (pralsetinib)." Genentech
- (2024) "Product Information. Gavreto (pralsetinib)." Roche Products Ltd
- (2024) "Product Information. Gavreto (pralsetinib)." Hoffmann-La Roche Limited
Therapeutic duplication warnings
Therapeutic duplication is the use of more than one medicine from the same drug category or therapeutic class to treat the same condition.
It can be intentional, when combining drugs with similar actions adds demonstrated therapeutic benefit — or unintentional, such as when a patient sees multiple prescribers or fills prescriptions at more than one pharmacy, which can lead to adverse effects.
Duplication:
Multikinase inhibitors
The recommended maximum number of medicines in the 'multikinase inhibitors' category to be taken concurrently is usually one. Your list includes two medicines belonging to the 'multikinase inhibitors' category:
- pralsetinib
- sorafenib
Note: In certain circumstances, the benefits of taking this combination of drugs may outweigh any risks. Always consult your healthcare provider before making changes to your medications or dosage.
Food/lifestyle interactions
Major food/lifestyle interactions
Major:
pralsetinib Food/Lifestyle
Applies to: pralsetinib
Adjust dosing interval
Food significantly increases the oral bioavailability of pralsetinib. According to the product labeling, administration of pralsetinib (200 mg) with a high-fat meal (approximately 800 to 1000 calories; 50% to 60% from fat) increased mean pralsetinib peak plasma concentration (Cmax) and systemic exposure (AUC) by 104% and 122%, respectively. The median time to maximum concentration (Tmax) was delayed from 4 hours to 8.5 hours, when compared to the fasted state.
Generally avoid
The juice of grapefruit and/or Seville oranges may increase the plasma concentrations of pralsetinib. The proposed mechanism is inhibition of CYP450 3A4-mediated first-pass metabolism in the gut wall by certain compounds present in grapefruit and Seville oranges. In general, the effect of grapefruit juice is concentration-, dose- and preparation-dependent, and can vary widely among brands. Certain preparations of grapefruit juice (e.g., high dose, double strength) have sometimes demonstrated potent inhibition of CYP450 3A4, while other preparations (e.g., low dose, single strength) have typically demonstrated moderate inhibition. Increased exposure to pralsetinib may increase the risk of adverse effects such as interstitial lung disease/pneumonitis, liver transaminase elevations, hypertension, and hemorrhage. Some clinical trials have also observed prolongation of the QT interval in patients on pralsetinib, though this was not observed in a study of 34 patients with rearranged during transfection (RET)-altered solid tumors on pralsetinib at the recommended dosage.
Management
Pralsetinib should be administered on an empty stomach, with no food intake recommended for at least 2 hours before and at least 1 hour after taking the medication. Patients should avoid consumption of grapefruit, grapefruit juice, Seville oranges, or Seville orange juice during treatment with pralsetinib.
References (4)
- (2023) "Product Information. Gavreto (pralsetinib)." Roche Products Pty Ltd, GAVRETO 20230406
- (2024) "Product Information. Gavreto (pralsetinib)." Genentech
- (2024) "Product Information. Gavreto (pralsetinib)." Roche Products Ltd
- (2024) "Product Information. Gavreto (pralsetinib)." Hoffmann-La Roche Limited
Moderate food/lifestyle interactions
Moderate:
SORAfenib Food/Lifestyle
Applies to: sorafenib
Adjust dosing interval
Food may reduce the oral absorption and bioavailability of sorafenib. According to the product labeling, sorafenib bioavailability was reduced by 29% when administered with a high-fat meal compared to administration in the fasted state. When given with a moderate-fat meal, bioavailability was similar to that in the fasted state.
Management
To ensure maximal and consistent oral absorption, sorafenib should be taken at least one hour before or two hours after eating.
References (1)
- (2005) "Product Information. Nexavar (sorafenib)." Bayer Pharmaceutical Inc
Disease interactions
9 potential interactions Applies to: 9 conditions, including High Blood Pressure, Hypokalemia, Hypocalcemia, Liver Disease, and Long QT Syndrome.
High Blood Pressure
Moderate:
pralsetinib
Pralsetinib has a moderate potential interaction with High Blood Pressure.
Hypertension has been reported in patients in treatment with pralsetinib. This drug should not be initiated in patients with uncontrolled hypertension. Caution and close monitoring is advised.
Hypocalcemia
Moderate:
pralsetinib
Pralsetinib has a moderate potential interaction with Hypocalcemia.
QT prolongation was reported in clinical trials in patients that received pralsetinib. Use with caution in patients with history of arrhythmias, QT prolongation or taking medications that can prolong the QT interval (e.g., strong CYP450 3A4 inhibitors). Monitor QT interval and serum electrolytes before initiation and regularly during treatment. Hypokalemia, hypomagnesemia, and hypocalcemia should be corrected prior and during treatment.
Hypokalemia
Moderate:
pralsetinib
Pralsetinib has a moderate potential interaction with Hypokalemia.
QT prolongation was reported in clinical trials in patients that received pralsetinib. Use with caution in patients with history of arrhythmias, QT prolongation or taking medications that can prolong the QT interval (e.g., strong CYP450 3A4 inhibitors). Monitor QT interval and serum electrolytes before initiation and regularly during treatment. Hypokalemia, hypomagnesemia, and hypocalcemia should be corrected prior and during treatment.
Interstitial Lung Disease
Moderate:
sorafenib
SORAfenib has a moderate potential interaction with Interstitial Lung Disease.
The use of certain multikinase inhibitors has been associated with pulmonary toxicity. Serious cases of interstitial lung disease (ILD), including fatal cases and interstitial pneumonitis or pulmonary fibrosis have been reported. Caution is recommended when using these agents in patients with a history of interstitial pneumonitis or pulmonary fibrosis or those patients presenting with acute onset of new or progressive unexplained pulmonary symptoms such as dyspnea, cough, and fever pending diagnostic evaluation. If ILD is confirmed, these agents should be permanently discontinued and appropriate measures should be instituted. Treatment should be immediately withheld in patients diagnosed with ILD/pneumonitis and permanently discontinued if no other potential causes of ILD/pneumonitis have been identified.
Liver Disease
Moderate:
pralsetinib
Pralsetinib has a moderate potential interaction with Liver Disease.
Pralsetinib has not been studied in patients with moderate or severe hepatic impairment. Additionally, clinical trials reported hepatotoxicity in some patients receiving treatment. Caution and close monitoring is advised if administering in patients with hepatic impairment.
Long QT Syndrome
Moderate:
pralsetinib
Pralsetinib has a moderate potential interaction with Long QT Syndrome.
QT prolongation was reported in clinical trials in patients that received pralsetinib. Use with caution in patients with history of arrhythmias, QT prolongation or taking medications that can prolong the QT interval (e.g., strong CYP450 3A4 inhibitors). Monitor QT interval and serum electrolytes before initiation and regularly during treatment. Hypokalemia, hypomagnesemia, and hypocalcemia should be corrected prior and during treatment.
Magnesium Imbalance
Moderate:
pralsetinib
Pralsetinib has a moderate potential interaction with Magnesium Imbalance.
QT prolongation was reported in clinical trials in patients that received pralsetinib. Use with caution in patients with history of arrhythmias, QT prolongation or taking medications that can prolong the QT interval (e.g., strong CYP450 3A4 inhibitors). Monitor QT interval and serum electrolytes before initiation and regularly during treatment. Hypokalemia, hypomagnesemia, and hypocalcemia should be corrected prior and during treatment.
Pulmonary Impairment
Moderate:
sorafenib
SORAfenib has a moderate potential interaction with Pulmonary Impairment.
The use of certain multikinase inhibitors has been associated with pulmonary toxicity. Serious cases of interstitial lung disease (ILD), including fatal cases and interstitial pneumonitis or pulmonary fibrosis have been reported. Caution is recommended when using these agents in patients with a history of interstitial pneumonitis or pulmonary fibrosis or those patients presenting with acute onset of new or progressive unexplained pulmonary symptoms such as dyspnea, cough, and fever pending diagnostic evaluation. If ILD is confirmed, these agents should be permanently discontinued and appropriate measures should be instituted. Treatment should be immediately withheld in patients diagnosed with ILD/pneumonitis and permanently discontinued if no other potential causes of ILD/pneumonitis have been identified.
Renal Dysfunction
Moderate:
pralsetinib
Pralsetinib has a moderate potential interaction with Renal Dysfunction.
Pralsetinib has not been studied in patients with severe renal impairment or end-stage renal disease. Caution is advised if administering in these patients.
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More resources
pralsetinib
A total of 740 drugs are known to interact with pralsetinib.
- Pralsetinib is in the drug class multikinase inhibitors.
- Pralsetinib is used to treat the following conditions:
sorafenib
A total of 451 drugs are known to interact with sorafenib.
- Sorafenib is in the following drug classes: multikinase inhibitors, VEGF/VEGFR inhibitors.
- Sorafenib is used to treat the following conditions:
Drug Interaction Classification
| Highly clinically significant. Avoid combinations; the risk of the interaction outweighs the benefit. | |
| Moderately clinically significant. Usually avoid combinations; use it only under special circumstances. | |
| Minimally clinically significant. Minimize risk; assess risk and consider an alternative drug, take steps to circumvent the interaction risk and/or institute a monitoring plan. | |
| No interaction information available. |
Further information
Always consult your healthcare provider to ensure the information displayed on this page applies to your personal circumstances.