Interactions between Cinvanti and Pexidartinib
1 drug interaction and 6 additional warnings found for the following 2 drugs:
- Cinvanti (aprepitant)
- pexidartinib
Drug interactions
Major drug interactions
Major:
aprepitant pexidartinib
Applies to: Cinvanti (aprepitant) and pexidartinib
Generally avoid
Coadministration of pexidartinib with moderate CYP450 3A4 inhibitors may significantly increase the plasma concentrations and the incidence and severity of adverse effects of pexidartinib, including potentially fatal hepatotoxicity. The proposed mechanism is inhibition of CYP450 3A4, the primary isoenzyme responsible for the metabolic clearance of pexidartinib. Concomitant administration of itraconazole, a strong CYP450 3A4 inhibitor, increased pexidartinib peak plasma concentration (Cmax) and systemic exposure (AUC) by 48% and 70%, respectively. No data are available regarding the effects that other, less potent CYP450 3A4 inhibitors may have on the pharmacokinetics of pexidartinib.
Management
The use of pexidartinib with a moderate CYP450 3A4 inhibitor should generally be avoided. If concomitant use is required, the dose of pexidartinib should be reduced according to the manufacturer's recommendations. If concomitant use of a moderate CYP450 3A4 inhibitor is discontinued, the dose of pexidartinib may be increased, after 3 plasma half-lives of the moderate CYP450 3A4 inhibitor, to the dose that was used prior to starting the moderate CYP450 3A4 inhibitor.
References (1)
- (2019) "Product Information. Turalio (pexidartinib)." Daiichi Sankyo, Inc.
Food/lifestyle interactions
Major food/lifestyle interactions
Major:
pexidartinib Food/Lifestyle
Applies to: pexidartinib
Adjust dosing interval
The presence of food may increase the absorption and toxicity of pexidartinib. Administration of pexidartinib with a high-fat meal increased peak plasma concentration (Cmax) and systemic exposure (AUC) by 100% and prolonged the time to reach peak plasma concentration (Tmax) by 2.5 hours.
Generally avoid
Grapefruit or grapefruit juice may increase the plasma concentration and risk of adverse effects of pexidartinib, including potentially fatal hepatotoxicity. The mechanism is inhibition of CYP450 3A4-mediated metabolism of pexidartinib by certain compounds present in grapefruits. Concomitant administration of itraconazole, a strong CYP450 3A4 inhibitor, increased pexidartinib peak plasma concentration (Cmax) and systemic exposure (AUC) by 48% and 70%, respectively.
Management
Pexidartinib should be administered on an empty stomach, at least one hour before or two hours after a meal or snack. Consumption of grapefruit or grapefruit juice should generally be avoided during pexidartinib therapy. If concomitant use is unavoidable, the dose of pexidartinib should be reduced according to the manufacturer's recommendations. If concomitant use of grapefruit or grapefruit juice is discontinued, the dose of pexidartinib may be increased (after 3 plasma half-lives of a strong CYP450 3A4 inhibitor) to the dose that was used prior to consumption of grapefruit or grapefruit juice.
References (1)
- (2019) "Product Information. Turalio (pexidartinib)." Daiichi Sankyo, Inc.
Disease interactions
5 potential interactions Applies to: 4 conditions, including Liver Disease, Renal Dysfunction, Bile Acid Synthesis Disorders, and Biliary Obstruction.
Bile Acid Synthesis Disorders
Major:
pexidartinib
Pexidartinib has a major potential interaction with Bile Acid Synthesis Disorders.
Pexidartinib can cause serious and potentially fatal liver injury. No dose adjustment is needed for patients with mild hepatic impairment. A dose reduction (125 mg twice a day) is recommended for patients with moderate hepatic impairment. Pexidartinib has not been studied in patients with severe hepatic impairment. Avoid this drug in patients with preexisting increased serum transaminases; total bilirubin or direct bilirubin (greater than ULN); or active liver or biliary tract disease, including increased alkaline phosphatase. It is recommended to monitor liver tests before initiation of treatment and at specified intervals during treatment. Withhold and reduce the dose or permanently discontinue pexidartinib based on the severity of hepatotoxicity.
Biliary Obstruction
Major:
pexidartinib
Pexidartinib has a major potential interaction with Biliary Obstruction.
Pexidartinib can cause serious and potentially fatal liver injury. No dose adjustment is needed for patients with mild hepatic impairment. A dose reduction (125 mg twice a day) is recommended for patients with moderate hepatic impairment. Pexidartinib has not been studied in patients with severe hepatic impairment. Avoid this drug in patients with preexisting increased serum transaminases; total bilirubin or direct bilirubin (greater than ULN); or active liver or biliary tract disease, including increased alkaline phosphatase. It is recommended to monitor liver tests before initiation of treatment and at specified intervals during treatment. Withhold and reduce the dose or permanently discontinue pexidartinib based on the severity of hepatotoxicity.
Liver Disease
Major:
pexidartinib
Pexidartinib has a major potential interaction with Liver Disease.
Pexidartinib can cause serious and potentially fatal liver injury. No dose adjustment is needed for patients with mild hepatic impairment. A dose reduction (125 mg twice a day) is recommended for patients with moderate hepatic impairment. Pexidartinib has not been studied in patients with severe hepatic impairment. Avoid this drug in patients with preexisting increased serum transaminases; total bilirubin or direct bilirubin (greater than ULN); or active liver or biliary tract disease, including increased alkaline phosphatase. It is recommended to monitor liver tests before initiation of treatment and at specified intervals during treatment. Withhold and reduce the dose or permanently discontinue pexidartinib based on the severity of hepatotoxicity.
Moderate:
Cinvanti
The aprepitant in Cinvanti has a moderate potential interaction with Liver Disease.
Aprepitant is primarily metabolized by the liver. In studies of patients with mild to moderate hepatic impairment (Child-Pugh score 5 to 9), aprepitant was well tolerated and no clinically significant alterations in its pharmacokinetics were observed. Thus, no dosage adjustment of aprepitant is necessary in this patient population. However, there are no clinical or pharmacokinetic data in patients with severe hepatic impairment (Child-Pugh score > 9), and caution is advised if aprepitant is used in such patients.
Renal Dysfunction
Moderate:
pexidartinib
Pexidartinib has a moderate potential interaction with Renal Dysfunction.
Dose modification of pexidartinib is needed for patients with renal impairment. It is recommended to reduce the dose when administering pexidartinib to patients with mild to severe renal impairment (CrCl 15 to 89 mL/min, estimated by Cockcroft-Gault using actual body weight). The recommended dosage is 125 mg in the morning and 250 mg in the evening with a low-fat meal.
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Cinvanti
A total of 485 drugs are known to interact with Cinvanti.
- Cinvanti is in the drug class NK1 receptor antagonists.
- Cinvanti is used to treat the following conditions:
pexidartinib
A total of 687 drugs are known to interact with pexidartinib.
- Pexidartinib is in the drug class multikinase inhibitors.
- Pexidartinib 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
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