Interactions between Dasatinib and Telotristat
1 drug interaction and 15 additional warnings found for the following 2 drugs:
- dasatinib
- telotristat
Drug interactions
Moderate drug interactions
Moderate:
dasatinib telotristat ethyl
Applies to: dasatinib and telotristat
Monitor
Coadministration with inducers of CYP450 3A4 may decrease the plasma concentrations of dasatinib, which is primarily metabolized by the isoenzyme. When a single morning dose of dasatinib was administered to 20 healthy subjects following 8 days of continuous evening dosing of 600 mg rifampin, a potent CYP450 3A4 inducer, mean dasatinib peak plasma concentration (Cmax) and systemic exposure (AUC) decreased by 81% and 82%, respectively, compared to dasatinib administered alone. The extent to which other, less potent CYP450 3A4 inducers may interact with dasatinib is unknown.
Management
The potential for diminished pharmacologic effects of dasatinib should be considered during coadministration with CYP450 3A4 inducers. Alternative treatments may be required if an interaction is suspected, or a dosage increase for dasatinib depending on patient tolerability. Close monitoring for toxicities (e.g., myelosuppression, bleeding complications, fluid retention, QT prolongation) is recommended if the dosage of dasatinib is increased. The dosage should be reduced to the indicated dosage following discontinuation of the potent CYP450 3A4 inducer.
References (3)
- Cerner Multum, Inc. "UK Summary of Product Characteristics."
- (2006) "Product Information. Sprycel (dasatinib)." Bristol-Myers Squibb
- Cerner Multum, Inc. "Australian Product Information."
Food/lifestyle interactions
Major food/lifestyle interactions
Major:
dasatinib Food/Lifestyle
Applies to: dasatinib
Generally avoid
Grapefruit and grapefruit juice may significantly increase the plasma concentrations of dasatinib. The proposed mechanism is inhibition of CYP450 3A4-mediated first-pass metabolism in the gut wall induced by certain compounds present in grapefruit. Because grapefruit juice inhibits primarily intestinal rather than hepatic CYP450 3A4, the magnitude of interaction is greatest for those drugs that undergo significant presystemic metabolism by CYP450 3A4 (i.e., drugs with low oral bioavailability). 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. Pharmacokinetic interactions involving grapefruit juice are also subject to a high degree of interpatient variability, thus the extent to which a given patient may be affected is difficult to predict. Because dasatinib prolongs the QT interval, high plasma levels of dasatinib may increase the risk of ventricular arrhythmias such as torsade de pointes and sudden death.
Management
Patients treated with dasatinib should avoid consumption of grapefruit, grapefruit juice, and any supplement containing grapefruit extract. Some authorities recommend close monitoring for toxicity (e.g., myelosuppression, bleeding complications, fluid retention, bradycardia or other conduction disturbances) and a reduction of dasatinib dosage to a range of 20 to 40 mg daily should be considered if there are no alternatives and concomitant use with a potent CYP450 3A4 inhibitor is necessary.
References (3)
- Cerner Multum, Inc. "UK Summary of Product Characteristics."
- (2006) "Product Information. Sprycel (dasatinib)." Bristol-Myers Squibb
- Cerner Multum, Inc. "Australian Product Information."
Moderate food/lifestyle interactions
Moderate:
telotristat ethyl Food/Lifestyle
Applies to: telotristat
Adjust dosing interval
Food increases the systemic exposure to both telotristat ethyl and its active metabolite, telotristat. Following administration of a single 500 mg dose of telotristat ethyl (twice the recommended dose) with a high-fat meal, telotristat ethyl peak plasma concentration (Cmax) and systemic exposure (AUC) were 112% and 264% higher, respectively, compared to administration under fasted conditions. The Cmax and AUC values for telotristat were also increased by 47% and 33%, respectively. The in vitro inhibitory potency of telotristat towards tryptophan hydroxylase has been shown to be approximately 29 times higher than that of the parent drug.
Management
Telotristat ethyl should be administered with food.
References (1)
- (2017) "Product Information. Xermelo (telotristat ethyl)." Lexicon Pharmaceuticals, Inc.
Disease interactions
13 potential interactions Applies to: 12 conditions, including Constipation, Heart Failure, Hypokalemia, Hemodialysis, and Fluid Retention.
Bone Marrow Depression/Low Blood Counts
Moderate:
dasatinib
Dasatinib has a moderate potential interaction with Bone Marrow Depression/Low Blood Counts.
Thrombocytopenia, aplastic anemia, agranulocytosis, and neutropenia occur with BCR-ABL tyrosine kinase inhibitors. Therapy with these drugs should be administered cautiously in patients with preexisting bone marrow suppression. A complete blood count should be performed every 1 to 2 weeks for the first month of therapy and then monthly thereafter, or as clinically indicated. To manage myelosuppression, withhold, reduce dose, or discontinue therapy as necessary.
Cardiovascular Conditions and Disorders
Moderate:
dasatinib
Dasatinib has a moderate potential interaction with Cardiovascular Conditions and Disorders.
Cardiovascular events (including arterial vascular occlusive events, peripheral arterial occlusive disease, and ischemic cerebrovascular events) have been reported in patients receiving BCR-ABL tyrosine kinase inhibitors. Patients should seek immediate medical attention if acute signs or symptoms of cardiovascular events occur. Cardiovascular status should be evaluated, and cardiovascular risk factors should be monitored and actively managed during treatment.
Constipation
Moderate:
telotristat
The telotristat ethyl in telotristat has a moderate potential interaction with Constipation.
The use of telotristat reduces bowel movement frequency and may cause gastrointestinal effects including, constipation, intestinal perforation and obstruction. It is recommended to monitor for the development of constipation and/or severe, persistent, or worsening abdominal pain in patients taking telotristat and to discontinue its use if severe constipation or severe persistent or worsening abdominal pain develops. Care is recommended when using telotristat in patients suffering from constipation. .
Fluid Retention
Moderate:
dasatinib
Dasatinib has a moderate potential interaction with Fluid Retention.
Fluid retention occurs with BCR-ABL tyrosine kinase inhibitors therapy and may manifest as pericardial effusion, pleural effusion, pulmonary edema, and/or peripheral edema. Caution should be taken when using these drugs in patients with preexisting fluid retention or congestive heart failure. Monitor and manage patients using standards of care. Interrupt, reduce dose or discontinue therapy as necessary.
Heart Failure
Moderate:
dasatinib
Dasatinib has a moderate potential interaction with Heart Failure.
Fluid retention occurs with BCR-ABL tyrosine kinase inhibitors therapy and may manifest as pericardial effusion, pleural effusion, pulmonary edema, and/or peripheral edema. Caution should be taken when using these drugs in patients with preexisting fluid retention or congestive heart failure. Monitor and manage patients using standards of care. Interrupt, reduce dose or discontinue therapy as necessary.
Hemodialysis
Moderate:
telotristat
The telotristat ethyl in telotristat has a moderate potential interaction with Hemodialysis.
Population pharmacokinetic (PK) analysis showed that creatine clearance does not affect the PK of telotristat. Care is recommended when using telotristat in patients with end-stage renal disease (ESRD) who require dialysis as this agent has not been studied in this patient population.
Hypokalemia
Moderate:
dasatinib
Dasatinib has a moderate potential interaction with Hypokalemia.
Dasatinib has shown to prolong QT interval in a concentration-dependent manner. Caution should be exercised specially in patients with congenital long QT syndrome, patients with hypokalemia, hypomagnesemia, or with history of arrhythmias and on antiarrhythmic medication. Hypokalemia or hypomagnesemia should be corrected before starting treatment. Patients at risk should be monitored with an EKG before treatment and periodically as clinically indicated. Dose adjustments might be needed.
Liver Disease
Moderate:
dasatinib
Dasatinib has a moderate potential interaction with Liver Disease.
Caution is advised when administering dasatinib to patients with hepatic impairment. Monitoring is recommended and dose adjustment might be necessary.
Moderate:
telotristat
The telotristat ethyl in telotristat has a moderate potential interaction with Liver Disease.
Population pharmacokinetic analysis showed that mild hepatic impairment does not affect the pharmacokinetics of telotristat. Care is recommended when using telotristat in patients with moderate or severe hepatic impairment as this agent has not been studied in this patient population.
Long QT Syndrome
Moderate:
dasatinib
Dasatinib has a moderate potential interaction with Long QT Syndrome.
Dasatinib has shown to prolong QT interval in a concentration-dependent manner. Caution should be exercised specially in patients with congenital long QT syndrome, patients with hypokalemia, hypomagnesemia, or with history of arrhythmias and on antiarrhythmic medication. Hypokalemia or hypomagnesemia should be corrected before starting treatment. Patients at risk should be monitored with an EKG before treatment and periodically as clinically indicated. Dose adjustments might be needed.
Magnesium Imbalance
Moderate:
dasatinib
Dasatinib has a moderate potential interaction with Magnesium Imbalance.
Dasatinib has shown to prolong QT interval in a concentration-dependent manner. Caution should be exercised specially in patients with congenital long QT syndrome, patients with hypokalemia, hypomagnesemia, or with history of arrhythmias and on antiarrhythmic medication. Hypokalemia or hypomagnesemia should be corrected before starting treatment. Patients at risk should be monitored with an EKG before treatment and periodically as clinically indicated. Dose adjustments might be needed.
Pleural Effusion
Moderate:
dasatinib
Dasatinib has a moderate potential interaction with Pleural Effusion.
Fluid retention occurs with BCR-ABL tyrosine kinase inhibitors therapy and may manifest as pericardial effusion, pleural effusion, pulmonary edema, and/or peripheral edema. Caution should be taken when using these drugs in patients with preexisting fluid retention or congestive heart failure. Monitor and manage patients using standards of care. Interrupt, reduce dose or discontinue therapy as necessary.
Pulmonary Heart or Vascular Disease
Moderate:
dasatinib
Dasatinib has a moderate potential interaction with Pulmonary Heart or Vascular Disease.
Dasatinib can increase the risk of developing pulmonary arterial hypertension (PAH) which may occur any time after treatment initiation, including after more than 1 year of treatment. Manifestations may include dyspnea, fatigue, hypoxia, and fluid retention. PAH may be reversible with treatment discontinuation. Caution should be exercised in patients with underlying cardiopulmonary disease. If PAH develops, treatment should be discontinued.
More resources
dasatinib
A total of 845 drugs are known to interact with dasatinib.
- Dasatinib is in the drug class BCR-ABL tyrosine kinase inhibitors.
- Dasatinib is used to treat the following conditions:
telotristat
A total of 371 drugs are known to interact with telotristat.
- Telotristat is in the drug class miscellaneous GI agents.
- Telotristat is used to treat Carcinoid Syndrome Diarrhea.
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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