Interactions between Tekturna and Telotristat
1 drug interaction and 11 additional warnings found for the following 2 drugs:
- Tekturna (aliskiren)
- telotristat
Drug interactions
Moderate drug interactions
Moderate:
aliskiren telotristat ethyl
Applies to: Tekturna (aliskiren) and telotristat
Monitor
Coadministration with telotristat ethyl may decrease the plasma concentrations of drugs that are substrates of CYP450 3A4 and/or 2B6 isoenzymes. The proposed mechanism is accelerated clearance due to induction of CYP450 3A4 and/or 2B6 (in vitro) isoenzymes by telotristat ethyl. When the probe CYP450 3A4 substrate midazolam (3 mg) was administered orally after 5 days of treatment with telotristat ethyl 500 mg three times daily (twice the recommended dosage), mean midazolam peak plasma concentration (Cmax) and systemic exposure (AUC) decreased by 25% and 48%, respectively, compared to administration of midazolam alone. The mean Cmax and AUC of the active metabolite, 1'-hydroxymidazolam, also decreased by 34% and 48%, respectively. This suggests induction by telotristat ethyl of the glucuronidation of 1'-hydroxymidazolam.
Management
When drugs that are known substrates of CYP450 3A4 and/or 2B6 are coadministered with telotristat ethyl, the possibility of a diminished therapeutic response to those drugs should be considered. Dosage adjustments as well as clinical and laboratory monitoring may be appropriate for some drugs, particularly those with a narrow therapeutic range, whenever telotristat ethyl is added to or withdrawn from therapy.
References (2)
- Cerner Multum, Inc. "UK Summary of Product Characteristics."
- (2017) "Product Information. Xermelo (telotristat ethyl)." Lexicon Pharmaceuticals, Inc.
Food/lifestyle interactions
Moderate food/lifestyle interactions
Moderate:
aliskiren Food/Lifestyle
Applies to: Tekturna (aliskiren)
Generally avoid
Coadministration with orange, apple, or grapefruit juice may significantly decrease the oral bioavailability and renin-inhibiting effect of aliskiren. The exact mechanism of interaction is unknown, but may include inhibition of OATP2B1-mediated influx of aliskiren in the small intestine, formation of insoluble complexes between fruit juice constituents and aliskiren, and/or increased ionization of aliskiren due to reduced intestinal pH. In 12 healthy volunteers, 200 mL of either orange juice or apple juice administered three times daily for 5 days in combination with a single 150 mg oral dose of aliskiren on day 3 reduced the mean aliskiren peak plasma concentration (Cmax) and systemic exposure (AUC) by approximately 80% and 60%, respectively, compared to water. Plasma renin activity was 87% and 67% higher at 24 hours postdose when aliskiren was administered with orange juice and apple juice, respectively, compared to water. No significant differences were observed in the blood pressure or heart rate between treatments. However, this may be due to the delayed onset of aliskiren's blood pressure-lowering effect, which would not be apparent following a single dose. A similar pharmacokinetic interaction has been reported with grapefruit juice. In 11 healthy volunteers, 200 mL of normal strength grapefruit juice administered three times daily for 5 days in combination with a single 150 mg oral dose of aliskiren on day 3 reduced the mean aliskiren Cmax and AUC by 81% and 61%, respectively, but there was no change in plasma renin activity compared to water. A high degree of interpatient variability was observed with all three interactions.
Monitor
High-fat meals can substantially reduce the gastrointestinal absorption of aliskiren. According to the product labeling, administration of aliskiren with a high-fat meal decreased the mean peak plasma concentration (Cmax) and systemic exposure (AUC) by 85% and 71%, respectively. In clinical trials, however, aliskiren was administered without a fixed requirement in relation to meals.
Management
To ensure steady systemic drug levels and therapeutic effects, patients should establish a routine pattern for administration of aliskiren with regard to meals. Coadministration with orange, apple, or grapefruit juice should be avoided, especially if these juices are to be consumed on a regular basis or shortly before or after aliskiren dosing.
References (4)
- (2007) "Product Information. Tekturna (aliskiren)." Novartis Pharmaceuticals
- Vaidyanathan S, Jarugula V, Dieterich HA, Howard D, Dole WP (2008) "Clinical pharmacokinetics and pharmacodynamics of aliskiren." Clin Pharmacokinet, 47, p. 515-31
- Tapaninen T, Neuvonen PJ, Niemi M (2010) "Grapefruit juice greatly reduces the plasma concentrations of the OATP2B1 and CYP3A4 substrate aliskiren." Clin Pharmacol Ther, 88, p. 339-42
- Tapaninen T, Neuvonen PJ, Niemi M (2010) "Orange and apple juices greatly reduce the plasma concentrations of the OATP2B1 substrate aliskiren." Br J Clin Pharmacol, 71, p. 718-26
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
9 potential interactions Applies to: 9 conditions, including Constipation, Heart Failure, Diabetes Mellitus, Hemodialysis, and Liver Disease.
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. .
Dehydration
Moderate:
Tekturna
The aliskiren in Tekturna has a moderate potential interaction with Dehydration.
Symptomatic hypotension may occur after treatment initiation with aliskiren in patients with marked volume depletion, salt depletion, or with combined use of aliskiren and other agents acting on the renin-angiotensin-aldosterone system. It is recommended to correct the volume or salt depletion before administering aliskiren. Close monitoring is recommended.
Diabetes Mellitus
Major:
Tekturna
The aliskiren in Tekturna has a major potential interaction with Diabetes Mellitus.
The use of aliskiren is contraindicated in patients with diabetes who are receiving angiotensin-converting enzyme (ACE) inhibitors or angiotensin II receptor blockers (ARBs), as there is an increased risk of renal impairment, hyperkalemia, and hypotension.
Heart Failure
Moderate:
Tekturna
The aliskiren in Tekturna has a moderate potential interaction with Heart Failure.
Renal function should be monitored periodically in patients treated with aliskiren, as changes can occur including acute renal failure. Patients on aliskiren whose renal function may depend in part of the RAAS (renin-angiotensin-aldosterone system), such as patients with renal artery stenosis, severe heart failure, or postmyocardial infarction may be at higher risk for developing acute renal failure. Treatment should be discontinued in any patients who develop clinically significant decrease in renal function. Patients with renal impairment should be observed closely. The safety and effectiveness of aliskiren have not been established in patients with severe renal impairment (CrCl < 30 mL/min), as these patients were excluded from clinical trials.
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.
History - Myocardial Infarction
Moderate:
Tekturna
The aliskiren in Tekturna has a moderate potential interaction with History - Myocardial Infarction.
Renal function should be monitored periodically in patients treated with aliskiren, as changes can occur including acute renal failure. Patients on aliskiren whose renal function may depend in part of the RAAS (renin-angiotensin-aldosterone system), such as patients with renal artery stenosis, severe heart failure, or postmyocardial infarction may be at higher risk for developing acute renal failure. Treatment should be discontinued in any patients who develop clinically significant decrease in renal function. Patients with renal impairment should be observed closely. The safety and effectiveness of aliskiren have not been established in patients with severe renal impairment (CrCl < 30 mL/min), as these patients were excluded from clinical trials.
Hyponatremia
Moderate:
Tekturna
The aliskiren in Tekturna has a moderate potential interaction with Hyponatremia.
Symptomatic hypotension may occur after treatment initiation with aliskiren in patients with marked volume depletion, salt depletion, or with combined use of aliskiren and other agents acting on the renin-angiotensin-aldosterone system. It is recommended to correct the volume or salt depletion before administering aliskiren. Close monitoring is recommended.
Liver Disease
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.
Renal Dysfunction
Moderate:
Tekturna
The aliskiren in Tekturna has a moderate potential interaction with Renal Dysfunction.
Renal function should be monitored periodically in patients treated with aliskiren, as changes can occur including acute renal failure. Patients on aliskiren whose renal function may depend in part of the RAAS (renin-angiotensin-aldosterone system), such as patients with renal artery stenosis, severe heart failure, or postmyocardial infarction may be at higher risk for developing acute renal failure. Treatment should be discontinued in any patients who develop clinically significant decrease in renal function. Patients with renal impairment should be observed closely. The safety and effectiveness of aliskiren have not been established in patients with severe renal impairment (CrCl < 30 mL/min), as these patients were excluded from clinical trials.
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Tekturna
A total of 318 drugs are known to interact with Tekturna.
- Tekturna is in the drug class renin inhibitors.
- Tekturna is used to treat High Blood Pressure.
telotristat
A total of 372 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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