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Drug Interactions between sofosbuvir / velpatasvir / voxilaprevir and telotristat

This report displays the potential drug interactions for the following 2 drugs:

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Interactions between your drugs

Moderate

velpatasvir telotristat ethyl

Applies to: sofosbuvir / velpatasvir / voxilaprevir 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for some drugs, particularly those with a narrow therapeutic range, whenever telotristat ethyl is added to or withdrawn from therapy.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)
  1. Cerner Multum, Inc. "UK Summary of Product Characteristics."
  2. (2017) "Product Information. Xermelo (telotristat ethyl)." Lexicon Pharmaceuticals, Inc.
Moderate

velpatasvir voxilaprevir

Applies to: sofosbuvir / velpatasvir / voxilaprevir and sofosbuvir / velpatasvir / voxilaprevir

MONITOR: Coadministration with inhibitors of organic anion transporting polypeptides (OATP) 1B1 and/or 1B3 may increase the plasma concentrations of voxilaprevir, which is a substrate of the hepatic uptake transporters. When a single 100 mg dose of voxilaprevir was administered with a single 600 mg dose of the potent OATP 1B1/1B3 inhibitor cyclosporine (n=24), mean voxilaprevir peak plasma concentration (Cmax) and systemic exposure (AUC) increased by approximately 19.0- and 9.4-fold, respectively. Inhibition of P-glycoprotein (P-gp)- and breast cancer resistance protein (BCRP)-mediated intestinal transport and CYP450 3A4-mediated metabolism of voxilaprevir may also contribute to the overall interaction with cyclosporine. The safety of such high levels of voxilaprevir has not been established.

MANAGEMENT: Caution and monitoring are advised when voxilaprevir is used with OATP 1B1 or 1B3 inhibitors.

References (1)
  1. (2017) "Product Information. Vosevi (sofosbuvir/velpatasvir/voxilaprevir)." Gilead Sciences

Drug and food interactions

Moderate

telotristat ethyl food

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)
  1. (2017) "Product Information. Xermelo (telotristat ethyl)." Lexicon Pharmaceuticals, Inc.
Moderate

voxilaprevir food

Applies to: sofosbuvir / velpatasvir / voxilaprevir

ADJUST DOSING INTERVAL: Administration with food enhances the oral bioavailability of sofosbuvir, velpatasvir, and voxilaprevir. Relative to fasting conditions, mean sofosbuvir systemic exposure (AUC) increased by 64% to 144%, mean velpatasvir AUC increased by 40% to 166%, and mean voxilaprevir AUC increased by 112% to 435% when the combined sofosbuvir/velpatasvir/voxilaprevir formulation is administered with food.

MANAGEMENT: Sofosbuvir/velpatasvir/voxilaprevir should be administered with food.

References (1)
  1. (2017) "Product Information. Vosevi (sofosbuvir/velpatasvir/voxilaprevir)." Gilead Sciences

Therapeutic duplication warnings

No warnings were found for your selected drugs.

Therapeutic duplication warnings are only returned when drugs within the same group exceed the recommended therapeutic duplication maximum.

See also

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Drug Interaction Classification

These classifications are only a guideline. The relevance of a particular drug interaction to a specific individual is difficult to determine. Always consult your healthcare provider before starting or stopping any medication.
Major Highly clinically significant. Avoid combinations; the risk of the interaction outweighs the benefit.
Moderate Moderately clinically significant. Usually avoid combinations; use it only under special circumstances.
Minor 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.
Unknown No interaction information available.

Further information

Always consult your healthcare provider to ensure the information displayed on this page applies to your personal circumstances.

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