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Drug Interactions between paricalcitol and telotristat

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

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Interactions between your drugs

Moderate

paricalcitol telotristat ethyl

Applies to: paricalcitol 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for some drugs, particularly those with a narrow therapeutic range, whenever telotristat ethyl is added to or withdrawn from therapy.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.

Drug and food interactions

Moderate

paricalcitol food

Applies to: paricalcitol

MONITOR: Additive effects and possible toxicity (e.g., hypercalcemia, hypercalciuria, and/or hyperphosphatemia) may occur when patients using vitamin D and/or vitamin D analogs ingest a diet high in vitamin D, calcium, and/or phosphorus. The biologically active forms of vitamin D stimulate intestinal absorption of calcium and phosphorus. This may be helpful in patients with hypocalcemia and/or hypophosphatemia. However, sudden increases in calcium or phosphorus consumption due to dietary changes could precipitate hypercalcemia and/or hyperphosphatemia. Patients with certain disease states, such as impaired renal function, may be more susceptible to toxic side effects like ectopic calcification. On the other hand, if dietary calcium is inadequate for the body's needs, the active form of vitamin D will stimulate osteoclasts to pull calcium from the bones. This may be detrimental in a patient with reduced bone density.

MANAGEMENT: Given the narrow therapeutic index of vitamin D and vitamin D analogs, the amounts of calcium, phosphorus, and vitamin D present in the patient's diet may need to be taken into consideration. Specific dietary guidance should be discussed with the patient and regular lab work should be monitored as indicated. Calcium, phosphorus, and vitamin D levels should be kept within the desired ranges, which may differ depending on the patient's condition. Patients should also be counseled on the signs and symptoms of hypervitaminosis D, hypercalcemia, and/or hyperphosphatemia.

References (10)
  1. (2023) "Product Information. Drisdol (ergocalciferol)." Validus Pharmaceuticals LLC
  2. (2024) "Product Information. Fultium-D3 (colecalciferol)." Internis Pharmaceuticals Ltd
  3. (2024) "Product Information. Ostelin Specialist Range Vitamin D (colecalciferol)." Sanofi-Aventis Healthcare Pty Ltd T/A Sanofi Consumer Healthcare
  4. (2021) "Product Information. Rocaltrol (calcitriol)." Atnahs Pharma UK Ltd
  5. (2019) "Product Information. Calcitriol (calcitriol)." Strides Pharma Inc.
  6. (2024) "Product Information. Calcitriol (GenRx) (calcitriol)." Apotex Pty Ltd
  7. (2022) "Product Information. Ergocalciferol (ergocalciferol)." RPH Pharmaceuticals AB
  8. (2020) "Product Information. Sandoz D (cholecalciferol)." Sandoz Canada Incorporated
  9. Fischer V, Haffner-Luntzer M, Prystaz K, et al. (2024) Calcium and vitamin-D deficiency marginally impairs fracture healing but aggravates posttraumatic bone loss in osteoporotic mice. https://www.nature.com/articles/s41598-017-07511-2
  10. National Institutes of Health Office of Dietary Supplements (2024) Vitamin D https://ods.od.nih.gov/factsheets/VitaminD-HealthProfessional/#h37
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.

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

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