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Drug Interactions between dasatinib and tremelimumab

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

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Interactions between your drugs

Moderate

dasatinib tremelimumab

Applies to: dasatinib and tremelimumab

MONITOR: Although immune checkpoint inhibitors (ICI) such as programmed cell death-1 (PD-1), programmed death ligand-1 inhibitors (PD-L1), and anti-CTLA-4 monoclonal antibodies may be indicated for use in combination in with other immunosuppressive agents, their pharmacodynamic effects and efficacy may be affected by corticosteroids and immunosuppressants. The mechanism of this interaction is related to the immunosuppressive effects of corticosteroids and other immunosuppressants, particularly their inhibition of T-cell activation, which may reduce the efficacy of immune checkpoint inhibitors that rely on a strong immune response to target tumor cells. Additionally, immune-related adverse events (irAEs) from ICIs may indicate a stronger immune response and improved tumor outcomes and treating them with immunosuppressive agents could therefore reduce immune activity and the efficacy of ICIs. For instance, data from the Dutch Melanoma Treatment Registry (DTMR) showed that patients with advanced melanoma who experienced severe ICI toxicity had a longer median overall survival (OS) (23 months vs. 15 months), but those needing anti-TNF therapy for steroid-refractory toxicity had worse outcomes (17 months vs. 27 months with steroids alone). In a study of patients with advanced NSCLC (n=640), oral or intravenous corticosteroid use (>/= 10 mg prednisone equivalent per day) at the time of or within 30 days of starting PD-1/PD-L1 blockade with either pembrolizumab, nivolumab, atezolizumab, or durvalumab (n=90) was associated with decreased response and overall poorer outcomes, compared to those who received and discontinued corticosteroid treatment prior to commencing PD-1/PD-L1 therapy. Further, an international multicenter cohort study in melanoma patients who developed irAEs with ICI therapy found that higher peak doses of corticosteroids, but not cumulative doses, were associated with worse survival, though the impact of second-line immunosuppressants remains unclear. A prospective observational study using data from a German multicenter skin cancer registry (ADOREG) evaluated patients with unresectable advanced melanoma who received immunosuppressive therapy (IST) (e.g., methylprednisolone, prednisolone, dexamethasone, infliximab, interferon, methotrexate) within 60 days before or within 30 days after the start of an ICI. The initiation of IST before, but not after the start of ICI, was associated with worse progression free survival in patients without brain metastasis, and worse OS in patients with brain metastasis. However, based on available literature, it is difficult to determine whether these effects are due to corticosteroid and/or immunosuppressant use or if they reflect subgroups of patients in studies with poorer prognoses.

MANAGEMENT: Caution and closer monitoring for reduced efficacy of immune checkpoint inhibitors (ICI) is advised if corticosteroids and/or other immunosuppressants are used concurrently. Based on available literature, the use of immunosuppressants and/or systemic corticosteroids (>=10 mg prednisone equivalent/day) should be avoided at the time of, or within 30 to 60 days of starting therapy with an ICI if clinically possible. Corticosteroids and/or immunosuppressants can generally be safely used for the treatment of immune-mediated reactions after starting an ICI. Some manufacturers advise that corticosteroids may be used as premedication when the ICI is used in combination with chemotherapy, as antiemetic prophylaxis, and/or to alleviate chemotherapy-related adverse effects. Individual product labeling for the ICI in question should be consulted for specific recommendations.

References (29)
  1. Arbour KC, Mezquita L, Long N, et al. (2018) "Impact of Baseline Steroids on Efficacy of Programmed Cell Death-1 and Programmed Death-Ligand 1 Blockade in Patients With Non-Small-Cell Lung Cancer." J Clin Oncol, 36, p. 2872-2878
  2. (2020) "Product Information. Novoeight (antihemophilic factor)." Novo Nordisk Pharmaceuticals Inc
  3. Horvat TZ, Adel NG, Dand TO, et al. (2015) "Immune-related adverse events, need for systemic immunosuppression, and effects on survival and time to treatment failure in patients with melanoma treated with ipilimumab at Memorial Sloan Kettering Cancer Center." J Clin Oncol, 33, p. 3193-8
  4. Jove M, Vilarino N, Nadal E (2019) "Impact of baseline steroids on efficacy of programmed cell death-1 (PD-1) and programmed death-ligand 1 (PD-L1) blockade in patients with advanced non-small cell lung cancer." Transl Lung Cancer Res, 8, S364-8
  5. Scott SC, Pennell NA (2018) "Early use of systemic corticosteroids in patients with advanced NSCLC treated with nivolumab." J Thorac Oncol, 13, p. 1771-5
  6. Fuca G, Galli G, Poggi M, et al. (2019) "Modulation of peripheral blood immune cells by early use of steroids and its association with clinical outcomes in patients with metastatic non-small cell lung cancer treated with immune checkpoint inhibitors." ESMO Open, 4, e000457
  7. (2022) "Product Information. Imfinzi (durvalumab)." AstraZeneca Pty Ltd
  8. (2023) "Product Information. Yervoy (ipilimumab)." Bristol-Myers Squibb, SUPPL-129
  9. (2021) "Product Information. Yervoy (ipilimumab)." Bristol-Myers Squibb Australia Pty Ltd, V15.0
  10. (2022) "Product Information. Yervoy (ipilimumab)." Bristol-Myers Squibb Pharmaceuticals Ltd
  11. (2023) "Product Information. Libtayo (cemiplimab)." Regeneron Pharmaceuticals Inc, SUPPL-16
  12. (2023) "Product Information. Libtayo (cemiplimab)." Sanofi-Aventis Australia Pty Ltd, lib-ccdsv7-piv4-05ju
  13. (2023) "Product Information. Libtayo (cemiplimab)." Sanofi
  14. (2023) "Product Information. Tecentriq (atezolizumab)." Genentech, SUPPL-51
  15. (2023) "Product Information. Imfinzi (durvalumab)." Astra-Zeneca Pharmaceuticals, SUPPL-42
  16. (2023) "Product Information. Opdualag (nivolumab-relatlimab)." Bristol-Myers Squibb Australia Pty Ltd, 2
  17. (2022) "Product Information. Opdualag (nivolumab-relatlimab)." Bristol-Myers Squibb
  18. (2024) "Product Information. Keytruda (pembrolizumab)." Merck Sharp & Dohme LLC, SUPPL-160
  19. (2024) "Product Information. Keytruda (pembrolizumab)." Merck Sharp & Dohme (Australia) Pty Ltd
  20. (2024) "Product Information. Keytruda (pembrolizumab)." Merck Sharp & Dohme (UK) Ltd
  21. (2024) "Product Information. Tecentriq (atezolizumab)." Roche Products Pty Ltd
  22. (2024) "Product Information. Tecentriq Hybreza (atezolizumab-hyaluronidase)." Genentech
  23. Kochanek C, Gilde C, Zimmer L, et al (2024) Effects of an immunosuppressive therapy on the efficacy of immune checkpoint inhibition in metastatic melanoma - An analysis of the prospective skin cancer registry ADOREG https://www.sciencedirect.com/science/article/pii/S0959804923008109#:~:text=Immuno
  24. Verheijden RJ, Burgers FH, Janssen J, et al (2024) Corticosteroids and other immunosuppressants for immune-related adverse events and checkpoint inhibitor effectiveness in melanoma https://www.ejcancer.com/article/S0959-8049(24)00828-1/fulltext#:~:text=Recent%20studies%20indicate%20an%20association,secon
  25. Verheijden RJ, May AM, Black CU, et al. (2024) Association of anti-TNF with decreased survival in steroid refractory ipilimumab and anti-PD1-treated patients in the dutch melanoma treatment registry https://pubmed.ncbi.nlm.nih.gov/31988197/
  26. (2024) "Product Information. Tecentriq (atezolizumab)." Roche Products Ltd
  27. (2024) "Product Information. Imfinzi (durvalumab)." AstraZeneca UK Ltd
  28. Kostine M, Mauric E, Tison A, et al. (2021) "Baseline co-medications may alter the anti-tumoural effect of checkpoint inhibitors as well as the risk of immune-related adverse events." Eur J Cancer, 157, p. 474-84
  29. BeiGene AUS (2025) Australian product information Tevimbra (tislelizumab (rch)) https://www.ebs.tga.gov.au/ebs/picmi/picmirepository.nsf/pdf?OpenAgent=&id=CP-2024-PI-02006-1&d=20250108172310101&d=20250108172310101.&d=20250130172310101

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Drug and food interactions

Major

dasatinib food

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)
  1. Cerner Multum, Inc. "UK Summary of Product Characteristics."
  2. (2006) "Product Information. Sprycel (dasatinib)." Bristol-Myers Squibb
  3. Cerner Multum, Inc. "Australian Product Information."

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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.


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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.