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Interactions between Topotecan and Toripalimab

1 drug interaction and 7 additional warnings found for the following 2 drugs:

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Drug interactions

Moderate drug interactions

Moderate:

topotecan toripalimab

Applies to: topotecan and toripalimab
Monitor

Although immune checkpoint inhibitors (ICIs) such as anti-cytotoxic T-lymphocyte-associated protein (CTLA)-4 monoclonal antibodies and inhibitors of programmed cell death-1 (PD-1) and/or programmed death ligand-1 (PD-L1) may be indicated for use in combination with other immunosuppressive agents, their pharmacodynamic effects and efficacy may be affected by systemic corticosteroids and immunosuppressants. The mechanism of this interaction is related to the immunosuppressive effects of systemic corticosteroids and other immunosuppressants, particularly their inhibition of T-cell activation, which may reduce the efficacy of ICIs 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; therefore, treating those irAEs with immunosuppressive agents could theoretically reduce immune activity and thus the efficacy of the ICI. For instance, data from the Dutch Melanoma Treatment Registry (DTMR) reported that patients with advanced melanoma who experienced severe ICI toxicity had a longer median overall survival (OS) compared to those without severe toxicity (23 months vs. 15 months). Among patients who experienced severe toxicity, those treated with anti-tumor necrosis factor (TNF) therapy with or without steroids for steroid-refractory toxicity had a significantly reduced median OS compared to those managed with steroids alone (17 months vs. 27 months). Likewise, in a study of patients with advanced non-small cell lung cancer (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 (ICIs) 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 adverse 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 more specific recommendations. For example, some ICIs may have recommendations regarding which medication to administer first when the ICI is being administered in combination with chemotherapy.

References (31)
  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)." (Obsolete) Bristol-Myers Squibb Australia Pty Ltd, 2
  17. (2022) "Product Information. Opdualag (nivolumab-relatlimab)." Bristol-Myers Squibb
  18. (2024) "Product Information. Tecentriq (atezolizumab)." Roche Products Pty Ltd
  19. (2024) "Product Information. Tecentriq Hybreza (atezolizumab-hyaluronidase)." Genentech
  20. 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
  21. 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
  22. 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/
  23. (2024) "Product Information. Tecentriq (atezolizumab)." Roche Products Ltd
  24. (2024) "Product Information. Imfinzi (durvalumab)." AstraZeneca UK Ltd
  25. 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
  26. (2024) "Product Information. Tevimbra (tislelizumab)." Beigene Aus Pty Ltd, v1
  27. (2025) "Product Information. Keytruda Qlex (berahyaluronidase alfa-pembrolizumab)." Merck Sharp & Dohme LLC, ORIG-2
  28. (2025) "Product Information. Keytruda (pembrolizumab)." Merck Sharp & Dohme LLC
  29. (2025) "Product Information. Keytruda (pembrolizumab)." Merck Canada Inc
  30. (2025) "Product Information. Keytruda (pembrolizumab)." Merck Sharp & Dohme (UK) Ltd
  31. (2025) "Product Information. Keytruda (pembrolizumab)." Merck Sharp & Dohme (Australia) Pty Ltd

Food/lifestyle interactions

No alcohol/food interactions were found. However, this does not necessarily mean no interactions exist. Always consult your healthcare provider.

Disease interactions

7 potential interactions Applies to: 7 conditions, including Diarrhea, Fever, Bleeding Disorder, Infection, and Renal Dysfunction.

Bleeding Disorder

Major:

topotecan

Topotecan has a major potential interaction with Bleeding Disorder.

Topotecan induces myelosuppression. Severe thrombocytopenia (< 25,000/mm3) has been reported during topotecan therapy. Patients should be instructed to immediately report any signs or symptoms suggesting bleeding such as petechiae, purpura, hematuria, or melena. Close clinical monitoring of hematopoietic function is recommended. Therapy with topotecan should not be initiated in patients with platelet counts < 100,000/mm3. Subsequent courses of topotecan should be withheld until platelet counts exceed 100,000/mm3.

Bone Marrow Depression/Low Blood Counts

Major:

topotecan

Topotecan has a major potential interaction with Bone Marrow Depression/Low Blood Counts.

Topotecan induces myelosuppression. Severe neutropenia (< 500/mm3), severe thrombocytopenia (< 25,000/mm3), and severe anemia (< 8 g/dl) have been reported frequently. Patients should be instructed to immediately report any signs or symptoms suggesting bone marrow suppression such as fever, sore throat, local infection, or bleeding. Close clinical monitoring of hematopoietic function is recommended. Therapy with topotecan should not be initiated in patients with neutrophil counts < 1500/mm3 and/or platelet counts < 100,000/mm3. Subsequent courses of topotecan should be withheld until neutrophil counts exceed 1000/mm3, platelet counts exceed 100,000/mm3, and/or hemoglobin levels are at least 9 g/dl.

Diarrhea

Moderate:

topotecan

Topotecan has a moderate potential interaction with Diarrhea.

Topotecan capsules can cause severe and life-threatening diarrhea that may require hospitalization. It is recommended to withhold treatment for severe diarrhea. Manage diarrhea caused by topotecan aggressively and do no administer topotecan capsules to patients with Grade 3 or 4 diarrhea. Reduce the dose of therapy after recovery to Grade 1 or less. Close monitoring is recommended.

Fever

Major:

topotecan

Topotecan has a major potential interaction with Fever.

Topotecan induces myelosuppression. Severe neutropenia (< 500/mm3), severe thrombocytopenia (< 25,000/mm3), and severe anemia (< 8 g/dl) have been reported frequently. Patients should be instructed to immediately report any signs or symptoms suggesting bone marrow suppression such as fever, sore throat, local infection, or bleeding. Close clinical monitoring of hematopoietic function is recommended. Therapy with topotecan should not be initiated in patients with neutrophil counts < 1500/mm3 and/or platelet counts < 100,000/mm3. Subsequent courses of topotecan should be withheld until neutrophil counts exceed 1000/mm3, platelet counts exceed 100,000/mm3, and/or hemoglobin levels are at least 9 g/dl.

Infection

Major:

topotecan

Topotecan has a major potential interaction with Infection.

Because of their cytotoxic effects on rapidly proliferating tissues, antineoplastic agents frequently can, to varying extent, induce myelosuppression. The use of these drugs may be contraindicated in patients with known infectious diseases. All patients should be instructed to immediately report any signs or symptoms suggesting infection such as fever, sore throat, or local infection during antineoplastic therapy. Close clinical monitoring of hematopoietic function is recommended.

Pulmonary Impairment

Moderate:

topotecan

Topotecan has a moderate potential interaction with Pulmonary Impairment.

Fatal cases of interstitial lung disease (ILD) have occurred with the use of topotecan. Risk factors include a history of ILD, pulmonary fibrosis, lung cancer, thoracic radiation, and use of pneumotoxic drugs and/or colony stimulating factors. It is recommended to monitor patients for pulmonary symptoms indicative of ILD and permanently discontinue treatment for confirmed ILD.

Renal Dysfunction

Major:

topotecan

Topotecan has a major potential interaction with Renal Dysfunction.

Topotecan is partially eliminated by the kidney. Approximately 30% of topotecan is excreted in the urine. Plasma clearance of topotecan was reduced 33% in patients with mild renal impairment (creatinine clearance of 40 to 60 mL/min) and 66% in patients with moderate renal impairment (creatinine clearance of 20 to 40 mL/min). Therapy with topotecan should be administered cautiously and at a reduced dosage in patients with moderate to severe renal dysfunction.

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topotecan

A total of 453 drugs are known to interact with topotecan.

toripalimab

A total of 628 drugs are known to interact with toripalimab.

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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