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Drug Interactions between procarbazine and tremelimumab

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

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Moderate

procarbazine tremelimumab

Applies to: procarbazine 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

procarbazine food

Applies to: procarbazine

CONTRAINDICATED: Foods that contain large amounts of tyramine may precipitate a hypertensive crisis in patients treated with monoamine oxidase inhibitors (MAOIs). The mechanism is inhibition of MAO-A, the enzyme responsible for metabolizing exogenous amines such as tyramine in the gut and preventing them from being absorbed intact. Once absorbed, tyramine is metabolized to octopamine, a substance that is believed to displace norepinephrine from storage granules.

GENERALLY AVOID: Alcohol may potentiate some of the pharmacologic effects of MAOIs. Use in combination may result in additive central nervous system depression and/or impairment of judgment, thinking, and psychomotor skills.

MANAGEMENT: In general, patients treated with MAOIs or other agents that possess MAOI activity (e.g., furazolidone, linezolid, procarbazine) should avoid consumption of products that contain large amounts of amines and protein foods in which aging or breakdown of protein is used to increase flavor. These foods include cheese (particularly strong, aged or processed cheeses), sour cream, wine (particularly red wine), champagne, beer, pickled herring, anchovies, caviar, shrimp paste, liver (particularly chicken liver), dry sausage, salamis, figs, raisins, bananas, avocados, chocolate, soy sauce, bean curd, sauerkraut, yogurt, papaya products, meat tenderizers, fava bean pods, protein extracts, yeast extracts, and dietary supplements. Caffeine may also precipitate hypertensive crisis so its intake should be minimized as well. At least 14 days should elapse following discontinuation of MAOI therapy before these foods may be consumed. Specially designed reference materials and dietary consultation are recommended so that an appropriate and safe diet can be planned. Patients should be advised to promptly seek medical attention if they experience potential signs and symptoms of a hypertensive crisis such as severe headache, visual disturbances, difficulty thinking, stupor or coma, seizures, chest pain, unexplained nausea or vomiting, and stroke-like symptoms. Patients should also be counseled not to use MAOIs with alcohol, and to avoid hazardous activities requiring complete mental alertness and motor coordination until they know how these agents affect them.

References (19)
  1. Pettinger WA, Soyangco FG, Oates JA (1968) "Inhibition of monoamine oxidase in man by furazolidone." Clin Pharmacol Ther, 9, p. 442-7
  2. Goldberg LI (1964) "Monoamine oxidase inhibitors: adverse reactions and possible mechanisms." JAMA, 190, p. 456-62
  3. Nuessle WF, Norman FC, Miller HE (1965) "Pickled herring and tranylcypromine reaction." JAMA, 192, p. 142-3
  4. Sweet RA, Liebowitz MR, Holt CS, Heimberg RG (1991) "Potential interactions between monoamine oxidase inhibitors and prescribed dietary supplements." J Clin Psychopharmacol, 11, p. 331-2
  5. Walker JI, Davidson J, Zung WWK (1984) "Patient compliance with MAO Inhibitor therapy." J Clin Psychiatry, 45, p. 78-80
  6. Ban TA (1975) "Drug interactions with psychoactive drugs." Dis Nerv Syst, 36, p. 164-6
  7. Darcy PF, Griffin JP (1995) "Interactions with drugs used in the treatment of depressive illness." Adverse Drug React Toxicol Rev, 14, p. 211-31
  8. Maxwell MB (1980) "Reexamining the dietary restrictions with procarbazine (an MAOI)." Cancer Nurs, 3, p. 451-7
  9. (2001) "Product Information. Matulane (procarbazine)." Roche Laboratories
  10. De Vita VT, Hahn MA, Oliverio VT (1965) "Monoamine oxidase inhibition by a new carcinostatic agent, n-isopropyl-a-(2-methylhydrazino)-p-toluamide (MIH). (30590)." Proc Soc Exp Biol Med, 120, p. 561-5
  11. Zetin M, Plon L, DeAntonio M (1987) "MAOI reaction with powdered protein dietary supplement." J Clin Psychiatry, 48, p. 499
  12. Domino EF, Selden EM (1984) "Red wine and reactions." J Clin Psychopharmacol, 4, p. 173-4
  13. Tailor SA, Shulman KI, Walker SE, Moss J, Gardner D (1994) "Hypertensive episode associated with phenelzine and tap beer--a reanalysis of the role of pressor amines in beer." J Clin Psychopharmacol, 14, p. 5-14
  14. Pohl R, Balon R, Berchou R (1988) "Reaction to chicken nuggets in a patient taking an MAOI." Am J Psychiatry, 145, p. 651
  15. (2001) "Product Information. Furoxone (furazolidone)." Roberts Pharmaceutical Corporation
  16. (2001) "Product Information. Nardil (phenelzine)." Parke-Davis
  17. (2001) "Product Information. Marplan (isocarboxazid)." Roche Laboratories
  18. (2001) "Product Information. Zyvox (linezolid)." Pharmacia and Upjohn
  19. Martin TG (1996) "Serotonin syndrome." Ann Emerg Med, 28, p. 520-6

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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.