Interactions between Penpulimab and Prolia
1 drug interaction and 11 additional warnings found for the following 2 drugs:
- penpulimab
- Prolia (denosumab)
Drug interactions
Moderate drug interactions
Moderate:
denosumab penpulimab
Applies to: Prolia (denosumab) and penpulimab
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)
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- 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
- 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
- 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
- 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
- (2022) "Product Information. Imfinzi (durvalumab)." AstraZeneca Pty Ltd
- (2023) "Product Information. Yervoy (ipilimumab)." Bristol-Myers Squibb, SUPPL-129
- (2021) "Product Information. Yervoy (ipilimumab)." Bristol-Myers Squibb Australia Pty Ltd, V15.0
- (2022) "Product Information. Yervoy (ipilimumab)." Bristol-Myers Squibb Pharmaceuticals Ltd
- (2023) "Product Information. Libtayo (cemiplimab)." Regeneron Pharmaceuticals Inc, SUPPL-16
- (2023) "Product Information. Libtayo (cemiplimab)." Sanofi-Aventis Australia Pty Ltd, lib-ccdsv7-piv4-05ju
- (2023) "Product Information. Libtayo (cemiplimab)." Sanofi
- (2023) "Product Information. Tecentriq (atezolizumab)." Genentech, SUPPL-51
- (2023) "Product Information. Imfinzi (durvalumab)." Astra-Zeneca Pharmaceuticals, SUPPL-42
- (2023) "Product Information. Opdualag (nivolumab-relatlimab)." (Obsolete) Bristol-Myers Squibb Australia Pty Ltd, 2
- (2022) "Product Information. Opdualag (nivolumab-relatlimab)." Bristol-Myers Squibb
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- (2024) "Product Information. Tecentriq Hybreza (atezolizumab-hyaluronidase)." Genentech
- 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
- 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
- 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/
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- (2024) "Product Information. Imfinzi (durvalumab)." AstraZeneca UK Ltd
- 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
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- (2025) "Product Information. Keytruda Qlex (berahyaluronidase alfa-pembrolizumab)." Merck Sharp & Dohme LLC, ORIG-2
- (2025) "Product Information. Keytruda (pembrolizumab)." Merck Sharp & Dohme LLC
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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
11 potential interactions Applies to: 10 conditions, including Hypocalcemia, Hypoparathyroidism, Thyroid Disease, Autoimmune Disorders, and Liver Disease.
Autoimmune Disorders
Moderate:
penpulimab
Penpulimab has a moderate potential interaction with Autoimmune Disorders.
Programmed death receptor-1/ligand-1 (PD-1/PD-L1) blocking antibodies can cause immune-mediated adverse reactions, which may be severe or fatal. Immune-mediated adverse reactions can occur in any organ system or tissue at any time after starting therapy. This may be considered when using PD-1/PD-L1 blocking antibodies in patients with immune system disorders (e.g., ulcerative colitis, Crohn's disease, lupus) or with conditions affecting the nervous system (e.g., myasthenia gravis, Guillain-Barre syndrome). It is recommended to monitor patients closely for signs/symptoms that may be clinical manifestations of underlying immune-mediated adverse reactions.
Bone Marrow Transplantation
Moderate:
penpulimab
Penpulimab has a moderate potential interaction with Bone Marrow Transplantation.
Fatal and other serious complications can occur in patients who receive allogeneic hematopoietic stem cell transplantation (HSCT) before or after being treated with a programmed death receptor-1/ligand-1 (PD-1/PD-L1) blocking antibody. Transplant-related complications include hyperacute graft-versus-host disease (GVHD), acute GVHD, chronic GVHD, hepatic veno-occlusive disease after reduced intensity conditioning, and steroid-requiring febrile syndrome (without an identified infectious cause). These complications may occur despite intervening therapy between PD-1/PD-L1 blockade and allogeneic HSCT. It is recommended to follow patients closely for evidence of transplant-related complications and intervene promptly. The benefit versus risks of treatment with a PD-1/PD-L1 blocking antibody before or after an allogeneic HSCT should be considered.
History, Radiation Therapy
Moderate:
penpulimab
Penpulimab has a moderate potential interaction with History, Radiation Therapy.
Penpulimab can cause immune-mediated pneumonitis. In general, the incidence of pneumonitis was higher in patients with prior thoracic radiation.
Hypocalcemia
Major:
Prolia
The denosumab in Prolia has a major potential interaction with Hypocalcemia.
Preexisting hypocalcemia must be corrected prior to initiating treatment with denosumab. Caution should be exercised in patients predisposed to hypocalcemia and any disturbances of mineral metabolism, such as history of hypoparathyroidism, thyroid or parathyroid surgery, malabsorption syndromes, excision of small intestine, severe renal impairment or dialysis. Clinical monitoring of calcium and mineral levels (phosphorus and magnesium) are highly recommended within 14 days of denosumab injection. It is important to maintain calcium levels with adequate calcium and vitamin D supplementation.
Hypoparathyroidism
Major:
Prolia
The denosumab in Prolia has a major potential interaction with Hypoparathyroidism.
Preexisting hypocalcemia must be corrected prior to initiating treatment with denosumab. Caution should be exercised in patients predisposed to hypocalcemia and any disturbances of mineral metabolism, such as history of hypoparathyroidism, thyroid or parathyroid surgery, malabsorption syndromes, excision of small intestine, severe renal impairment or dialysis. Clinical monitoring of calcium and mineral levels (phosphorus and magnesium) are highly recommended within 14 days of denosumab injection. It is important to maintain calcium levels with adequate calcium and vitamin D supplementation.
Immunodeficiency
Moderate:
Prolia
The denosumab in Prolia has a moderate potential interaction with Immunodeficiency.
Denosumab should be used with caution in patients with impaired immune systems or taking concomitant immunosuppressant agents as they may be at increased risk for serious infections.
Liver Disease
Moderate:
penpulimab
Penpulimab has a moderate potential interaction with Liver Disease.
The effect of severe hepatic dysfunction (total bilirubin greater than 3 times ULN and any AST) on the pharmacokinetics of penpulimab is unknown. Additionally, this drug can cause immune-mediated hepatitis and hepatotoxicity. Evaluate liver enzymes at baseline and periodically during treatment.
Organ Transplant
Moderate:
penpulimab
Penpulimab has a moderate potential interaction with Organ Transplant.
Solid organ transplant rejection and other transplant (including corneal graft) rejection have been reported with the use of programmed death receptor-1/ligand-1 (PD-1/PD-L1) blocking antibodies. This may be considered when using PD-1/PD-L1 blocking antibodies in patients who have received a solid organ or other transplant.
Renal Dysfunction
Major:
Prolia
The denosumab in Prolia has a major potential interaction with Renal Dysfunction.
Preexisting hypocalcemia must be corrected prior to initiating treatment with denosumab. Caution should be exercised in patients predisposed to hypocalcemia and any disturbances of mineral metabolism, such as history of hypoparathyroidism, thyroid or parathyroid surgery, malabsorption syndromes, excision of small intestine, severe renal impairment or dialysis. Clinical monitoring of calcium and mineral levels (phosphorus and magnesium) are highly recommended within 14 days of denosumab injection. It is important to maintain calcium levels with adequate calcium and vitamin D supplementation.
Moderate:
penpulimab
Penpulimab has a moderate potential interaction with Renal Dysfunction.
The effect of severe renal dysfunction (CrCl below 30 mL/min) on the pharmacokinetics of penpulimab is unknown. Additionally, this drug can cause immune-mediated nephritis and renal dysfunction. Patients should be monitored for early identification and management. Evaluate creatinine levels at baseline and periodically during treatment.
Thyroid Disease
Major:
Prolia
The denosumab in Prolia has a major potential interaction with Thyroid Disease.
Preexisting hypocalcemia must be corrected prior to initiating treatment with denosumab. Caution should be exercised in patients predisposed to hypocalcemia and any disturbances of mineral metabolism, such as history of hypoparathyroidism, thyroid or parathyroid surgery, malabsorption syndromes, excision of small intestine, severe renal impairment or dialysis. Clinical monitoring of calcium and mineral levels (phosphorus and magnesium) are highly recommended within 14 days of denosumab injection. It is important to maintain calcium levels with adequate calcium and vitamin D supplementation.
More resources
penpulimab
A total of 614 drugs are known to interact with penpulimab.
- Penpulimab is in the drug class Immune checkpoint inhibitors (PD-1 and PD-L1 inhibitors).
- Penpulimab is used to treat Nasopharyngeal Carcinoma.
Prolia
A total of 324 drugs are known to interact with Prolia.
- Prolia is in the drug class miscellaneous bone resorption inhibitors.
- Prolia is used to treat Osteoporosis.
Drug Interaction Classification
| Highly clinically significant. Avoid combinations; the risk of the interaction outweighs the benefit. | |
| Moderately clinically significant. Usually avoid combinations; use it only under special circumstances. | |
| 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. | |
| No interaction information available. |
Further information
Always consult your healthcare provider to ensure the information displayed on this page applies to your personal circumstances.