Imjudo (tremelimumab-actl)

No dosing information is available for this tab.

Tremelimumabinjection concentrate for IV infusionis available as single-dose vials containing 25 mg/1.25 mL (20 mg/mL) or 300 mg/15 mL (20 mg/mL). The drug is administered as an IV infusion after dilution. Store vialsin a refrigerator at 2-8oC in original carton to protect from light; do not freeze. Do not shake.

No dosing information is available for this tab.

The manufacturer does not provide any information ondrug interactions with tremelimumab in the prescribing information. Consult the prescribing information for drug interactions of the agents administered in combination with tremelimumab.

There are no contraindication interactions for this drug.

Severe Interaction: Action is required to reduce the risk of severe adverse interaction.

Igg Antibodies And Derivatives/Efgartigimod-Alfa

SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction.

MECHANISM OF ACTION: The neonatal Fc receptor (FcRn) prevents catabolism and mediates recycling of IgG and albumin, which leads to their long persistence in the body.(1,2) Efgartigimod-alfa binds to FcRn and may decrease systemic exposure of other ligands of FcRn, like immunoglobulins and IgG-based antibodies.(3)

CLINICAL EFFECTS: The effectiveness of medicines that bind to FcRn may be decreased.(3)

PREDISPOSING FACTORS: None determined.

PATIENT MANAGEMENT: The manufacturer of efgartigimod-alfa states that efgartigimod-alfa should not be combined with long-term use of FcRn-binding medications. If the medication is essential for the patient, efgartigimod-alfa should be discontinued.(3)

DISCUSSION: Clinical drug interaction studies with efgartigimod-alfa have not been performed. Efgartigimod-alfa may decrease concentrations of compounds that bind to the human FcRn.(3)

Igg Antibodies And Derivatives/Nipocalimab-Aahu

SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction.

MECHANISM OF ACTION: The neonatal Fc receptor (FcRn) prevents catabolism and mediates recycling of IgG and albumin, which leads to their long persistence in the body.(1,2) Nipocalimab-aahu binds to FcRn and may decrease systemic exposure of other ligands of FcRn, like immunoglobulins and IgG-based antibodies.(3)

CLINICAL EFFECTS: The effectiveness of medicines that bind to FcRn may be decreased.(3)

PREDISPOSING FACTORS: None determined.

PATIENT MANAGEMENT: The manufacturer of nipocalimab-aahu states that nipocalimab-aahu should not be combined with long-term use of FcRn-binding medications. If the medication is essential for the patient, nipocalimab-aahu should be discontinued.(3)

DISCUSSION: Clinical drug interaction studies with nipocalimab-aahu have not been performed. Nipocalimab-aahu may decrease concentrations of compounds that bind to the human FcRn.(3)

Moderate Interaction: Assess the risk to the patient and take action as needed.

Igg Antibodies And Derivatives/Rozanolixizumab-Noli

SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed.

MECHANISM OF ACTION: The neonatal Fc receptor (FcRn) prevents catabolism and mediates recycling of IgG and albumin, which leads to their long persistence in the body.(1,2) Rozanolixizumab-noli binds to FcRn and may decrease systemic exposure of other ligands of FcRn, like immunoglobulins and IgG-based antibodies.(3)

CLINICAL EFFECTS: The effectiveness of medications that bind to FcRn may be decreased.(3)

PREDISPOSING FACTORS: None determined.

PATIENT MANAGEMENT: The manufacturer of rozanolixizumab-noli states that concurrent use with medications that bind to the human neonatal Fc receptor (FcRn) should be closely monitored for reduced effectiveness of these medications. If long-term use of such medications is essential for the patient, consider discontinuing rozanolixizumab-noli and use alternative therapies.(3)

DISCUSSION: Clinical drug interaction studies with rozanolixizumab-noli have not been performed. Rozanolixizumab-noli may decrease concentrations of compounds that bind to the human FcRn.(3)

Immune Checkpoint Inhibitors/Proton Pump Inhibitors

SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed.

MECHANISM OF ACTION: The mechanism of this interaction has not been fully investigated. Proposed mechanisms include: 1. Proton pump inhibitor (PPI)-induced changes of the microbiota (dysbiosis) causing resistance to immune checkpoint inhibitors, 2. Co-administration of PPIs with corticosteroids or non steroidal anti-inflammatory drugs (NSAIDs) and immune checkpoint inhibitors resulting in poorer prognosis.(1)

CLINICAL EFFECTS: PPIs may decrease the therapeutic effects of immune checkpoint inhibitors. Several observational studies have shown a reduction in progression free survival (PFS), overall survival (OS), and tumor response in patients on concurrent treatment with immune checkpoint inhibitors and PPIs.(1)

PREDISPOSING FACTORS: None determined.

PATIENT MANAGEMENT: Concurrent use of immune checkpoint inhibitors and PPIs should be approached with caution. Manufacturers of immune checkpoint inhibitors do not provide recommendations on the concurrent use of PPIs. Primary literature on the concurrent use of these agents include recommendations to evaluate the risks and benefits of PPI use and consideration of alternative therapy when possible such as histamine H2-receptor antagonists (H2RAs) or antacids.(1-3)

DISCUSSION: A meta analysis of 23 studies evaluating the impact of acid suppressing therapy on the efficacy of immune checkpoint inhibitors found coadministration of a PPI decreased PFS (HR 1.34 [95% confidence interval (CI), 1.13 to 1.58]) and OS (HR 1.43 [95% CI, 1.21 to 1.69]) compared with patients not treated with PPIs. Furthermore, the meta analysis identified that H2RAs did not affect OS. These results were consistent across cancer types.(1) In another meta analysis of 22 studies (5 prospective and 17 retrospective, n=16,072) evaluating the impact of concomitant medications on survival outcomes in patients treated with systemic therapy for advanced unresectable or metastatic renal cell carcinoma, concomitant use of PPIs (n=3959) was significantly associated with worse OS in patients treated with immune checkpoint inhibitors (HR 1.22, P=0.01).(4) A retrospective analysis of 635 patients treated with immune checkpoint inhibitors found PPI use was associated with significantly decreased OS (9 vs 26.5 months), PFS (3.5 vs. 8 months), and tumor response (61% vs. 72%).(5) Analysis of retrospective data from clinical trials of atezolizumab for urothelial carcinoma and non-small-cell lung cancer, among patients using a PPI within 30 days before or after therapy initiation, OS was significantly worse for patients randomized to treatment with atezolizumab than for patients randomized to chemotherapy.(6,7) A retrospective study of 381 patients treated with immune checkpoint inhibitors found use of acid-suppression therapy (n=168 PPIs, n=37 potassium competitive acid blocker, n=13 H2RAs) was associated with significantly shorter PFS and OS (2.9 vs. 6.2 months and 12.3 vs. 24 months, respectively) compared with patients who did not use acid-suppression therapy. However, when stratified by concomitant use of corticosteroids or NSAIDs, use of acid-suppression therapy was not associated with worse progression-free or overall survival.(8) In a retrospective cohort study of patients with advanced non-small-cell lung cancer treated with pembrolizumab, exposure to PPIs was associated with worse OS (HR, 1.13; 95% CI, 1.10-1.17).(9) Analysis of US and Japanese adverse drug event reporting system databases found administration of immune checkpoint inhibitors and PPIs was associated with an increased risk of adverse events including acute kidney injury (10) and congenital, familial and genetic disorders.(11) In a meta analysis of 14 observational studies, the risk of immune checkpoint inhibitor related AKI (ICI-AKI) in cancer patients concurrently using PPIs was found to be significantly higher (pooled OR of 1.84 [95% CI 1.16-2.90]) in comparison to the overall incidence of AKI from all-causes (1.57 [95% CI 1.02-2.40]).(12) In contrast to these findings, other studies have not found a negative effect on PFS or OS when patients are co-administered PPIs and immune checkpoint inhibitors. In a retrospective study of 159 patients treated with ipilimumab, coadministration of PPIs was associated with increased odds of experiencing a partial or complete response to ipilimumab (OR 3.73 [95% CI, 1.26 to 11.04]).(13) In another retrospective study of 233 patients who received nivolumab or pembrolizumab, use of PPI had no effect on OS (HR 1.2 [95% CI, 0.8-1.9]) or PFS (HR 1.1 [95% CI, 0.8 to 1.5]).(14) A nested case-control study of patients (n=38,930) with cancer who were new PPI or immune checkpoint inhibitor users and had no history of AKI before cohort entry, found the risk of AKI in patients treated with both PPIs and immune checkpoint inhibitors was not higher than then additional or multiplication of the risks in those who were treated with PPIs or immune checkpoint inhibitors alone. The study reinforces the association between PPIs and immune checkpoint inhibitors use and the increased risk of AKI and the need for careful monitoring and evaluation of kidney function when treated with both medicines.(15)

*None.

• Lactation

• Pregnancy

• Hyperglycemia
• Hyperthyroidism
• Hypothyroidism
• Kidney disease with reduction in glomerular filtration rate (GFr)
• Myasthenia gravis

The most common adverse effects (>=20%) in patients with unresectable hepatocellular carcinoma (uHCC) receiving tremelimumab are rash, diarrhea, fatigue, pruritus, musculoskeletal pain, and abdominal pain. The most common laboratory abnormalities (>=40%) of patients with uHCC receiving tremelimumab are increased AST, increased ALT, decreased hemoglobin, decreased sodium, increased bilirubin, increased alkaline phosphatase, and decreased lymphocytes.

The most common adverse effects (>=20%) in patients with metastatic NSCLC are nausea, fatigue, musculoskeletal pain, decreased appetite, rash, and diarrhea.

More Frequent

• Anemia
• Hyperbilirubinemia
• Hyponatremia
• Increased alanine transaminase
• Increased alkaline phosphatase
• Increased aspartate transaminase
• Lymphopenia

Less Frequent

• Adrenocortical insufficiency
• Autoimmune hepatitis
• Colitis
• Hyperthyroidism
• Hypophysitis
• Hypothyroidism
• Interstitial nephritis
• Interstitial pneumonitis
• Pancreatitis
• Thyroiditis

Rare or Very Rare

• Acute inflammatory syndrome
• Aplastic anemia
• Autoimmune encephalitis
• Autoimmune hemolytic anemia
• Autoimmune thrombocytopenia
• Demyelinating disorder
• Duodenitis
• Encephalitis
• Guillain-barre syndrome
• Hemophagocytic lymphohistiocytosis
• Histiocytic necrotizing lymphadenitis
• Hypoparathyroidism
• Iritis
• Meningitis
• Myasthenia gravis
• Myocarditis
• Myositis
• Pericarditis
• Polymyalgia rheumatica
• Polymyositis
• Retinal detachment
• Rhabdomyolysis
• Sarcoidosis
• Uveitis
• Vasculitis

More Frequent

• Acute abdominal pain
• Anorexia
• Diarrhea
• Fatigue
• Musculoskeletal pain
• Nausea
• Pruritus of skin
• Skin rash

Less Frequent

• Headache disorder
• Hyperglycemia
• Skin inflammation

Rare or Very Rare

• Arthritis
• Gastritis
• Muscle weakness
• Peripheral sensory neuropathy

No enhanced messaging available.

The safety and efficacy of tremelimumab have not been established in pediatric patients.

There are no available data on the use of tremelimumab in pregnant women. However, based on findings from animal studies and its mechanism of action, tremelimumab can cause fetal harm when administered to a pregnant woman.

Administration of tremelimumab to pregnant cynomolgus monkeys during the period of organogenesis was not associated withadverse maternal or embryo-fetal effects at exposure levels approximately 4-31 times higher than those observed at a recommended dose range of 75-300 mg based on AUC. In a murine modelof pregnancy,CTLA-4 blockade was associated with anincreased risk of immune-mediated rejection of the developing fetus and fetal death. Based on the mechanism of action of tremelimumab, fetal exposure to the drug may increase the risk of developing immune-mediated disorders or altering the normal immune response.

Human immunoglobulin G2 (IgG2) is known to cross the placental barrier; therefore, tremelimumab may be transmitted from the mother to the developing fetus. Advise pregnant women and females of reproductive potential of the potential risk to the fetus.

It is not known whether tremelimumab is distributed into human milk; the effects of the drug on breast-fed infants or on milk production also areunknown. Maternal IgG is known to be present in human milk. The effects of local GI exposure and limited systemic exposure in the breast-fed child to tremelimumab are unknown. Due to the potential for serious adverse reactions in the breast-fed child, advise women not to breast-feed during treatment with tremelimumab and for 3 months after the last dose.

Consult the full prescribing information for breast-feeding considerations of agents administered in combination with tremelimumab.

The manufacturer makes no specific dosage recommendations for geriatric patients.

In clinical studies of patients with unresectable hepatocellular carcinoma or metastatic non-small cell lung cancer treated with tremelimumab in combination with durvalumab, no overall differences in safety or efficacy of tremelimumab were observed between patients 65 years of ageor older and younger adults.