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Interactions between Meropenem and Tremelimumab

1 drug interaction and 9 additional warnings found for the following 2 drugs:

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Drug interactions

Moderate drug interactions

Moderate:

meropenem tremelimumab

Applies to: meropenem and tremelimumab
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Use of systemic antibiotics during or close to therapy with immune checkpoint inhibitors (ICIs) such as anti-cytotoxic T-lymphocyte-associated protein (CTLA)-4 monoclonal antibodies and/or inhibitors of programmed cell death-1 (PD-1)/programmed death ligand-1 (PD-L1) may result in reduced clinical efficacy of the ICI. The exact mechanism of this interaction has not been fully characterized, but may be related to alterations in the gut microbiota by the systemic antibiotic, potentially resulting in immune dysregulation and a decreased response to the ICI. A meta-analysis of 6 studies involving nivolumab for the treatment of advanced or metastatic non-small cell lung cancer (NSCLC) found that the median progression-free survival (PFS) and overall survival (OS) were reduced by 1.6 months and 8.8 months, respectively, in patients who were exposed to systemic antibiotics before, during, or after nivolumab therapy. Similarly, a single-site retrospective review of patients (n=291) with advanced cancer (melanoma, NSCLC, or renal cell carcinoma) treated with ICI(s) also revealed poorer clinical outcomes associated with the receipt of systemic antibiotics. This study divided patients into 3 groups: no antibiotics, single course of antibiotics, or cumulative courses of antibiotics (i.e., administration of concurrent or successive antibiotics for >7 days) during the 2 weeks prior to and 6 weeks after ICI treatment. The median PFS (6.3 months vs. 3.7 months vs. 2.8 months, respectively) and median OS (21.7 months vs. 17.7 months vs. 6.3 months, respectively) decreased as the antibiotic use increased, though the difference between no antibiotic use and cumulative courses of antibiotics was the only difference determined to be clinically significant. Additionally, a different retrospective analysis of patients (n=635) with advanced cancer treated with ICIs found that antibiotic use was associated with significantly shorter median OS (8 months vs. 23 months), median PFS (4 months vs. 7 months), as well as a reduction in tumor response (57% vs. 71%) when compared to patients who did not receive antibiotics. In contrast, a retrospective study of patients (n=302) with stage IV NSCLC treated with first-line chemo-immunotherapy combinations (i.e., ICI and cytotoxic chemotherapy) had similar OS, PFS, and objective response rate between those who did and did not receive antibiotics during the 30 days prior to initiating an ICI. The receipt of concurrent systemic antibiotics in this patient population was likewise not associated with changes in OS nor PFS.

Management

Until more information is available, caution and clinical monitoring for reduced efficacy of immune checkpoint inhibitors (ICIs) are advised if systemic antibiotics are indicated prior to, concurrently with, or after an ICI. Antibiotic use should be limited to clinically appropriate indications and durations. Clinicians should consult relevant literature, local and national treatment guidelines, and package labeling for further guidance.

References (6)
  1. 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
  2. Huo GW, Zuo R, Song Y, et al. (2021) "Effect of antibiotic use on the efficacy of nivolumab in the treatment of advanced/metastatic non-small cell lung cancer: a meta-analysis." Open Med (Wars), 16, p. 728-36
  3. Tinsley N, Zhou C, Tan G, et al. (2020) "Cumulative antibiotic use significantly decreases efficacy of checkpoint inhibitors in patients with advanced cancer." Oncologist, 25, p. 55-63
  4. Cortellini A, Ricciuti B, Facchinetti F, et al. (2021) "Antibiotic-exposed patients with non-small-cell lung cancer preserve efficacy outcomes following first-line chemo-immunotherapy." Ann Oncol, 32, p. 1391-9
  5. Hakozaki T, richard c, Elkrief A, et al. (2020) "The gut microbiome associates with immune checkpoint inhibition outcomes in patients with advanced non-small cell lung cancer." Cancer Immunol Res, 8, p. 1243-50
  6. Wu HJ, Wu E (2012) "The role of gut microbiota in immune homeostasis and autoimmunity." Gut Microbes, 3, p. 4-14

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

9 potential interactions Applies to: 9 conditions, including High Blood Pressure, Heart Failure, Seizures, Hemodialysis, and Fluid Retention.

Central Nervous System Disorders

Moderate:

meropenem

Meropenem has a moderate potential interaction with Central Nervous System Disorders.

The intravenous use of carbapenems has been associated with central nervous system adverse effects such as seizures (up to 1.5%) and, less frequently, somnolence, encephalopathy, myoclonus, tremor, paresthesia, confusion, agitation, depression, and hallucinations. Therapy with carbapenems, regardless of route of administration, should be administered cautiously in patients with or predisposed to seizures or other neurologic disturbances. The normally recommended dosages should not be exceeded in such patients. In those with a known seizure disorder, anticonvulsant therapy should be continued during carbapenem therapy.

Fluid Retention

Moderate:

meropenem

Meropenem has a moderate potential interaction with Fluid Retention.

Parenteral meropenem is formulated with sodium carbonate to adjust the pH of the reconstituted solution and contains 90.2 mg (3.92 mEq) of sodium per each gram of meropenem activity. The sodium content should be considered in patients with conditions that may require sodium restriction, such as congestive heart failure, hypertension, and fluid retention.

Heart Failure

Moderate:

meropenem

Meropenem has a moderate potential interaction with Heart Failure.

Parenteral meropenem is formulated with sodium carbonate to adjust the pH of the reconstituted solution and contains 90.2 mg (3.92 mEq) of sodium per each gram of meropenem activity. The sodium content should be considered in patients with conditions that may require sodium restriction, such as congestive heart failure, hypertension, and fluid retention.

Hemodialysis

Moderate:

meropenem

Meropenem has a moderate potential interaction with Hemodialysis.

In patients undergoing hemodialysis, carbapenems are recommended only if the benefit outweighs the potential risk of seizures. Carbapenems are removed by hemodialysis and should be administered after dialysis to avoid premature removal of the drug. There is not enough information regarding the use of some carbapenems such as meropenem for injection in patients on dialysis.

High Blood Pressure

Moderate:

meropenem

Meropenem has a moderate potential interaction with High Blood Pressure.

Parenteral meropenem is formulated with sodium carbonate to adjust the pH of the reconstituted solution and contains 90.2 mg (3.92 mEq) of sodium per each gram of meropenem activity. The sodium content should be considered in patients with conditions that may require sodium restriction, such as congestive heart failure, hypertension, and fluid retention.

Hypernatremia

Moderate:

meropenem

Meropenem has a moderate potential interaction with Hypernatremia.

Parenteral meropenem is formulated with sodium carbonate to adjust the pH of the reconstituted solution and contains 90.2 mg (3.92 mEq) of sodium per each gram of meropenem activity. The sodium content should be considered in patients with conditions that may require sodium restriction, such as congestive heart failure, hypertension, and fluid retention.

Noninfectious Colitis

Major:

meropenem

Meropenem has a major potential interaction with Noninfectious Colitis.

Clostridioides difficile-associated diarrhea (CDAD), formerly pseudomembranous colitis, has been reported with almost all antibacterial drugs and may range from mild diarrhea to fatal colitis. The most common culprits include clindamycin and lincomycin. Antibacterial therapy alters the normal flora of the colon, leading to overgrowth of C difficile, whose toxins A and B contribute to CDAD development. Morbidity and mortality are increased with hypertoxin-producing strains of C difficile; these infections can be resistant to antimicrobial therapy and may require colectomy. CDAD must be considered in all patients who present with diarrhea after antibacterial use. Since CDAD has been reported to occur more than 2 months after antibacterial use, careful medical history is necessary. Therapy with broad-spectrum antibacterials and other agents with significant antibacterial activity should be administered cautiously in patients with history of gastrointestinal disease, particularly colitis; pseudomembranous colitis (generally characterized by severe, persistent diarrhea and severe abdominal cramps, and sometimes associated with the passage of blood and mucus), if it occurs, may be more severe in these patients and may be associated with flares in underlying disease activity. Antibacterial drugs not directed against C difficile may need to be stopped if CDAD is suspected or confirmed. Appropriate fluid and electrolyte management, protein supplementation, antibacterial treatment of C difficile, and surgical evaluation should be started as clinically indicated.

Renal Dysfunction

Major:

meropenem

Meropenem has a major potential interaction with Renal Dysfunction.

Carbapenems are primarily eliminated by the kidney. Patients with renal impairment may be at greater risk for adverse effects from carbapenems, including seizures and other central nervous system disturbances, due to decreased drug clearance. Dosage adjustments should be considered, with modifications based on degree of renal impairment and severity of infection in accordance with the individual product package labeling. Renal function tests should be performed periodically during therapy.

Seizures

Moderate:

meropenem

Meropenem has a moderate potential interaction with Seizures.

The intravenous use of carbapenems has been associated with central nervous system adverse effects such as seizures (up to 1.5%) and, less frequently, somnolence, encephalopathy, myoclonus, tremor, paresthesia, confusion, agitation, depression, and hallucinations. Therapy with carbapenems, regardless of route of administration, should be administered cautiously in patients with or predisposed to seizures or other neurologic disturbances. The normally recommended dosages should not be exceeded in such patients. In those with a known seizure disorder, anticonvulsant therapy should be continued during carbapenem therapy.

More resources

meropenem

A total of 58 drugs are known to interact with meropenem.

tremelimumab

A total of 610 drugs are known to interact with tremelimumab.

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.