Drug Interactions between dexamethasone / ketorolac / moxifloxacin and toripalimab

Moxifloxacin and other medications in its class can cause tendinitis and tendon rupture, and the risk may be increased when combined with a steroid such as dexAMETHasone. Older adults over 60 years of age and those who have received a kidney, heart, and/or lung transplant may be particularly susceptible. Tendon rupture can occur during or up to several months after finishing moxifloxacin treatment and may require surgery or result in prolonged disability. Talk to your doctor if you have any questions or concerns. Your doctor may be able to prescribe alternatives that do not interact, or you may need a dose adjustment or more frequent monitoring to safely use both medications. Stop taking moxifloxacin and call your doctor immediately if you experience pain, swelling, or inflammation of a tendon area such as the back of the ankle, shoulder, biceps, hand, or thumb. You should also avoid exercise or use of the affected area until further instruction from your doctor. It is important to tell your doctor about all other medications you use, including vitamins and herbs. Do not stop using any medications without first talking to your doctor.

Using dexAMETHasone together with ketorolac may increase the risk of side effects in the gastrointestinal tract such as inflammation, bleeding, ulceration, and rarely, perforation. Gastrointestinal perforation is a potentially fatal condition and medical emergency where a hole forms all the way through the stomach or intestine. You should take these medications with food to lessen the risk. Talk to your doctor if you have any questions or concerns. Your doctor may be able to prescribe alternatives that do not interact, or you may need a dose adjustment or more frequent monitoring to safely use both medications. Your doctor may also be able to recommend medications to help protect the stomach and intestine if you are at high risk for developing serious gastrointestinal complications. You should seek immediate medical attention if you experience any unusual bleeding or bruising, or have other signs and symptoms of bleeding such as dizziness; lightheadedness; red or black, tarry stools; coughing up or vomiting fresh or dried blood that looks like coffee grounds; severe headache; and weakness. It is important to tell your doctor about all other medications you use, including vitamins and herbs. Do not stop using any medications without first talking to your doctor.

Using dexAMETHasone may decrease the effects of toripalimab, which may make the medication less effective in treating your condition. Talk to your doctor if you have any questions or concerns. Your doctor may be able to prescribe alternatives that do not interact or may choose to postpone treatment with toripalimab. It is important to tell your doctor about all other medications you use, including vitamins and herbs. Do not stop using any medications without first talking to your doctor.

Moxifloxacin may rarely cause central nervous system side effects such as tremors, involuntary muscle movements, anxiety, confusion, depression, hallucinations or seizures, and combining it with other medications that can also affect the central nervous system such as ketorolac may increase that risk. Talk to your doctor if you have any questions or concerns. Your doctor may be able to prescribe alternatives that do not interact, or you may need a dose adjustment or more frequent monitoring by your doctor to safely use both medications. It is important to tell your doctor about all other medications you use, including vitamins and herbs. Do not stop using any medications without first talking to your doctor.

Consumer information for this interaction is not currently available.

MONITOR: 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.