Drug Interactions between dexamethasone / ketorolac / moxifloxacin and ocrelizumab

MONITOR CLOSELY: Concomitant administration of corticosteroids may potentiate the risk of tendinitis and tendon rupture associated with fluoroquinolone treatment. The mechanism is unknown. Tendinitis and tendon rupture have most frequently involved the Achilles tendon, although cases involving the rotator cuff (the shoulder), the hand, the biceps, and the thumb have also been reported. Some have required surgical repair or resulted in prolonged disability. Tendon rupture can occur during or up to several months after completion of fluoroquinolone therapy.

MANAGEMENT: Caution is recommended if fluoroquinolones are prescribed in combination with corticosteroids, particularly in patients with other concomitant risk factors (e.g., age over 60 years; recipient of kidney, heart, and/or lung transplant). Patients should be advised to stop taking the fluoroquinolone, avoid exercise and use of the affected area, and promptly contact their physician if they experience pain, swelling, or inflammation of a tendon. In general, fluoroquinolones should only be used to treat conditions that are proven or strongly suspected to be caused by bacteria and only if the benefits outweigh the risks.

MONITOR: The combined use of corticosteroids and nonsteroidal anti-inflammatory drugs (NSAIDs) may increase the potential for serious gastrointestinal (GI) toxicity, including inflammation, bleeding, ulceration, and perforation. In a large, case-control study of elderly patients, those who used corticosteroids and NSAIDs concurrently had an estimated relative risk (RR) for peptic ulcer disease and GI hemorrhage of 14.6 compared to those who used neither. Corticosteroid use was associated with a doubling of the risk (estimated RR = 2.0), but the risk was confined to those who also used NSAIDs. It is possible that both categories of agents are ulcerogenic and have additive effects on the GI mucosa during coadministration. Some investigators have also suggested that the primary effect of corticosteroids in this interaction is to delay healing of erosions caused by NSAIDs rather than cause de novo ulcerations.

MANAGEMENT: Caution is advised if corticosteroids and NSAIDs are used together, especially in patients with a prior history of peptic ulcer disease or GI bleeding and in elderly and debilitated patients. During concomitant therapy, patients should be advised to take the medications with food and to immediately report signs and symptoms of GI ulceration and bleeding such as severe abdominal pain, dizziness, lightheadedness, and the appearance of black, tarry stools. The selective use of prophylactic anti-ulcer therapy (e.g., antacids, H2-antagonists) may be considered.

MONITOR: The concomitant use of the CD20-directed cytolytic antibody ocrelizumab with other immune-modulating or immunosuppressive therapies, including immunosuppressant doses of corticosteroids, may result in an increased risk of immunosuppression. However, data is conflicting. Factors that appear to be associated with a risk of serious infections include higher doses of ocrelizumab than those recommended for multiple sclerosis (MS), other comorbidities, and concomitant use in patients on chronic immunosuppressants/corticosteroids. Ocrelizumab alone has been reported to increase the risk for respiratory tract infections and herpes-related infections in MS trials. In the postmarketing setting, hepatitis B reactivation, cases of progressive multifocal leukoencephalopathy (PML), and immune-mediated colitis have been reported. In relapsing MS (RMS) studies, 58% of ocrelizumab-treated patients experienced infections compared to 52% of interferon-treated patients. However, the proportion of patients reporting serious infection was higher in the interferon-treated group (2.9% versus 1.3%). On the other hand, when ocrelizumab is used concomitantly with immunosuppressants in other autoimmune conditions (e.g., rheumatoid arthritis) some studies have reported an increase in serious infections such as atypical pneumonia, pneumocystis jirovecii pneumonia, varicella pneumonia, tuberculosis, and histoplasmosis have been reported from some studies, including rare reports of fatalities.

MANAGEMENT: The increased risk of additive immunosuppression should be considered if co-administering ocrelizumab with other immunosuppressive therapy. Some authorities recommend avoiding concomitant use of other immunosuppressive therapies with ocrelizumab, except for the use of corticosteroids for symptomatic treatment of a MS relapse. Patients should be advised to notify their doctor if they develop signs or symptoms of infection, including upper or lower respiratory tract infection, skin infection, herpes related infection, or PML. If switching from a drug with prolonged immune effects (e.g., daclizumab, fingolimod, natalizumab, teriflunomide, mitoxantrone), the duration and mechanism of action should be considered prior to starting ocrelizumab therapy. The product labeling should be consulted for more specific recommendations.

MONITOR: Coadministration with nonsteroidal anti-inflammatory drugs (NSAIDs) may potentiate the risk of central nervous system toxicity sometimes associated with fluoroquinolone use. The interaction has been reported most often with enoxacin. It may occur with other fluoroquinolones as well, but is poorly documented. The exact mechanism of interaction is unknown. Some investigators suggest that the piperazine ring of fluoroquinolones may inhibit the binding of gamma-aminobutyric acid (GABA) to brain receptors and that NSAIDs may synergistically add to this effect. Patients with a history of seizures may be at greater risk.

MANAGEMENT: Clinical monitoring for signs of CNS stimulation such as tremors, involuntary muscle movements, hallucinations, or seizures is recommended if fluoroquinolone antibiotics are prescribed in combination with NSAIDs.