Drug Interactions between bcg and dexamethasone / ketorolac / moxifloxacin

CONTRAINDICATED: Administration of intravesical BCG during immunosuppressant or intense antineoplastic therapy may be associated with a risk of disseminated infection due to enhanced replication of the BCG strain of Mycobacterium bovis in the presence of diminished immune competence. Deaths have been reported as a result of systemic BCG infection and sepsis. Patients may be immunosuppressed if they have recently received or are receiving alkylating agents, antimetabolites, radiation, some antirheumatic agents, high dosages of corticosteroids or adrenocorticotropic agents (e.g., greater than or equal to 2 mg/kg/day or 20 mg/day of prednisone or equivalent for 14 consecutive days or more), or long-term topical or inhaled corticosteroids. In addition, these patients may not develop an adequate immune response to BCG, which would reduce its anti-tumor efficacy.

MANAGEMENT: Use of intravesical BCG in immunosuppressed patients with congenital or acquired immune deficiencies, including those due to concurrent disease (e.g., AIDS, leukemia, lymphoma), cancer therapy (e.g., cytotoxic drugs, radiation) or immunosuppressive therapy (e.g., corticosteroids), is considered contraindicated. Clinicians should be aware that BCG may persist in the urinary tract for several months after BCG instillations, and delayed manifestations of disseminated BCG infection may develop months or years after BCG therapy. Patients who receive cancer or immunosuppressive therapy after BCG instillation may be at increased risk.

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.

CONTRAINDICATED: Antituberculosis drugs may interfere with the anti-tumor activity of intravesical BCG, which contains a live, attenuated strain of Mycobacterium bovis. Available data suggest that intravesical BCG may be sensitive to most antibiotics, particularly those that are routinely used in the treatment of tuberculosis such as streptomycin, para-aminosalicylic acid (PAS), isoniazid (INH), rifampin, and ethambutol. It is reportedly not sensitive to pyrazinamide or cycloserine. Regardless of clinical susceptibility data, however, most antibacterials may still interfere with BCG in the bladder due to their high urinary recovery.

MANAGEMENT: Concomitant use of antituberculosis drugs is considered contraindicated during intravesical BCG therapy. Moreover, intravesical BCG should not be used in patients with active tuberculosis. If persistent fever develops or an acute febrile illness consistent with BCG infection occurs during intravesical BCG therapy, the medication should be permanently discontinued and the patient immediately evaluated and treated for BCG infection. An infectious disease consultation should be sought in determining the appropriate treatment. There are no data to suggest that the acute, local urinary tract toxicity common with intravesical administration of BCG is due to mycobacterial infection, thus antituberculosis drugs should not be used to prevent or treat the local, irritative toxicities of intravesical BCG.

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: 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.