Drug Interactions between dexamethasone / ketorolac / moxifloxacin and levothyroxine / liothyronine

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: Concomitant use of androgens and/or anabolic steroids or corticosteroids with thyroid hormone replacement therapy, may cause a transient decrease in thyroid hormone replacement requirements. The proposed mechanism is a decrease in T4 binding globulin resulting in an initial transient increase in free T4. However, continued administration results in a decrease in serum T4 and normal free T4 and TSH concentrations. In addition, the clearance of corticosteroids may be increased in hyperthyroid patients, and decreased in hypothyroid patients, changes in thyroid hormone replacement dosage may affect corticosteroid dosage. Glucocorticoids may also inhibit the peripheral conversion of T4 to its active form T3. In addition, initiation of thyroid hormone replacement prior to initiating glucocorticoid therapy may precipitate an acute adrenal crisis in patients with adrenal insufficiency.

MANAGEMENT: Clinical and laboratory monitoring of thyroid function is recommended for patients receiving thyroid hormone replacement therapy and androgens and/or anabolic steroids, or corticosteroids. Thyroid hormone dosage adjustments may be needed. Patients should be advised to contact their physician if clinical manifestations of hyperthyroidism occur, such as appetite changes, unexplained weight loss, insomnia, and fatigue. In addition, when the dosage of the thyroid medication is changed, the corticosteroid dosage may need to be adjusted. Patients with adrenal insufficiency should be treated with replacement glucocorticoids prior to initiating thyroid hormone replacement.

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.