Drug Interactions between insulin inhalation, rapid acting and moxifloxacin / triamcinolone

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 CLOSELY: Quinolone antibiotics may interfere with the therapeutic effects of insulin and other antidiabetic agents. The use of quinolones has been associated with disturbances in blood glucose homeostasis possibly stemming from effects on pancreatic beta cell ATP-sensitive potassium channels that regulate insulin secretion. Both hyperglycemia and hypoglycemia have been reported, usually in diabetic patients receiving concomitant treatment with an oral hypoglycemic agent or insulin. Although hyperglycemia is significantly more common and infection itself may be an underlying risk factor, hypoglycemia may cause greater morbidity and mortality. An internal safety review conducted by the U.S. Food and Drug Administration (FDA) identified at least 67 reports of severe hypoglycemia associated with quinolone use resulting in coma, death, or permanent and disabling injuries, primarily in elderly and diabetic patients with renal impairment and/or complicated infections. This is in addition to the numerous cases that have been reported for gatifloxacin, which led to its withdrawal from the U.S. market in 2008. Of the five quinolones that the FDA reviewed, levofloxacin had the most cases (44), followed by ciprofloxacin (12), moxifloxacin (9), ofloxacin (2), and gemifloxacin (0). Other quinolones such as nalidixic acid and norfloxacin, as well as some others that have never been marketed or are no longer marketed such as clinafloxacin and temafloxacin, have also been associated with dysglycemia, thus it is generally believed to be a class effect, albeit with varying risks amongst the individual agents. Available data also seem to indicate different time frames for the development of hypo- and hyperglycemia, with the former generally occurring within 1 to 3 days following quinolone initiation and the latter within 4 to 10 days later. Pharmacokinetically, ciprofloxacin is also a known inhibitor of CYP450 1A2 and 3A4 and may inhibit the hepatic metabolism of glyburide. Hypoglycemia in association with elevated serum glyburide level occurred in a patient after one week of ciprofloxacin therapy.

MANAGEMENT: Blood glucose should be closely monitored whenever quinolones are prescribed to diabetic patients, especially if they are elderly, have renal impairment, or are severely ill. Due to the risk of profound and potentially life-threatening hypoglycemia, particular caution is advised during concomitant use of insulin and insulin secretagogues (e.g., sulfonylureas, meglitinides). Patients should also be apprised of the increased risk of hypoglycemia and be alert to potential signs and symptoms such as headache, dizziness, drowsiness, nervousness, confusion, tremor, hunger, weakness, perspiration, palpitation, and tachycardia. If hypoglycemia occurs, patients should initiate appropriate remedial therapy immediately, discontinue the quinolone, and contact their physician. Alternative antibiotics may need to be considered.

ADJUST DOSING INTERVAL: Bronchodilators and other orally inhaled products may alter the absorption of inhaled human insulin. In nondiabetic subjects with mild asthma (n=36) and moderate asthma (n=31), administration of albuterol 30 minutes prior to inhaled human insulin resulted in a mean increase in insulin systemic exposure (AUC) and peak plasma concentration (Cmax) of 25% to 50% compared to administration of inhaled human insulin alone.

MONITOR: Systemic administration or systemic absorption of orally inhaled corticosteroids and sympathomimetic amines (bronchodilators) may result in diminished efficacy of insulin. These drugs may interfere with blood glucose control because they can cause hyperglycemia, glucose intolerance, new-onset diabetes mellitus, and/or exacerbation of preexisting diabetes.

MANAGEMENT: Consistent timing of dosing of other inhaled products relative to inhaled human insulin administration is recommended. Blood glucose should be monitored closely, and the insulin dose adjusted accordingly.