Drug Interactions between dexamethasone / ketorolac / moxifloxacin and estradiol

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: Estrogens may enhance the systemic effects of both endogenous and exogenous corticosteroids. The proposed mechanism is an increase in serum cortisol-binding globulin (transcortin) induced by estrogens, resulting in a decreased rate of corticosteroid metabolic clearance. The interaction has been reported with estrogens or estrogen-containing oral contraceptives (OCs) and hydrocortisone, prednisone, and prednisolone. In one pharmacokinetic study, the mean plasma clearance of total prednisolone (40 mg IV) in eight female OC users was less than half that of five healthy female non-OC users and eight healthy males, and the prednisolone half-life and mean residence time were longer. There was also a 2-fold increase in the area under the plasma concentration-time curve for unbound prednisolone compared to controls.

MANAGEMENT: Patients treated concomitantly with an estrogen-containing drug may require lower dosages of corticosteroids or adrenocorticotropic agents. Pharmacologic response to these agents should be monitored more closely whenever an estrogen is added to or withdrawn from therapy in patients stabilized on their existing corticosteroid or adrenocorticotropic regimen, and the dosage(s) adjusted as necessary.

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.

MONITOR: The effectiveness of estrogen-containing medications may be impaired by concomitant treatment with antimicrobial agents. During metabolism, the estrogen component is conjugated, resulting in sulfation or glucuronidation of the original estrogenic steroid. The conjugates reach the intestine by way of the bile duct where hydrolytic enzymes of intestinal bacteria break down the conjugates into free, active estrogenic hormone. The active hormone is then available for enterohepatic cycling, which helps to maintain estrogen levels. It is important to note that the progestin component of a combined hormonal product does not undergo this process. It has been suggested that broad-spectrum antibiotics may reduce the effectiveness of estrogen-containing contraceptives because of their potential to reduce the number of intestinal bacteria and thus interfere with enterohepatic cycling of estrogen. Most of the research regarding this possible interaction has been done with oral contraceptives, but all estrogens appear to undergo enterohepatic recirculation so theoretically this interaction is a possibility with estrogen containing medications that are being used for alternative purposes. However, the risk appears to be small, and supportive data are primarily limited to anecdotal evidence from case reports and findings from uncontrolled or poorly controlled studies. Most antimicrobials, with the exception of enzyme inducing medications like the rifamycins and possibly griseofulvin, have not been shown to significantly increase the clearance of oral contraceptive estrogens. It is possible that a small number of women may be more sensitive to the effects of antimicrobials on estrogen disposition in vivo, but risk factors or genetic predispositions have yet to be identified.

MANAGEMENT: If a person is using estrogen for a purpose other than contraception, it is important to note that there is a theoretical possibility of lower levels of systemic estrogen available during treatment with an antibiotic due to interference with enterohepatic cycling. These patients should be counseled to report any changes in efficacy of the hormonal product to their healthcare provider. In the case of contraception specifically, the Centers for Disease Control and Prevention do not consider most broad-spectrum antibiotics to significantly interfere with the effectiveness of combined hormonal contraception. However, the manufacturers of certain combined hormonal contraceptives and/or certain antibiotics do recommend using a back-up method of birth control for varying amounts of time; therefore, consulting the product labeling of each medication involved is advised. Some illnesses, as well as some antibiotics, may cause nausea, vomiting, and/or diarrhea. If the patient vomits within a few hours of taking an oral contraceptive pill, consult the product labeling for instructions on what to do in the event of a missed pill. Some authorities recommend a back-up method of birth control if an individual has persistent vomiting or diarrhea.

ADJUST DOSING INTERVAL: The non-hormonal placebo pills included in some oral contraceptive preparations may contain iron, usually ferrous fumarate. Concomitant administration of these iron pills may significantly decrease the gastrointestinal absorption of antibiotics such as quinolones and tetracyclines. The mechanism is chelation of the antibiotic by the iron cation, forming a complex that is poorly absorbed from the gastrointestinal tract.

MANAGEMENT: In general, quinolone antibiotics should be dosed either 2 to 6 hours before or 4 to 8 hours after iron preparations to minimize the potential for interaction. The administration of tetracycline antibiotics and iron preparations should be separated by at least 2 to 3 hours, although this may not prevent the interaction with all tetracyclines. Some manufacturers advise against the use of iron-containing medications while patients are on tetracycline antibiotics. The antibiotic product labeling should be consulted for more specific information regarding timing of doses and/or avoidance of iron.