Drug Interactions between benzgalantamine and dexamethasone / ketorolac / moxifloxacin

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 acetylcholinesterase inhibitors and corticosteroids or adrenocorticotropic agents may result in severe muscle weakness in patients with myasthenia gravis. The mechanism of the interaction is unknown. It has been suggested that corticosteroids at high doses have a direct effect on neuromuscular transmission. Marked deterioration in muscle strength has been reported in patients with myasthenia gravis shortly after the initiation of corticosteroid therapy, particularly when high dosages were used. The use of cortisone appears to be associated with the highest rate of myasthenia gravis exacerbation, with an intermediate rate for prednisone and the lowest rate for methylprednisolone. In most cases, the decline in muscular function was relatively refractory to acetylcholinesterase inhibitors. However, clinical improvement generally occurs during prolonged corticosteroid therapy when administered properly.

MANAGEMENT: Caution and monitoring for muscle weakness is recommended with the use of corticosteroids or adrenocorticotropic agents in combination with acetylcholinesterase inhibitors in the treatment of patients with myasthenia gravis. Prednisone or prednisolone are often considered part of the standard treatment for this condition. Recommendations in the medical literature have advised that corticosteroid therapy should be instituted at relatively low dosages and in a controlled setting in patients with myasthenia gravis. Respiratory support should be available, and the dosage should be increased stepwise as tolerated. Dose reductions of the acetylcholinesterase inhibitor may be required as symptoms improve, which often may be delayed and gradual. However, according to some manufacturers of the corticosteroids dexamethasone and triamcinolone, anticholinesterase agents should be discontinued at least 24 hours before initiating corticosteroid therapy in patients with myasthenia gravis. Other management recommendations in the medical literature suggest avoiding the use of corticosteroids at high doses; however, if high doses are required, consider pre-treatment with intravenous immunoglobulin or plasmapheresis. Local protocols and/or the manufacturer's product labeling should be consulted for specific guidance.

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 concomitant use of acetylcholinesterase inhibitors (ACHEIs) (e.g., donepezil, galantamine, benzgalantamine physostigmine, rivastigmine, tacrine) with nonsteroidal anti-inflammatory drugs (NSAIDs) may increase the risk of gastrointestinal (GI) bleeding. ACHEIs can increase gastric acid secretion due to their cholinergic effects and NSAIDS may increase the risk of GI bleeding and ulceration. In a Swedish retrospective case study of 70,060 patients aged 65 years and older with new prescriptions for both ACHEIs and NSAIDs, 1500 persons were diagnosed with incident peptic ulcer. The results suggested that the risk of peptic ulcer was significantly increased for the combination of ACHEIs and NSAIDs compared to NSAIDs alone. No increased risks were found for the use of ACHEIs alone.


MANAGEMENT: Caution and clinical monitoring are recommended if concomitant use of ACHEIs and NSAIDs is required, especially in patients with a prior history of peptic ulcer disease, the elderly, or debilitated patients. Patients should be advised to seek prompt medical attention if they experience symptoms that could indicate the occurrence gastrointestinal bleeding such as black or tarry stools, bright red blood in vomit, coffee ground like vomit, abdominal pain or cramping, diarrhea, dizziness or lightheadedness, weakness or fatigue and pale skin.

MONITOR: Acetylcholinesterase inhibitors may have vagotonic effects on the sinoatrial and atrioventricular nodes, which occasionally manifest as bradycardia or heart block (<2%). Because bradycardia is a risk factor for torsade de pointes, a theoretical risk exists when combined with agents that prolong the QT interval. In general, the risk of an individual agent or a combination of agents causing ventricular arrhythmia in association with QT prolongation is largely unpredictable but may be increased by certain underlying risk factors including, but not limited to congenital long QT syndrome, cardiac disease, and electrolyte disturbances (e.g., hypokalemia, hypomagnesemia). In addition, the extent of drug-induced QT prolongation may vary depending on the dosage(s) and specific drug(s) involved.

MANAGEMENT: Caution is advised when acetylcholinesterase inhibitors are used with drugs that can prolong the QT interval. Patients should be monitored for bradycardia, atrioventricular block and syncope, and advised to seek medical attention if they experience dizziness, lightheadedness, fainting, shortness of breath, or slow or irregular heartbeat.