Drug Interactions between dexamethasone / ketorolac / moxifloxacin and ginkgo

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.

GENERALLY AVOID: Ginkgo may potentiate the risk of bleeding associated with anticoagulants, platelet inhibitors, nonsteroidal anti-inflammatory drugs (NSAIDs), and thrombolytic agents. Ginkgolide B, a component of ginkgo, inhibits platelet-activating factor by displacing it from its receptor-binding site, resulting in reduced platelet aggregation. There have been isolated reports of bleeding complications (e.g., spontaneous intracranial bleeding; spontaneous hyphema; peri- and postoperative bleeding) and prolonged bleeding times associated with the ingestion of ginkgo, some of which resolved following discontinuation of ginkgo use. Possible interactions with warfarin and aspirin have also been described in the medical literature. A patient stabilized on warfarin for five years developed intracerebral hemorrhage two months after starting ginkgo, and another who had been taking aspirin 325 mg/day for three years developed spontaneous bleeding of the iris into the anterior chamber of the eye one week after he began using ginkgo. In contrast, an investigative study found no significant effect of ginkgo pretreatment for 7 days on clotting status or the pharmacokinetics or pharmacodynamics of a single 25 mg dose of warfarin in 12 healthy volunteers. Another study consisting of 24 patients stabilized on warfarin for at least several months also found no significant effect of ginkgo on INR or warfarin dosage compared to placebo, and no major bleedings were observed in the study. However, it is important to recognize that pharmacologic effects of herbal products may be highly variable due to inconsistencies in formulation and potency of commercial preparations.

MANAGEMENT: Patients should consult a healthcare provider before taking any herbal or alternative medicine. In general, consumption of ginkgo should be avoided during use of coagulation-modifying agents and at least two weeks prior to surgery. In patients who have used this herb extensively prior to receiving anticoagulation, antiplatelet, NSAID or thrombolytic therapy, the potential for an interaction should be considered. Close clinical and laboratory observation for hematologic complications is recommended. Patients should be advised to promptly report any signs of bleeding to their physician, including pain, swelling, headache, dizziness, weakness, prolonged bleeding from cuts, increased menstrual flow, vaginal bleeding, nosebleeds, bleeding of gums from brushing, unusual bleeding or bruising, red or brown urine, or red or black stools.

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.

GENERALLY AVOID: Certain preparations of ginkgo biloba have been reported to induce seizures. There may be a theoretical risk of increased seizure potential when used with other agents that can lower the seizure threshold such as selective serotonin reuptake inhibitors (SSRI antidepressants or anorectics), monoamine oxidase inhibitors, neuroleptic agents, central nervous system stimulants, opioids, tricyclic antidepressants, other tricyclic compounds (e.g., cyclobenzaprine, phenothiazines), carbapenems, cholinergic agents, fluoroquinolones, interferons, chloroquine, mefloquine, lindane, and theophylline. Ginkgo products may contain varying amounts of 4'-O-methylpyridoxine (ginkgotoxin), a known neurotoxin found primarily in ginkgo biloba seeds but also detected in lesser amounts in the leaves. In vivo, 4'-O-methylpyridoxine competes with vitamin B6, which causes an indirect inhibition of glutamate decarboxylase and subsequent decrease in the formation of gamma-aminobutyric acid (GABA) in the brain. There have been published case reports of generalized convulsions and vomiting within several hours after ingestion of large amounts of ginkgo nuts/seeds, including in young children and healthy individuals with no known personal or family history of epilepsy. Many more cases, including fatalities, occurred in Japan in the 1930s to the 1960s during a food shortage when ginkgo nuts served as an important source of food. Some investigators have suggested that the amounts of ginkgotoxin in commercial extracts are too low to exert a detrimental effect. Nevertheless, a case report describes two elderly, previously well controlled epileptic patients who presented with recurrent seizures within two weeks of initiating treatment with a ginkgo extract. Both patients remained seizure-free several months after discontinuing the extract, with no alteration to their anticonvulsant medications.

MANAGEMENT: Patients should consult a healthcare provider before taking any herbal or alternative medicine. Because of inconsistencies in formulation and potency of commercial herbal preparations, there is no way to verify without laboratory testing if and in what quantity 4'-O-methylpyridoxine may be present in a given ginkgo preparation. Patients treated with agents that can lower the seizure threshold should preferably avoid the use of products containing ginkgo biloba.