Drug Interactions between Lithobid and Xylon 10

MONITOR CLOSELY: Coadministration with nonsteroidal anti-inflammatory drugs (NSAIDs) may increase serum lithium levels and induce toxicity in some patients. The exact mechanism of interaction is unknown, but is thought to involve inhibition of renal prostaglandin synthesis by NSAIDs, resulting in decreased renal blood flow and lithium excretion. There have been numerous published reports of lithium toxicity, including severe cases, following the introduction of various NSAIDs including diclofenac, ibuprofen, indomethacin, ketorolac, mefenamic acid, piroxicam, and COX-2 inhibitors. However, pharmacokinetic studies have been somewhat inconsistent, with no significant effects reported for benoxaprofen and etodolac, and up to a 58% increase in serum lithium levels reported for indomethacin. Both decreased serum concentrations of lithium and no effect have been reported for sulindac and aspirin. The interaction is apparently subject to marked interpatient variability.

MANAGEMENT: Given the narrow therapeutic index of lithium, caution is advised during coadministration with NSAIDs, particularly in the elderly or patients with other risk factors (e.g., sodium restriction; renal impairment; congestive heart failure; dehydration; concomitant use of diuretics, ACE inhibitors, or angiotensin II receptor antagonists). Patients should have serum lithium levels checked every 4 to 5 days after starting an NSAID until the extent of any potential interaction can be evaluated. A reduction in lithium dosage may be needed in some cases. Renal function should also be monitored regularly. Patients should be advised to seek medical attention if they experience potential signs and symptoms of lithium toxicity such as drowsiness, dizziness, confusion, muscle weakness, vomiting, diarrhea, polydipsia, polyuria, tinnitus, tremor, ataxia, and blurred vision.

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MONITOR: Opioids may potentiate the effects of serotonergic agents and increase the risk of serotonin syndrome. The interaction has primarily been reported with the phenylpiperidine opioids (e.g., meperidine, fentanyl) and tramadol, which are known to possess some serotonergic activity, although a few cases have involved other opioids such as oxycodone, methadone, morphine, hydromorphone, codeine, and buprenorphine. Serotonin syndrome is a rare but serious and potentially fatal condition thought to result from hyperstimulation of brainstem 5-HT1A and 2A receptors. Symptoms of the serotonin syndrome may include mental status changes such as irritability, altered consciousness, confusion, hallucinations, and coma; autonomic dysfunction such as tachycardia, hyperthermia, diaphoresis, shivering, blood pressure lability, and mydriasis; neuromuscular abnormalities such as hyperreflexia, myoclonus, tremor, rigidity, and ataxia; and gastrointestinal symptoms such as abdominal cramping, nausea, vomiting, and diarrhea. Since many serotonergic agents can also cause central nervous system depression, concomitant use with opioids may result in increased sedation and impairment of judgment, thinking, and psychomotor skills.

MANAGEMENT: Caution is advised when opioids are used concomitantly with serotonergic agents such as selective serotonin reuptake inhibitors (SSRIs), serotonin and norepinephrine reuptake inhibitors (SNRIs), monoamine oxidase inhibitors (MAOIs), tricyclic antidepressants (TCAs), other antidepressants/psychotropic agents (e.g., amoxapine, buspirone, lithium, maprotiline, mirtazepine, nefazodone, trazodone, vilazodone), 5-HT1 receptor agonists (triptans), 5-HT3 receptor antagonists, cyclobenzaprine, dextromethorphan, 5-hydroxytryptophan, and St. John's wort. Patients should be monitored for symptoms of the serotonin syndrome during treatment. Particular caution is advised when increasing the dosages of these agents. If serotonin syndrome develops or is suspected during the course of therapy, all serotonergic agents should be discontinued immediately and supportive care rendered as necessary. Moderately ill patients may also benefit from the administration of a serotonin antagonist (e.g., cyproheptadine, chlorpromazine). Severe cases should be managed under consultation with a toxicologist and may require sedation, neuromuscular paralysis, intubation, and mechanical ventilation in addition to the other measures. Patients should also be advised of potentially additive central nervous system effects from these agents and to avoid hazardous activities requiring complete mental alertness and motor coordination until they know how these agents affect them.

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