Drug Interactions between 5-hydroxytryptophan / melatonin / pyridoxine and morphine liposomal

MONITOR: Central nervous system- and/or respiratory-depressant effects may be additively or synergistically increased in patients taking multiple drugs that cause these effects, especially in elderly or debilitated patients. Sedation and impairment of attention, judgment, thinking, and psychomotor skills may increase.

MANAGEMENT: During concomitant use of these drugs, patients should be monitored for potentially excessive or prolonged CNS and respiratory depression. Cautious dosage titration may be required, particularly at treatment initiation. Ambulatory patients should be counseled to avoid hazardous activities requiring mental alertness and motor coordination until they know how these agents affect them, and to notify their physician if they experience excessive or prolonged CNS effects that interfere with their normal activities.

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.