Drug Interactions between aspirin / caffeine / dihydrocodeine and UriSym

GENERALLY AVOID: Coadministration of narcotic analgesics with monoamine oxidase inhibitors (MAOIs) has been associated with rare reports of anxiety, confusion, hypotension, respiratory depression, cyanosis, and coma. The mechanism of interaction is unknown, but may involve potentiation of central nervous system (CNS) and respiratory depressant effects by MAOIs. There have also been reports of serotonin syndrome, which 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, hallucination, 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. Some opioids such as fentanyl, meperidine, methadone, tapentadol, and tramadol can inhibit serotonin reuptake. However, serotonin syndrome has also occurred with other opioids. Concomitant use of pentazocine with MAOIs may also cause CNS excitation and hypertension through their respective effects on catecholamines.

MANAGEMENT: Narcotic analgesics should generally not be used with MAOIs or other agents that possess MAOI activity (e.g., furazolidone, linezolid, methylene blue, procarbazine). At least 14 days should elapse between discontinuation of MAOI therapy and initiation of treatment with opioids.

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GENERALLY AVOID: Concomitant use of more than one salicylate at a time may increase the potential for gastrointestinal adverse effects (e.g., inflammation, pain, bleeding, ulceration) and bruising or bleeding.

MANAGEMENT: Concomitant use of more than one salicylate at a time should generally be avoided. Patients treated with a salicylate should be advised to take it 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.

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MONITOR: Coadministration of opioids with anticholinergic agents may result in additive central nervous system (CNS), gastrointestinal, and genitourinary effects. The risk and/or severity of adverse effects such as sedation, dizziness, confusion, cognitive and psychomotor impairment, dry mouth, constipation, and urinary retention may increase. Severe constipation may lead to paralytic ileus in some cases.

MANAGEMENT: Caution and close monitoring of central nervous system, gastrointestinal, and genitourinary adverse effects are recommended when opioids are used with anticholinergic agents. 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.

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One study has reported that coadministration of caffeine and aspirin lead to a 25% increase in the rate of appearance and 17% increase in maximum concentration of salicylate in the plasma. A significantly higher area under the plasma concentration time curve of salicylate was also reported when both drugs were administered together. The exact mechanism of this interaction has not been specified. Physicians and patients should be aware that coadministration of aspirin and caffeine may lead to higher salicylate levels faster.

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