Drug Interactions between Atapryl and Azuphen MB

CONTRAINDICATED: Coadministration of methylene blue with serotonergic agents may potentiate the risk 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. Current research suggests that methylene blue has structural properties similar to monoamine oxidase inhibitors (MAOIs). As such, it may enhance serotonergic effects by inhibiting serotonin metabolism. 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. Serotonin syndrome has been reported when methylene blue was administered intravenously at dosages ranging from 1 to 8 mg/kg to patients exposed to drugs that interfere with serotonin reuptake. Several cases required admission to the intensive care unit. The risk of administering methylene blue intravenously at dosages less than 1 mg/kg or by non-intravenous routes (e.g., orally or by local injection) is unclear, although the potential for interaction with serotonergic agents should be considered.

MANAGEMENT: Serotonergic agents should not be used in patients receiving methylene blue intravenously. Most serotonergic psychiatric drugs should be stopped 1 to 2 weeks (i.e., 4 to 5 half-lives) prior to treatment with methylene blue if possible, while others such as fluoxetine may require discontinuation up to 5 weeks in advance due to its prolonged half-life. Treatment with serotonergic medications may be resumed 24 hours after the last dose of methylene blue. In patients receiving methylene blue who require urgent treatment of a psychiatric condition, other interventions including hospitalization should be considered. Conversely, when urgent treatment with methylene blue is required (e.g., methemoglobinemia, ifosfamide-induced encephalopathy, cyanide poisoning) in patients receiving serotonergic agents, the benefit of methylene blue treatment should be weighed against the risk of serotonin toxicity. If a decision is made to use methylene blue, the serotonergic drug must be immediately stopped, and the patient closely monitored for emergent symptoms of CNS toxicity for two weeks (five weeks if fluoxetine was taken; three weeks if vortioxetine was taken) or until 24 hours after the last dose of methylene blue, whichever comes first. Patients and/or their caregivers should be advised to seek medical attention if potential symptoms of serotonin syndrome develop.

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MONITOR CLOSELY: The following interaction applies only to products containing sodium biphosphate that are used for bowel cleansing. It does not apply to products containing sodium biphosphate that are used for other, non-laxative related purposes.

Coadministration with agents that affect renal function or perfusion such as diuretics, ACE inhibitors, angiotensin receptor blockers, and nonsteroidal anti-inflammatory drugs (NSAIDs) may increase the risk of acute phosphate nephropathy associated with the use of bowel-cleansing phosphate solutions. The risk and/or severity of fluid and electrolyte disturbances may also be increased, which can lead to serious adverse events including cardiac arrhythmias, seizures, and renal impairment. Acute phosphate nephropathy is a rare adverse event that presents as acute renal failure with minimal proteinuria and a bland urine sediment. Renal biopsy findings are consistent with nephrocalcinosis and include acute and/or chronic renal tubular injury, calcium-phosphate crystal deposition in the distal tubules and collecting ducts, and no other pattern of histological injury. The risk of acute phosphate nephropathy stems from the large phosphate load, fluid shifts, and decreased intravascular volume, which can be exacerbated in the presence of medications that affect renal perfusion or function. In reported cases, acute renal failure was typically diagnosed within two to five months of colonoscopy. These cases often resulted in permanent impairment of renal function, some requiring long-term dialysis.

MANAGEMENT: Caution is advised when bowel-cleansing phosphate preparations are prescribed in patients treated with agents that affect renal function or perfusion, particularly if they are frail or elderly. Bowel-cleansing phosphate preparations should not be used in patients who have impaired renal function or perfusion, dehydration, or uncorrected electrolyte abnormalities. In patients at risk for acute phosphate nephropathy, baseline and postprocedure labs including serum electrolytes, calcium, phosphate, BUN, and creatinine should be performed. Patients should be advised not to exceed the recommended dosage of their bowel-cleansing preparation and to drink sufficient quantities of clear fluids during before, during, and after bowel cleansing. Limited data suggest that administration of an electrolyte rehydration solution may attenuate the electrolyte abnormalities and hypovolemia. Hospitalization and intravenous fluid hydration may be appropriate for frail or elderly patients who may be unable to drink an adequate volume of fluid.

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