Drug Interactions between quetiapine and Urimar-T

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.

MONITOR: Agents with anticholinergic properties (e.g., sedating antihistamines; antispasmodics; neuroleptics; phenothiazines; skeletal muscle relaxants; tricyclic antidepressants; disopyramide) may have additive effects when used in combination. Excessive parasympatholytic effects may result in paralytic ileus, hyperthermia, heat stroke, and the anticholinergic intoxication syndrome. Peripheral symptoms of intoxication commonly include mydriasis, blurred vision, flushed face, fever, dry skin and mucous membranes, tachycardia, urinary retention, and constipation. Central symptoms may include memory loss, disorientation, incoherence, hallucinations, psychosis, delirium, hyperactivity, twitching or jerking movements, stereotypy, and seizures. Central nervous system-depressant effects may also be additively or synergistically increased when these agents are combined, especially in elderly or debilitated patients. Use of neuroleptics in combination with other neuroleptics or anticholinergic agents may increase the risk of tardive dyskinesia. In addition, some neuroleptics and tricyclic antidepressants may cause prolongation of the QT interval and theoretically, concurrent use of two or more drugs that can cause QT interval prolongation may result in additive effects and increased risk of ventricular arrhythmias including torsade de pointes and sudden death.

MANAGEMENT: Caution is advised when agents with anticholinergic properties are combined, particularly in the elderly and those with underlying organic brain disease, who tend to be more sensitive to the central anticholinergic effects of these drugs and in whom toxicity symptoms may be easily overlooked. Patients should be advised to notify their physician promptly if they experience potential symptoms of anticholinergic intoxication such as abdominal pain, fever, heat intolerance, blurred vision, confusion, and/or hallucinations. Ambulatory patients should be counseled to avoid activities requiring mental alertness until they know how these agents affect them. A reduction in anticholinergic dosages may be necessary if excessive adverse effects develop.

MONITOR: The following interactions apply only to products containing sodium biphosphate that are used for bowel cleansing. They do not apply to products containing sodium biphosphate that are used for other, non-laxative related purposes.

The risk of seizures induced by the use of bowel cleansing preparations may be increased in patients on concomitant medications that can lower the seizure threshold, including psychotherapeutic agents (antidepressants; neuroleptics; lithium), fluoroquinolones, some antimalarial agents (chloroquine; hydroxychloroquine; mefloquine), and some narcotic analgesics. Rare cases of generalized tonic-clonic seizures and/or loss of consciousness in association with low serum osmolality and electrolyte abnormalities (e.g., hyponatremia, hypokalemia, hypocalcemia, hypomagnesemia) have been reported with the use of bowel cleansing products in patients with no prior history of seizures. The condition resolved with correction of fluid and electrolyte abnormalities.

The use of bowel cleansing preparations may increase the risk of ventricular arrhythmia, particularly torsade de pointes, in patients treated with drugs that can prolong the QT interval, including psychotherapeutic agents (antidepressants; neuroleptics; lithium), fluoroquinolones, some antimalarial agents (chloroquine; mefloquine; halofantrine; lumefantrine), and some narcotic analgesics (methadone; propoxyphene). Severe and potentially fatal cases of electrolyte disorders and arrhythmias have been reported in elderly patients using bowel cleansing products. Electrolyte disturbances such as hypokalemia and hypomagnesemia are known risk factors for torsade de pointes associated with QT interval prolongation.

MANAGEMENT: Caution is advised when bowel cleansing preparations are prescribed in patients treated with agents that can lower the seizure threshold and/or prolong the QT interval. Bowel cleansing preparations should not be used if these patients have impaired renal function or perfusion, dehydration, or uncorrected electrolyte abnormalities. Baseline and postprocedure labs including serum electrolytes, phosphate, BUN, and creatinine should be considered, particularly in the elderly. Patients should be advised not to exceed the recommended dosage of their bowel cleansing preparation and to drink sufficient quantities of clear fluids before, during, and after the bowel preparation process. Administration of an electrolyte rehydration solution may help attenuate the electrolyte abnormalities and hypovolemia. Patients should be advised to seek prompt medical attention if they experience symptoms that could indicate the occurrence of torsade de pointes such as dizziness, lightheadedness, fainting, palpitation, irregular heart rhythm, shortness of breath, or syncope.

MONITOR: Coadministration of quetiapine with drugs that possess serotonergic activity (e.g., selective serotonin reuptake inhibitors (SSRIs), serotonin-norepinephrine reuptake inhibitors (SNRIs), monoamine oxidase inhibitors (MAOIs), tricyclic antidepressants (TCAs), etc.) may increase the risk of serotonin syndrome, a rare but serious and potentially fatal condition. Combining quetiapine with other serotonergic drugs may increase the risk of serotonin syndrome by relatively enhancing 5-HT1A receptor activity. However, data are currently limited to case reports. In one case report, an 85-year-old woman developed serotonin syndrome within hours of increasing quetiapine from 12.5 mg to 25 mg/day while also taking escitalopram, mirtazapine, sulpiride, and olanzapine; symptoms resolved within 48 hours after the discontinuation of all serotonergic medications. Symptoms of 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. In addition, central nervous system- and/or respiratory-depressant effects may be additively or synergistically increased in patients taking multiple drugs that also cause these effects (e.g., buspirone, desvenlafaxine, dextromethorphan, mianserin, reboxetine).

MANAGEMENT: Some authorities advise caution and closer monitoring for serotonin syndrome when quetiapine is coadministered with other serotonergic agents, especially during initiation and dose escalations. Patients should be instructed to promptly notify their healthcare provider if they experience symptoms of serotonin syndrome. If serotonin syndrome is suspected, a dose reduction or discontinuation of therapy should be considered depending on the severity of the symptoms. If serotonin syndrome develops during therapy, all serotonergic agents should be discontinued immediately, and supportive care rendered as necessary. Due to variability and occasionally prolonged half-lives of these coadministered agents, consulting individual product labeling for specific guidance is advised.