Drug Interactions between esketamine and hyoscyamine / methenamine / methylene blue / phenyl salicylate / sodium biphosphate

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 CLOSELY: Coadministration with psychostimulants (e.g., amphetamines) or monoamine oxidase inhibitors (MAOIs) may potentiate the hypertensive effects of esketamine. According to the prescribing information, esketamine causes increases in systolic and/or diastolic blood pressure (BP) at all recommended doses. Increases in BP peak approximately 40 minutes after esketamine administration and last about 4 hours. In clinical studies, approximately 8% to 17% of esketamine-treated patients experienced an increase of more than 40 mmHg in systolic BP and/or 25 mmHg in diastolic BP within 1.5 hours after administration at least once during the first 4 weeks of treatment, compared to 1% to 3% of placebo-treated patients. A substantial increase in BP could occur after any dose, even if smaller BP effects were observed with previous administrations. The mean placebo-adjusted increases in systolic and diastolic blood pressure (SBP and DBP) over time were about 7 to 9 mmHg in SBP and 4 to 6 mmHg in DBP at 40 minutes post-dose and 2 to 5 mmHg in SBP and 1 to 3 mmHg in DBP at 1.5 hours post-dose in patients receiving esketamine with oral antidepressants.

MANAGEMENT: Caution is advised and blood pressure should be closely monitored during concomitant use of esketamine with psychostimulants or MAOIs. All patients receiving esketamine should have BP assessed prior to administration. If BP is elevated (e.g., >140 mmHg systolic, >90 mmHg diastolic), a delay in esketamine treatment may be necessary, taking into consideration the benefits versus risks in individual patients. BP should be monitored for at least 2 hours after esketamine administration, starting at approximately 40 minutes post-dose and subsequently as clinically warranted. In patients with a history of hypertensive encephalopathy, more intensive monitoring is warranted due to increased risk for developing encephalopathy with even small increases in BP. If at any point BP is elevated and remains high, promptly seek assistance from practitioners experienced in BP management. Patients experiencing symptoms of a hypertensive crisis (e.g., chest pain, shortness of breath) or hypertensive encephalopathy (e.g., sudden severe headache, visual disturbances, seizures, diminished consciousness or focal neurological deficits) should be immediately referred for emergency care.