Drug Interactions between ketamine and Urelle

MONITOR CLOSELY: Coadministration of ketamine with other central nervous system (CNS) depressants, including alcohol, may result in profound sedation, respiratory depression, coma, and death. In addition, opioid analgesics, barbiturates, and benzodiazepines may prolong the time to complete recovery from anesthesia.

MANAGEMENT: During concomitant use of ketamine with other CNS depressants, including alcohol, close monitoring of neurologic status and respiratory parameters, including respiratory rate and pulse oximetry, is recommended. Dosage adjustments should be considered according to the patient's clinical situation. 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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GENERALLY AVOID: Alcohol may potentiate some of the pharmacologic effects of ketamine. Use in combination may result in additive central nervous system (CNS) depression and/or impairment of judgment, thinking, and psychomotor skills.

GENERALLY AVOID: Coadministration of oral ketamine with grapefruit juice may significantly increase the plasma concentrations of S(+) ketamine, the dextrorotatory enantiomer of ketamine. The proposed mechanism is inhibition of CYP450 3A4-mediated first-pass metabolism in the gut wall by certain compounds present in grapefruit. Inhibition of hepatic CYP450 3A4 may also contribute. When a single 0.2 mg/kg dose of S(+) ketamine was administered orally on study day 5 with grapefruit juice (200 mL three times daily for 5 days) in 12 healthy volunteers, mean S(+) ketamine peak plasma concentration (Cmax) and systemic exposure (AUC) increased by 2.1- and 3.0-fold, respectively, compared to administration with water. In addition, the elimination half-life of S(+) ketamine increased by 24% with grapefruit juice, and the ratio of the main metabolite norketamine to ketamine was decreased by 57%. The pharmacodynamics of ketamine were also altered by grapefruit juice. Specifically, self-rated relaxation was decreased and performance in the digit symbol substitution test was increased with grapefruit juice, but other behavioral or analgesic effects were not affected.

MANAGEMENT: Patients receiving ketamine should not drink alcohol. Caution is advised when ketamine is used in patients with acute alcohol intoxication or a history of chronic alcoholism. Following anesthesia with ketamine, patients should be counseled to avoid hazardous activities requiring complete mental alertness and motor coordination, such as driving or operating hazardous machinery, for at least 24 hours and until they know how the medication affects them. Patients treated with oral ketamine should also avoid consumption of grapefruit and grapefruit juice during treatment. Otherwise, dosage reductions of oral ketamine should be considered.

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ADJUST DOSING INTERVAL: Bowel cleansing products can increase the gastrointestinal transit rate. Oral medications administered within one hour of the start of administration of the bowel cleansing solution may be flushed from the gastrointestinal tract and not properly absorbed.

MANAGEMENT: Patients should be advised that absorption of oral medications may be impaired during bowel cleansing treatment. Oral medications (e.g., anticonvulsants, oral contraceptives, antidiabetic agents, antibiotics) should not be administered during and within one hour of starting bowel cleansing treatment whenever possible. However, if concomitant use cannot be avoided, monitoring for reduced therapeutic effects may be advisable.

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GENERALLY AVOID: Use of anticholinergic agents with alcohol may result in sufficient impairment of attention so as to render driving and operating machinery more hazardous. In addition, the potential for abuse may be increased with the combination. The mechanism of interaction is not established but may involve additive depressant effects on the central nervous system. No effect of oral propantheline or atropine on blood alcohol levels was observed in healthy volunteers when administered before ingestion of a standard ethanol load. However, one study found impairment of attention in subjects given atropine 0.5 mg or glycopyrrolate 1 mg in combination with alcohol.

MANAGEMENT: Alcohol should generally be avoided during therapy with anticholinergic agents. Patients should be counseled to avoid activities requiring mental alertness until they know how these agents affect them.

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