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Drug Interactions between esketamine and Phenytoin Sodium, Prompt

This report displays the potential drug interactions for the following 2 drugs:

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Interactions between your drugs

Major

phenytoin esketamine

Applies to: Phenytoin Sodium, Prompt (phenytoin) and esketamine

MONITOR CLOSELY: Concomitant use of esketamine with central nervous system (CNS) depressants may increase sedation and impairment of attention, judgment, thinking, reaction speed, and psychomotor skills. In clinical trials, 49% to 61% of esketamine-treated patients developed sedation based on the Modified Observer's Alertness/Sedation scale (MOAA/s), and 0.3% of esketamine-treated patients experienced loss of consciousness (MOAA/s score of 0). In the MOAA/s scale, 5 means "responds readily to name spoken in normal tone" and 0 means "no response after painful trapezius squeeze," and any decrease in MOAA/s from pre-dosing of esketamine is considered to indicate presence of sedation. Dose-related increases in the incidence of sedation were also observed in a fixed-dose study. Additionally, cognitive performance decline was reported in a study in healthy volunteers who received a single intranasal dose of esketamine. Compared to placebo-treated subjects, esketamine-treated subjects required a greater effort to complete cognitive tests at 40 minutes post-dose, although results were comparable between the two groups at 2 hours post-dose. Drowsiness was comparable after 4 hours post-dose.

MANAGEMENT: Caution is advised and patients should be closely monitored during concomitant use of esketamine with CNS depressants or other drugs that can cause sedation or dizziness. Due to the risk of delayed or prolonged sedation and other adverse effects, patients should be monitored for at least 2 hours after esketamine administration, followed by an assessment to determine when the patient is considered clinically stable and ready to leave the healthcare setting. Patients should be instructed not to engage in potentially hazardous activities that require complete mental alertness and motor coordination, such as driving a motor vehicle or operating machinery, until the next day after a restful sleep.

References

  1. Cerner Multum, Inc. "UK Summary of Product Characteristics."
  2. Cerner Multum, Inc. "Australian Product Information."
  3. Cerner Multum, Inc. (2015) "Canadian Product Information."
  4. (2019) "Product Information. Spravato (esketamine)." Janssen Pharmaceuticals
View all 4 references

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Drug and food interactions

Moderate

phenytoin food

Applies to: Phenytoin Sodium, Prompt (phenytoin)

ADJUST DOSING INTERVAL: Phenytoin bioavailability may decrease to subtherapeutic levels when the suspension is given concomitantly with enteral feedings. The mechanism may be related to phenytoin binding to substances in the enteral formula (e.g., calcium, protein) and/or binding to the tube lumen. Data have been conflicting and some studies have reported no changes in phenytoin levels, while others have reported significant reductions.

MONITOR: Acute consumption of alcohol may increase plasma phenytoin levels. Chronic consumption of alcohol may decrease plasma phenytoin levels. The mechanism of this interaction is related to induction of phenytoin metabolism by ethanol during chronic administration. Other hydantoin derivatives may be similarly affected by ethanol.

MANAGEMENT: Some experts have recommended interrupting the feeding for 2 hours before and after the phenytoin dose, giving the phenytoin suspension diluted in water, and flushing the tube with water after administration; however, this method may not entirely avoid the interaction and is not always clinically feasible. Patients should be closely monitored for clinical and laboratory evidence of altered phenytoin efficacy and levels upon initiation and discontinuation of enteral feedings. Dosage adjustments or intravenous administration may be required until therapeutic serum levels are obtained. In addition, patients receiving phenytoin therapy should be warned about the interaction between phenytoin and ethanol and they should be advised to notify their physician if they experience worsening of seizure control or symptoms of toxicity, including drowsiness, visual disturbances, change in mental status, nausea, or ataxia.

References

  1. Sandor P, Sellers EM, Dumbrell M, Khouw V (1981) "Effect of short- and long-term alcohol use on phenytoin kinetics in chronic alcoholics." Clin Pharmacol Ther, 30, p. 390-7
  2. Holtz L, Milton J, Sturek JK (1987) "Compatibility of medications with enteral feedings." JPEN J Parenter Enteral Nutr, 11, p. 183-6
  3. Sellers EM, Holloway MR (1978) "Drug kinetics and alcohol ingestion." Clin Pharmacokinet, 3, p. 440-52
  4. (2001) "Product Information. Dilantin (phenytoin)." Parke-Davis
  5. Doak KK, Haas CE, Dunnigan KJ, et al. (1998) "Bioavailability of phenytoin acid and phenytoin sodium with enteral feedings." Pharmacotherapy, 18, p. 637-45
  6. Rodman DP, Stevenson TL, Ray TR (1995) "Phenytoin malabsorption after jejunostomy tube delivery." Pharmacotherapy, 15, p. 801-5
  7. Au Yeung SC, Ensom MH (2000) "Phenytoin and enteral feedings: does evidence support an interaction?" Ann Pharmacother, 34, p. 896-905
  8. Ozuna J, Friel P (1984) "Effect of enteral tube feeding on serum phenytoin levels." J Neurosurg Nurs, 16, p. 289-91
  9. Faraji B, Yu PP (1998) "Serum phenytoin levels of patients on gastrostomy tube feeding." J Neurosci Nurs, 30, p. 55-9
  10. Marvel ME, Bertino JS (1991) "Comparative effects of an elemental and a complex enteral feeding formulation on the absorption of phenytoin suspension." JPEN J Parenter Enteral Nutr, 15, p. 316-8
  11. Fleisher D, Sheth N, Kou JH (1990) "Phenytoin interaction with enteral feedings administered through nasogastric tubes." JPEN J Parenter Enteral Nutr, 14, p. 513-6
  12. Haley CJ, Nelson J (1989) "Phenytoin-enteral feeding interaction." DICP, 23, p. 796-8
  13. Guidry JR, Eastwood TF, Curry SC (1989) "Phenytoin absorption in volunteers receiving selected enteral feedings." West J Med, 150, p. 659-61
  14. Krueger KA, Garnett WR, Comstock TJ, Fitzsimmons WE, Karnes HT, Pellock JM (1987) "Effect of two administration schedules of an enteral nutrient formula on phenytoin bioavailability." Epilepsia, 28, p. 706-12
  15. Cerner Multum, Inc. "UK Summary of Product Characteristics."
  16. Cerner Multum, Inc. "Australian Product Information."
View all 16 references

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Moderate

esketamine food

Applies to: esketamine

GENERALLY AVOID: Concomitant use of esketamine with central nervous system (CNS) depressants such as alcohol may increase sedation and impairment of attention, judgment, thinking, reaction speed, and psychomotor skills.

ADJUST DOSING INTERVAL: Nausea and vomiting may occur following intranasal administration of esketamine. In clinical studies, nausea and vomiting were reported in approximately 25% and 10% of esketamine-treated patients, respectively.

MANAGEMENT: Patients receiving esketamine should be advised to avoid or limit the consumption of alcohol. In addition, to help prevent nausea and vomiting, patients should be advised not to eat for at least 2 hours before intranasal administration of esketamine and not to drink liquids for at least 30 minutes prior to administration.

References

  1. Cerner Multum, Inc. "Australian Product Information."
  2. (2019) "Product Information. Spravato (esketamine)." Janssen Pharmaceuticals

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Therapeutic duplication warnings

No warnings were found for your selected drugs.

Therapeutic duplication warnings are only returned when drugs within the same group exceed the recommended therapeutic duplication maximum.

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Drug Interaction Classification

These classifications are only a guideline. The relevance of a particular drug interaction to a specific individual is difficult to determine. Always consult your healthcare provider before starting or stopping any medication.
Major Highly clinically significant. Avoid combinations; the risk of the interaction outweighs the benefit.
Moderate Moderately clinically significant. Usually avoid combinations; use it only under special circumstances.
Minor Minimally clinically significant. Minimize risk; assess risk and consider an alternative drug, take steps to circumvent the interaction risk and/or institute a monitoring plan.
Unknown No interaction information available.

Further information

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