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Drug Interactions between Diazepam Intensol and esketamine

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

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Major

diazePAM esketamine

Applies to: Diazepam Intensol (diazepam) 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 (4)
  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

Drug and food interactions

Moderate

diazePAM food

Applies to: Diazepam Intensol (diazepam)

GENERALLY AVOID: Acute alcohol ingestion may potentiate the CNS depression and other CNS effects of many benzodiazepines. Tolerance may develop with chronic ethanol use. The mechanism may be decreased clearance of the benzodiazepines because of CYP450 hepatic enzyme inhibition. Also, it has been suggested that the cognitive deficits induced by benzodiazepines may be increased in patients who chronically consume large amounts of alcohol.

MONITOR: Grapefruit juice may increase the plasma concentrations of orally administered drugs that are substrates of the CYP450 3A4 isoenzyme. However, the interaction seems to affect primarily those drugs that undergo significant presystemic metabolism by CYP450 3A4 (i.e., drugs with low oral bioavailability), presumably due to the fact that grapefruit juice inhibits intestinal rather than hepatic CYP450 3A4. Because pharmacokinetic interactions involving grapefruit juice are often subject to a high degree of interpatient variability, the extent to which a given patient may be affected is difficult to predict.

MANAGEMENT: Patients should be advised to avoid alcohol during benzodiazepine therapy. Patients who regularly consume grapefruit or grapefruit juice should be monitored for adverse effects and altered plasma concentrations of drugs that undergo significant presystemic metabolism by CYP450 3A4. Grapefruit and grapefruit juice should be avoided if an interaction is suspected. Orange juice is not expected to interact with these drugs.

References (34)
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  2. Jonkman JH, Sollie FA, Sauter R, Steinijans VW (1991) "The influence of caffeine on the steady-state pharmacokinetics of theophylline." Clin Pharmacol Ther, 49, p. 248-55
  3. (2002) "Product Information. Valium (diazepam)." Roche Laboratories
  4. Bailey DG, Arnold JM, Munoz C, Spence JD (1993) "Grapefruit juice--felodipine interaction: mechanism, predictability, and effect of naringin." Clin Pharmacol Ther, 53, p. 637-42
  5. Bailey DG, Arnold JMO, Spence JD (1994) "Grapefruit juice and drugs - how significant is the interaction." Clin Pharmacokinet, 26, p. 91-8
  6. (2001) "Product Information. Doral (quazepam)." Wallace Laboratories
  7. Sigusch H, Hippius M, Henschel L, Kaufmann K, Hoffmann A (1994) "Influence of grapefruit juice on the pharmacokinetics of a slow release nifedipine formulation." Pharmazie, 49, p. 522-4
  8. Bailey DG, Arnold JM, Strong HA, Munoz C, Spence JD (1993) "Effect of grapefruit juice and naringin on nisoldipine pharmacokinetics." Clin Pharmacol Ther, 54, p. 589-94
  9. Yamreudeewong W, Henann NE, Fazio A, Lower DL, Cassidy TG (1995) "Drug-food interactions in clinical practice." J Fam Pract, 40, p. 376-84
  10. (1995) "Grapefruit juice interactions with drugs." Med Lett Drugs Ther, 37, p. 73-4
  11. Hukkinen SK, Varhe A, Olkkola KT, Neuvonen PJ (1995) "Plasma concentrations of triazolam are increased by concomitant ingestion of grapefruit juice." Clin Pharmacol Ther, 58, p. 127-31
  12. Min DI, Ku YM, Geraets DR, Lee HC (1996) "Effect of grapefruit juice on the pharmacokinetics and pharmacodynamics of quinidine in healthy volunteers." J Clin Pharmacol, 36, p. 469-76
  13. Majeed A, Kareem A (1996) "Effect of grapefruit juice on cyclosporine pharmacokinetics." Pediatr Nephrol, 10, p. 395
  14. Clifford CP, Adams DA, Murray S, Taylor GW, Wilkins MR, Boobis AR, Davies DS (1996) "Pharmacokinetic and cardiac effects of terfenadine after inhibition of its metabolism by grapefruit juice." Br J Clin Pharmacol, 42, p662
  15. Josefsson M, Zackrisson AL, Ahlner J (1996) "Effect of grapefruit juice on the pharmacokinetics of amlodipine in healthy volunteers." Eur J Clin Pharmacol, 51, p. 189-93
  16. Kantola T, Kivisto KT, Neuvonen PJ (1998) "Grapefruit juice greatly increases serum concentrations of lovastatin and lovastatin acid." Clin Pharmacol Ther, 63, p. 397-402
  17. Ozdemir M, Aktan Y, Boydag BS, Cingi MI, Musmul A (1998) "Interaction between grapefruit juice and diazepam in humans." Eur J Drug Metab Pharmacokinet, 23, p. 55-9
  18. Bailey DG, Malcolm J, Arnold O, Spence JD (1998) "Grapefruit juice-drug interactions." Br J Clin Pharmacol, 46, p. 101-10
  19. Bailey DG, Kreeft JH, Munoz C, Freeman DJ, Bend JR (1998) "Grapefruit juice felodipine interaction: Effect of naringin and 6',7'-dihydroxybergamottin in humans." Clin Pharmacol Ther, 64, p. 248-56
  20. Garg SK, Kumar N, Bhargava VK, Prabhakar SK (1998) "Effect of grapefruit juice on carbamazepine bioavailability in patients with epilepsy." Clin Pharmacol Ther, 64, p. 286-8
  21. Lilja JJ, Kivisto KT, Neuvonen PJ (1998) "Grapefruit juice-simvastatin interaction: Effect on serum concentrations of simvastatin, simvastatin acid, and HMG-CoA reductase inhibitors." Clin Pharmacol Ther, 64, p. 477-83
  22. Fuhr U, Maier-Bruggemann A, Blume H, et al. (1998) "Grapefruit juice increases oral nimodipine bioavailability." Int J Clin Pharmacol Ther, 36, p. 126-32
  23. Lilja JJ, Kivisto KT, Neuvonen PJ (1999) "Grapefruit juice increases serum concentrations of atorvastatin and has no effect on pravastatin." Clin Pharmacol Ther, 66, p. 118-27
  24. Eagling VA, Profit L, Back DJ (1999) "Inhibition of the CYP3A4-mediated metabolism and P-glycoprotein-mediated transport of the HIV-I protease inhibitor saquinavir by grapefruit juice components." Br J Clin Pharmacol, 48, p. 543-52
  25. Damkier P, Hansen LL, Brosen K (1999) "Effect of diclofenac, disulfiram, itraconazole, grapefruit juice and erythromycin on the pharmacokinetics of quinidine." Br J Clin Pharmacol, 48, p. 829-38
  26. Lee AJ, Chan WK, Harralson AF, Buffum J, Bui BCC (1999) "The effects of grapefruit juice on sertraline metabolism: An in vitro and in vivo study." Clin Ther, 21, p. 1890-9
  27. Dresser GK, Spence JD, Bailey DG (2000) "Pharmacokinetic-pharmacodynamic consequences and clinical relevance of cytochrome P450 3A4 inhibition." Clin Pharmacokinet, 38, p. 41-57
  28. Gunston GD, Mehta U (2000) "Potentially serious drug interactions with grapefruit juice." S Afr Med J, 90, p. 41
  29. Takanaga H, Ohnishi A, Maatsuo H, et al. (2000) "Pharmacokinetic analysis of felodipine-grapefruit juice interaction based on an irreversible enzyme inhibition model." Br J Clin Pharmacol, 49, p. 49-58
  30. Libersa CC, Brique SA, Motte KB, et al. (2000) "Dramatic inhibition of amiodarone metabolism induced by grapefruit juice." Br J Clin Pharmacol, 49, p. 373-8
  31. Bailey DG, Dresser GR, Kreeft JH, Munoz C, Freeman DJ, Bend JR (2000) "Grapefruit-felodipine interaction: Effect of unprocessed fruit and probable active ingredients." Clin Pharmacol Ther, 68, p. 468-77
  32. Zaidenstein R, Soback S, Gips M, Avni B, Dishi V, Weissgarten Y, Golik A, Scapa E (2001) "Effect of grapefruit juice on the pharmacokinetics of losartan and its active metabolite E3174 in healthy volunteers." Ther Drug Monit, 23, p. 369-73
  33. Sato J, Nakata H, Owada E, Kikuta T, Umetsu M, Ito K (1993) "Influence of usual intake of dietary caffeine on single-dose kinetics of theophylline in healthy human subjects." Eur J Clin Pharmacol, 44, p. 295-8
  34. Flanagan D (2005) "Understanding the grapefruit-drug interaction." Gen Dent, 53, 282-5; quiz 286
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 (2)
  1. Cerner Multum, Inc. "Australian Product Information."
  2. (2019) "Product Information. Spravato (esketamine)." Janssen Pharmaceuticals
Minor

diazePAM food

Applies to: Diazepam Intensol (diazepam)

One study has reported a 22% reduction in diazepam plasma levels when coadministered with caffeine. The exact mechanism of this interaction has not been specified. Physicians and patients should be aware that changes to caffeine consumption habits may impact the efficacy of diazepam therapy.

References (1)
  1. Ghoneim MM, Hinrichs JV, Chiang CK, Loke WH (1986) "Pharmacokinetic and pharmacodynamic interactions between caffeine and diazepam." J Clin Psychopharmacol, 6, p. 75-80

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.

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