Diazepam interactions

Food & lifestyle

• alcohol

  Moderate

  Metabolism

  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.

  What to do: 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.

  34 sources

  1. Edgar B, Bailey D, Bergstrand R, et al. "Acute effects of drinking grapefruit juice on the pharmacokinetics and dynamics on felodipine and its potential clinical relevance." Eur J Clin Pharmacol 42 (1992): 313-7
  2. Jonkman JH, Sollie FA, Sauter R, Steinijans VW "The influence of caffeine on the steady-state pharmacokinetics of theophylline." Clin Pharmacol Ther 49 (1991): 248-55
  3. "Product Information. Valium (diazepam)." Roche Laboratories (2002):
  4. Bailey DG, Arnold JM, Munoz C, Spence JD "Grapefruit juice--felodipine interaction: mechanism, predictability, and effect of naringin." Clin Pharmacol Ther 53 (1993): 637-42
  5. Bailey DG, Arnold JMO, Spence JD "Grapefruit juice and drugs - how significant is the interaction." Clin Pharmacokinet 26 (1994): 91-8
  6. "Product Information. Doral (quazepam)." Wallace Laboratories (2001):
  7. Sigusch H, Hippius M, Henschel L, Kaufmann K, Hoffmann A "Influence of grapefruit juice on the pharmacokinetics of a slow release nifedipine formulation." Pharmazie 49 (1994): 522-4
  8. Bailey DG, Arnold JM, Strong HA, Munoz C, Spence JD "Effect of grapefruit juice and naringin on nisoldipine pharmacokinetics." Clin Pharmacol Ther 54 (1993): 589-94

  Show all 34 sourcesShow fewer sources

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

Conditions

Conditions in which Diazepam needs care, as documented in this source.

• Alcoholic Intoxication

  Major

  The use of benzodiazepines with alcohol is not recommended. Patients with acute alcohol intoxication exhibit depressed vital signs. The central nervous system depressant effects of benzodiazepines may be additive with those of alcohol, and severe respiratory depression and death may occur. Therapy with benzodiazepines should be administered cautiously in patients who might be prone to acute alcohol intake.

  14 sources

  1. "Product Information. Xanax (alprazolam)." Pharmacia and Upjohn (2002):
  2. "Product Information. Valium (diazepam)." Roche Laboratories (2002):
  3. "Product Information. Ativan (lorazepam)." Wyeth-Ayerst Laboratories (2002):
  4. "Product Information. Serax (oxazepam)." Wyeth-Ayerst Laboratories (2001):
  5. "Product Information. Restoril (temazepam)." Sandoz Pharmaceuticals Corporation (2001):
  6. "Product Information. Halcion (triazolam)." Pharmacia and Upjohn (2001):
  7. "Product Information. Dalmane (flurazepam)." Roche Laboratories (2001):
  8. "Product Information. Tranxene (clorazepate)." Abbott Pharmaceutical (2001):

  Show all 14 sourcesShow fewer sources

  9. "Product Information. Klonopin (clonazepam)." Roche Laboratories (2001):
  10. "Product Information. Prosom (estazolam)." Abbott Pharmaceutical (2022):
  11. "Product Information. Librium (chlordiazepoxide)." Roche Laboratories (2001):
  12. "Product Information. Doral (quazepam)." Wallace Laboratories (2001):
  13. "Product Information. Versed (midazolam)." Roche Laboratories (2001):
  14. "Product Information. Onfi (clobazam)." Lundbeck Inc (2011):

• Glaucoma, Angle-Closure

  Major

  The manufacturers consider the use of benzodiazepines to be contraindicated in patients with acute angle-closure glaucoma or untreated open-angle glaucoma. These agents do not possess anticholinergic activity but have very rarely been associated with increased intraocular pressure.

  14 sources

  1. "Product Information. Xanax (alprazolam)." Pharmacia and Upjohn (2002):
  2. "Product Information. Valium (diazepam)." Roche Laboratories (2002):
  3. "Product Information. Ativan (lorazepam)." Wyeth-Ayerst Laboratories (2002):
  4. "Product Information. Serax (oxazepam)." Wyeth-Ayerst Laboratories (2001):
  5. "Product Information. Restoril (temazepam)." Sandoz Pharmaceuticals Corporation (2001):
  6. "Product Information. Halcion (triazolam)." Pharmacia and Upjohn (2001):
  7. "Product Information. Dalmane (flurazepam)." Roche Laboratories (2001):
  8. "Product Information. Tranxene (clorazepate)." Abbott Pharmaceutical (2001):

  Show all 14 sourcesShow fewer sources

  9. "Product Information. Klonopin (clonazepam)." Roche Laboratories (2001):
  10. "Product Information. Prosom (estazolam)." Abbott Pharmaceutical (2022):
  11. "Product Information. Librium (chlordiazepoxide)." Roche Laboratories (2001):
  12. "Product Information. Doral (quazepam)." Wallace Laboratories (2001):
  13. "Product Information. Versed (midazolam)." Roche Laboratories (2001):
  14. Fraunfelder FT, Fraunfelder FW; Randall JA "Drug-Induced Ocular Side Effects" Boston, MA: Butterworth-Heinemann (2001):

• Hypotension

  Major

  Benzodiazepines should not be administered by injection to patients in shock or coma. The hypnotic and hypotensive effects of these agents may be prolonged and intensified in such patients.

  5 sources

  1. "Product Information. Valium (diazepam)." Roche Laboratories (2002):
  2. "Product Information. Ativan (lorazepam)." Wyeth-Ayerst Laboratories (2002):
  3. "Product Information. Librium (chlordiazepoxide)." Roche Laboratories (2001):
  4. "Product Information. Versed (midazolam)." Roche Laboratories (2001):
  5. "Product Information. Byfavo (remimazolam)." Acacia Pharma, Inc (2020):

• Liver Diseases

  Major

  Benzodiazepines are metabolized by the liver, and the metabolites are excreted in the urine. Chlordiazepoxide, clorazepate, diazepam, flurazepam and quazepam undergo oxidative N-dealkylation to active metabolites that are substantially longer-acting than the parent compound. These metabolites then undergo further biotransformation to pharmacologically inactive products before excretion by the kidney. Therapy with benzodiazepines should be administered cautiously at lower initial dosages in patients with impaired renal and/or hepatic function. Agents that are converted to weakly active, short-acting, or inactive metabolites may be preferable in hepatic impairment. Lorazepam, oxazepam and temazepam are conjugated to inactive metabolites, while alprazolam, estazolam and triazolam undergo hydroxylation to weakly active or inactive metabolites.

  47 sources

  1. Sellers EM, Greenblatt DJ, Giles HG, et al. "Chlordiazepoxide and oxazepam disposition in cirrhosis." Clin Pharmacol Ther 26 (1979): 240-6
  2. Hicks R, Dysken MW, Davis JM, et al. "The pharmacokinetics of psychotropic medication in the elderly: a review." J Clin Psychiatry 42 (1981): 374-85
  3. Murray TG, Chiang ST, Koepke HH, Walker BR "Renal disease, age, and oxazepam kinetics." Clin Pharmacol Ther 30 (1981): 805-9
  4. Hoyumpa AM "Disposition and elimination of minor tranquilizers in the aged and in patients with liver disease." South Med J 71 (1978): 23-8
  5. Kraus JW, Desmond PV, Marshall JP, Johnson RF, Schenker S, Wilkinson GR "Effects of age and liver disease on disposition of lorazepam." Clin Pharmacol Ther 24 (1978): 411-9
  6. Verbeeck RK, Tjandramaga TB, de Schepper PJ, Verberckmoes R "Impaired elimination of lorazepam following subchronic administration in two patients with renal failure." Br J Clin Pharmacol 12 (1981): 749-50
  7. Greenblatt DJ "Clinical pharmacokinetics of oxazepam and lorazepam." Clin Pharmacokinet 6 (1981): 89-105
  8. Morrison G, Chiang ST, Koepke HH, Walker BR "Effect of renal impairment and hemodialysis on lorazepam kinetics." Clin Pharmacol Ther 35 (1984): 646-52

  Show all 47 sourcesShow fewer sources

  9. Klotz U, Avant GR, Hoyumpa A, Schenker S, Wikinson GR "The effects of age and liver disease on the disposition and elimination of diazepam in adult man." J Clin Invest 55 (1975): 347-59
  10. Cutler RE, Blair AD "Pharmacokinetics of diazepam in normal and uremic humans." Clin Pharmacol Ther 25 (1979): 219-20
  11. Ochs HR, Greenblatt DJ, Kaschell HJ, Klehr U, Divoll M, Abernathy DR "Diazepam kinetics in patients with renal insufficiency or hyperthyroidism." Br J Clin Pharmacol 12 (1981): 829-32
  12. Schmith VD, Piraino B, Smith RB, Kroboth PD "Alprazolam in end-stage renal disease: I. Pharmacokinetics." J Clin Pharmacol 31 (1991): 571-9
  13. Dehlin O, Kullingsjo H, Liden A, Agrell B, Moser G, Olsen I "Pharmacokinetics of alprazolam in geriatric patients with neurotic depression." Pharmacol Toxicol 68 (1991): 121-4
  14. Sellers EM, Greenblatt DJ, Giles HG, et al. "Chlordiazepoxide and oxazepam disposition in cirrhosis." Clin Pharmacol Ther 26 (1979): 240-6
  15. Morgan DD, Robinson JD, Mendenhall CL "Clinical pharmacokinetics of chlordiazepoxide in patients with alcoholic hepatitis." Eur J Clin Pharmacol 19 (1981): 279-85
  16. Tedesco FJ, Mills LR "Diazepam (valium) hepatitis." Dig Dis Sci 27 (1982): 470-2
  17. de Silva JAF, Strojny N "Determination of flurazepam and its major biotransformation products in blood and urine by spectrophotofluorometry and spectrophotometry." J Pharm Sci 60 (1971): 1303-14
  18. Kaplan SA, de Silva JAF, Jack ML, et al. "Blood level profile in man following chronic oral administration of flurazepam hydrochloride." J Pharm Sci 62 (1973): 1932-5
  19. Greenblatt DJ, Divoll M, Harmatz JJ "Kinetics and clinical effects of flurazepam in young and elderly noninsomniacs." Clin Pharmacol Ther 30 (1981): 475-86
  20. Ghabrial H, Desmond PV, Watson KJ, et al. "The effects of age and chronic liver disease on the elimination of temazepam." Eur J Clin Pharmacol 30 (1986): 93-7
  21. Busch U, Molzahn M, Bozler G, Koss FW "Pharmacokinetics of oxazepam following multiple administration in volunteers and patients with chronic renal disease." Arzneimittelforschung 31 (1981): 1507-11
  22. Juhl RP, Van Thiel DH, Dittert LW, Smith RB "Alprazolam pharmacokinetics in alcoholic liver disease." J Clin Pharmacol 24 (1984): 113-9
  23. Johnson J, Padilla BG, Carter J, Holt JH, Ozawa T "Adverse effects of flurazepam in a hemodialysis patient." J Am Assoc Nephrol Nurses Tech 4 (1977): 93-5
  24. Kroboth PD, Smith RB, Rault R, Silver MR, Sorkin MI, Puschett JB, Juhl RP "Effects of end-stage renal disease and aluminum hydroxide on temazepam kinetics." Clin Pharmacol Ther 37 (1985): 453-9
  25. Wilensky AJ, Levy RH, Troupin AS, Moretti-Ojemann L "Clorazepate kinetics in treated epileptics." Clin Pharmacol Ther 24 (1978): 22-30
  26. Greenblatt DJ, Divoll MK, Soong MH, Boxenbaum HG, Harmatz JS, Shader RI "Desmethyldiazepam pharmacokinetics: studies following intravenous and oral desmethyldiazepam, oral clorazepate, and intravenous diazepam." J Clin Pharmacol 28 (1988): 853-9
  27. Ochs HR, Rauh HW, Greenblatt DJ, Kaschell HJ "Clorazepate dipotassium and diazepam in renal insufficiency: serum concentrations and protein binding of diazepam and desmethyldiazepam." Nephron 37 (1984): 100-4
  28. Roberts RK, Wilkinson GR, Branch RA, Schenker S "Effect of age and parenchymal liver disease on the disposition and elimination of chlordiazepoxide (librium)." Gastroenterology 75 (1978): 479-85
  29. Kroboth PD, Smith RB, Silver MR, Rault R, Sorkin MI, Puschett JB, Juhl RP "Effects of end stage renal disease and aluminium hydroxide on triazolam pharmacokinetics." Br J Clin Pharmacol 19 (1985): 839-42
  30. Kroboth PD, Smith RB, Van Thiel DH, Juhl RP "Nighttime dosing of triazolam in patients with liver disease and normal subjects: kinetics and daytime effects." J Clin Pharmacol 27 (1987): 555-60
  31. Hilbert JM, Chung M, Radwanski E, Gural R, Symchowicz S, Zampaglione N "Quazepam kinetics in the elderly." Clin Pharmacol Ther 36 (1984): 566-9
  32. Chung M, Hilbert JM, Gural RP, Radwanski E, Symchowicz S, Zampaglione N "Multiple-dose quazepam kinetics." Clin Pharmacol Ther 35 (1984): 520-4
  33. Gustavson LE, Carrigan PJ "The clinical pharmacokinetics of single doses of estazolam." Am J Med 88 (1990): s2-5
  34. Allen MD, Greenblatt DJ, Arnold JD "Single- and multiple-dose kinetics of estazolam, a triazolo benzodiazepine." Psychopharmacology (Berl) 66 (1979): 267-74
  35. "Product Information. Xanax (alprazolam)." Pharmacia and Upjohn (2002):
  36. "Product Information. Valium (diazepam)." Roche Laboratories (2002):
  37. "Product Information. Ativan (lorazepam)." Wyeth-Ayerst Laboratories (2002):
  38. "Product Information. Serax (oxazepam)." Wyeth-Ayerst Laboratories (2001):
  39. "Product Information. Restoril (temazepam)." Sandoz Pharmaceuticals Corporation (2001):
  40. "Product Information. Halcion (triazolam)." Pharmacia and Upjohn (2001):
  41. "Product Information. Dalmane (flurazepam)." Roche Laboratories (2001):
  42. "Product Information. Tranxene (clorazepate)." Abbott Pharmaceutical (2001):
  43. "Product Information. Klonopin (clonazepam)." Roche Laboratories (2001):
  44. "Product Information. Prosom (estazolam)." Abbott Pharmaceutical (2022):
  45. "Product Information. Librium (chlordiazepoxide)." Roche Laboratories (2001):
  46. "Product Information. Doral (quazepam)." Wallace Laboratories (2001):
  47. American Medical Association, Division of Drugs and Toxicology "Drug evaluations annual 1994." Chicago, IL: American Medical Association; (1994):

• Myasthenia Gravis

  Major

  The use of diazepam is contraindicated in patients with myasthenia gravis.

  1 source

  1. "Product Information. Valium (diazepam)." Roche Laboratories (2002):

• Respiratory Insufficiency

  Major

  Benzodiazepines may cause respiratory depression and apnea, usually when given in high dosages and/or by intravenous administration. However, some patients may be susceptible at commonly used dosages, including the elderly, debilitated or severely ill patients, those receiving other CNS depressants, and those with limited ventilatory reserve, chronic pulmonary insufficiency or other respiratory disorders. Therapy with benzodiazepines should be administered cautiously in these patients. Appropriate monitoring and individualization of dosage are particularly important, and equipment for resuscitation should be immediately available if the parenteral route is used. Benzodiazepines, especially injectable formulations, should generally be avoided in patients with sleep apnea, severe respiratory insufficiency, or hypoxia.

  31 sources

  1. Iber FL, Livak A, Kruss DM "Apnea and cardiopulmonary arrest during and after endoscopy." J Clin Gastroenterol 14 (1992): 109-13
  2. Cohen S, Khan A "Respiratory distress with use of lorazepam in mania." J Clin Psychopharmacol 7 (1987): 199-200
  3. Donaldson D, Gibson G "System complications with intravenous diazepam." Oral Surg Oral Med Oral Patho 49 (1980): 126-30
  4. Eldridge PR, Punt JA "Risks associated with giving benzodiazepines to patients with acute neurological injuries." Br Med J 300 (1990): 1189-90
  5. Man GC, Hsu K, Sproule BJ "Effect of alprazolam on exercise and dyspnea in patients with chronic obstructive pulmonary disease." Chest 90 (1986): 832-6
  6. Mendelson WB, Weingartner H, Greenblatt DJ, Garnett D, Gillin JC "A clinical study of flurazepam." Sleep 5 (1982): 350-60
  7. "Product Information. Xanax (alprazolam)." Pharmacia and Upjohn (2002):
  8. "Product Information. Valium (diazepam)." Roche Laboratories (2002):

  Show all 31 sourcesShow fewer sources

  9. "Product Information. Ativan (lorazepam)." Wyeth-Ayerst Laboratories (2002):
  10. "Product Information. Serax (oxazepam)." Wyeth-Ayerst Laboratories (2001):
  11. "Product Information. Restoril (temazepam)." Sandoz Pharmaceuticals Corporation (2001):
  12. Pierce MW, Shu VS, Groves LJ "Safety of estazolam. The United States clinical experience." Am J Med 88 (1990): s12-7
  13. Skatrud JB, Badr S, Begle RL, Juan D "Ventilatory response to single, high dose estazolam in healthy humans." J Clin Pharmacol 30 (1990): 543-8
  14. Sullivan RJ, Jr "Respiratory depression requiring ventilatory support following 0.5 mg of triazolam." J Am Geriatr Soc 37 (1989): 450-2
  15. "Product Information. Halcion (triazolam)." Pharmacia and Upjohn (2001):
  16. "Product Information. Dalmane (flurazepam)." Roche Laboratories (2001):
  17. Model DG, Berry DJ "Effects of chlordiazepoxide in respiratory failure due to chronic bronchitis." Lancet 2 (1974): 869-70
  18. Dixon D "Respiratory depression following midazolam." Anaesthesia 40 (1985): 922
  19. Yakel DL, Jr Whittaker SE, Elstad MR "Midazolam-induced angioedema and bronchoconstriction." Crit Care Med 20 (1992): 307-8
  20. Berggren L, Eriksson I, Mollenholt P, Sunzel M "Changes in respiratory pattern after repeated doses of diazepam and midazolam in healthy subjects." Acta Anaesthesiol Scand 31 (1987): 667-72
  21. Taylor JW, Simon KB "Possible intramuscular midazolam-associated cardiorespiratory arrest and death." DICP 24 (1990): 695-7
  22. Munoz HR, Dagnino JA, Rufs JA, Bugedo GJ "Benzodiazepine premedication causes hypoxemia during spinal anesthesia in geriatric patients." Reg Anesth 17 (1992): 139-42
  23. "Product Information. Tranxene (clorazepate)." Abbott Pharmaceutical (2001):
  24. "Product Information. Klonopin (clonazepam)." Roche Laboratories (2001):
  25. "Product Information. Prosom (estazolam)." Abbott Pharmaceutical (2022):
  26. "Product Information. Librium (chlordiazepoxide)." Roche Laboratories (2001):
  27. Murphy PJ, Erskine R, Langton JA "The effect of intravenously administered diazepam, midazolam and flumazenil on the sensitivity of upper airway reflexes." Anaesthesia 49 (1994): 105-10
  28. "Product Information. Doral (quazepam)." Wallace Laboratories (2001):
  29. "Product Information. Versed (midazolam)." Roche Laboratories (2001):
  30. Berry RB, Kouchi K, Bower J, Prosise G, Light RW "Triazolam in patients with obstructive sleep apnea." Am J Respir Crit Care Med 151 (1995): 450-4
  31. "Product Information. Byfavo (remimazolam)." Acacia Pharma, Inc (2020):

• Seizures

  Major

  The use of benzodiazepines in patients with seizure disorders may increase the incidence or precipitate the onset of generalized tonic-clonic seizures (grand mal). Appropriate anticonvulsant medication might need to be initiated or the dosage increased. Abrupt cessation of benzodiazepine therapy may precipitate seizures and other withdrawal symptoms, particularly after prolonged use and/or excessive dosages. Status epilepticus may occur in patients with a history of seizures withdrawn rapidly from benzodiazepine therapy. Following chronic administration, cessation of benzodiazepine therapy should occur gradually with incrementally reduced dosages. Patients should be advised not to discontinue medication without first consulting with the physician.

  35 sources

  1. Ananth J "Abstinence syndrome from therapeutic doses of oxazepam." Can J Psychiatry 28 (1983): 592
  2. Wilbur R, Kulik AV "Abstinence syndrome from therapeutic doses of oxazepam." Can J Psychiatry 28 (1983): 298-300
  3. Busto U, Sellers EM, Naranjo CA, et al. "Withdrawal reaction after long-term therapeutic use of benzodiazepines." N Engl J Med 315 (1986): 854-9
  4. Hersch EL, Billings RF "Acute confusional state with status petit mal as a withdrawal syndrome: and five year follow-up." Can J Psychiatry 33 (1988): 157-9
  5. Howe JG "Lorazepam withdrawal seizures." Br Med J 280 (1980): 1163-4
  6. Kales A, Bixler EO, Soldatos CR, Jacoby JA, Kales JD "Lorazepam: effects on sleep and withdrawal phenomena." Pharmacology 32 (1986): 121-30
  7. Robinson GM, Sellers EM "Diazepam withdrawal seizures." Can Med Assoc J 126 (1982): 944-5
  8. Browne JL, Hauge KJ "A review of alprazolam withdrawal." Drug Intell Clin Pharm 20 (1986): 837-41

  Show all 35 sourcesShow fewer sources

  9. Ghadirian AM, Gauthier S, Wong T "Convulsions in patients abruptly withdrawn from clonazepam while receiving neuroleptic medication ." Am J Psychiatry 144 (1987): 686
  10. Hauser P, Devinsky O, De Bellis M, Theodore WH, Post RM "Benzodiazepine withdrawal delirium with catatonic features. Occurrence in patients with partial seizure disorders." Arch Neurol 46 (1989): 696-9
  11. Specht U, Boenigk HE, Wolf P "Discontinuation of clonazepam after long-term treatment." Epilepsia 30 (1989): 458-63
  12. Alvarez N, Hartford E, Doubt C "Epileptic seizures induced by clonazepam." Clin Electroencephalogr 12 (1981): 57-65
  13. Berlin RM, Conell LJ "Withdrawal symptoms after long-term treatment with therapeutic doses of flurazepam: a case report." Am J Psychiatry 140 (1983): 488-90
  14. Bond WS, Schwartz M "Withdrawal reactions after long-term treatment with flurazepam." Clin Pharm 3 (1984): 316-8
  15. "Product Information. Xanax (alprazolam)." Pharmacia and Upjohn (2002):
  16. "Product Information. Valium (diazepam)." Roche Laboratories (2002):
  17. "Product Information. Ativan (lorazepam)." Wyeth-Ayerst Laboratories (2002):
  18. "Product Information. Serax (oxazepam)." Wyeth-Ayerst Laboratories (2001):
  19. "Product Information. Restoril (temazepam)." Sandoz Pharmaceuticals Corporation (2001):
  20. Tien AY, Gujavarty KS "Seizure following withdrawal from triazolam." Am J Psychiatry 142 (1985): 1516-7
  21. Patterson WM "Triazolam withdrawal." J Clin Psychiatry 49 (1988): 369
  22. Schneider LS, Syapin PJ, Pawluczyk S "Seizures following triazolam withdrawal despite benzodiazepine treatment." J Clin Psychiatry 48 (1987): 418-9
  23. "Product Information. Halcion (triazolam)." Pharmacia and Upjohn (2001):
  24. "Product Information. Dalmane (flurazepam)." Roche Laboratories (2001):
  25. Ryan GP, Boisse NR "Experimental induction of benzodiazepine tolerance and physical dependence." J Pharmacol Exp Ther 226 (1983): 100-7
  26. Petursson H, Lader MH "Benzodiazepine dependence." Br J Addict 76 (1981): 133-45
  27. Finley PR, Nolan PE, Jr "Precipitation of benzodiazepine withdrawal following sudden discontinuation of midazolam." DICP 23 (1989): 151-2
  28. "Product Information. Tranxene (clorazepate)." Abbott Pharmaceutical (2001):
  29. "Product Information. Klonopin (clonazepam)." Roche Laboratories (2001):
  30. "Product Information. Prosom (estazolam)." Abbott Pharmaceutical (2022):
  31. "Product Information. Librium (chlordiazepoxide)." Roche Laboratories (2001):
  32. Roy-Byrne PP, Sullivan MD, Cowley DS, Ries RK "Adjunctive treatment of benzodiazepine discontinuation syndromes - a review." J Psychiatr Res 27 Suppl (1993): 143-53
  33. "Product Information. Doral (quazepam)." Wallace Laboratories (2001):
  34. "Product Information. Versed (midazolam)." Roche Laboratories (2001):
  35. Frattola L, Garreau M, Piolti R, Bassi S, Albizzati MG, Borghi C, Morselli PL "Comparison of the efficacy, safety and withdrawal of alpidem and alprazolam in anxious patients." Br J Psychiatry 165 (1994): 94-100

• Substance-Related Disorders

  Major

  Benzodiazepines have the potential to cause dependence and abuse. Tolerance as well as physical and psychological dependence can develop, particularly after prolonged use and/or excessive dosages. However, abrupt cessation following continual use of as few as 6 weeks at therapeutic levels has occasionally precipitated withdrawal symptoms. Addiction- prone individuals, such as those with a history of alcohol or substance abuse, should be under careful surveillance when treated with benzodiazepines. It may be prudent to refrain from dispensing large quantities of medication to these patients. After prolonged use or if dependency is suspected, withdrawal of benzodiazepine therapy should be undertaken gradually using a dosage- tapering schedule. If withdrawal symptoms occur, temporary reinstitution of benzodiazepines may be necessary.

  14 sources

  1. "Product Information. Xanax (alprazolam)." Pharmacia and Upjohn (2002):
  2. "Product Information. Valium (diazepam)." Roche Laboratories (2002):
  3. "Product Information. Ativan (lorazepam)." Wyeth-Ayerst Laboratories (2002):
  4. "Product Information. Serax (oxazepam)." Wyeth-Ayerst Laboratories (2001):
  5. "Product Information. Restoril (temazepam)." Sandoz Pharmaceuticals Corporation (2001):
  6. "Product Information. Halcion (triazolam)." Pharmacia and Upjohn (2001):
  7. "Product Information. Dalmane (flurazepam)." Roche Laboratories (2001):
  8. "Product Information. Tranxene (clorazepate)." Abbott Pharmaceutical (2001):

  Show all 14 sourcesShow fewer sources

  9. "Product Information. Klonopin (clonazepam)." Roche Laboratories (2001):
  10. "Product Information. Prosom (estazolam)." Abbott Pharmaceutical (2022):
  11. "Product Information. Librium (chlordiazepoxide)." Roche Laboratories (2001):
  12. "Product Information. Doral (quazepam)." Wallace Laboratories (2001):
  13. "Product Information. Onfi (clobazam)." Lundbeck Inc (2011):
  14. "Product Information. Byfavo (remimazolam)." Acacia Pharma, Inc (2020):

• Depressive Disorder

  Moderate

  Benzodiazepines depress the central nervous system and may cause or exacerbate mental depression and cause suicidal behavior and ideation. Episodes of mania and hypomania have also been reported in depressed patients treated with some of these agents. Therapy with benzodiazepines should be administered cautiously in patients with a history of depression or other psychiatric disorders. Patients should be monitored for any changes in mood or behavior. It may be prudent to refrain from dispensing large quantities of medication to these patients.

  13 sources

  1. "Product Information. Xanax (alprazolam)." Pharmacia and Upjohn (2002):
  2. "Product Information. Valium (diazepam)." Roche Laboratories (2002):
  3. "Product Information. Ativan (lorazepam)." Wyeth-Ayerst Laboratories (2002):
  4. "Product Information. Serax (oxazepam)." Wyeth-Ayerst Laboratories (2001):
  5. "Product Information. Restoril (temazepam)." Sandoz Pharmaceuticals Corporation (2001):
  6. "Product Information. Halcion (triazolam)." Pharmacia and Upjohn (2001):
  7. "Product Information. Dalmane (flurazepam)." Roche Laboratories (2001):
  8. "Product Information. Tranxene (clorazepate)." Abbott Pharmaceutical (2001):

  Show all 13 sourcesShow fewer sources

  9. "Product Information. Klonopin (clonazepam)." Roche Laboratories (2001):
  10. "Product Information. Prosom (estazolam)." Abbott Pharmaceutical (2022):
  11. "Product Information. Librium (chlordiazepoxide)." Roche Laboratories (2001):
  12. "Product Information. Doral (quazepam)." Wallace Laboratories (2001):
  13. "Product Information. Onfi (clobazam)." Lundbeck Inc (2011):

• Obesity

  Moderate

  The plasma half-lives of benzodiazepines may be prolonged in obese patients, presumably due to increased distribution into fat. Marked increases in distribution (> 100%) have been reported for diazepam and midazolam, and moderate increases (25% to 100%) for alprazolam, lorazepam, and oxazepam. Therapy with benzodiazepines should be administered cautiously in obese patients, with careful monitoring of CNS status. Longer dosing intervals may be appropriate. When dosing by weight, loading doses should be based on actual body weight, while maintenance dose should be based on ideal body weight to avoid toxicity.

  14 sources

  1. "Product Information. Xanax (alprazolam)." Pharmacia and Upjohn (2002):
  2. "Product Information. Valium (diazepam)." Roche Laboratories (2002):
  3. "Product Information. Ativan (lorazepam)." Wyeth-Ayerst Laboratories (2002):
  4. "Product Information. Serax (oxazepam)." Wyeth-Ayerst Laboratories (2001):
  5. "Product Information. Restoril (temazepam)." Sandoz Pharmaceuticals Corporation (2001):
  6. "Product Information. Halcion (triazolam)." Pharmacia and Upjohn (2001):
  7. "Product Information. Dalmane (flurazepam)." Roche Laboratories (2001):
  8. "Product Information. Tranxene (clorazepate)." Abbott Pharmaceutical (2001):

  Show all 14 sourcesShow fewer sources

  9. "Product Information. Klonopin (clonazepam)." Roche Laboratories (2001):
  10. "Product Information. Prosom (estazolam)." Abbott Pharmaceutical (2022):
  11. "Product Information. Librium (chlordiazepoxide)." Roche Laboratories (2001):
  12. "Product Information. Doral (quazepam)." Wallace Laboratories (2001):
  13. "Product Information. Versed (midazolam)." Roche Laboratories (2001):
  14. American Medical Association, Division of Drugs and Toxicology "Drug evaluations annual 1994." Chicago, IL: American Medical Association; (1994):

• Psychotic Disorders

  Moderate

  Paradoxical reactions, including excitability, irritability, aggressive behavior, agitation, nervousness, hostility, anxiety, sleep disturbances, nightmares and vivid dreams, have been reported with the use of benzodiazepines in psychiatric patients and pediatric patients with hyperactive aggressive disorders. Such patients should be monitored for signs of paradoxical stimulation during therapy with benzodiazepines. The manufacturers do not recommend the use of benzodiazepines for the treatment of psychosis.

  35 sources

  1. French AP "Dangerously aggressive behavior as a side effect of alprazolam." Am J Psychiatry 146 (1989): 276
  2. Goodman WK, Charney DS "A case of alprazolam, but not lorazepam, inducing manic symptoms." J Clin Psychiatry 48 (1987): 117-8
  3. Edwards JG, Inman WH, Pearce GL, Rawson NS "Prescription-event monitoring of 10,895 patients treated with alprazolam." Br J Psychiatry 158 (1991): 387-92
  4. Wysowski DK, Barash D "Adverse behavioral reactions attributed to triazolam in the Food and Drug Administration's Spontaneous Reporting System." Arch Intern Med 151 (1991): 2003-8
  5. Bixler EO, Kales A, Brubaker BH, Kales JD "Adverse reactions to benzodiazepine hypnotics: spontaneous reporting system." Pharmacology 35 (1987): 286-300
  6. Cohen LS, Rosenbaum JF "Clonazepam: new uses and potential problems." J Clin Psychiatry 48 (1987): 50-6
  7. White MC, Silverman JJ, Harbison JW "Psychosis associated with clonazepam therapy for blepharospasm." J Nerv Ment Dis 170 (1982): 117-9
  8. Dorevitch A "Mania associated with clonazepam." DICP 25 (1991): 938-9

  Show all 35 sourcesShow fewer sources

  9. Marchevsky S, Isaacs G, Nitzan I "Behavioral disinhibition with clonazepam." Gen Hosp Psychiatry 10 (1988): 447
  10. Binder RL "Three case reports of behavioral disinhibition with clonazepam." Gen Hosp Psychiatry 9 (1987): 151-3
  11. Koczerginski D, Kennedy SH, Swinson RP "Clonazepam and lithium--a toxic combination in the treatment of mania?" Int Clin Psychopharmacol 4 (1989): 195-9
  12. Fava M, Borofsky GF "Sexual disinhibition during treatment with a benzodiazepine: a case report." Int J Psychiatry Med 21 (1991): 99-104
  13. Cunningham TA "Letter: Adverse reaction to flurazepam." Can Med Assoc J 112 (1975): 805
  14. Pollack MH "Clonazepam: a review of open clinical trials." J Clin Psychiatry 48 (1987): 12-5
  15. "Product Information. Xanax (alprazolam)." Pharmacia and Upjohn (2002):
  16. "Product Information. Valium (diazepam)." Roche Laboratories (2002):
  17. "Product Information. Ativan (lorazepam)." Wyeth-Ayerst Laboratories (2002):
  18. "Product Information. Serax (oxazepam)." Wyeth-Ayerst Laboratories (2001):
  19. "Product Information. Restoril (temazepam)." Sandoz Pharmaceuticals Corporation (2001):
  20. Karch FE "Rage reaction associated with clorazepate dipotassium." Ann Intern Med 91 (1979): 61-2
  21. Weilburg JB, Sachs G, Falk WE "Triazolam-induced brief episodes of secondary mania in a depressed patient." J Clin Psychiatry 48 (1987): 492-3
  22. Rothschild AJ "Disinhibition, amnestic reactions, and other adverse reactions secondary to triazolam: a review of the literature." J Clin Psychiatry 53 (1992): 69-79
  23. Schogt B, Conn D "Paranoid symptoms associated with triazolam." Can J Psychiatry 30 (1985): 462-3
  24. "Product Information. Halcion (triazolam)." Pharmacia and Upjohn (2001):
  25. "Product Information. Dalmane (flurazepam)." Roche Laboratories (2001):
  26. Viscott DS "Chlordiazepoxide and hallucinations. Report of cases." Arch Gen Psychiatry 19 (1968): 370-6
  27. Fiset L, Milgrom P, Beirne OR, Roy-Byrne P "Disinhibition of behaviors with midazolam: report of a case." J Oral Maxillofac Surg 50 (1992): 645-9
  28. Lobo BL, Miwa LJ "Midazolam disinhibition reaction." Drug Intell Clin Pharm 22 (1988): 725
  29. "Product Information. Tranxene (clorazepate)." Abbott Pharmaceutical (2001):
  30. "Product Information. Klonopin (clonazepam)." Roche Laboratories (2001):
  31. "Product Information. Prosom (estazolam)." Abbott Pharmaceutical (2022):
  32. "Product Information. Librium (chlordiazepoxide)." Roche Laboratories (2001):
  33. Rush CR, Higgins ST, Hughes JR, Bickel WK "A comparison of the acute behavioral effects of triazolam and temazepam in normal volunteers." Psychopharmacology (Berl) 112 (1993): 407-14
  34. "Product Information. Doral (quazepam)." Wallace Laboratories (2001):
  35. "Product Information. Versed (midazolam)." Roche Laboratories (2001):

Therapeutic duplication

Drug classes that overlap with Diazepam, so taking both doubles up the same effect. This source publishes no per-row citations for duplication.

• benzodiazepines

  The recommended maximum number of medicines in the 'benzodiazepines' category to be taken concurrently is usually one.Your list includes two medicines belonging to the 'benzodiazepines' category.

  Example product in the source data (US market): Librax

• benzodiazepines

  The recommended maximum number of medicines in the 'benzodiazepines' category to be taken concurrently is usually one.Your list includes two medicines belonging to the 'benzodiazepines' category.

  Example product in the source data (US market): Limbitrol ds

• tranquilizers

  The recommended maximum number of medicines in the 'tranquilizers' category to be taken concurrently is usually one.Your list includes two medicines belonging to the 'tranquilizers' category.

  Example product in the source data (US market): Phrenilin with caffeine and codeine

• tranquilizers

  The recommended maximum number of medicines in the 'tranquilizers' category to be taken concurrently is usually one.Your list includes two medicines belonging to the 'tranquilizers' category.

  Example product in the source data (US market): Phrenilin

• tranquilizers

  The recommended maximum number of medicines in the 'tranquilizers' category to be taken concurrently is usually one.Your list includes two medicines belonging to the 'tranquilizers' category.

  Example product in the source data (US market): Butabarbital/hyoscyamine/phenazopyridine

• tranquilizers

  The recommended maximum number of medicines in the 'tranquilizers' category to be taken concurrently is usually one.Your list includes two medicines belonging to the 'tranquilizers' category.

  Example product in the source data (US market): Aspirin/butalbital/caffeine/codeine

• tranquilizers

  The recommended maximum number of medicines in the 'tranquilizers' category to be taken concurrently is usually one.Your list includes two medicines belonging to the 'tranquilizers' category.

  Example product in the source data (US market): Micrainin

• tranquilizers

  The recommended maximum number of medicines in the 'tranquilizers' category to be taken concurrently is usually one.Your list includes two medicines belonging to the 'tranquilizers' category.

  Example product in the source data (US market): Nodolor

• tranquilizers

  The recommended maximum number of medicines in the 'tranquilizers' category to be taken concurrently is usually one.Your list includes two medicines belonging to the 'tranquilizers' category.

  Example product in the source data (US market): Laniroif

• tranquilizers

  The recommended maximum number of medicines in the 'tranquilizers' category to be taken concurrently is usually one.Your list includes two medicines belonging to the 'tranquilizers' category.

  Example product in the source data (US market): Phenohytro

• tranquilizers

  The recommended maximum number of medicines in the 'tranquilizers' category to be taken concurrently is usually one.Your list includes two medicines belonging to the 'tranquilizers' category.

  Example product in the source data (US market): Nonbac