Oxymorphone Hydrochloride interactions

Food & lifestyle

• alcohol

  Moderate

  Synergy

  Ethanol may potentiate the central nervous system (CNS) depressant effects of opioid analgesics. Concomitant use may result in additive CNS depression and impairment of judgment, thinking, and psychomotor skills. In more severe cases, hypotension, respiratory depression, profound sedation, coma, or even death may occur.

  What to do: Concomitant use of opioid analgesics with ethanol should be avoided.

  9 sources

  1. Linnoila M, Hakkinen S "Effects of diazepam and codeine, alone and in combination with alcohol, on simulated driving." Clin Pharmacol Ther 15 (1974): 368-73
  2. Sturner WQ, Garriott JC "Deaths involving propoxyphene: a study of 41 cases over a two-year period." JAMA 223 (1973): 1125-30
  3. Girre C, Hirschhorn M, Bertaux L, et al. "Enhancement of propoxyphene bioavailability by ethanol: relation to psychomotor and cognitive function in healthy volunteers." Eur J Clin Pharmacol 41 (1991): 147-52
  4. Levine B, Saady J, Fierro M, Valentour J "A hydromorphone and ethanol fatality." J Forensic Sci 29 (1984): 655-9
  5. Sellers EM, Hamilton CA, Kaplan HL, Degani NC, Foltz RL "Pharmacokinetic interaction of propoxyphene with ethanol." Br J Clin Pharmacol 19 (1985): 398-401
  6. Carson DJ "Fatal dextropropoxyphene poisoning in Northern Ireland. Review of 30 cases." Lancet 1 (1977): 894-7
  7. Rosser WW "The interaction of propoxyphene with other drugs." Can Med Assoc J 122 (1980): 149-50
  8. Edwards C, Gard PR, Handley SL, Hunter M, Whittington RM "Distalgesic and ethanol-impaired function." Lancet 2 (1982): 384

  Show all 9 sourcesShow fewer sources

  9. Kiplinger GF, Sokol G, Rodda BE "Effect of combined alcohol and propoxyphene on human performance." Arch Int Pharmacodyn Ther 212 (1974): 175-80

Conditions

Conditions in which Oxymorphone Hydrochloride needs care, as documented in this source.

• Alcoholic Intoxication

  Major

  The use of opiate agonists is contraindicated in patients with acute alcohol intoxication exhibiting depressed vital signs. The central nervous system depressant effects of opiate agonists may be additive with those of alcohol. Severe respiratory depression and death may occur. Therapy with opiate agonists should be administered cautiously in patients who might be prone to acute alcohol intake.

  16 sources

  1. "Product Information. Calcidrine (codeine)." Abbott Pharmaceutical (2002):
  2. "Product Information. Demerol (meperidine)." Sanofi Winthrop Pharmaceuticals (2002):
  3. "Product Information. Dolophine (methadone)." Lilly, Eli and Company (2002):
  4. "Product Information. MS Contin (morphine)." Purdue Frederick Company (2002):
  5. "Product Information. Levo-Dromoran (levorphanol)." Roche Laboratories (2001):
  6. "Product Information. Dilaudid (hydromorphone)." Knoll Pharmaceutical Company (2001):
  7. "Multum Information Services, Inc. Expert Review Panel"
  8. "Product Information. Darvon (propoxyphene)." Lilly, Eli and Company (2001):

  Show all 16 sourcesShow fewer sources

  9. "Product Information. Duragesic Transdermal System (fentanyl)." Janssen Pharmaceutica, Titusville, NJ.
  10. "Product Information. Sublimaze (fentanyl)." Janssen Pharmaceuticals (2001):
  11. "Product Information. OxyContin (oxycodone)." Purdue Frederick Company (2001):
  12. "Product Information. Kadian (morphine)." Astra-Zeneca Pharmaceuticals (2001):
  13. "Product Information. Vicoprofen (hydrocodone-ibuprofen)." Knoll Pharmaceutical Company (2001):
  14. "Product Information. Opium (opium)." Lilly, Eli and Company (2022):
  15. "Product Information. Numorphan (oxymorphone)." Endo Laboratories LLC (2001):
  16. "Product Information. Nucynta (tapentadol)." PriCara Pharmaceuticals (2009):

• Dysentery

  Major

  Narcotic (opioid) analgesic agents may prolong and/or worsen diarrhea associated with organisms that invade the intestinal mucosa, such as toxigenic E. coli, Salmonella, Shigella, and pseudomembranous colitis due to broad-spectrum antibiotics. These agents decrease gastrointestinal motility, which may delay the excretion of infective gastroenteric organisms and/or their toxins. Other symptoms and complications such as fever, shedding of organisms and extraintestinal illness may also be increased or prolonged. Therapy with opioids should be avoided or administered cautiously in patients with infectious diarrhea, particularly that due to pseudomembranous enterocolitis or enterotoxin-producing bacteria or if accompanied by high fever, pus, or blood in the stool.

  27 sources

  1. Kreek MJ, Hartman N "Chronic use of opioids and antipsychotic drugs: side effects, effects on endogenous opioids, and toxicity." Ann N Y Acad Sci 398 (1982): 151-72
  2. Bellville JW, Forrest WH, Elashoff J, Laska E "Evaluating side effects of analgesics in a cooperative clinical study." Clin Pharmacol Ther 9 (1968): 303-13
  3. "Product Information. Calcidrine (codeine)." Abbott Pharmaceutical (2002):
  4. "Product Information. Demerol (meperidine)." Sanofi Winthrop Pharmaceuticals (2002):
  5. "Product Information. Dolophine (methadone)." Lilly, Eli and Company (2002):
  6. "Product Information. MS Contin (morphine)." Purdue Frederick Company (2002):
  7. "Product Information. Levo-Dromoran (levorphanol)." Roche Laboratories (2001):
  8. White MJ, Berghausen EJ, Dumont SW, Tsueda K, Schroeder JA, Vogel RL, Heine MF, Huang KC "Side effects during continuous epidural infusion of morphine and fentanyl." Can J Anaesth 39 (1992): 576-82

  Show all 27 sourcesShow fewer sources

  9. "Product Information. Dilaudid (hydromorphone)." Knoll Pharmaceutical Company (2001):
  10. Thorn SE, Wattwil M, Kallander A "Effects of epidural morphine and epidural bupivacaine on gastroduodenal motility during the fasted state and after food intake." Acta Anaesthesiol Scand 38 (1994): 57-62
  11. Bennett MWR, Shah MV, Bembridge JL "A comparison of the effect on gastric emptying of alfentanil or morphine given during anaesthesia for minor surgery." Anaesthesia 49 (1994): 155-6
  12. "Product Information. Darvon (propoxyphene)." Lilly, Eli and Company (2001):
  13. "Product Information. Duragesic Transdermal System (fentanyl)." Janssen Pharmaceutica, Titusville, NJ.
  14. "Product Information. Fentanyl Oralet (fentanyl)." Abbott Pharmaceutical, Abbott Park, IL.
  15. "Product Information. OxyContin (oxycodone)." Purdue Frederick Company (2001):
  16. "Product Information. Kadian (morphine)." Astra-Zeneca Pharmaceuticals (2001):
  17. "Product Information. Vicoprofen (hydrocodone-ibuprofen)." Knoll Pharmaceutical Company (2001):
  18. "Product Information. Stadol (butorphanol nasal)." Bristol-Myers Squibb (2001):
  19. "Product Information. Nubain (nalbuphine)." Endo Laboratories LLC (2001):
  20. "Product Information. Buprenex (buprenorphine)." Reckitt and Colman Pharmaceuticals Inc (2001):
  21. "Product Information. Talwin NX (pentazocine)." Sanofi Winthrop Pharmaceuticals (2001):
  22. "Product Information. Stadol (butorphanol)." Allscrips Pharmaceutical Company (2001):
  23. "Product Information. Dalgan (dezocine)." Astra-Zeneca Pharmaceuticals (2001):
  24. "Product Information. Opium (opium)." Lilly, Eli and Company (2022):
  25. "Product Information. Numorphan (oxymorphone)." Endo Laboratories LLC (2001):
  26. "Product Information. Orlaam (levomethadyl acetate)." Roxane Laboratories Inc (2001):
  27. "Product Information. Nucynta (tapentadol)." PriCara Pharmaceuticals (2009):

• Gastrointestinal Diseases

  Major

  Narcotic (opioid) analgesic agents increase smooth muscle tone in the gastrointestinal tract and decrease peristalsis, which can lead to elevated intraluminal pressure, spasm, and constipation following prolonged use. In patients with severe or acute inflammatory bowel disease, the decrease in colonic motility may induce toxic megacolon. Therapy with opioids should be administered cautiously in patients with gastrointestinal obstruction, constipation, inflammatory bowel disease, or recent gastrointestinal tract surgery. Gastrointestinal effects appear to be the most pronounced with morphine.

  27 sources

  1. Kreek MJ, Hartman N "Chronic use of opioids and antipsychotic drugs: side effects, effects on endogenous opioids, and toxicity." Ann N Y Acad Sci 398 (1982): 151-72
  2. Bellville JW, Forrest WH, Elashoff J, Laska E "Evaluating side effects of analgesics in a cooperative clinical study." Clin Pharmacol Ther 9 (1968): 303-13
  3. "Product Information. Calcidrine (codeine)." Abbott Pharmaceutical (2002):
  4. "Product Information. Demerol (meperidine)." Sanofi Winthrop Pharmaceuticals (2002):
  5. "Product Information. Dolophine (methadone)." Lilly, Eli and Company (2002):
  6. "Product Information. MS Contin (morphine)." Purdue Frederick Company (2002):
  7. "Product Information. Levo-Dromoran (levorphanol)." Roche Laboratories (2001):
  8. White MJ, Berghausen EJ, Dumont SW, Tsueda K, Schroeder JA, Vogel RL, Heine MF, Huang KC "Side effects during continuous epidural infusion of morphine and fentanyl." Can J Anaesth 39 (1992): 576-82

  Show all 27 sourcesShow fewer sources

  9. "Product Information. Dilaudid (hydromorphone)." Knoll Pharmaceutical Company (2001):
  10. Thorn SE, Wattwil M, Kallander A "Effects of epidural morphine and epidural bupivacaine on gastroduodenal motility during the fasted state and after food intake." Acta Anaesthesiol Scand 38 (1994): 57-62
  11. Bennett MWR, Shah MV, Bembridge JL "A comparison of the effect on gastric emptying of alfentanil or morphine given during anaesthesia for minor surgery." Anaesthesia 49 (1994): 155-6
  12. "Product Information. Darvon (propoxyphene)." Lilly, Eli and Company (2001):
  13. "Product Information. Duragesic Transdermal System (fentanyl)." Janssen Pharmaceutica, Titusville, NJ.
  14. "Product Information. Fentanyl Oralet (fentanyl)." Abbott Pharmaceutical, Abbott Park, IL.
  15. "Product Information. OxyContin (oxycodone)." Purdue Frederick Company (2001):
  16. "Product Information. Kadian (morphine)." Astra-Zeneca Pharmaceuticals (2001):
  17. "Product Information. Vicoprofen (hydrocodone-ibuprofen)." Knoll Pharmaceutical Company (2001):
  18. "Product Information. Stadol (butorphanol nasal)." Bristol-Myers Squibb (2001):
  19. "Product Information. Nubain (nalbuphine)." Endo Laboratories LLC (2001):
  20. "Product Information. Buprenex (buprenorphine)." Reckitt and Colman Pharmaceuticals Inc (2001):
  21. "Product Information. Talwin NX (pentazocine)." Sanofi Winthrop Pharmaceuticals (2001):
  22. "Product Information. Stadol (butorphanol)." Allscrips Pharmaceutical Company (2001):
  23. "Product Information. Dalgan (dezocine)." Astra-Zeneca Pharmaceuticals (2001):
  24. "Product Information. Opium (opium)." Lilly, Eli and Company (2022):
  25. "Product Information. Numorphan (oxymorphone)." Endo Laboratories LLC (2001):
  26. "Product Information. Orlaam (levomethadyl acetate)." Roxane Laboratories Inc (2001):
  27. "Product Information. Nucynta (tapentadol)." PriCara Pharmaceuticals (2009):

• Hypotension

  Major

  Opiate agonists can induce vasodilation and significant hypotension, particularly when given in high dosages and/or by rapid intravenous administration. Opiate analgesics cause vasodilatation that may exacerbate hypotension and hypoperfusion and, therefore, are contraindicated in circulatory shock. At therapeutic analgesic dosages, ambulatory patients are more likely to experience dizziness and hypotension than patients who are confined to bed. However, orthostatic hypotension may occur in supine patients upon rising. Therapy with opiate agonists should be administered cautiously and initiated at reduced dosages in patients with hypovolemia, or a predisposition to hypotension. When given by intramuscular or subcutaneous administration, clinicians should also be aware that impaired perfusion in these patients may prevent complete absorption of the drug. With repeated injections, an excessive amount may be absorbed suddenly if normal circulation is reestablished.

  26 sources

  1. Parke TJ, Nandi PR, Bird KJ, Jewkes DA "Profound hypotension following intravenous codeine phosphate: three case reports and some recommendations." Anaesthesia 47 (1992): 852-4
  2. "Product Information. Calcidrine (codeine)." Abbott Pharmaceutical (2002):
  3. "Product Information. Demerol (meperidine)." Sanofi Winthrop Pharmaceuticals (2002):
  4. "Product Information. Dolophine (methadone)." Lilly, Eli and Company (2002):
  5. "Product Information. MS Contin (morphine)." Purdue Frederick Company (2002):
  6. "Product Information. Levo-Dromoran (levorphanol)." Roche Laboratories (2001):
  7. Sebel PS, Bovill JG, Boekhorst RA, Rog N "Cardiovascular effects of high-dose fentanyl anaesthesia." Acta Anaesthesiol Scand 26 (1982): 308-15
  8. "Product Information. Dilaudid (hydromorphone)." Knoll Pharmaceutical Company (2001):

  Show all 26 sourcesShow fewer sources

  9. "Product Information. Darvon (propoxyphene)." Lilly, Eli and Company (2001):
  10. "Product Information. Duragesic Transdermal System (fentanyl)." Janssen Pharmaceutica, Titusville, NJ.
  11. "Product Information. Sublimaze (fentanyl)." Janssen Pharmaceuticals (2001):
  12. "Product Information. Fentanyl Oralet (fentanyl)." Abbott Pharmaceutical, Abbott Park, IL.
  13. American Medical Association, Division of Drugs and Toxicology "Drug evaluations annual 1994." Chicago, IL: American Medical Association; (1994):
  14. Cox RG "Hypoxaemia and hypotension after intravenous codeine phosphate." Can J Anaesth 41 (1994): 1211-3
  15. "Product Information. Alfenta (alfentanil)." Janssen Pharmaceuticals (2001):
  16. "Product Information. Sufenta (sufentanil)." Janssen Pharmaceuticals (2001):
  17. "Product Information. OxyContin (oxycodone)." Purdue Frederick Company (2001):
  18. "Product Information. Ultiva (remifentanil)." Mylan Institutional (formally Bioniche Pharma USA Inc) (2001):
  19. "Product Information. Kadian (morphine)." Astra-Zeneca Pharmaceuticals (2001):
  20. "Product Information. Vicoprofen (hydrocodone-ibuprofen)." Knoll Pharmaceutical Company (2001):
  21. "Product Information. Opium (opium)." Lilly, Eli and Company (2022):
  22. "Product Information. Numorphan (oxymorphone)." Endo Laboratories LLC (2001):
  23. "Product Information. Orlaam (levomethadyl acetate)." Roxane Laboratories Inc (2001):
  24. "Product Information. DepoDur (morphine liposomal)." Endo Laboratories LLC (2004):
  25. "Product Information. Nucynta (tapentadol)." PriCara Pharmaceuticals (2009):
  26. "Product Information. Apadaz (acetaminophen-benzhydrocodone)." KemPharm, Inc (2018):

• Intestinal Obstruction

  Major

  Opioid agonists are contraindicated in patients with known or suspected gastrointestinal obstruction, including paralytic ileus.

  4 sources

  1. "Product Information. Ultram (tramadol)." McNeil Pharmaceutical (2001):
  2. "Product Information. OxyContin (oxycodone)." Purdue Frederick Company (2001):
  3. "Product Information. Kadian (morphine)." Astra-Zeneca Pharmaceuticals (2001):
  4. "Product Information. Apadaz (acetaminophen-benzhydrocodone)." KemPharm, Inc (2018):

• Intracranial Hypertension

  Major

  The hypoventilation associated with administration of opiate agonists, particularly by the intravenous route, can induce cerebral hypoxia and vasodilatation with resultant increase in intracranial pressure. Opiate agonists should not be used in patients with suspected or known head injury or increased intracranial pressure. Also, clinicians treating such patients should be aware that opiate agonists may interfere with the evaluation of CNS function, especially with respect to consciousness levels, respiratory status, and pupillary changes.

  23 sources

  1. "Product Information. Calcidrine (codeine)." Abbott Pharmaceutical (2002):
  2. "Product Information. Demerol (meperidine)." Sanofi Winthrop Pharmaceuticals (2002):
  3. "Product Information. Dolophine (methadone)." Lilly, Eli and Company (2002):
  4. "Product Information. MS Contin (morphine)." Purdue Frederick Company (2002):
  5. "Product Information. Levo-Dromoran (levorphanol)." Roche Laboratories (2001):
  6. "Product Information. Dilaudid (hydromorphone)." Knoll Pharmaceutical Company (2001):
  7. "Product Information. Darvon (propoxyphene)." Lilly, Eli and Company (2001):
  8. "Product Information. Duragesic Transdermal System (fentanyl)." Janssen Pharmaceutica, Titusville, NJ.

  Show all 23 sourcesShow fewer sources

  9. "Product Information. Sublimaze (fentanyl)." Janssen Pharmaceuticals (2001):
  10. "Product Information. Fentanyl Oralet (fentanyl)." Abbott Pharmaceutical, Abbott Park, IL.
  11. American Medical Association, Division of Drugs and Toxicology "Drug evaluations annual 1994." Chicago, IL: American Medical Association; (1994):
  12. "Product Information. Alfenta (alfentanil)." Janssen Pharmaceuticals (2001):
  13. "Product Information. Sufenta (sufentanil)." Janssen Pharmaceuticals (2001):
  14. "Product Information. OxyContin (oxycodone)." Purdue Frederick Company (2001):
  15. "Product Information. Ultiva (remifentanil)." Mylan Institutional (formally Bioniche Pharma USA Inc) (2001):
  16. "Product Information. Kadian (morphine)." Astra-Zeneca Pharmaceuticals (2001):
  17. "Product Information. Vicoprofen (hydrocodone-ibuprofen)." Knoll Pharmaceutical Company (2001):
  18. "Product Information. Opium (opium)." Lilly, Eli and Company (2022):
  19. "Product Information. Numorphan (oxymorphone)." Endo Laboratories LLC (2001):
  20. "Product Information. Orlaam (levomethadyl acetate)." Roxane Laboratories Inc (2001):
  21. "Product Information. DepoDur (morphine liposomal)." Endo Laboratories LLC (2004):
  22. "Product Information. Nucynta (tapentadol)." PriCara Pharmaceuticals (2009):
  23. "Product Information. Apadaz (acetaminophen-benzhydrocodone)." KemPharm, Inc (2018):

• Liver Diseases

  Major

  Narcotic (opioid) analgesic agents are extensively metabolized by the liver, and several of them (e.g., codeine, hydrocodone, meperidine, methadone, morphine, propoxyphene) have active metabolites that are further converted to inactive substances. The serum concentrations of these agents and their metabolites may be increased and the half-lives prolonged in patients with impaired hepatic function. Therapy with opioids should be administered cautiously and initiated at reduced dosages in patients with liver disease. Subsequent doses should be titrated based on individual response rather than a fixed dosing schedule.

  59 sources

  1. Yue QY, Hasselstrom J, Svensson JO, Sawe J "Pharmacokinetics of codeine and its metabolites in Caucasian healthy volunteers: comparisons between extensive and poor hydroxylators of debrisoquine." Br J Clin Pharmacol 31 (1991): 635-42
  2. Pond SM, Tong T, Benowitz NL, et al. "Presystemic metabolism of meperidine to normeperidine in normal and cirrhotic subjects." Clin Pharmacol Ther 30 (1981): 183-8
  3. Neal EA, Meffin PJ, Gregory PB, Blaschke TF "Enhanced bioavailability and decreased clearance of analgesics in patients with cirrhosis." Gastroenterology 77 (1979): 96-102
  4. Bower S, Sear JW, Roy RC, Carter RF "Effects of different hepatic pathologies on disposition of alfentanil in anaesthetized patients." Br J Anaesth 68 (1992): 462-5
  5. Parab PV, Ritschel WA, Coyle DE, et al. "Pharmacokinetics of hydromorphone after intravenous, peroral and rectal administration to human subjects." Biopharm Drug Dispos 9 (1988): 187-99
  6. Hill HF, Coda BA, Tanaka A, Schaffer R "Multiple-dose evaluation of intravenous hydromorphone pharmacokinetics in normal human subjects." Anesth Analg 72 (1991): 330-6
  7. Poyhia R, Seppala T, Olkkola KT, Kalso E "The pharmacokinetics and metabolism of oxycodone after intramuscular and oral administration to healthy subjects." Br J Clin Pharmacol 33 (1992): 617-21
  8. Mazoit J-X, Sandouk P, Zetlaoui P, Scherrmann J-M "Pharmacokinetics of unchanged morphine in normal and cirrhotic subjects." Anesth Analg 66 (1987): 293-8

  Show all 59 sourcesShow fewer sources

  9. Poyhia R, Olkkola KT, Seppala T, Kalso E "The pharmacokinetics of oxycodone after intravenous injection in adults." Br J Clin Pharmacol 32 (1991): 516-8
  10. Osborne R, Joel S, Trew D, Slevin M "Morphine and metabolite behavior after different routes of morphine administration: demonstration of the importance of the active metabolite morphine-6-glucoronide." Clin Pharmacol Ther 47 (1990): 12-9
  11. Glare PA, Walsh TD "Clinical pharmacokinetics of morphine." Ther Drug Monit 13 (1991): 1-23
  12. Gram LF, Schou J, Way WL, et al. "delta-Propoxyphene kinetics after single oral and intravenous doses in man." Clin Pharmacol Ther 26 (1979): 473-82
  13. Yun CH, Wood M, Wood AJ, Guengerich FP "Identification of the pharmacogenetic determinants of alfentanil metabolism: cytochrome P-450 3A4: an explanation of the variable elimination clearance." Anesthesiology 77 (1992): 467-74
  14. Cone EJ, Darwin WD, Gorodetzky CW "Comparative metabolism of codeine in man, rat, dog, guinea-pig and rabbit: identification of four new metabolites." J Pharm Pharmacol 31 (1979): 314-7
  15. McHorse TS, Klotz U, Wilkinson G, Schenker S "Impaired elimination of meperidine in patients with liver disease." Trans Assoc Am Physicians 87 (1974): 281-7
  16. Hasselstrom J, Eriksson S, Persson A, Rane A, Svensson JO, Sawe J "The metabolism and bioavailability of morphine in patients with severe liver cirrhosis." Br J Clin Pharmacol 29 (1990): 289-97
  17. Novick DM, Kreek MJ, Arns PA, et al. "Effect of severe alcoholic liver disease on the disposition of methadone in maintenance patients." Alcohol Clin Exp Res 9 (1985): 349
  18. Kreek MJ, Fanizza AM, et al. "Methadone disposition in patients with chronic liver disease." Clin Pharmacol Ther 30 (1981): 353-62
  19. Leow KP, Smith MT, Williams B, Cramond T "Single-dose and steady-state pharmacokinetics and pharmacodynamics of oxycodone in patients with cancer." Clin Pharmacol Ther 52 (1992): 487-95
  20. Leow KP, Smith MT, Watt JA, Williams BE, Cramond T "Comparative oxycodone pharmacokinetics in humans after intravenous, oral, and rectal administration." Ther Drug Monit 14 (1992): 479-84
  21. Goromaru T, Matsuura H, Yoshimura N, Miyawaki T, Sameshima T, Miyao J, Furuta T, Baba S "Identification and quantitative determination of fentanyl metabolites in patients by gas chromatography--mass spectrometry." Anesthesiology 61 (1984): 73-7
  22. Haberer JP, Schoeffler P, Couderc E, Duvaldestin P "Fentanyl pharmacokinetics in anaesthetized patients with cirrhosis." Br J Anaesth 54 (1982): 1267-70
  23. McClain DA, Hug CC, Jr "Intravenous fentanyl kinetics." Clin Pharmacol Ther 28 (1980): 106-14
  24. "Product Information. Calcidrine (codeine)." Abbott Pharmaceutical (2002):
  25. "Product Information. Demerol (meperidine)." Sanofi Winthrop Pharmaceuticals (2002):
  26. "Product Information. Dolophine (methadone)." Lilly, Eli and Company (2002):
  27. "Product Information. MS Contin (morphine)." Purdue Frederick Company (2002):
  28. Dixon R, Crews T, Inturrisi C, Foley K "Levorphanol: pharmacokinetics and steady-state plasma concentrations in patients with pain." Res Commun Chem Pathol Pharmacol 41 (1983): 3-17
  29. "Product Information. Levo-Dromoran (levorphanol)." Roche Laboratories (2001):
  30. Otton SV, Schadel M, Cheung SW, Kaplan HL, Busto UE, Sellers EM "CYP2D6 phenotype determines the metabolic conversion of hydrocodone to hydromorphone." Clin Pharmacol Ther 54 (1993): 463-72
  31. Cone EJ, Darwin WD, Gorodetzky CW, Tan T "Comparative metabolism of hydrocodone in man, rat, guinea pig, rabbit, and dog." Drug Metab Dispos 6 (1978): 488-93
  32. Hasselstrom J, Sawe J "Morphine pharmacokinetics and metabolism in humans. Enterohepatic cycling and relative contribution of metabolites to active opioid concentrations." Clin Pharmacokinet 24 (1993): 344-54
  33. "Product Information. Dilaudid (hydromorphone)." Knoll Pharmaceutical Company (2001):
  34. Giacomini KM, Giacomini JC, Gibson TP, Levy G "Propoxyphene and norpropoxyphene plasma concentrations after oral propoxyphene in cirrhotic patients with and without surgically constructed portacaval shunt." Clin Pharmacol Ther 28 (1980): 417-24
  35. Flanagan RJ, Johnston A, White AS, Crome P "Pharmacokinetics of dextropropoxyphene and nordextropropoxyphene in young and elderly volunteers after single and multiple dextropropoxyphene dosage." Br J Clin Pharmacol 28 (1989): 463-9
  36. Chen ZR, Somogy AA, Reynolds G, Bochner F "Disposition and metabolism of codeine after single and chronic doses in one poor and seven extensive metabolisers." Br J Clin Pharmacol 31 (1991): 381-90
  37. "Product Information. Darvon (propoxyphene)." Lilly, Eli and Company (2001):
  38. "Product Information. Duragesic Transdermal System (fentanyl)." Janssen Pharmaceutica, Titusville, NJ.
  39. Hagen N, Thirlwell MP, Dhaliwal HS, Babul N, Harsanyi Z, Darke AC "Steady-state pharmacokinetics of hydromorphone and hydromorphone-3-glucuronide in cancer patients after immediate and controlled-release hydromorphone." J Clin Pharmacol 35 (1995): 37-44
  40. "Product Information. Alfenta (alfentanil)." Janssen Pharmaceuticals (2001):
  41. "Product Information. Sufenta (sufentanil)." Janssen Pharmaceuticals (2001):
  42. Beckett AH, Vaughan DP, Essien EE "N-Oxidation--an important route in the metabolism of methadone in man." J Pharm Pharmacol 24 (1972): 244
  43. Beckett AH, Taylor JF, Casy AF, Hassan MM "The biotransformation of methadone in man: synthesis and identification of a major metabolite." J Pharm Pharmacol 20 (1968): 754-62
  44. "Product Information. OxyContin (oxycodone)." Purdue Frederick Company (2001):
  45. Dershwitz M, Randel GI, Rosow CE, Fragen RJ, Connors PM, Librojo ES, Shaw DL, Peng AW, Jamerson BD "Initial clinical experience with remifentanil, a new opioid metabolized by esterases." Anesth Analg 81 (1995): 619-23
  46. Dershwitz M, Hoke JF, Rosow CE, Michalowski P, Connors PM, Muir KT, Dienstag JL "Pharmacokinetics and pharmacodynamics of remifentanil in volunteer subjects with severe liver disease." Anesthesiology 84 (1996): 812-20
  47. Westmoreland CL, Hoke JF, Sebel PS, Hug CC Jr, Muir KT "Pharmacokinetics of remifentanil (GI87084B) and its major metabolite (GI90291) in patients undergoing elective inpatient surgery." Anesthesiology 79 (1993): 893-903
  48. "Product Information. Ultiva (remifentanil)." Mylan Institutional (formally Bioniche Pharma USA Inc) (2001):
  49. "Product Information. Kadian (morphine)." Astra-Zeneca Pharmaceuticals (2001):
  50. "Product Information. Vicoprofen (hydrocodone-ibuprofen)." Knoll Pharmaceutical Company (2001):
  51. "Product Information. Nubain (nalbuphine)." Endo Laboratories LLC (2001):
  52. "Product Information. Buprenex (buprenorphine)." Reckitt and Colman Pharmaceuticals Inc (2001):
  53. "Product Information. Talwin NX (pentazocine)." Sanofi Winthrop Pharmaceuticals (2001):
  54. "Product Information. Stadol (butorphanol)." Allscrips Pharmaceutical Company (2001):
  55. "Product Information. Dalgan (dezocine)." Astra-Zeneca Pharmaceuticals (2001):
  56. "Product Information. Opium (opium)." Lilly, Eli and Company (2022):
  57. "Product Information. Numorphan (oxymorphone)." Endo Laboratories LLC (2001):
  58. "Product Information. Orlaam (levomethadyl acetate)." Roxane Laboratories Inc (2001):
  59. "Product Information. Nucynta (tapentadol)." PriCara Pharmaceuticals (2009):

• Premature Birth

  Major

  The use of narcotic (opioid) analgesic agents is contraindicated in premature infants. These agents may cross the immature blood-brain barrier to a greater extent than in adults, resulting in disproportionate respiratory depression.

  2 sources

  1. "Product Information. Calcidrine (codeine)." Abbott Pharmaceutical (2002):
  2. "Multum Information Services, Inc. Expert Review Panel"

• Respiratory Insufficiency

  Major

  Opiate agonists may produce significant central nervous system and respiratory depression of varying duration, particularly when given in high dosages and/or by rapid intravenous administration. Apnea may result from decreased respiratory drive as well as increased airway resistance, and rigidity of respiratory muscles may occur during rapid IV administration or when these agents are used in the induction of anesthesia. At therapeutic analgesic dosages, the respiratory effects are usually not clinically important except in patients with preexisting pulmonary impairment. Therapy with opiate agonists should be avoided or administered with extreme caution and initiated at reduced dosages in patients with severe CNS depression; sleep apnea; hypoxia, anoxia, or hypercapnia; upper airway obstruction; chronic pulmonary insufficiency; a limited ventilatory reserve; or other respiratory disorders. In the presence of excessive respiratory secretions, the use of opiate agonists may also be problematic because they decrease ciliary activity and reduce the cough reflex. Caution is also advised in patients who may be at increased risk for respiratory depression, such as comatose patients or those with head injury, intracranial lesions, or intracranial hypertension. Clinical monitoring of pulmonary function is recommended, and equipment for resuscitation should be immediately available if parenteral or neuraxial routes are used. Naloxone may be administered to reverse clinically significant respiratory depression, which may be prolonged depending on the opioid agent, cumulative dose, and route of administration.

  47 sources

  1. Redpath JB, Pleuvry BJ "Double-blind comparison of the respiratory and sedative effects of codeine phosphate and (+/-)-glaucine phosphate in human volunteers." Br J Clin Pharmacol 14 (1982): 555-8
  2. Rigg JR, Ilsley AH, Vedig AE "Relationship of ventilatory depression to steady-state blood pethidine concentrations." Br J Anaesth 53 (1981): 613-9
  3. Samuels SI, Rabinov W "Difficulty reversing drug-induced coma in a patient with sleep apnea." Anesth Analg 65 (1986): 1222-4
  4. Elloway R, Sherman S, Maas L, et al. "Meperidine-induced bronchospasm." Gastrointest Endosc 38 (1992): 93
  5. Kreek MJ, Hartman N "Chronic use of opioids and antipsychotic drugs: side effects, effects on endogenous opioids, and toxicity." Ann N Y Acad Sci 398 (1982): 151-72
  6. Bellville JW, Forrest WH, Elashoff J, Laska E "Evaluating side effects of analgesics in a cooperative clinical study." Clin Pharmacol Ther 9 (1968): 303-13
  7. Bigler D, Eriksen J, Christensen CB "Prolonged respiratory depression caused by slow release morphine." Lancet 06/30/84 (1984): 1477
  8. Covington EC, Gonsalves-Ebrahim L, Currie KO, et al. "Severe respiratory depression from patient-controlled analgesia in renal failure." Psychosomatics 30 (1989): 226-8

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  9. "Product Information. Calcidrine (codeine)." Abbott Pharmaceutical (2002):
  10. "Product Information. Demerol (meperidine)." Sanofi Winthrop Pharmaceuticals (2002):
  11. "Product Information. Dolophine (methadone)." Lilly, Eli and Company (2002):
  12. "Product Information. MS Contin (morphine)." Purdue Frederick Company (2002):
  13. "Product Information. Levo-Dromoran (levorphanol)." Roche Laboratories (2001):
  14. Sackner MA "Effects of hydrocodone bitartrate on breathing pattern of patients with chronic obstructive pulmonary disease and restrictive lung disease." Mt Sinai J Med 51 (1984): 222-6
  15. Comstock MK, Carter JG, Moyers JR, Stevens WC "Rigidity and hypercarbia associated with high dose fentanyl induction of anesthesia." Anesth Analg 60 (1981): 362-3
  16. Eisenach JC "Respiratory depression following intrathecal opioids." Anesthesiology 75 (1991): 712
  17. Palmer CM "Early respiratory depression following intrathecal fentanyl-morphine combination." Anesthesiology 74 (1991): 1153-5
  18. Brockway MS, Noble DW, Sharwood-Smith GH, McClure JH "Profound respiratory depression after extradural fentanyl." Br J Anaesth 64 (1990): 243-5
  19. Harper MH, Hickey RF, Cromwell TH, Linwood S "The magnitude and duration of respiratory depression produced by fentanyl and fentanyl plus droperidol in man." J Pharmacol Exp Ther 199 (1976): 464-8
  20. Varrassi G, Celleno D, Capogna G, et al. "Ventilatory effects of subarachnoid fentanyl in the elderly." Anaesthesia 47 (1992): 558-62
  21. "Product Information. Dilaudid (hydromorphone)." Knoll Pharmaceutical Company (2001):
  22. Ogawa K, Iranami H, Yoshiyama T, Maeda H, Hatano Y "Severe respiratory depression after epidural morphine in a patient with myotonic dystrophy." Can J Anaesth 40 (1993): 968-70
  23. Noble DW, Morrison LM, Brockway MS, Mcclure JH "Respiratory depression after extradural fentanyl." Br J Anaesth 72 (1994): 251
  24. Houghton IT, Aun CST, Wong YC, Chan K, Lau JTF, Oh TE "The respiratory depressant effect of morphine - a comparative study in three ethnic groups." Anaesthesia 49 (1994): 197-201
  25. Jackson FW "Fentanyl and the wooden chest." Gastroenterology 106 (1994): 820-1
  26. Etches RC "Respiratory depression associated with patient-controlled analgesia - a review of eight cases." Can J Anaesth 41 (1994): 125-32
  27. "Product Information. Darvon (propoxyphene)." Lilly, Eli and Company (2001):
  28. "Product Information. Duragesic Transdermal System (fentanyl)." Janssen Pharmaceutica, Titusville, NJ.
  29. "Product Information. Sublimaze (fentanyl)." Janssen Pharmaceuticals (2001):
  30. "Product Information. Fentanyl Oralet (fentanyl)." Abbott Pharmaceutical, Abbott Park, IL.
  31. American Medical Association, Division of Drugs and Toxicology "Drug evaluations annual 1994." Chicago, IL: American Medical Association; (1994):
  32. Sandler AN, Baxter AD, Katz J, Samson B, Friedlander M, Norman P, Koren G, Roger S, Hull K, Klein J "A double-blind, placebo-controlled trial of transdermal fentanyl after abdominal hysterectomy: analgesic, respiratory, and pharmacokinetic effects." Anesthesiology 81 (1994): 1169-80
  33. "Product Information. Alfenta (alfentanil)." Janssen Pharmaceuticals (2001):
  34. "Product Information. Sufenta (sufentanil)." Janssen Pharmaceuticals (2001):
  35. Hudson RJ "Apnoea and unconsciousness after apparent recovery from alfentanil- supplemented anaesthesia." Can J Anaesth 37 (1990): 255-7
  36. "Product Information. OxyContin (oxycodone)." Purdue Frederick Company (2001):
  37. Morley AD "Profound respiratory depression with morphine patient-controlled analgesia in an elderly patient." Anaesth Intensive Care 24 (1996): 287
  38. Amin HM, Sopchak AM, Esposito BF, Henson LG, Batenhorst RL, Fox AW, Camporesi EM "Naloxone-induced and spontaneous reversal of depressed ventilatory responses to hypoxia during and after continuous infusion of remifentanil or alfentanil." J Pharmacol Exp Ther 274 (1995): 34-9
  39. "Product Information. Ultiva (remifentanil)." Mylan Institutional (formally Bioniche Pharma USA Inc) (2001):
  40. "Product Information. Kadian (morphine)." Astra-Zeneca Pharmaceuticals (2001):
  41. "Product Information. Vicoprofen (hydrocodone-ibuprofen)." Knoll Pharmaceutical Company (2001):
  42. "Product Information. Opium (opium)." Lilly, Eli and Company (2022):
  43. "Product Information. Numorphan (oxymorphone)." Endo Laboratories LLC (2001):
  44. "Product Information. Orlaam (levomethadyl acetate)." Roxane Laboratories Inc (2001):
  45. "Product Information. DepoDur (morphine liposomal)." Endo Laboratories LLC (2004):
  46. "Product Information. Nucynta (tapentadol)." PriCara Pharmaceuticals (2009):
  47. "Product Information. Apadaz (acetaminophen-benzhydrocodone)." KemPharm, Inc (2018):

• Substance-Related Disorders

  Major

  Opiate agonists have the potential to cause dependence and abuse. Tolerance as well as physical and psychological dependence can develop after prolonged use. Abrupt cessation, reduction in dosage, or administration of an opiate antagonist such as naloxone may precipitate withdrawal symptoms. In patients who have developed tolerance to an opiate agonist, overdosage can still produce respiratory depression and death, and cross-tolerance usually will occur with other agents in the class. Addiction-prone individuals, such as those with a history of alcohol or substance abuse, should be under careful surveillance or medical supervision when treated with opiate agonists. 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 opiate therapy should be undertaken gradually using a dosage-tapering schedule.

  27 sources

  1. Fishbain DA, Goldberg M, Rosomoff RS, Rosomoff H "Atypical withdrawal syndrome (organic delusional syndrome) secondary to oxycodone detoxification ." J Clin Psychopharmacol 8 (1988): 441-2
  2. "Product Information. Calcidrine (codeine)." Abbott Pharmaceutical (2002):
  3. "Product Information. Demerol (meperidine)." Sanofi Winthrop Pharmaceuticals (2002):
  4. "Product Information. Dolophine (methadone)." Lilly, Eli and Company (2002):
  5. "Product Information. MS Contin (morphine)." Purdue Frederick Company (2002):
  6. Miser AW, Chayt KJ, Sandlund JT, Cohen PS, Dothage JA, Miser JS "Narcotic withdrawal syndrome in young adults after the therapeutic use of opiates." Am J Dis Child 140 (1986): 603-4
  7. "Product Information. Levo-Dromoran (levorphanol)." Roche Laboratories (2001):
  8. Morrison AB "Toxicity and abuse of hydrocodone bitartrate." Can Med Assoc J 120 (1979): 1338

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  9. "Product Information. Dilaudid (hydromorphone)." Knoll Pharmaceutical Company (2001):
  10. Azorlosa JL, Stitzer ML, Greenwald MK "Opioid physical dependence development - effects of single versus repeated morphine pretreatments and of subjects opioid exposure history." Psychopharmacology (Berl) 114 (1994): 71-80
  11. Strode SW "Propoxyphene dependence and withdrawal." Am Fam Physician 32 (1985): 105-8
  12. Wall R, Linford SM, Akhter MI "Addiction to Distalgesic (dextropropoxyphene)." Br Med J 280 (1980): 1213-4
  13. Salguero CH, Villarreal JE, Hug CC Jr, Domino EF "Propoxyphene dependence." JAMA 210 (1969): 135-6
  14. Claghorn JL, Schoolar JC "Propoxyphene hydrochloride, a drug of abuse." JAMA 196 (1966): 1089-91
  15. Whittington RM "Dextropropoxyphene addiction." Lancet 2 (1979): 743-4
  16. Collins GB, Kiefer KS "Propoxyphene dependence: an update." Postgrad Med 70 (1981): 57-61
  17. Ng B, Alvear M "Dextropropoxyphene addiction--a drug of primary abuse." Am J Drug Alcohol Abuse 19 (1993): 153-8
  18. "Product Information. Darvon (propoxyphene)." Lilly, Eli and Company (2001):
  19. "Product Information. Duragesic Transdermal System (fentanyl)." Janssen Pharmaceutica, Titusville, NJ.
  20. "Product Information. Sublimaze (fentanyl)." Janssen Pharmaceuticals (2001):
  21. Hedenmalm K "A case of severe withdrawal syndrome due to dextropropoxyphene." Ann Intern Med 123 (1995): 473
  22. "Product Information. OxyContin (oxycodone)." Purdue Frederick Company (2001):
  23. "Product Information. Kadian (morphine)." Astra-Zeneca Pharmaceuticals (2001):
  24. "Product Information. Vicoprofen (hydrocodone-ibuprofen)." Knoll Pharmaceutical Company (2001):
  25. "Product Information. Opium (opium)." Lilly, Eli and Company (2022):
  26. "Product Information. Numorphan (oxymorphone)." Endo Laboratories LLC (2001):
  27. "Product Information. Nucynta (tapentadol)." PriCara Pharmaceuticals (2009):

• Adrenal Insufficiency

  Moderate

  Patients with Addison's disease may have increased risk of respiratory depression and prolonged CNS depression associated with the use of narcotic (opioid) analgesic agents. Conversely, these agents may cause or potentiate adrenal insufficiency. Therapy with opioids should be administered cautiously and initiated at reduced dosages in patients with adrenocortical insufficiency. Subsequent doses should be titrated based on individual response rather than a fixed dosing schedule.

  27 sources

  1. "Product Information. Calcidrine (codeine)." Abbott Pharmaceutical (2002):
  2. "Product Information. Demerol (meperidine)." Sanofi Winthrop Pharmaceuticals (2002):
  3. "Product Information. Dolophine (methadone)." Lilly, Eli and Company (2002):
  4. "Product Information. Roxanol (morphine)." Roxane Laboratories Inc (2002):
  5. "Product Information. Levo-Dromoran (levorphanol)." Roche Laboratories (2001):
  6. "Product Information. Dilaudid (hydromorphone)." Knoll Pharmaceutical Company (2001):
  7. "Product Information. Darvon (propoxyphene)." Lilly, Eli and Company (2001):
  8. "Product Information. Duragesic Transdermal System (fentanyl)." Janssen Pharmaceutica, Titusville, NJ.

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  9. "Product Information. Sublimaze (fentanyl)." Janssen Pharmaceuticals (2001):
  10. "Product Information. Fentanyl Oralet (fentanyl)." Abbott Pharmaceutical, Abbott Park, IL.
  11. "Product Information. Alfenta (alfentanil)." Janssen Pharmaceuticals (2001):
  12. "Product Information. Sufenta (sufentanil)." Janssen Pharmaceuticals (2001):
  13. "Product Information. OxyContin (oxycodone)." Purdue Frederick Company (2001):
  14. "Product Information. Ultiva (remifentanil)." Mylan Institutional (formally Bioniche Pharma USA Inc) (2001):
  15. "Product Information. Kadian (morphine)." Astra-Zeneca Pharmaceuticals (2001):
  16. "Product Information. Vicoprofen (hydrocodone-ibuprofen)." Knoll Pharmaceutical Company (2001):
  17. "Product Information. Stadol (butorphanol nasal)." Bristol-Myers Squibb (2001):
  18. "Product Information. Nubain (nalbuphine)." Endo Laboratories LLC (2001):
  19. "Product Information. Buprenex (buprenorphine)." Reckitt and Colman Pharmaceuticals Inc (2001):
  20. "Product Information. Talwin NX (pentazocine)." Sanofi Winthrop Pharmaceuticals (2001):
  21. "Product Information. Stadol (butorphanol)." Allscrips Pharmaceutical Company (2001):
  22. "Product Information. Dalgan (dezocine)." Astra-Zeneca Pharmaceuticals (2001):
  23. Braunwald E, Hauser SL, Kasper DL, Fauci AS, Isselbacher KJ, Longo DL, Martin JB, eds., Wilson JD "Harrison's Principles of Internal Medicine." New York, NY: McGraw-Hill Health Professionals Division (1998):
  24. "Product Information. Opium (opium)." Lilly, Eli and Company (2022):
  25. "Product Information. Numorphan (oxymorphone)." Endo Laboratories LLC (2001):
  26. "Product Information. Orlaam (levomethadyl acetate)." Roxane Laboratories Inc (2001):
  27. "Product Information. Olinvyk (oliceridine)." Trevena Inc (2020):

• Arrhythmias, Cardiac

  Moderate

  Opiate agonists have cholinergic activity. Large doses and/or rapid intravenous administration may produce bradycardia and arrhythmia via stimulation of medullary vagal nuclei. Unlike other agents in the class, meperidine also has anticholinergic activity and may cause either bradycardia or tachycardia. Therapy with opiate agonists should be administered cautiously in patients with a history of arrhythmias. Clinical monitoring of cardiovascular status is recommended during therapy. Bradycardia and other cholinergic effects produced by these agents may be controlled with atropine.

  21 sources

  1. "Product Information. Calcidrine (codeine)." Abbott Pharmaceutical (2002):
  2. "Product Information. Demerol (meperidine)." Sanofi Winthrop Pharmaceuticals (2002):
  3. "Product Information. Dolophine (methadone)." Lilly, Eli and Company (2002):
  4. "Product Information. MS Contin (morphine)." Purdue Frederick Company (2002):
  5. "Product Information. Levo-Dromoran (levorphanol)." Roche Laboratories (2001):
  6. Hilgenberg JC, Johantgen WC "Bradycardia after intravenous fentanyl during subarachnoid anesthesia." Anesth Analg 59 (1980): 162-3
  7. Blair JR, Pruett JK, Crumrine RS, Balser JJ "Prolongation of QT interval in association with the administration of large doses of opiates." Anesthesiology 67 (1987): 442-3
  8. Sebel PS, Bovill JG, Boekhorst RA, Rog N "Cardiovascular effects of high-dose fentanyl anaesthesia." Acta Anaesthesiol Scand 26 (1982): 308-15

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  9. "Product Information. Dilaudid (hydromorphone)." Knoll Pharmaceutical Company (2001):
  10. Heaney RM "Left bundle branch block associated with propoxyphene hydrochloride poisoning." Ann Emerg Med 12 (1983): 780-2
  11. "Product Information. Darvon (propoxyphene)." Lilly, Eli and Company (2001):
  12. "Product Information. Duragesic Transdermal System (fentanyl)." Janssen Pharmaceutica, Titusville, NJ.
  13. "Product Information. Sublimaze (fentanyl)." Janssen Pharmaceuticals (2001):
  14. "Product Information. Alfenta (alfentanil)." Janssen Pharmaceuticals (2001):
  15. "Product Information. Sufenta (sufentanil)." Janssen Pharmaceuticals (2001):
  16. "Product Information. OxyContin (oxycodone)." Purdue Frederick Company (2001):
  17. "Product Information. Ultiva (remifentanil)." Mylan Institutional (formally Bioniche Pharma USA Inc) (2001):
  18. "Product Information. Kadian (morphine)." Astra-Zeneca Pharmaceuticals (2001):
  19. "Product Information. Vicoprofen (hydrocodone-ibuprofen)." Knoll Pharmaceutical Company (2001):
  20. "Product Information. Opium (opium)." Lilly, Eli and Company (2022):
  21. "Product Information. Numorphan (oxymorphone)." Endo Laboratories LLC (2001):

• Epilepsy

  Moderate

  Narcotic (opioid) analgesic agents may exacerbate seizures in patients with seizure disorders and, at higher dosages, have been reported to induce seizures in patients without previous history of seizures. The proconvulsant activity may be the greatest with meperidine, the active metabolite of which is thought to be responsible. Therapy with opioids should be administered cautiously in patients with or predisposed to seizures.

  44 sources

  1. Kaiko RF, Foley KM, Grabinski PY, et al. "Central nervous system excitatory effects of meperidine in cancer patients." Ann Neurol 13 (1983): 180-5
  2. Goetting MG, Thirman MJ "Neurotoxicity of meperidine." Ann Emerg Med 14 (1985): 1007-9
  3. Mauro VF, Bonfiglio MF, Spunt AL "Meperidine-induced seizure in a patient without renal dysfunction or sickle cell anemia." Clin Pharm 5 (1986): 837-9
  4. Reutens DC, Stewart-Wynne EG "Norpethidine induced myoclonus in a patient with renal failure." J Neurol Neurosurg Psychiatry 52 (1989): 1450-1
  5. Armstrong PJ, Bersten A "Normeperidine toxicity." Anesth Analg 65 (1986): 536-8
  6. "Product Information. Calcidrine (codeine)." Abbott Pharmaceutical (2002):
  7. "Product Information. Demerol (meperidine)." Sanofi Winthrop Pharmaceuticals (2002):
  8. "Product Information. Dolophine (methadone)." Lilly, Eli and Company (2002):

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  9. "Product Information. Roxanol (morphine)." Roxane Laboratories Inc (2002):
  10. "Product Information. MS Contin (morphine)." Purdue Frederick Company (2002):
  11. Babul N, Darke AC "Putative role of hydromorphone metabolites in myoclonus." Pain 51 (1992): 260-1
  12. Hagmeyer KO, Mauro LS, Mauro VF "Meperidine-related seizures associated with patient-controlled analgesia pumps." Ann Pharmacother 27 (1993): 29-32
  13. "Product Information. Levo-Dromoran (levorphanol)." Roche Laboratories (2001):
  14. Sebel PS, Bovill JG "Fentanyl and convulsions." Anesth Analg 62 (1983): 858-9
  15. Rao TL, Mummaneni N, El-Etr AA "Convulsions: an unusual response to intravenous fentanyl administration." Anesth Analg 61 (1982): 1020-1
  16. Goroszeniuk T, Albin M, Jones RM "Generalized grand mal seizure after recovery from uncomplicated fentanyl-etomidate anesthesia." Anesth Analg 65 (1986): 979-81
  17. Hoien AO "Another case of grand mal seizure after fentanyl administration." Anesthesiology 60 (1984): 387-8
  18. Safwat AM, Daniel D "Grand mal seizure after fentanyl administration." Anesthesiology 59 (1983): 78
  19. Smith NT, Benthuysen JL, Bickford RG, Sanford TJ, Blasco T, Duke PC, Head N, Dec-Silver H "Seizures during opioid anesthetic induction--are they opioid-induced rigidity?" Anesthesiology 71 (1989): 852-62
  20. Benthuysen JL, Stanley TH "Concerning the possible nature of reported fentanyl seizures." Anesthesiology 62 (1985): 205
  21. "Product Information. Dilaudid (hydromorphone)." Knoll Pharmaceutical Company (2001):
  22. Stone PA, Macintyre PE, Jarvis DA "Norpethidine toxicity and patient controlled analgesia." Br J Anaesth 71 (1993): 738-40
  23. Sjogren P, Dragsted L, Christensen CB "Myoclonic spasms during treatment with high doses of intravenous morphine in renal failure." Acta Anaesthesiol Scand 37 (1993): 780-2
  24. "Product Information. Darvon (propoxyphene)." Lilly, Eli and Company (2001):
  25. "Product Information. Duragesic Transdermal System (fentanyl)." Janssen Pharmaceutica, Titusville, NJ.
  26. "Product Information. Sublimaze (fentanyl)." Janssen Pharmaceuticals (2001):
  27. "Product Information. Fentanyl Oralet (fentanyl)." Abbott Pharmaceutical, Abbott Park, IL.
  28. "Product Information. Alfenta (alfentanil)." Janssen Pharmaceuticals (2001):
  29. "Product Information. Sufenta (sufentanil)." Janssen Pharmaceuticals (2001):
  30. Strong WE, Matson M "Probable seizure after alfentanil." Anesth Analg 68 (1989): 692-3
  31. "Product Information. OxyContin (oxycodone)." Purdue Frederick Company (2001):
  32. "Product Information. Ultiva (remifentanil)." Mylan Institutional (formally Bioniche Pharma USA Inc) (2001):
  33. "Product Information. Kadian (morphine)." Astra-Zeneca Pharmaceuticals (2001):
  34. "Product Information. Vicoprofen (hydrocodone-ibuprofen)." Knoll Pharmaceutical Company (2001):
  35. "Product Information. Stadol (butorphanol nasal)." Bristol-Myers Squibb (2001):
  36. "Product Information. Nubain (nalbuphine)." Endo Laboratories LLC (2001):
  37. "Product Information. Buprenex (buprenorphine)." Reckitt and Colman Pharmaceuticals Inc (2001):
  38. "Product Information. Talwin NX (pentazocine)." Sanofi Winthrop Pharmaceuticals (2001):
  39. "Product Information. Stadol (butorphanol)." Allscrips Pharmaceutical Company (2001):
  40. "Product Information. Dalgan (dezocine)." Astra-Zeneca Pharmaceuticals (2001):
  41. "Product Information. Opium (opium)." Lilly, Eli and Company (2022):
  42. "Product Information. Numorphan (oxymorphone)." Endo Laboratories LLC (2001):
  43. "Product Information. Orlaam (levomethadyl acetate)." Roxane Laboratories Inc (2001):
  44. "Product Information. Nucynta (tapentadol)." PriCara Pharmaceuticals (2009):

• Gallbladder Diseases

  Moderate

  Narcotic (opioid) analgesic agents increase smooth muscle tone in the biliary tract, which can lead to spasm and elevated biliary tract pressure, especially in the sphincter of Oddi. Biliary effects appear to be the most pronounced with morphine, although they do not always occur with therapeutic doses. Therapy with opioids should be administered cautiously in patients with biliary or gallbladder disease.

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  1. Jones RM, Fiddian-Green R, Knight PR "Narcotic-induced choledochoduodenal sphincter spasm reversed by glucagon." Anesth Analg 59 (1980): 946-7
  2. Hey VM, Ostick DG, Mazumder JK, Lord WD "Pethidine, metoclopramide and the gastro-oesophageal sphincter." Anaesthesia 36 (1981): 173-6
  3. Lang DW, Pilon RN "Naloxone reversal of morphine-induced biliary colic." Anesth Analg 59 (1980): 619-20
  4. "Product Information. Calcidrine (codeine)." Abbott Pharmaceutical (2002):
  5. "Product Information. Demerol (meperidine)." Sanofi Winthrop Pharmaceuticals (2002):
  6. "Product Information. Dolophine (methadone)." Lilly, Eli and Company (2002):
  7. "Product Information. MS Contin (morphine)." Purdue Frederick Company (2002):
  8. "Product Information. Levo-Dromoran (levorphanol)." Roche Laboratories (2001):

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  9. McCammon RL, Viegas OJ, Stoelting RK, Dryden GE "Naloxone reversal of choledochoduodenal sphincter spasm associated with narcotic administration." Anesthesiology 48 (1978): 437
  10. "Product Information. Dilaudid (hydromorphone)." Knoll Pharmaceutical Company (2001):
  11. Zsigmond EK, Vieira ZEG, Duarte B, Renigers SA, Hirota K "Double-blind placebo-controlled ultrasonographic confirmation of constriction of the common bile duct by morphine." Int J Clin Pharmacol Ther Toxicol 31 (1993): 506-9
  12. Ford MJ, Kellett RJ, Busuttil A, Finlayson ND "Dextropropoxyphene and jaundice." Br Med J 2 (1977): 674
  13. Daikos GK, Kosmidis JC "Propoxyphene jaundice." JAMA 232 (1975): 835
  14. "Product Information. Darvon (propoxyphene)." Lilly, Eli and Company (2001):
  15. "Product Information. Duragesic Transdermal System (fentanyl)." Janssen Pharmaceutica, Titusville, NJ.
  16. "Product Information. Sublimaze (fentanyl)." Janssen Pharmaceuticals (2001):
  17. "Product Information. Fentanyl Oralet (fentanyl)." Abbott Pharmaceutical, Abbott Park, IL.
  18. American Medical Association, Division of Drugs and Toxicology "Drug evaluations annual 1994." Chicago, IL: American Medical Association; (1994):
  19. "Product Information. OxyContin (oxycodone)." Purdue Frederick Company (2001):
  20. "Product Information. Kadian (morphine)." Astra-Zeneca Pharmaceuticals (2001):
  21. "Product Information. Vicoprofen (hydrocodone-ibuprofen)." Knoll Pharmaceutical Company (2001):
  22. "Product Information. Stadol (butorphanol nasal)." Bristol-Myers Squibb (2001):
  23. "Product Information. Nubain (nalbuphine)." Endo Laboratories LLC (2001):
  24. "Product Information. Buprenex (buprenorphine)." Reckitt and Colman Pharmaceuticals Inc (2001):
  25. "Product Information. Talwin NX (pentazocine)." Sanofi Winthrop Pharmaceuticals (2001):
  26. "Product Information. Stadol (butorphanol)." Allscrips Pharmaceutical Company (2001):
  27. "Product Information. Dalgan (dezocine)." Astra-Zeneca Pharmaceuticals (2001):
  28. "Product Information. Opium (opium)." Lilly, Eli and Company (2022):
  29. "Product Information. Numorphan (oxymorphone)." Endo Laboratories LLC (2001):
  30. "Product Information. Orlaam (levomethadyl acetate)." Roxane Laboratories Inc (2001):
  31. "Product Information. Nucynta (tapentadol)." PriCara Pharmaceuticals (2009):

• Hypothyroidism

  Moderate

  Patients with hypothyroidism may have increased risk of respiratory depression and prolonged CNS depression associated with the use of narcotic (opioid) analgesic agents. These agents may also exacerbate the effects of hypothyroidism such as lethargy, impaired mentation, depression, and constipation. Therapy with opioids should be administered cautiously and initiated at reduced dosages in patients with uncontrolled hypothyroidism or myxedema. Subsequent doses should be titrated based on individual response rather than a fixed dosing schedule.

  25 sources

  1. "Product Information. Calcidrine (codeine)." Abbott Pharmaceutical (2002):
  2. "Product Information. Demerol (meperidine)." Sanofi Winthrop Pharmaceuticals (2002):
  3. "Product Information. Dolophine (methadone)." Lilly, Eli and Company (2002):
  4. "Product Information. MS Contin (morphine)." Purdue Frederick Company (2002):
  5. "Product Information. Levo-Dromoran (levorphanol)." Roche Laboratories (2001):
  6. "Product Information. Dilaudid (hydromorphone)." Knoll Pharmaceutical Company (2001):
  7. "Product Information. Darvon (propoxyphene)." Lilly, Eli and Company (2001):
  8. "Product Information. Duragesic Transdermal System (fentanyl)." Janssen Pharmaceutica, Titusville, NJ.

  Show all 25 sourcesShow fewer sources

  9. "Product Information. Sublimaze (fentanyl)." Janssen Pharmaceuticals (2001):
  10. "Product Information. Fentanyl Oralet (fentanyl)." Abbott Pharmaceutical, Abbott Park, IL.
  11. "Product Information. Alfenta (alfentanil)." Janssen Pharmaceuticals (2001):
  12. "Product Information. Sufenta (sufentanil)." Janssen Pharmaceuticals (2001):
  13. "Product Information. OxyContin (oxycodone)." Purdue Frederick Company (2001):
  14. "Product Information. Ultiva (remifentanil)." Mylan Institutional (formally Bioniche Pharma USA Inc) (2001):
  15. "Product Information. Kadian (morphine)." Astra-Zeneca Pharmaceuticals (2001):
  16. "Product Information. Vicoprofen (hydrocodone-ibuprofen)." Knoll Pharmaceutical Company (2001):
  17. "Product Information. Stadol (butorphanol nasal)." Bristol-Myers Squibb (2001):
  18. "Product Information. Nubain (nalbuphine)." Endo Laboratories LLC (2001):
  19. "Product Information. Buprenex (buprenorphine)." Reckitt and Colman Pharmaceuticals Inc (2001):
  20. "Product Information. Talwin NX (pentazocine)." Sanofi Winthrop Pharmaceuticals (2001):
  21. "Product Information. Stadol (butorphanol)." Allscrips Pharmaceutical Company (2001):
  22. "Product Information. Dalgan (dezocine)." Astra-Zeneca Pharmaceuticals (2001):
  23. "Product Information. Opium (opium)." Lilly, Eli and Company (2022):
  24. "Product Information. Numorphan (oxymorphone)." Endo Laboratories LLC (2001):
  25. "Product Information. Orlaam (levomethadyl acetate)." Roxane Laboratories Inc (2001):

• Kidney Diseases

  Moderate

  Although narcotic (opioid) analgesic agents are generally metabolized by the liver, renal impairment can alter the elimination of these agents and their metabolites (some of which are pharmacologically active), resulting in drug accumulation and increased risk of toxicity. Therapy with opioids should be administered cautiously and initiated at reduced dosages in patients with significantly impaired renal function. Subsequent doses should be titrated based on individual response rather than a fixed dosing schedule.

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  2. Barnes JN, Williams AJ, Tomson MJ, et al. "Dihydrocodeine in renal failure: further evidence for an important role of the kidney in the handling of opioid drugs." Br Med J (Clin Res Ed) 290 (1985): 740-2
  3. Matske GR, Chan GL, Abraham PA "Codeine dosage in renal failure." Clin Pharm 5 (1986): 15-6
  4. Guy DR, Awni WM, Findlay JW, et al. "Pharmacokinetics and pharmacodynamics of codeine in end-stage renal disease." Clin Pharmacol Ther 43 (1988): 63-71
  5. Charuvastra VC, Ouren J "Renal failure and treatment of a methadone maintenance patient." Med J Aust 09/24/77 (1977): 433-4
  6. Verbeeck RK, Branch RA, Wilkinson GR "Drug metabolites in renal failure: pharmacokinetic and clinical implications." Clin Pharmacokinet 6 (1981): 329-45
  7. Drayer DE "Active drug metabolites and renal failure." Am J Med 62 (1977): 486-9
  8. Drayer DE "Pharmacologically active drug metabolites: therapeutic and toxic activities, plasma and urine data in man, accumulation in renal failure." Clin Pharmacokinet 1 (1976): 426-43

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  9. Parab PV, Ritschel WA, Coyle DE, et al. "Pharmacokinetics of hydromorphone after intravenous, peroral and rectal administration to human subjects." Biopharm Drug Dispos 9 (1988): 187-99
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  11. Poyhia R, Seppala T, Olkkola KT, Kalso E "The pharmacokinetics and metabolism of oxycodone after intramuscular and oral administration to healthy subjects." Br J Clin Pharmacol 33 (1992): 617-21
  12. Wolff J, Bigler D, Christensen CB, et al. "Influence of renal function on the elimination of morphine and morphine glucoronides." Eur J Clin Pharmacol 34 (1988): 353-7
  13. Covington EC, Gonsalves-Ebrahim L, Currie KO, et al. "Severe respiratory depression from patient-controlled analgesia in renal failure." Psychosomatics 30 (1989): 226-8
  14. Poyhia R, Olkkola KT, Seppala T, Kalso E "The pharmacokinetics of oxycodone after intravenous injection in adults." Br J Clin Pharmacol 32 (1991): 516-8
  15. Glare PA, Walsh TD "Clinical pharmacokinetics of morphine." Ther Drug Monit 13 (1991): 1-23
  16. Gram LF, Schou J, Way WL, et al. "delta-Propoxyphene kinetics after single oral and intravenous doses in man." Clin Pharmacol Ther 26 (1979): 473-82
  17. Bechtel WD, Sinterhauf K "Plasma level and renal excretion of [3H] codeine phosphate in man and in the dog." Arzneimittelforschung 28 (1978): 308-11
  18. Wolfert AI, Sica DA "Narcotic usage in renal failure." Int J Artif Organs 11 (1988): 411-5
  19. Inturrisi CE "Disposition of narcotics in patients with renal disease." Am J Med 62 (1977): 528-9
  20. Chan K, Jennings F, Orme ML "Pharmacokinetics of low-dose intravenous pethidine in patients with renal dysfunction." J Clin Pharmacol 27 (1987): 516-22
  21. Chauvin M, Sandouk P, Scherrmann JM, Farinotti R, Strumza P, Duvaldestin P "Morphine pharmacokinetics in renal failure." Anesthesiology 66 (1987): 327-31
  22. Aitkenhead AR, Vater M, Achola K, Cooper CM, Smith G "Pharmacokinetics of single-dose i.v. morphine in normal volunteers and patients with end-stage renal failure." Br J Anaesth 56 (1984): 813-9
  23. Sawe J, Odar-Cederlof I "Kinetics of morphine in patients with renal failure." Eur J Clin Pharmacol 32 (1987): 377-82
  24. Baselt RC, Casarett LJ "Urinary excretion of methadone in man." Clin Pharmacol Ther 13 (1972): 64-70
  25. Kreek MJ, Schecter AJ, Gutjahr CL, et al. "Methadone use in patients with chronic renal failure." Drug Alcohol Depend 5 (1980): 197-205
  26. Leow KP, Smith MT, Williams B, Cramond T "Single-dose and steady-state pharmacokinetics and pharmacodynamics of oxycodone in patients with cancer." Clin Pharmacol Ther 52 (1992): 487-95
  27. Leow KP, Smith MT, Watt JA, Williams BE, Cramond T "Comparative oxycodone pharmacokinetics in humans after intravenous, oral, and rectal administration." Ther Drug Monit 14 (1992): 479-84
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  29. "Product Information. Demerol (meperidine)." Sanofi Winthrop Pharmaceuticals (2002):
  30. "Product Information. Dolophine (methadone)." Lilly, Eli and Company (2002):
  31. "Product Information. MS Contin (morphine)." Purdue Frederick Company (2002):
  32. Dixon R, Crews T, Inturrisi C, Foley K "Levorphanol: pharmacokinetics and steady-state plasma concentrations in patients with pain." Res Commun Chem Pathol Pharmacol 41 (1983): 3-17
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  34. Hanna MH, D'Costa F, Peat SJ, Fung C, Venkat N, Zilkha TR, Davies S "Morphine-6-glucuronide disposition in renal impairment." Br J Anaesth 70 (1993): 511-4
  35. "Product Information. Dilaudid (hydromorphone)." Knoll Pharmaceutical Company (2001):
  36. Gibson TP, Giacomini KM, Briggs WA, Whitman W, Levy G "Propoxyphene and norpropoxyphene plasma concentrations in the anephric patient." Clin Pharmacol Ther 27 (1980): 665-70
  37. Flanagan RJ, Johnston A, White AS, Crome P "Pharmacokinetics of dextropropoxyphene and nordextropropoxyphene in young and elderly volunteers after single and multiple dextropropoxyphene dosage." Br J Clin Pharmacol 28 (1989): 463-9
  38. Giacomini KM, Gibson TP, Levy G "Plasma protein binding of d-propoxyphene in normal subjects and anephric patients." J Clin Pharmacol 18 (1978): 106-9
  39. Sjogren P, Dragsted L, Christensen CB "Myoclonic spasms during treatment with high doses of intravenous morphine in renal failure." Acta Anaesthesiol Scand 37 (1993): 780-2
  40. "Product Information. Darvon (propoxyphene)." Lilly, Eli and Company (2001):
  41. "Product Information. Duragesic Transdermal System (fentanyl)." Janssen Pharmaceutica, Titusville, NJ.
  42. Dhonneur G, Gilton A, Sandouk P, Scherrmann JM, Duvaldestin P "Plasma and cerebrospinal fluid concentrations of morphine and morphine glucuronides after oral morphine - the influence of renal failure." Anesthesiology 81 (1994): 87-93
  43. "Product Information. Alfenta (alfentanil)." Janssen Pharmaceuticals (2001):
  44. "Product Information. Sufenta (sufentanil)." Janssen Pharmaceuticals (2001):
  45. "Product Information. OxyContin (oxycodone)." Purdue Frederick Company (2001):
  46. "Product Information. Ultiva (remifentanil)." Mylan Institutional (formally Bioniche Pharma USA Inc) (2001):
  47. "Product Information. Kadian (morphine)." Astra-Zeneca Pharmaceuticals (2001):
  48. "Product Information. Vicoprofen (hydrocodone-ibuprofen)." Knoll Pharmaceutical Company (2001):
  49. "Product Information. Nubain (nalbuphine)." Endo Laboratories LLC (2001):
  50. "Product Information. Buprenex (buprenorphine)." Reckitt and Colman Pharmaceuticals Inc (2001):
  51. "Product Information. Talwin NX (pentazocine)." Sanofi Winthrop Pharmaceuticals (2001):
  52. "Product Information. Stadol (butorphanol)." Allscrips Pharmaceutical Company (2001):
  53. "Product Information. Dalgan (dezocine)." Astra-Zeneca Pharmaceuticals (2001):
  54. "Product Information. Opium (opium)." Lilly, Eli and Company (2022):
  55. "Product Information. Numorphan (oxymorphone)." Endo Laboratories LLC (2001):
  56. "Product Information. Orlaam (levomethadyl acetate)." Roxane Laboratories Inc (2001):
  57. "Product Information. Nucynta (tapentadol)." PriCara Pharmaceuticals (2009):

• Urinary Retention

  Moderate

  Narcotic (opioid) analgesic agents may inhibit the urinary voiding reflex and increase the tone of the vesical sphincter in the bladder. Acute urinary retention requiring catheterization may occur, particularly in patients with prostatic hypertrophy or urethral stricture and in elderly patients. These agents may also decrease urine production via direct effects on the kidney and central stimulation of the release of vasopressin. Therapy with opioids should be administered cautiously in patients with or predisposed to urinary retention and/or oliguria. The effects on smooth muscle tone appear to be the most pronounced with morphine.

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  1. Kreek MJ, Hartman N "Chronic use of opioids and antipsychotic drugs: side effects, effects on endogenous opioids, and toxicity." Ann N Y Acad Sci 398 (1982): 151-72
  2. Petersen TK, Husted SE, Rybro L, et al. "Urinary retention during I.M. and extradural morphine analgesia." Br J Anaesth 54 (1982): 1175-8
  3. "Product Information. Calcidrine (codeine)." Abbott Pharmaceutical (2002):
  4. "Product Information. Demerol (meperidine)." Sanofi Winthrop Pharmaceuticals (2002):
  5. "Product Information. Dolophine (methadone)." Lilly, Eli and Company (2002):
  6. "Product Information. Roxanol (morphine)." Roxane Laboratories Inc (2002):
  7. Petros JG, Mallen JK, Howe K, Rimm EB, Robillard RJ "Patient-controlled analgesia and postoperative urinary retention after open appendectomy." Surg Gynecol Obstet 177 (1993): 172-5
  8. "Product Information. Levo-Dromoran (levorphanol)." Roche Laboratories (2001):

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  9. "Product Information. Dilaudid (hydromorphone)." Knoll Pharmaceutical Company (2001):
  10. "Product Information. Darvon (propoxyphene)." Lilly, Eli and Company (2001):
  11. "Product Information. Duragesic Transdermal System (fentanyl)." Janssen Pharmaceutica, Titusville, NJ.
  12. "Product Information. Sublimaze (fentanyl)." Janssen Pharmaceuticals (2001):
  13. "Product Information. Fentanyl Oralet (fentanyl)." Abbott Pharmaceutical, Abbott Park, IL.
  14. American Medical Association, Division of Drugs and Toxicology "Drug evaluations annual 1994." Chicago, IL: American Medical Association; (1994):
  15. "Product Information. Alfenta (alfentanil)." Janssen Pharmaceuticals (2001):
  16. "Product Information. Sufenta (sufentanil)." Janssen Pharmaceuticals (2001):
  17. "Product Information. OxyContin (oxycodone)." Purdue Frederick Company (2001):
  18. "Product Information. Ultiva (remifentanil)." Mylan Institutional (formally Bioniche Pharma USA Inc) (2001):
  19. "Product Information. Kadian (morphine)." Astra-Zeneca Pharmaceuticals (2001):
  20. "Product Information. Vicoprofen (hydrocodone-ibuprofen)." Knoll Pharmaceutical Company (2001):
  21. "Product Information. Stadol (butorphanol nasal)." Bristol-Myers Squibb (2001):
  22. "Product Information. Nubain (nalbuphine)." Endo Laboratories LLC (2001):
  23. "Product Information. Buprenex (buprenorphine)." Reckitt and Colman Pharmaceuticals Inc (2001):
  24. "Product Information. Talwin NX (pentazocine)." Sanofi Winthrop Pharmaceuticals (2001):
  25. "Product Information. Stadol (butorphanol)." Allscrips Pharmaceutical Company (2001):
  26. "Product Information. Dalgan (dezocine)." Astra-Zeneca Pharmaceuticals (2001):
  27. "Product Information. Opium (opium)." Lilly, Eli and Company (2022):
  28. "Product Information. Numorphan (oxymorphone)." Endo Laboratories LLC (2001):
  29. "Product Information. Orlaam (levomethadyl acetate)." Roxane Laboratories Inc (2001):
  30. "Product Information. Nucynta (tapentadol)." PriCara Pharmaceuticals (2009):