Pharmacokinetic evaluation of hydrocodone/acetaminophen for pain management

Authors

  • Aarti Singla, MD Department of Anesthesiology, University of Kentucky Medical Center, Lexington, Kentucky.
  • Paul Sloan, MD Department of Anesthesiology, University of Kentucky Medical Center, Lexington, Kentucky.

DOI:

https://doi.org/10.5055/jom.2013.0149

Keywords:

chronic pain, acute pain, opioids, hydrocodone, analgesia

Abstract

Hydrocodone/acetaminophen is not only the most commonly prescribed opioid in the United States but also the most common prescription medication written in America. Although original and early trials confirmed its ability to manage acute pain from surgery and musculoskeletal injury, it is perhaps more widely used today in the management of chronic pain. However, the opioid product was introduced for the management of moderate to moderately severe pain. Because it has been greatly abused as a prescription opioid medication, physicians need to be aware of the current knowledge regarding this analgesic drug. This review summarizes the current knowledge of the pharmacokinetics, pharmacodynamics, and metabolism of hydrocodone. Recent information regarding the possibility of hydrocodone as a prodrug for hydromorphone is discussed. The available clinical trials for the use of hydrocodone in the management of acute, chronic, and cancer pain are presented. Keywords: chronic pain, acute pain, opioids, hydrocodone, analgesia DOI:10.5055/jom.2013.0149

References

Centers for Disease Control and Prevention: Inpatient Surgery. Available at http://cdc.gov/nchs/fastats/insurg.htm. Accessed June 11, 2011.

Centers for Disease Control and Prevention: U.S. Outpatient Surgeries on the Rise. Available at http://cdc.gov/nchs/pressroom/09newsreleases/outpatientsurgeries.htm. Accessed June 11, 2011.

Hopkinson JH: Hydrocodone–A unique challenge for an established drug: Comparison of repeated oral doses of hydrocodone (10 mg) and codeine (60 mg) in the treatment of postpartum pain. Curr Ther Res. 1978; 24(5): 503-516.

Eddy NB, Halbach H, Braenden OJ: Synthetic substances with morphine-like effect clinical experience: Potency, side-effects, addiction liability. Bull World Health Org. 1957; 17: 595-600.

DeNoon D: The 10 most prescribed drugs. Available at http://www.webmd.com/news/20110420/the-most-prescribeddrugs. Accessed January 28, 2013.

Nerenberg DM, Fudin J: Maximum daily dose of hydrocodone. Am J Health Syst Pharm. 2010; 67(19): 1588-1589.

Prommer E: Hydrocodone: Does it have a role in palliative care? J Opioid Manag. 2010; 6(4): 295-299.

Hydrocodone Bitartrate [product insert]. Hazelwood, MO: Mallinckrodt Inc., 2009.

US Department of Justice Drug Enforcement Administration: Controlled Substance Schedules. Available at http://www.deadiversion.usdoj.gov/schedules/index.html. Accessed September 12, 2012.

US Department of Justice Drug Enforcement Administration: Pharmacist’s Manual Section IX–Valid Prescription Requirements. Available at http://www.deadiversion.usdoj.gov/pubs/manuals/pharm2/pharm_content.htm. Accessed September 12, 2012.

Kaplan HL, Busto UE, Baylon GJ, et al.: Inhibition of cytochrome P450 2D6 metabolism of hydrocodone to hydromorphone does not importantly affect abuse liability. J Pharmacol Exp Ther. 1997; 281(1): 103-108.

Cone EJ, Darwin WD, Gorodetzky CW, et al.: Comparative metabolism of hydrocodone in man, rat, guinea pig, rabbit, and dog. Drug Metab Dispos. 1979; 6(4): 488-493.

ARUP Laboratories: Drugs of Abuse-Opiates and Related Drugs. 2011. Available at www.aruplab.com/Testing-Information/resources/Technical Bulletins/drugs_of_abuse_opiates.pdf. Accessed June 2011.

Barakat NH, Atayee RS, Best BM, et al.: Relationship between the concentration of hydrocodone and its conversion to hydromorphone in chronic pain patients using urinary excretion data. J Anal Toxicol. 2012; 36(4): 257-264.

Armstrong SC, Cozza KL: Pharmacokinetic drug interactions of morphine, codeine, and their derivatives: Theory and clinical reality, Part II. Psychosomatics. 2003; 44(6): 515-520.

Otton SV, Schadel M, Cheung SW, et al.: CYP2D6 phenotype determines the metabolic conversion of hydrocodone to hydromorphone. Clin Pharmacol Ther. 1993; 54(5): 463-472.

Hutchinson MR, Menelaou A, Foster DJ, et al.: CYP2D6 and CYP3A4 involvement in the primary oxidative metabolism of hydrocodone by human liver microsomes. Br J Clin Pharmacol. 2004; 57(3): 287-297.

McLellan RA, Oscarson M, Seidegard J, et al.: Frequent occurrence of CYP2D6 gene duplication in Saudi Arabians. Pharmacogenetics. 1997; 7(3): 187-191.

Marco CA, Plewa MC, Buderer N, et al.: Comparison of oxycodone and hydrocodone for the treatment of acute pain associated with fractures: A double-blind, randomized, control trial. Acad Emerg Med. 2005; 12(4): 282-288.

Sunshine A, Olson NZ, O’Neill E, et al.: Analgesic efficacy of a hydrocodone with ibuprofen combination compared with ibuprofen alone for the treatment of acute postoperative pain. J Clin Pharmacol. 1997; 37(10): 908-915.

Litkowski LJ, Christensen SE, Adamson DN, et al.: Analgesic efficacy and tolerability of oxycodone 5 mg/ibuprofen 400 mg compared with those of oxycodone 5 mg/acetaminophen 325 mg and hydrocodone 7.5 mg/acetaminophen 500 mg in patients with moderate to severe postoperative pain: A randomized, double-blind, placebo-controlled, single-dose, parallel-group study in a dental pain model. Clin Ther. 2005; 27(4): 418-429.

Miner JR: Randomized double-blind placebo controlled crossover study of acetaminophen, ibuprofen, acetaminophen/hydrocodone, and placebo for the relief from a standard painful stimulus. Acad Emerg Med. 2009; 16(9): 911-914.

Rodriguez RF, Castillo JM, Castillo MP, et al.: Hydrocodone/ acetaminophen and tramadol chloral hydrate combination tablets for the management of chronic cancer pain: A double-blind comparative trial. Clin J Pain. 2008; 24(1): 1-4.

Rodriguez RF, Castillo JM, Castillo MP, et al.: Codeine/acetaminophen and hydrocodone/acetaminophen combination tablets for the management of chronic cancer pain in adults: A 23-day, prospective, double-blind, randomized, parallel group study. Clin Ther. 2007; 29(4): 581-587.

Rodriguez RF, Bravo LE, Castro F, et al.: Incidence of weak opioids adverse events in the management of cancer pain: A doubleblind comparative trial. J Palliat Med. 2007; 10(1): 56-60.

Hewitt DJ, Todd KH, Xiang J, et al.: Tramadol/acetaminophen or hydrocodone/acetaminophen for the treatment of ankle sprain: A randomized, placebo-controlled trial. Ann Emerg Med. 2007; 49(4): 468-480.

Church CA, Stewart C IV, O-Lee TJ, et al.: Rofecoxib versus hydrocodone/acetaminophen for postoperative analgesia in functional endoscopic sinus surgery. Laryngoscope. 2006; 116(4): 602-606.

Freedman BM, Balakrishnan TP, O’Hara EL: Celecoxib reduces narcotic use and pain following augmentation mammoplasty. Aesthet Surg J. 2006; 26(1): 24-28.

Bentancourt JW, Kupp LI, Jasper SJ, et al.: Efficacy of ibuprofenhydrocodone for the treatment of postoperative pain after periodontal surgery. J Periodotol. 2004; 75(6): 872-876.

Fricke JR Jr, Karim R, Jordan D, et al.: A double-blind, single dose comparison of the analgesic efficacy of tramadol/acetaminophen combination tablets, hydrocodone/acetaminophen combination tablets, and placebo after oral surgery. Clin Ther. 2002; 24(6): 953-968.

Palangio M, Morris E, Doyle RT Jr, et al.: Combination hydrocodone and ibuprofen versus combination oxycodone and acetaminophen in the treatment of moderate or severe acute low back pain. Clin Ther. 2002; 24(1): 87-99.

Gimbel JS, Brugger A, Zhao W, et al.: Efficacy and tolerability of celecoxib versus hydrocodone/acetaminophen in the treatment of pain after ambulatory orthopedic surgery in adults. Clin Ther. 2001; 23(2): 228-241.

Palangio M, Wideman GL, Keffer M, et al.: Dose-response effect of combination hydrocodone with ibuprofen in patients with moderate to severe postoperative pain. Clin Ther. 2000; 22(8): 990-1002.

Palangio M, Damask MJ, Morris E, et al.: Combination hydrocodone and ibuprofen versus combination codeine and acetaminophen for the treatment of chronic pain. Clin Ther. 2000; 22(7): 879-892.

Ziccardi VB, Desjardins PJ, Daly-DeJoy E, et al.: Single-dose vicoprofen compared with acetaminophen with codeine and placebo in patients with acute postoperative pain after third molar extractions. J Oral Maxillofac Surg. 2000; 58(6): 622-628.

Wideman GL, Keffer M, Morris E, et al.: Analgesic efficacy of a combination of hydrocodone with ibuprofen for postoperative pain. Clin Pharmacol Ther. 1999; 65(1): 66-76.

Barber FA, Gladu DE: Comparison of oral ketorolac and hydrocodone for pain relief after anterior cruciate ligament reconstruction. Arthroscopy. 1998; 14(6): 605-612.

Turturro MA, Paris PM, Larkin GL: Tramadol versus hydrocodone-acetaminophen in acute musculoskeletal pain: A randomized, double-blind clinical trial. Ann Emerg Med. 1998; 32(2): 139-143.

White PF, Joshi GP, Carpenter RL, et al.: A comparison of oral ketorolac and hydrocodone-acetaminophen for analgesia after ambulatory surgery: Arthroscopy versus laparoscopic tubal ligation. Anesth Analg. 1997; 85(1): 37-43.

Reed KL, Smith JR, Lie T, et al.: A pilot study comparing ketoprofen and acetaminophen with hydrocodone for the relief of postoperative periodontal discomfort. Anesth Prog. 1997; 44(2): 49-54.

Tucker PW, Smith JR, Adams DF: A comparison of 2 analgesic regimens for the control of postoperative periodontal discomfort. J Periodontol. 1996; 67(2): 125-129.

Forbes JA, Bates JA, Edquist IA, et al.: Evaluation of two opioidacetaminophen combinations and placebo in postoperative oral surgery pain. Pharmacotherapy. 1994; 14(2): 139-146.

Fricke JR, Halladay SC, Bynum L, et al.: Pain relief after dental impaction surgery using ketorolac, hydrocodone plus acetaminophen, or placebo. Clin Ther. 1993; 15(3): 500-509.

Turturro MA, Paris PM, Yealy DM, et al.: Hydrocodone versus codeine in acute musculoskeletal pain. Ann Emerg Med. 1991; 20(10): 1100-1103.

Sloan PA, Moulin D, Hays H: A clinical evaluation of TTSFentanyl for the treatment of cancer pain. J Pain Symptom Manage. 1998; 16(2): 102-111.

Sloan PA, Plymale M, LaFountain P, et al.: Equipping medial students to manage cancer pain: A comparison of three teaching educational methods among medical students. J Pain Symptom Manage. 2004; 27(4): 333-342.

Sloan PA: Review of oral oxymorphone in the management of pain. Ther Clin Risk Manag. 2008; 4(4): 777-787.

Sloan PA, Babul N: Embeda™: Morphine sulfate extended-release with sequestered naltrexone, a novel opioid formulation for the treatment of chronic pain. Int J Clin Rheumatol. 2010; 5(2): 155-164.

Morrow PL, Faris EC: Death associated with inadvertent hydrocodone overdose in a child with a respiratory tract infection. Am J Forensic Med Pathol. 1987; 8(1): 60-63.

US Food and Drug Administration: Madadi P, Hildebrandt D, Gong IY, et al.: Fatal hydrocodone overdose in a child: Pharmacogenetics and drug interactions. Pediatrics. 2010; 126(4): 986-989.

US Food and Drug Administration: Long-acting hydrocodonecontaining cough products (marketed as Tussionex® Pennkinetic Extended-Release). Available at http://www.fda.gov/ Safety/MedWatch/SafetyInformation/SafetyAlertsforHumanMedicalProducts/ucm091793.htm. Accessed September 12, 2012.

US Food and Drug Administration: Prescription acetaminophen products to be limited to 325 mg per dosage unit; boxed warning highlight potential for severe liver failure. FDA Drug Safety Communication. Washington, DC. Available at www.fda. gov/Drugs/DrugSafety/ucm239821.htm. Accessed May 13, 2011.

Krenzelok EP: The FDA acetaminophen Advisory Committee Meeting–What is the future of acetaminophen in the United States? The perspective of a committee member. Clin Toxicol. 2009; 47(8): 784-789.

Ceelie I, James LP, Gijsen V, et al.: Acute liver failure after recommended doses of acetaminophen in patients with myopathies. Crit Care Med. 2011; 39(4): 678-682.

Zogenix®: ER™ (hydrocodone bitartrate extended release). Available at http://www.zogenix.com/content/pipeline/zohydro.htm. Accessed September 12, 2012.

Sauberban JB, Anderson PO, Lane JR, et al.: Breast milk hydrocodone and hydromorphone levels in mothers using hydrocodone for postpartum pain. Obset Gynecol. 2011; 117(3): 611-617.

Ho T, Vrabec JT, Burton AW: Hydrocodone use and sensorineural hearing loss. Pain Physician. 2007; 10(3): 467-472.

Yorgason JG, Kalinec GM, Luxford WM, et al.: Acetaminophen ototoxicity after acetaminophen/hydrocodone abuse: Evidence from two parallel in vitro mouse models. Otolaryngol Head Neck Surg. 2010; 142(6): 814-819.

Korff MV, Saunders K, Thomas Ray G, et al.: De facto long-term opioid therapy for noncancer pain. Clin J Pain. 2008; 24(6): 521-527.

Published

01/01/2013

How to Cite

Singla, MD, A., and P. Sloan, MD. “Pharmacokinetic Evaluation of hydrocodone/Acetaminophen for Pain Management”. Journal of Opioid Management, vol. 9, no. 1, Jan. 2013, pp. 71-80, doi:10.5055/jom.2013.0149.

Issue

Section

Review Articles