Description

Simple

A medication used to treat severe pain.

Clinical

An opioid agonist used as an analgesic and antitussive agent.

Overview

Hydrocodone is a synthetic opioid derivative of codeine.[14] It is commonly used in combination with [acetaminophen] to control moderate to severe pain. Historically, hydrocodone has been used as a cough suppressant although this has largely been replaced by [dextromethorphan] in current cough and cold formulations. Hydrocodone's more potent metabolite, [hydromorphone] has also found wide use as an analgesic and is frequently used in cases of severe pain. The FDA first approved Hydrocodone for use as part of the cough suppressant syrup Hycodan in March of 1943.[17]

Pharmacology

Indication

Hydrocodone is indicated for the management of acute pain, sometimes in combination with [acetaminophen] or [ibuprofen], as well as the symptomatic treatment of the common cold and allergic rhinitis in combination with decongestants, antihistamines, and expectorants.[label, Read more

Pharmacodynamic

Hydrocodone inhibits pain signaling in both the spinal cord and brain [12]. Its actions in the brain also produce euphoria, respirat... Read more

Mechanism of action

Hydrocodone binds to the mu opioid receptor (MOR) with the highest affinity followed by the delta opioid receptors (DOR).[ Read more

Absorption

The absolute bioavailability of hydrocodone has not been characterized due to lack of an IV formulation. The liquid formulations of hydrocodone have a Tmax of 0.83-1.33 h.[ Read more

Protein binding

Hydrocodone is 36% bound to plasma proteins.[label]

Volume of distribution

The apparent volume of distribution ranges widely in published literature. The official FDA labeling reports a value of 402 L.[label] Pharmacokinetic studies report values from 210-714 L with higher values associated with higher doses or single dose studies and lower values associated with lower dos... Read more

Clearance

Official FDA labeling reports an apparent clearance of 83 L/h.[label] Pharmacokinetic studies report values ranging from 24.5-58.8 L/h largely dependent on CYP2D6 metabolizer status.[ Read more

Half life

The half-life of elimination reported for hydrocodone is 7-9 h.[label, Read more

Route of elimination

Most hydrocodone appears to be eliminated via a non-renal route as renal clearance is substantially lower than total apparent clearance.[label] Hepatic metabolism may account for a portion of this, however the slight increase in serum concentration and AUC seen in hepatic impairment indicates a diff... Read more

Toxicity

Overdosage with hydrocodone presents as opioid intoxication including respiratory depression, somnolence, coma, skeletal muscle flaccidity, cold and clammy skin, constricted pupils, pulmonary edema, bradycardia, hypotension, partial or complete airway obstruction, atypical snoring, and death.[ Read more

Adverse Effects

Contraindications

  • Recommended Actions:
    • Allow 2 weeks washout time before use.
  • Regions: Canada
  • With Categories:
      • Name: Monoamine Oxidase Inhibitors
      • Drugbank Id: DBCAT001004
      • Mesh Id: D008996
  • Regions: Canada
  • Patient Conditions:
      • Name: Head Injury
      • Drugbank Id: DBCOND0028168
  • Regions: Canada
  • Patient Conditions:
      • Name: Increased Intracranial Pressure
      • Drugbank Id: DBCOND0035283
  • Regions: Canada
  • Patient Conditions:
      • Name: Increased cerebrospinal pressure
      • Drugbank Id: DBCOND0108655
  • Regions: Canada
  • Patient Conditions:
      • Name: Severe CNS depression
      • Drugbank Id: DBCOND0107893
      • Modification Of:
        • Base:
          • Name: CNS depression
          • Drugbank Id: DBCOND0094584
        • Severity:
          • Includes:
            • severe
  • Regions: Canada
  • Patient Conditions:
      • Name: Convulsive disorder
      • Drugbank Id: DBCOND0100202
  • Regions: Canada
  • Patient Conditions:
      • Name: Delirium tremens
      • Drugbank Id: DBCOND0011983
  • Regions: Canada
  • Patient Conditions:
      • Name: Acute alcoholism
      • Drugbank Id: DBCOND0107892
      • Modification Of:
        • Base:
          • Name: Alcoholism
          • Drugbank Id: DBCOND0006017
        • Severity:
          • Includes:
            • acute
  • Regions: Canada
  • Patient Conditions:
      • Name: Cor Pulmonale
      • Drugbank Id: DBCOND0042897
  • Regions: Canada
  • Patient Conditions:
      • Name: Elevated carbon dioxide levels in the blood
      • Drugbank Id: DBCOND0107891
  • Regions: Canada
  • Patient Conditions:
      • Name: Status Asthmaticus
      • Drugbank Id: DBCOND0001831
  • Regions: Canada
  • Patient Conditions:
      • Name: Chronic obstructive airway
      • Drugbank Id: DBCOND0107887
  • Regions: Canada
  • Patient Conditions:
      • Name: Suspected surgical abdomen
      • Drugbank Id: DBCOND0107886
  • Regions: US
  • Below Age:
    • Amount: 6
    • Unit: year
  • Hypersensitivity:
    • true
  • Regions: US
  • Regions: US
  • With Therapies:
      • Name: Paralytic Ileus
      • Drugbank Id: DBCOND0047064
  • Regions: US
  • Patient Conditions:
      • Name: Gastrointestinal obstruction
      • Drugbank Id: DBCOND0010786
  • Regions: US
  • Patient Conditions:
      • Name: Unmonitored severe bronchial asthma
      • Drugbank Id: DBCOND0108052
  • Regions: US
  • Patient Conditions:
      • Name: Unmonitored acute bronchial asthma
      • Drugbank Id: DBCOND0107581
  • Regions: US
  • Patient Conditions:
      • Name: Acute bronchial asthma in the absence of resuscitative equipment
      • Drugbank Id: DBCOND0121758
  • Regions: US
  • Patient Conditions:
      • Name: Severe bronchial asthma in the absence of resuscitative equipment
      • Drugbank Id: DBCOND0121759
  • Regions: US
  • Patient Conditions:
      • Name: Significant respiratory depression
      • Drugbank Id: DBCOND0107580

Food Interactions

  • Avoid alcohol.
  • Take with food.
  • To avoid constipation: increase your daily intake of fiber (beans, whole grains, vegetables).

Interactions

Type in a drug name to check for interaction with Hydrocodone
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  • Paracetamol(acetaminophen)
  • Paxil(paroxetine)
  • Pamelor(nortriptyline)
  • Panadol(acetaminophen)
  • Patanol(olopatadine ophthalmic)
  • Pataday(olopatadine ophthalmic)
  • Parnate(tranylcypromine)
  • Pazeo(olopatadine ophthalmic)
1-(2-Phenylethyl)-4-phenyl-4-acetoxypiperidine
The metabolism of Hydrocodone can be decreased when combined with 1-(2-Phenylethyl)-4-phenyl-4-acetoxypiperidine.
2,5-Dimethoxy-4-ethylamphetamine
The risk or severity of serotonin syndrome can be increased when Hydrocodone is combined with 2,5-Dimethoxy-4-ethylamphetamine.
2,5-Dimethoxy-4-ethylthioamphetamine
The risk or severity of serotonin syndrome can be increased when Hydrocodone is combined with 2,5-Dimethoxy-4-ethylthioamphetamine.
4-Bromo-2,5-dimethoxyamphetamine
The risk or severity of serotonin syndrome can be increased when Hydrocodone is combined with 4-Bromo-2,5-dimethoxyamphetamine.
4-Methoxyamphetamine
4-Methoxyamphetamine may increase the central nervous system depressant (CNS depressant) activities of Hydrocodone.
5-methoxy-N,N-dimethyltryptamine
The risk or severity of serotonin syndrome can be increased when Hydrocodone is combined with 5-methoxy-N,N-dimethyltryptamine.
6-Deoxyerythronolide B
The metabolism of Hydrocodone can be decreased when combined with 6-Deoxyerythronolide B.
7-ethyl-10-hydroxycamptothecin
The metabolism of Hydrocodone can be decreased when combined with 7-ethyl-10-hydroxycamptothecin.
7-Nitroindazole
7-Nitroindazole may increase the central nervous system depressant (CNS depressant) activities of Hydrocodone.
7,8-Dichloro-1,2,3,4-tetrahydroisoquinoline
7,8-Dichloro-1,2,3,4-tetrahydroisoquinoline may increase the serotonergic and central nervous system depressant (CNS depressant) activities of Hydrocodone.
Abiraterone
The metabolism of Hydrocodone can be decreased when combined with Abiraterone.
Acalabrutinib
The metabolism of Hydrocodone can be decreased when combined with Acalabrutinib.
Acebutolol
The metabolism of Hydrocodone can be decreased when combined with Acebutolol.
Acepromazine
Acepromazine may increase the central nervous system depressant (CNS depressant) activities of Hydrocodone.
Aceprometazine
Aceprometazine may increase the central nervous system depressant (CNS depressant) activities of Hydrocodone.
Acetazolamide
The metabolism of Hydrocodone can be decreased when combined with Acetazolamide.
Acetophenazine
Acetophenazine may increase the central nervous system depressant (CNS depressant) activities of Hydrocodone.
Acetylglycinamide chloral hydrate
Acetylglycinamide chloral hydrate may increase the central nervous system depressant (CNS depressant) activities of Hydrocodone.
Aclidinium
Hydrocodone may increase the central nervous system depressant (CNS depressant) activities of Aclidinium.
Adinazolam
Hydrocodone may increase the central nervous system depressant (CNS depressant) activities of Adinazolam.
17 References
  1. 1 . Melhem MR, Rubino CM, Farr SJ, Robinson CY: Population pharmacokinetic analysis for hydrocodone following the administration of hydrocodone bitartrate extended-release capsules. Clin Pharmacokinet. 2013 Oct;52(10):907-17. doi: 10.1007/s40262-013-0081-6.PubMed: 23719682
  2. 2 . Linares OA, Fudin J, Daly AL, Boston RC: Individualized Hydrocodone Therapy Based on Phenotype, Pharmacogenetics, and Pharmacokinetic Dosing. Clin J Pain. 2015 Dec;31(12):1026-35. doi: 10.1097/AJP.0000000000000214.PubMed: 25621429
  3. 3 . Liu W, Dutta S, Kearns G, Awni W, Neville KA: Pharmacokinetics of hydrocodone/acetaminophen combination product in children ages 6-17 with moderate to moderately severe postoperative pain. J Clin Pharmacol. 2015 Feb;55(2):204-11. doi: 10.1002/jcph.394. Epub 2014 Sep 26.PubMed: 25196888
  4. 4 . 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. 1993 Nov;54(5):463-72. doi: 10.1038/clpt.1993.177.PubMed: 7693389
  5. 5 . Deng S, Huang W, Ni X, Zhang M, Lu H, Wang Z, Hu J, Zhu X, Qiu C, Shang D, Zhang Y, Xiong L, Wen Y: Pharmacokinetics of guaifenesin, pseudoephedrine and hydrocodone in a combination oral liquid formulation, administered as single and multiple doses in healthy Chinese volunteers, and comparison with data for individual compounds formulated as Antuss(R). Xenobiotica. 2017 Oct;47(10):870-878. doi: 10.1080/00498254.2016.1241451. Epub 2016 Oct 24.PubMed: 27662264
  6. 6 . Farr SJ, Robinson CY, Rubino CM: Effects of food and alcohol on the pharmacokinetics of an oral, extended-release formulation of hydrocodone in healthy volunteers. Clin Pharmacol. 2015 Jan 19;7:1-9. doi: 10.2147/CPAA.S70831. eCollection 2015.PubMed: 25653563
  7. 7 . Cardia L, Calapai G, Quattrone D, Mondello C, Arcoraci V, Calapai F, Mannucci C, Mondello E: Preclinical and Clinical Pharmacology of Hydrocodone for Chronic Pain: A Mini Review. Front Pharmacol. 2018 Oct 1;9:1122. doi: 10.3389/fphar.2018.01122. eCollection 2018.PubMed: 30327606
  8. 8 . Cone EJ, Darwin WD, Gorodetzky CW, Tan T: Comparative metabolism of hydrocodone in man, rat, guinea pig, rabbit, and dog. Drug Metab Dispos. 1978 Jul-Aug;6(4):488-93.PubMed: 28931
  9. 9 . Hutchinson MR, Menelaou A, Foster DJ, Coller JK, Somogyi AA: CYP2D6 and CYP3A4 involvement in the primary oxidative metabolism of hydrocodone by human liver microsomes. Br J Clin Pharmacol. 2004 Mar;57(3):287-97.PubMed: 14998425
  10. 10 . Kapil RP, Cipriano A, Wen W, Yu Lynch S, He E, Colucci SV, Harris SC: Pharmacokinetic Profile and Sustained 24-hour Analgesia of a Once-daily Hydrocodone Bitartrate Extended-release Tablet with Abuse-deterrent Properties. Clin Ther. 2016 Feb;38(2):302-14. doi: 10.1016/j.clinthera.2015.12.003. Epub 2015 Dec 31.PubMed: 26749219
  11. 11 . Sauberan JB, Anderson PO, Lane JR, Rafie S, Nguyen N, Rossi SS, Stellwagen LM: Breast milk hydrocodone and hydromorphone levels in mothers using hydrocodone for postpartum pain. Obstet Gynecol. 2011 Mar;117(3):611-7. doi: 10.1097/AOG.0b013e31820ca504.PubMed: 21343764
  12. 12 . Trescot AM, Datta S, Lee M, Hansen H: Opioid pharmacology. Pain Physician. 2008 Mar;11(2 Suppl):S133-53.PubMed: 18443637
  13. 13 . Olson KM, Duron DI, Womer D, Fell R, Streicher JM: Comprehensive molecular pharmacology screening reveals potential new receptor interactions for clinically relevant opioids. PLoS One. 2019 Jun 6;14(6):e0217371. doi: 10.1371/journal.pone.0217371. eCollection 2019.PubMed: 31170174
  14. 14 . Brunton LL, Hilal-Dandan R, Knollmann BC. eds (2018). Goodman & Gilman's: The Pharmacological Basis of Therapeutics (13th ed.). McGraw-Hill Education.
  15. 15 . FDA Label: Hydrocodone Tab ER Link
  16. 16 . DPD Monograph: Dimetane Syrup Link
  17. 17 . Drugs@FDA: Hycodan Link