Hydrocodone

As extended-release cap: Initiate at a low dose; monitor closely for respiratory depression, sedation and hypotension. As extended-release tab: Moderate to severe or ESRD: Initiate with 50% of the usual initial dose, then monitor for respiratory depression, sedation and hypotension.

Severe: As extended-release cap: Initially, 10 mg 12 hourly, then titrate carefully while monitoring for respiratory depression, sedation and hypotension. As extended-release tab: Initiate with 50% of the usual initial dose, then monitor for respiratory depression, sedation and hypotension.

Significant respiratory depression; acute or severe bronchial asthma in unmonitored setting or absence of resuscitative equipment; known or suspected gastrointestinal obstruction (including paralytic ileus).

Patient with personal or family history of substance abuse (including drug or alcohol addiction or abuse) or mental illness (e.g. major depression); hypovolaemia, increased intracranial pressure, brain tumours, head injury, seizure disorder, oesophageal or colon cancer with small gastrointestinal lumen, heart failure, bradyarrhythmias, electrolyte abnormalities, unstable angina, post-MI; hypersensitivity to other phenanthrene derivative opioid agonists (e.g. codeine, hydromorphone, levorphanol, oxycodone, oxymorphone), adrenal insufficiency (e.g. Addison's disease), biliary tract dysfunction, acute pancreatitis, prostatic hyperplasia and/or urinary stricture, delirium tremens, sleep-related disorders (e.g. sleep apnoea), thyroid dysfunction; significant COPD or cor pulmonale. Debilitated or cachectic patients. Not indicated for use as an as-needed analgesic. Avoid abrupt withdrawal. Avoid use in patients with impaired consciousness, congenital long QT syndrome or circulatory shock. Moderate to severe renal impairment; ESRD (extended-release tab). Severe hepatic impairment. Elderly. Pregnancy and lactation. Concomitant use with benzodiazepines or other CNS depressants.

Significant: Opioid-induced hyperalgesia; adrenal insufficiency (particularly after >1 month of use); severe hypotension, including orthostatic hypotension and syncope; spasm of sphincter of Oddi; QT prolongation (after doses of 160 mg daily); increased risk of seizures; CNS depression, constipation. Rarely, oesophageal obstruction, dysphagia, choking (extended-release tab).
Cardiac disorders: Chest pain.
Ear and labyrinth disorders: Tinnitus.
Gastrointestinal disorders: Abdominal pain, diarrhoea, dyspepsia, viral gastroenteritis, GERD, nausea, vomiting, xerostomia.
General disorders and administration site conditions: Peripheral oedema, chills, lethargy, pain, fever.
Infections and infestations: Influenza.
Investigations: Increased GGT and blood cholesterol.
Metabolism and nutrition disorders: Dehydration, decreased appetite, hypokalaemia.
Musculoskeletal and connective tissue disorders: Arthralgia, back pain, foot fracture, joint sprain or injury, limb pain, muscle spasms or strain, musculoskeletal pain, myalgia, neck pain, osteoarthritis.
Nervous system disorders: Dizziness, drowsiness, migraine, paraesthesia, sedated state.
Psychiatric disorders: Anxiety, insomnia, depression.
Renal and urinary disorders: UTI.
Respiratory, thoracic and mediastinal disorders: Bronchitis, cough, dyspnoea, nasal congestion, nasopharyngitis, oropharyngeal pain, sinusitis, URTI.
Skin and subcutaneous tissue disorders: Rash, hyperhidrosis, pruritus.
Vascular disorders: Hypertension, hot flush.
Potentially Fatal: Risks of opioid addiction, abuse and misuse; respiratory depression (particularly during initiation or after dose increase); risk of neonatal opioid withdrawal syndrome (prolonged use during pregnancy).

PO: C (Prolonged use may cause neonatal opioid withdrawal syndrome.)

This drug may cause CNS depression which may impair mental or physical abilities, if affected, do not drive or operate machinery.

Monitor blood pressure, pain relief, respiratory and mental status, and bowel function. Assess individual risk for opioid addiction, abuse or misuse before initiation and regularly during treatment.

Symptoms: Respiratory depression, somnolence progressing to stupor or coma, skeletal muscle flaccidity, cold and clammy skin, constricted pupils, pulmonary oedema, bradycardia, hypotension, hypoglycaemia, partial or complete airway obstruction, atypical snoring; marked mydriasis with hypoxia.

Management: Supportive and symptomatic treatment. Reestablish patent and protected airway while initiating assisted or controlled ventilation as needed. Administer oxygen and vasopressors for circulatory shock and pulmonary oedema as indicated. Perform advanced life-support measures in cardiac arrest or arrhythmias. Give opioid antagonists (e.g. naloxone) for respiratory or circulatory depression. Monitor until spontaneous respiration is reliably reestablished.

Concomitant use with CYP3A4 inducers or discontinuation of concomitantly used CYP3A4 inhibitors may decrease the plasma concentration and efficacy of hydrocodone. Concomitant use with mixed agonist/antagonist (e.g. pentazocine, nalbuphine, butorphanol) or partial agonist (e.g. buprenorphine) opioid analgesics may decrease the analgesic effect of hydrocodone and/or precipitate withdrawal symptoms. Increased risk of severe hypotension with certain CNS depressants (e.g. phenothiazine, general anaesthetics). Increased risk of serotonin syndrome with serotonergic agents (e.g. SSRIs, SNRIs, TCAs, triptans) or other drugs affecting serotonin neurotransmitter system (e.g. MAOIs, mirtazapine, trazodone, tramadol). May enhance the neuromuscular blocking effects of skeletal muscle relaxants (e.g. cyclobenzaprine, metaxalone), resulting in increased degree of respiratory depression. May reduce the efficacy of diuretics. Increased risk of urinary retention and/or severe constipation with anticholinergic drugs. Increased risk of QT prolongation with QT-prolonging drugs. Strong laxatives that rapidly increase gastrointestinal motility (e.g. lactulose) may reduce the absorption and plasma concentrations of hydrocodone extended-release tab.
Potentially Fatal: Concomitant use with CYP3A4 inhibitors (e.g. erythromycin, ketoconazole, ritonavir) or discontinuation of concomitantly used CYP3A4 inducers (e.g. rifampicin, carbamazepine, phenytoin) may increase the plasma concentration of hydrocodone, which may lead to respiratory depression. Increased risk of profound sedation, respiratory depression and coma with benzodiazepines or other CNS depressants (e.g. non-benzodiazepine sedatives or hypnotics, anxiolytics, tranquillisers, muscle relaxants, general anaesthetics, antipsychotics, other opioids).

Increased risk of profound sedation, respiratory depression and coma with alcohol.

Description:
Overview: Hydrocodone is a phenanthrene derivative opioid agonist with a relative selectivity for the mu-opioid receptor.
Mechanism of Action: Hydrocodone binds to opioid receptors in the CNS which suppress ascending pain pathways, resulting in altered perception of and response to pain.
Pharmacodynamics: For pain relief, the minimum effective analgesic concentration of hydrocodone varies widely among patients, particularly in those previously treated with opioid agonists. In an individual patient, this concentration may increase over time due to the development of tolerance, as well as increases in pain and the emergence of new pain syndromes.

Hydrocodone causes respiratory depression by directly acting on the brainstem respiratory centres, reducing their responsiveness to increased carbon dioxide tension and electrical stimulation. Higher hydrocodone plasma concentrations are associated with increased frequency of adverse reactions (e.g. nausea, vomiting, CNS effects, respiratory depression). However, in opioid-tolerant patients, this relationship may be altered due to the development of tolerance to opioid-related adverse effects.
Pharmacokinetics:
Absorption: Time to peak plasma concentration: Approx 5 hours (extended-release cap); 6-30 hours (extended-release tab).
Distribution: Crosses the placenta and enters breast milk. Plasma protein binding: 36%.
Metabolism: Metabolised in the liver via N-demethylation by CYP3A4 to norhydrocodone (major metabolite), O-demethylation by CYP2D6 to hydromorphone (major active metabolite), and 6-ketosteroid reduction to 6-α-hydrocol and 6-β-hydrocol.
Excretion: Via urine (26%; approx 12% as unchanged drug, 5% as norhydrocodone, 4% as conjugated hydrocodone, 3% as 6-hydrocodol and 0.21% as conjugated 6-hydromorphol). Elimination half-life: Approx 8 hours (extended-release cap); approx 7-9 hours (extended-release tab).

Source: National Center for Biotechnology Information. PubChem Compound Summary for CID 5284569, Hydrocodone. https://pubchem.ncbi.nlm.nih.gov/compound/Hydrocodone. Accessed Dec. 18, 2025.

Store between 15-30°C.

Analgesics (Opioid)

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Hydrocodone Bitartrate Capsule, Extended Release (Alvogen Inc.). DailyMed. Source: U.S. National Library of Medicine. https://dailymed.nlm.nih.gov/dailymed. Accessed 05/11/2025.

Hydrocodone Bitartrate Tablet, Extended Release (Alvogen Inc.). DailyMed. Source: U.S. National Library of Medicine. https://dailymed.nlm.nih.gov/dailymed. Accessed 05/11/2025.

Hydrocodone. Gold Standard Drug Database in ClinicalKey [online]. Elsevier Inc. https://www.clinicalkey.com. Accessed 16/12/2025.

Hydrocodone. UpToDate Lexidrug, Lexi-Drugs Multinational Online. Waltham, MA. UpToDate, Inc. https://online.lexi.com. Accessed 05/11/2025.