Oxycodone

Oxycodone is a semisynthetic full mu-opioid agonist with oral bioavailability of 60 to 87%, making it a more predictable oral strong opioid than morphine. It is used for moderate to severe acute and cancer pain, and as an alternative to morphine when morphine causes intolerable adverse effects.

Class. Full mu-opioid agonist (semisynthetic).

Mechanism. Mu receptor agonism with minor kappa activity.

Pharmacokinetics. Oral immediate release: onset 15 to 30 minutes, peak 1 to 1.5 hours, duration 4 to 6 hours. Modified-release tablets last 12 hours. Half-life about 3 to 4.5 hours. Metabolised by CYP3A4 (to noroxycodone) and CYP2D6 (to oxymorphone); active metabolites contribute little. Renal excretion.

Potency. Oral oxycodone is about 1.5 to 2 times as potent as oral morphine; parenteral oxycodone is about 1.5 times as potent as parenteral morphine.

Indications are moderate to severe acute pain (postoperative, trauma), cancer pain and other severe chronic pain not controlled by weaker analgesics.

Opioid-naive adults

• Immediate release: 5 mg orally every 4 to 6 hours (2.5 mg in older or frail patients). Titrate by 25 to 50% based on response.
• Modified release: 10 mg every 12 hours as a starting dose after immediate-release dose is established. Do not crush.
• Breakthrough: one sixth of the 24-hour total as immediate-release oxycodone.
• Parenteral (intravenous bolus, subcutaneous): 1 to 2 mg increments intravenously every 5 minutes for titration; 2.5 to 5 mg subcutaneously every 4 hours. Continuous subcutaneous infusion: parenteral dose is one half of the oral dose.
• No fixed maximum dose, but review the need for specialist input above 120 mg oral morphine-equivalent a day.

Conversion. Oral morphine 10 mg is roughly equal to oral oxycodone 5 mg (some practice uses 1.5 to 1). Reduce the calculated dose by 25 to 30% when converting because of incomplete cross-tolerance.

Children. Specialist use only: 0.1 to 0.2 mg/kg orally every 4 to 6 hours for severe pain.

Combination products. Oxycodone with naloxone modified-release is used to reduce opioid-induced constipation; maximum 160 mg oxycodone daily in the combination. Combination with paracetamol: the paracetamol ceiling limits the daily dose.

Contraindications. Respiratory depression without ventilatory support; acute severe asthma; paralytic ileus; raised intracranial pressure (relative); concurrent monoamine oxidase inhibitor within 14 days; hypersensitivity; severe liver impairment (combination with naloxone).

Boxed-warning-level risks. Addiction, abuse and misuse; life-threatening respiratory depression; accidental ingestion; neonatal opioid withdrawal syndrome; interactions with CYP3A4 inhibitors; risk with benzodiazepines and other central nervous system depressants.

Adverse effects. Common: nausea, vomiting, constipation, drowsiness, dizziness, pruritus, sweating. Serious: respiratory depression, hypotension, urinary retention, biliary spasm, delirium, hyperalgesia, serotonin syndrome and opioid use disorder.

Interactions. CYP3A4 inhibitors (ritonavir, clarithromycin, azole antifungals, diltiazem) raise concentrations substantially. CYP3A4 inducers (rifampicin, carbamazepine, phenytoin) lower them. CYP2D6 inhibitors (fluoxetine, paroxetine) have little clinical effect. Additive sedation with benzodiazepines, alcohol and gabapentinoids. Monoamine oxidase inhibitors risk serotonin syndrome.

Common prescribing errors. Treating oxycodone and morphine as dose-for-dose equal; crushing modified-release tablets; omitting a laxative; failing to reduce the dose with new interacting drugs; stopping a CYP3A4 inducer without a dose review.

Special groups

• Pregnancy: use only if necessary; neonatal respiratory depression if used near delivery, withdrawal after prolonged use.
• Breastfeeding: avoid prolonged or high doses; short courses with infant observation.
• Older adults: start at 2.5 mg.
• Kidney impairment: exposure rises by about 50% with creatinine clearance under 60 mL/min; start at one third to one half of the usual dose.
• Liver impairment: start at one third to one half of the usual dose; avoid in severe disease.
• Regional: availability is limited in some settings; morphine is the usual alternative.

Formulations. Immediate-release capsules and tablets (5, 10, 20 mg), oral solution (5 mg/5 mL, 10 mg/mL), modified-release tablets (5 to 80 mg), and injection (10 and 50 mg/mL).

Administration. Oral doses with or without food. Swallow modified-release tablets whole. Dilute injection for intravenous bolus in 0.9% sodium chloride to 1 mg/mL and give slowly.

Baseline. Respiratory rate, sedation score, renal and hepatic function, concurrent medicines (especially CYP3A4 inhibitors), opioid exposure and substance use history.

Monitoring. Pain, respiratory rate, sedation and bowel function. Check 30 to 60 minutes after oral doses and each titration step, and continuous oximetry after parenteral loading. Reassess at each dose increase.

Therapeutic drug monitoring. Not used.

Dose reduction and stopping thresholds. Reduce or hold for respiratory rate under 10 breaths/minute, excessive sedation, hypotension, delirium. After more than 1 week of regular use, reduce by 10 to 25% every few days.

Referral and escalation. Respiratory depression needs airway support and naloxone (repeated, because the opioid outlasts it). Escalating requirements, intolerable adverse effects or suspected opioid use disorder need pain or palliative care review.