naloxone hydrochloride dihydrate + oxycodone hydrochloride: clinical use

Prescribing considerations

• Confirm an opioid is appropriate and agree treatment goals, review arrangements and a discontinuation plan before initiation.
• The prolonged-release formulation is unsuitable for breakthrough pain or acute postoperative pain.
• Assess respiratory disease, sleep apnoea, renal and hepatic function, frailty, mental health, substance-use history and concurrent CNS depressants.
• For restless legs syndrome, confirm severe idiopathic disease and failure of previous dopaminergic treatment; specialist supervision and periodic benefit–harm review are required.
• Counsel about sedation, driving, alcohol, safe storage, dependence, overdose and the danger of crushing the tablets.

Contraindications and cautions

• Hypersensitivity to oxycodone, naloxone or an excipient
• Severe respiratory depression with hypoxia or hypercapnia
• Severe chronic obstructive pulmonary disease, cor pulmonale or severe bronchial asthma
• Non-opioid-induced paralytic ileus
• Moderate or severe hepatic impairment
• For restless legs syndrome, a history of opioid abuse

Monitoring

• Pain or restless-legs symptom response, function and continued need for treatment
• Sedation, respiratory rate and signs of sleep-related breathing disorder, especially with CNS depressants
• Bowel function, nausea and other opioid adverse effects
• Renal and hepatic function where clinically indicated
• Tolerance, hyperalgesia, withdrawal, early refill requests and other signs of opioid use disorder
• Infant sedation, feeding, weight gain and breathing if specialist advice supports breastfeeding exposure
• INR when used with a coumarin anticoagulant

Clinical pharmacology

Oxycodone is a mu-, kappa- and delta-opioid receptor agonist. Orally administered naloxone is an opioid receptor antagonist with extensive first-pass metabolism and very low systemic availability, allowing predominantly local antagonism of opioid effects in the gut. Oxycodone is metabolised mainly through CYP3A4 and partly through CYP2D6.

Formulation and product differences

• The selected product is an oral dual-polymer prolonged-release tablet and must remain intact.
• The selected tablet contains lactose and may be unsuitable in specified rare hereditary disorders of carbohydrate metabolism.
• Other strengths are available for individual adjustment; tablet appearance and excipient quantities may differ.
• The formulation is not interchangeable with immediate-release oxycodone products for practical use.

Modified-release tablet

Route: Oral

Strengths: 5 mg + 2.5 mg, 10 mg + 5 mg, 20 mg + 10 mg, 40 mg + 20 mg