Adult: Available preparations:
Modified-release tab:
Oxycodone 2.5 mg and Naloxone 1.25 mg
Oxycodone 5 mg and Naloxone 2.5 mg
Oxycodone 10 mg and Naloxone 5 mg
Oxycodone 15 mg and Naloxone 7.5 mg
Oxycodone 20 mg and Naloxone 10 mg
Oxycodone 30 mg and Naloxone 15 mg
Oxycodone 40 mg and Naloxone 20 mg
Oxycodone 60 mg and Naloxone 30 mg
Oxycodone 80 mg and Naloxone 40 mg
Opioid-naive patient: Initially, oxycodone 10 mg and naloxone 5 mg 12 hourly. Patient taking other oral oxycodone: Initiate at same total daily dose, 12 hourly. Max: Oxycodone 80 mg and naloxone 40 mg daily. Patient taking other opioids: Initiate at lowest strength, 12 hourly. Max: Oxycodone 80 mg and naloxone 40 mg daily. Dose may be titrated every 1-2 days, according to response. Max: Oxycodone 160 mg and naloxone 80 mg daily.
Oral Restless leg syndrome
Adult: Available preparations:
Modified-release tab:
Oxycodone 2.5 mg and Naloxone 1.25 mg
Oxycodone 5 mg and Naloxone 2.5 mg
Oxycodone 10 mg and Naloxone 5 mg
Oxycodone 15 mg and Naloxone 7.5 mg
Oxycodone 20 mg and Naloxone 10 mg
Oxycodone 30 mg and Naloxone 15 mg
Oxycodone 40 mg and Naloxone 20 mg
Oxycodone 60 mg and Naloxone 30 mg
Oxycodone 80 mg and Naloxone 40 mg
In patients with restless leg syndrome for at least 6 months and occurring ≥4 days per week during daytime after failure of previous dopaminergic treatment: Initially, oxycodone 5 mg and naloxone 2.5 mg 12 hourly. May titrate dose at weekly intervals, according to response. Max: Oxycodone 60 mg and naloxone 30 mg daily.
Renal Impairment
Moderate to severe pain: Mild to moderate: Reduce dose to 33-50% of the usual dose. Severe: Contraindicated.
Hepatic Impairment
Mild: Reduce dose to 33-50% of the usual dose. Moderate to severe: Contraindicated.
Contraindications
Known or suspected gastrointestinal obstruction, paralytic ileus, acute appendicitis, pancreatitis, circulatory shock, acute or severe bronchial asthma, COPD, status asthmaticus, acute or severe respiratory depression, hypercapnia, cor pulmonale, acute alcoholism, delirium tremens, convulsive disorder, severe CNS depression, increased cerebrospinal or intracranial pressure, head injury, opioid dependency, moderate to severe sleep-apnoea syndrome; history of opioid abuse (when used for treatment of restless leg syndrome). Perioperative use (24 hours before or after procedure). Moderate to severe hepatic and severe renal impairment. Pregnancy and lactation. Concurrent administration of MAOIs or within 2 weeks of discontinuation of use.
Special Precautions
Patient with hypovolaemia, CV diseases (e.g. acute MI), adrenocortical insufficiency (e.g. Addison disease), biliary tract dysfunction, mental health conditions (e.g. depression, anxiety disorders, post-traumatic stress disorders), morbid obesity, prostatic hyperplasia, urinary stricture, toxic psychosis, risk factors for sleep-apnoea syndrome, thyroid dysfunction, history of drug or alcohol abuse. Not indicated for the treatment of breakthrough pain or cancer pain associated with peritoneal carcinomatosis. Avoid abrupt withdrawal and dose reduction. Mild to moderate renal and mild hepatic impairment.
Adverse Reactions
Significant: CNS depression, diarrhoea, hyperalgesia (high dose), severe hypotension, secondary hypogonadism (long-term use), sphincter of Oddi constriction, opioid dependence, withdrawal syndrome. Blood and lymphatic system disorders: Anaemia. Eye disorders: Visual impairment. Gastrointestinal disorders: Abdominal pain, vomiting, nausea, constipation, xerostomia, dyspepsia, flatulence, hiccups, thirst. General disorders and administration site conditions: Weakness, fatigue, pain, peripheral oedema, chills, chest pain. Investigations: Increased hepatic enzymes, decreased Hb. Metabolism and nutrition disorders: Anorexia. Musculoskeletal and connective tissue disorders: Back pain. Neoplasms benign, malignant and unspecified: Cancer progression. Nervous system disorders: Headache, dizziness, somnolence, vertigo, tremor, paraesthesia. Psychiatric disorders: Insomnia, depression, altered mood, personality change, decreased activity, psychomotor hyperactivity, attention disturbance. Renal and urinary disorders: UTI, dysuria. Skin and subcutaneous tissue disorders: Hyperhidrosis, pruritus, rash. Vascular disorders: Increased/decreased blood pressure, hot flush. Potentially Fatal: Respiratory depression.
Patient Counseling Information
This drug may cause somnolence and/or sudden sleep onset, if affected, do not drive or operate machinery.
Monitoring Parameters
Monitor for CNS depression, and hypotension during initiation of therapy or dose increase. Monitor for respiratory depression, mental status, blood pressure, constipation, signs of abuse and misuse, signs and symptoms of hypogonadism and hypoadrenalism.
Overdosage
Symptoms: Miosis, respiratory depression, somnolence progressing to stupor, hypotonia, bradycardia, hypotension, coma, pulmonary oedema, circulatory failure. Management: Symptomatic and supportive treatment. Administer opioid antagonist if necessary. Consider gastric lavage. Maintain fluid and electrolyte balance.
Drug Interactions
Additive respiratory and CNS depressant effects with other opioid agonist analgesics (e.g. pethidine, morphine). May precipitate withdrawal symptoms with opioid agonist/antagonist or partial agonist (e.g. nalbuphine, butorphanol, buprenorphine).
Oxycodone: May enhance the effect of neuromuscular blockers resulting in respiratory depression. Increased risk of severe constipation and urinary retention with anticholinergics (e.g. TCAs, antihistamines, muscle relaxants). Increased plasma concentration with CYP2D6 inhibitor (e.g. quinidine), cimetidine, and CYP3A4 inhibitors (e.g. ketoconazole, erythromycin). Decreased plasma concentration with CYP3A4 inducers (e.g. carbamazepine, rifampicin). Increased risk of orthostatic hypotension with antihypertensives. Enhanced CNS depression with other CNS depressants and other opioid derivatives (e.g. methadone, antitussives, analgesics), barbiturates, clonidine, neuroleptics, clonidine, anxiolytics other than benzodiazepines, sedative H1-receptor antagonists, certain antidepressants. May potentiate anticoagulant activity of coumarin derivatives. May antagonise gastrointestinal motility effect of metoclopramide. Potentially Fatal: Significant respiratory depression with MAOIs.
Food Interaction
High-fat meal may increase absorption. May potentiate the CNS sedative/depressant effect of alcohol. Decreased plasma concentration with St John’s wort. Increased plasma concentration with grapefruit juice.
Action
Description: Oxycodone is a phenanthrene derivative opiate agonist. It binds to opiate receptors in the CNS, causing inhibition of ascending pain pathways, altering the perception of and response to pain. It produces generalised CNS depression.
Naloxone is a potent antagonist which competes and displaces opioids at opioids receptors sites, causing complete or partial reversal of opiate-induced depression. It blocks the action of oxycodone at opioid receptors locally in the gut, thus reducing bowel function disorders (e.g. constipation). Pharmacokinetics: Absorption: Oxycodone: Absorbed from the gastrointestinal tract. Food, particularly high-fat meal increases absorption. Bioavailability: Approx 60-87%.
Naloxone: Absorbed from the gastrointestinal tract. Bioavailability: <3%. Distribution: Oxycodone: Distributed throughout the entire body. Crosses the placenta and enters breast milk. Volume of distribution: 2.6 L/kg. Plasma protein binding: Approx 45%.
Naloxone: Extensively distributed into body tissues and fluids, particularly the brain; Crosses the placenta. Plasma protein binding: Approx 32-45%. Metabolism: Oxycodone: Metabolised in the gut and liver by the CYP3A isoenzymes into noroxycodone and to a lesser extent, by CYP2D6 into oxymorphone. Undergoes first-pass metabolism.
Naloxone: Metabolised in the liver via glucuronide conjugation to form major metabolite, naloxone-3-glucuronide. Undergoes first-pass metabolism. Excretion: Oxycodone: Via urine (approx 19% as unchanged drug, >64% as metabolites); also via faeces. Elimination half-life: 3.7 hours.
Naloxone: Via urine, as metabolites. Elimination half-life: 30-81 minutes.
Chemical Structure
Oxycodone Source: National Center for Biotechnology Information. PubChem Database. Oxycodone, CID=5284603, https://pubchem.ncbi.nlm.nih.gov/compound/Oxycodone (accessed on Jan. 22, 2020)
Naloxone Source: National Center for Biotechnology Information. PubChem Database. Naloxone, CID=5284596, https://pubchem.ncbi.nlm.nih.gov/compound/Naloxone (accessed on Jan. 22, 2020)
N02AA55 - oxycodone and naloxone ; Belongs to the class of natural opium alkaloids. Used to relieve pain.
References
Anon. Naloxone. Lexicomp Online. Hudson, Ohio. Wolters Kluwer Clinical Drug Information, Inc. https://online.lexi.com. Accessed 07/03/2018.Anon. Oxycodone and Naloxone. Lexicomp Online. Hudson, Ohio. Wolters Kluwer Clinical Drug Information, Inc. https://online.lexi.com. Accessed 07/03/2018.Anon. Oxycodone. Lexicomp Online. Hudson, Ohio. Wolters Kluwer Clinical Drug Information, Inc. https://online.lexi.com. Accessed 07/03/2018.Buckingham R (ed). Naloxone Hydrochloride. Martindale: The Complete Drug Reference [online]. London. Pharmaceutical Press. https://www.medicinescomplete.com. Accessed 07/03/2018.Buckingham R (ed). Oxycodone. Martindale: The Complete Drug Reference [online]. London. Pharmaceutical Press. https://www.medicinescomplete.com. Accessed 07/03/2018.Joint Formulary Committee. Oxycodone with Naloxone. British National Formulary [online]. London. BMJ Group and Pharmaceutical Press. https://www.medicinescomplete.com. Accessed 07/03/2018.McEvoy GK, Snow EK, Miller J et al (eds). Naloxone Hydrochloride. AHFS Drug Information (AHFS DI) [online]. American Society of Health-System Pharmacists (ASHP). https://www.medicinescomplete.com. Accessed 07/03/2018.McEvoy GK, Snow EK, Miller J et al (eds). Oxycodone, Oxycodone Hydrochloride, Oxycodone Myristate. AHFS Drug Information (AHFS DI) [online]. American Society of Health-System Pharmacists (ASHP). https://www.medicinescomplete.com. Accessed 07/03/2018.
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