Oxycodone hydrochloride and naloxone hydrochloride oral modified release
- Drugs List
- Therapeutic Indications
- Dosage
- Contraindications
- Precautions and Warnings
- Pregnancy and Lactation
- Side Effects
- Monograph
Presentation
Modified release tablets of oxycodone hydrochloride and naloxone hydrochloride
Drugs List
Therapeutic Indications
Uses
Pain - severe
Severe to very severe idiopathic Restless Leg Syndrome: Secondary treatment
Severe pain, which can be adequately managed only with opioid analgesics.
Second line symptomatic treatment of patients with severe to very severe idiopathic restless legs syndrome (RLS) after failure of dopaminergic therapy.
Oxycodone and naloxone is indicated for patients suffering from RLS for at least 6 months. RLS symptoms should be present daily and during daytime. Previous treatment with at least one dopaminergic drug should have lasted in general 4 weeks.
The opioid antagonist naloxone is added to counteract opioid-induced constipation by blocking the action of oxycodone at opioid receptors locally in the gut.
Dosage
Symmetric administration (the same dose mornings and evenings) subject to a fixed time schedule (every 12 hours) is appropriate for the majority of patients. However, some patients may benefit from asymmetric dosing tailored to the individual patient, depending on the individual situation. In general, the lowest effective dose should be selected.
Analgesia
The dosage should be adjusted to the intensity of the pain and the sensitivity of the individual patient.
Oxycodone and naloxone modified release tablets are not intended for the 'rescue' treatment of breakthrough pain. A single dose of an immediate release analgesics should be used, amounting to one sixth of the equivalent daily dose of oxycodone hydrochloride. The need for more than two 'rescues' per day is usually an indication that the dose of oxycodone and naloxone modified release tablet requires upward adjustment. Adjustment should be made every 1 to 2 days in steps of 5mg/2.5mg tablets twice daily, or where necessary 2.5mg/1.25mg or 10mg/5mg until a stable dose is reached, with the aim of establishing a patient-specific twice daily dose that will maintain adequate analgesia and use as little rescue medication as possible for as long as pain therapy is necessary.
Restless Leg Syndrome
The dosage should be adjusted to the sensitivity of the individual patient and should be under the supervision of a clinician with experience in the management of restless legs syndrome.
Adults
Analgesia
Opioid naive patients
The usual starting dose is 10mg/5mg at 12 hourly intervals.
Patients already receiving opioids
May be started on higher doses, depending on their previous opioid experience.
The maximum daily dose is 160mg oxycodone hydrochloride and 80mg naloxone hydrochloride. Patients requiring higher doses should be administered supplemental modified-release oxycodone at the same time intervals. The analgesic efficacy of the oxycodone and naloxone modified release tablets is equivalent to oxycodone alone modified release preparations. The maximum daily dose of modified release oxycodone hydrochloride is 400mg.
Oxycodone and naloxone modified release tablets should not be administered for longer than necessary.
Restless Leg Syndrome
The usual starting dose is 5mg/2.5mg oxycodone hydrochloride/naloxone hydrochloride at 12 hourly intervals. Titration on a weekly basis is recommended in case higher doses are required. The mean daily dose in the pivotal study was 10mg/5mg every 12 hours. Some patients may benefit from higher daily doses up to a maximum of 30mg/15mg every 12 hours.
Prior to continuation of treatment beyond 1 year a discharge regimen by gradually tapering down of oxycodone and naloxone over a period of approximately one week should be considered to establish if continued treatment is indicated.
Contraindications
24 hours post-operatively
Acute abdomen
Children under 18 years
Pre-operative administration
Risk of paralytic ileus
Within 2 weeks of discontinuing MAOIs
Breastfeeding
Cardiac failure secondary to pulmonary disorder
Chronic constipation
Coma
Delayed gastric emptying
Head trauma
Hypercapnia
Hypoxia
Labour
Moderate hepatic impairment
Paralytic ileus
Raised intracranial pressure
Severe asthma
Severe chronic obstructive pulmonary disease
Severe respiratory depression
Precautions and Warnings
Debilitation
Elderly
Predisposition to seizures
Adrenal insufficiency
Asthma
Benign prostatic hyperplasia
Biliary tract disorder
Carcinomatosis
Cardiovascular disorder
Cholelithiasis
Delirium tremens
Epileptic disorder
Galactosaemia
Glucose-galactose malabsorption syndrome
History of alcohol abuse
History of drug misuse
Hypertension
Hypotension
Hypothyroidism
Inflammatory bowel disease
Lactose intolerance
Mild hepatic impairment
Mild renal impairment
Myasthenia gravis
Myxoedema
Opioid dependence
Pancreatitis
Partial gastrointestinal obstruction
Pregnancy
Respiratory impairment
Sleep apnoea
Toxic psychosis
Advise patient ability to drive or operate machinery may be impaired
Advise patient not to drive until they know how the medicine affects them
Advise patient this medicine may be subject to driving restrictions
Not all available brands are licensed for all indications
Some formulations contain lactose
Monitor patients with renal impairment
Neonate exposed in utero: Monitor for neonatal withdrawal syndrome
Patients on long-term therapy should be regularly reviewed
Potential for drug abuse
Restless Leg Syndrome: Evaluate continuation of treatment every 3 months
Restless Leg Syndrome: Review therapy by controlled withdrawal after 1 year
Restless Leg Syndrome: Treatment to be supervised by a specialist
Tolerance and dependence may occur
Consider dose reduction if sleep-related breathing disorders occur
Increased risk of central sleep apnoea and sleep-related hypoxemia
Neonate exposed in labour: Risk of respiratory depression
Prolonged use at high doses may result in hyperalgesia
Withdrawal symptoms after long-term normal use on abrupt cessation
May affect results of some laboratory tests
Progressive withdrawal recommended
Consider dose reduction or alternative opioid in cases of hyperalgesia
Advise patient not to take St John's wort concurrently
Advise patient to avoid alcohol during treatment
Advise that effects are potentiated by CNS depressants (including alcohol)
Advise patient grapefruit products may increase plasma level
Advise patients that empty tablet/capsule may be observed in stools
Oxycodone and naloxone is contraindicated in patients with a history of opioid abuse for the treatment of RLS.
Oxycodone and naloxone is not recommended within the first 12 to 24 hours post-operatively. Depending on the type and extent of surgery, the anaesthetic procedure selected, other co-medication and the individual condition of the patient, the exact timing for initiating post-operative treatment with oxycodone and naloxone depends on a careful risk benefit assessment for each individual patient.
There is no clinical experience in patients with cancer associated to peritoneal carcinomatosis or with sub-occlusive syndrome in advanced stages of digestive and pelvic cancers. The treatment with oxycodone and naloxone in this population is not recommended.
After complete discontinuation of therapy with oxycodone and naloxone with a subsequent switch to another opioid a worsening of the bowel function is expected.
In patients under long-term opioid treatment with higher doses of opioids, the switch to oxycodone and naloxone can initially provoke withdrawal symptoms. Such patients may require specific attention. Oxycodone and naloxone is not suitable for the treatment of withdrawal symptoms.
Pregnancy and Lactation
Pregnancy
Use oxycodone and naloxone with caution during pregnancy.
The manufacturer concludes that oxycodone and naloxone modified release tablets should only be used during pregnancy if the benefit outweighs the possible risk to foetus or neonate. At the time of writing, there are no data from the use of oxycodone and naloxone modified release tablets in pregnant women and during childbirth. Both oxycodone and naloxone pass into the placenta. No animal studies have currently been performed with oxycodone and naloxone in combination, but animal studies with administration of the single drugs have not revealed any teratogenic or embryotoxic effects. The limited data on the use of oxycodone during pregnancy reveal no evidence of an increased risk of congenital abnormalities.
Schaefer (2015) indicates that the use of oxycodone is acceptable in pregnancy under strict indication. Long-term use is limited to special situations only. Depending upon dose, timing and duration of exposure, the newborn may suffer from respiratory depression and withdrawal symptoms.
Lactation
Oxycodone and naloxone is contraindicated during breastfeeding.
The manufacturer recommends that breastfeeding should be discontinued during treatment with oxycodone and naloxone modified release tablets. Oxycodone passes into breast milk with a milk-plasma concentration ratio of 3.4:1. Oxycodone effects in the infant are therefore conceivable, including drowsiness in particular. In a case of six exposed neonates, no effects were observed in the nursing infants. It is not known whether naloxone also passes into the breast milk. However, after taking these tablets systemic naloxone levels are very low. A risk to the infant cannot be excluded.
Schaefer (2015) indicates that oxycodone should not be undertaken during breastfeeding and should be critically viewed, especially in the first postpartum weeks.
Effects on Ability to Drive and Operate Machinery
This class of medicine is in the list of drugs included in regulations under 5a of the Road Traffic Act 1988 (England and Wales). When prescribing this medicine: Advise patient the medicine can affect cognitive function and is likely to affect ability to drive. Advise patient not to drive until they know how the medicine affects them.
Side Effects
Abdominal distension
Abdominal pain
Abnormal thinking
Accidental injury
Agitation
Amenorrhoea
Anaphylactic reaction
Angina pectoris
Anxiety
Asthenia
Attention disturbances
Biliary colic
Changes of blood pressure
Chest pain
Chills
Cholestasis
Confusion
Constipation
Cough
Dehydration
Dependence
Depression
Diarrhoea
Disturbances of appetite
Dizziness
Dry mouth
Dry skin
Dysgeusia
Dyspepsia
Dysphagia
Dysphonia
Dyspnoea
Dysuria
Erectile dysfunction
Eructation
Euphoria
Fatigue
Flatulence
Gingival disorder
Hallucinations
Headache
Hearing disturbances
Herpes simplex
Hiccups
Hot flushes
Hyperalgesia
Hyperhidrosis
Hypersensitivity reactions
Hypertonia
Hypoaesthesia
Ileus
Impaired co-ordination
Impaired concentration
Increases in hepatic enzymes
Insomnia
Involuntary muscle contractions
Malaise
Melaena
Micturition disorders
Migraine
Mood changes
Mouth ulcers
Muscle spasm
Muscle twitch
Myalgia
Nausea
Nervousness
Nightmares
Oedema
Palpitations
Paraesthesia
Perceptual disturbances
Peripheral oedema
Personality change
Pruritus
Psychomotor hyperactivity
Reduced libido
Respiratory depression
Restlessness
Rhinorrhoea
Sedation
Seizures
Skin reactions
Somnolence
Speech disturbances
Stomatitis
Syncope
Tachycardia
Thirst
Tooth disorder
Tremor
Urinary retention
Urticaria
Vasodilatation
Vertigo
Visual disturbances
Vomiting
Weight changes
Withdrawal symptoms
Yawning
Effects on Laboratory Tests
Athletes must be aware that this medicine may cause a positive reaction to 'anti-doping' tests.
Overdosage
It is strongly recommended that the UK National Poisons Information Service be consulted on cases of suspected or actual overdose where there is doubt over the degree of risk or about appropriate management.
The following number will direct the caller to the relevant local centre (0844) 892 0111
Information may be obtained if you have access to ToxBase the primary clinical toxicology database of the National Poisons Information Service. This is available via password on the internet ( www.toxbase.org ) or if this is unavailable at the backup site ( www.toxbasebackup.org ).
Further Information
Last Full Review Date: September 2020
Reference Sources
Drugs During Pregnancy and Lactation: Treatment Options and Risk Assessment, 3rd edition (2015) ed. Schaefer, C., Peters, P. and Miller, R. Elsevier, London.
Drugs in Pregnancy and Lactation: A Reference Guide to Fetal and Neonatal Risk, 10th edition (2015) ed. Briggs, G., Freeman, R. Wolters Kluwer Health, Philadelphia.
Summary of Product Characteristics: Myloxifin 5mg/2.5mg, 10mg/5mg, 20mg/10mg and 40mg/20mg prolonged release tablets. Zentiva. Revised September 2019.
Summary of Product Characteristics: Oxyargin 5mg/2.5mg, 10mg/5mg, 20mg/10mg and 40mg/20mg prolonged release tablets. Mylan. Revised February 2020.
Summary of Product Characteristics: Targinact 5mg/2.5mg, 10mg/5mg, 20mg/10mg and 40mg/20mg prolonged release tablets. Napp Pharmaceuticals Ltd. Revised March 2021.
Gov.uk. Government departments. Department for Transport. Publications. Drug driving and medicine: Advice for healthcare professionals. Drug driving: Guidance for healthcare professionals on drug driving. Available at: https://www.gov.uk/ Last accessed: 16 September 2020
New drug driving offence: implications for medicines packaging. Medicines Regulatory News. 10 December 2013. Available at: https://www.mhra.gov.uk Last accessed: 16 September 2020
NICE Evidence Services Available at: www.nice.org.uk Last accessed: 22 February 2021
US National Library of Medicine. Toxicology Data Network. Drugs and Lactation Database (LactMed).
Available at: https://www.ncbi.nlm.nih.gov/books/NBK501922/
Naloxone Last revised: 20 July 2020
Last accessed: 16 September 2020
US National Library of Medicine. Toxicology Data Network. Drugs and Lactation Database (LactMed).
Available at: https://www.ncbi.nlm.nih.gov/books/NBK501922/
Oxycodone Last revised: 20 July 2020
Last accessed: 16 September 2020
Medscape UK | Univadis prescription drug monographs & interactions are based on FDB Multilex Content
FDB Disclaimer : FDB Multilex is intended for the use of healthcare professionals and is provided on the basis that the healthcare professionals will retain FULL and SOLE responsibility for deciding what treatment to prescribe or dispense for any particular patient or circumstance.