Oxycodone hydrochloride
OXYNORM is available in the following presentations for oral use:
OXYNORM capsules 5 mg (orange/beige), 10mg (white/beige), 20 mg (pink/beige), in blister
packs of 20 capsules.
Liquid (solution)
OXYNORM liquid 5 mg/5 mL is a clear, colourless to straw-coloured solution in bottles of 250 mL.
Oxycodone is a full opioid agonist with no antagonist properties whose principal therapeutic
action is analgesia. It has affinity for kappa, mu and delta opiate receptors in the brain and spinal
cord. Oxycodone is similar to morphine in its action. Other pharmacological actions of
oxycodone are in the central nervous system (CNS: respiratory depression, antitussive,
anxiolytic, sedative and miosis), smooth muscle (constipation, reduction in gastric, biliary and
pancreatic secretions, spasm of sphincter of Oddi and transient elevations in serum amylase) and
cardiovascular system (release of histamine and/or peripheral vasodilatation, possibly causing
pruritus, flushing, red eyes, sweating and/or orthostatic hypotension).
Opioids may influence the hypothalamic-pituitary-adrenal or –gonadal axes. Some changes that
can be seen include an increase in serum prolactin, and decreases in plasma cortisol and
testosterone. Clinical symptoms may be manifest from these hormonal changes.
Compared with morphine, which has an absolute bioavailability of approximately 30%, oxycodone
undergoes relatively low “first-pass” metabolism and has a high absolute bioavailability of up to
87% following oral administration. Peak plasma concentrations of oxycodone are reached
approximately one hour after administration of OXYNORM capsules, and less than one hour
(approximately 45 minutes) after administration of OXYNORM liquid.
No data are available on the effect of food on the absorption of OXYNORM capsules. Limited
data indicate that the absorption of oxycodone from an oral solution may be significantly affected
by food. An increase in mean AUC of approximately 20% and decrease of Cmax of approximately
20% have been reported.
Metabolism and Elimination
Oxycodone has an elimination half-life of approximately three hours and is metabolised in the
liver to form noroxycodone, oxymorphone, noroxymorphone, 6  and  oxycodol and conjugated
glucuronides. CYP3A4 and CYP2D6 are involved in the formation of noroxycodone and
oxymorphone, respectively (see Interactions with other medicines). The contribution of these
metabolites to the analgesic effect is insignificant.
The management of opioid-responsive moderate to severe pain.
2 October 2014
Dosage and Administration
OXYNORM capsules should be swallowed whole and not opened, chewed or crushed.
Limited data suggest that food may significantly increase the amount of oxycodone absorbed
from an oral solution – see ‘Absorption’ under Pharmacokinetics.
Alcoholic beverages should be avoided while the patient is being treated with OXYNORM
capsules or liquid.
Non-malignant pain
In common with other strong opioids, the need for continued treatment should be assessed at
regular intervals.
Adults, elderly and children over 18 Years
Prior to initiation and titration of doses, refer to the Precautions section for information on special
risk groups such as females and the elderly.
OXYNORM capsules or liquid should be taken at 4-6 hourly intervals. The dosage is dependent
on the severity of the pain, and the patient’s previous history of analgesic requirements.
Increasing severity of pain will require an increased dosage of OXYNORM capsules or liquid.
The correct dosage for any individual patient is that which controls the pain and is well tolerated
throughout the dosing period. Patients should be titrated to pain relief unless unmanageable
adverse drug reactions prevent this.
OXYNORM capsules or liquid will generally be used in a short term trial (4-6 weeks) to determine
if the pain is opioid responsive, before transferring to a longer acting oxycodone preparation such
as OXYCONTIN tablets, in accordance with the clinical guidelines on the use of opioid
analgesics in such patients (e.g. those published by the Australian Pain Society in the Medical
Journal of Australia 1997; 167: 30-4). However, OXYNORM liquid may be used longer term in
patients unable to take solid oral dosage forms, or when more precise dose titration is necessary.
The usual starting dose for opioid-naïve patients or patients presenting with severe pain
uncontrolled by weaker opioids is 5mg, 4-6 hourly. The dose should then be carefully titrated, as
frequently as once a day if necessary, to achieve pain relief. The majority of patients will not
require a daily dose greater than 400 mg. However, a few patients may require higher doses.
Patients receiving oral morphine before oxycodone therapy should have their daily dose based
on the following ratio: 10 mg of oral oxycodone is equivalent to 20 mg of oral morphine. It must
be emphasized that this is a guide to the dose of OXYNORM capsules or liquid required only.
Inter-patient variability requires that each patient be carefully titrated to the appropriate dose.
Controlled pharmacokinetic studies in elderly patients (aged over 65 years) have shown that
compared with younger adults, the clearance of oxycodone is only slightly reduced. No untoward
adverse drug reactions were seen based on age, therefore, adult doses and dosage intervals are
Adults with mild to moderate renal impairment and mild hepatic impairment
The plasma concentration in this patient population may be increased. Therefore, dose initiation
should follow a conservative approach (refer Precautions section).
Children under 18 years
OXYNORM capsules or liquid should not be used in patients under 18 years.
2 October 2014
Multiplication Factors for Converting the Daily Dose
of Prior Opioids to the Daily Dose of Oral Oxycodone*
(mg/day prior opioid x Factor = mg/day oral oxycodone)
Oral Prior Opioid
Parenteral Opioid
Pethidine (Meperidine)
* To be used for conversion to oral oxycodone. For patients receiving high-dose parenteral
opioids, a more conservative conversion is warranted. For example, for high-dose parenteral
morphine, use 1.5 instead of 3 as a multiplication factor.
Hypersensitivity to opioids or to any of the constituents of OXYNORM capsules or liquid, acute
respiratory depression, cor pulmonale, cardiac arrhythmias, acute asthma or other obstructive
airways disease, paralytic ileus, suspected surgical abdomen, severe renal impairment
(creatinine clearance < 10mL/min refer to Special Risk Groups), severe hepatic impairment,
delayed gastric emptying, acute alcoholism, brain tumour, increased cerebrospinal or intracranial
pressure, head injury (due to risk of raised intracranial pressure), severe CNS depression,
convulsive disorders, delirium tremens, hypercarbia, concurrent administration of monoamine
oxidase inhibitors or within two weeks of discontinuation of their use. Pregnancy.
Not recommended for pre-operative use.
Warnings and Precautions
The major risk of opioid excess is respiratory depression including subclinical respiratory
depression. As with all opioids, a reduction in dosage may be advisable in hypothyroidism. Use
with caution in opioid-dependent patients and in patients with hypotension, hypovolaemia,
diseases of the biliary tract, pancreatitis, inflammatory bowel disorders, prostatic hypertrophy,
adrenocortical insufficiency, (Addison’s disease), toxic psychosis, chronic pulmonary, renal or
hepatic disease, myxoedema and debilitated elderly or infirm patients. As with all opioid
preparations, patients who are to undergo cordotomy or other pain-relieving surgical procedures
should not receive OXYNORM capsules or liquid for 6 hours before surgery. As with all opioid
preparations, OXYNORM capsules or liquid should be used with caution following abdominal
surgery as opioids are known to impair intestinal motility and should not be used until the
physician is assured of normal bowel function. Should paralytic ileus be suspected or occur
during use, OXYNORM capsules or liquid should be discontinued immediately.
Hyperalgesia that will not respond to a further dose increase of oxycodone may very rarely occur
in particular at high doses. An oxycodone dose reduction or change in opioid may be required.
Drug Dependence
As with other opioids, tolerance and physical dependence tend to develop upon repeated
administration of oxycodone. There is potential for abuse of the medicine and for development of
strong psychological dependence. OXYNORM capsules or liquid should therefore be prescribed
and handled with a high degree of caution appropriate to the use of a medicine with strong abuse
2 October 2014
In the absence of a clear indication for a strong opioid analgesic, drug-seeking behaviour must be
suspected and resisted, particularly in individuals with a history of, or propensity for, drug abuse.
Withdrawal symptoms may occur following abrupt discontinuation of oxycodone therapy or upon
administration of an opioid antagonist. Therefore, patients on prolonged therapy should be
withdrawn gradually from the medicine if it is no longer required for pain control.
Oxycodone should be used with caution and under close supervision in patients with pain not due
to malignancy who have a prior history of substance abuse. However, in such cases, prior
psychological assessment is essential and the prescribing doctor should consider that the benefit
of treatment outweighs the risk of abuse. OXYNORM capsules and oral liquids are intended for
oral use only. Parenteral injection can be expected to result in severe adverse reactions which
may be fatal.
Effects on Fertility
In reproductive toxicology studies, no evidence of impaired fertility was seen in male or female
rats at oral oxycodone doses of 8 mg/kg/day, with estimated exposure (plasma AUC) equivalent
to 8 mg/day in men and 17 mg/day in women.
Despite these fertility studies in animals, prolonged use of opioids may result in impairment of
reproductive function, including fertility and sexual dysfunction in both sexes, and irregular
menses in women.
Use in Pregnancy
Australian Pregnancy Category C: Drugs which, owing to their pharmacological effects, have
caused or may be suspected of causing, harmful effects on the human fetus or neonate without
causing malformations. These effects may be reversible.
Oxycodone used during pregnancy or labour, may cause withdrawal symptoms and/or respiratory
depression in the newborn infant. Oral administration of oxycodone during the period of
organogenesis did not elicit teratogenicity or embryofoetal toxicity in rats or rabbits at doses up to
8 mg/kg/day in rats (equivalent to 17 mg/day in women, based on estimated plasma AUC values)
or 125 mg/kg/day in rabbits.
Oral administration of oxycodone to rats from early gestation to weaning did not affect post-natal
development parameters at doses up to 6 mg/kg/day (equivalent to 9 mg/day in women, based
on estimated AUC values). In a study designed specifically to investigate the effect of pre-natal
oxycodone on the hypothalamic-pituitary-adrenal axis in adolescent rats, intravenous
administration of oxycodone 0.8 mg/kg/day (equivalent to 11 mg/day in pregnant women, based
on estimated AUC values) had no effect on the corticosterone response, but delayed and
enhanced the peak ACTH response to corticotrophin releasing hormone in males, but not
females. The clinical significance of this observation is unknown.
There are no adequate and well controlled studies with oxycodone in pregnant women. Because
animal reproduction studies are not always predictive of human responses, oxycodone should not
be used during pregnancy unless clearly needed. Prolonged use of oxycodone during pregnancy
can result in neonatal opioid withdrawal syndrome. Oxycodone is not recommended for use in
women during or immediately prior to labour. Infants born to mothers who have received opioids
during pregnancy should be monitored for respiratory depression.
Use in Lactation
Oxycodone accumulates in human milk, with a median maternal milk:plasma ratio of 3:1 recorded
in one study. Oxycodone (7.5 ng/mL) was detected in the plasma of one of forty-one infants 72
hours after Caesarean section. Opioids may cause respiratory depression in the newborn and
withdrawal symptoms can occur in breastfeeding infants when maternal administration of an
opioid analgesic is stopped. OXYNORM capsules or liquid should not be used in breastfeeding
mothers unless the benefits outweigh the risks. Breastfed infants should be monitored for
respiratory depression, sedation, poor attachment and gastrointestinal signs.
2 October 2014
Special Risk Groups
Use in renal and hepatic impairment
In renal and hepatic impairment, the administration of OXYNORM capsules or liquid does not
result in significant levels of active metabolites. However, the plasma concentration of
oxycodone in this patient population may be increased compared with patients having normal
renal or hepatic function. Therefore, initiation of dosing in patients with renal impairment
(CLcr<60mL/min) or hepatic impairment should be reduced to ⅓ to ½ of the usual dose with
cautious titration.
Use in the elderly
The plasma concentrations of oxycodone are only nominally affected by age, being
approximately 15% greater in elderly as compared with young subjects. There were no
differences in adverse event reporting between young and elderly subjects.
Use in the elderly, debilitated patients
As with other opioid initiation and titration, doses in elderly patients who are debilitated should be
reduced to ⅓ to ½ of the usual doses.
Female subjects have, on average, plasma oxycodone concentrations up to 25% higher than
males on a body weight adjusted basis. The reason for this difference is unknown. There were
no significant male/female differences detected for efficacy or adverse events in clinical trials.
Studies of oxycodone in animals to evaluate its carcinogenic potential have not been conducted.
Oxycodone was not genotoxic in bacterial gene mutation assays but was positive in the mouse
lymphoma assay. In assays of chromosomal damage, genotoxic effects occurred in the human
lymphocyte chromosomal aberration assay in vitro, but not in the in vivo bone marrow
micronucleus assay in mice.
Driving and operating dangerous machinery
Oxycodone may modify patients’ reactions to a varying extent depending on the dosage and
individual susceptibility. If affected, patients should not drive or operate machinery.
Adverse Effects
Immediate release formulations such as OXYNORM capsules or liquid may have a higher
incidence of some adverse reactions than controlled-release formulations such as OXYCONTIN
tablets. Adverse drug reactions are typical of full opioid agonists, and tend to reduce with time,
with the exception of constipation. Anticipation of adverse drug reactions and appropriate patient
management can improve acceptability.
Cardiac disorders
bradycardia, chest pain, ST depression, palpitations (as part of withdrawal syndrome),
supraventricular tachycardia
Ear and labyrinth disorders
2 October 2014
Eye disorders
miosis, visual impairment
Gastrointestinal disorders
Very common
nausea, vomiting, constipation
abdominal pain, diarrhoea, dry mouth, dyspepsia, gastritis, hiccup
colic, dental caries, dysphagia, eructation, flatulence, gastrointestinal disorder, ileus, stomatitis
General disorders and administration site conditions
asthenia, fatigue, chills, fever
accidental injury, drug tolerance, drug withdrawal syndrome (with or without seizures), oedema,
peripheral oedema, malaise, facial flushing, lymphadenopathy, muscular rigidity, neck pain, pain,
Not known
drug withdrawal syndrome neonatal
Hepatobiliary disorders
biliary spasm, cholestasis, hepatic enzymes increased
Immune system disorders
allergic reaction, anaphylactic reaction, anaphylactoid reaction, hypersensitivity
Metabolic and nutritional disorders
decreased appetite
increased appetite, dehydration, hyponatraemia
Nervous system disorders
Very common
dizziness, headache, somnolence
faintness, sedation, twitching, tremor, lethargy
abnormal gait, amnesia, drowsiness, hyperkinesia, hypertonia, hypoaesthesia, hypothermia,
muscle contractions involuntary, paraesthesia, raised intracranial pressure, seizures, speech
disorder, stupor, syncope, dysgeusia (taste perversion), convulsion
Not known
Psychiatric disorders
abnormal dreams, anxiety, confusional state, insomnia, nervousness, thinking abnormal,
affect lability, agitation, disorientation, drug dependence, dysphoria, euphoric mood, hallucination,
libido decreased, mood altered, restlessness
2 October 2014
Renal and urinary disorders
ureteric spasm, urinary abnormalities, urinary infection, urinary retention
Reproductive system and breast disorders
amenorrhoea, erectile dysfunction, hypogonadism
Respiratory, thoracic and mediastinal disorders
bronchospasm, dyspnoea, pharyngitis, voice alteration
respiratory depression
Skin and subcutaneous tissue disorders
Very common
hyperhidrosis, rash
angioedema, dry skin, exfoliative dermatitis, urticaria and other skin rashes
Vascular disorders
Orthostatic hypotension
hypotension, migraine, vasodilation
Very common
Very rare
Not known
(≥ 1/10)
(≥ 1/100 to < 1/10)
(≥ 1/1000 to < 1/100)
(≥ 1/10,000 to < 1/1,000)
(< 1/10,000)
(cannot be estimated from the available data)
If nausea and vomiting are troublesome oxycodone may be combined with an antiemetic.
Constipation must be treated with appropriate laxatives. Overdose may produce respiratory
depression. Compared with other opioids oxycodone is associated with low histamine release
although urticaria and pruritus may occur.
Anticholinergic agents
Concurrent use of oxycodone with anticholinergics or medications with anticholinergic activity
(e.g. tricyclic antidepressants, antihistamines, antipsychotics, muscle relaxants and antiParkinson medications) may result in increased anticholinergic adverse effects, including an
increased risk of severe constipation and/or urinary retention.
Antihypertensive agents
Hypotensive effects of these medications may be potentiated when used concurrently with
oxycodone, leading to increased risk of orthostatic hypotension.
CNS depressants (including sedatives or hypnotics, general anaesthetics, phenothiazines,
other tranquillisers, alcohol, other opioids and neuroleptic agents, etc.)
Concurrent use with oxycodone may result in increased respiratory depression, hypotension,
profound sedation or coma. Caution is recommended and the dosage of one or both agents
should be reduced. Intake of alcoholic beverages while being treated with OXYNORM capsules
2 October 2014
or liquid should be avoided because this may lead to more frequent undesirable effects such as
somnolence and respiratory depression. Oxycodone hydrochloride containing products should
be avoided in patients with a history of or present alcohol, drug or medicines abuse.
Coumarin derivatives
Although there is little substantiating evidence, opiate agonists have been reported to potentiate
the anticoagulant activity of coumarin derivatives.
CYP2D6 and CYP3A4 inhibitors and inducers
Oxycodone is metabolised in part via the CYP2D6 and CYP3A4 pathways. The activities of
these metabolic pathways may be inhibited or induced by various co-administered drugs or
dietary elements, which may alter plasma oxycodone concentrations. Oxycodone doses may
need to be adjusted accordingly. Medicines that inhibit CYP2D6 activity such as paroxetine and
quinidine, may cause decreased clearance of oxycodone which could lead to an increase in
oxycodone plasma concentrations. Concurrent administration of quinidine does not alter the
pharmacodynamic effects of oxycodone. CYP3A4 inhibitors such as macrolide antibiotics (e.g.
clarithromycin), azole antifungal agents (e.g. ketoconazole), protease inhibitors (e.g. ritonavir)
and grapefruit juice may cause decreased clearance of oxycodone which could lead to an
increase in oxycodone plasma concentrations. Oxycodone metabolism may be blocked by a
variety of medicines (e.g. cimetidine, certain cardiovascular drugs and antidepressants), although
such blockade has not yet been shown to be of clinical significance with OXYNORM capsules or
CYP3A4 inducers, such as rifampin, carbamazepine, phenytoin and St John’s wort, may induce
the metabolism of oxycodone and cause increased clearance of the drug, resulting in a decrease
in oxycodone plasma concentrations.
Oxycodone did not inhibit the activity of P450 isozymes 2D6, 3A4, 1A2, 2A6, 2C19 or 2E1 in
human liver microsomes in vitro. Non-clinical data in vitro and in vivo indicate that oxycodone
can act as a P-glycoprotein substrate and can induce overexpression of P-glycoprotein in rats.
Concurrent use with oxycodone may antagonise the effects of metoclopramide on gastrointestinal
Monoamine Oxidase Inhibitors (MAOIs)
Non-selective MAOIs intensify the effects of opioid agents which can cause anxiety, confusion
and significant respiratory depression. Severe and sometimes fatal reactions have occurred in
patients concurrently administered MAOIs and pethidine. Oxycodone should not be given to
patients taking non-selective MAOIs or within 14 days of stopping such treatment. As it is
unknown whether there is an interaction between selective MAOIs (e.g. selegiline) and
oxycodone, caution is advised with this medicine combination.
Neuromuscular blocking agents
Oxycodone may enhance the effects of neuromuscular blocking agents resulting in increased
respiratory depression.
Opioid agonist analgesics (including morphine, pethidine)
Additive CNS depressant, respiratory depressant and hypotensive effects may occur if two or
more opioid agonist analgesics are used concurrently.
Opioid agonist-antagonist analgesics (including pentazocine, butorphanol, buprenorphine)
Mixed agonist/antagonist analgesics may reduce the analgesic effect of oxycodone and/or may
precipitate withdrawal symptoms.
2 October 2014
Acute overdosage with oxycodone can be manifested by respiratory depression (reduced
respiratory rate and/or tidal volume, Cheyne-Stokes respiration, cyanosis), extreme somnolence
progressing to stupor or coma, hypotonia, skeletal muscle flaccidity, cold and/or clammy skin,
miosis (dilated if hypoxia is severe), and sometimes bradycardia, hypotension, and death.
Severe overdose may result in apnoea, pulmonary oedema, circulatory collapse and death.
Treatment of oxycodone overdosage
Primary attention should be given to immediate supportive therapy with the establishment of
adequate respiratory exchange through the provision of a patent airway and institution of assisted
or controlled ventilation. Adequate body temperature and fluid balance should be maintained.
Oxygen, intravenous fluids, vasopressors and other supportive measures should be used as
indicated to manage the circulatory shock accompanying an overdose. Cardiac arrest or
arrhythmias may require cardiac massage or defibrillation.
Activated charcoal may reduce absorption of the drug if given within one or two hours after
ingestion. Administration of activated charcoal should be restricted to patients who are fully
conscious with an intact gag reflex or protected airway. A saline cathartic or sorbitol added to the
first dose of activated charcoal may speed gastrointestinal passage of the product. In patients
who are not fully conscious or have an impaired gag reflex, consideration should be given to
administering activated charcoal via a nasogastric tube, once the airway is protected.
If there are signs of clinically significant respiratory or cardiovascular depression, the use of an
opioid antagonist should be considered. The opioid antagonist naloxone hydrochloride is a
specific antidote for respiratory depression due to overdosage or as a result of unusual
sensitivity. The usual intravenous adult dose of naloxone is 0.4mg or higher (please refer to
naloxone Data Sheet for more information). The onset of naloxone effect may be delayed by 30
minutes or more. Concomitant efforts at respiratory resuscitation should be carried out. Since
the duration of action of oxycodone may exceed that of the antagonist, the patient should be
under continued surveillance and doses of the antagonist should be repeated as needed to
maintain adequate respiration.
In an individual physically dependent on, or tolerant to, opioids, the administration of the usual
dose of opioid antagonist will precipitate an acute withdrawal syndrome. The severity of this
syndrome will depend on the degree of physical dependence and the dose of antagonist
administered. The use of opioid antagonists in such individuals should be avoided if possible. If
an opioid antagonist must be used to treat serious respiratory depression in the physically
dependent patient, the antagonist should be administered with extreme care by using dosage
titration, commencing with 10 to 20% of the usual recommended initial dose.
Oxycodone toxicity may result from overdosage but because of the great interindividual variation
in sensitivity to opioids it is difficult to determine an exact dose of any opioid that is toxic or lethal.
The toxic effects and signs of overdosage may be less pronounced than expected, when pain
and/or tolerance are manifest.
Please phone the Poisons Information Centre on 0800 POISON or 0800 764 766 for advice on
managing overdose.
Pharmaceutical Precautions
Store below 30°C.
2 October 2014
- 10 -
Medicine Classification
Controlled Drug B3.
Package Quantities
OXYNORM is available in the following presentations for oral use:
OXYNORM capsules 5 mg, 10 mg, 20 mg, in blister packs of 20 capsules.
Liquid (solution)
OXYNORM liquid 5 mg/5 mL, is a clear, colourless to straw coloured solution in bottles of 250
Further Information
Non-proprietary name:
Chemical name:
CAS No.:
Molecular formula:
Molecular weight:
Oxycodone hydrochloride
The structural formula for oxycodone hydrochloride is:
Oxycodone hydrochloride is a white, crystalline, odourless powder readily soluble in water,
sparingly soluble in ethanol and nearly insoluble in ether.
The inactive ingredients in OXYNORM capsules are: microcrystalline cellulose and magnesium
The capsule shells and printing ink contain the following materials:
Indigo carmine CI 73015 (E132)
Iron oxide red CI 77491 (E172)
Iron oxide yellow CI 77492 (E172)
Sunset yellow FCF CI 15985 (E110)
Titanium dioxide (E171)
Empty Hard Gelatin Capsules 4722-1
5 mg capsule
10 mg capsule
20 mg capsule
2 October 2014
- 11 -
Empty Hard Gelatin Capsules 4723-1
Empty Hard Gelatin Capsules 4724-1
OPACODE monogramming ink
S-1-277002 BLACK
The inactive ingredients in OXYNORM liquid are saccharin sodium, sodium benzoate, citric acid
monohydrate, sodium citrate and hypromellose.
Name and Address
Distributed on behalf of Mundipharma New Zealand Limited by:
Pharmaco (N.Z.) Ltd
P O Box 4079
Ph: (09) 377-3336
Toll Free [Medical Enquiries]: 0800 773 310
Date of Preparation
2 October 2014
® OXYNORM is a Registered Trademark
(Based on Aust PI 150210 [17 Sept 2014] and CCDS 2014)
Orbis NZR-0022 Oct 14
2 October 2014