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OXYCONTIN 15MG PROLONGED RELEASE TABLETS

Active substance: OXYCODONE HYDROCHLORIDE

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SUMMARY OF PRODUCT CHARACTERISTICS

1

NAME OF THE MEDICINAL PRODUCT
OxyContin 15 mg prolonged release tablets

2

QUALITATIVE AND QUANTITATIVE COMPOSITION
Each tablet contains 13.5 mg of oxycodone as 15 mg of oxycodone
hydrochloride. For excipients see Section 6.1. Contains lactose monohydrate.

3

PHARMACEUTICAL FORM
Prolonged release tablet.
Grey, round, convex tablets marked OC on one side and 15 on the other.

4

CLINICAL PARTICULARS

4.1

Therapeutic indications
For the treatment of moderate to severe pain in patients with cancer and
post-operative pain. For the treatment of severe pain requiring the use of a
strong opioid.

4.2

Posology and method of administration
OxyContin tablets must be swallowed whole, and not broken, chewed or crushed.
Elderly and adults over 18 years:

OxyContin tablets should be taken at 12-hourly intervals. The dosage is dependent on
the severity of the pain, and the patient’s previous history of analgesic requirements.
OxyContin is not intended for use as a prn analgesic.
Increasing severity of pain will require an increased dosage of OxyContin tablets,
using individual tablet strengths, either alone or in combination, to achieve pain relief.
The correct dosage for any individual patient is that which controls the pain and is well
tolerated for a full 12 hours. Patients should be titrated to pain relief unless
unmanageable adverse drug reactions prevent this. If higher doses are necessary,
increases should be made where possible, in 25% - 50% increments. The need for
escape medication more than twice a day indicates that the dosage of OxyContin
tablets should be increased.
The usual starting dose for opioid naïve patients or patients presenting with severe
pain uncontrolled by weaker opioids is 10 mg, 12-hourly. Some patients may benefit
from a starting dose of 5 mg to minimise the incidence of side effects. The dose
should then be carefully titrated, as frequently as once a day if necessary, to achieve
pain relief. For the majority of patients, the maximum dose is 200 mg 12-hourly.
However, a few patients may require higher doses. Doses in excess of 1000 mg daily
have been recorded.
Patients receiving oral morphine before OxyContin 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 emphasised that this is a guide to the dose of OxyContin
tablets required. Inter-patient variability requires that each patient is 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 appropriate.
Children under 18 years:
OxyContin should not be used in patients under 18 years of age.
Adults with mild to moderate renal impairment and mild hepatic impairment:
The plasma concentration in this population may be increased. Therefore dose
initiation should follow a conservative approach. Patients should be started on
OxyContin tablets 5 mg 12-hourly or OxyNorm liquid 2.5 mg 6-hourly and titrated to
pain relief as described above.
Use in non-malignant pain:
Opioids are not first-line therapy for chronic non-malignant pain, nor are they
recommended as the only treatment. Types of chronic pain which have been shown to
be alleviated by strong opioids include chronic osteoarthritic pain and intervertebral
disc disease. The need for continued treatment in non-malignant pain should be
assessed at regular intervals.
Cessation of Therapy:
When a patient no longer requires therapy with oxycodone, it may be advisable to
taper the dose gradually to prevent symptoms of withdrawal.

4.3

Contraindications
Hypersensitivity to any of the constituents respiratory depression, head injury,
paralytic ileus, acute abdomen, delayed gastric emptying, chronic obstructive
airways disease, cor pulmonale, severe bronchial asthma, hypercarbia, known
oxycodone sensitivity or in any situation where opioids are contraindicated,
moderate to severe hepatic impairment, severe renal impairment (creatinine
clearance <10ml/min), chronic constipation, concurrent administration of
monoamine oxidase inhibitors or within 2 weeks of discontinuation of their
use. Not recommended for pre-operative use or for the first 24 hours postoperatively. Patients with rare hereditary problems of galactose intolerance,
the Lapp lactase deficiency or glucose-galactose malabsorption should not take
this medicine. Pregnancy.

4.4

Special warnings and precautions for use
The major risk of opioid excess is respiratory depression. As with all narcotics, a
reduction in dosage may be advisable in hypothyroidism. Use with caution in patients
with raised intracranial pressure, hypotension, hypovolaemia, toxic psychosis, diseases
of the biliary tract, inflammatory bowel disorders, prostatic hypertrophy,
adrenocortical insufficiency, alcoholism, delirium tremens, pancreatitis, chronic renal
and hepatic disease, or severe pulmonary disease, and debilitated elderly and infirm
patients. OxyContin tablets should not be used where there is a possibility of paralytic
ileus occurring. Should paralytic ileus be suspected or occur during use, OxyContin
tablets should be discontinued immediately. As with all opioid preparations, patients
who are about to undergo additional pain relieving procedures (e.g. surgery, plexus
blockade) should not receive OxyContin tablets for 12 hours
prior to the intervention. If further treatment with OxyContin tablets is indicated then
the dosage should be adjusted to the new post-operative requirement.
OxyContin 60 mg, 80 mg and 120 mg tablets should not be used in patients not
previously exposed to opioids. Thes tablet strengths may cause fatal respiratory
depression when administered to opioid naïve patients.
As with all opioid preparations, OxyContin tablets 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.
For appropriate patients who suffer with chronic non-malignant pain, opioids should
be used as part of a comprehensive treatment programme involving other medications
and treatment modalities. A crucial part of the assessment of a patient with chronic
non-malignant pain is the patient’s addiction and substance abuse history. There is
potential for development of psychological dependence (addiction) to opioid
analgesics, including oxycodone. OxyContin tablets, like all opioids, should be
avoided in patients with a history of, or present alcohol and drug abuse.
If opioid treatment is considered appropriate for the patient, then the main aim of
treatment is not to minimise the dose of opioid but rather to achieve a dose which

provides adequate pain relief with a minimum of side effects. There must be frequent
contact between physician and patient so that dosage adjustments can be made. It is
strongly recommended that the physician defines treatment outcomes in accordance
with pain management guidelines. The physician and patient can then agree to
discontinue treatment if these objectives are not met.
OxyContin has an abuse profile similar to other strong opioids. Oxycodone may be
sought and abused by people with latent or manifest addiction disorders.
As with other opioids, infants who are born to dependent mothers may exhibit
withdrawal symptoms and may have respiratory depression at birth.
OxyContin tablets must be swallowed whole, and not broken, chewed or crushed. The
administration of broken, chewed, or crushed OxyContin tablets leads to a rapid
release and absorption of a potentially fatal dose of oxycodone (see Section 4.9).
Concomitant use of alcohol and OxyContin may increase the undesirable effects of
OxyContin; concomitant use should be avoided.
Abuse of the tablets by parenteral administration can be expected to result in other
serious adverse events, such as local tissue necrosis, infection, pulmonary
granulomas, increased risk of endocarditis, and valvular heart injury, which may be
fatal.

4.5

Interaction with other medicinal products and other forms of interaction
OxyContin, like other opioids, potentiates the effects of tranquillisers, anaesthetics,
hypnotics, anti-depressants, sedatives, phenothiazines, neuroleptic drugs, other
opioids, muscle relaxants and antihypertensives. Monoamine oxidase inhibitors are
known to interact with narcotic analgesics, producing CNS excitation or depression
with hypertensive or hypotensive crisis.
Alcohol may enhance the pharmacodynamic effects of OxyContin; concomitant use
should be avoided.
Concurrent administration of quinidine, an inhibitor of cytochrome P450-2D6,
resulted in an increase in oxycodone Cmax by 11%, AUC by 13%, and t½ elim. by
14%. Also an increase in noroxycodone level was observed, (Cmax by 50%; AUC by
85%, and t½ elim. by 42%). The pharmacodynamic effects of oxycodone were not
altered. This interaction may be observed for other potent inhibitors of cytochrome
P450-2D6 enzyme. Cimetidine and inhibitors of cytochrome P450-3A such as
ketoconazole, voriconazole and erythromycin may inhibit the metabolism of
oxycodone.

4.6

Pregnancy and lactation
OxyContin tablets are not recommended for use in pregnancy nor during
labour. Infants born to mothers who have received opioids during pregnancy
should be monitored for respiratory depression.
Oxycodone may be secreted in breast milk and may cause respiratory
depression in the newborn. OxyContin tablets should, therefore, not be used in
breast-feeding mothers.

4.7

Effects on ability to drive and use machines
Oxycodone may modify patients’ reactions to a varying extent depending on the
dosage and individual susceptibility. Therefore, patients should not drive or operate
machinery if affected.
This medicine can impair cognitive function and can affect a patient’s ability to drive
safely. This class of medicine is in the list of drugs included in regulations under 5a
of the Road Traffic Act 1988. When prescribing this medicine, patients should be
told:








The medicine is likely to affect your ability to drive.
Do not drive until you know how the medicine affects you.
It is an offence to drive while you have this medicine in your body over a
specified limit unless you have a defence (called the ‘statutory defence’).
This defence applies when:
o The medicine has been prescribed to treat a medical or dental
problem; and
o You have taken it according to the instructions given by the prescriber
and in the information provided with the medicine.
Please note that it is still an offence to drive if you are unfit because of the
medicine (i.e. your ability to drive is being affected).”

Details regarding a new driving offence concerning driving after drugs have been
taken in the UK may be found here: https://www.gov.uk/drug-driving-law

4.8

Undesirable effects
Adverse drug reactions are typical of full opioid agonists. Tolerance and dependence
may occur (see Tolerance and Dependence, below). Constipation may be prevented
with an appropriate laxative. If nausea and vomiting are troublesome, oxycodone may
be combined with an anti-emetic.
Common (incidence of 1%) and uncommon (incidence of 1%) adverse drug reactions
are listed in the table below.





Body System

Common

Immune system disorders

Uncommon
Anaphylactic reaction
Anaphylactoid reaction
Hypersensitivity

Metabolism and nutritional disorders

Anorexia

Dehydration

Psychiatric disorders

Anxiety
Confusional state
Insomnia
Nervousness

Affect lability
Agitation
Depression
Drug dependence

Body System

Common

Uncommon

Thinking abnormal
Abnormal dreams

Nervous system disorders

Euphoria
Hallucinations
Libido decreased
Disorientation
Mood altered
Restlessness
Dysphoria

Headache
Dizziness
Sedation
Somnolence

Amnesia
Hypertonia
Tremor
Hypoaesthesia
Hypotonia
Paraesthesia
Speech disorder
Convulsions
Muscle contractions involuntary
Taste perversion
Syncope

Eye disorders

Miosis
Vision abnormal

Ear and labyrinth disorders

Vertigo

Cardiac disorders

Supraventricular tachycardia

Vascular disorders

Hypotension
Orthostatic hypotension
Vasodilatation
Facial flushing

Respiratory, thoracic and mediastinal
disorders

Bronchospasm
Dyspnoea
Cough decreased

Respiratory depression
Hiccups

Gastrointestinal disorders

Constipation
Nausea
Vomiting
Dry mouth
Dyspepsia
Abdominal pain
Diarrhoea

Dental caries
Dysphagia
Eructation
Flatulence
Gastrointestinal disorders
Ileus
Gastritis

Hepato-biliary disorders

Skin and subcutaneous tissue disorders

Biliary colic
Cholestasis
Increased hepatic enzymes
Hyperhidrosis
Pruritus
Rash

Dry skin
Exfoliative dermatitis
Urticaria

Body System

Common

Uncommon

Musculoskeletal and connective tissue
disorders

Muscular rigidity

Renal and urinary disorders

Urinary retention
Ureteral spasm

Reproductive system and breast
disorders

Amenorrhoea
Erectile dysfunction

General disorders and administration
site conditions

Asthenic conditions
Chills

Drug tolerance
Oedema
Oedema peripheral
Malaise
Thirst
Pyrexia
Drug withdrawal syndrome

Tolerance and Dependence:
The patient may develop tolerance to the drug with chronic use and require
progressively higher doses to maintain pain control. Prolonged use of OxyContin
tablets may lead to physical dependence and a withdrawal syndrome may occur upon
abrupt cessation of therapy. When a patient no longer requires therapy with
oxycodone, it may be advisable to taper the dose gradually to prevent symptoms of
withdrawal. The opioid abstinence or withdrawal syndrome is characterised by some
or all of the following: restlessness, lacrimation, rhinorrhoea, yawning, perspiration,
chills, myalgia, mydriasis and palpitations. Other symptoms also may develop,
including: irritability, anxiety, backache, joint pain, weakness, abdominal cramps,
insomnia, nausea, anorexia, vomiting, diarrhoea, or increased blood pressure,
respiratory rate or heart rate.
Reporting of suspected adverse reactions
Reporting suspected adverse reactions after authorisation of the medicinal product is
important. It allows continued monitoring of the benefit/risk balance of the medicinal
product. Healthcare professionals are asked to report any suspected adverse reactions
via the Yellow Card Scheme at: www.mhra.gov.uk/yellowcard.

4.9

Overdose
Signs of oxycodone toxicity and overdosage are pin-point pupils, respiratory
depression, hypotension and hallucinations.
Circulatory failure and
somnolence progressing to stupor or deepening coma, skeletal muscle
flaccidity, bradycardia and death may occur in more severe cases.
The effects of overdosage will be potentiated by the simultaneous ingestion of
alcohol or other psychotropic drugs.

Treatment of oxycodone overdosage: primary attention should be given to the
establishment of a patent airway and institution of assisted or controlled
ventilation.
In the case of massive overdosage, administer naloxone intraveneously (0.4 to
2 mg for an adult and 0.01 mg/kg body weight for children) if the patient is in a
coma or respiratory depression is present. Repeat the dose at 2 minute intervals
if there is no response. If repeated doses are required then an infusion of 60%
of the initial dose per hour is a useful starting point. A solution of 10 mg made
up in 50 ml dextrose will produce 200 micrograms/ml for infusion using an IV
pump (dose adjusted to the clinical response). Infusions are not a substitute for
frequent review of the patient’s clinical state. Intramuscular naloxone is an
alternative in the event that IV access is not possible. As the duration of action
of naloxone is relatively short, the patient must be carefully monitored until
spontaneous respiration is reliably re-established. Naloxone is a competitive
antagonist and large doses (4 mg) may be required in seriously poisoned
patients.
For less severe overdosage, administer naloxone 0.2 mg intravenously followed
by increments of 0.1 mg every 2 minutes if required.
The patient should be observed for at least 6 hours after the last dose of
naloxone.
Naloxone should not be administered in the absence of clinically significant
respiratory or circulatory depression secondary to oxycodone overdosage.
Naloxone should be administered cautiously to persons who are known, or
suspected, to be physically dependent on oxycodone. In such cases, an abrupt
or complete reversal of opioid effects may precipitate pain and an acute
withdrawal syndrome.
Additional/other considerations:

Consider activated charcoal (50 g for adults, 10-15 g for children), if a
substantial amount has been ingested within 1 hour, provided the
airway can be protected. It may be reasonable to assume that late
administration of activated charcoal may be beneficial for prolonged
release preparations; however there is no evidence to support this.


OxyContin tablets will continue to release and add to the oxycodone
load for up to 12 hours after administration and the management of
oxycodone overdosage should be modified accordingly. Gastric
contents may therefore need to be emptied as this can be useful in
removing unabsorbed drug, particularly when a prolonged release
formulation has been taken.

5

PHARMACOLOGICAL PROPERTIES

5.1

Pharmacodynamic properties
Pharmacotherapeutic group: Natural opium alkaloids
ATC code: N02A A05
Oxycodone is a full opioid agonist with no antagonist properties. It has an
affinity for kappa, mu and delta opiate receptors in the brain and spinal cord.
Oxycodone is similar to morphine in its action. The therapeutic effect is
mainly analgesic, anxiolytic, antitussive and sedative.
Endocrine system
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.
Other pharmacological effects
In-vitro and animal studies indicate various effects of natural opioids, such as
morphine, on components of the immune system; the clinical significance of
these findings is unknown. Whether oxycodone, a semisynthetic opioid, has
immunological effects similar to morphine is unknown.
Clinical studies
The efficacy of OxyContin tablets has been demonstrated in cancer pain, postoperative pain and severe non-malignant pain such as diabetic neuropathy,
postherpetic neuralgia, low back pain and osteoarthritis. In the latter indication,
treatment was continued for up to 18 months and proved effective in many
patients for whom NSAIDs alone provided inadequate relief. The efficacy of
OxyContin tablets in neuropathic pain was confirmed by three placebocontrolled studies.
In patients with chronic non-malignant pain, maintenance of analgesia with
stable dosing was demonstrated for up to three years.

5.2

Pharmacokinetic properties
Compared with morphine, which has an absolute bioavailability of
approximately 30%, oxycodone has a high absolute bioavailability of up to
87% following oral administration. Oxycodone has an elimination half-life of
approximately 3 hours and is metabolised principally to noroxycodone and
oxymorphone. Oxymorphone has some analgesic activity but, is present in the

plasma in low concentrations and is not considered to contribute to
oxycodone’s pharmacological effect.
The release of oxycodone from OxyContin tablets is biphasic with an initial
relatively fast release providing an early onset of analgesia followed by a more
controlled release, which determines the 12 hour duration of action. The mean
apparent elimination half-life of OxyContin is 4.5 hours, which leads to steadystate being achieved in about one day.
Release of oxycodone from OxyContin tablets is independent of pH.
OxyContin tablets have an oral bioavailability comparable with conventional
oral oxycodone, but the former achieve maximal plasma concentrations at
about 3 hours rather than about 1 to 1.5 hours. Peak and trough concentrations
of oxycodone from OxyContin tablets 10 mg administered 12-hourly are
equivalent to those achieved from conventional oxycodone 5 mg administered
6-hourly.
All strengths of OxyContin tablets are bioequivalent in terms of both rate and
extent of absorption. Ingestion of a standard high-fat meal does not alter the
peak oxycodone concentration or the extent of oxycodone absorption from
OxyContin tablets.
Elderly
The AUC in elderly subjects is 15% greater when compared with young
subjects.
Gender
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.
Patients with renal impairment
Preliminary data from a study of patients with mild to moderate renal
dysfunction show peak plasma oxycodone and noroxycodone concentrations
approximately 50% and 20% higher, respectively and AUC values for
oxycodone, noroxycodone and oxymorphone approximately 60%, 60% and
40% higher than normal subjects, respectively. There was an increase in t½ of
elimination for oxycodone of only 1 hour.
Patients with mild to moderate hepatic impairment
Patients with mild to moderate hepatic dysfunction showed peak plasma
oxycodone and noroxycodone concentrations approximately 50% and 20%
higher, respectively, than normal subjects. AUC values were approximately
95% and 75% higher, respectively. Oxymorphone peak plasma concentrations
and AUC values were lower by 15% to 50%. The t½ elimination for
oxycodone increased by 2.3 hours.

5.3

Preclinical safety data
Teratogenicity
Oxycodone had no effect on fertility or early embryonic development in male
and female rats at doses as high as 8 mg/kg/d. Also, oxycodone did not induce
any deformities in rats at doses as high as 8 mg/kg/d or in rabbits at doses as
high as 125 mg/kg/d. Dose-related increases in developmental variations
(increased incidences of extra (27) presacral vertebrae and extra pairs of ribs)
were observed in rabbits when the data for individual foetuses were analyzed.
However, when the same data were analyzed using litters as opposed to
individual foetuses, there was no dose-related increase in developmental
variations although the incidence of extra presacral vertebrae remained
significantly higher in the 125 mg/kg/d group compared to the control group.
Since this dose level was associated with severe pharmacotoxic effects in the
pregnant animals, the foetal findings may have been a secondary consequence
of severe maternal toxicity.
In a study of peri- and postnatal development in rats, maternal body weight
and food intake parameters were reduced for doses ≥ 2 mg/kg/d compared to
the control group. Body weights were lower in the F1 generation from
maternal rats in the 6 mg/kg/d dosing group. There were no effects on
physical, reflexological, or sensory developmental parameters or on
behavioural and reproductive indices in the F1 pups (the NOEL for F1 pups
was 2 mg/kg/d based on body weight effects seen at 6 mg/kg/d). There were
no effects on the F2 generation at any dose in the study.
Carcinogenicity
Studies of oxycodone in animals to evaluate its carcinogenic potential have not
been conducted owing to the length of clinical experience with the drug
substance.
Mutagenicity
The results of in-vitro and in-vivo studies indicate that the genotoxic risk of
oxycodone to humans is minimal or absent at the systemic oxycodone
concentrations that are achieved therapeutically.
Oxycodone was not genotoxic in a bacterial mutagenicity assay or in an invivo micronucleus assay in the mouse. Oxycodone produced a positive
response in the in-vitro mouse lymphoma assay in the presence of rat liver S9
metabolic activation at dose levels greater than 25 μg/mL. Two in-vitro
chromosomal aberrations assays with human lymphocytes were conducted. In
the first assay, oxycodone was negative without metabolic activation but was
positive with S9 metabolic activation at the 24 hour time point but not at other
time points or at 48 hour after exposure. In the second assay, oxycodone did

not show any clastogenicity either with or without metabolic activation at any
concentration or time point.

6

PHARMACEUTICAL PARTICULARS

6.1

List of excipients
Lactose monohydrate
Povidone
Ammoniomethacrylate co-polymer
Sorbic acid
Triacetin
Stearyl alcohol
Talc
Magnesium stearate
Film coat
Hypromellose (E464)
Titanium dioxide (E171)
Macrogol
Iron oxide (E172)

6.2

Incompatibilities
Not applicable.

6.3

Shelf life
Three years

6.4

Special precautions for storage
Do not store above 25°C

6.5

Nature and contents of container
PVC blister packs with aluminium foil backing (containing 28, 56 or 112*
tablets).
* Not all pack sizes may be marketed

6.6

Special precautions for disposal
None.

7

MARKETING AUTHORISATION HOLDER
Napp Pharmaceuticals Ltd
Cambridge Science Park
Milton Road
Cambridge CB4 0GW

8

MARKETING AUTHORISATION NUMBER(S)
PL 16950/ 0139

9

DATE OF FIRST AUTHORISATION/RENEWAL OF THE
AUTHORISATION
07/09/2010

10

DATE OF REVISION OF THE TEXT
13/08/2014

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Source: Medicines and Healthcare Products Regulatory Agency

Disclaimer: Every effort has been made to ensure that the information provided here is accurate, up-to-date and complete, but no guarantee is made to that effect. Drug information contained herein may be time sensitive. This information has been compiled for use by healthcare practitioners and consumers in the United States. The absence of a warning for a given drug or combination thereof in no way should be construed to indicate that the drug or combination is safe, effective or appropriate for any given patient. If you have questions about the substances you are taking, check with your doctor, nurse or pharmacist.

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