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LONGTEC 60 MG PROLONGED RELEASE TABLETS

Active substance(s): OXYCODONE HYDROCHLORIDE / OXYCODONE HYDROCHLORIDE

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Transcript
SUMMARY OF PRODUCT CHARACTERISTICS

1

NAME OF THE MEDICINAL PRODUCT
Longtec 60 mg prolonged release tablets

2

QUALITATIVE AND QUANTITATIVE COMPOSITION
Each tablet contains 54 mg of oxycodone as 60 mg of oxycodone
hydrochloride.
Excipient with known effect
Contains lactose monohydrate.
For the full list of excipients, see Section 6.1.

3

PHARMACEUTICAL FORM
Prolonged release tablet.
Red, round, convex tablets marked OC on one side and 60 on the other.

4

CLINICAL PARTICULARS

4.1

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

4.2

Posology and method of administration
Adults over 18 years:
Longtec 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.
Longtec tablets are not intended for use as a prn analgesic.

Increasing severity of pain will require an increased dosage of Longtec tablets,
using the 5 mg, 10 mg, 20 mg, 40 mg or 80 mg 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
in 25% - 50% increments. The need for escape medication more than twice a
day indicates that the dosage of Longtec 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.
Conversion from oral morphine:
Patients receiving oral morphine before Longtec 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
Longtec tablets required. Inter-patient variability requires that each patient is
carefully titrated to the appropriate dose.
Elderly patients:
A dose adjustment is not usually necessary in elderly patients.
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.
Paediatric population
Longtec should not be used in patients under 18 years of age.
Patients with renal or hepatic impairment:
The plasma concentration in this population may be increased. The dose
initiation should follow a conservative approach in these patients. The
recommended adult starting dose should be reduced by 50% (for example a total
daily dose of 10 mg orally in opioid naïve patients), and each patient should be
titrated to adequate pain control according to their clinical situation.
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 nonmalignant pain should be assessed at regular intervals.
Method of administration
Longtec tablets are for oral use.

Longtec tablets must be swallowed whole and not broken, chewed or crushed.
Duration of treatment
Oxycodone should not be used for longer than necessary.
Discontinuation of treatment
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 oxycodone or to any of the excipients listed in section 6.1.
Oxycodone must not be used in any situation where opioids are contraindicated:
severe respiratory depression with hypoxia, paralytic ileus, acute abdomen,
delayed gastric emptying, severe chronic obstructive lung disease, cor
pulmonale, severe bronchial asthma, elevated carbon dioxide levels in the blood,
moderate to severe hepatic impairment, chronic constipation.
Patients with rare hereditary problems of galactose intolerance, the Lapp lactase
deficiency or glucose-galactose malabsorption should not take this medicine.

4.4

Special warnings and precautions for use
The major risk of opioid excess is respiratory depression. Caution must be
exercised when administering oxycodone to the debilitated elderly, patients with
severely impaired pulmonary function, patients with impaired hepatic or renal
function; patients with myxedema, hypothyroidism, Addison’s disease, toxic
psychosis, prostate hypertrophy, adrenocortical insufficiency, alcoholism,
delirium tremens, diseases of the biliary tract, pancreatitis, inflammatory bowel
disorders, hypotension, hypovolaemia, raised intracranial pressure, head injury
(due to risk of increased intracranial pressure) or patients taking MAO
inhibitors.
Longtec tablets should not be used where there is a possibility of paralytic
ileus occurring. Should paralytic ileus be suspected or occur during use,
Longtec tablets should be discontinued immediately.
Longtec tablets are not recommended for pre-operative use or within the first
12-24 hours post-operatively.
As with all opioid preparations, oxycodone products 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.
Patients who are about to undergo additional pain relieving procedures (e.g.
surgery, plexus blockade) should not receive Longtec tablets for 12 hours prior
to the intervention. If further treatment with Longtec tablets is indicated then
the dosage should be adjusted to the new post-operative requirement.

Longtec 60 mg tablets should not be used in patients not previously exposed to
opioids. This tablet strength may cause fatal respiratory depression when
administered to opioid naïve patients.
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.
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.
The patient may develop tolerance to the drug with chronic use and require
progressively higher doses to maintain pain control. Prolonged use of this
product 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.
Hyperalgesia that will not respond to a further dose increase of oxycodone may
occur, particularly in high doses. An oxycodone dose reduction or change to
an alternative opioid may be required.
Oxycodone has an abuse profile similar to other strong opioids. Oxycodone
may be sought and abused by people with latent or manifest addiction
disorders. There is potential for development of psychological dependence
[addiction] to opioid analgesics, including oxycodone. Longtec should be used
with particular care in patients with a history of alcohol and drug abuse.
As with other opioids, infants who are born to dependent mothers may exhibit
withdrawal symptoms and may have respiratory depression at birth.
Longtec tablets must be swallowed whole, and not broken, chewed or crushed.
The administration of broken, chewed, or crushed Longtec tablets leads to a
rapid release and absorption of a potentially fatal dose of oxycodone (see
Section 4.9).

Concomitant use of alcohol and Longtec may increase the undesirable effects
of Longtec; concomitant use should be avoided.
Abuse of oral dosage forms by parenteral administration can be expected to
result in serious adverse events, such as local tissue necrosis, infection,
pulmonary granulomas, increased risk of endocarditis, and valvular heart
injury, which may be fatal.
Empty matrix (tablets) may be seen in the stools.

4.5

Interaction with other medicinal products and other forms of interaction
There can be an enhanced CNS depressant effect during concomitant therapy
with drugs which affect the CNS such as tranquillisers, anaesthetics, hypnotics,
anti-depressants, sedatives, phenothiazines, neuroleptic drugs, other opioids,
muscle relaxants and antihypertensives.
Concomitant administration of oxycodone with anticholinergics or medicines with
anticholinergic activity (e.g. tricyclic anti-depressants, antihistamines, antipsychotics,
muscle relaxants, anti-Parkinson drugs) may result in increased anticholinergic
adverse effects. Oxycodone should be used with caution and the dosage may need to
be reduced in patients using these medications.

MAO inhibitors are known to interact with narcotic analgesics. MAO inhibitors
cause CNS excitation or depression associated with hypertensive or hypotensive
crisis (see section 4.4).
Alcohol may enhance the pharmacodynamic effects of Longtec; concomitant
use should be avoided.
Oxycodone is metabolised mainly by CYP3A4, with a contribution from
CYP2D6. The activities of these metabolic pathways may be inhibited or
induced by various co-administered drugs or dietary elements.
CYP3A4 inhibitors, such as macrolide antibiotics (e.g. clarithromycin,
erythromycin and telithromycin), azole-antifungals (e.g. ketoconazole,
voriconazole, itraconazole, and posaconazole), protease inhibitors (e.g.
boceprevir, ritonavir, indinavir, nelfinavir and saquinavir), cimetidine and
grapefruit juice may cause a reduced clearance of oxycodone that could cause an
increase of the plasma concentrations of oxycodone. Therefore the oxycodone
dose may need to be adjusted accordingly.
Some specific examples are provided below:


Itraconazole, a potent CYP3A4 inhibitor, administered 200 mg orally for
five days, increased the AUC of oral oxycodone. On average, the AUC
was approximately 2.4 times higher (range 1.5 - 3.4).



Voriconazole, a CYP3A4 inhibitor, administered 200 mg twice-daily for
four days (400 mg given as first two doses), increased the AUC of oral
oxycodone. On average, the AUC was approximately 3.6 times higher
(range 2.7 - 5.6).



Telithromycin, a CYP3A4 inhibitor, administered 800 mg orally for four
days, increased the AUC of oral oxycodone. On average, the AUC was
approximately 1.8 times higher (range 1.3 – 2.3).



Grapefruit Juice, a CYP3A4 inhibitor, administered as 200 ml three
times a day for five days, increased the AUC of oral oxycodone. On
average, the AUC was approximately 1.7 times higher (range 1.1 – 2.1).

CYP3A4 inducers, such as rifampicin, carbamazepine, phenytoin and St John´s
Wort may induce the metabolism of oxycodone and cause an increased
clearance of oxycodone that could cause a reduction of the plasma
concentrations of oxycodone. The oxycodone dose may need to be adjusted
accordingly.
Some specific examples are provided below:


St Johns Wort, a CYP3A4 inducer, administered as 300 mg three times a
day for fifteen days, reduced the AUC of oral oxycodone. On average,
the AUC was approximately 50% lower (range 37-57%).



Rifampicin, a CYP3A4 inducer, administered as 600 mg once-daily for
seven days, reduced the AUC of oral oxycodone. On average, the AUC
was approximately 86% lower

Drugs 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
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.

4.6

Fertility, pregnancy and lactation
Pregnancy
Longtec tablets are not recommended for use in pregnancy nor during labour.
There are limited data from the use of oxycodone in pregnant women. Infants
born to mothers who have received opioids during the last 3 to 4 weeks before
giving birth should be monitored for respiratory depression. Withdrawal
symptoms may be observed in the newborn of mothers undergoing treatment
with oxycodone.
Breastfeeding

4.7

Oxycodone may be secreted in breast milk and may cause respiratory
depression in the newborn. Longtec tablets should, therefore, not be used in
breast-feeding mothers.
Effects on ability to drive and use machines
Oxycodone may impair the 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:

The medicine has been prescribed to treat a medical or dental problem;
and

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 Section 4.4). Constipation may be prevented with
an appropriate laxative. If nausea and vomiting are troublesome, oxycodone
may be combined with an anti-emetic.
The following frequency categories form the basis for classification of the
undesirable effects:
Term
Very common
Common
Uncommon
Rare
Very rare
Frequency not known

Frequency
≥ 1/10
≥ 1/100 to <1/10
≥ 1/1,000 to <1/100
≥1/10,000 to <1/1,000
<1/10,000
Cannot be estimated from the available data

Immune system disorders:
Uncommon: hypersensitivity.
Frequency not known: anaphylactic reaction, anaphylactoid reaction

Metabolism and nutrition disorders:
Common: decreased appetite.
Uncommon: dehydration.
Psychiatric disorders:
Common: anxiety, confusional state, depression, insomnia, nervousness,
abnormal thinking, abnormal dreams
Uncommon: agitation, affect lability, euphoric mood, hallucinations, decreased
libido, drug dependence (see section 4.4), disorientation, mood altered,
restlessness, dysphoria
Frequency not known: aggression.
Nervous system disorders:
Very common: somnolence, dizziness, headache.
Common: tremor, lethargy, sedation.
Uncommon: amnesia, convulsion, hypertonia, hypoaesthesia, involuntary
muscle contractions, speech disorder, syncope, paraesthesia, dysgeusia,
hypotonia.
Frequency not known: hyperalgesia.
Eye disorders:
Uncommon: visual impairment, miosis.
Ear and labyrinth disorders:
Uncommon: vertigo.
Cardiac disorders:
Uncommon: palpitations (in the context of withdrawal syndrome),
supraventricular tachycardia.
Vascular disorders:
Uncommon: vasodilatation, facial flushing,
Rare: hypotension, orthostatic hypotension.
Respiratory, thoracic and mediastinal disorders:
Common: dyspnoea, bronchospasm, cough decreased.
Uncommon: respiratory depression, hiccups.
Gastrointestinal disorders:
Very common: constipation, nausea, vomiting.
Common: abdominal pain, diarrhoea, dry mouth, dyspepsia.
Uncommon: dysphagia, flatulence, eructation, ileus, gastritis.
Frequency not known: dental caries
Hepato-biliary disorders:
Uncommon: increased hepatic enzymes, biliary colic.
Frequency not known: cholestasis
Skin and subcutaneous tissue disorders:
Very common: pruritus.

Common: rash, hyperhidrosis.
Uncommon: dry skin, exfoliative dermatitis, urticaria.
Rare: urticaria
Renal and urinary disorders:
Uncommon: urinary retention, ureteral spasm.
Reproductive system and breast disorders:
Uncommon: amenorrhoea, erectile dysfunction, hypogonadism
Frequency not known: amenorrhoea
General disorders and administration site conditions:
Common: asthenia, fatigue
Uncommon: drug withdrawal syndrome, malaise, oedema, peripheral oedema,
drug tolerance, thirst, pyrexia,chills .
Frequency not known: drug withdrawal syndrome neonatal.
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
Acute overdose with oxycodone can be manifested by miosis, respiratory
depression, hypotension and hallucinations. Circulatory failure and somnolence
progressing to stupor or deepening coma, hypotonia, bradycardia, pulmonary
oedema 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. The pure opioid antagonists such as naloxone are specific antidotes
against symptoms from opioid overdose. Other supportive measures should be
employed as needed.
In the case of massive overdosage, administer naloxone intravenously (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 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.


Longtec 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.
Gastrointestial Systems
Opioids may induce spasm of the sphincter of Oddi.

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 Longtec 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
Longtec tablets in neuropathic pain was confirmed by three placebo-controlled
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 Longtec 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 Longtec is 4.5 hours, which leads to steadystate being achieved in about one day.
Release of oxycodone from Longtec tablets is independent of pH.
Longtec 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 Longtec tablets 10 mg administered 12-hourly are equivalent
to those achieved from conventional oxycodone 5 mg administered 6-hourly.

All strengths of Longtec 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
Longtec 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 in-vivo
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 400
Polysorbate 80 (E433)

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
Qdem Pharmaceuticals Ltd
Cambridge Science Park
Milton Road
Cambridge
CB4 0AB

8

MARKETING AUTHORISATION NUMBER(S)
PL 40431/0008

9

DATE OF FIRST AUTHORISATION/RENEWAL OF THE
AUTHORISATION
19/07/2013

10

DATE OF REVISION OF THE TEXT
02/08/2016

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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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