SCHEDULING STATUS PROPRIETARY NAMES AND DOSAGE FORM … · Page 1 of 31 SCHEDULING STATUS PROPRIETARY NAMES AND DOSAGE FORM OxyContin® 5 mg Prolonged Release Tablets OxyContin®

Page 1 of 31

SCHEDULING STATUS

PROPRIETARY NAMES AND DOSAGE FORM

OxyContin® 5 mg Prolonged Release Tablets





COMPOSITION

Each OxyContin® 5 mg Prolonged Release Tablet contains 5 mg of oxycodone hydrochloride.





Inactive ingredients:

Tablet core: ammoniomethacrylate co-polymer, lactose monohydrate, magnesium stearate,

povidone, stearyl alcohol, talc, triacetin.

Tablet coat: hypromellose, macrogol, talc, titanium dioxide.

OxyContin® 5 mg contains Brilliant blue FCF aluminium lake.

OxyContin® 10 mg contains hydroxypropylcellulose and no additional colourant.

OxyContin® 20 mg contains polysorbate and iron oxide red.

OxyContin® 40 mg contains polysorbate and iron oxide yellow.

OxyContin® 80 mg contains hydroxypropylcellulose, iron oxide yellow and indigo carmine.

Contains sugar. This product contains lactose monohydrate.

S6

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PHARMACOLOGICAL CLASSIFICATION

A 2.9 Other Analgesics

PHARMACOLOGICAL ACTION

Pharmacodynamic properties:

Oxycodone is a full opioid agonist with no antagonist properties. It has 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 and sedative (see INDICATIONS).

Pharmacokinetic properties:

Oxycodone has an absolute bioavailability of up to 87 % following oral administration.

Oxycodone is metabolised principally to noroxycodone via CYP450-3A and oxymorphone via

CYP450-2D6. Oxymorphone has some analgesic activity but is present in plasma in low

concentrations and is not considered to contribute to oxycodone’s pharmacological effect.

Oxycodone has an elimination half-life of approximately 3 hours.

The release of oxycodone from OxyContin® Prolonged Release Tablets is biphasic with an initial

relatively fast release providing an early onset of analgesia followed by a more controlled release

that determines the 12-hour duration of action.

The mean apparent elimination half-life of OxyContin® Prolonged Release Tablets is 4,5 hours

which leads to steady state being achieved in about one day.

OxyContin® Prolonged Release 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® 10 mg Prolonged Release

Tablets administered 12 hourly are equivalent to those achieved from conventional oxycodone 5

mg administered 6 hourly.

OxyContin® 5 mg, 10 mg, 20 mg, 40 mg and 80 mg Prolonged Release Tablets are

bioequivalent in terms of both rate and extent of absorption.

Ingestion of a standard high-fat meal does not alter peak oxycodone concentration or the extent of

oxycodone absorption from OxyContin® Prolonged Release Tablets.

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Elderly: The AUC in elderly subjects is 15 % greater when compared with younger 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 of oxycodone, noroxycodone and

oxymorphone approximately 60 %, 60 % and 40% higher than normal subjects, respectively.

There was an increase in t1/2 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 t1/2 elimination for oxycodone increased by 2,3 hours.

INDICATIONS

OxyContin® Prolonged Release Tablets are indicated for the treatment of moderate to severe

pain in patients with cancer and post-operative pain after gastrointestinal function has returned.

OxyContin® Prolonged Release Tablets are indicated for the treatment of severe pain requiring

the use of a strong opioid analgesic.

CONTRAINDICATIONS

OxyContin® Prolonged Release Tablets are contraindicated in patients with known

hypersensitivity to oxycodone or to any of the excipients or in any situation where opioids are

contraindicated (see COMPOSITION).

OxyContin® Prolonged Release Tablets are contraindicated in patients presenting with

respiratory depression, head injury, paralytic ileus, acute abdomen, delayed gastric emptying,

chronic obstructive airways disease, cor pulmonale, chronic bronchial asthma, hypercarbia,

moderate to severe hepatic impairment, severe renal impairment (creatinine clearance < 10

ml/min), chronic constipation. OxyContin® Prolonged Release Tablets are contraindicated in

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patients on concurrent administration of monoamine oxidase inhibitors or within 2 weeks of

discontinuation of their use.

OxyContin® Prolonged Release Tablets must not be used during pregnancy.

OxyContin® Prolonged Release Tablets are not recommended for pre-operative use or for the

first 24 hours post-operatively.

Patients with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or

glucose-galactose malabsorption should not take this medicine.

WARNINGS and SPECIAL PRECAUTIONS

The major risk of all opioid excess is respiratory depression. A reduction in dosage may be

advisable in hypothyroidism.

OxyContin® Prolonged Release Tablets should be used with caution in patients with raised

intracranial pressure, hypotension, hypovolaemia, toxic psychosis, disease of the biliary tract,

pancreatitis, inflammatory bowel disorders, prostatic hypertrophy, adrenocortical insufficiency,

acute alcoholism, delirium tremens, chronic renal and hepatic disease or severe pulmonary

disease and debilitated elderly and infirm patients.

OxyContin® Prolonged Release Tablets should not be used where there is a possibility of

paralytic ileus occurring. Should paralytic ileus be suspected or occur during use, OxyContin®

Prolonged Release Tablets should be discontinued immediately.

Patients who are to undergo cordotomy or other pain relieving surgical procedures should not

receive OxyContin® Prolonged Release Tablets for 24 hours before surgery. If further treatment

with OxyContin® Prolonged Release Tablets is then indicated the dosage should be adjusted to

the new post-operative requirement.

OxyContin® 80 mg Prolonged Release Tablets should not be used in patients not previously

exposed to opioids. These tablet’s strengths may cause fatal respiratory depression when

administrated to opioid naïve patients.

OxyContin® Prolonged Release 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.

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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. OxyContin® Prolonged Release Tablets has an abuse

liability similar to other strong opioids and should be used with caution in opioid dependent patients

and in patients with a history of alcohol and drug abuse. Oxycodone may be sought and abused

by people with latent or manifest addiction disorders.

OxyContin® Prolonged Release Tablets should be used with particular care in patients with

a history of 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 that provides adequate pain relief with

minimum side effects.

There must be frequent contact between physician and patient so that the dosage adjustments can

be made. It is strongly suggested 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.

Tolerance and dependence:

The patient may develop tolerance to OxyContin® Prolonged Release Tablets with chronic use

and require progressively higher doses to maintain pain control. Prolonged use of OxyContin®

Prolonged Release 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.

For detail on withdrawal symptoms, please see SIDE EFFECTS.

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Infants who are born to dependent mothers may exhibit withdrawal symptoms and may have

respiratory depression at birth.

OxyContin® Prolonged Release Tablets must be swallowed whole and not broken, chewed or

crushed. The administration of broken, chewed or crushed OxyContin® Prolonged Release

Tablets lead to a rapid release and absorption of a potentially fatal dose of oxycodone.

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 that might be fatal.

Effect on the ability to drive or 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.

INTERACTIONS

OxyContin® Prolonged Release Tablets potentiates the effects of tranquillisers, anaesthetics,

hypnotics, anti-depressants, sedatives, phenothiazines, neuroleptic drugs, alcohol, 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.

Concurrent administration of quinidine, an inhibitor of cytochrome P450-2D6, resulted in an

increase in oxycodone Cmax by 11 %, AUC by 13 % and t1/2 elimination by 14 %. Also, an increase

in noroxycodone level was observed, (Cmax by 50 %, AUC by 85 % and t1/2 elimination by 42 %).

The pharmacodynamic effects of oxycodone were not altered. This interaction may be observed

for other potent inhibitors of cytochrome P450-2D6 enzyme.

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Cimetidine and inhibitors of cytochrome P450-3A such as ketoconazole and erythromycin may

inhibit the metabolism of oxycodone.

PREGNANCY AND LACTATION

OxyContin® Prolonged Release Tablets are not recommended for the use in pregnancy nor

during labour. Infants born to mothers who have received opioids during pregnancy should be

monitored for respiratory depression (see CONTRAINDICATIONS).

Oxycodone may be secreted in breast milk and may cause respiratory depression in the newborn.

OxyContin® Prolonged Release Tablets should therefore not be used by breast-feeding mothers.

DOSAGE AND DIRECTIONS FOR USE

OxyContin® Prolonged Release Tablets must be swallowed whole and not chewed.

Elderly and adults over 18 years:

OxyContin® Prolonged Release 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.

Increasing severity of pain will require an increased dose of OxyContin® Prolonged Release

Tablets using the 5 mg, 10 mg, 20 mg, 40 mg or 80 mg tablets 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® Prolonged Release Tablets should be increased.

The usual starting dose for opioid naïve 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.

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Patients receiving oral morphine before OxyContin® Prolonged Release Tablets 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®

Prolonged Release 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 (see Pharmacokinetics).

Children under 18 years:

The safety and efficacy of OxyContin® Prolonged Release Tablets in patients under 18 years of

age has not been established.

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. Opioid naïve patients should be started on OxyContin® 5 mg

Prolonged Release Tablets 12 hourly and titrated to pain relief as described (see

Pharmacokinetics).

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.

SIDE EFFECTS

Adverse drug reactions are typical of full opioid agonists. Tolerance and dependence may occur.

Constipation may be prevented with an appropriate laxative. If nausea and vomiting are

troublesome, oxycodone may be combined with an anti-emetic. The reactions are listed as

MeDRA preferred term by system organ class and absolute frequency.

Body System Frequency of Occurrence

Page 9 of 31

Very Common

> 10 %

Common

> 1 % and <

10 %

Uncommon

> 0.1 % and <

1 %

Rare

> 0.01 % and <

0.1 %

Very Rare

< 0.01 %

Gastrointestin

al disorders

constipation,

nausea,

vomiting

abdominal

pain,

diarrhoea,

dry mouth,

hiccups,

dyspepsia

mouth

ulceration,

stomatitis,

flatulence

melaena,

tooth disorder,

gingival

bleeding,

dysphagia

ileus

Hepatobiliary

disorders

biliary colic hepatic

enzymes

increased

Metabolism

and nutrition

disorders

decreased

apetite up to

loss of

appetite

dehydration,

increased

appetite

Nervous

system

disorders

headache,

dizziness,

sedation

(somnolence up

to a depressed

level of

consciousness)

syncope,

paraesthesia

concentration

impaired,

migraine,

dysgeusia,

hypermyotonia,

tremor,

involuntary

muscle

contractions,

hypoaesthesia,

abnormal

coordination

convulsions

(especially in

persons with

epileptic

disorder or

predisposition

to

convulsions),

amnesia

speech

disorder

Page 10 of 31

Psychiatric

disorders

altered mood

and

personality

change (e.g.

anxiety,

depression,

euphoric

mood),

decreased

activity,

restlessness,

psychomotor

hyperactivity,

agitation,

nervousness,

insomnia,

abnormal

thinking,

confusion

perception

disturbances

(e.g.

hallucination,

derealisation),

reduced libido

Infections and

infestations

herpes simplex

Immune

system

disorders

hypersensitivity anaphylactic

reaction

Eye disorders visual

disturbances

Ear and

labyrinth

disorders

hearing

impaired

Renal and

urinary

disorders

urinary

retention,

dysuria,

micturition

urgency

Page 11 of 31

Reproductive

system and

breast

disorders

erectile

dysfunction

amenorrhoea

Cardiac

disorders

tachycardia palpitations

Vascular

disorders

hypotension vasodilatation

Respiratory,

thoracic and

mediastinal

disorders

dyspnoea

dysphonia,

cough

Skin and

subcutaneous

tissue

disorders

pruritus skin reactions

/ rash

dry skin urticaria

Injury,

poisoning and

procedural

complications

injury from

accidents

General

disorders and

administration

site conditions

hyperhidrosis

up to chills,

asthenia

physical

dependence

with drug

withdrawal

syndrome, pain

(e.g. chest

pain), malaise,

oedema

weight

increase,

weight

decrease,

thirst

Symptoms of withdrawal:

Opioid abstinence or withdrawal syndrome is characterised by some or all of the following:

restlessness, lacrimation, rhinorrhoea, yawning, perspiration, chills, myalgia and mydriasis. Other

Page 12 of 31

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. The development of psychological dependence (addiction) to opioid

analgesics in properly managed patients with pain has been reported to be rare. However, data

are not available to establish the true incidence of psychological dependence (addiction) in chronic

pain patients.

KNOWN SYMPTOMS OF OVERDOSAGE AND PARTICULARS OF ITS TREATMENT

Signs of oxycodone toxicity and overdosage are pinpoint pupils, respiratory depression and

hypotension. Circulatory failure and somnolence progressing to stupor or deepening coma,

skeletal muscle flaccidy, bradycardia and death may occur in more severe cases.

Treatment of oxycodone overdosage: primary attention should be given to the establishment of

a patent airway and institution of assisted or controlled ventilation.

In 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 repeat 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.

Naloxone should 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 dependant on oxycodone. In such cases,

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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® Prolonged Release Tablets will continue to release and add to the oxycodone load

for up to 12 hours after administration and 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.

IDENTIFICATION

OxyContin® 5 mg Prolonged Release Tablets are pale blue, round, bi-convex, film coated

tablets, imprinted with OC on one side and 5 on the other side.

OxyContin® 10 mg Prolonged Release Tablets are white, round, bi-convex, film coated tablets,

imprinted with OC on one side and 10 on the other side.

OxyContin® 20 mg Prolonged Release Tablets are pink, round, bi-convex, film coated tablets,


OxyContin® 40 mg Prolonged Release Tablets are yellow, round, bi-convex, film coated tablets,


OxyContin® 80 mg Prolonged Release Tablets are green, round, bi-convex, film coated tablet,


PRESENTATION

OxyContin® 5 mg Prolonged Release Tablets are supplied in clear PVC and aluminium foil

blister packs of 28.



Page 14 of 31







STORAGE INSTRUCTIONS

Store at or below 25 ⁰C. Store in original package in the outer carton in order to protect from light.

Store this medicine out of the reach of children.

REGISTRATION NUMBERS

South Africa: S6

OxyContin® 5 mg Prolonged Release Tablets: 41/2.9/1098





Namibia: NS4






Botswana: S1A

OxyContin® 5 mg Prolonged Release Tablets: BOT1402343

Page 15 of 31





NAME AND BUSINESS ADDRESS OF THE HOLDER OF THE CERTIFICATE OF

REGISTRATION

Mundipharma (Pty) Ltd

2nd floor Mariendahl House

Newlands on Main

Claremont

7708

www.mundipharma.co.za

DATE OF PUBLICATION OF THIS PACKAGE INSERT

9 October 2009

® = OxyContin is a registered trademark.

http://www.mundipharma.co.za/

Page 16 of 31

SKEDULERINGSTATUS

EIENDOMSNAAM EN DOSEERVORM






SAMESTELLING

Elke OxyContin® 5 mg Prolonged Release Tablet bevat 5 mg oksikodoonhidrochloried.





Onaktiewe bestanddele:

Tablet kern: ammoniometakrilaat ko-polimeer, laktosemonohidraat, magnesiumstearaat, povidoon,

stearielalkohol, talk en triasetaat.

Tablet bedekking: hipromellose, makrogol, talc, titanium dioksied.

OxyContin® 5 mg bevat skitterende blou FCF aluminiumlak kleurstof.

OxyContin® 10 mg bevat hidroksipropielsellulose en geen addisionele kleurstowwe.

OxyContin® 20 mg bevat polysorbaat en ysteroksied rooi kleurstof.

OxyContin® 40 mg bevat polysorbaat en ysteroksied geel kleurstof.

OxyContin® 80 mg bevat hidroksipropielsellulose, ysteroksied geel en indigo karmyn as kleurstowwe.

Bevat suiker: Die produk bevat laktosemonohidraat.

FARMAKOLOGIESE KLASSIFIKASIE

S6

Page 17 of 31

A 2.9 Ander Analgetika

FARMAKOLOGIESE WERKING

Farmakodinamiese eienskappe:

Oksikodoon is 'n vol opioïed agonis en het geen antagonistiese eienskappe nie. Dit het affiniteit vir

kappa-, mu- en delta-opiaatreseptore in die brein en rugmurg. Oksikodoon is soortgelyk aan

morfien in sy werking. Die terapeutiese effek is hoofsaaklik analgeties, angsiolities en sederend

(sien INDIKASIES).

Farmakokinetiese eienskappe:

Oksikodoon het 'n absolute biobeskikbaarheid tot 87 % na mondelingse toediening.

Oksikodoon word hoofsaaklik na noroksikodoon via CYP450-3A en oksimorfoon via CYP450-2D6,

gemetaboliseer. Oksimorfoon het geringe analgetiese werking, maar is in lae konsentrasies in

plasma teenwoordig en word nie beskou om tot oksikodoon se farmakologiese effek by te dra nie.

Oksikodoon het 'n eliminasie halfleeftyd van ongeveer 3 uur.

Die vrystelling van oksikodoon vanuit OxyContin® Prolonged Release Tablets is bifasies met 'n

aanvanklike relatiewe vinnige vrystelling wat 'n vroeë aanvang van pynverligting verskaf wat

gevolg word deur 'n meer gekontroleerde vrystelling wat die 12-uur werkingsduur bepaal.

Die gemiddelde klaarblyklike eliminasie halfleeftyd van OxyContin® Prolonged Release Tablets

is 4,5 uur wat tot konstante bloedvlakke lei binne een dag.

OxyContin® Prolonged Release Tablets het 'n orale biobeskikbaarheid wat vergelykbaar is met

konvensionele orale oksikodoon, maar die eersgenoemde bereik maksimale plasmakonsentrasies

na ongeveer 3 uur in vergelyk met 1 tot 1,5 uur.

Piek- en dal konsentrasies van oksikodoon vanaf OxyContin® 10 mg Prolonged Release Tablets

wat 12 uurliks toegedien word, is ekwivalent aan konvensionele orale oksikodoon waar 5 mg 6

uurliks toegedien word.

OxyContin® 5 mg, 10 mg, 20 mg, 40 mg and 80 mg Prolonged Release Tablets is bio-

ekwivalent in terme van beide tempo en omvang van absorpsie.

Inname van ’n standaard, hoë-vet maaltyd verander nie die piek oksikodoon konsentrasie of die

omvang van die absorpsie daarvan vanuit OxyContin® Prolonged Release Tablets, nie.

Page 18 of 31

Bejaardes: Die AOK by bejaarde persone is 15 % groter wanneer vergelyk word met jonger

persone.

Geslag: Vroulike persone het gemiddeld, tot 25 % hoër oksikodoon plasma konsentrasies as

mans wanneer dit basseer word op 'n liggaamsgewig aangepaste basis. Die rede vir die verskil is

onbekend.

Pasiënte met renale inkorting: Voorlopige data van 'n studie het getoon dat pasiënte met ligte

tot matige renale inperking, piek plasma oksikodoon- en noroksikodoon konsentrasies van

ongeveer 50 % en 20 %, en AOK waardes van oksikodoon, noroksikodoon en oksimorfoon

ongeveer 60 %, 60 % and 40% onderskeidelik hoër as normale persone sin was. Daar was 'n

verhoging van slegs een uur in t1/2 van eliminasie vir oksikodoon.

Pasiënte met ligte tot matige hepatiese inkorting: Pasiënte met ligte tot matige hepatiese

disfunksie wys piek plasma oksikodoon- en noroksikodoonkonsentrasies van ongeveer 50 % en 20

% hoër as normale persone, onderskeidelik. AOK waardes was onderskeidelik ongeveer 95 % en

75 % hoër, respektiewelik. Oksimorfoon piek plasmakonsentrasies en AOK waardes was met 15

% tot 50 % laer. Die t1/2 eliminasie vir oksikodoon het met 2,3 uur verhoog.

INDIKASIES

OxyContin® Prolonged Release Tablets is aangedui vir die behandeling van matige tot erge pyn

by pasiënte met kanker en post-operatiewe pyn nadat die gastroïntestinale funksie teruggekeer

het.

OxyContin® Prolonged Release Tablets is aangedui vir die behandeling van erge pyn wat die

gebruik van 'n sterk opioïed analgetikum vereis.

KONTRA-INDIKASIES

OxyContin® Prolonged Release Tablets is teenaangedui by pasiënte met bekende

hipersensitiwiteit teenoor oksikodoon of teenoor enige van die ander bestanddele of in enige

situasie waar opioïede teenaangedui is (sien SAMESTELLING).

OxyContin® Prolonged Release Tablets is teenaangedui by pasiënte wat aan respiratoriese

depressie, hoofbesering, paralitiese ileus, akute abdomen, vertraagde gastriese lediging, kroniese

Page 19 of 31

obstruktiewe lugwegsiekte, cor pulmonale, kroniese brongiale asma, hiperkarbie, matige tot erge

hepatiese inkorting, erge renale inkorting (kreatinienopruiming < 10 ml/min) of kroniese

hardlywigheid ly. OxyContin® Prolonged Release Tablets is teenaangedui by pasiënte wat

gelyktydige toediening van monoamienoksidaseïnhibeerders ontvang of binne 2 weke van staking

van hul gebruik.

OxyContin® Prolonged Release Tablets word nie aanbeveel vir pre-operatiewe gebruik of vir die

eerste 24 uur post-operatief nie.

OxyContin® Prolonged Release Tablets moet nie gebruik word deur swanger of borsvoedende

vrouens nie.

Pasiënte met seldsame, oorerflike probleme van galaktose intoleransie, die Lapp laktase tekort of

glukose-galaktose wanabsorpsie moet nie hierdie medisyne neem nie.

WAARSKUWINGS en SPESIALE VOORSORGMAATREËLS

Die groot risiko van alle opioïed oormaat is respiratoriese depressie. 'n Verlaging in dosis mag

nodig wees by hypotiroïedisme.

OxyContin® Prolonged Release Tablets moet versigtig gebruik word by pasiënte met verhoogde

intrakraniale druk, hipotensie, hipovolemie, toksiese psigose, siekte van die biliêre kanaal,

pankreatitis, inflammatoriese ingewandsafwykings, prostaat hipertrofie, adrenokortikale

ontoereikendheid, akute alkoholisme, delirium tremens, kroniese renale en hepatiese siekte of

erge pulmonale siekte en verswakte bejaardes en sieklike pasiënte.

OxyContin® Prolonged Release Tablets moet nie gebruik word as daar 'n moontlikheid is dat

paralitiese ileus kan ontwikkel nie. Indien paralitiese ileus vermoed word of voorkom tydens

gebruik van OxyContin® Prolonged Release Tablets, moet dit onmiddellik gestaak word.

Pasiënte wat kordotomie of ander pynverligtende chirurgiese prosedures ondergaan moet nie

OxyContin® Prolonged Release Tablets vir 24 uur voor chirurgie ontvang nie. Indien verdere

behandeling met OxyContin® Prolonged Release Tablets dan aangedui is, moet die dosis na die

nuwe post-operatiewe vereistes aangepas word.

Page 20 of 31

OxyContin® 80 mg Prolonged Release Tablets moet nie deur pasiënte wat voorheen nie aan

opioïede blootgestel is, gebruik word nie. Hierdie tablette se sterkte kan fatale respiratoriese

depressie veroorsaak wanneer dit aan opioïed naïewe pasiënte toegedien word.

OxyContin® Prolonged Release Tablets moet versigtig gebruik word na abdominale chirurgie,

aangesien opioïede bekend is daarvoor om intestinale motiliteit in te kort - dit moet nie gebruik

word totdat die geneesheer seker is dat normale ingewandsfunksie herstel is nie.

Vir geskikte pasiënte wat aan kroniese, nie-kwaadaardige pyn ly, moet opioïede gebruik word as

deel van 'n omvattende behandelingsprogram wat ander medisyne en behandelingsmodaliteite

insluit.

Dit is baie belangrik om die geskiedenis van verslawing en misbruik te oorweeg om die kroniese,

nie-kwaadaardige pyn van die pasiënt te evalueer. OxyContin® Prolonged Release Tablets het

’n potensiaal vir misbruik wat soortgelyk is aan ander sterk opioïede, en moet daarom met sorg

gebruik word by opioïedafhanklike pasiënte, of indien die geneesheer of apteker bekommerd is oor

die risiko van misbruik. Oksikodoon kan gesoek en misbruik word deur persone met latente of

duidelike tendens vir verslawing.

OxyContin® Prolonged Release Tablets moet met spesifieke sorg by pasiënte met 'n

geskiedenis van alkohol- en dwelmmisbruik, gebruik word.

Indien opioïedbehandeling as geskik beskou word vir die pasiënt, is die hoof doel van behandeling

nie om die dosis van die opioïed te verminder nie, maar eerder om 'n dosis te bereik wat

genoegsame pynverligting met die minimum newe-effekte verskaf.

Daar moet gereelde kontak tussen die geneesheer en pasiënt wees sodat dosisaanpassings

gemaak kan word. Dit word sterk aanbeveel dat die geneesheer die uitkoms vir die behandeling

bepaal soos dit in die pynbeheer riglyne voorgeskryf word. Die geneesheer en pasiënt kan dan

ooreenkom om behandeling te staak as hierdie doelwitte nie bereik word nie.

Toleransie en afhanklikheid:

Page 21 of 31

Die pasiënt kan toleransie ontwikkel teenoor OxyContin® Prolonged Release Tablets wanneer

dit kronies gebruik word en mag aanhoudende hoër dosisse vereis om die pyn te beheer.

Langdurige gebruik van OxyContin® Prolonged Release Tablets kan tot fisiese afhanklikheid lei

en 'n onttrekkingsindroom kan ontwikkel na skielike staking van die behandeling. Wanneer die

pasiënt nie verdere behandeling met oksikodoon benodig nie, mag dit raadsaam wees om die

dosis geleidelik te verminder om onttrekkingsimptome te voorkom.

Vir meer inligting oor onttrekkingsindroom, sien NEWE-EFFEKTE.

Babas van afhanklike moeders, kan onttrekkingsimptome toon en respiratoriese depressie by

geboorte hê.

OxyContin® Prolonged Release Tablets moet heel ingesluk word en nie gebreek, gekou of

fyngedruk word nie. Die gebruik van gebreekte, gekoude of fyngedrukte OxyContin® Prolonged

Release Tablets lei tot vinnige vrystelling en absorpsie van 'n potensieel fatale dosis van

oksikodoon.

Dit is te verwagte dat die misbruik van die tablette deur parenterale toediening, ander ernstige

nadelige effekte soos lokale weefsel nekrose, infeksie, pulmonale granulomas, verhoogde risiko

van endokarditis en hartbesering, wat fataal mag wees, tot gevolg kan hê.

Effek op die vermoë om te betuur of masjienerie te gebruik:

Oksikodoon kan die pasiënt se reaksie tot 'n afwisselende omvang verander, afhangend van die

dosis en die individuele vatbaarheid. Daarom moet pasiënte nie bestuur of met masjienerie werk

indien hul geaffekteer word nie.

INTERAKSIES

Page 22 of 31

OxyContin® Prolonged Release Tablets versterk die effek van kalmeermiddels, anestetika,

hipnotika, anti-depressante, sedeermiddels, fenotiasiene, neuroleptiese geneesmiddels, alkohol,

ander opioïede, spierverslappers en antihipertensiewe middels.

Monoamienoksidaseïnhibeerders is bekend om ’n interaksie te hê met narkotiese analgetika, wat

SSS prikkeling of depressie met hipertensiewe of hipotensiewe krisis veroorsaak.

Gelyktydige toediening van kinidien, 'n inhibeerder van sitochroom P450-2D6, lei tot 'n verhoging in

oksikodoon Cmaks van 11 %, AOK van 13 % en t1/2 eliminasie van 14 %. Daar is ook 'n verhoging in

noroksikodoonvlak opgemerk, (Cmaks van 50 %, AOK van 85 % en t1/2 eliminasie van 42 %). Die

farmakodinamiese effekte van oksikodoon was onveranderd. Hierdie interaksie kan ook verwag

word wanneer ander kragtige inhibeerders van sitochroom P450-2D6 ensiem gelyktydig toegedien

word.

Simetidien en inhibeerders van sitochroom P450-3A, soos ketokonasool en eritromisien, kan die

metabolisme van oksikodoon inhibeer.

SWANGERSKAP EN LAKTASIE

OxyContin® Prolonged Release Tablets word nie aanbeveel gedurende swangerskap of kraam

nie. Babas wat gebore is aan moeders wat opioïede tydens swangerskap ontvang het, moet

gemoniteer word vir respiratoriese depressie (sien KONTRA-INDIKASIES).

Oksikodoon kan in borsmelk uitgeskei word en kan respiratoriese depressie by pasgeborenes

veroorsaak. OxyContin® Prolonged Release Tablets moet daarom nie by borsvoedende

moeders gebruik word nie.

DOSIS EN GEBRUIKSAANWYSINGS

OxyContin® Prolonged Release Tablets moet heel ingesluk word en nie gekou word nie.

Bejaardes en volwassenes ouer as 18 jaar:

OxyContin® Prolonged Release Tablets moet in 12-uurlikse intervalle geneem word. Die dosis is

afhanklik van die pynvlak en die pasiënt se geskiedenis van analgetiese vereistes.

Page 23 of 31

’n Verhoging in die pynvlak sal 'n verhoging in dosis van OxyContin® Prolonged Release Tablets

vereis, met gebruik van die 5 mg, 10 mg, 20 mg, 40 mg of 80 mg tablet sterktes òf alleen òf in

kombinasie, om pynverligting te bereik.

Die korrekte dosis vir enige individuele pasiënt is dit wat die pyn beheer en goed verdra word vir

die volle 12 uur. Pasiënte moet getitreer word tot pynverligting, tensy onbeheerde nadelige

geneesmiddelreaksies dit verhoed. Indien hoër dosisse nodig is, moet verhogings, waar moontlik,

in 25 % - 50 % inkremente gemaak word. Die behoefte aan reddings-medisyne meer as twee keer

per dag wys daarop dat die dosis OxyContin® Prolonged Release Tablets verhoog moet word.

Die gewone aanvangsdosis vir opioïed naïewe pasiënte wat erge pyn vertoon wat nie met swakker

opioïede beheer word nie, is 10 mg 12-uurliks. Sommige pasiënte kan voordeel trek daaruit om 'n

aanvangsdosis van 5 mg te gebruik om sodoende die kanse van newe-effekte te verminder. Die

dosis moet daarna sorgvuldig getitreer word, so dikwels as een keer per dag, indien nodig om

pynverligting te bereik. Vir die meerderheid van pasiënte is die maksimum dosis 200 mg 12-

uurliks. Nogtans, kan 'n klein hoeveelheid pasiënte hoër dosisse benodig. Dosisse groter as 1000

mg daagliks is al aangeteken.

Pasiënte wat orale morfien ontvang het voor die behandeling met OxyContin® Prolonged

Release Tablets, moet hul daaglikse dosis op die volgende verhouding baseer: 10 mg orale

oksikodoon is ekwivalent aan 20 mg orale morfien. Dit moet beklemtoon word dat dit slegs 'n riglyn

is tot die dosis van OxyContin® Prolonged Release Tablets wat benodig word. Inter-pasiënt

wisselvalligheid vereis dat elke pasiënt sorgvuldig getitreer moet word tot die geskikte dosis.

Gekontroleerde farmakokinetiese studies by bejaarde pasiënte (ouer as 65 jaar) het aangetoon dat

die opruiming van oksikodoon slegs effens verlaag is in vergelyking met jonger volwassenes. Geen

onverwagse reaksies is waargeneem gebaseer op die ouderdom nie, daarom is volwasse dosisse

en dosisintervalle geskik (sien Farmakokinetika).

Kinders jonger as 18 jaar:

Die veiligheid en doeltreffendheid van OxyContin® Prolonged Release Tablets by pasiënte

jonger as 18 jaar is nog nie vasgestel nie.

Volwassenes met ligte tot matige renale inkorting en matige hepatiese inkorting:

Page 24 of 31

Die plasmakonsentrasie in hierdie populasie kan verhoog wees. Daarom moet die aanvang van

die dosis, 'n konserwatiewe benadering volg. Opioïed naïewe pasiënte moet met OxyContin® 5

mg Prolonged Release Tablets 12 uurliks begin word en getitreer word tot pynverligting bereik

word soos voorgeskryf (sien Farmakokinetika).

Staking van behandeling:

Wanneer 'n pasiënt nie langer behandeling met oksikodoon benodig nie, is dit raadsaam om die

dosis geleidelik te verminder om onttrekkingsimptome te verhoed.

NEWE-EFFEKTE

Newe-effekte is tipies van vol opioïed agoniste. Toleransies en afhanklikheid kan voorkom.

Hardlywigheid kan voorkom word met 'n geskikte purgeermiddel. Indien naarheid en braking ’n

probleem is, kan oksikodoon met anti-emetika gekombineer word. Die reaksies is gelys as

MeDRA voorkeurterme in stelsel-orgaanklas en absolute frekwensie.

Liggaamstelsel Frekwensie van voorkoms

Baie

Algemeen

> 10 %

Algemeen

> 1 % en < 10

%

Nie algemeen

> 0.1 % en < 1

%

Seldsaam

> 0.01 % en <

0.1 %

Baie

Seldsaam

< 0.01 %

Gastroïntestinale

afwykings

konstipasie,

naarheid,

braking

abdominale

pyn,

diarree,

droë mond, hik,

dispepsie

mond

ulserasie,

stomatitis,

winderigheid

melaena,

tandafwyking,

tandvleis-

bloeding,

disfagie

ileus

Hepatobiliêre

afwykings

biliêre koliek verhoogde

hepatiese

ensieme

Metabolisme en

voedings-

afwykings

verlaag aptyt

tot verlies aan

aptyt

dehidrasie,

verhoogde

aptyt

Page 25 of 31

Senuweestelsel

afwykings

hoofpyn,

duiseligheid,

sedasie

(slaperigheid

tot by vlak

van

bewusteloos-

heid)

sinkopee,

parestesie

ingekorte

konsentrasie,

migraine,

dysgeusie,

hipermiotonie,

bewing,

onwillekeurige

spiersame-

trekkings,

hipo-astesie,

abnormale

koördinasie

konvulsies

(veral by

persone met

epileptiese

afwyking of

neiging tot

konvulsies),

amnesie

spraak

afwyking

Page 26 of 31

Psigiatriese

afwykings

veranderde

gemoed en

persoonlikheids

-verandering

(bv. angs,

depressie,

euforiese

gemoed),

verlaagde

aktiwiteit,

rusteloosheid,

psigo-

motoriese

hiper-aktiwiteit,

agitasie,

senuwee-

agtigheid,

insomnie,

abnormale

denke,

verwarring

persepsie

steurnisse

(bv.

hallusinasies,

derealisering),

verlaagde

libido

Infeksies en

infestasies

herpes

simplex

Immuunstelsel

afwykings

hiper-

sensitiwiteit

anafilaktiese

reaksie

Oogafwykings visuele

steurnisse

Oor en Labarint-

afwykings

gehoor

inkorting

Renale en urinêre

afwykings

urinêre

retensie,

disurie,

mikturasie

dringendheid

Page 27 of 31

Voortplanting-

stelsel en

borsafwykings

erektiele

disfunksie

amenorree

Kardiale

afwykings

tagikardie palpitasies

Vaskulêre

afwykings

hipotensie vasodilatasie

Respiratoriese en

torakale en

mediastinale

afwykings

dispnee

disfonie, hoes

Vel en

subkutaneuse

weefsel

afwykings

pruritus velreaksies/

uitslag

droë vel urtikarie

Besering,

vergiftiging en

prosedure

komplikasies

besering van

ongelukke

Algemene

afwykings en

toedieningsplek

toestande

hiperhidrose tot

en met koue

rillings, astenie

fisiese

afhanklikheid

met

geneesmiddel

onttrekking-

sindroom, pyn

(bv. borspyn),

malaise,

edeem

gewigs-

toename,

gewigs-

afname, dors

Simptome geassosieer met onttrekkingsindroom:

Die opioïed onthouding- of onttrekkingsindroom word gekarakteriseer deur sommige van die

volgende: rusteloosheid, lakrimasie, rinorree, gaap, sweet, koue rillings, mialgie en midriase.

Ander simptome mag ook ontwikkel wat die volgende insluit: geïrriteerdheid, angs, rugpyn,

gewrigspyn, swakheid, abdominale krampe, slapeloosheid, naarheid, anoreksie, braking, diarree of

verhoogde bloeddruk, - respiratoriese snelheid of - hartsnelheid.

Page 28 of 31

Die ontwikkeling van psigologiese afhanklikheid (verslawing) aan opioïed analgetika by pasiënte

waarvan pyn behoorlik beheer word, is as seldsaam aangemeld. Data om die ware insidensie van

psigologiese afhanlikheid by kroniese pasiënte vas te stel, is egter nie beskikbaar nie.

BEKENDE SIMPTOME VAN OORDOSERING EN DIE BESONDERHEDE VAN BEHANDELING

DAARVAN

Tekens van oksikodoontoksisiteit en -oordosering is: klein pupille, respiratoriese depressie en

hipotensie. Sirkulatoriese versaking en slaperigheid wat tot stupor en verdiepte koma vorder, slap

skelet spiere, bradikardie en dood kan voorkom in meer erge gevalle.

Behandeling van oksikodoon oordosis: primêre aandag moet geskenk word aan die instelling

van 'n patente lugweg en die instelling van ondersteunende of beheerde ventilasie.

In geval van massiewe oordosering, dien naloksoon intraveneus toe (0,4 tot 2 mg vir 'n

volwassene en 0,01 mg/kg liggaamsgewig vir kinders) indien die pasiënt in 'n koma is of

respiratoriese depressie teenwoordig is. Herhaal die dosis met 2 minute intervalle indien daar

geen respons is nie. Indien herhaaldosisse nodig is, dan is 'n infusie van 60 % van die

aanvanklike dosis per uur 'n bruikbare beginpunt. 'n Oplossing van 10 mg wat opgemaak is tot 50

ml dekstrose sal 'n 200 mikrogram/ml vir infusie lewer met gebruik van 'n IV pomp (dosis aangepas

tot die kliniese respons). Infusies is nie 'n plaasvervanger vir dikwelse oorsig van die pasiënt se

kliniese toestand nie. Intramuskulêre naloksoon is 'n alternatief in die geval waar IV toegang nie

moontlik is nie.

Siende die werkingsduur van naloksoon relatief kort is, moet die pasiënt versigtig gemoniteer word

totdat spontane asemhaling betroubaar teruggekeer het. Naloksoon is 'n kompeterende antagonis

en groot dosisse (4 mg) mag nodig wees by ernstig vergiftigde pasiënte.

Vir ‘n minder ernstige oordosis, dien 0,2 mg naloksoon intraveneus toe, gevolg deur inkremente

van 0,1 mg elke 2 minute, indien nodig.

Naloksoon moet in die afwesigheid van kliniese beduidende respiratoriese of sirkulatoriese

depressie sekondêr tot oksikodoon oordosis toegedien word. Naloksoon moet versigtig toegedien

word aan persone wat bekend is of verdink word van fisiese afhanklikheid van oksikodoon. In

Page 29 of 31

sulke gevalle kan 'n skielike of volledige omkering van opioïed effekte, pyn en 'n akute

onttrekkingsindroom presipiteer.

Addisionele/ander oorwegings: Oorweeg geaktiveerde steenkool (50 g vir volwassenes, 10 - 15

g vir kinders), indien 'n groot hoeveelheid binne 1 uur ingeneem is, op voorwaarde dat die lugweg

beskerm kan word. Dit mag ‘n regverdigende aanname wees dat die laat toediening van

geaktiveerde steenkool voordelig kan wees vir verlengde vrystellingspreparate, alhoewel daar nie

bewys is om dit te ondersteun nie.

OxyContin® Prolonged Release Tablets sal voortgaan om vrygestel te word en toevoeg tot die

oksikodoonlading tot en met 12 uur na toediening en beheer van oksikodoon-oordosis moet

daarvolgens aangepas word. Gastriese inhoud moet daarom geledig word, aangesien dit

voordelig kan wees om die ongeabsorbeerde geneesmiddel te verwyder, veral as 'n verlengde

vrystellingsvorm geneem is.

IDENTIFIKASIE

OxyContin® 5 mg Prolonged Release Tablets is vaal blou, ronde, bikonvekse, filmbedekte

tablette wat met OC op een kant en 5 op die ander kant gedruk is.

OxyContin® 10 mg Prolonged Release Tablets is wit, ronde, bikonvekse, filmbedekte tablette

wat met OC op een kant en 10 op die ander kant gedruk is.

OxyContin® 20 mg Prolonged Release Tablets is pienk, ronde, bikonvekse, filmbedekte tablette


OxyContin® 40 mg Prolonged Release Tablets is geel, ronde, bikonvekse, filmbedekte tablette


OxyContin® 80 mg Prolonged Release Tablets is groen, ronde, bikonvekse, filmbedekte tablette


Page 30 of 31

AANBIEDING

OxyContin® 5 mg Prolonged Release Tablets word verskaf in deursigtige PVC en aluminium

foelie stulpverpakkings van 28.









BERGINGSINSTRUKSIES

Bewaar by of benede 25 ⁰C. Bewaar in oorspronkilke verpakking in die kartonhouer om sodoende

teen lig te beskerm. Bewaar hierdie medisyne buite die bereik van kinders.

REGISTRASIENOMMERS:

Suid Afrika: S6






Namibië: NS4




Page 31 of 31



Botswana: S1A






NAAM EN BESIGHEIDSADRES VAN DIE HOUER VAN DIE REGISTRASIESERTIFIKAAT:

Mundipharma (Edms) Bpk

2de vloer, Mariendahl House

Newlands on Main

Claremont

7708

www.mundipharma.co.za

DATUM VAN PUBLIKASIE VAN DIE VOUBILJET:

9 Oktober 2009

® = OxyContin is 'n geregistreerde handelsmerk.

http://www.mundipharma.co.za/

Documents

SCHEDULING STATUS PROPRIETARY NAMES AND DOSAGE FORM … · Page 1 of 31 SCHEDULING STATUS PROPRIETARY NAMES AND DOSAGE FORM OxyContin® 5 mg Prolonged Release Tablets OxyContin®