Page 1 of 31 SCHEDULING STATUS PROPRIETARY NAMES AND DOSAGE FORM. OxyContin 5 mg Prolonged Release Tablets. OxyContin 10 mg Prolonged Release Tablets

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1 SCHEDULING STATUS S6 PROPRIETARY NAMES AND DOSAGE FORM OxyContin 5 mg Prolonged Release Tablets OxyContin 10 mg Prolonged Release Tablets OxyContin 20 mg Prolonged Release Tablets OxyContin 40 mg Prolonged Release Tablets OxyContin 80 mg Prolonged Release Tablets COMPOSITION Each OxyContin 5 mg Prolonged Release Tablet contains 5 mg of oxycodone hydrochloride. Each OxyContin 10 mg Prolonged Release Tablet contains 10 mg of oxycodone hydrochloride. Each OxyContin 20 mg Prolonged Release Tablet contains 20 mg of oxycodone hydrochloride. Each OxyContin 40 mg Prolonged Release Tablet contains 40 mg of oxycodone hydrochloride. Each OxyContin 80 mg Prolonged Release Tablet contains 80 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. Page 1 of 31

2 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. Page 2 of 31

3 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 t 1/2 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 t 1/2 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 Page 3 of 31

4 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. Page 4 of 31

5 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. Page 5 of 31

6 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 C max by 11 %, AUC by 13 % and t 1/2 elimination by 14 %. Also, an increase in noroxycodone level was observed, (C max by 50 %, AUC by 85 % and t 1/2 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. Page 6 of 31

7 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. Page 7 of 31

8 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. troublesome, oxycodone may be combined with an anti-emetic. If nausea and vomiting are The reactions are listed as MeDRA preferred term by system organ class and absolute frequency. Body System Frequency of Occurrence Page 8 of 31

9 Very Common Common Uncommon Rare Very Rare > 10 % > 1 % and < > 0.1 % and < > 0.01 % and < < 0.01 % 10 % 1 % 0.1 % Gastrointestin constipation, abdominal mouth melaena, ileus al disorders nausea, pain, ulceration, tooth disorder, vomiting diarrhoea, stomatitis, gingival dry mouth, flatulence bleeding, hiccups, dysphagia dyspepsia Hepatobiliary biliary colic hepatic disorders enzymes increased Metabolism decreased dehydration, and nutrition apetite up to increased disorders loss of appetite appetite Nervous headache, syncope, concentration convulsions speech system dizziness, paraesthesia impaired, (especially in disorder disorders sedation migraine, persons with (somnolence up dysgeusia, epileptic to a depressed hypermyotonia, disorder or level of tremor, predisposition consciousness) involuntary to muscle convulsions), contractions, amnesia hypoaesthesia, abnormal coordination Page 9 of 31

10 Psychiatric disorders Infections and infestations Immune system disorders Eye disorders Ear and labyrinth disorders Renal and urinary disorders altered mood and personality change (e.g. anxiety, depression, euphoric mood), decreased activity, restlessness, psychomotor hyperactivity, agitation, nervousness, insomnia, abnormal thinking, confusion urinary retention, dysuria, micturition urgency perception disturbances (e.g. hallucination, derealisation), reduced libido hypersensitivity visual disturbances hearing impaired herpes simplex anaphylactic reaction Page 10 of 31

11 Reproductive erectile amenorrhoea system and dysfunction breast disorders Cardiac tachycardia palpitations disorders Vascular hypotension vasodilatation disorders Respiratory, dyspnoea dysphonia, thoracic and cough mediastinal disorders Skin and pruritus skin reactions dry skin urticaria subcutaneous / rash tissue disorders Injury, injury from poisoning and accidents procedural complications General hyperhidrosis physical weight disorders and up to chills, dependence increase, administration asthenia with drug weight site conditions withdrawal decrease, syndrome, pain thirst (e.g. chest pain), malaise, oedema 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 11 of 31

12 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, Page 12 of 31

13 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, 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, imprinted with OC on one side and 20 on the other side. OxyContin 40 mg Prolonged Release Tablets are yellow, round, bi-convex, film coated tablets, imprinted with OC on one side and 40 on the other side. OxyContin 80 mg Prolonged Release Tablets are green, round, bi-convex, film coated tablet, imprinted with OC on one side and 80 on the other side. PRESENTATION OxyContin 5 mg Prolonged Release Tablets are supplied in clear PVC and aluminium foil blister packs of 28. OxyContin 10 mg Prolonged Release Tablets are supplied in clear PVC and aluminium foil blister packs of 28. Page 13 of 31

14 OxyContin 20 mg Prolonged Release Tablets are supplied in clear PVC and aluminium foil blister packs of 28. OxyContin 40 mg Prolonged Release Tablets are supplied in clear PVC and aluminium foil blister packs of 28. OxyContin 80 mg Prolonged Release Tablets are supplied in clear PVC and aluminium foil blister packs of 28. STORAGE INSTRUCTIONS Store at or below 25 ⁰ C. 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 OxyContin 10 mg Prolonged Release Tablets: 41/2.9/1099 OxyContin 20 mg Prolonged Release Tablets: 41/2.9/1100 OxyContin 40 mg Prolonged Release Tablets: 41/2.9/1101 OxyContin 80 mg Prolonged Release Tablets: 41/2.9/1102 Namibia: NS4 OxyContin 5 mg Prolonged Release Tablets: 12/2.9/0259 OxyContin 10 mg Prolonged Release Tablets: 12/2.9/0260 OxyContin 20 mg Prolonged Release Tablets: 12/2.9/0261 OxyContin 40 mg Prolonged Release Tablets: 12/2.9/0262 OxyContin 80 mg Prolonged Release Tablets: 12/2.9/0263 Botswana: S1A OxyContin 5 mg Prolonged Release Tablets: BOT Page 14 of 31

15 OxyContin 10 mg Prolonged Release Tablets: BOT OxyContin 20 mg Prolonged Release Tablets: BOT OxyContin 40 mg Prolonged Release Tablets: BOT OxyContin 80 mg Prolonged Release Tablets: BOT NAME AND BUSINESS ADDRESS OF THE HOLDER OF THE CERTIFICATE OF REGISTRATION Mundipharma (Pty) Ltd 2 nd floor Mariendahl House Newlands on Main Claremont DATE OF PUBLICATION OF THIS PACKAGE INSERT 9 October 2009 = OxyContin is a registered trademark. Page 15 of 31

16 SKEDULERINGSTATUS S6 EIENDOMSNAAM EN DOSEERVORM OxyContin 5 mg Prolonged Release Tablets OxyContin 10 mg Prolonged Release Tablets OxyContin 20 mg Prolonged Release Tablets OxyContin 40 mg Prolonged Release Tablets OxyContin 80 mg Prolonged Release Tablets SAMESTELLING Elke OxyContin 5 mg Prolonged Release Tablet bevat 5 mg oksikodoonhidrochloried. Elke OxyContin 10 mg Prolonged Release Tablet bevat 10 mg oksikodoonhidrochloried. Elke OxyContin 20 mg Prolonged Release Tablet bevat 20 mg oksikodoonhidrochloried. Elke OxyContin 40 mg Prolonged Release Tablet bevat 40 mg oksikodoonhidrochloried. Elke OxyContin 80 mg Prolonged Release Tablet bevat 80 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 Page 16 of 31

17 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 bioekwivalent 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 17 of 31

18 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 t 1/2 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 t 1/2 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 18 of 31

19 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 19 of 31

20 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 20 of 31

21 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 21 of 31

22 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 C maks van 11 %, AOK van 13 % en t 1/2 eliminasie van 14 %. Daar is ook 'n verhoging in noroksikodoonvlak opgemerk, (C maks van 50 %, AOK van 85 % en t 1/2 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 22 of 31

23 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 23 of 31

24 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 Nie algemeen Seldsaam Baie Algemeen > 1 % en < 10 > 0.1 % en < 1 > 0.01 % en < Seldsaam > 10 % % % 0.1 % < 0.01 % Gastroïntestinale konstipasie, abdominale mond melaena, ileus afwykings naarheid, pyn, ulserasie, tandafwyking, braking diarree, stomatitis, tandvleis- droë mond, hik, winderigheid bloeding, dispepsie disfagie Hepatobiliêre biliêre koliek verhoogde afwykings hepatiese ensieme Metabolisme en verlaag aptyt dehidrasie, voedings- tot verlies aan verhoogde afwykings aptyt aptyt Page 24 of 31

25 Senuweestelsel hoofpyn, sinkopee, ingekorte konvulsies spraak afwykings duiseligheid, parestesie konsentrasie, (veral by afwyking sedasie migraine, persone met (slaperigheid dysgeusie, epileptiese tot by vlak hipermiotonie, afwyking of van bewing, neiging tot bewusteloos- onwillekeurige konvulsies), heid) spiersame- amnesie trekkings, hipo-astesie, abnormale koördinasie Page 25 of 31

26 Psigiatriese afwykings Infeksies en infestasies persepsie steurnisse (bv. hallusinasies, derealisering), verlaagde libido herpes simplex Immuunstelsel afwykings Oogafwykings Oor en Labarintafwykings veranderde gemoed en persoonlikheids -verandering (bv. angs, depressie, euforiese gemoed), verlaagde aktiwiteit, rusteloosheid, psigomotoriese hiper-aktiwiteit, agitasie, senuweeagtigheid, insomnie, abnormale denke, verwarring hipersensitiwiteit visuele steurnisse gehoor inkorting anafilaktiese reaksie Renale en urinêre afwykings urinêre retensie, disurie, mikturasie dringendheid Page 26 of 31

27 Voortplanting- erektiele amenorree stelsel en disfunksie borsafwykings Kardiale tagikardie palpitasies afwykings Vaskulêre hipotensie vasodilatasie afwykings Respiratoriese en dispnee disfonie, hoes torakale en mediastinale afwykings Vel en pruritus velreaksies/ droë vel urtikarie subkutaneuse uitslag weefsel afwykings Besering, besering van vergiftiging en ongelukke prosedure komplikasies Algemene hiperhidrose tot fisiese gewigs- afwykings en en met koue afhanklikheid toename, toedieningsplek rillings, astenie met gewigs- toestande geneesmiddel afname, dors onttrekkingsindroom, pyn (bv. borspyn), malaise, edeem 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 27 of 31

28 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 28 of 31

29 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, 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 wat met OC op een kant en 20 op die ander kant gedruk is. OxyContin 40 mg Prolonged Release Tablets is geel, ronde, bikonvekse, filmbedekte tablette wat met OC op een kant en 40 op die ander kant gedruk is. OxyContin 80 mg Prolonged Release Tablets is groen, ronde, bikonvekse, filmbedekte tablette wat met OC op een kant en 80 op die ander kant gedruk is. Page 29 of 31

30 AANBIEDING OxyContin 5 mg Prolonged Release Tablets word verskaf in deursigtige PVC en aluminium foelie stulpverpakkings van 28. OxyContin 10 mg Prolonged Release Tablets word verskaf in deursigtige PVC en aluminium foelie stulpverpakkings van 28. OxyContin 20 mg Prolonged Release Tablets word verskaf in deursigtige PVC en aluminium foelie stulpverpakkings van 28. OxyContin 40 mg Prolonged Release Tablets word verskaf in deursigtige PVC en aluminium foelie stulpverpakkings van 28. OxyContin 80 mg Prolonged Release Tablets word verskaf in deursigtige PVC en aluminium foelie stulpverpakkings van 28. BERGINGSINSTRUKSIES Bewaar by of benede 25 ⁰ C. 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 OxyContin 5 mg Prolonged Release Tablets: 41/2.9/1098 OxyContin 10 mg Prolonged Release Tablets: 41/2.9/1099 OxyContin 20 mg Prolonged Release Tablets: 41/2.9/1100 OxyContin 40 mg Prolonged Release Tablets: 41/2.9/1101 OxyContin 80 mg Prolonged Release Tablets: 41/2.9/1102 Namibië: NS4 OxyContin 5 mg Prolonged Release Tablets: 12/2.9/0259 OxyContin 10 mg Prolonged Release Tablets: 12/2.9/0260 OxyContin 20 mg Prolonged Release Tablets: 12/2.9/0261 Page 30 of 31

31 OxyContin 40 mg Prolonged Release Tablets: 12/2.9/0262 OxyContin 80 mg Prolonged Release Tablets: 12/2.9/0263 Botswana: S1A OxyContin 5 mg Prolonged Release Tablets: BOT OxyContin 10 mg Prolonged Release Tablets: BOT OxyContin 20 mg Prolonged Release Tablets: BOT OxyContin 40 mg Prolonged Release Tablets: BOT OxyContin 80 mg Prolonged Release Tablets: BOT NAAM EN BESIGHEIDSADRES VAN DIE HOUER VAN DIE REGISTRASIESERTIFIKAAT: Mundipharma (Edms) Bpk 2 de vloer, Mariendahl House Newlands on Main Claremont DATUM VAN PUBLIKASIE VAN DIE VOUBILJET: 9 Oktober 2009 = OxyContin is 'n geregistreerde handelsmerk. Page 31 of 31