- 1. Name of the medicinal product
- 2. Qualitative and quantitative composition
- 3. Pharmaceutical form
- 4. Clinical particulars
- 4.1 Therapeutic indications
- 4.2 Posology and method of administration
- 4.3 Contraindications
- 4.4 Special warnings and precautions for use
- 4.5 Interaction with other medicinal products and other forms of interaction
- 4.6 Fertility, pregnancy and lactation
- 4.7 Effects on ability to drive and use machines
- 4.8 Undesirable effects
- 4.9 Overdose
- 5. Pharmacological properties
- 5.1 Pharmacodynamic properties
- 5.2 Pharmacokinetic properties
- 5.3 Preclinical safety data
- 6. Pharmaceutical particulars
- 6.1 List of excipients
- 6.2 Incompatibilities
- 6.3 Shelf life
- 6.4 Special precautions for storage
- 6.5 Nature and contents of container
- 6.6 Special precautions for disposal and other handling
- 7. Marketing authorisation holder
- 8. Marketing authorisation number(s)
- 9. Date of first authorisation/renewal of the authorisation
- 10. Date of revision of the text
- 11. Legal category
Elderly and adults over 18 years:Longtec tablets should be taken at 12-hourly intervals. The dosage is dependent on the severity of the pain, and the patient's previous history of analgesic requirements.Longtec tablets are not intended for use as a prn analgesic.Increasing severity of pain will require an increased dosage of Longtec tablets, using the 5 mg, 10 mg, 20 mg, 40 mg or 80 mg tablet strengths, either alone or in combination, to achieve pain relief. The correct dosage for any individual patient is that which controls the pain and is well tolerated for a full 12 hours. Patients should be titrated to pain relief unless unmanageable adverse drug reactions prevent this. If higher doses are necessary, increases should be made in 25% - 50% increments. The need for escape medication more than twice a day indicates that the dosage of Longtec tablets should be increased.The usual starting dose for opioid naïve patients or patients presenting with severe pain uncontrolled by weaker opioids is 10 mg, 12-hourly. Some patients may benefit from a starting dose of 5 mg to minimise the incidence of side effects. The dose should then be carefully titrated, as frequently as once a day if necessary, to achieve pain relief. For the majority of patients, the maximum dose is 200 mg 12-hourly. However, a few patients may require higher doses. Doses in excess of 1000 mg have been recorded.Patients receiving oral morphine before Longtec therapy should have their daily dose based on the following ratio: 10 mg of oral oxycodone is equivalent to 20 mg of oral morphine. It must be emphasised that this is a guide to the dose of Longtec tablets required. Inter-patient variability requires that each patient is carefully titrated to the appropriate dose.Controlled pharmacokinetic studies in elderly patients (aged over 65 years) have shown that, compared with younger adults, the clearance of oxycodone is only slightly reduced. No untoward adverse drug reactions were seen based on age, therefore adult doses and dosage intervals are appropriate.
Children under 18 years:Longtec should not be used in patients under 18 years.
Adults with mild to moderate renal impairment and mild hepatic impairment:The plasma concentration in this population may be increased. Therefore dose initiation should follow a conservative approach. Patients should be started on Longtec 5 mg 12-hourly or OxyNorm liquid 2.5 mg 6-hourly and titrated to pain relief as described above.
Use in non-malignant pain:Opioids are not first line therapy for chronic non-malignant pain, nor are they recommended as the only treatment. Types of chronic pain which have been shown to be alleviated by strong opioids include chronic osteoarthritic pain and intervertebral disc disease. The need for continued treatment in non-malignant pain should be assessed at regular intervals.
Cessation of therapy:When a patient no longer requires therapy with oxycodone, it may be advisable to taper the dose gradually to prevent symptoms of withdrawal.
|Immune system disorders||Anaphylactic reaction|
|Metabolism and nutritional disorders||Anorexia||Dehydration|
|Psychiatric disorders||Anxiety||Affect lability|
|Nervous system disorders||Headache||Amnesia|
|Muscle contractions involuntary|
|Ear and labyrinth disorders||Vertigo|
|Cardiac disorders||Supraventricular tachycardia|
|Respiratory, thoracic and mediastinal disorders||Bronchospasm||Respiratory depression|
|Gastrointestinal disorders||Constipation||Dental caries|
|Hepato-biliary disorders||Biliary colic|
|Increased hepatic enzymes|
|Skin and subcutaneous tissue disorders||Hyperhidrosis||Dry skin|
|Musculoskeletal and connective tissue disorders||Muscular rigidity|
|Renal and urinary disorders||Urinary retention|
|Reproductive system and breast disorders||Amenorrhoea|
|General disorders and||Asthenic conditions||Drug tolerance|
|administration site conditions||Chills||Oedema|
|Drug withdrawal syndrome|
Tolerance and Dependence:The patient may develop tolerance to the drug with chronic use and require progressively higher doses to maintain pain control. Prolonged use of Longtec tablets may lead to physical dependence and a withdrawal syndrome may occur upon abrupt cessation of therapy. When a patient no longer requires therapy with oxycodone, it may be advisable to taper the dose gradually to prevent symptoms of withdrawal. The opioid abstinence or withdrawal syndrome is characterised by some or all of the following: restlessness, lacrimation, rhinorrhea, yawning, perspiration, chills, myalgia, mydriasis and palpitations. Other symptoms also may develop, including: irritability, anxiety, backache, joint pain, weakness, abdominal cramps, insomnia, nausea, anorexia, vomiting, diarrhoea, or increased blood pressure, respiratory rate or heart rate.
Endocrine systemOpioids may influence the hypothalamic-pituitary-adrenal or gonadal axes. Some changes that can be seen include an increase in serum prolactin, and decreases in plasma cortisol and testosterone. Clinical symptoms may be manifest from these hormonal changes.
Other pharmacological effectsIn- vitro and animal studies indicate various effects of natural opioids, such as morphine, on components of the immune system; the clinical significance of these findings is unknown. Whether oxycodone, a semisynthetic opioid, has immunological effects similar to morphine is unknown.
Clinical studiesThe efficacy of Longtec tablets has been demonstrated in cancer pain, post-operative pain and severe non-malignant pain such as diabetic neuropathy, postherpetic neuralgia, low back pain and osteoarthritis. In the latter indication, treatment was continued for up to 18 months and proved effective in many patients for whom NSAIDs alone provided inadequate relief. The efficacy of Longtec tablets in neuropathic pain was confirmed by three placebo-controlled studies.In patients with chronic non-malignant pain, maintenance of analgesia with stable dosing was demonstrated for up to three years.
ElderlyThe AUC in elderly subjects is 15% greater when compared with young subjects.
GenderFemale 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 impairmentPreliminary data from a study of patients with mild to moderate renal dysfunction show peak plasma oxycodone and noroxycodone concentrations approximately 50% and 20% higher, respectively and AUC values for oxycodone, noroxycodone and oxymorphone approximately 60%, 60% and 40% higher than normal subjects, respectively. There was an increase in t½ of elimination for oxycodone of only 1 hour.
Patients with mild to moderate hepatic impairmentPatients with mild to moderate hepatic dysfunction showed peak plasma oxycodone and noroxycodone concentrations approximately 50% and 20% higher, respectively, than normal subjects. AUC values were approximately 95% and 75% higher, respectively. Oxymorphone peak plasma concentrations and AUC values were lower by 15% to 50%. The t½ elimination for oxycodone increased by 2.3 hours.
TeratogenicityOxycodone had no effect on fertility or early embryonic development in male and female rats at doses as high as 8 mg/kg/d. Also, oxycodone did not induce any deformities in rats at doses as high as 8 mg/kg/d or in rabbits at doses as high as 125 mg/kg/d. Dose-related increases in developmental variations (increased incidences of extra (27) presacral vertebrae and extra pairs of ribs) were observed in rabbits when the data for individual foetuses were analyzed. However, when the same data were analyzed using litters as opposed to individual foetuses, there was no dose-related increase in developmental variations although the incidence of extra presacral vertebrae remained significantly higher in the 125 mg/kg/d group compared to the control group. Since this dose level was associated with severe pharmacotoxic effects in the pregnant animals, the foetal findings may have been a secondary consequence of severe maternal toxicity. In a study of peri- and postnatal development in rats, maternal body weight and food intake parameters were reduced for doses ≥ 2 mg/kg/d compared to the control group. Body weights were lower in the F1 generation from maternal rats in the 6 mg/kg/d dosing group. There were no effects on physical, reflexological, or sensory developmental parameters or on behavioural and reproductive indices in the F1 pups (the NOEL for F1 pups was 2 mg/kg/d based on body weight effects seen at 6 mg/kg/d). There were no effects on the F2 generation at any dose in the study.
CarcinogenicityStudies of oxycodone in animals to evaluate its carcinogenic potential have not been conducted owing to the length of clinical experience with the drug substance.
MutagenicityThe results of in-vitro and in-vivo studies indicate that the genotoxic risk of oxycodone to humans is minimal or absent at the systemic oxycodone concentrations that are achieved therapeutically.Oxycodone was not genotoxic in a bacterial mutagenicity assay or in an in-vivo micronucleus assay in the mouse. Oxycodone produced a positive response in the in-vitro mouse lymphoma assay in the presence of rat liver S9 metabolic activation at dose levels greater than 25 μg/mL. Two in-vitro chromosomal aberrations assays with human lymphocytes were conducted. In the first assay, oxycodone was negative without metabolic activation but was positive with S9 metabolic activation at the 24 hour time point but not at other time points or at 48 hour after exposure. In the second assay, oxycodone did not show any clastogenicity either with or without metabolic activation at any concentration or time point.
|5 mg||Brilliant blue (E133)|
|20 mg and 40 mg||Polysorbate 80, iron oxide (E172).|
|80 mg||Hydroxypropylcellulose, iron oxide (E172), indigo carmine (E132)|
Qdem Pharmaceuticals Limited
Cambridge Science Park, Milton Road, Cambridge, CB4 0AB
+44(0)1223 426 929
+44(0)1223 426 929
+44(0)1223 426 929