- 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
PosologyThe dosage depends on the intensity of pain and the patient's individual susceptibility to the treatment. The following general dose recommendations apply:
Adults and adolescents over 12 years of age
Dose initiationIn general, the initial dose for opioid naïve patients is 5 mg oxycodone hydrochloride given at intervals of 6 hours. Patients already receiving opioids may start treatment with higher doses taking into account their experience with former opioid therapies.Patients receiving oral morphine before oxycodone 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 should be noted that this is a guide to the dose of oxycodone hydrochloride capsules required. Inter-patient variability requires that each patient is carefully titrated to the appropriate dose.
Dose adjustmentIncreasing severity of pain will require an increased dose of Lynlor capsules. The dose should be carefully titrated, as frequently as once a day if necessary, to achieve pain relief. In doing so, the dosing interval may be reduced to 4 hours. The correct dose for any individual patient is that which controls the pain and is well tolerated throughout the dosing period.The majority of patients will not require a daily dose greater than 400 mg. However, a few patients may require higher doses.In patients receiving a prolonged-release formulation of oxycodone, Lynlor capsules may be used to control breakthrough pain. The dose should be adjusted according to the patient´s need but as a general rule the single dose should amount to 1/8 to 1/6 of the daily dose of the prolonged-release formulation. The rescue medication should not be used more frequently than every 6 hours.
Method of administrationFor oral use.Lynlor capsules should be administered using a fixed schedule at the dose determined but not more often than every 4 to 6 hours.The capsules may be taken with or without food with a sufficient amount of liquid.The medicinal product should not be taken with alcoholic beverages.
Duration of administrationLynlor capsules should not be taken longer than necessary. If long-term treatment is necessary due to the type and severity of the illness careful and regular monitoring is required to determine whether and to what extent treatment should be continued. If opioid therapy is no longer indicated it may be advisable to reduce the daily dose gradually in order to prevent symptoms of a withdrawal syndrome.
Paediatric populationLynlor capsules is not recommended for children under 12 years of age as the safety and efficacy has not been established.
Elderly patientsThe lowest dose should be administered with careful titration to pain control.
Patients with renal or hepatic impairmentThe dose initiation should follow a conservative approach in these patients. The recommended adult starting dose should be reduced by 50% (for example a total daily dose of 10 mg orally in opioid naïve patients), and each patient should be titrated to adequate pain control according to their clinical situation.
Risk patientsRisk patients, for example patients with low body weight or slow metabolism of medicinal products, should initially receive half the recommended adult dose if they are opioid naïve.Therefore the lowest recommended dose, i.e. 5 mg, may not be suitable as a starting dose.Dose titration should be performed in accordance with the individual clinical situation and using the appropriate formulation as available.
Paediatric populationOxycodone has not been studied in children younger than 12 years of age. The safety and efficacy of the capsules have not been demonstrated and the use in children younger than 12 years of age is therefore not recommended.
PregnancyThere are limited data from the use of oxycodone in pregnant women. Infants born to mothers who have received opioids during the last 3 to 4 weeks before giving birth should be monitored for respiratory depression. Withdrawal symptoms may be observed in the newborn of mothers undergoing treatment with oxycodone. Oxycodone passes into the placenta. Animal studies with oxycodone have not revealed any teratogenic or embryotoxic effects. Oxycodone should only be used during pregnancy if the benefit outweighs the possible risks to the unborn child or neonate.
LactationOxycodone may be secreted in breast milk and may cause respiratory depression in the newborn. Oxycodone should, therefore, not be used in breastfeeding mothers.
|Very common||≥ 1/10|
|Common||≥ 1/100 to <1/10|
|Uncommon||≥ 1/1,000 to <1/100|
|Rare||≥1/10,000 to <1/1,000|
|Frequency unknown||Cannot be estimated from the available data|
|Infections and infestations|
|Blood and lymphatic system disorders|
|Immune system disorders|
|Frequency unknown:||Anaphylactic responses.|
|Uncommon:||Syndrome of inappropriate antidiuretic hormone secretion.|
|Metabolism and nutrition disorders|
|Common:||Anorexia; loss of appetite.|
|Common:||Various psychological adverse reactions including changes in mood (e.g. anxiety, depression), changes in activity (mostly suppression sometimes associated with lethargy, occasionally increase with nervousness and insomnia) and changes in cognitive performance (abnormal thinking, confusional state).|
|Uncommon:||Change in perception such as depersonalisation, hallucinations; decreased libido. Agitation; affect lability; euphoric mood; drug dependence (see section 4.4)|
|Nervous system disorders|
|Very common:||Somnolence; dizziness; headache.|
|Uncommon:||Both increased and decreased muscle tone; involuntary muscle contractions; Convulsions, in particular in epileptic patients or patients with tendency to convulsions; hypertonia; hypoaesthesia; Speech disorder; syncope; paraesthesia; coordination disturbances; change in taste; migraine; vertigo, amnesia.|
|Uncommon:||Lacrimation disorder; miosis; visual impairment.|
|Ear and labyrinth disorders|
|Uncommon:||Supraventricular tachycardia; palpitations (in the context of withdrawal syndrome).|
|Rare:||Hypotension; orthostatic hypotension.|
|Respiratory, thoracic and mediastinal disorders|
|Common:||bronchospasm; dyspnoea; hiccups.|
|Uncommon:||Respiratory depression; cough; pharyngitis; rhinitis; voice changes.|
|Very common:||Constipation; nausea; vomiting.|
|Common:||Dry mouth; abdominal pain; diarrhoea; dyspepsia.|
|Uncommon:||Dysphagia; oral ulcers; gingivitis; stomatitis; flatulence; eructation; ileus.|
|Rare:||Gum bleeding; tarry stools; tooth staining and damage.|
|Frequency unknown:||dental caries.|
|Uncommon:||Increased hepatic enzymes.|
|Frequency unknown:||Cholestasis; biliary colic|
|Skin and subcutaneous tissue disorders|
|Common:||Skin eruptions including rash; hyperhidrosis.|
|Very rare:||exfoliative dermatitis.|
|Musculoskeletal and connective tissue disorders|
|Renal and urinary disorders|
|Common:||Increased urge to urinate.|
|Reproductive system and breast disorders|
|General disorders and administration site conditions|
|Uncommon:||Pain (e.g. chest pain); chills, oedema; peripheral oedema; malaise; physical dependence with withdrawal syndrome; drug tolerance; thirst.|
|Rare:||Weight changes (increase or decrease); cellulitis.|
|Injury, poisoning and procedural complications|
Counteractive measures:As constipation is a very common side effect it may be helpful to instruct the patient that this may be prevented by a fiber enriched diet and increased intake of fluids.For nausea and vomiting, prescribing antiemetics may be considered.
Reporting of suspected adverse reactionsReporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions via the Yellow Card Scheme; website: www.mhra.gov.uk/yellowcard.
Symptoms of overdoseMiosis, respiratory depression, somnolence, reduced skeletal muscle tone and drop in blood pressure. In severe cases circulatory collapse, stupor, coma, bradycardia and non-cardiogenic lung oedema, hypotension and death may occur; abuse of high doses of strong opioids such as oxycodone can be fatal.
Therapy of overdosePrimary attention should be given to the establishment of a patent airway and institution of assisted or controlled ventilation.In the event of overdosing intravenous administration of an opiate antagonist (e.g. 0.4-2 mg intravenous naloxone) may be indicated. Administration of single doses must be repeated depending on the clinical situation at intervals of 2 to 3 minutes. Intravenous infusion of 2 mg of naloxone in 500 ml isotonic saline or 5% dextrose solution (corresponding to 0.004 mg naloxone/ml) is possible. The rate of infusion should be adjusted to the previous bolus injections and the response of the patient.Gastric lavage can be taken into consideration. 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.For speeding up the passage a suitable laxative (e.g. a PEG based solution) may be useful.Supportive measures (artificial respiration, oxygen supply, administration of vasopressors and infusion therapy) should, if necessary, be applied in the treatment of accompanying circulatory shock. Upon cardiac arrest or cardiac arrhythmias cardiac massage or defibrillation may be indicated. If necessary, assisted ventilation as well as maintenance of water and electrolyte balance.
Absorption:The absolute bioavailability of oxycodone is 60-87% following oral administration and the peak plasma concentration is achieved after approximately 1 to 1.5 hours.
Distribution:At steady state, the volume of distribution of oxycodone amounts to 2.6 l/kg and plasma protein binding to 38-45%.
Biotransformation:Oxycodone is metabolised in the intestine and liver via the P450 cytochrome system to noroxycodone (CYP3A4) and oxymorphone (CYP2D6) as well as to several glucuronide conjugates. The contribution of the metabolites to the overall pharmacodynamic effect is irrelevant.
Elimination:At steady state, the plasma elimination half-life amounts to approximately 3 hours. Oxycodone and its metabolites are excreted via urine. Faecal excretion has not been studied.
Linearity/non-linearity:After administration of the capsule formulation of oxycodone hydrochloride the plasma concentration increases linear over the dose range of 5 to 20 mg.
Capsule content:Microcrystalline celluloseMagnesium stearate
Capsule shell:GelatineSodium laurilsulfateTitanium dioxide (E71)Iron oxide yellow (E172)Iron oxide red (E172)Indigotine (E132)
Printing ink:ShellacIron oxide black (E172)Potassium hydroxide (for pH-adjustment)
Instructions for use of child resistant blisters:1. Do not push the capsule directly out of the pocket2. Separate one blister cell from the strip at the perforations3. Carefully peel off the backing to open the pocket
Actavis UK Ltd
Whiddon Valley, Barnstaple, Devon, EX32 8NS, UK
+44 (0)1271 346 106
+44 (0)1271 311 200
+44 (0)1271 385 257