- oxycodone hydrochloride
POM: Prescription only medicine
This information is intended for use by health professionals
Lynlor 5mg Capsules, hard
Each capsule contains 5 mg oxycodone hydrochloride corresponding to 4.48 mg oxycodone.
For the full list of excipients, see section 6.1.
Capsule, hard (capsule).
Hard capsules, 14.4 mm in length, with a dark pink body marked with '5' and a brown cap marked with 'OXY'.
Severe pain, which can only be adequately managed with opioid analgesics.
Prior to starting treatment with opioids, a discussion should be held with patients to put in place a strategy for ending treatment with Lynlor capsules in order to minimise the risk of addiction and drug withdrawal syndrome (see section 4.4).
The 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
In 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.
Increasing severity of pain will require an increased dose of Lynlor. 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 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.
Duration of administration
Lynlor 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.
Lynlor is not recommended for children under 12 years of age as the safety and efficacy has not been established.
The lowest dose should be administered with careful titration to pain control.
Patients with renal or hepatic impairment
The dose initiation should follow a conservative approach in these patients. The recommended adult starting dose should be reduced by 50% (for example a total daily dose of 10 mg orally in opioid naïve patients), and each patient should be titrated to adequate pain control according to their clinical situation.
Risk 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.
Method of administration
For oral use.
Lynlor 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.
Hypersensitivity to oxycodone or to any of the excipients listed in section 6.1. Oxycodone must not be used in any situation where opioids are contraindicated: severe respiratory depression with hypoxia, paralytic ileus, acute abdomen, delayed gastric emptying, severe chronic obstructive lung disease, cor pulmonale, severe bronchial asthma, elevated carbon dioxide levels in the blood , moderate to severe hepatic impairment, chronic constipation.
The major risk of opioid excess is respiratory depression. Caution must be exercised when administering oxycodone to the debilitated elderly; opioid-dependent patients; patients with severely impaired pulmonary function, patients with impaired hepatic or renal function; patients with myxedema, hypothyroidism, Addison's disease, toxic psychosis, prostate hypertrophy, adrenocortical insufficiency, alcoholism, delirium tremens, diseases of the biliary tract, pancreatitis, inflammatory bowel disorders, hypotension, hypovolaemia, raised increased intracranial pressure, head injury (due to risk of increased intracranial pressure) or patients taking benzodiazepines, other CNS depressants (including alcohol) or MAO inhibitors.
Concomitant use of benzodiazepines and opioids may result in sedation, respiratory depression, coma and death.
Because of these risks, concomitant prescribing of sedative medicines such as benzodiazepines or related drugs with opioids should be reserved for patients for whom alternative treatment options are not possible.
If a decision is made to prescribe benzodiazepines concomitantly with opioids, the lowest effective dose should be used, and the duration of treatment should be as short as possible (see also general dose recommendation in section 4.2).
The patients should be followed closely for signs and symptoms of respiratory depression and sedation. In this respect, it is strongly recommended to inform patients and their environment to be aware of these symptoms (see section 4.5).
Lynlor capsules should not be used where there is a possibility of paralytic ileus occurring. Should paralytic ileus be suspected or occur during use, Lynlor capsules should be discontinued immediately.
Lynlor capsules should be used with caution pre-operatively and within the first 12-24 hours post-operatively.
As with all opioid preparations, oxycodone products should be used with caution following abdominal surgery as opioids are known to impair intestinal motility and should not be used until the physician is assured of normal bowel function.
Patients about to undergo additional pain relieving procedures (e.g. surgery, plexus blockade) should not receive Lynlor capsules for 6 hours prior to the intervention. If further treatment with oxycodone is indicated then the dosage should be adjusted to the new post-operative requirement.
For appropriate patients who suffer with chronic non-malignant pain, opioids should be used as part of a comprehensive treatment programme involving other medications and treatment modalities. A crucial part of the assessment of a patient with chronic non-malignant pain is the patient's addiction and substance abuse history.
If opioid treatment is considered appropriate for the patient, then the main aim of treatment is not to minimise the dose of opioid, but rather to achieve a dose which provides adequate pain relief with a minimum of side effects. There must be frequent contact between physician and patient so that dosage adjustments can be made. It is strongly recommended that the physician defines treatment outcomes in accordance with pain management guidelines. The physician and patient can then agree to discontinue treatment if these objectives are not met.
Drug dependence, tolerance and potential for abuse
For all patients, prolonged use of this product may lead to drug dependence (addiction), even at therapeutic doses. The risks are increased in individuals with current or past history of substance misuse disorder (including alcohol misuse) or mental health disorder (e.g., major depression).
Additional support and monitoring may be necessary when prescribing for patients at risk of opioid misuse.
A comprehensive patient history should be taken to document concomitant medications, including over-the-counter medicines and medicines obtained on-line, and past and present medical and psychiatric conditions.
Patients may find that treatment is less effective with chronic use and express a need to increase the dose to obtain the same level of pain control as initially experienced. Patients may also supplement their treatment with additional pain relievers. These could be signs that the patient is developing tolerance. The risks of developing tolerance should be explained to the patient.
Overuse or misuse may result in overdose and/or death. It is important that patients only use medicines that are prescribed for them at the dose they have been prescribed and do not give this medicine to anyone else.
Patients should be closely monitored for signs of misuse, abuse, or addiction.
The clinical need for analgesic treatment should be reviewed regularly.
Drug withdrawal syndrome
Prior to starting treatment with any opioids, a discussion should be held with patients to put in place a withdrawal strategy for ending treatment with Lynlor capsules.
Drug withdrawal syndrome may occur upon abrupt cessation of therapy or dose reduction. When a patient no longer requires therapy, it is advisable to taper the dose gradually to minimise symptoms of withdrawal. Tapering from a high dose may take weeks to months.
The opioid drug withdrawal syndrome is characterised by some or all of the following: restlessness, lacrimation, rhinorrhoea, yawning, perspiration, chills, myalgia, mydriasis and palpitations. Other symptoms may also develop including irritability, agitation, anxiety, hyperkinesia, tremor, weakness, insomnia, anorexia, abdominal cramps, nausea, vomiting, diarrhoea, increased blood pressure, increased respiratory rate or heart rate.
If women take this drug during pregnancy, there is a risk that their newborn infants will experience neonatal withdrawal syndrome.
Hyperalgesia may be diagnosed if the patient on long-term opioid therapy presents with increased pain. This might be qualitatively and anatomically distinct from pain related to disease progression or to breakthrough pain resulting from development of opioid tolerance. Pain associated with hyperalgesia tends to be more diffuse than the pre-existing pain and less defined in quality. Symptoms of hyperalgesia may resolve with a reduction of opioid dose.
The capsules should be swallowed whole, and not chewed or crushed.
Abuse of oral dosage forms by parenteral administration can be expected to result in serious adverse events, which may be fatal.
Concomitant use of alcohol and Lynlor capsules may increase the undesirable effects of Lynlor capsules; concomitant use should be avoided.
Opioids, such as oxycodone hydrochloride. 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 manifest from these hormonal changes.
Oxycodone 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.
There can be an enhanced CNS depressant effect which can result in profound sedation, respiratory depression, coma and death during concomitant therapy with benzodiazepines or other drugs which affect the CNS such as tranquillisers, anaesthetics, hypnotics, anti-depressants, non-benzodiazepine sedatives, phenothiazines, neuroleptic drugs, alcohol, other opioids, muscle relaxants and antihypertensives.
Concomitant administration of oxycodone with serotonin agents, such as a Selective Serotonin Re-uptake Inhibitor (SSRI) or a Serotonin Norepinephrine Re-uptake Inhibitor (SNRI) may cause serotonin toxicity. The symptoms of serotonin toxicity may include mental-status changes (e.g., agitation, hallucinations, coma), autonomic instability (e.g., tachycardia, labile blood pressure, hyperthermia), neuromuscular abnormalities (e.g., hyperreflexia, incoordination, rigidity), and/or gastrointestinal symptoms (e.g., nausea, vomiting, diarrhoea). Oxycodone should be used with caution and the dosage may need to be reduced in patients using these medications.
Concomitant administration of oxycodone with anticholinergics or medicines with anticholinergic activity (e.g. tricyclic anti-depressants, antihistamines, antipsychotics, muscle relaxants, anti-Parkinson drugs) may result in increased anticholinergic adverse effects. Oxycodone should be used with caution and the dosage may need to be reduced in patients using these medications.
MAO inhibitors are known to interact with narcotic analgesics. MAO-inhibitors cause CNS excitation or depression associated with hypertensive or hypotensive crisis (see section 4.4).
Alcohol may enhance the pharmacodynamic effects of Lynlor, concomitant use should be avoided.
Oxycodone is metabolised mainly by CYP3A4, with a contribution from CYP2D6. The activities of these metabolic pathways may be inhibited or induced by various co-administered drugs or dietary elements.
CYP3A4 inhibitors, such as macrolide antibiotics (e.g. clarithromycin, erythromycin and telithromycin), azole-antifungals (e.g. ketoconazole, voriconazole, itraconazole, and posaconazole), protease inhibitors (e.g. boceprevir, ritonavir, indinavir, nelfinavir and saquinavir), cimetidine and grapefruit juice may cause a reduced clearance of oxycodone that could cause an increase of the plasma concentrations of oxycodone. Therefore, the oxycodone dose may need to be adjusted accordingly.
Some specific examples are provided below:
• Itraconazole, a potent CYP3A4 inhibitor, administered 200 mg orally for five days, increased the AUC of oral oxycodone. On average, the AUC was approximately 2.4 times higher (range 1.5 - 3.4).
• Voriconazole, a CYP3A4 inhibitor, administered 200 mg twice-daily for four days (400 mg given as first two doses), increased the AUC of oral oxycodone. On average, the AUC was approximately 3.6 times higher (range 2.7 - 5.6).
• Telithromycin, a CYP3A4 inhibitor, administered 800 mg orally for four days, increased the AUC of oral oxycodone. On average, the AUC was approximately 1.8 times higher (range 1.3 – 2.3).
• Grapefruit Juice, a CYP3A4 inhibitor, administered as 200 ml three times a day for five days, increased the AUC of oral oxycodone. On average, the AUC was approximately 1.7 times higher (range 1.1 – 2.1).
CYP3A4 inducers, such as rifampicin, carbamazepine, phenytoin and St John´s Wort may induce the metabolism of oxycodone and cause an increased clearance of oxycodone that could cause a reduction of the plasma concentrations of oxycodone. The oxycodone dose may need to be adjusted accordingly.
Some specific examples are provided below:
• St Johns Wort, a CYP3A4 inducer, administered as 300 mg three times a day for fifteen days, reduced the AUC of oral oxycodone. On average, the AUC was approximately 50% lower (range 37-57%).
• Rifampicin, a CYP3A4 inducer, administered as 600 mg once-daily for seven days, reduced the AUC of oral oxycodone. On average, the AUC was approximately 86% lower
Drugs that inhibit CYP2D6 activity, such as paroxetine and quinidine, may cause decreased clearance of oxycodone which could lead to an increase in oxycodone plasma concentrations. Concurrent administration of quinidine resulted in an increase in oxycodone Cmax by 11%, AUC by 13%, and t½ elim. by 14%. Also an increase in noroxycodone level was observed, (Cmax by 50%; AUC by 85%, and t½ elim. by 42%). The pharmacodynamic effects of oxycodone were not altered.
Regular use during pregnancy may cause drug dependence in the foetus, leading to withdrawal symptoms in the neonate.
If opioid use is required for a prolonged period in a pregnant woman, advise the patient of the risk of neonatal opioid withdrawal syndrome and ensure that appropriate treatment will be available.
Administration during labour may depress respiration in the neonate and an antidote for the child should be readily available.
Administration to nursing women is not recommended as oxycodone may be secreted in breast milk and may cause respiratory depression in the infant.
Oxycodone may impair the ability to drive and use machines. Oxycodone may modify patients' reactions to a varying extent depending on the dosage and individual susceptibility. Therefore, patients should not drive or operate machinery if affected.
This medicine can impair cognitive function and can affect a patient's ability to drive safely. This class of medicine is in the list of drugs included in regulations under 5a of the Road Traffic Act 1988. When prescribing this medicine, patients should be told:
• The medicine is likely to affect your ability to drive.
• Do not drive until you know how the medicine affects you.
• It is an offence to drive while you have this medicine in your body over a specified limit unless you have a defence (called the 'statutory defence').
• This defence applies when:
- The medicine has been prescribed to treat a medical or dental problem; and
- You have taken it according to the instructions given by the prescriber and in the information provided with the medicine.
• Please note that it is still an offence to drive if you are unfit because of the medicine (i.e. your ability to drive is being affected).”
Details regarding a new driving offence concerning driving after drugs have been taken in the UK may be found here: https://www.gov.uk/drug-driving-law.
Adverse drug reactions are typical of full opioid agonists. Tolerance and dependence may occur (see Section 4.4). Constipation may be prevented with an appropriate laxative. If nausea and vomiting are troublesome, oxycodone may be combined with an anti-emetic.
The following frequency categories form the basis for classification of the undesirable effects:
≥ 1/100 to <1/10
≥ 1/1,000 to <1/100
≥1/10,000 to <1/1,000
Frequency not known
Cannot be estimated from the available data
Immune system disorders:
Frequency not known: anaphylactic reaction, anaphylactoid reaction.
Metabolism and nutrition disorders:
Common: decreased appetite.
Common: anxiety, confusional state, depression, insomnia, nervousness, abnormal thinking, abnormal dreams
Uncommon: agitation, affect lability, euphoric mood, hallucinations, decreased libido, disorientation, mood altered, restlessness, dysphoria
Frequency not known: aggression, drug dependence (see section 4.4).
Nervous system disorders:
Very common: somnolence, dizziness, headache.
Common: tremor, lethargy, sedation.
Uncommon: amnesia, convulsion, hypertonia, hypoaesthesia, involuntary muscle contractions, speech disorder, syncope, paraesthesia, dysgeusia, hypotonia.
Frequency not known: hyperalgesia.
Uncommon: visual impairment, miosis.
Ear and labyrinth disorders:
Uncommon: palpitations (in the context of withdrawal syndrome), supraventricular tachycardia.
Uncommon: vasodilatation, facial flushing.
Rare: hypotension, orthostatic hypotension.
Respiratory, thoracic and mediastinal disorders:
Common: dyspnoea, bronchospasm, cough decreased.
Uncommon: respiratory depression, hiccups.
Very common: constipation, nausea, vomiting.
Common: abdominal pain, diarrhoea, dry mouth, dyspepsia.
Uncommon: dysphagia, flatulence, eructation, ileus, gastritis.
Frequency not known: dental caries.
Uncommon: increased hepatic enzymes, biliary colic.
Frequency not known: cholestasis.
Skin and subcutaneous tissue disorders:
Very common: pruritus.
Common: rash, hyperhidrosis.
Uncommon: dry skin, exfoliative dermatitis.
Renal and urinary disorders:
Uncommon: urinary retention, ureteral spasm.
Reproductive system and breast disorders:
Uncommon: erectile dysfunction, hypogonadism.
Frequency not known: amenorrhoea.
General disorders and administration site conditions:
Common: asthenia, fatigue.
Uncommon: drug withdrawal syndrome, malaise, oedema, peripheral oedema, drug tolerance, thirst, pyrexia, chills.
Frequency not known: drug withdrawal syndrome, drug withdrawal syndrome neonatal
Reporting of suspected adverse reactions
Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions via the Yellow Card Scheme; website: www.mhra.gov.uk/yellowcard or search for MHRA Yellow Card in the Google Play or Apple App Store.
Patients should be informed of the signs and symptoms of overdose and to ensure that family and friends are also aware of these signs and to seek immediate medical help if they occur.
Acute overdose with oxycodone can be manifested by miosis, respiratory depression, hypotension and hallucinations. Circulatory failure and somnolence progressing to stupor or deepening coma, hypotonia, bradycardia, pulmonary oedema and death may occur in more severe cases.
Treatment of oxycodone overdosage: primary attention should be given to the establishment of a patent airway and institution of assisted or controlled ventilation. The pure opioid antagonists such as naloxone are specific antidotes against symptoms from opioid overdose. Other supportive measures should be employed as needed.
In the case of massive overdosage, administer naloxone intravenously (0.4 to 2 mg for an adult and 0.01 mg/kg body weight for children) if the patient is in a coma or respiratory depression is present. Repeat the dose at 2minute intervals if there is no response. If repeated 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 not be administered in the absence of clinically significant respiratory or circulatory depression secondary to oxycodone overdosage. Naloxone should be administered cautiously to persons who are known, or suspected, to be physically dependent on oxycodone. In such cases, an abrupt or complete reversal of opioid effects may precipitate pain and an acute withdrawal syndrome.
• 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.
• Gastric contents may need to be emptied as this can be useful in removing unabsorbed drug.
Pharmacotherapeutic group: Natural opium alkaloids, ATC-Code: N02AA05
Mechanism of action:
Oxycodone is a full opioid agonist with no antagonist properties. It has an affinity for kappa, mu and delta opiate receptors in the brain and spinal cord. The therapeutic effect is mainly analgesic, anxiolytic and sedative.
Opioids may induce spasm of the sphincter of Oddi.
See section 4.4.
Other pharmacological effects
In- vitro and animal studies indicate various effects of natural opioids, such as morphine, on components of the immune system; the clinical significance of these findings is unknown. Whether oxycodone, a semisynthetic opioid, has immunological effects similar to morphine is unknown.
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.
At steady state, the volume of distribution of oxycodone amounts to 2.6 l/kg and plasma protein binding to 38-45%.
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.
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.
After administration of the capsule formulation of oxycodone hydrochloride the plasma concentration increases linear over the dose range of 5 to 20 mg.
Oyxcodone had no effect on fertility and early embryonic development in male and female rats in doses of up to 8 mg/kg body weight and induced no malformations in rats in doses of up to 8 mg/kg and in rabbits in doses of 125 mg/kg bodyweight. However, in rabbits, when individual foetuses were used in statistical evaluation, a dose related increase in developmental variations was observed (increased incidences of 27 presacral vertebrae, extra pairs of ribs). When these parameters were statistically evaluated using litters, only the incidence of 27 presacral vertebrae was increased and only in the 125 mg/kg group, a dose level that produced severe pharmacotoxic effects in the pregnant animals. In a study on pre- and postnatal development in rats F1 body weights were lower at 6 mg/kg/d when compared to body weights of the control group at doses which reduced maternal weight and food intake (NOAEL 2 mg/kg body weight). There were neither effects on physical, reflexological, and sensory developmental parameters nor on behavioural and reproductive indices.
Long-term carcinogenicity studies were not performed.
Oxycodone shows a clastogenic potential in in vitro assays. No similar effects were observed, however, under in vivo conditions, even at toxic doses. The results indicate that the mutagenic risk of oxycodone to humans at therapeutic concentrations may be ruled out with adequate certainty.
Titanium dioxide (E171)
Iron oxide yellow (E172)
Iron oxide red (E172)
Iron oxide black (E172)
Potassium hydroxide (for pH-adjustment)
<[For HDPE container only:]>
After opening: 6 months
Do not store above 30°C.
Blister packs (PVC/PVdC/Al).
Pack sizes: 10, 14, 20, 28, 30, 50, 56, 90, 98 and 100 capsules
Child resistant blister packs (PVC/PVdC/Al/PET/paper).
Pack sizes: 10, 14, 20, 28, 30, 50, 56, 90, 98 and 100 capsules
Child resistant HDPE containers with threaded neck with PP Cap (Twist off Cap).
Pack sizes: 56, 98, 100 and 250 capsules
Not all pack sizes may be marketed.
No special requirements.
Instructions for use of child resistant blisters:
1. Do not push the capsule directly out of the pocket
2. Separate one blister cell from the strip at the perforations
3. Carefully peel off the backing to open the pocket
(Trading style: Accord)