RENOCONTIN

The dosage depends on the intensity of pain and the patient’s individual susceptibility to the treatment.

The following general dosage recommendations apply:

Adults and adolescents 12 years of age and older Dose titration and adjustment In general, the initial dose for opioid naïve patients is 10 mg oxycodone hydrochloride given at intervals of 12 hours. Some patients may benefit from a starting dose of 5 mg oxycodone hydrochloride to minimize the incidence of adverse reactions.

Patients already receiving opioids may start treatment with higher dosages taking into account their experience with former opioid therapies. For doses not realisable/practicable with this strength other strengths of this medicinal product are available.

Because of individual differences in sensitivity for different opioids, it is recommended that patients should start conservatively with Renocontin after conversion from other opioids, with 50-75% of the calculated oxycodone dose. Some patients who take Renocontin following a fixed schedule need rapid release analgesics as rescue medication in order to control breakthrough pain.

Renocontin is not indicated for the treatment of acute pain and/or breakthrough pain. The single dose of the rescue medication should amount to 1/6 of the equianalgesic daily dose of Renocontin. Use of the rescue medication more than twice daily indicates that the dose of Renocontin needs to be increased.

The dose should not be adjusted more often than once every 1-2 days until a stable twice daily administration has been achieved. Following a dose increase from 10 mg to 20 mg taken every 12 hours dose adjustments should be made in steps of approximately one third of the daily dose.

The aim is a patient-specific dosage which, with twice daily administration, allows for adequate analgesia with tolerable undesirable effects and as little rescue medication as possible as long as pain therapy is needed. Even distribution (the same dose mornings and evenings) following a fixed schedule (every 12 hours) is appropriate for the majority of the patients.

For some patients it may be advantageous to distribute the doses unevenly. In general, the lowest effective analgesic dose should be chosen. For the treatment of non-malignant pain a daily dose of 40 mg is generally sufficient; but higher dosages may be necessary.

Patients with cancer-related pain may require dosages of 80 to 120 mg, which in individual cases can be increased to up to 400 mg. If even higher doses are required, the dose should be decided individually balancing efficacy with the tolerance and risk of undesirable effects.

Doses in excess of 1000mg have been recorded. Conversion from oral morphine According to well-controlled clinical studies 10-13 mg oxycodone ¬hydrochloride correspond to approximately 20 mg morphine sulphate, both in the prolonged-release formulation.

Elderly patients Elderly patients without clinical manifestation of impaired liver and/or kidney function usually do not require dose adjustments. 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. Patients with low body weight or slow metabolism Risk patients, for example patients with low body weight or slow metabolism of medicinal products, should initially half the recommended adult dose if they are opioid naïve.

e. 10 mg, may not be suitable as a starting dose. Dose titration should be performed in accordance with the individual clinical situation. Patients with renal or hepatic impairment The dose initiation should follow a conservative approach as the plasma concentration may be increased 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.

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.

Children under 12 years of age Oxycodone has not been studied in children younger than 12 years of age. The safety and efficacy of Renocontin have not been demonstrated and the use in children younger than 12 years of age is therefore not recommended.

Method of administration For oral use. Renocontin should be taken twice daily based on a fixed schedule at the dosage determined. The prolonged-release tablets may be taken with or independent of meals with a sufficient amount of liquid.

Renocontin must be swallowed whole, not chewed, divided or crushed. Taking chewed, divided or crushed Renocontin tablets may lead to a rapid release and absorption of a potentially fatal dose of oxycodone. Renocontin should not be taken with alcoholic beverages.

Treatment goals and discontinuation Before initiating treatment with Renocontin, a treatment strategy including treatment duration and treatment goals, and a plan for end of the treatment, should be agreed together with the patient, in accordance with pain management guidelines.

During treatment, there should be frequent contact between the physician and the patient to evaluate the need for continued treatment, consider discontinuation and to adjust dosages if needed. When a patient no longer requires therapy with oxycodone, it may be advisable to taper the dose gradually to prevent symptoms of withdrawal.

4). Duration of treatment Renocontin should not be taken longer […]

Summary of the safety profile Due to its pharmacological properties oxycodone may cause respiratory depression, miosis, bronchial spasm and spasm of unstriated muscles and may suppress the cough reflex. The most frequently reported undesirable effects are nausea (especially at the beginning of treatment) and constipation.

Respiratory depression is the chief hazard of an opioid overdose and occurs most commonly in elderly or debilitated patients. g. 4) Not known: Aggression Nervous system disorders Very common: Somnolence, sedation, dizziness, headache Common: Tremor, lethargy Uncommon: Amnesia, convulsion (especially in persons with epileptic disorder or predisposition to convulsions), concentration impaired, migraine, hypertonia, involuntary muscle contractions, hypoaesthesia, abnormal coordination, speech disorder, syncope, paraesthesia, dysgeusia Not known: Hyperalgesia Eye disorders Uncommon: Visual impairment, miosis, Ear and labyrinth disorders Uncommon: Hearing impaired, vertigo Cardiac disorders Uncommon: Tachycardia, Palpitations (in the context of withdrawal syndrome) Vascular disorders Uncommon: Vasodilatation Rare: Hypotension, orthostatic hypotension.

g. chest pain), malaise, oedema, peripheral oedema, drug tolerance, thirst Rare: Weight increase, weight decrease Not known: Drug withdrawal syndrome neonatal Injury, poisoning and procedural complications Uncommon: Injuries from accidents Description of selected adverse reactions Drug dependence Repeated use of Renocontin can lead to drug dependence, even at therapeutic doses.

4). 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. uk/yellowcard.

4 Special warnings and special precautions for use Respiratory and cardiac depression Respiratory depression is the most significant risk induced by opioids and is most likely to occur in elderly or debilitated patients. The respiratory depressant effect of oxycodone can lead to increased carbon dioxide concentrations in blood and hence in cerebrospinal fluid.

In predisposed patients opioids can cause severe decrease in blood pressure. Oxycodone 60mg, 80mg and 120mg tablets should not be used in patients not previously exposed to opioids. These tablet strengths may cause fatal respiratory depression when administered to opioid naïve patients.

Opioid Use Disorder (abuse and dependence) Tolerance and physical and/or psychological dependence may develop upon repeated administration of opioids such as oxycodone. Repeated use of Renocontin may lead to Opioid Use Disorder (OUD).

A higher dose and longer duration of opioid treatment can increase the risk of developing OUD. Abuse or intentional misuse of Renocontin may result in overdose and/or death. g. major depression, anxiety and personality disorders). 2). Before and during treatment the patient should also be informed about the risks and signs of OUD.

If these signs occur, patients should be advised to contact their physician. g. too early requests for refills). This includes the review of concomitant opioids and psycho- active drugs (like benzodiazepines). For patients with signs and symptoms of OUD, consultation with an addiction specialist should be considered.

Tolerance and dependence 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. Long-term use of Renocontin can cause the development of tolerance which leads to the use of higher doses in order to achieve the desired analgesic effect.

There is a cross-tolerance to other opioids. Chronic use of Renocontin can cause physical dependence. Withdrawal symptoms may occur following abrupt discontinuation of therapy. If therapy with oxycodone is no longer required it may be advisable to reduce the daily dose gradually in order to avoid the occurrence of a withdrawal syndrome.

Withdrawal symptoms may include restlessness, perspiration, chills, myalgia, palpitations, yawning, mydriasis, lacrimation, rhinorrhoea, tremor, hyperhidrosis, anxiety, agitation, convulsions and insomnia. Other symptoms also may develop, including: irritability, backache, joint pain, weakness, abdominal cramps, nausea, anorexia, vomiting, diarrhoea, or increased blood pressure, respiratory rate or heart rate.

Hyperalgesia that will not respond to a further dose increase of oxycodone may occur, particularly in high doses. An oxycodone dose reduction or change to an alternative opioid may be required. Renocontin has a primary dependence potential.

In patients with a history of alcohol and drug abuse the medicinal product must be prescribed with special care. Abuse Abuse of oral dosage forms 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, which may be fatal.

Alcohol Concomitant use of alcohol and Renocontin may increase the undesirable effects of Renocontin; concomitant use should be avoided. g. alcohol), prostatic hypertrophy, adrenocortical insufficiency, alcoholism, known opioid dependence, delirium tremens, pancreatitis, disease of the biliary tract, biliary or renalcolic, inflammatory bowel disorders, raised intracranial pressure, hypotension, hypovolemia, epilepsy or seizure tendency and in patients taking MAO inhibitors within the last two weeks.

Patients with severe hepatic impairment should be closely monitored. Oxycodone should not be used where there is a possibility of paralytic ileus occurring. Should paralytic ileus be suspected or occur during use, oxycodone should be discontinued immediately.

Surgical procedures Special care should be taken when oxycodone is applied to patients undergoing bowel-surgery as opioids are known to impair intestinal motility. Opioids should only be administered post-operatively when the bowel function has been restored.

The safety of Renocontin used pre-operatively has not been established. Renocontin is not recommended for pre-operative use or within the first 12 – 24 hours post operatively. g. surgery, plexus blockade) should not receive oxycodone tablets for 12 hours prior to the intervention.

If further treatment with oxycodone tablets is indicated then the dosage should be adjusted to the new post-operative requirement. Sleep-related breathing disorders Opioids can cause sleep-related breathing disorders including […]

1. • Severe respiratory depression with hypoxia and/or elevated carbon dioxide levels in the blood (hypercapnia). • Severe chronic obstructive pulmonary disease. • Cor pulmonale. • Severe bronchial asthma. • Paralytic ileus. • Acute abdomen, delayed gastric emptying.

• Head injury. • Moderate to severe hepatic impairment. • Severe renal impairment (creatinine clearance <10 ml/min). • Chronic constipation. • Concurrent administration of monoamine oxidase inhibitors or within 2 weeks of discontinuation of their use.