MAXITRAM SR

Posology The dose should be adjusted to the intensity of the pain and the sensitivity of the individual patient. The lowest effective dose for analgesia should generally be selected. Adults and adolescents aged 12 years and over 100-200 mg tramadol hydrochloride twice daily (corresponding to 200 – 400 mg of tramadol hydrochloride/day), morning and evening administration recommended.

If required, other forms of administration can be used. The smallest effective analgesic dose should always be used. Daily doses of 400 mg of active substance must not be exceeded, unless exceptional medical reasons require so. A minimum interval of 8 hours must be respected between administrations.

Paediatric Population MAXITRAM SR is not suitable for use in children below 25 kg body weight which in general does not allow for individualized dosage in children below 12 years of age. Consequently, a more suitable form of administration should be used.

Geriatric patients A dose adjustment is not usually necessary in patients up to 75 years without clinically manifest hepatic or renal insufficiency. In elderly patients over 75 years elimination may be prolonged. Therefore, if necessary the dosage interval is to be extended according to the patient's requirements.

Renal insufficiency/dialysis and hepatic impairment In patients with renal and/or hepatic insufficiency the elimination of tramadol is delayed. In these patient’s prolongation of the dosage intervals should be carefully considered according to the patient's requirements.

In cases of severe renal and/or severe hepatic insufficiency MAXITRAM SR prolonged-release hard capsules are not recommended.

Note:

The recommended dosages are indicative only. In general, the smallest effective analgesic dose should be used. For the treatment of chronic pain, a pre-established posology must be respected. For doses not realisable/practicable with this medicinal product other strengths of this medicinal product or other pharmaceutical forms and products are available.

Method of administration The prolonged-release capsule, hard, must be swallowed whole with sufficient liquid, irrespective of mealtimes. MAXITRAM SR must never be used for longer than therapeutically absolutely necessary. Should prolonged pain treatment according to the nature and severity of the illness be necessary, a careful evaluation should be carried out at short regular intervals (if necessary by instituting treatment pauses) to check whether or to what extent prolonged treatment is medically necessary.

Treatment goals and discontinuation Before initiating treatment with MAXITRAM SR 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 tramadol, it may be advisable to taper the dose gradually to prevent symptoms of withdrawal.

4).

The most frequent side effects occurring during treatment with MAXITRAM SR are nausea and vertigo, which occur in more than 1 out of 10 patients. The reactions are classified according to frequency (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); very rare (<1/10,000); not known (cannot be estimated from the available data).

, dyspnea, bronchospasm, wheezing, angioneurotic oedema), anaphylaxis Metabolism and change in appetite hypoglycaemia System organ class Very common (≥ 1/10) Common (≥1/100 to <1/10) Uncommon (≥1/1000 to <1/100) Rare (≥1/10,000 to <1/1,000) Not known (cannot be estimated from the available data) nutrition disorders Psychiatric disorders hallucinations, confusion, sleep disturbances, delirium, anxiety, night-mares Nervous system disorders dizziness headaches, somnolence paraesthesia, tremor, epileptiform convulsions, involuntary muscle contractions, abnormal coordination, syncope, speech disorders Serotonin syndrome Eye disorders blurred vision, miosis, mydriasis Cardiac disorders effects on cardiovascular regulation: palpitations, tachycardia.

bradycardia Vascular disorders cardiovascular regulation (postural hypotension or cardiovascular collapse. , pruritus, rash, urticaria) Musculoskeletal and connective tissue disorders motorial weakness Renal and urinary disorders disorders of micturition (dysuria and urinary retention) General disorders and administration site conditions fatigue Investigations increased blood pressure Drug dependence Repeated use of MAXITRAM SR can lead to drug dependence, even at therapeutic doses.

4). For cardiac disorders, adverse reactions may occur especially on intravenous administration and in patients who are physically stressed. For vascular disorders, adverse reactions may occur especially on intravenous administration and in patients who are physically stressed.

5). Psychic adverse reactions may occur following administration of tramadol which vary individually in intensity and nature (depending on personality and duration of treatment). g. decision behaviour, perception disorders). Drug dependence may occur.

Symptoms of withdrawal syndrome, similar to those occurring during opiate withdrawal, may occur as follows: agitation, anxiety, nervousness, insomnia, hyperkinesias, tremor and gastrointestinal symptoms. e. confusion, delusions, depersonalisation, derealisation, paranoia).

5), respiratory depression may occur. Worsening of asthma has been reported, though a causal relationship has not been established. In a few isolated cases an increase in liver enzyme values has been reported in a temporal connection with the therapeutic use of tramadol.

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 or search for MHRA Yellow Card in the Google Play or Apple App Store.

MAXITRAM SR should only be used following a strict benefit-risk evaluation and appropriate precautionary measures in the following cases: − opioid-dependent patients, − impaired consciousness of unclear aetiology, shock − impaired respiratory centre or function, − increased intracranial pressure, head injury, or brain disease, − impaired liver or kidney function.

The medicinal product should be used with caution in patients showing sensitivity reactions to opiates. 9) as the possibility of respiratory depression cannot be excluded in these situations. Tolerance and opioid use disorder (abuse and dependence) Tolerance, physical and psychological dependence, and opioid use disorder (OUD) may develop upon repeated administration of opioids such as MAXITRAM SR.

Repeated use of MAXITRAM SR can 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 MAXITRAM SR 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.

Sleep-related breathing disorders Opioids can cause sleep-related breathing disorders including central sleep apnoea (CSA) and sleep-related hypoxemia. Opioid use increases the risk of CSA in a dose- dependent fashion. In patients who present with CSA, consider decreasing the total opioid dosage.

Adrenal insufficiency Opioid analgesics may occasionally cause reversible adrenal insufficiency requiring monitoring and glucocorticoid replacement therapy. g. severe abdominal pain, nausea and vomiting, low blood pressure, extreme fatigue, decreased appetite, and weight loss.

9). If concomitant treatment with other serotonergic agents is clinically warranted, careful observation of the patient is advised, particularly during treatment initiation and dose escalations. Symptoms of serotonin syndrome may include mental status changes, autonomic instability, neuromuscular abnormalities and/or gastrointestinal symptoms.

If serotonin syndrome is suspected, a dose reduction or discontinuation of therapy should be considered depending on the severity of the symptoms. Withdrawal of the serotonergic drugs usually brings about a rapid improvement. Risk from concomitant use of sedative medicinal products such as benzodiazepines or related active substances Concomitant use of tramadol and sedative medicinal products such as benzodiazepines or related active substances may result in sedation, respiratory depression, coma and death.

Because of these risks, concomitant prescribing with these sedative medicinal products should be reserved for patients for whom alternative treatment options are not possible. If a decision is made to prescribe MAXITRAM SR concomitantly with sedative medicinal products, the lowest effective dose should be used, and the duration of treatment should be as short as possible.

The patients should be followed closely for signs and symptoms of respiratory depression and sedation. 5). Convulsions have been reported in patients taking tramadol at the recommended dosage. Increased risk may be associated with the administration of doses exceeding the recommended daily dose (400 mg).

5). Patients with a history of epilepsy or those susceptible to convulsions should only be treated with tramadol if there are compelling circumstances. MAXITRAM SR is not suitable for use as a substitute in opioid-dependent patients.

Although it is an opiate agonist, tramadol cannot suppress morphine withdrawal symptoms. CYP2D6 metabolism Tramadol is metabolised by the liver enzyme CYP2D6. If a patient has a deficiency or is completely lacking this enzyme an adequate analgesic effect may not be obtained.

Estimates indicate that up to 7% of the Caucasian population may have this deficiency. However, if the patient is an ultra-rapid metaboliser there is a risk of developing side effects of opioid toxicity even at commonly prescribed doses.

General symptoms of opioid toxicity include confusion, somnolence, shallow breathing, small pupils, nausea, vomiting, constipation and lack of appetite. In severe cases this may include symptoms of circulatory and respiratory depression, which may be life threatening and very rarely fatal.

Estimates of prevalence of ultra-rapid metabolisers in different […]

5); − epilepsy uncontrolled by treatment. MAXITRAM SR must not be used for the treatment of opioid dependence. This medicinal product is contraindicated in children below 12 years of age.