THERADOL 50 mg Effervescent tablets 1 Summary of product characteristics SUMMARY OF PRODUCT CHARACTERISTICS 1. NAME OF THE MEDICINAL PRODUCT THERADOL 50 mg Effervescent tablets. 2. QUALITATIVE AND QUANTITATIVE COMPOSITION 2.1 General description Round, biplane white or off-white tablets with bevel-edges on both sides. 2.2 Qualitative and quantitative composition Tramadol hydrochloride 50 mg per effervescent tablet. This product also contains sodium 214 mg, lactose 75 mg and aspartame 10 mg per tablet. For a full list of excipients, see section 6.1. 3. PHARMACEUTICAL FORM Effervescent tablet. 4. CLINICAL PARTICULARS 4.1. Therapeutic indications Treatment of moderate to severe acute and chronic pain, such as pain due to surgery, trauma, malignancy. 4.2. Posology and method of administration Posology As with all analgesic drugs, the dose of THERADOL 50 mg Effervescent tablets should be adjusted according 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 children aged 12 years and over: The usual dose is 50 to 100 mg (1 to 2 effervescent tablets), 3 to 4 times a day. In children from 12 to 14 years, it is recommended to use the lowest dose. Geriatric patients THERADOL 50 mg Effervescent tablets 2 Summary of product characteristics 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 impairment/ dialysis and hepatic impairment: In patients with renal and/or hepatic insufficiency the elimination of tramadol is delayed. In these patients prolongation of the dosage intervals should be carefully considered according to the patient's requirements. Tramadol is not recommended for use in patients with severe renal impairment (creatinine clearance < 10 ml/min). As tramadol is only removed very slowly by haemodialysis or haemofiltration, post-dialysis administration to maintain analgesia is not usually necessary. Tramadol is not recommended for use in patients with severe hepatic impairment. Use in children below 12 years: Tramadol is not recommended for use in children below 12 years because its safety and efficacy have not been established. For acute pain an initial dose of 100 mg is usually necessary. In case THERADOL 50 mg Effervescent tablets are used for acute pain, it should be stressed that its activity is somewhat delayed in comparison to that of other analgesics. For pain associated with chronic conditions an initial dose of 50 mg is advised. It is recommended, when possible in case of chronic treatment, to slowly increase tramadol dosage to its final recommended dose (with increments every 2 to 3 days) in order to reduce the incidence of adverse events. Method of administration The effervescent tablets should be dissolved in a glass of water prior to intake. THERADOL 50 Effervescent tablets can be taken without regard to food. In general, a total daily dose of 400 mg (8 effervescent tablets) should not be exceeded. The interval between the doses should be at least 4 hours. This should also be taken into account in case of any violation of the regular schedule, eg because of missing doses or delayed intervals. Treatment periods should usually be limited and intermittent. Withdrawal symptoms may occur if tramadol is discontinued abruptly. 4.3. Contraindications - Known hypersensitivity to the active substance or to any of the excipients or to other opioids. - Patients receiving Monoamino Oxidase Inhibitors or within two weeks of their withdrawal (see 4.5.). - Acute intoxication with alcohol, hypnotics, analgesics or any other central nervous system (CNS) acting drugs (see 4.5.). - Patients suffering from uncontrolled epilepsy. - For use in narcotic withdrawal treatment. 4.4. Special warnings and precautions for use Relative contraindications THERADOL 50 mg Effervescent tablets 3 Summary of product characteristics In one study the use of tramadol during general anaesthesia with enflurane and nitrous oxide was reported to enhance intraoperative recall. Until further information is available use of THERADOL 50 mg Effervescent tablets during light phases of general anaesthesia should be avoided. Warnings THERADOL 50 mg Effervescent tablets should be used with caution in patients with head injury or increased intra-cranial pressure, excessive bronchial secretion and in patients prone to convulsive disorders or in shock. Care should be taken when treating patients with respiratory depression, if concomitant CNS-depressing drugs are being administered (see 4.5.), or if the recommended dose of THERADOL 50 mg Effervescent tablets is abnormally high. Respiratory depression cannot be excluded in these situations. Diagnosis of, for example, acute abdominal injury can be disguised. Seizures have been observed in predisposed patients or receiving a combination of drugs known to reduce the seizure threshold, mainly anti-psychotic, anti-depressant, central analgesic or local anaesthetic drugs. Therefore, special care should be taken in these patients. In case of moderate renal (creatinine clearance <30 ml/min) or hepatic impairment, THERADOL 50 mg Effervescent tablets should be used with caution and dosage interval increased to 12 hours (see 4.2.). Tramadol has been shown to have a low potential to cause physical dependence, however, cases of abuse, dependence and withdrawal syndrome have occurred. Consequently, in patients with tendency to or history of drug abuse or dependence, treatment with tramadol is not recommended. Precautions for use It is recommended, when possible in case of chronic treatment, to slowly increase tramadol dosage to its final recommended dose in order to reduce the incidence of adverse events such as nausea, vomiting, dizziness and sedation (see 4.8.). THERADOL 50 mg Effervescent tablets should be used with caution in case of concomitant administration of coumarin-derivatives (e.g. warfarin) because anticoagulation manifestations such as increase of INR and ecchymoses might occur (see 4.5.). THERADOL 50 mg Effervescent tablets should be used with caution in patients receiving treatment with another serotonergic agent, e.g. clomipramine, fluoxetine, fluvoxamine, nefazodone, paroxetine, sertraline and venlafaxine, due to the risk of seizures and serotonin syndrome (see 4.5.). In patients known to be poor metabolizers (P450 2D6) and in patients receiving inhibitors of P450 2D6, e.g. paroxetine, fluoxetine, quinidine, ritonavir and cimetidine, the analgesic effect of THERADOL 50 mg Effervescent tablets will be less intensive (see 4.5.). This medicine contains 214 mg sodium per effervescent tablet. This should be taken into consideration by patients on a controlled sodium diet. This medicine contains aspartame which is a source of phenylalanine. This medicine may therefore be harmful for patients with phenylketonuria. Patients with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose- galactose malabsorption should not take this medicine. THERADOL 50 mg Effervescent tablets should be used with caution in patients with acute porphyria because in vitro tests have shown a risk of hepatic porphyrin accumulation which could lead to porphyric crisis. 4.5. Interaction with other medicinal products and other forms of interaction THERADOL 50 mg Effervescent tablets 4 Summary of product characteristics Interactions affecting the use of THERADOL 50 mg Effervescent tablets - Concomitant therapeutic use of tramadol and serotonergic drugs, such as selective serotonin reuptake inhibitors (SSRIs), serotonin-norepinephrine reuptake inhibitors (SNRIs), MAO inhibitors (see section 4.3), tricyclic antidepressants and mirtazapine may cause serotonin toxicity. Serotonin syndrome is likely when one of the following is observed: • Spontaneous clonus • Inducible or ocular clonus with agitation or diaphoresis • Tremor and hyperreflexia • Hypertonia and body temperature > 38 °C and inducible or ocular clonus. Withdrawal of the serotonergic drugs usually brings about a rapid improvement. Treatment depends on the type and severity of the symptoms. - Concomitant administration of THERADOL 50 mg Effervescent tablets with anaesthetics and other centrally acting drugs, including alcohol, may potentiate CNS depressant effects. Caution should be taken in case of concomitant use with these drugs or alcohol. - THERADOL 50 mg Effervescent tablets should be used with caution in patients receiving treatment with another serotonergic agent, e.g. clomipramine, fluoxetine, fluvoxamine, nefazodone, paroxetine, sertraline and venlafaxine, due to the risk of seizures and serotonin syndrome (see 4.4.). - Tramadol is metabolized through cytochrome P450 2D6 to an active metabolite. The analgesic effect of tramadol is less intensive in patients known to be poor metabolizers (P450 2D6) and in patients receiving inhibitors of P450 2D6, e.g. paroxetine, fluoxetine, quinidine, ritonavir and cimetidine (see 4.4.). - Simultaneous administration of carbamazepine markedly decreases serum concentrations of tramadol and its active metabolite to an extent that a decrease in analgesic effectiveness and a shorter duration of action may occur. - Simultaneous administration with agonist-antagonist opioids (buprenorphine, nalbufine, pentazocine) may reduce the analgesic effect by competitive blocking