TRAMADOL

4). 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.

Unless otherwise prescribed, Tramadol drops should be administered as follows:

Adults and adolescents above the age of 12 years: The usual daily dose is 50 to 100 mg (20 to 40 drops), 3 to 4 times a day. In children from 12 to 14 years, it is recommended to use the lowest dose. For acute pain an initial dose of 100 mg is usually necessary.

In case TRAMADOL Drops is 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.

Elderly:

A dose adjustment is not usually necessary in elderly 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 Tramadol drops are not recommended.

Paediatric population:

Tramadol drops is not suitable for children below the age of 12 years. Method of administration the drops should be administered orally and be diluted with water before administration, independent of meals. Treatment goals and discontinuation Before initiating treatment with Tramadol oral drops, 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 commonly reported adverse reactions are nausea and dizziness, both occurring in more than 10 % of patients.

The frequencies are defined as follows:

Very common: ≥1/10 Common: ≥1/100, <1/10 Uncommon: ≥1/1000, <1/100 Rare: ≥1/10 000, <1/1000 Very rare: <1/10 000 Not known: cannot be estimated from the available data A tabulated list of undesirable effects is outlined below: System Organ Class Frequency Adverse reactions Immune system disorders Uncommon Toxic epidermal necrolysis (TEN), Stevens- Johnson-syndrome (SJS) cross reactivity with non-steroidal anti-inflammatory drugs, allergic reaction Metabolism and nutrition disorders Not known Hypoglycemia, hyponatremia Psychiatric disorders Rare Not known Delirium, hallucinations, confusion, sleep disturbance, anxiety, nightmares, changes in mood (elation, occasionally dysphoria), changes in activity (suppression, decision behaviour, perception disorders), suicidal ideation.

4) Nervous system disorders Very common Common Dizziness Headache, drowsiness, somnolence Rare Not known Changes in appetite, paraesthesia, tremor, respiratory depression, involuntary muscle contractions, abnormal coordination, syncope, hypertonia, dysgeusia, respiratory depression, epileptiform convulsions Serotonin syndrome, Speech disorders Rare Miosis, blurred visionEye disorders Not known Mydriasis Uncommon Palpitation, tachycardia, postural hypotension or cardiovascular collapse Cardiovascular disorders Rare Bradycardia, increase in blood pressure Respiratory disorders Rare Dyspnoea, worsening of asthma.

Gastrointestinal disorders:

Very common Common Uncommon Nausea Constipation, dry mouth, vomiting, dyspepsia, abdominal pain Anorexia, retching, gastrointestinal irritation (a feeling of pressure in the stomach, bloating), diarrhoea Skin and subcutaneous tissue disorders Common Uncommon Sweating Dermal reactions (Pruritus, rash, urticaria) Musculo-skeletal disorders: Rare Motorial weakness Renal and urinary disorders Rare Micturition disorders (difficulty in passing urine, dysuria and urinary retention) Hepatobiliary disorders Very rare Elevated liver enzymes Reproductive system and breast disorders: Common Menopausal symptoms Drug dependence Repeated use of Tramadol oral drops 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 or search for MHRA Yellow Card in the Google Play or Apple App Store.

Tramadol drops may only be used with particular caution in opioid-dependent patients, patients with head injury, shock, a reduced level of consciousness of uncertain origin, disorders of the respiratory centre or function, increased intracranial pressure.

In patients sensitive to opiates Tramadol drops should only be used with caution. 9) as the possibility of respiratory depression cannot be excluded in these situations. Convulsions have been reported in patients receiving tramadol at the recommended dose levels.

The risk may be increased when doses of tramadol hydrochloride exceed the recommended upper daily dose limit (400 mg). 5). Patients with epilepsy or those susceptible to seizures should only be treated with tramadol if there are compelling circumstances.

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 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 Tramadol oral drops.

Repeated use of Tramadol oral drops 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 Tramadol oral drops 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.

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 tramadol 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 new born infants will experience neonatal withdrawal syndrome. Hyperalgesia 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. Risk from concomitant use of sedative medicines such as benzodiazepines or related drugs: Concomitant use of Tramadol oral drops and sedative medicines such as benzodiazepines or related drugs may result in sedation, respiratory depression, coma and death.

Because of these risks, concomitant prescribing with these sedative medicines should be reserved for patients for whom alternative treatment options are not possible. If a decision is made to prescribe Tramadol oral drops concomitantly with sedative medicines, 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). 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.

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5), - in patients with epilepsy not adequately controlled by treatment, - for use in narcotic withdrawal treatment.