TRAMADOL HYDROCHLORIDE/PARACETAMOL

Treatment goals and discontinuation Before initiating treatment with Tramadol Hydrochloride/Paracetamol, 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). Posology The use of Tramadol Hydrochloride/Paracetamol should be restricted to patients whose moderate to severe pain is considered to require a combination of tramadol and paracetamol. The dose should be adjusted to intensity of pain and the sensitivity of the individual patient.

The lowest effective dose for analgesia should generally be selected. The total dose of 8 tablets (equivalent to 300 mg tramadol hydrochloride and 2600 mg paracetamol) per day should not be exceeded. The dosing interval should not be less than six hours.

Adults and adolescents (12 years and older) An initial dose of two tablets of Tramadol hydrochloride/Paracetamol is recommended. Additional doses can be taken as needed, not exceeding 8 tablets (equivalent to 300 mg tramadol and 2600 mg paracetamol) per day.

The dosing interval should not be less than six hours. 4 - Special warnings and precautions for use). If repeated use or long term treatment with Tramadol hydrochloride/Paracetamol is required as a result of the nature and severity of the illness, then careful, regular monitoring should take place (with breaks in the treatment, where possible), to assess whether continuation of the treatment is necessary.

Paediatric population The effective and safe use of Tramadol hydrochloride/Paracetamol has not been established in children below the age of 12 years. Treatment is therefore not recommended in this population. Older patients A dose adjustment is not usually necessary in patients up to 75 years without clinically manifest hepatic or renal insufficiency.

In older people 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 In patients with renal 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. Hepatic impairment In patients with hepatic impairment the elimination of tramadol is delayed. 4). 3). Method of administration Oral use Tablets must be swallowed whole, with a sufficient quantity of liquid.

They must not be broken or chewed.

The most commonly reported undesirable effects during the clinical trials performed with the paracetamol/tramadol hydrochloride combination were nausea, dizziness and somnolence, observed in more than 10 % of the patients.

The frequencies are defined as follows:

Very common: ≥1/10 Common: ≥1/100 to <1/10 Uncommon: ≥1/1000 to <1/100 Rare: ≥1/10 000 to <1/1000 Very rare: <1/10 000 Unknown: Frequency cannot be estimated from the available data Within each frequency grouping, undesirable effects are presented in order of decreasing seriousness.

Cardiac disorders: - Uncommon: palpitations, tachycardia, arrythmia. Eye disorders: - Rare: vision blurred, miosis, mydriasis Ear and labyrinth disorders: - Uncommon: tinnitus Gastro-intestinal disorders: - Very common: nausea - Common: vomiting, constipation, dry mouth, diarrhoea abdominal pain, dyspepsia, flatulence - Uncommon: dysphagia, melaena General disorders and administration site conditions: - Uncommon: chills, chest pain, drug withdrawal syndrome Investigations: - Uncommon: transaminases increased Metabolism and nutrition disorders: - Unknown: hypoglycaemia -Not known: high anion gap metabolic acidosis Nervous system disorders: - Very common: dizziness, somnolence - Common: headache trembling - Uncommon: involuntary muscular contractions, paraesthesia, amnesia - Rare: ataxia, convulsions, syncope, speech disorders.

- Not known: serotonin syndrome. 4) Post marketing surveillance very rare: abuse. rash, urticaria). 4). Pyroglutamic acidosis may occur as a consequence of low glutathione levels in these patients. Although not observed during clinical trials, the occurrence of the following undesirable effects known to be related to the administration of tramadol or paracetamol cannot be excluded: Tramadol - Postural hypotension, bradycardia, collapse (tramadol).

- Post-marketing surveillance of tramadol has revealed rare alterations of warfarin effect, including elevation of prothrombin times. g. dyspnoea, bronchospasm, wheezing, angioneurotic oedema) and anaphylaxis - Rare cases (≥ 1/10000 to < 1/1000): changes in appetite, motor weakness, and respiratory depression - Psychic side-effects may occur following administration of tramadol which vary individually in intensity and nature (depending on personality and duration of medication).

g. decision behaviour perception disorders). - Worsening of asthma has been reported though a causal relationship has not been established. - Symptoms of drug withdrawal syndrome, similar to those occurring during opiate withdrawal may occur as follows: agitation, anxiety, nervousness, insomnia, hyperkinesia, tremor and gastrointestinal symptoms.

Other symptoms that have very rarely been seen if tramadol hydrochloride is discontinued abruptly include: panic attacks, severe anxiety, hallucinations, paraesthesia, tinnitus and unusual CNS symptoms. -Respiratory, thoracic and mediastinal disorders: frequency not known: hiccups.

Paracetamol - Adverse effects of paracetamol are rare but hypersensitivity including skin rash may occur. There have been reports of blood dyscrasias including thrombocytopenia and agranulocytosis, but these were not necessarily causally related to paracetamol.

- There have been several reports that suggest that paracetamol may produce hypoprothrombinemia when administered with warfarin-like compounds. In other studies, prothrombin time did not change. - Very rare cases of serious skin reactions have been reported.

Drug dependence Repeated use of Tramadol hydrochloride/Paracetamol 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.

4. Special Warnings). 4 Special warnings and precautions for use Warnings: - In adults and adolescents 12 years and older. The maximum dose of 8 tablets of Tramadol hydrochloride/Paracetamol should not be exceeded. In order to avoid inadvertent overdose, patients should be advised not to exceed the recommended dose and not to use any other paracetamol (including over the counter) or tramadol hydrochloride containing products concurrently without the advice of a physician.

- In severe renal insufficiency (creatinine clearance <10 ml/mm), Tramadol hydrochloride/Paracetamol is not recommended. 3). The hazards of paracetamol overdose are greater in patients with non-cirrhotic alcoholic liver disease. In moderate cases prolongation of dosage interval should be carefully considered.

- In severe respiratory insufficiency, Tramadol hydrochloride/Paracetamol is not recommended. - Tramadol is not suitable as a substitute in opioid-dependent patients. Although it is an opioid agonist, tramadol cannot suppress morphine withdrawal symptoms.

- Convulsions have been reported in tramadol-treated patients susceptible to seizures or taking other medications that lower the seizure threshold, especially selective serotonin re-uptake inhibitors, tricyclic antidepressants, antipsychotics, centrally acting analgesics or local anaesthesia.

Epileptic patients controlled by a treatment or patients susceptible to seizures should be treated with this medicine only if there are compelling circumstances. Convulsions have been reported in patients receiving tramadol at the recommended dose levels.

The risk may be increased when doses of tramadol exceed the recommended upper dose limit. - Concomitant use of opioid agonists-antagonists (nalbuphine, buprenorphine, pentazocine) is not recommended (see

1, - acute intoxication with alcohol, hypnotic drugs, centrally-acting analgesics, opioids or psychotropic drugs, - Tramadol hydrochloride/Paracetamol should not be administered to patients who are receiving monoamine oxidase inhibitors or within two weeks of their withdrawal (see