PARACETAMOL / CAFFEINE

Oral use.

Adults (16 years and over):

Two tablets up to four times daily. The dose should not be repeated more frequently than every 4 hours. Do not exceed 8 tablets in 24 hours.

Elderly:

As for adults. Not recommended for children under 16 years.

Impaired Renal Function:

In case of renal insufficiency dose adjustment is necessary: Impaired Hepatic Function: In patients with impaired hepatic function or Gilbert’s syndrome, the dose must be reduced or the dosing interval prolonged. The daily effective dose of paracetamol should not exceed 60 mg/kg/day (up to maximum 2 g paracetamol /day) in the following situations: _ Adults or adolescents weighing less than 50 kg _ Mild to moderate hepatic insufficiency, Gilbert’s syndrome (familial non- heamolytic jaundice) _ Dehydration _ Chronic malnutrition _ Chronic alcoholism Method of administration Route of administration: Oral

Adverse events from historical clinical trial data are both infrequent and from small patient exposure. Accordingly, considered attributable are tabulated below by MedDRA System Organ Class. Adverse reactions identified during postmarketing use are reported voluntarily from a population of uncertain size, the frequency of these reactions is unknown but likely to be listed below by system organ class and frequency.

Frequencies are defined as: 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 including isolated reports) and not known (cannot be estimated from available data).

Blood and lymphatic system disorders Very Rare Thrombocytopenia, Leukopenia, Neutropenia, hemolytic anemia, agranulocytosis, Immune system disorders Rare Anaphylaxis Cutaneous hypersensitivity reactions including (amongst others) skin rashes and angioedema, allergic dermatitis Metabolism and nutrition disorders Very Rare Hypoglycaemia Not known High anion gap metabolic acidosis Common Insomnia, restlessness, anxietyPsychiatric disorders: Rare Depression NOS, confusion, hallucinations.

Gastrointestinal Common Gastrointestinal disorder disorders Rare Haemorrhage NOS, abdominal pain NOS, diarrhoea NOS, nausea, vomiting Common Dizziness, NervousnessNervous system disorders Rare Tremor NOS, headache NOS Eye disorders Rare Abnormal vision.

Cardiac disorders Rare Oedema. Respiratory, thorasic and mediastinal disorder Very Rare Bronchospasm- more likely in patients sensitive to aspirin and other NSAIDs Rare hepatic failure, Hepatic dysfunction, hepatic necrosis, jaundice.

Hepato-biliary disorders Very Rare Hepatotoxicity, increased transaminases Rare Pruritus, rash, sweating, purpura, angioedema, urticaria Skin and subcutaneous tissue disorders Very Rare Serious skin reactions have been reported. Renal and urinary disorders Very Rare Sterile pyuria (cloudy urine) and renal side effects Rare Dizziness (excluding vertigo), malaise, pyrexia, sedation, drug interaction NOS.

General disorders and administration site conditions Very Rare hypersensitivity reaction (requiring discontinuation of treatment) Injury, poisoning and procedural complications Rare Overdose and poisoning Not known: Irritability, Palpitations, tachycardia, Edema of the larynx, anaphylactic shock, anaemia, bronchospasm*, liver alteration and hepatitis, renal alteration (severe renal impairment, nephrite interstitial, haematuria, anuresis), gastrointestinal effects and vertigo have been reported.

* There have been cases of bronchospasm with paracetamol, but these are more likely in asthmatics sensitive to aspirin or other NSAIDs. 4). Pyroglutamic acidosis may occur as a consequence of low glutathione levels in these patients.

When the recommended dosing regimen is combined with dietary caffeine intake, the resulting higher dose of caffeine may increase the potential for caffeine-related adverse effects such as nervousness, dizziness, insomnia, restlessness, anxiety, irritability, headache, gastrointestinal disorder and palpitations.

CAFFEINE When the recommended paracetamol-caffeine dosing regimen is combined with dietary caffeine intake, the resulting higher dose of caffeine may increase the potential for caffeine-related adverse effects. Body System Undesirable effect Central nervous system Dizziness Headache Cardiac disorders Palpitation Psychiatric disorders Insomnia Restlessness Anxiety and irritability Gastrointestinal disorders Gastrointestinal disturbances 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.

2). Do not exceed stated dose. Contains paracetamol. Do not use with any other paracetamol containing products. The concomitant use with other products containing paracetamol may lead to an overdose. Paracetamol overdose may cause liver failure which may require liver transplant or lead to death.

Care is advised in the administration of paracetamol to patients with renal or hepatic impairment. The hazard of overdose is greater in those with non- cirrhotic alcoholic liver disease. 9). g. chronic alcoholism) who were treated with paracetamol at therapeutic dose for a prolonged period or a combination of paracetamol and flucloxacillin.

If HAGMA due to pyroglutamic acidosis is suspected, prompt discontinuation of paracetamol and close monitoring is recommended. The measurement of urinary 5-oxoproline may be useful to identify pyroglutamic acidosis as underlying cause of HAGMA in patients with multiple risk factors.

The hazards of overdose are greater in those with non-cirrhotic alcoholic liver disease. Caution should be exercised in cases of chronic alcoholism. The daily dose should not exceed 2 grams in such cases. Alcohol should not be used during the treatment with paracetamol.

Caution is advised in asthmatic patients sensitive to aspirin, because light reaction bronchospasm with paracetamol (cross-reaction) has been reported in less than 5% of the patients tested. Paracetamol / Caffeine 500 mg/65 mg Tablets should be given with care to patients with gout, hyperthyroidism and arrhythmia.

g. coffee, tea and some canned drinks) should be avoided while taking this product as excess caffeine may cause nervousness, irritability, sleeplessness and occasionally rapid heart beat. Glomerular filtration Dose 10-50 ml/min 1 tablet every 6 hours < 10 ml/min 1 tablet every 8 hours As caffeine is found naturally in tea, coffee and chocolate, and in some carbonated drinks there is the potential for users to take more than the recommended 390 mg/day of caffeine (6 tablets) per day.

Patients should take account of dietary and other medicinal sources of caffeine and ensure that they do not exceed the stated dose. Typical amounts of caffeine available from dietary sources are Brewed coffee; 50-100mg/100ml* Instant coffee and tea: 20-73mg/100ml* Carbonated drinks (cola) 9-19mg/100ml* Chocolate 5-20mg/100ml (*100ml is equivalent to about 1 small cup of fluid) If symptoms persist, medical advice must be sought.

Keep out of the sight and reach of children. Important information regarding the excipients in this medicine This medicine contains less than 1 mmol sodium (23 mg) per tablet, that is to say essentially ‘sodium-free’.

1.