PARACETAMOL AND CAFFEINE 500 MG / 50 MG SOLUBLE TABLETS - Summary of medicine characteristics

1 NAME OF THE MEDICINAL PRODUCT

Paracetamol and Caffeine 500mg/50mg Soluble Tablets

2 QUALITATIVE AND QUANTITATIVE COMPOSITION

Each tablet contains paracetamol 500 mg and caffeine 50 mg

Excipients with known effect:

Sodium 316 mg (13.7 mmol)

Lactose monohydrate 108 mg

Sorbitol 80 mg

For the full list of excipients, see section 6.1.

3 PHARMACEUTICAL FORM

White, round, biplane soluble tablet, 23mm in diameter with a score line on one face.

4 CLINICAL PARTICULARS

4.1 Therapeutic indications

For the treatment of mild to moderate pain and febrile conditions, for example, headache including migraine, backache, toothache, colds and influenza, sore throat, rheumatic pain and dysmenorrhoea.

4.2 Posology and method of administration

Posology:

Adults:

1 – 2 tablets dissolved in water not more frequently than every 4 – 6 hours as required up to a maximum of 8 tablets in 24 hours.

Elderly:

No special dosage regimen required, but care should be taken to observe the contraindications, precautions and warnings, which may be particularly applicable to elderly persons.

Paediatric population

Children aged 16 – 18 years:

One to two tablets dissolved in water every 4 – 6 hours when necessary to a maximum of 8 tablets in 24 hours.

Children aged 12–15 years:

One tablet dissolved in water every 6 hours when necessary to a maximum of 4 tablets in 24 hours.

Not recommended for children under 12 years.

Method of administration

Paracetamol and Caffeine 500mg / 50mg Soluble Tablets should be dissolved in at least half a tumbler of water.

4.3 Contraindications

Hypersensitivity to the active substances or to any of the excipients listed in section 6.1.

4.4 Special warnings and precautions for use

Paracetamol should be used with caution in patients with severe renal disease or liver dysfunction. The hazards of overdose are greater in those with non-cirrhotic alcoholic liver disease.

Excessive intake of caffeine from coffee and tea should be avoided while taking this product.

Keep out of the sight and reach of children.

Do not exceed the stated dose.

If symptoms persist consult your doctor.

The label will say: Contains paracetamol. Do not take with any other paracetamol – containing products. Immediate medical advice should be sought in the event of an overdose, even if you feel well.

The leaflet (including label – leaflets) will say: Immediate medical advice should be sought in the event of an overdose, even if you feel well, because of the risk of delayed, serious liver damage

This medicinal product contains 316 mg sodium per tablet, equivalent to 15.8% of the WHO recommended maximum daily intake of 2 g sodium for an adult.

These tablets contain sorbitol. Patients with hereditary fructose intolerance (HFI) should not take/be given this medicinal product.

These tablets contain lactose. Patients with rare hereditary problems of galactose intolerance, total lactase deficiency or glucose-galactose malabsorption should not take this medicine.

4.5 Interaction with other medicinal products and other forms of interaction Paracetamol:

The anticoagulant effect of warfarin and other coumarins may be enhanced by prolonged regular use of paracetamol with increased risk of bleeding. Occasional doses have no significant effect.

Metoclopramide/dom­peridone: The speed of absorption of paracetamol may be increased by metoclopramide or domperidone. Concurrent use need not be avoided.

Cholestyramine: The speed of absorption of paracetamol may be reduced by cholestyramine if given at the same time, but the reduction in absorption is small if given an hour later.

Caffeine:

The effects of caffeine may be enhanced by isoniazid and meprobamate.

If taking other prescribed medicines a doctor should be consulted before taking the product.

4.6 Fertility, pregnancy and lactation

Pregnancy

Paracetamol:

A large amount of data on pregnant women indicate neither malformative, nor feto/neonatal toxicity. Epidemiological studies on neurodevelopment in children exposed to paracetamol in utero show inconclusive results. If clinically needed, paracetamol can be used during pregnancy however it should be used at the lowest effective dose for the shortest possible time and at the lowest possible frequency.

Caffeine:

Caffeine crosses the placental barrier. Some animal studies have shown foetal malformations from caffeine, but no abnormalities have been observed in humans following administration during pregnancy.

However, it is recommended that the product is only used during pregnancy on medical advice.

Lactation

Paracetamol:

Paracetamol is excreted in breast milk but not in a clinically significant amount. Available published data do not contraindicate breast feeding for paracetamol.

Caffeine:

Care is advisable during lactation since caffeine passes into the maternal milk.

Fertility

There is insufficient information available on the effects of paracetamol and caffeine on human fertility.

4.7 Effects on ability to drive and use machines None

4.8 Undesirable effects

Adverse events from historical clinical trial data are both infrequent and from small patient exposure. Accordingly, events reported from extensive post- marketing experience at therapeutic/la­belled dose and considered attributable are tabulated below by system class. Due to limited clinical trial data, the frequency of these adverse events is not known (cannot be estimated from available data), but postmarketing experience indicates that adverse reactions to paracetamol are rare and serious reactions are very rare.

Hypersensitivity, including skin rash, may occur but is rare. There have been very rare reports of blood dyscrasias including thrombocytopenia and agranulocytosis but these were not necessarily causally related to paracetamol.

Post marketing data

*There have been cases of bronchospasm with paracetamol, but these are more likely in asthmatics sensitive to aspirin or other NSAIDs.

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 such as insomnia, restlessness, anxiety, irritability, headaches, gastrointestinal disturbances and palpitations.

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. Healthcare professionals are asked to report any suspected adverse reactions via the Yellow Card Scheme; website: www.mhra.gov.uk/yellowcard or search for MHRA Yellow Card in the Google Play or Apple App Store

4.9 Overdose

Paracetamol:

Liver damage is possible in adults who have taken 10g or more of paracetamol. Ingestion of 5g or more of paracetamol may lead to liver damage if the patient has risk factors (see below).

Risk factors

a) If the patient is on long term treatment with carbamazepine, phenobarbitone, phenytoin, primidone, rifampicin, St John’s Wort or other drugs that induce liver enzymes.

or

b) Regularly consumes ethanol in excess of recommended amounts.

or

c) Is likely to be glutathione deplete e.g eating disorders, cystic fibrosis, HIV infection, starvation, cachexia.

Symptoms

Symptoms of paracetamol overdosage in the first 24 hours are pallor, nausea, vomiting, anorexia and abdominal pain. Liver damage may become apparent 12 to 48 hours after ingestion. Abnormalities of glucose metabolism and metabolic acidosis may occur. In severe poisoning, hepatic failure may progress to encephalopathy, haemorrhage, hypoglycaemia, cerebral oedema, and death. Acute renal failure with acute tubular necrosis, strongly suggested by loin pain, haematuria and proteinuria, may develop even in the absence of severe liver damage. Cardiac arrhythmias and pancreatitis have been reported.

Management

Immediate treatment is essential in the management of paracetamol overdose. Despite a lack of significant early symptoms, patients should be referred to hospital urgently for immediate medical attention. Symptoms may be limited to nausea or vomiting and may not reflect the severity of overdose or the risk of organ damage. Management should be in accordance with established treatment guidelines, see BNF overdose section. Treatment with activated charcoal should be considered if the overdose has been taken within 1 hour. Plasma paracetamol concentration should be measured at 4 hours or later after ingestion (earlier concentrations are unreliable). Treatment with N-acetylcysteine may be used up to 24 hours after ingestion of paracetamol, however, the maximum protective effect is obtained up to 8 hours post-ingestion. The effectiveness of the antidote declines sharply after this time. If required the patient should be given intravenous N-acetylcysteine, in line with the established dosage schedule. If vomiting is not a problem, oral methionine may be a suitable alternative for remote areas, outside hospital. Management of patients who present with serious hepatic dysfunction beyond 24h from ingestion should be discussed with the NPIS or a liver unit.

Caffeine:

Symptoms

Common symptoms include anxiety, nervousness, restlessness, insomnia, excitement, diuresis, facial flushing, muscle twitching, gastrointestinal disorders, confusion, convulsions. For high intake of caffeine, hyperglycemia could also appear. Cardiac symptoms include tachycardia and cardiac arrhythmia. It must be noted that for clinically significant symptoms of caffeine overdose to occur with this product, the amount ingested would be associated with serious paracetamol related toxicity.

Management

Patients should receive general supportive care (e.g. hydration and maintenance of vital signs). The administration of activated charcoal may be beneficial when performed within one hour of the overdose but can be considered for up to four hours after the overdose. The CNS effects of overdose may be treated with intravenous sedatives.

Sodium bicarbonate

High doses of sodium bicarbonate may be expected to induce gastrointestinal symptoms including belching and nausea. In addition, high doses of sodium bicarbonate may cause hypernatraemia; electrolytes should be monitored and patients managed accordingly.

5.1 Pharmacodynamic properties

Pharmacotherapeutic Group : Analgesics, Other Analgesics and Antipyretics;

Analides: Paracetamol, combinations excl.

ATC code: N02BE51

The combination of paracetamol and caffeine is a well-established analgesic combination

Paracetamol is an analgesic and antipyretic agent. Caffeine is a central nervous system stimulant.

5.2 Pharmacokinetic properties

Paracetamol is rapidly and completely absorbed from the gastro-intestinal tract giving peak blood levels 40–60 minutes after ingestion. Paracetamol is metabolised by the liver and its metabolites excreted via the kidneys principally as the glucuronide and sulphate conjugates.

Caffeine is rapidly and completely absorbed from the gastro-intestinal tract and maximum plasma levels are usually attained between several minutes and one hour after ingestion and the plasma half-life is about 3.5 hours. Caffeine is metabolised by the liver and 65–85% of the administrated dose is excreted via the kidney as 1-methyluric acid and 1-methylxanthine..

5.3 Preclinical safety data

6   PHARMACEUTICAL PARTICULARS

6.1 List of excipients

Povidone

Sodium bicarbonate

Citric acid anhydrous

Sorbitol

Lactose monohydrate

Sodium saccharin

L-leucine

Magnesium stearate

6.2 Incompatibilities

None

6.3 Shelf life

3 years

6.4 Special precautions for storage

Store in the original packaging to protect from light and moisture.

6.5 Nature and contents of container

Carton containing 2 polypropylene tubes of 16 soluble tablets each.

Pack size: 32

6.6 Special precautions for disposal

Not applicable

7 MARKETING AUTHORISATION HOLDER

Apollo Generics Limited Unit 1, 76 Stephenson Way Formby Business Park Liverpool

Merseyside

L37 8EG

United Kingdom

8 MARKETING AUTHORISATION NUMBER(S)

PL 31603/0022

9 DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION

29/11/2018