PARACETAMOL AND CAFFEINE 500 MG / 65 MG EFFERVESCENT TABLETS, BOOTS PARACETAMOL EXTRA EFFERVESCENT TABLETS 500 MG / 65 MG, PARASOLVE EXTRA 500 MG / 65 MG EFFERVESCENT TABLETS, PARAVESCENT EXTRA 500 MG / 65 MG EFFERVESCENT TABLETS - summary of medicine characteristics

1 NAME OF THE MEDICINAL PRODUCT

Paracetamol and Caffeine 500 mg/65 mg Effervescent Tablets Boots Paracetamol Extra Effervescent Tablets 500 mg/65 mg Parasolve® Extra 500 mg/65 mg Effervescent Tablets

Paravescent Extra 500mg/65mg Effervescent Tablets

2 QUALITATIVE AND QUANTITATIVE COMPOSITION

Each tablet contains Paracetamol 500 mg and Caffeine 65 mg.

For a full list of excipients, see Section 6.1.

3 PHARMACEUTICAL FORM

Effervescent Tablet.

Paracetamol and Caffeine 500 mg/65 mg Effervescent Tablets are white to off white coloured circular flat bevelled tablets plain on both sides.

4 CLINICAL PARTICULARS

4.1 Therapeutic indications

Paracetamol & Caffeine Effervescent Tablets are a mild analgesic and antipyretic formulated to give extra pain relief. The tablets are recommended for the treatment of most painful and febrile conditions, for example, headache, including migraine, backache, toothache, rheumatic pain and dysmenorrhoea, and relief of the symptoms of colds, influenza and sore throat.

4.2 Posology and method of administration

Paracetamol & Caffeine Effervescent Tablets should be dissolved in at least half a tumbler of water.

One to two tablets dissolved in water not more frequently than every 4–6 hours when necessary to a maximum of 8 tablets in 24 hours.

Same as adult dose. A reduced dose may be required

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.

Children aged less than 12 years: Not

recommended for children under

12years. Method of Administration

Paracetamol & Caffeine Effervescent Tablets are for oral administration on­ly.

4.3 Contraindications

Hypersensitivity to paracetamol, caffeine or any of the other constituents.

4.4 Special warnings and precautions for use

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.

Excessive intake of caffeine (e.g. coffee, tea and some canned drinks) should be avoided while taking this product.

Do not exceed the stated dose.

Patients should be advised to consult their doctor if their headaches become persistent.

Patients should be advised not to take other paracetamol-containing products concurrently.

This medicinal product contains 409 mg sodium per dose (one tablet), equivalent to 20.45% of the WHO recommended maximum daily intake for sodium. The maximum daily dose of this product is equivalent to 163.6% of the WHO recommended maximum daily intake for sodium. Paracetamol and Caffeine 500 mg/65 mg Effervescent Tablets is considered high in sodium. This should be particularly taken into account for those on a low salt diet.

Patients with rare hereditary problems of fructose intolerance should not take this medicine.

If symptoms persist consult your doctor.

Keep out of the sight and reach of children.

This product contains aspartame, a source of phenylalanine which may be harmful for people with phenylketonuria.

Pack Label:

Immediate medical advice should be sought in the event of an overdose, even if you feel well. Do not take with any other paracetamol-containing products.

Patient Information Leaflet:

.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.

4.5 Interaction with other medicinal products and other forms of interaction

The speed of absorption of paracetamol may be increased by metoclopramide or domperidone and absorption reduced by colestyramine. The anticoagulant effect of warfarin and other coumarins may be enhanced by prolonged regular daily use of paracetamol with increased risk of bleeding; occasional doses have no significant effect.

4.6 Fertility, pregnancy and lactation

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.

However, paracetamol-caffeine is not recommended for use during pregnancy due to the possible increased risk of lower birth weight and spontaneous abortion associated with caffeine consumption.

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

Caffeine in breast milk may potentially have a stimulating effect on breast fed infants.

Therefore, due to the caffeine content of this product it should not be used if you are pregnant or breast feeding.”

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 postmarketing 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 post-marketing experience indicates that adverse reactions to paracetamol are rare and serious reactions are very rare.

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 at 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 10 g or more of paracetamol. Ingestion of 5 g or more of paracetamol may lead to liver damage if the patient has risk factors (see below).

Risk Factors:

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

Regularly consumes ethanol in excess of recommended amounts.

Or

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

Symptoms

Symptoms of paracetamol overdose in the first 24 hours are pallor, nausea, vomiting, anorexia and abdominal pain. Liver damage may become appar ent

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 beenreported.

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

Overdose of caffeine may result in epigastric pain, vomiting, diuresis, tachycardia or cardiac arrhythmia, CNS stimulation (insomnia, restlessness, excitement, agitation, jitteriness, tremors and convulsions).

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.

Summary

Treatment of overdose with Cope Sachets requires assessment of plasma paracetamol levels for antidote treatment, with signs and symptoms of codeine and caffeine toxicity being managed symptomatically.

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 PHARMACOLOGICAL PROPERTIES

5.1 Pharmacodynamic properties

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

5.2 Pharmacokinetic properties

Paracetamol is rapidly and almost completely absorbed from the gastrointestinal tract, it is relatively uniformly distributed throughout most body fluids and exhibits variable protein binding. Excretion is almost exclusively renal, in the form of conjugated metabolites.

Caffeine is absorbed readily after oral administration, maximal plasma concentrations are achieved within one hour and the plasma half-life is about 3.5 hours. 65 – 80% of administered caffeine is excreted in the urine as 1-methyluric acid and 1-methylxanthine.

5.3 Preclinical safety data

There are no pre-clinical data of relevance to the prescriber which are additional to that

Paracetamol: Conventional studies using the currently accepted standards for the evaluation of toxicity already included in other sections of the SPC.of reproduction and development are not available

toxicity, embryofoetal toxicity (resorptions), lower foetal body weights, tail and vertebral malformations, reduced ossification (vertebrae, sternebrae, and phalanges), and extra lumbar vertebrae and ribs were observed at high exposures. In rabbits, embryo-foetal toxicity (resorptions), reduced ossification (hyoid), and an increased incidence of 13th rib were observed at high exposures. In a peri-postnatal study in rats, no adverse effects on offspring were observed. In a separate study wherein entecavir was administered to pregnant lactating rats at 10 mg/kg, both foetal exposure to entecavir and secretion of entecavir into milk were demonstrated. In juvenile rats administered entecavir from postnatal days 4 to 80, a moderately reduced acoustic startle response was noted during the recovery period (postnatal days 110 to 114) but not during the dosing period at AUC values > 92 times those in humans at the 0.5 mg dose or paediatric equivalent dose. Given the exposure margin, this finding is considered of unlikely clinical significance.

No evidence of genotoxicity was observed in an Ames microbial mutagenicity assay, a mammaliancell gene mutation assay, and a transformation assay with Syrian hamster embryo cells. A micronucleus study and a DNA repair study in rats were also negative. Entecavir was clastogenic to human lymphocyte cultures at concentrations substantially higher than those achieved clinically.

Two-year carcinogenicity studies: in male mice, increases in the incidences of lung tumours were observed at exposures > 4 and > 2 times that in humans at 0.5 mg and 1 mg respectively. Tumour development was preceded by pneumocyte proliferation in the lung which was not observed in rats, dogs, or monkeys, indicating that a key event in lung tumour development observed in mice likely was species-specific. Increased incidences of other tumours including brain gliomas in male and female rats, liver carcinomas in male mice, benign vascular tumours in female mice, and liver adenomas and carcinomas in female rats were seen only at high lifetime exposures. However, the no effect levels could not be precisely established. The predictivity of the findings for humans is not known.

6 PHARMACEUTICAL PARTICULARS

6.1 List of excipients

Citric Acid (anhydrous) (E330), Povidone, Saccharin Sodium, Sodium Hydrogen Carbonate (E500) , Sodium Carbonate Anhydrous, Simeticone, Polysorbate 80 (E433), and Aspartame (E951).

6.2 Incompatibilities

Not applicable.

6.3 Shelf life

3 years.

6.4 Special precautions for storage

Store in the original package and protect from moisture.

6.5 Nature and contents of container

4– Ply laminate strip pack

These tablets are available in a pack size of 24.

6.6 Special precautions for disposal

7   MARKETING AUTHORISATION HOLDER

8 MARKETING AUTHORISATION NUMBER(S)

PL 51463/0023