PARACETAMOL EXTRA STRENGTH PAIN RELIEF TABLETS, SUPERDRUG PARACETAMOL PLUS PAIN RELIEF TABLETS, HEALTH ESSENTIALS PAIN RELIEF EXTRA 500 MG / 65 MG TABLETS - summary of medicine characteristics

1 NAME OF THE MEDICINAL PRODUCT

Paracetamol Extra Strength Pain Relief Tablets

Superdrug Paracetamol Plus Pain Relief Tablets

Health Essentials Pain Relief Extra 500mg/65mg Tablets

2 QUALITATIVE AND QUANTITATIVE COMPOSITION

Paracetamol 500mg

Caffeine 65mg

For the full list of excipients, see section 6.1.

3 PHARMACEUTICAL FORM

Tablets

Capsule shaped tablets.

4 CLINICAL PARTICULARS

4.1 Therapeutic indications

For mild to moderate pain, including headache, toothache, period pain, symptomatic relief of rheumatic aches and pains and pain associated with muscular disorder.

4.2 Posology and method of administration

Dose: Unless otherwise directed by a doctor –

Adults, Elderly and children 16 years and over: 1 to 2 tablets every 4 – 6 hours. Do not take more than 8 tablets in 24 hours.

Dose should not be taken more frequently than at 4 hourly intervals and not more than 4 times in any 24 hour period.

Children 12 – 15 years: One tablet every 4–6 hours when necessary to a maximum of 4 doses in any 24 hours.

Children under 12 years of age: Do not give to children unless advised by a doctor.

Route of administration: Oral with water.

4.3 Contraindications

Paracetamol:

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

Caffeine:

Hypersensitivity to caffeine.

Do not give to patients with a history of peptic ulceration.

4.4 Special warnings and precautions for use

Paracetamol:

Care is advised in the administration of paracetamol to patients with renal or hepatic impairment. The hazards of overdose are greater in those with alcoholic liver disease. Paracetamol should be given with care to patients with alcohol dependence. Paracetamol is well tolerated by the majority of people with asthma. However a small percentage of aspirin sensitive asthmatics are also sensitive to paracetamol. The likelihood of a reaction to paracetamol increases with a patient’s level of sensitivity to aspirin. (See also 4.8 Undesirable effects).

Caution should be exercised when using paracetamol prior to (less than 72 hours) or concurrently with intravenous busulfan (see section 4.5 Interactions).

Caffeine:

Care is advised in the administration of caffeine to patients with cardiac disease.

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

Generally:

* Do not exceed the stated dose

* If symptoms persist, consult your doctor. Do not take for more than 3 days without consulting your doctor.

* If you are receiving a course of medicinal treatment, consult your doctor.

The label text shall state:

Do not take more medicine than the label tells you to. If you do not get better, talk to your doctor.

Do not take anything else containing paracetamol while taking this medicine.

Talk to a doctor at once if you take too much of this medicine, even if you feel well.

The leaflet text shall state:

Talk to a doctor at once if you take too much of this medicine even if you feel well. This is because too much paracetamol can cause delayed, serious liver damage.

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

Alcohol: Paracetamol should be given with care to patients with alcohol dependence (see Section 4.4)

Analgesics: Diflunisal increases blood concentrations of paracetamol.

Anion- exchange resins: Absorption reduced by colestyramine; administration should be separated by at least 1 hour.

Antibacterials: Isoniazid may increase the risk of hepatotoxicity with therapeutic doses of paracetamol.

Anticoagulants. The anticoagulant effect of warfarins and other coumarins may be enhanced by prolonged regular daily use of paracetamol, with increased risk of bleeding, but occasional doses have no significant effect.

Antiepileptics: Carbamazepine, phenobarbital, phenytoin and primidone can reduce the effects of paracetamol and increase the risk of hepatotoxicity.

Cytotoxic drugs: Paracetamol possibly inhibits metabolism of intravenous busulfan (manufacturer of intravenous busulfan advises caution within 72 hours of paracetamol).

Motility stimulants: The speed of absorption of paracetamol may be increased by metoclopramide or domperidone.

Oral contraceptives: Paracetamol is cleared from the body more quickly in women taking oral contraceptives and the analgesic effects may be reduced.

Uricosurics: Probenecid can reduce the loss of paracetamol from the body.

Antibacterials: Some quinolone antibiotics, including enoxacin, pipemidic acid and ciprofloxacin can reduce the clearance of caffeine and prolong its plasma half-life.

Antidepressants: Fluvoxamine can reduce the clearance of caffeine and increase its stimulant and side effects.

Antiepileptics: Phenytoin may increase the clearance of caffeine.

Antipsychotics: Caffeine may increase serum clozapine levels.

Benzodiazepines: Caffeine can reduce the sedative effects of diazepam.

Disulfiram: may reduce the clearance of caffeine.

Diuretics: Concomitant use of xanthines with diuretics may increase the risk of hypokalaemia.

Ephedrine/ephedra alkaloids in dietary supplements (Ma Huang): Concomitant use may raise blood pressure; hypertension, tachycardia, subarachnoid haemorrhage, cardiac arrest and neurosis have been reported.

Lithium: Caffeine may increase the clearance of lithium.

Mexiletine: may reduce the clearance of caffeine.

Oestrogens and progestogens: Oral contraceptives or oestrogen replacement therapy may reduce the clearance of caffeine.

Phenylpropano­lamine: Concomitant administration may increase blood pressure, resulting in hypertensive crises in a few susceptible individuals. Manic psychosis has occurred. Phenylpropanolamine can increase serum caffeine levels.

Theophylline: concomitant administration can increase plasma theophylline and plasma caffeine levels.

4.6 Fertility, pregnancy and lactationParacetamol:

Epidemiological studies in human pregnancy have shown no ill effects due to paracetamol use in the recommended dosage, but patients should follow the advice of their doctor regarding its use. 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.

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

Caffeine:

Taken during pregnancy it appears that the half-life of caffeine is prolonged. Caffeine crosses the placenta, and foetal blood and tissue levels similar to maternal concentrations are achieved. This is a possible contributing factor in hyperemesis gravidarum. Cardiac dysrhythmias have been noted in the foetuses and neonates of mothers consuming varying levels of caffeine during pregnancy. Decreased birth weight may be associated with maternal caffeine intake and cigarette smoking. Limited evidence suggests that high maternal caffeine intake may be associated with fetotoxicity including spontaneous abortion, however, other factors may have contributed to the findings.

Decreased fertility may be associated with maternal caffeine intake. Caffeine intake during pregnancy should be kept to a minimum.

Caffeine is excreted in breast milk, but with moderate intake amounts are probably too low to be clinically significant. Regular intake of large amounts of caffeine by nursing mothers can affect the infant including irritability and poor sleeping patterns.

4.7 Effects on ability to drive and use machines

Paracetamol & Caffeine:

None reported

4.8 Undesirable effects

Paracetamol:

Adverse effects of paracetamol are rare.

Haematological : There have been reports of blood dyscrasias including thrombocytopenia and agranulocytosis, but these were not necessarily causally related to paracetamol. Leucopenia, neutropenia and pancytopenia have been reported in association with paracetamol.

Immune system: Hypersensitivity including skin rashes, urticaria or angioedema may occur. A small percentage of aspirin-sensitive asthmatics are also sensitive to paracetamol. In such cases, the deterioration in respiratory function induced by paracetamol is milder and shorter than with aspirin (see also Special warnings and precautions for use)

Skin and subcutaneous tissue disorders: Very rare cases of serious skin reactions have been reported.

Renal: Nephropathy has been associated with chronic high dose use.

Caffeine:

Cardiac disorders: Cardiac arrhythmias including tachycardia.

Gastrointestinal disorders: Nausea, vomiting, increased gastric secretions and gastro-oesophageal reflux.

General disorders: Irritability

Nervous system disorders: Tremor may be experienced.

Psychiatric disorders: Restlessness, anxiety and insomnia may be experienced.

Renal and urinary disorders: Diuresis.

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 OverdoseParacetamol:

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.

If the patient

a. Is on long term treatment with carbmazepine, phenobarbital, 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 depleted e.g. eating disorders, cystic fibrosis, HIV infection, starvation, cachexia.

Symptoms

Symptoms of paracetamol overdose in the first 24 hours are sweating, 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, hypotension, cerebral oedema, coma and death. Prothrombin time may increase with deteriorating liver function. 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 arrythmias and pancreatitis have been reported.

Treatment

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 at least 24 hours post ingestion of paracetamol, however, the maximum protective effect is obtained up to 8 hours after 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.

Symptoms: Large doses may cause restlessness, excitement, psychosis, muscle tremor, tinnitus, hyperglycaemia, hypokalaemia, diuresis, dehydration, tachycardia and extrasystoles. Emesis and convulsions may occur.

Treatment

No specific antidote. Elimination may be enhanced by repeated oral doses of activated charcoal. Symptomatic and supportive treatment.

Hypokalemia should be corrected by intravenous infusion of potassium chloride.

Intravenous diazepam or barbiturates may be used to control convulsions.

5 PHARMACOLOGICAL PROPERTIES

5.1 Pharmacodynamic properties

Paracetamol:

Paracetamol is an effective analgesic and antipyretic agent but has only weak anti-inflammatory properties. Its mechanism of action is not fully understood. It has been suggested that it may act predominantly by inhibiting prostaglandin synthesis in the CNS and to a lesser extent through a peripheral action by blocking pain-impulse generation. The peripheral action may also be due to inhibition of prostaglandin synthesis or to inhibition of the synthesis or actions of other substances that sensitise pain receptors to mechanical or chemical stimulation. Paracetamol probably produces an antipyretic action by a central effect on the hypothalamic heat-regulating centre to produce peripheral vasodilatation resulting in increased blood flow through the skin, sweating and heat loss. The central action probably involves inhibition of prostaglandin synthesis in the hypothalamus. The drug has no effect on the cardiovascular and respiratory systems, and unlike salicylates it does not cause gastric irritation or bleeding.

Caffeine:

Acts on the central nervous system, on muscle including cardiac muscle and the kidneys. Its action on the central nervous system is mainly on the higher centres and produces a condition of wakefulness and increased mental activity. It facilitates the performance of muscular work and increases the total work that can be performed by a muscle. It may stimulate the respiratory centre, increasing the rate and depths of respiration. Its stimulant action on the medullary basomotor centre is usually compensated by its peripheral vasodilator effect on the arterioles, so that the blood pressure usually remains unchanged. The diuretic action of caffeine has been accounted for in many ways. It may increase renal blood flow and glomerular filtration rate, but its main action may be due to the regulation of the normal tubular absorption. It is less effective as a diuretic than theobromine, which has less central stimulating effect and does not cause insomnia. The xanthines are rarely of great value in promoting increased renal function when this is depressed. Caffeine is claimed to enhance the action of ergotamine and is frequently given with ergotamine in the treatment of migraine.

5.2 Pharmacokinetic properties

Paracetamol:

Paracetamol is readily absorbed from the gastro-intestinal tract with peak plasma concentrations occurring 30 minutes to 2 hours after ingestion. It is metabolised in the liver(90–95%) and excreted in the urine, mainly as the glucoronide and sulphate conjugates. Less than 5% is excreted as unchanged Paracetamol. The elimination half-life varies from about 1–4 hours. Plasmaprotein binding is negligible at usual therapeutic concentrations but increases with increasing concentration. A minor hydroxylated metabolite (N-acetyl-p-benzoquinonei­mine)(which is usually produced in very small amounts by mixed-function oxidases in the liver and which is usually detoxified by conjugation with liver glutathione) may accumulate following paracetamol overdosage and causes liver damage. The time to peak concentration of paracetamol is 0.5 to 2 hours, the time to peak effect 1 to 3 hours and the duration of action 3 to 4 hours.

Caffeine:

Caffeine is absorbed readily after oral administration and is widely distributed throughout the body. Caffeine passes readily into the CNS and into saliva; low concentrations are also present in breast milk. Caffeine crosses the placenta. In adults, caffeine is metabolised almost completely via oxidation, demethylation and acetylation and is excreted in the urine as1-methyluric acid, 1-methylxanthine, 7-methyxanthine, 1,7-dimethylxanthine (paraxanthine), 5-acetylamino-6-formylaminol-3-methyluracil (AFMU) and other metabolites with only about 1% unchanged. The elimination half life is about 3 to 5 hours in adults.

5.3 Preclinical safety data

There is no pre-clinical data of relevance to the prescriber which is additional to that already included in the other sections of the SmPC.

Conventional studies using the currently accepted standards for the evaluation of toxicity to reproduction and development are not available

6 PHARMACEUTICAL PARTICULARS

6.1 List of excipients

Starch (potato)

Pregelatinised starch (maize)

Povidone

Magnesium stearate

Purified talc

Croscarmellose sodium

Stearic acid

Water

6.2 Incompatibilities

None

6.3 Shelf life

3 years from the date of manufacture.

6.4 Special precautions for storage

Store in a dry place below 25°C. Protect from light.

6.5 Nature and contents of containerBlister Pack

Pack sizes: 8,10,12,16 as GSL.

Blister strips consist of a 35gsm paper/9^ soft tempered aluminium foil lid and 250^ PVC film base in cartons.