Paracetamol capsules 500 mg – Summary of Product Characteristics (SmPC) for healthcare professionals

1 NAME OF THE MEDICINAL PRODUCT

Paracetamol 500mg Capsules

Boots Paracetamol 500mg Capsules

2 QUALITATIVE AND QUANTITATIVE COMPOSITION

Each capsule contains paracetamol 500mg.

Excipients with known effect: Also contains methyl parahydroxybenzoate (E218) and propyl parahydroxybenzoate (E216).

For the full list of excipients, see section 6.1.

3 PHARMACEUTICAL FORM

Hard Gelatin Capsules (capsules)

Red cap, white body, hard gelatin capsule, containing a white free flowing powder.

4 CLINICAL PARTICULARS

4.1 Therapeutic indications

Paracetamol Capsules is a mild analgesic and antipyretic and is recommended for the treatment of most painful and febrile conditions, for example, headache including migraine and tension headaches, toothache, backache, rheumatic and muscle pains, dysmenorrhoea, sore throat, and for relieving the fever, aches and pains of colds and flu.

4.2 Posology and method of administration

Posology

Adults, the elderly and children aged 16 years and over:

2 capsules up to 4 times a day.

The doses should not be repeated more frequently than every four hours and not more than eight capsules should be taken in 24 hours.

Children aged 12 to 15 years:

One capsule every 4 – 6 hours when necessary to a maximum of 4 doses in 24 hours.

Do not take more than 4 capsules in any 24 hour period.

Children under 12 years of age:

Not recommended for children under 12 years of age.

Method of Administration

For oral use only

Intake of paracetamol with food and drink does not affect the efficacy of the medicinal product.

4.3 Contraindications

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

4.4 Special warnings and precautions for use

Prolonged or frequent use is discouraged. Patients should be advised not to take other Paracetamol containing products concurrently. Taking multiple daily doses in one administration can severely damage the liver; in such case unconsciousness does not occur. However, medical assistance should be sought immediately. Prolonged use except under medical supervision may be harmful. In adolescents treated with 60mg/kg daily of Paracetamol, the combination with another antipyretic is not justified except in the case of ineffectiveness.

Cases of high anion gap metabolic acidosis (HAGMA) due to pyroglutamic acidosis have been reported in patients with severe illness such as severe renal impairment and sepsis, or in patients with malnutrition or other sources of glutathione deficiency (e.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.

Caution is advised in the administration of Paracetamol to patients with moderate and severe renal insufficiency, mild to moderate hepatic insufficiency (including Gilbert's syndrome), severe hepatic insufficiency (child-pugh>9), acute hepatitis, concomitant treatment with medicinal products affecting hepatic functions, glucose-6-phosphatedehydrogenase deficiency, hemolytic anemia, alcohol abuse dehydration and chronic malnutrition (see section 4.2).

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 case. 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.

Underlying liver disease increases the risk or paracetamol related liver damage. Patients who have been diagnosed with liver or kidney impairment must seek medical advice before taking this medication.

Do not exceed the stated dose.

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

Caution should be exercised in patients with glutathione depleted states, as the use of paracetamol may increase the risk of metabolic acidosis (refer also to section 4.9)

In the case of high fever, or signs of secondary infection or persistence of symptoms a doctor should be consulted.

Immediate medical advice should be sought in the event of overdosage even if the patient feels well because of the risk of irreversible liver damage (see section 4.9).

If symptoms persist, medical advice must be sought.

Contains no animal derived ingredients.

Keep out of the sight and reach of children.

The label contains the following wordings:

• 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 contains the following wordings:

• 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.

Important information regarding the excipients of this medicine

Methyl and propyl parahydroxybenzoate: This medicine contains excipients methyl parahydroxybenzoate (E218) and propyl parahydroxybenzoate (E216), which may cause allergic reactions (possibly delayed).

Sodium: This medicine contains less than 1 mmol sodium (23 mg) per capsule, that is to say essentially 'sodium-free'.

4.5 Interaction with other medicinal products and other forms of interaction

Hepatotoxic substances may increase the possibility of Paracetamol accumulation and overdose. The risk of hepatotoxicity of paracetamol may be increased by drugs which induce liver microsomal enzymes such as barbiturates, tricyclic antidepressants, and alcohol.

Probenecid causes an almost 2-fold reduction in clearance of Paracetamol by inhibiting its conjugation with glucuronic acid. A reduction of the Paracetamol dose should be considered for concomitant treatment with probenecid.

Salicylamide may prolong the elimination t1/2 of Paracetamol Cholestyramine: The speed of absorption of paracetamol is reduced by cholestyramine. Therefore, the cholestyramine should not be taken within one hour if maximal analgesia is required.

Metoclopramide and Domperidone: The speed of absorption of paracetamol may be increased by metoclopramide and domperidone. However, concurrent use need not be avoided.

Concomitant use of Paracetamol (4 g per day for at least 4 days) with oral anticoagulants may lead to slight variations of INR values. In this case, increased monitoring of INR values should be done during the duration of the combination and after its discontinuation. 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.

Isoniazid: Reduction of paracetamol clearance, with possible potentiation of its action and/or toxicity, by inhibiting its metabolism in the liver.

Lamotrigine: Decrease in the bioavailability of lamotrigine, with possible reduction of its effect, due to possible induction of its metabolism in the liver.

Interference with laboratory tests: Paracetamol may affect uric acid tests by wolframatop phosphoric acid, and blood sugar tests by glucose-oxydase-peroxydase.

Flucloxacillin: Caution should be taken when paracetamol is used concomitantly with flucloxacillin as concurrent intake has been associated with high anion gap metabolic acidosis due to pyroglutamic acidosis, especially in patients with risks factors (see section 4.4).

4.6 Fertility, pregnancy and lactation

Pregnancy

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, as with any medicine it should be used at the lowest effective dose for the shortest possible time.

Breast-feeding

Following oral administration, Paracetamol is excreted into breast milk in small quantities. To date, no adverse reactions or undesirable effects are known in association with lactation. Therapeutic doses of Paracetamol can be administered during breast-feeding.

4.7 Effects on ability to drive and use machines

Paracetamol has no influence on the ability to drive and use machines.

4.8 Undesirable effects

Adverse events of paracetamol 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 and frequency.

The frequency using the following convention: very common (> 1/10); common (>1/100 to < 1/10); uncommon (>1/1000 to < 1/100); rare (>1/10000 to < 1/1000); very rare (< 1/10000), including isolated reports; not known: frequency cannot be estimated from the available data. Within each frequency grouping, undesirable effects are presented in order of decreasing seriousness.

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

Description of selected adverse reactions

High anion gap metabolic acidosis

Cases of high anion gap metabolic acidosis due to pyroglutamic acidosis have been observed in patients with risk factors using paracetamol (see section 4.4). Pyroglutamic acidosis may occur as a consequence of low glutathione levels in these patients.

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

There is a risk of poisoning, particularly in elderly subjects, in young adolescents, in patients with liver disease, in cases of chronic alcoholism, in patients with chronic malnutrition. Overdosing may be fatal.

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 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 over dosage 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-acetyl cysteine 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-acetyl cysteine, 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 24 h from ingestion should be discussed with the NPIS or a liver unit.

5.1 Pharmacodynamic properties

Pharmacotherapeutic group: Other analgesics and antipyretics. ATC code: N02B E01

Mechanism of Action

Analgesic – the mechanism of analgesic action has been fully determined. Paracetamol may act predominantly by inhibiting prostaglandin synthesis in the central nervous system (CNS) and to a lesser extent, through a peripheral action by blocking pain-impulse generation.

Antipyretic – paracetamol probably produces antipyresis by acting centrally on the hypothalamic heat-regulation centre to produce peripheral vasodilation resulting in increased blood flow through the skin, sweating and heat loss. The central action probably involves inhibition of prostaglandin synthesis in the hypothalamus.

5.2 Pharmacokinetic properties

Paracetamol is rapidly and almost completely absorbed from the gastrointestinal tract with peak plasma concentrations occurring about 30 minutes to 2 hours after ingestion. Plasma protein binding is negligible at usual therapeutic concentrations but increases with increasing concentrations. The elimination half-life varies from about 1-4 hours. Paracetamol is metabolised predominantly in the liver and excreted in the urine mainly as the glucuronide and sulphate conjugates. Less than 5% is excreted as unchanged paracetamol.

A minor hydroxylated metabolite which is usually produced in very small amounts by mixed function oxidases in the liver and kidney which is usually detoxified by conjugation with liver glutathione, may accumulate following paracetamol over dosage and cause liver damage.

5.3 Preclinical safety data

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

Pregelatinised maize starch

Magnesium stearate

Sodium laurilsulfate

Capsule shell:

Titanium dioxide E171

Erythrosine E127

Quinoline yellow E104

Patent Blue V E131

Gelatin

Methyl parahydroxybenzoate E218

Propyl parahydroxybenzoate E216

6.2 Incompatibilities

Not applicable

6.3 Shelf life

4 years

6.4 Special precautions for storage

Do not store above 25ºC. Store in the original package.

6.5 Nature and contents of container

Child resistant blister packs comprised of 20µm hard aluminium foil laminated to 15µm rigid PVC, and 250µm PVC. Pack sizes of 6, 8, 10, 12, 16 capsules.

Not all pack sizes may be marketed.

6.6 Special precautions for disposal

No special requirements.

7 MARKETING AUTHORISATION HOLDER

Bristol Laboratories Ltd

Unit 3, Canalside

Northbridge Road

Berkhamsted

Hertfordshire

HP4 1EG

8 MARKETING AUTHORISATION NUMBER(S)

PL 17907/0048

9 DATE OF FIRST AUTHORISATION/RENEWAL OF THE

AUTHORISATION

16/02/2006 / 08/03/2011

10 DATE OF REVISION OF THE TEXT

04/08/2025