Paracetamol/Caffeine 500 mg/65 mg Tablets – Summary of Product Characteristics (SmPC) for healthcare professionals

1 NAME OF THE MEDICINAL PRODUCT

Paracetamol/Caffeine 500 mg/65 mg Tablets

2 QUALITATIVE AND QUANTITATIVE COMPOSITION

Active Ingredients

Each tablet contains: - Paracetamol: 500 mg

Caffeine: 65 mg

For the full list of excipients, see section 6.1.

3 PHARMACEUTICAL FORM

Tablet

White capsule shaped tablets with ‘aP’ and ‘X’ and breakline in the middle debossed (stamped into) one side and plain on the other side. The breakline can be used to break the tablet for ease of swallowing but not to divide it into equal doses.

4. CLINICAL PARTICULARS

4.1 Therapeutic Indications

For the relief of pain associated with headache, migraine, neuralgia, toothache, period pain, sciatica, lumbago, fibrositis, joint swelling and stiffness, influenza. Feverishness and feverish cold, symptomatic relief of rheumatic aches and pains, and pain associated with muscular disorder.

4.2 Posology and method of administration

The tablet to be administered orally only.

Adults and children over 16 years: One or two tablets to be taken every four to six hours when necessary to a maximum of four doses in 24 hours.

Children 12-15 years: One tablet to be taken every four to six hours when necessary to a maximum of four doses in 24 hours.

Not suitable for children under 12 years of age except on the advice of a doctor. Children should not be given this medicine for more than 3 days without consulting a doctor.

4.3. Contra-indications

Known hyper sensitivity to Paracetamol, caffeine or any of the other constituents (or similar). Do not give to patients with a history of peptic ulceration in view of the caffeine content.

4.4 Special warnings and precautions for use

Paracetamol:

Paracetamol should be given with care to patients with impaired liver or kidney function and to patients taking others drugs that affect the liver. The hazard of overdose is greater in those with non-cirrhotic alcoholic liver disease. Liver function tests may be required at periodic intervals during high dose or long-term therapy, especially in-patients with pre-existing hepatic disease. Care should be taken when giving Paracetamol to patients with alcohol dependence. Care should be taken giving paracetamol to patients with glucose 6 phosphate dehydrogenase deficiency.

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 and 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.

Caffeine:

Caution is advised in-patients with cardiovascular disease. Care should be taken giving paracetamol to patients with glucose 6 phosphate dehydrogenase deficiency. Excessive intake of tea or coffee should be avoided.

Generally:

If symptoms persist for more than 3 days, consult your doctor.

If you are receiving a course of medicinal treatment, consult your doctor before taking this product.

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.

Patients should be advised to consult a doctor if they suffer from non-serious arthritis and need to take painkillers every day.

Keep medicines out of the sight and reach of children.

The dosage (4 doses in 24 hours) interval should be consistent with other solid dose paracetamol: 4-6 hours. Accidental overdose by shortening the dosage interval is a real public health risk.

Pack Label:

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

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

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

Patient Information Leaflet:

Talk to a doctor at once if you take too much of this medicine, 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

Paracetamol

Alcohol and hepatotoxic medications reduce the capacity of the liver to metabolise paracetamol. Chronic use of paracetamol enhances the effects of anticoagulants.

The anticoagulant effect of Warfarins and other Coumarins may be enhanced by prolonged or regular daily use of paracetamol with increased risk of bleeding; occasional use has no significant effect.

Cholestyramine reduces absorption of paracetamol. Metoclopramide and domperidone accelerate absorption of paracetamol. Plasma levels of chloramphenicol may increase with concurrent administration of paracetamol. Concurrent use of paracetamol with NSAIDs may increase the risk of adverse renal effects.

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 risk factors (see section 4.4).

4.6. Fertility, Pregnancy and lactation

Paracetamol

Paracetamol crosses the placenta. 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 there is no evidence that this is clinically significant.

Caffeine

Taken during pregnancy it appears that the half-life of caffeine is prolonged. This is a possible contributing factor in hyperemesis gravidarum.

With reference to the above, it should be noted that no medicines should be taken during pregnancy unless authorised by a Doctor.

Caffeine is excreted in breast milk but not in a clinically significant amount.

4.7. Effects on Ability to Drive and Use Machines

Paracetamol & Caffeine

None reported

4.8 Undesirable effects

Paracetamol

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. 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

d

n

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

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.

Metabolism and nutrition disorders

High anion gap metabolic acidosis with frequency “Not known” (cannot be estimated from the available data)

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 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 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, 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 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;

Emesis and convulsions may occur. No specific antidote. However, treatment is usually fluid therapy. Fatal poisoning is rare. If symptoms become apparent or overdose is suspected, consult a doctor immediately.

5. PHARMACOLOGICAL PROPERTIES

5.1. Pharmacodynamic Properties

Pharmacotherapeutic group: Analgesic

ATC code: N02 BE71

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 on 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 depth of respiration. Its stimulant action on the medullary vasomotor 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 glucuronide and sulphate conjugates. Less than 5% is excreted as unchanged paracetamol. The elimination half-life varies from about 1-4 hours. Plasma protein 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 cause 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

It is absorbed readily after oral, rectal, or parenteral administration but absorption from the gastro-intestinal tract may be erratic. There is little evidence of accumulation in any particular tissue. Caffeine passes readily into the central nervous system and into saliva. Concentrations have also been detected in breast milk. It is metabolised almost completely and is excreted in the urine as 1-methyluric acid, 1-methylxanthine and other metabolites with only about 1% unchanged.

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

Starch (Potato)

Pre-gelatinised starch

Povidone K-30 & K-90

Croscarmellose sodium

Talc

Stearic acid

Magnesium Stearate

6.2. Incompatibilities

None known

6.3. Shelf Life

36 months

6.4 Special precautions for storage

Store below 25°C.

Keep tablets in their original pack to protect from light.

6.5. Nature and contents of container

Blister: blister film with white PVC coated with PVDC and foil consisting of hard tempered aluminium foil

Pack sizes: 8’s & 16’s.

6.6. Instruction for use and handling

No special requirements

7. MARKETING AUTHORISATION HOLDER

Aspar Pharmaceuticals Ltd,

Albany House,

Acrewood way,

St Albans,

AL4 0JY,

United Kingdom

8. MARKETING AUTHORISATION NUMBER

PL 08977/0025

9 DATE OF FIRST AUTHORISATION/RENEWAL OF THE

AUTHORISATION

12/12/2024

10 DATE OF REVISION OF THE TEXT

06/12/2025