PARACETAMOL EXTRA CAPLETS - summary of medicine characteristics

1 NAME OF THE MEDICINAL PRODUCT

Paracetamol Extra Caplets

2. QUALITATIVE AND QUANTITATIVE COMPOSITION

Active Ingredients Each caplet contains:-

Paracetamol: 500mg

Caffeine:      65mg

For the full list of excipients, see section 6.1.

3. PHARMACEUTICAL FORM

Tablet

Embossed ‘ap and x’ on one face on either side of a break line.

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 caplet to be administered orally only.

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

Children 12–15 years: One caplet 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 advise of a doctor. Children should not be given this medicine for more than 3 days without consulting a doctor.

4.3. Contraindications

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 Special Precautions for Use

Paracetamol:

Paracetamol should be given with care to patients with impaired liver or kidney function and to patients taking other 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 per-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.

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:

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

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.

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, because of the risk of delayed serious liver damage.

Keep medicines out of sight and reach of children.

4.5. Interactions with other medicinal products and other forms of interaction

Paracetamol

None reported

4.8 Undesirable effects

Paracetamol

Side effects are usually mild, though haematological reactions, blood dyscrasias and anaemia have been reported. Rashes and other allergic reactions occur occasionally. Very rare cases of serious skin reactions have been reported.

There are isolated reports of thrombocytopenic purpura, methaemoglobi­naemia, and agranulocytosis. Rarely renal colic, sterile pyuria, uraemia, azotaemia, acute pancreatitis and hepatitis have occurred.

Caffeine

Nausea, headache and insomnia may be experienced. Excessive consumption of beverages containing caffeine cause headache, irritability and symptoms of anxiety neurosis. Large doses may cause restlessness, excitement and extra systoles.

Caffeine increases gastric secretions and cause gastric ulceration.

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.

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).

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 examination 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

Do not store above 25°C. Keep caplets 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: 24, 28 & 32’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 08977/0024