Paracetamol Extra Caplets
SUMMARY OF PRODUCT 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 excipients, see 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
Dose: Unless otherwise directed by a doctor: Adults, the elderly and children over 12 years: 1-2 caplets to be swallowed with water. This may be repeated every four hours but no more than 4 doses (8 caplets) should be taken in 24 hours.
Do not give to children under 12 years of age except on the advice of a doctor. Route of administration: Oral with water.
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 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 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.
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 exceed the stated dose.
• 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 these tablets if you are taking any other medicine containing PARACETAMOL.
• 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
• Keep out of the reach and sight of children.
4.5. Interactions 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.
4.6. Pregnancy and Lactation
Paracetamol
Paracetamol crosses the placenta. There is no known hazard in normal dosage, but like all non-essential medications paracetamol should be avoided, especially during the first trimester, unless considered essential by the physician. 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
Side effects are usually mild, though haematological reactions, blood dyscrasias and anaemia have been reported. Rashes and other allergic reactions occur occasionally. 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.
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 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
There are no pre-clinical safety data of relevance to the prescriber, which are additional to that already included in other sections of the SPC.
6. PHARMACEUTICAL PARTICULARS
6.1. List of excipients
Starch (Potato)
Pre-gelatinised starch Povidone K-30 & K90 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,
9
29 - 30 Capitol Way Capitol Way Industrial Park Colindale London NW9 0EQ