Paracetamol 60 Mg Suppositories Bp
SUMMARY OF PRODUCT CHARACTERISTICS
1 NAME OF THE MEDICINAL PRODUCT
Paracetamol 60 mg Suppositories BP
2. Qualitative and Quantitative Composition
Each Suppository contains 60 mg Paracetamol For a full list of excipients see section 6.1.
3. Pharmaceutical Form
Suppository
Clean white to off-white conical or torpedo shaped suppositories
4. Clinical particulars
4.1. Therapeutic Indications
Paracetamol 60mg Suppositories are indicated for the treatment of mild to moderate pain and pyrexia in children.
4.2. Posology and Method of Administration
For rectal administration.
Children:
1-2 years (8 - 11 kg) 2 suppositories.
Dose may be repeated every 4 - 6 hours up to a maximum of 4 doses in 24 hours. Dose should be based on age and weight.
4.3. Contra-indications
Hypersensitivity to paracetamol or any of the other constituents.
4.4. Special Warnings and Precautions for Use
Use with caution in the presence of renal or hepatic dysfunction. The hazards of overdose are that much greater in those with non-cirrhotic alcoholic liver disease. Do not exceed the recommended dose.
Paracetamol should be used with caution in patients with anaemia or an infection.
Patients should be advised not to take other paracetamol containing products concurrently. If symptoms persist, medical opinion should be sought.
Keep out of the reach and sight of children.
4.5. Interaction with other Medicinal Products and other forms of Interaction
The speed of absorption of paracetamol may be increased by metoclopramide or domperidone and absorption reduced by cholestyramine.
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.
Drugs that induce hepatic microsomal enzymes such as barbiturates and other anticonvulsants, may increase the hepatotoxic potential of paracetamol particularly after overdosage. Alcohol abuse increases the risk for paracetamol toxicity.
Rifampicin can interact to reduce the effectiveness of paracetamol.
4.6. Pregnancy and Lactation
Epidemiological studies in human pregnancy have shown no ill effects due to paracetamol used in the recommended dosage, but patients should follow the advice of their doctor regarding its use.
Paracetamol is excreted in breast milk but not in a clinically significant amount. Available published data do not contraindicate breast feeding.
4.7. Effects on Ability to Drive and Use Machines
None Known
4.8. Undesirable Effects
Adverse effects at therapeutic doses are rare, but hypersensitivity including skin rash may occur. There have been a few reports of blood dyscrasias, including thrombocytopenia and agranulocytosis, but these were not necessarily causality related to paracetamol.
Redness of the mucous membrane of the rectum and minor vascular changes have been reported. Isolated cases of liver damage have also been rarely reported.
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).
It is considered that excess quantities of a toxic metabolite (usually adequately detoxified by glutathione when normal doses of paracetamol are ingested) become irreversibly bound to liver tissue.
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 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 in the absence of severe liver damage. Cardiac arrythmias 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 sharpy 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 hosptial. Management of patients who present with serious hepatic dysfunction beyond 24h from ingestion should be discussed with NPIS or a liver unit.
Pharmacological Properties
5.1. Pharmacodynamic Properties
ATC Code: N02BE01
Paracetamol is an aniline derivative with analgesic and antipyretic actions.
Paracetamol produces its analgesic effect from the inhibition of prostaglandin synthesis. Prostoglandins appear to sensitise pain receptors to mechanical stimulation or to other chemical mediators. Paracetamol lowers the body temperature in patients with fever but rarely lowers normal body temperature. This is again due to the inhibition of synthesis and release of prostoglandins. The drug also acts on the hypothalamus to produce antipyresis; heat dissipation is increased as a result of vasodilation and increased peripheral blood flow.
Paracetamol is generally well tolerated by patients hypersensitive to acetylsalicylic acid.
5.2. Pharmacokinetic Properties
Paracetamol is well absorbed by both oral and rectal routes. Peak plasma concentrations occur about 2 to 3 hours after rectal administration. Paracetamol is distributed into most body tissues. It crosses the placenta and is present in breast milk. Plasma-protein binding is negligible at usual therapeutic concentrations. The plasma half life is about 2 hours. Paracetamol is primarily metabolised in the liver by conjugation to glucuronide and sulphate. A small amount (about 3 - 10% of a therapeutic dose) is metabolised by oxidation and the reactive intermediate metabolite thus formed is bound preferentially to the liver glutathione and excreted as cystein and mercapturic acid conjugates. Excretion occurs via the kidneys. 2 - 3% of a therapeutic dose is excreted unchanged; 80 - 90% as glucuronide and sulphate and a smaller amount as cystein and mercapturic acid derivatives.
5.3. Preclinical Safety Data
Paracetamol is a well established drug substance whose pre-clinical profile has been thoroughly investigated and is established.
Pharmaceutical Particulars
6.1. List of Excipients
Hard Fat
Polyoxyl 40 Stearate
6.2. Incompatibilities
None known
24 months
6.4. Special Precautions for Storage
Do not store above 25°C. Keep the blister strips in the outer carton.
6.5. Nature and Contents of Container
Strips of opaque white suppository moulds composed of PVC/PE with polyurethane adhesive. Packed in outer cartons. Each strip contains 6 suppositories. Pack-size of 12 suppositories.
6.6. Instruction for Use/Handling
Wash hands thoroughly before opening the individual packaging. The suppository is shaped for rectal insertion, ensure the tip of the suppository is inserted first.
Do not open until immediately before use.
Administrative Data
7. Marketing Authorisation Holder
MARTINDALE PHARMACEUTICALS LTD Bampton Road Romford Essex RM3 8UG
8. Marketing Authorisation Number
PL 00156/0099
9 DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION 29/06/2009
10 DATE OF REVISION OF THE TEXT
29/06/2009