Paracetamol Adult 500mg/5ml Oral Suspension
SUMMARY OF PRODUCT CHARACTERISTICS
1 NAME OF THE MEDICINAL PRODUCT
Paracetamol Adult 500mg/5ml Oral Suspension
2 QUALITATIVE AND QUANTITATIVE COMPOSITION
Each 5ml contains 500mg Paracetamol Excipients:
Methyl parahydroxybenzoate - 6mg/5ml Propyl parahydroxybenzoate - 1.5mg/5ml Liquid maltitol - 2.05g/5ml
For a full list of excipients, see section 6.1.
3 PHARMACEUTICAL FORM
Oral suspension
An opaque, pink/brown suspension
4 CLINICAL PARTICULARS
4.1 Therapeutic indications
For the treatment of mild to moderate pain in patients who are unable to receive other paracetamol formulations such as lower strength liquid preparations, effervescent tablets or tablets.
4.2 Posology and method of administration
For oral administration only
Adults and adolescents over 16 years: 500mg (5ml) or 1000mg (10ml) up to three to four times a day, as required. Maximum daily dose should not exceed 4g (40ml).
The dose should not be repeated more frequently than every four hours, and not more than four doses should be taken in any 24 hour period.
4.3 Contraindications
Hypersensitivity to paracetamol and/or other constituents. Patients with severe hepatic dysfunction.
Do not use this medicine in children and adolescents under 16 years.
4.4 Special warnings and precautions for use
Care is advised in the administration of paracetamol to patients with severe renal or severe hepatic impairment. The hazards of overdose are greater in those with noncirrhotic alcoholic liver disease.
Do not take with any other paracetamol-containing products.
Immediate medical advice should be sought in the event of an overdose, even if you feel well, because of the risk of delayed serious or irreversible liver damage.
Do not exceed the recommended dose.
Keep out of the reach and sight of children.
Excipient warnings:
This product contains the following excipients:
Parahydroxybenzoates: these may cause allergic reactions (possibly delayed).
Liquid maltitol: patients with rare hereditary problems of fructose intolerance should not take this medicine.
4.5 Interaction with other medicinal products and other forms of interaction
The hepatotoxicity of Paracetamol, particularly after overdosage, may be increased by drugs which induce liver microsomal enzymes such as barbiturates, tricyclic antidepressants and alcohol.
The speed of absorption of paracetamol may be increased by metoclopramide or domperidone and absorption reduced by colestyramine.
The anticoagulant effect of warfarin and other coumarins may be enhanced by prolonged regular use of paracetamol with increased risk of bleeding; occasional doses have no significant effect.
Antivirals: Regular use of Paracetamol possibly reduces metabolism of Zidovudine (increased risk of neutropenia).
4.6 Fertility, 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 clinically significant quantities. Available published data do not contraindicate breast feeding.
4.7 Effects on ability to drive and use machines
None
4.8 Undesirable effects
Adverse effects of paracetamol are rare but hypersensitivity including skin rash may occur. There have been reports of blood dyscrasias including thrombocytopenia and agranulocytosis, but these were not necessarily causality related to paracetamol.
Very rare cases of serious skin reactions have been reported.
Cases of acute pancreatitis have been reported. Paracetamol has been widely used and reports of adverse reactions are rare, and are generally associated with overdosage.
Allergic reactions occur occasionally.
Nephrotoxic effects are uncommon and have not been reported in association with therapeutic doses, except after prolonged administration.
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 depleted 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 24 hours from ingestion should be discussed with the NPIS or a liver unit.
5 PHARMACOLOGICAL PROPERTIES
5.1 Pharmacodynamic properties
Pharmacotherapeutic group: Analgesics and antipyretics, Anilides ATC Code: N02 BE01
The mechanism of analgesic action has not 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. 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 antipyresis by acting centrally on the hypothalamic heat regulating centre to produce peripheral vaso-dilation 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
Oral absorption is rapid and almost complete, it may be decreased if paracetamol is taken following a high carbohydrate meal.
There is no significant protein binding with doses producing plasma concentrations below 60mcg (pg)/ml, but may reach moderate levels with high or toxic doses.
Approximately 90 - 95% of a dose is metabolised in the liver, primarily by conjugation with glucuronic acid, sulphuric acid and cysteine. An intermediate metabolite, which may accumulate in overdosage after primary metabolic pathways become saturated, is hepatotoxic and possibly nephrotoxic.
Half life is 1 to 4 hours; does not change with renal failure but may be prolonged in acute overdosage, in some forms of hepatic disease, in the elderly, and in the neonate; may be somewhat shortened in children.
Time to peak concentration, 0.5 - 2 hours; peak plasma concentrations, 5 - 20mcg (pg)/ml (with doses up to 650mg); time to peak effect, 1 - 3 hours; duration of action, 3 - 4 hours.
Elimination is by the renal route, as metabolites, primarily conjugates, 3% of a dose may be excreted unchanged.
Peak concentrations of 10 - 15mcg (pg)/ml have been measured in breast milk, 1 - 2 hours following maternal ingestion of a single 650mg dose. Half life in breast milk is 1.35 - 3.5 hours.
5.3 Preclinical safety data
There are no pre-clinical 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
Propylene glycol (E1520)
Methyl parahydroxybenzoate (E218)
Propyl parahydroxybenzoate (E216)
Liquid maltitol (E965)
Saccharin sodium Acesulfame potassium (E950)
Sodium dihydrogen phosphate dihydrate Disodium hydrogen phosphate dihydrate Magnesium aluminium silicate
Masking flavour (containing propylene glycol (E1520))
Strawberry flavour (C9987) (containing propylene glycol (E1520))
Purified water
6.2 Incompatibilities
In the absence of compatibility studies this medicinal product must not be mixed with other medicinal products.
24 months 1 month once open
6.4 Special precautions for storage
Do not store above 25°C. Do not refrigerate or freeze. Store in the original package.
6.5 Nature and contents of container
Bottle: Amber (Type III) glass with capacity of 150ml.
Closure: HDPE, EPE wadded, tamper evident, child resistant closure Syringe: Polypropylene body and plunger with a capacity of 5ml.
Bottle adaptor: Low Density Polyethylene.
6.6 Special precautions for disposal
Any unused product or waste material should be disposed of in accordance with local requirements.
7 MARKETING AUTHORISATION HOLDER
Rosemont Pharmaceuticals Ltd
Rosemont House
Yorkdale Industrial Park
Braithwaite Street
Leeds
LS11 9XE
UK
MARKETING AUTHORISATION NUMBER(S)
8
PL 00427/0160
9 DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION
27/03/2012
10 DATE OF REVISION OF THE TEXT
23/01/2015