Ricesteele Manufacturing Ltd

Clinical Particulars

4.1.      Therapeutic Indications

Paralink Paracetamol Solution is indicated as an analgesic and antipyretic.  It is used in the treatment of mild to moderate pain, for the relief of symptoms of colds and influenza and to reduce fever, including post-vaccination fever in childhood.

4.2.            Posology and Method of Administration

This product is for oral administration.

Age 2-3 months: For post-vaccination fever, the recommended dose is

               2.5ml (half a teaspoonful), followed if necessary by a

   second dose six hours later.  Paralink Paracetamol Oral

                           Solution should only be used in infants > 3.0 kg.

In the case of infants less than three months, do not give for more than 2 days without consulting a doctor.

Age 3 months –

1 year:                  2.5 – 5ml (1/2 – 1 teaspoonful) 3-4 times daily

Age 1 – 5 years:  5 – 10ml (1-2 teaspoonsful) 3-4 times daily

Age 6 years and 

over:                     10 – 20ml (2-4 teaspoonsful) 3-4 times daily,

or as directed by the physician.

4.3.            Contra-indications

Patients with rare hereditary problems of fructose intolerance should not take this medicine.

Hypersensitivity to paracetamol or to any of the other constituents.

4.4.      Special Warnings and Precautions for Use

Prolonged use without medical supervision can be harmful.

Maximum duration of continued use without medical advice: 3 days.

If symptoms persist consult your doctor.

Do not exceed the stated dose.

Do not take with other products containing paracetamol.

The product should be administered with caution to patients with known liver or renal impairment.

Immediate medical advice should be sought in the event of an overdose, because of the risk of irreversible liver damage.

In the case of infants less than three months, do not give for more than 2 days without consulting a doctor.

4.5.      Interactions with other Medicaments and other forms of Interaction

‘The anticoagulant effect of warfarin and other coumarins may be 

enhanced by prolonged regular use of paracetamol with increased

bleeding; occasional doses have no significant effect.

The rate of absorption of paracetamol may be increased by

metoclopramide or domperidone and absorption reduced by

choleystyramine.

Chronic alcohol intake can increase the hepatotoxicity of paracetamol overdose. Acute alcohol intake may diminish an individual's ability to metabolise large doses of paracetamol, the plasma half-life of which can be prolonged.

The use of drugs that induce hepatic micosomal enzymes, such as anticonvulsants and oral contraceptives, may increase the extent of metabolism of paracetamol, resulting in reduced plasma concentrations of the drug and a faster elimination rate.

4.6.      Pregnancy and Lactation

Epidemologal 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 it’s use.

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

Available published data does 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 a few reports of blood dyscrasias including thrombocytopenia and agranulocytosis.

Chronic hepatic necrosis has been reported in a patient who took daily therapeutic doses of paracetamol for about a year and liver damage has been reported after daily ingestion of excessive amounts for shorter periods.

A review of a group of patients with chronic active hepatitis failed to reveal differences in the abnormalities of liver function in those who were long-term users of paracetamol nor was the control of the disease improved after paracetamol withdrawal.

Nephrotoxic effects following therapeutic doses of paracetamol are uncommon. Papillary necrosis has been reported after prolonged administration.

4.9.      Overdose

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, including the following ones:

Risk factors

a)      Long term treatment with carbamazepine, phenobarbitone, phenytoin, primidone, rifampicin, St John’s Wort or other drugs that induce liver enzymes, or

b)      regular consumption of ethanol in excess of recommended amounts, or

c)      likely glutathione depletion, 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.

Treatment

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.

Paracetamol has analgesic and antipyretic actions but only weak anti-inflammatory properties.

Paracetamol is rapidly and almost completely absorbed from the gastrointestinal tract. Peak plasma concentrations occur within 30 to 60 minutes, with slightly faster absorption of liquid preparations. Usual analgesic doses produce total serum concentrations of 5 to 20mg/ml. A good correlation between serum concentration and analgesic effect has not been found.

Paracetamol is distributed into most body tissues, it crosses the placenta and it is present in breast milk.  Serum protein binding varies from 20% to 50% at toxic serum concentrations.

Paracetamol is metabolised predominantly in the liver and excreted in the urine mainly as glucuronide and sulfate conjugates. Less than 5% is excreted as unchanged paracetamol. The elimination half-life varies from about 1 to 3

            hours and is prolonged in neonates and in patients with hepatic impairment.