Paracetamol Tablets 500mg from the Makers of Disprin

Section 4.1:
A mild analgesic and antipyretic.  The tablets are recommended for use in the short-term management of the symptoms of headache, musculoskeletal disorders, menstrual pains, toothache and for relieving the fever, aches and pains of common colds and flu.


Section 4.3:
·        Hypersensitivity to paracetamol or any of the other constituents.
·        Use in children under 6 years of age.
·        Severe hepatocellular insufficiency.

Section 4.4

Patients in whom oxidative liver enzymes have been induced, including alcoholics, those receiving barbiturates and patients who are chronically malnourished may be more sensitive to the toxic effects of paracetamol.

Care is advised in the administration of paracetamol to patients with severe renal or severe hepatic impairment. The hazard of overdose is greater in those with non-cirrhotic alcoholic liver disease.

Special labelling requirements;

1.         Prolonged use without medical supervision could be harmful.

2.         Do not exceed the stated dose.

3.         Consult your doctor if symptoms persist.

4.         This product should only be used when clearly necessary.

            5.         Keep out of reach of children.

            6.         Patients should be advised not to take other paracetamol-containing products concurrently.

Paracetamol should be used in particular caution in patients with

·        Hepatocellular insufficiency

·        Chronic alcohol abuse

·        Severe renal insufficiency (creatinine clearance < 10 ml/min)

·        Gilbert’s syndrome (constitutional hepatic dysfunction).

With high fever, signs of a secondary infection, or if symptoms persist for more than a few days a doctor must be consulted.

In general, medicines containing paracetamol should only be used for a few days and not in high doses without doctor’s or dentist’s advice.

Prolonged use of painkillers, especially when several painkilling drugs are taken in combination, may produce permanent kidney damage with the risk of kidney failure (analgesic drug-induced nephropathy).

Abrupt withdrawal after prolonged, highly dosed use of analgesics at variance with their intended use may produce headaches as well as fatigue, muscle pain, nervousness and vegetative symptoms.  These withdrawal symptoms abate within a few days.  Until then, all painkillers should be avoided and not used again without consulting a doctor.

Section 4.5 

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.

·        Use of probnecide inhibits binding of paracetamol to glucoronic acid and thereby leads to reduction of paracetamol clearance of approximately factor 2.  In concurrent use with probenecide the paracetamol dose should be reduced.

·        Salicylamides may prolong elimination half-life of paracetamol.

·        Special caution is necessary in concurrent sue of drugs causing enzyme induction as well as potentially hepatotoxic substances.

·        Repeated use of paracetamol over several weeks increases the effect of anticoagulants.  The occasional use of paracetamol has no significant effect.

·        Concomitant use of paracetamol and AZT (zidovudine) increases the risk of neutropenia.  This medication and AZT should, therefore, only be used at the same time on doctor’s advice.

For oral preparations.

·        Concurrent use of drugs that slow gastric emptying, e.g., propantheline, may delay absorption and effect of paracetamol.

Effect of laboratory values

Use of paracetamol may influence uric acid evaluation by phosphorous-wolfram acid and blood glucose level assessment by glucose oxidase peroxidase.

Section 4.6:

Pregnancy

There is epidemiological evidence of the safety of paracetamol in human pregnancy. Paracetamol is the mild analgesic of choice during pregnancy.  However, as with all drugs, caution should be exercised in its use during the first trimester.

Lactation

Paracetamol is excreted in breast milk. However the level of paracetamol present is not considered to be harmful.  During nursing, no adverse effects or side effects have emerged up until now.  Therapeutic doses of paracetamol can be administered during nursing 


Section 4.8

Events reported from extensive post-marketing experience at therapeutic/labelled dose and considered attributable are tabulated below by System Organ Class and frequency.

Frequencies are defined as: very common ( ≥ 1/10), common ( ≥ 1/100, < 1/10), uncommon ( ≥ 1/1000, < 1/100), rare ( ≥ 1/10,000, < 1/1000), very rare (< 1/10,000), non known (cannot be estimated from available data).

Adverse event frequencies have been estimated from spontaneous reports received through post-marketing data.

4.9       Overdose

Risk for intoxication is especially high in elderly patients, small children, patients with liver diseases, chronic alcohol abuse, chronic malnutrition and concurrent use of medicines that lead to enzyme induction.  In these cases overdosing may lead to death.

Immediate medical attention (in-hospital if possible) is required in the event of overdose, even if there are no significant early symptoms. There may be no early symptoms following a life threatening overdose. Ingestion of more than 12 g paracetamol (24 standard 500 mg tablets) or more than 150 mg paracetamol per kg bodyweight (9g paracetamol in a 60 kg individual), whichever is the smaller, can cause severe liver damage. An overdose with 6 g or more of paracetamol in a single adult dose or of 140 mg/Kg body weight in children leads to liver necrosis, which could lead to a totally irreversible necrosis and later to hepatocellular insufficiency, metabolic acidosis and encephalopathy.  These again could lead to coma, also with death as a result.  At the same time, elevated concentrations of transaminases (AST, ALT), lactate dehydrogenase and of bilrubin in combination with an increased thromboplastin time were observed, which can occur after 12-48 hours of use.  Clinical symptoms of liver damage become apparent after 2 days and reach a peak after 4-6 days.  Acute renal failure and necrosis of the renal tubules can occur, even if there are no serious liver damages.  Other not liver-related symptoms that were observed after a paracetamol overdose are myocardial anomalies and pancreatitis. 

Intravenous N-acetylcysteine (NAC) is effective when initiated within 8 hours of the overdose. Efficacy declines progressively after this time, but NAC may provide some benefit up to and possibly beyond 24 hours. Oral methionine is also effective provided that it is given within 10 to 12 hours of the overdose. Activated charcoal should be considered if the dose of paracetamol ingested exceeds 12 g or 150 mg/kg, which ever is the smaller, and the procedure can be undertaken within 1 hour of the overdose. Dialysis may reduce the plasma concentration of paracetamol.  Evaluation of the plasma concentration of paracetamol is advised.  There is little evidence that undertaking gastric lavage will be of benefit to a patient in whom paracetamol is known to have been the only substance ingested.

Symptoms of paracetamol overdose in the first 24 hours may include pallor, nausea, vomiting, anorexia and abdominal pain; followed by a subjective improvement in overall well-being, although mild abdominal pain remains as indication of liver damage. Abnormalities of glucose metabolism and metabolic acidosis may occur. In severe poisoning, hepatic failure may progress to encephalopathy, coma and death. Liver damage results when excess quantities of a toxic metabolite (usually adequately detoxified by glutathione when normal doses of paracetamol are ingested) becomes irreversibly bound to liver tissue. Acute renal failure with acute tubular necrosis may develop even in the absence of severe liver damage. Cardiac

arrhythmias and pancreatitis have been reported.

5.1       Pharmacodynamic properties

            Pharmacotherapeutic group: Analgesics and antipyretics. Anilides.

            ATC Code:  N02B E01.

            Paracetamol has analgesic and antipyretic actions.