Macadol 500

CHEMISTRY

Paracetamol is white odourless crystals or crystalline powder with a bitter taste. It is soluble 1 in 70 of water.
Paracetamol or acetaminophen is N-acetyl-p- aminophenol or 4′- Hydroxyacetanilide or N-(4- Hydroxyphenyl) acetamide.

COMPOSITION

Each tablet contains:
Paracetamol BP 500 mg

MECHANISM OF ACTION

Paracetamol has analgesic and antipyretic effects but weak anti-inflammatory activity. Paracetamol is a clinically proven
analgesic and antipyretic. Paracetamol produces analgesia by elevation of the pain threshold and antipyresis through
action on the hypothalamic heat regulatory center. Paracetamol is equal to aspirin in analgesic and antipyretic
effectiveness and it is unlikely to produce many of the side effects associated with aspirin and aspirin containing
products.

PHARMACOLOGY

Paracetamol is rapidly and almost completely absorbed from the gastro-intestinal tract. The peak plasma levels of 5 to
20 mcg/ml occur in 30 to 60 minutes with usual analgesic doses, but there is no correlation between serum concentration
and analgesic effect. Significant serum protein binding does not occur with therapeutic doses. It is relatively uniformly
distributed throughout most body fluids, and apparent volume of distribution is about 1L/Kg. The plasma half life in
healthy subjects ranges from 1 to 2.5 hours with therapeutic doses.
Paracetamol is metabolized in the liver, largely to glucuronide (about 60%), sulfate conjugates (about 35%), cysteine
(3%) and small amounts are hydroxylated and deacetylated. It has been suggested that hydroxylated metabolite is
responsible for hepatotoxicity with overdosage. The metabolites (90% to 100%) are excreted in the urine in 24 hours.
Single or repeated therapeutic doses of paracetamol have no effect on the cardiovascular and respiratory systems. Acid
base changes do not occur. It does not produce gastric irritation, erosion or bleeding that may occur after salicylates.
It has only a weak effect upon platelets and no effect on bleeding time or the excretion of uric acid.

INDICATIONS

Paracetamol is an analgesic and antipyretic. It is used for relief of pains associated with headache, muscular aches,
backache, minor arthritis pain, common cold, toothache, chronic pain of cancer, menstrual cramps and for the reduction
of fever. Paracetamol is often the analgesic and antipyretic of choice especially in patients in whom salicylates and
other NSAIDs are contraindicated. Such patients include asthamatics or those with history of peptic ulcer, or children
in whom salicylates are contraindicated because of the risk of Reye’s syndrome

ADVERSE DRUG REACTIONS

Adverse effects of paracetamol are rare but hypersensitivity including skin rash may occur. There have been very rare
reports of blood dyscrasias including thrombocytopenia, leucopenia, neutropenia and agranulocytosis but these were not
necessarily causally related to Paracetamol. Liver damage (and less frequently renal damage)

DRUG INTERACTIONS

Chronic, excessive consumption of alcohol may increase the risk of paracetamol- induced hepatotoxicity, chronic
alcoholics should be cautioned to avoid regular or excessive use of paracetamol or alternatively, to avoid chronic
ingestion of alcohol. Anticonvulsants (including phenytoin, barbiturates, carbamazepine) that induce hepatic microsomal
enzymes may increase paracetamol-induced liver toxicity. Concomitant administration of isoniazide with paracetamol has
been reported to potentiate the effects of anticoagulants. The possibility of severe hypothermia should be considered in
patients receiving concomitant phenothiazine and antipyretic (e.g. paracetamol) therapy.

CONTRAINDICATIONS

Paracetamol should not be administered for more than 10 days and in patients with known hypersensitivity to it.

• 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.

PRECAUTIONS AND WARNINGS

If a rare sensitivity reaction occurs, the drug should be discontinued. Paracetamol should be given with caution to
patients with impaired hepatic and/or renal function. Paracetamol should be given with caution to patients taking other
drugs that affect the liver.

WARNING OF PARACETAMOL WITH WARFARIN

“Chronic ingestion of large doses of paracetamol has been reported to potentiate the effects of coumarin and
indandione-derivative anticoagulants. Some studies and isolated reports have demonstrated an increased risk of bleeding
in patients taking regular doses of paracetamol while on an anticoagulant. As with other drugs that may interact with
warfarin, when concomitant paracetamol therapy is initiated or discontinued or paracetamol dosage is modified, the INR
(International normalized ratio) values and prothrombin time (PT) should be monitored more frequently and warfarin
dosage adjusted if necessary until these values have stabilized.”

DOSAGE AND ADMINISTRATION

Adult:
Usual adult dose is 0.5 to 1g every 4 to 6 hours upto maximum of 4 gms daily.
Children:
Under 3 months: 10mg/Kg/body weight (reduced to 5mg/Kg if jaundiced) 3 months to 1 year: 60mg to 120mg
1 year to 5 years: 120mg to 250mg 6 years to 12 years: 250 mg to 500mg
These doses may be given every 4 to 6 hours when necessary upto a maximum of 4 doses in 24 hours.
For post immunization pyrexia, a dose of 60mg has been recommended for children 2 to 3 months of age. A second dose may
be given after 4 to 6 hours; if the pyrexia persists after the dose, the parent should seek medical advice.

OVERDOSAGE

• Ingestion of large doses of paracetamol

  I) in a single dose of 10 to 15gm (200 to 250mg/kg) or
  II) 5 to 8 gm/day for several weeks may cause severe hepatic damage and death. A dose of 25gm or more is
  potentially fatal.
  The first sign of toxicity occurs about 12 to 24 hours after acute overdose and include nausea, vomiting,
  diarrhoea, diaphoresis, pallor, and abdominal pain. Hepatic injury is manifested about 24 to 48 hours after
  overdose by increased serum transaminases, lactic dehydrogenase, prothrombin time and serum bilirubin
  concentrations. Severe hepatic damage may progress to hepatic failure, encephalopathy, coma and death.

• Treatment

  *Early diagnosis
  *Procedures to limit continuing absorption of paracetamol: induction of vomiting or gastric lavage followed by
  oral administration of activated charcoal.
  *N-acetylcysteine administration: a loading dose of 140mg/Kg is given orally, followed by administration of
  70mg/kg, every 4 hours for 17 doses.
  III) Liver damage is possible in adults who have taken 10g or more of Paracetamol.

PRESENTATION

Blister strip of 10 tablets

STORAGE

Do not store above 30°C
Keep out of the reach of children