PANADOL(r) TABLETS (with the OPTIZORB(tm) formulation) are white to off- white, film-coated round tablets embossed with the circled "P" on one side and a breakline on the other. Packs of 12, 20, 50 or 100 Caplets. PANADOL(r) CAPLETS (with the OPTIZORB(tm) formulation) are white to off- white, capsule-shaped, film-coated tablets with "P" in a circle on one side and a break line on the other. Packs of 12, 20, 48 or 96 tablets Each tablet (round or capsule-shaped) contains 500 mg of paracetamol.
Actions
Paracetamol is an antipyretic and analgesic. Its mechanism of action is believed to include inhibition of prostaglandin synthesis, primarily within the central nervous system. The lack of peripheral prostaglandin inhibition confers important pharmacological properties such as the maintenance of the protective prostaglandins within the gastrointestinal tract. Paracetamol is therefore particularly suitable for patients with a history of acid peptic disease, or on concomitant medication, where peripheral prostaglandin inhibition would be undesirable (such as, for example, those with a history of gastrointestinal bleeding or in the elderly).
Pharmacokinetics
Paracetamol is readily absorbed from the gastrointestinal tract with peak plasma concentrations occurring about 10 to 60 minutes after oral administration. Paracetamol is distributed into most body tissues. Plasma protein binding is negligible at usual therapeutic doses but increases with increasing doses. The elimination half-life varies from about 1 to 3 hours. Paracetamol is metabolised extensively in the liver and excreted in the urine mainly as inactive glucuronide and sulphate conjugates. Less than 5% is excreted unchanged. The metabolites of paracetamol include a minor hydroxylated intermediate which has hepatotoxic activity. This intermediate metabolite is detoxified by conjugation with glutathione, however, it can accumulate following paracetamol over dosage (more than 150mg/kg or 10g total paracetamol ingested) and if left untreated can cause irreversible liver damage. Paracetamol is metabolised differently by premature infants, newborns, infants and young children compared to adults, the sulphate conjugate being predominant. PANADOL TABLETS / CAPLETS (with the OPTIZORB(tm) formulation) contain a disintegrant system which optimises tablet dissolution compared to standard PANADOL tablets. In a human scintigraphy study, the mean time to onset of disintegration for PANADOL CAPLETS (with the OPTIZORB formulation) was 6.4 minutes. Human pharmacokinetic data demonstrate that early absorption of paracetamol (fraction of dose over the first 60 minutes) is 32% greater from PANADOL(r) CAPLETS(r) (with the OPTIZORB(tm) formulation) compared to standard PANADOL tablets (p<0.0001). There is also less between-subject and less within-subject variability (p<0.0001) in early absorption of paracetamol from PANADOL CAPLETS (with the OPTIZORB formulation) compared to standard PANADOL tablets. Maximum plasma concentration of paracetamol is reached faster for PANADOL CAPLETS (with the OPTIZORB formulation) compared to standard PANADOL tablets in fasted and fed states (p < 0.01). Total extent of absorption of paracetamol from PANADOL CAPLETS (with the OPTIZORB formulation) is equivalent to that from standard PANADOL tablets.
Indications
For the fast effective relief of pain and discomfort associated with headache, tension headache, muscular aches, toothache, migraine headache, cold & flu symptoms, arthritis/osteoarthritis, backache and period pain. Helps reduce fever.
PANADOL TABLETS / CAPLETS (with the OPTIZORB formulation) are to be administered orally, with or without food.
1 to 2 tablets / caplets every four to six hours with water. Maximum of 8 tablets / caplets in 24 hours. Maximum daily dose: 4000 mg.
1/2 to 1 tablet / caplet every four to six hours with water. Maximum of 4 tablets / caplets in 24 hours.
Do not use for more than a few days at a time, except on medical advice.
Do not use for more than 48 hours, except on medical advice.
Do not exceed the stated dose. PANADOL TABLETS / CAPLETS (with the OPTIZORB formulation) should not be used with other paracetamol containing products.
Contraindicated in patients with a previous history of hypersensitivity to paracetamol or to any of the excipients.
Paracetamol should be administered with care in patients with hepatic or renal dysfunction.
Use in Pregnancy and Lactation
Human and animal studies with paracetamol have not identified any risk to pregnancy or embryo-foetal development. Category A - Paracetamol has been taken by a large number of pregnant women and women of childbearing age without any proven increase in the frequency of malformations or other direct or indirect harmful effects on the foetus having been observed. Human studies with paracetamol have not identified any risk to lactation or the breast fed offspring. Paracetamol crosses the placental barrier and is excreted in breast milk.
Use in children
Not recommended for children below age 7, except on medical advice.
Effects on ability to drive and use machines
Panadol Tablets / Caplets (with Optizorb formulation) have no significant effect on the ability to drive or use machines.
Adverse events from historical clinical trial data are both infrequent and from small patient exposure. Accordingly, 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) and very rare (<1/10,000) including isolated reports.
Skin and subcutaneous tissue disorders:
Very rare dermatitis allergic (hypersensitivity reactions, including skin rashes and angioedema).
The following interactions with paracetamol have been noted: 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. Paracetamol absorption is increased by substances that increase gastric emptying, e.g. metoclopramide. Paracetamol absorption is decreased by substances that decrease gastric emptying, e.g. propantheline, antidepressants with anticholinergic properties, and narcotic analgesics. Paracetamol may increase chloramphenicol concentrations. The risk of paracetamol toxicity may be increased in patients receiving other potentially hepatotoxic drugs or drugs that induce liver microsomal enzymes such as alcohol and anticonvulsant agents. Paracetamol excretion may be affected and plasma concentrations altered when given with probenecid. Colestyramine reduces the absorption of paracetamol if given within 1 hour of paracetamol.
Paracetamol overdose may cause liver failure, if left untreated. Immediate medical management is required in the event of overdose, even if symptoms of overdose are not present. Administration of N-acetylcysteine or methionine may be required. If an overdose is taken or suspected, phone the Poisons Information Centre should be contacted immediately for advice (131 126), or the patient should go to the hospital straight away, even if they feel well, because of the risk of delayed, serious liver damage. See ADVERSE EFFECTS.
Store below 30degC. Keep out of reach of children. Shelf life of the product is 3 years from the date of manufacture.
General Sale Medicine in packs of 12, 20 tablets / caplets. Pharmacy Only medicine: packs of 48, 96 caplets; 50 or 100 tablets
Blister packs of 12, 20, 48, 96 caplets. Blister packs of 12, 20, 50, 100 tablets
Excipients
Starch - pregelatinised maize, calcium carbonate, alginic acid, crospovidone, povidone, magnesium stearate, silica - colloidal anhydrous, parahydroxybenzoates (sodium methyl, sodium ethyl, sodium propyl), OPADRY complete film coating system YS-1-7003 WHITE, carnauba wax, water - purified. It contains no sugar, lactose or gluten.
GlaxoSmithKline (NZ) Ltd trading as GlaxoSmithKline Consumer Healthcare Private Bag 106600, Auckland, New Zealand Telephone: (09) 367 2970
30 January 2012