MIMS Revision Date: 01 April 2026

1 Name of Medicine

Paracetamol.

2 Qualitative and Quantitative Composition

Each modified release tablet contains 665 mg paracetamol.
For the full list of excipients see Section 6.1 List of Excipients.

3 Pharmaceutical Form

Modified release tablets; white to off-white caplet shaped coated tablets with 665 debossed on one side and plain on other side.

4 Clinical Particulars

4.1 Therapeutic Indications

APOHealth Osteo Relief Paracetamol 665 mg provides effective relief from persistent pain for up to 8 hours. Effective for the relief of persistent pain associated with osteoarthritis and muscle aches and pains such as backache. APOHealth Osteo Relief Paracetamol 665 mg also provides effective, temporary relief of pain and discomfort associated with headache, tension headache, period pain, toothache and pain after dental procedures, and cold and flu. Reduces fever.

4.2 Dose and Method of Administration

Dosage. Adults and children aged 12 years and over. 2 tablets swallowed whole three times a day, every six to eight hours. Maximum of 6 tablets in 24 hours.
Adults. Not to be used for longer than a few days at a time except on medical advice.
Children and adolescents (12-17 years). Not to be used for longer than 48 hours at a time except on medical advice.
The tablets must not be crushed. Take with water or other fluid. Tablets can be taken with or without food. Do not exceed the stated dose. Not to be taken with other medicines containing paracetamol unless advised to do so by a doctor or pharmacist.
Children under 12 years. Not recommended for children under 12 years.
Renal and hepatic impairment. Patients who have been diagnosed with liver or kidney impairment must seek medical advice before taking this medication. The restrictions related to the use of paracetamol products in patients with hepatic impairment are primarily a consequence of the paracetamol content of the drug (see Section 4.4 Special Warnings and Precautions for Use).

4.3 Contraindications

Hypersensitivity to paracetamol or to any of the excipients.

4.4 Special Warnings and Precautions for Use

If symptoms persist, medical advice must be sought. Keep out of sight and reach of children.
High anion gap metabolic acidosis. Cases of high anion gap metabolic acidosis (HAGMA) due to pyroglutamic acidosis have been reported in patients with severe illness such as severe renal impairment and sepsis, or patients with malnutrition and other sources of glutathione deficiency (e.g. chronic alcoholism) who were treated with paracetamol at therapeutic dose for a prolonged period or a combination of paracetamol and flucloxacillin. If HAGMA due to pyroglutamic acidosis is suspected, prompt discontinuation of paracetamol and close monitoring is recommended. The measurement of urinary 5-oxoproline may be useful to identify pyroglutamic acidosis as underlying cause of HAGMA in patients with multiple risk factors.
Renal impairment. Paracetamol should be used with caution in patients with impaired renal function. Administration of paracetamol to patients with moderate to severe renal impairment may result in accumulation of paracetamol conjugates.
Patients who have been diagnosed with kidney impairment must seek medical advice before taking this medicine.
Hepatic impairment. Paracetamol should be used with caution in patients with impaired hepatic function. Underlying liver disease increases the risk of paracetamol related liver damage. Patients who have been diagnosed with liver impairment must seek medical advice before taking this medicine. The restrictions related to the use of paracetamol products in patients with hepatic impairment are primarily a consequence of the paracetamol content of the drug.
Cases of hepatic dysfunction/failure have been reported in patients with depleted glutathione levels, such as those who are severely malnourished, anorexic, have a low body mass index, are chronic heavy users of alcohol or have sepsis.
If patients with glutathione depleted states, the use of paracetamol may increase the risk of metabolic acidosis.
If symptoms persist, medical advice must be sought.
Use in the elderly. No data available.
Paediatric use. Not recommended for children under 12 years of age.
Effects on laboratory tests. No data available.

4.5 Interactions with Other Medicines and Other Forms of Interactions

Caution should be taken when paracetamol is used concomitantly with flucloxacillin as concurrent intake has been associated with high anion gap metabolic acidosis due to pyroglutamic acidosis, especially in patients with risks factors (see Section 4.4).
The anticoagulant effect of warfarin and other coumarins may be enhanced by prolonged regular daily use of paracetamol with increased risk of bleeding. Anticoagulant dosage may require reduction if paracetamol and anticoagulants are taken for a prolonged period of time.
The rate of paracetamol absorption is increased by drugs which increase gastric emptying, e.g. metoclopramide.
Paracetamol absorption is decreased by drugs which 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 drugs.
Co-administration of paracetamol with probenecid may cause a decrease in the plasma clearance of paracetamol (by almost 50%) due to inhibition of paracetamol glucuronidation.
Colestyramine reduces the absorption of paracetamol if given within one hour of paracetamol.

4.6 Fertility, Pregnancy and Lactation

Effects on fertility. No data available.
Use in pregnancy. (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.
As with the use of any medicine during pregnancy, pregnant women should seek medical advice before taking paracetamol. The lowest effective dose and shortest duration of treatment should be considered.
Use in lactation. Paracetamol is excreted in breast milk. Human studies with paracetamol have not identified any risk to lactation or the breastfed offspring. These results are based on immediate release preparations of paracetamol. There is no data available on the excretion of sustained release paracetamol preparations in breast milk. However, it is not expected that paracetamol 665 mg modified release tablets would provide any increase in the excretion of paracetamol in breast milk as this product is designed to maintain rather than increase plasma paracetamol concentrations compared to immediate release preparations. Maternal ingestion of paracetamol in usual analgesic doses does not appear to present a risk to the breastfed infant.

4.7 Effects on Ability to Drive and Use Machines

The effects of this medicine on a person's ability to drive and use machines were not assessed as part of its registration.

4.8 Adverse Effects (Undesirable Effects)

Adverse events from historical clinical trial data are both infrequent and from a small patient exposure. Accordingly, events reported from extensive postmarketing experience at therapeutic/labeled dose and considered attributable are listed below by system organ class and frequency.
The following convention has been utilised for the classification of undesirable effects: very common (≥ 1/10), common (≥ 1/100, < 1/10), uncommon (≥ 1/1,000, < 1/100), rare (≥ 1/10,000, < 1/1,000), very rare (< 1/10,000), not known (cannot be estimated from available data).
Adverse event frequencies have been estimated from spontaneous reports received through postmarketing data.
Blood and lymphatic system disorders. Very rare: thrombocytopenia.
Immune system disorders. Very rare: anaphylaxis, cutaneous hypersensitivity reactions including skin rashes, angioedema, Stevens-Johnson syndrome and toxic epidermal necrolysis.
Respiratory, thoracic and mediastinal disorders. Very rare: bronchospasm, especially in patients sensitive to aspirin and other NSAIDS.
Hepatobiliary disorders. Very rare: hepatic dysfunction.
Metabolism and nutrition disorders. Not known: high anion gap metabolic acidosis. Cases of high anion gap metabolic acidosis due to pyroglutamic acidosis have been observed in patients with risk factors using paracetamol (see Section 4.4). Pyroglutamic acidosis may occur as a consequence of low glutathione levels in these patients.
Reporting suspected adverse effects. Reporting suspected adverse reactions after registration of the medicinal product is important. It allows continued monitoring of the benefit-risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions at www.tga.gov.au/reporting-problems and contact Apotex Medical Information Enquiries/Adverse Drug Reaction Reporting on 1800 195 055.

4.9 Overdose

If an overdose is taken or suspected, contact the Poisons Information Centre immediately for advice (131 126), or the patient should go to the nearest hospital straight away. This should be done even if they feel well because of the risk of delayed, serious liver damage (see Section 4.8 Adverse Effects (Undesirable Effects)).
Because APOHealth Osteo Relief Paracetamol 665 mg contains a sustained release formulation of paracetamol, absorption will be prolonged in overdose. It is recommended that for the management of overdose, where APOHealth Osteo Relief Paracetamol 665 mg is suspected, that an additional plasma paracetamol level be obtained four to six hours after the initial measurement. If either level is above or close to the treatment line on the paracetamol overdose nomogram, administration of antidote would be indicated.
Treatment. Paracetamol overdose may cause liver failure. Immediate medical management is required in the event of an overdose, even if the symptoms of overdose are not present.
Administration of acetylcysteine may be required.
In cases of overdosage, methods of reducing absorption of ingested drug are important. Activated charcoal may reduce absorption of the medicine if given within one hour after ingestion. In patients who are not fully conscious or have impaired gag reflex, consideration should be given to administering activated charcoal via a nasogastric tube, once the airway is protected.
For information on the management of overdose, contact the Poisons Information Centre on 131126 (Australia).

5 Pharmacological Properties

5.1 Pharmacodynamic Properties

Mechanism of action. Paracetamol is a para-aminophenol derivative that exhibits analgesic and antipyretic activity. The mechanism of action of paracetamol is believed to include the inhibition of prostaglandin synthesis, primarily within the central nervous system. It does not possess anti-inflammatory activity. It provides relief from mild to moderate pain and fever.
Clinical trials. Chronic pain. In patients with pain associated with osteoarthritis of the knee, paracetamol 665 mg modified release tablets (two tablets taken three times daily) and standard immediate release paracetamol (two tablets taken four times daily) were clinically equivalent at a total daily dose of 4 g based on patient global assessment after treatment for seven days.
Paracetamol 665 mg modified release tablets and standard immediate release paracetamol were not significantly different for a range of secondary efficacy parameters including pain during the day, pain on walking, pain relief, number of times woken during the night due to pain and duration or morning stiffness. Since paracetamol 665 mg modified release tablets (three times daily) was clinically equivalent to standard immediate release paracetamol (four times daily), it was concluded that paracetamol 665 mg modified release tablets provides pain relief for up to eight hours after dosing.
Acute pain. In patients with postsurgical dental pain, a single dose of paracetamol 665 mg modified release tablets (two tablets) was therapeutically equivalent to standard immediate release paracetamol (two tablets) based on patient global assessment four hours after treatment. Onset of action was apparent 30 minutes after administration.
There was no significant difference between paracetamol 665 mg modified release tablets and standard immediate release paracetamol in either development of analgesia or peak analgesic effect. Trends in favour of paracetamol 665 mg modified release tablets were observed at the later time points. Furthermore, paracetamol 665 mg modified release tablets was significantly more effective than standard immediate release paracetamol for the summed pain intensity difference at six hours (p = 0.0344) and eight hours (p = 0.0500), as measured on a visual analogue scale.
From these results, it was concluded that paracetamol 665 mg modified release tablets has a similar time to onset of action compared to standard immediate release paracetamol and provides more prolonged analgesia than standard immediate release paracetamol. For the patient, this translates to longer lasting pain relief and the improved convenience of fewer doses. This is as expected for a formulation containing sustained release paracetamol and consistent with results from the pharmacokinetic studies.

5.2 Pharmacokinetic Properties

The combination of immediate release and sustained release paracetamol provides pain relief, which may last up to 8 hours.
Absorption. Paracetamol is rapidly and almost completely absorbed from the gastrointestinal tract. Food intake delays paracetamol absorption.
Paracetamol 665 mg modified release tablets are bilayer tablets incorporating an immediate release and a sustained release dose of paracetamol.
The sustained release layer is formulated in such a manner that it rapidly hydrates to form a gel layer at the matrix periphery; the drug is then released from the matrix by a combination of diffusion and erosion of the gel layer.
Paracetamol 665 mg modified release tablets release drug at a rate which ensures that therapeutically active plasma paracetamol concentrations are rapidly attained and maintained until up to eight hours after administration.
Bioequivalence. Paracetamol 665 mg modified release tablets and standard immediate release paracetamol were bioequivalent in volunteers with respect to dose corrected AUC_(0-t) and AUC_(0-∞) in both fed and fasted states following administration of a single dose. This indicates that the extent of paracetamol absorption from paracetamol 665 mg modified release tablets was equivalent to that of standard immediate release paracetamol. Food had little effect on the extent of paracetamol absorption from paracetamol 665 mg modified release tablets demonstrating that paracetamol 665 mg modified release tablets is suitable to be taken with or without meals. Paracetamol was rapidly absorbed after administration of paracetamol 665 mg modified release tablets and was generally measurable in plasma within 15 minutes in fasted subjects. Mean plasma paracetamol concentrations above the minimum level required for analgesia (> 4 microgram/mL) were maintained until up to six to seven hours after administration in fasted subjects and seven to eight hours in fed subjects.
At steady state, paracetamol 665 mg modified release tablets was bioequivalent with standard immediate release paracetamol based on the comparison of AUCs during the final 24 hour dosing period of the study. Furthermore, comparison of the pharmacokinetic parameters indicated that paracetamol 665 mg modified release tablets has the characteristics of a formulation containing sustained release paracetamol. Fluctuations in the peak and trough values for plasma paracetamol concentrations were significantly smaller for paracetamol 665 mg modified release tablets than for standard immediate release paracetamol (mean fluctuation index = 0.957 and 1.388, respectively, p < 0.001). Consequently, paracetamol 665 mg modified release tablets provided more consistent levels of paracetamol. Furthermore, the AUCs at steady state were equivalent indicating that there was no additional accumulation of paracetamol from paracetamol 665 mg modified release tablets compared to standard immediate release paracetamol.
Distribution. Paracetamol is distributed into most body tissues. Binding to the plasma proteins is minimal at therapeutic concentrations but increases with increasing doses.
Metabolism. Paracetamol is metabolised extensively in the liver and excreted in the urine mainly as inactive glucuronide and sulfate conjugates. 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 overdosage (more than 150 mg/kg or 10 g 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 sulfate conjugate being predominant.
Excretion. Paracetamol is excreted in the urine mainly as the glucuronide and sulphate conjugates. Less than 5% is excreted unchanged. Approximately 85% of a dose of paracetamol is excreted in urine as free and conjugated paracetamol within 24 hours of ingestion. Administration of paracetamol to patients with moderate to severe renal impairment may result in accumulation of paracetamol conjugates. The elimination half-life varies from one to three hours.

5.3 Preclinical Safety Data

Genotoxicity. No data available.
Carcinogenicity. No data available.

6 Pharmaceutical Particulars

6.1 List of Excipients

Maize starch, sodium starch glycollate type A, colloidal anhydrous silica, povidone, magnesium stearate, pregelatinised maize starch, hypromellose, microcrystalline cellulose, macrogol 6000, purified talc, titanium dioxide.

6.2 Incompatibilities

Incompatibilities were either not assessed or not identified as part of the registration of this medicine.

6.3 Shelf Life

In Australia, information on the shelf life can be found on the public summary of the Australian Register of Therapeutic Goods (ARTG). The expiry date can be found on the packaging.

6.4 Special Precautions for Storage

Store below 25°C.

6.5 Nature and Contents of Container

PVC/PVDC/aluminium foil blister packs of 96 tablets and HDPE bottle pack of 100 tablets and 1000 tablets.
Not all pack sizes will be marketed.

6.6 Special Precautions for Disposal

In Australia, any unused medicine or waste material should be disposed of by taking to your local pharmacy.

6.7 Physicochemical Properties

Chemical structure. Chemical Name: N-acetyl-p-aminophenol.
Structural Formula:

Molecular formula: C₈H₉NO₂.
Molecular weight: 151.17.
CAS number. 103-90-2.

7 Medicine Schedule (Poisons Standard)

Pharmacist Only Medicine - S3.

Date of First Approval

28 October 2016

Date of Revision

03 March 2026

Summary Table of Changes