Consumer medicine information

Boxed Warnings

Limitations of use. Because of the risks associated with the use of opioids, Dolased Forte should only be used in patients for whom other treatment options, including non-opioid analgesics, are ineffective, not tolerated or otherwise inadequate to provide appropriate management of pain (see Section 4.4 Special Warnings and Precautions for Use).
Hazardous and harmful use. Dolased Forte tablets poses risks of hazardous and harmful use which can lead to overdose and death. Assess the patient's risk of hazardous and harmful use before prescribing and monitor the patient regularly during treatment (see Section 4.4 Special Warnings and Precautions for Use).
Life threatening respiratory depression. Serious, life-threatening or fatal respiratory depression may occur with the use of Dolased Forte tablets. Be aware of situations which increase the risk of respiratory depression, modify dosing in patients at risk and monitor patients closely, especially on initiation or following a dose increase (see Section 4.4 Special Warnings and Precautions for Use).
Concomitant use of benzodiazepines and other central nervous system (CNS) depressants, including alcohol. Concomitant use of opioids with benzodiazepines, gabapentinoids, antihistamines, tricyclic antidepressants, antipsychotics, cannabis or other central nervous system (CNS) depressants, including alcohol, may result in profound sedation, respiratory depression, coma, and death. Limit dosages and durations to the minimum required; and monitor patients for signs and symptoms of respiratory depression and sedation. Caution patients not to drink alcohol while taking Dolased Forte tablets.

1 Name of Medicine

Paracetamol, codeine phosphate hemihydrate and doxylamine succinate.

2 Qualitative and Quantitative Composition

List of excipients with known effect. Contains sugars as lactose.
For the full list of excipients, see Section 6.1 List of Excipients.

3 Pharmaceutical Form

Each tablet contains paracetamol 450 mg, codeine phosphate hemihydrate 30 mg, doxylamine succinate 5 mg. Tablets are round flat, white uncoated with bevelled edge with 'T' on one side of a break-bar.

4 Clinical Particulars

4.9 Overdose

For information on the management of overdose, contact the Poisons Information Centre on 13 11 26 (Australia).
Paracetamol. There is a risk of poisoning, particularly in elderly subjects, in young children, in patients with liver disease, in cases of chronic alcoholism, in patients with chronic malnutrition and in patients receiving enzyme inducers. Poisoning may be fatal in these cases. Acute overdose with paracetamol may also lead to acute renal tubular necrosis.
Overdose, 7.5 g (17 Dolased Forte tablets) or more of paracetamol in a single administration in adults or 140 mg/kg of body weight in a single administration in children, causes cytolytic hepatitis likely to induce complete and irreversible hepatic necrosis, resulting in acute or fulminant hepatic failure, hepatocellular insufficiency, metabolic acidosis and encephalopathy which may lead to coma and death.
Symptoms and signs of paracetamol poisoning. The early stage of acute poisoning is typically characterized by nausea, vomiting, anorexia, pallor, abdominal pain and sweating and general malaise. This is usually followed by a 24 to 48 hour period in which the patient feels better; the symptoms however do not disappear altogether. The following stage is characterized by rapid increase in the size of the liver; serum transaminases and bilirubin rise, prothrombin time increases abnormally; urine excretion decreases and a slight increase in nitrogenous substances may develop. 3 to 5 days after poisoning, the clinical features most typically encountered are commonly jaundice, fever, foetor hepaticus, abnormal bleeding tendency, hypoglycaemia, etc., as well as all stages of hepatic encephalopathy.
Nausea, vomiting, anorexia, pallor and abdominal pain generally appear during the first 24 hours of overdosage with paracetamol. Overdosage with paracetamol may cause hepatic cytolysis which can lead to hepatocellular insufficiency, gastrointestinal bleeding, metabolic acidosis, encephalopathy, disseminated intravascular coagulation, coma and death. Increased levels of hepatic transaminases, lactate dehydrogenase and bilirubin with a reduction in prothrombin level can appear 12 to 48 hours after acute overdosage. It can also lead to pancreatitis, acute renal failure and pancytopenia.
Reactions associated with doxylamine succinate overdosage may vary from central nervous depression to stimulation. Stimulation is particularly likely in children. Atropine-like signs and symptoms: dry mouth; fixed, dilated pupils; flushing and gastrointestinal symptoms may also occur. Severe rhabdomyolysis after doxylamine succinate overdose has been reported in humans.
In an evaluation of codeine intoxication in children, symptoms ranked by decreasing order of frequency included: sedation, rash, miosis, vomiting, itching, ataxia and swelling of the skin. Respiratory failure may occur. Blood concentrations of codeine ranged from 1.4 to 5.6 micrograms per mL in eight adults whose deaths were attributed to codeine overdosage.
The ingestion of very high doses of codeine can cause initial excitation, anxiety, insomnia followed by drowsiness in certain cases, areflexia progressing to stupor or coma, headache, miosis, alterations in blood pressure, arrhythmias, dry mouth, hypersensitivity reactions, cold clammy skin, bradycardia, tachycardia, convulsions, gastrointestinal disorders, nausea, vomiting and respiratory depression.
Severe intoxication can lead to apnoea, circulatory collapse, cardiac arrest and death.
Treatment of poisoning. Despite lack of significant early symptoms, patients should be referred to hospital urgently for immediate medical attention.
Consists primarily of management of paracetamol toxicity; naloxone hydrochloride is the treatment of choice for codeine intoxication and must be administered intravenously. In cases of overdosage, methods of reducing the absorption of ingested drug are important. Prompt administration of 50 g activated charcoal and 500 mL iced mannitol 20% by mouth may reduce absorption.
Determinations of the plasma concentration of paracetamol are recommended. Plasma concentrations of paracetamol should be measured at 4 hours or later after ingestion (earlier concentrations are unreliable).
If the history suggests that 15 g paracetamol or more has been ingested, administer one of the following antidotes.
Acetylcysteine 20% i.v. Administer 20% acetylcysteine immediately without waiting for positive urine test or plasma level results: initial dose 150 mg/kg over 15 minutes, followed by continuous infusion of 50 mg/kg in 500 mL 5% glucose over 4 hours and 100 mg/kg in 1 L 5% glucose over 16 hours; or
Oral methionine. 2.5 g immediately followed by three further doses of 2.5 g at four hourly intervals. For a 3 year old child, 1 g methionine 4 hourly for four doses has been used.
If more than ten hours have elapsed since the overdosage was taken, the antidote may be ineffective.
In general, treatment for codeine overdose should be symptomatic: re-establish adequate respiratory exchange by ensuring a clear airway and using mechanical ventilation. When treatment for paracetamol toxicity has been initiated; naloxone 400 microgram may be administered SC, IM or IV; IV may be repeated at intervals of 2 to 3 minutes if necessary. Assisted respiration may be required.
Further measures will depend on the severity, nature and course of clinical symptoms of intoxication and should follow standard intensive care protocols.
Doxylamine. In an evaluation of 109 cases of intoxication with doxylamine, no correlation was found between the amount ingested or plasma concentration and the frequency or extent of symptoms. The most common symptom was impaired consciousness. Psychotic behaviour, seizures, and antimuscarinic symptoms such as tachycardia and mydriasis were also seen. Rhabdomyolysis occurred in one patient and was accompanied by transient impairment of renal function. The same group commented that rhabdomyolysis had been noted in 7 of 442 cases of doxylamine overdosage, with an associated rise in plasma creatine kinase and myoglobinuria, and suggested that doxylamine has a direct toxic effect on striated muscle.
Overdosage and toxicity (including death) have been reported in children younger than 2 years of age receiving preparations containing antihistamines (including doxylamine), cough suppressants, expectorants, and nasal decongestants alone or in combination for relief of symptoms of upper respiratory tract infection.

5 Pharmacological Properties

5.3 Preclinical Safety Data

Genotoxicity. No data is available.
Carcinogenicity. Toxicity studies in animals have shown that high doses of paracetamol cause testicular atrophy and inhibition of spermatogenesis; the relevance of this finding to use in humans is not known.

6 Pharmaceutical Particulars

6.7 Physicochemical Properties

Paracetamol. Chemical Name: N-(4-hydroxyphenyl)acetamide.
Chemical structure.
https://stagingapi.mims.com/au/public/v2/images/fullchemgif/CSPARCET.gif CAS number. 103-90-2.
Molecular formula: C₈H₉NO₂.
Molecular Weight: 151.20.
Paracetamol: White to almost white crystalline powder. Paracetamol is sparingly soluble in water, freely soluble in alcohol, very slightly soluble in methylene chloride.
Codeine phosphate hemihydrate. Chemical Name: 7,8-didehydro-4,5α-epoxy-3-methoxy-17-methylmorphinan-6α-ol phosphate hemihydrate.
Chemical structure.
https://stagingapi.mims.com/au/public/v2/images/fullchemgif/CSCOPHHE.gif CAS number. 41444-62-6.
Molecular formula: C₁₈H₂₄NO₇P.½H₂O.
Molecular Weight: 406.4.
Codeine phosphate hemihydrate: White to almost white crystalline powder or small, colourless crystals. Freely soluble in water, slightly soluble or very slightly soluble in ethanol (96%). Melting point - 238-240°C.
Doxylamine succinate. Chemical Name: N,N-dimethyl-2-[(1RS)-1-phenyl-1-(pyridin-2-yl)ethoxy] (ethanamine hydrogen butanedioate).
Chemical structure.
https://stagingapi.mims.com/au/public/v2/images/fullchemgif/CSDOXSUC.gif CAS number. 562-10-7.
Molecular formula: C₂₁H₂₈N₂O₅.
Molecular Weight: 388.47.
Doxylamine succinate: White to creamy white crystalline powder with a characteristic odour. Very soluble in water and freely soluble in alcohol.

7 Medicine Schedule (Poisons Standard)

Prescription Only Medicine (Schedule 4).

Summary Table of Changes

https://stagingapi.mims.com/au/public/v2/images/fulltablegif/DOLFORST.gif