Consumer medicine information

Dolased Tablets

Paracetamol; Codeine phosphate hemihydrate; Doxylamine succinate

BRAND INFORMATION

Brand name

Dolased

Active ingredient

Paracetamol; Codeine phosphate hemihydrate; Doxylamine succinate

Schedule

S4

 

Consumer medicine information (CMI) leaflet

Please read this leaflet carefully before you start using Dolased Tablets.

What is in this leaflet

This leaflet answers some common questions about Dolased. It does not contain all the available information.

It does not take the place of talking to your doctor or pharmacist.

All medicines have risks and benefits. Your doctor or pharmacist has weighed the risks of you taking Dolased against the benefits this medicine is expected to have for you.

If you have any concerns about taking this medicine, ask your doctor or pharmacist.

Keep this leaflet with the medicine. You may need to read it again.

What is Dolased

The name of your medicine is Dolased.

It contains the active ingredients paracetamol, doxylamine succinate and codeine phosphate hemihydrate.

Paracetamol, an analgesic with antipyretic action also reduces fever.

Doxylamine succinate is an antihistamine with pronounced sedative effects.

Codeine phosphate hemihydrate is an opioid analgesic, and in combination with paracetamol and doxylamine produces greater analgesia than any of these drugs alone and avoids the side effects associated with large doses of these components.

Dolased tablets contain no aspirin.

What Dolased is used for

Dolased provides temporary relief of acute moderate pain and fever.

Your doctor or pharmacist may recommend Dolased for another reason. If you want more information ask your doctor or pharmacist.

Before you take Dolased

When you must not take it

Do not take Dolased if:

you have an allergy to:

  • Paracetamol, codeine or doxylamine succinate, or any of the ingredients listed at the end of this leaflet
  • you have had an allergic reaction to other opioid analgesic such as morphine or pethidine
  • you have had an allergic reaction to other antihistamines

Symptoms of an allergic reaction to these medicines may include:

  • asthma, wheezing or shortness of breath
  • swelling of the face, lips or tongue which may cause difficulty in swallowing or breathing
  • hives, itching or skin rash
  • fainting

Do not take Dolased if you have or have had any of the following medical conditions:

  • Ultra-rapid metaboliser of CYP 2D6
  • Known intolerance to medicines used to treat or prevent pain
  • Diarrhoea caused by antibiotics or poisoning
  • Liver failure

Do not take Dolased if the packaging is torn or shows signs of tampering.

Do not take Dolased if the expiry date (EXP) printed on the pack has passed. If you take this medicine after the expiry date has passed, it may not work as well.

If you are not sure whether you should start taking Dolased contact your doctor or pharmacist.

Do not give Dolased to a child under 12 years. The safety and effectiveness of Dolased in children have not been established.

Do not give to children aged between 12 - 18 years in whom respiratory function might be compromised, including post tonsillectomy and/or adenoidectomy for obstructive sleep apnoea, due to an increased risk of developing serious and life-threatening adverse reactions

Dolased is distributed to the breast milk so do not take if you are breastfeeding. However, if your doctor advises you require codeine therapy while breastfeeding, then breastfeeding should be suspended and alternative arrangements should be made for feeding the infant for any period during codeine treatment.

Before you start to take it

Tell your doctor if:

  1. you have any allergies to:
  • any other medicines or any other substances, such as foods, preservatives or dyes
  1. you are pregnant or intend to become pregnant.
Your doctor will discuss the possible risks and benefits of using Dolased during pregnancy.
  1. you are breast-feeding or plan to breast-feed.
Your doctor will discuss the possible risks and benefits of using Dolased during breastfeeding.
  1. you have or have had any medical conditions, especially the following:
  • kidney or liver disease
  • breathing problems (eg. asthma)
  • glaucoma
  • bladder problems (urinary retention)
  • prostate problems
  • stomach ulcer or other stomach problems
  1. you are a heavy drinker.

If you have not told your doctor or pharmacist about any of the above, tell them before you take any Dolased.

Taking other medicines

Do not take Dolased with other products containing paracetamol, unless advised to do so by a doctor or pharmacist.

Tell your doctor or pharmacist if you are taking any other medicines, including any that you buy without a prescription from your pharmacy, supermarket or health food shop.

Some medicines may interfere with Dolased. These include:

  • some drugs used to treat depression (eg. barbiturates, monoamine oxidase inhibitors)
  • medication for epilepsy
  • medications used to control fits (eg. Dilantin or Tegretol)
  • medicines to help you sleep, or relieve anxiety
  • opioid analgesics (eg. morphine or pethidine)
  • some drugs used to thin the blood (anti-coagulants)
  • alcohol
  • Paracetamol excretion may be affected and plasma concentrations altered when given with probenecide.
  • Colestyramine reduces the absorption of paracetamol if given within 1 hour of paracetamol.

These medicines may be affected by Dolased, or may affect how well it works.

Your doctor and pharmacist may have more information on medicines to be careful with or avoid while taking Dolased.

If you have not told your doctor or pharmacist about any of the above, tell them before you take any Dolased.

How to take Dolased

How to take it

WARNING: Keep to the recommended dose.

Adults: Do not take this medicine for longer than a few days at a time unless advised to by a doctor.

Children and adolescent: Do not take this medicine for longer than 48 hours at a time unless advised to by a doctor.

Do not take with other medicines containing paracetamol unless advised to do so by a doctor.

How much to take

Dolased should be swallowed with a glass of water. They can be taken with or without food.

This medicine may cause constipation.

Adults and children over 12 years: Take 1 - 2 tablets every 4 - 6 hours as necessary.

Do not exceed 8 tablets in a 24-hour period.

Do not give to children under 12 years of age.

If you do not understand the instructions on the box, ask your doctor or pharmacist for help.

How long to take it

Continue taking your medicine for as long as your doctor tells you. If you stop having this medicine suddenly, your pain may worsen and you may experience some or all of the following withdrawal symptoms:

  • nervousness, restlessness, agitation, trouble sleeping or anxiety
  • body aches, weakness or stomach cramps
  • loss of appetite, nausea, vomiting or diarrhoea
  • increased heart rate, breathing rate or pupil size
  • watery eyes, runny nose, chills or yawning
  • increased sweating.

Dolased given to the mother during labour can cause breathing problems and signs of withdrawal in the newborn.

If you take too much (overdose)

If you or someone else receive too much (overdose), and experience one or more of the symptoms below call triple zero (000) for an ambulance. Keep the person awake by talking to them or gently shaking them every now and then. You should follow the above steps even if someone other than you have accidentally used Dolased that was prescribed for you. If someone takes an overdose they may experience one or more of the following symptoms:

  • Slow, unusual or difficult breathing
  • Drowsiness, dizziness or unconsciousness
  • Slow or weak heartbeat
  • Nausea or vomiting
  • Convulsions or fits

If you think you or someone else may have used too much Dolased you should immediately:

  • phone the Poisons Information Centre (by calling 13 11 26), or
  • contact your doctor, or
  • go to the Emergency Department at your nearest hospital.

You should do this even if there are no signs of discomfort or poisoning. When seeking medical attention, take this leaflet and remaining medicine with you to show the doctor. Also tell them about any other medicines or alcohol which have been taken.

Depending on your body’s individual ability to break down codeine, you may experience signs of overdose even when you take Dolased as recommended by your doctor. If overdose symptoms occur, seek immediate medical advice.

Things to be careful of:

You can become addicted to Dolased even if you take it exactly as prescribed. Dolased may become habit forming causing mental and physical dependence. If abused it may become less able to reduce pain.

As with all other opioid containing products, your body may become used to you taking Dolased. Taking it may result in physical dependence. Physical dependence means that you may experience withdrawal symptoms if you stop taking Dolased suddenly, so it is important to take it exactly as directed by your doctor.

Tolerance to Dolased may develop, which means that the effect of the medicine may decrease. If this happens, more may be needed to maintain the same effect.

While you are taking Dolased

Things you must do

If you are about to start taking any new medicine tell your doctor and pharmacist that you are taking Dolased.

Tell all of the doctors, dentists, and pharmacists that are treating you that you are taking Dolased.

If you plan to have surgery that needs a general anaesthetic, tell you doctor or dentist that you are taking Dolased.

Things you must not do

Do not give Dolased to anyone else, even if they have the same condition as you.

Do not use Dolased to treat any other complaints unless your doctor or pharmacist tells you to.

Do not drink alcohol.

Things to be careful of

Be careful driving or operating machinery until you know how Dolased affects you.

Dolased may cause drowsiness or light-headedness in some people and affect mental alertness. Make sure you know how you react to Dolased before you drive a car, operate machinery, or do anything else that could be dangerous if you are dizzy. If you drink alcohol, dizziness or drowsiness could be worse.

Codeine may be habit forming if taken frequently and over a long period of time. Please ask your doctor or pharmacist if you are concerned about this.

About 8% of people are poor metabolisers of codeine and Dolased may not work as well if you are one of those people.’

Side effects

Like other medicines, Dolased can cause some side effects. If they occur, most are likely to be minor and temporary. However, some may be serious and need medical attention.

The more common side effects of Dolased are:

  • skin rashes,
  • dry mouth,
  • constipation
  • sedation or drowsiness
  • dizziness,
  • nausea and vomiting,
  • stomach pain

Tell your doctor or pharmacist if you notice any of these side effects and they worry you.

After taking Dolased

Storage

Keep your tablets in the pack until it is time to take them. If you take the tablets out of the pack they will not keep well.

Keep the tablets in a cool dry place where the temperature stays below 30 degrees Celcius. Do not store Dolased or any other medicine in the bathroom or near a sink. Do not leave it in the car or on window sills. Heat and dampness can destroy some medicines.

Keep medicines where children cannot reach it. A locked cupboard at least one-and-a-half metres above the ground is a good place to store medicines.

Disposal

If your doctor or pharmacist tells you to stop taking Dolased or the tablets have passed their expiry date, ask your pharmacist what to do with any that are left over.

Product description

What it looks like

Dolased is a white biconvex capsule-shaped tablet. They are available in blister packs of 20 and 40 tablets.

Ingredients

Each Dolased tablet contains the following active ingredients:

  • Paracetamol 500mg
  • Codeine Phosphate Hemihydrate 10mg
  • Doxylamine Succinate 5.1mg

The following inactive ingredients are found in Dolased:

  • Crospovidone
  • Stearic acid
  • Magnesium stearate
  • Lactose monohydrate
  • Glyceryl monostearate - self-emulsifying
  • Povidone.

Dolased contains lactose, but does not contain sucrose, gluten, tartrazine or any other azo dyes.

Manufacturer

Aspen Pharma Pty Ltd
34-36 Chandos Street
St Leonards NSW 2065
Website: www.aspencmi.com.au

The Australian Registration number for Dolased is AUST R 157880

This leaflet was updated in November 2020.

Published by MIMS October 2025

BRAND INFORMATION

Brand name

Dolased

Active ingredient

Paracetamol; Codeine phosphate hemihydrate; Doxylamine succinate

Schedule

S4

 

1 Name of Medicine

Dolased paracetamol, codeine phosphate hemihydrate and doxylamine succinate tablets.

2 Qualitative and Quantitative Composition

Each Dolased tablet contains paracetamol 500 mg, codeine phosphate hemihydrate 10 mg, doxylamine succinate 5.1 mg.

List of excipients with known effects.

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

3 Pharmaceutical Form

Dolased tablets are white biconvex capsule-shaped tablet.

4 Clinical Particulars

4.1 Therapeutic Indications

For the temporary relief of acute moderate pain and fever.

4.2 Dose and Method of Administration

Adults and children over 12 years.

One to two tablets with water every 4-6 hours if necessary. Do not exceed 8 tablets in 24 hours period.

Children.

Not for use in children as follows:
younger than 12 years (see Section 4.3 Contraindications);
aged between 12 - 18 years in whom respiratory function might be compromised, including post tonsillectomy and/or adenoidectomy for obstructive sleep apnoea, due to an increased risk of developing serious and life-threatening adverse reactions (see Section 4.3 Contraindications; Section 4.4 Special Warnings and Precautions for Use, Paediatric use).

4.3 Contraindications

This medicine should not be given to patients with:
known sensitivity to paracetamol, codeine phosphate hemihydrate or other opioid analgesics, doxylamine succinate or to other antihistamines of the ethanolamine class or any of the other ingredients;
severe respiratory disease, acute respiratory disease and respiratory depression/ insufficiency, e.g. acute asthma, acute exacerbations of chronic obstructive pulmonary disease since codeine may exacerbate the condition. Patients with severe hepatocellular insufficiency. Patients with glucose-6-phosphate-dehydrogenase deficiency;
active alcoholism (as this may predispose patients to paracetamol hepatoxicity);
diarrhoea due to pseudomembranous colitis or poisoning (until the causative organism or toxin has been eliminated from the gastrointestinal tract since codeine may slow their elimination.
Dolased is contraindicated for use in patients who are:
CYP2D6 ultra-rapid metabolisers (see Section 4.4 Special Warnings and Precautions for Use, CYP2D6 metabolism);
younger than 12 years (see Section 4.4 Special Warnings and Precautions for Use, Paediatric use);
aged between 12 - 18 years in whom respiratory function might be compromised, including post tonsillectomy and/or adenoidectomy for obstructive sleep apnoea, obesity and pulmonary disease due to an increased risk of developing serious and life-threatening adverse reactions (see Section 4.4 Special Warnings and Precautions for Use, Paediatric use);
breastfeeding (see Section 4.6, Use in lactation);
using monoamine inhibitors (MAOIs) or have stopped treatment within the last 14 days (see Section 4.5 Interactions with Other Medicines and Other Forms of Interactions).

4.4 Special Warnings and Precautions for Use

Hepatotoxicity may occur with paracetamol even at therapeutic doses, after short treatment duration and in patients without pre-existing liver dysfunction.

To avoid the risk of overdose.

Check that paracetamol is absent from the composition of other medicinal products taken concomitantly.
Avoid alcohol.
This medication may be dangerous when used in large amounts or for long periods. Hepatotoxicity may develop following a dose of 10 g of paracetamol and hepatic failure is known to occur occasionally with the long term use of paracetamol.
Patients with known analgesic intolerance or known bronchial asthma must only use Dolased after having consulted a physician (hypersensitivity reactions including bronchospasm are possible).
Caution is advised in patients with underlying sensitivity to aspirin and/or to nonsteroidal anti-inflammatory drugs (NSAIDs).

Severe cutaneous adverse reactions (SCARs).

Life-threatening cutaneous reactions Stevens-Johnson syndrome (SJS), and toxic epidermal necrolysis (TEN) have been reported with the use of paracetamol. If symptoms or signs of SJS and TEN (e.g. progressive skin rash often with blisters or mucosal lesions) occur, patients should stop immediately paracetamol treatment and seek medical advice.

Paracetamol should be used upon medical advice in patients with.

Mild to moderate hepatocellular insufficiency;
severe renal insufficiency;
chronic alcohol use including recent cessation of alcohol intake;
low glutathione reserves;
Gilbert's syndrome.
Codeine must be administered with caution in certain patients such as those who present with impaired cardiac, hepatic or renal function, hypotension, benign prostatic hyperplasia, urethral stenosis, adrenal insufficiency (Addison's disease), hypothyroidism, multiple sclerosis, chronic colitis ulcerative, gallbladder conditions and diseases that present with reduced respiratory capacity such as emphysema, kyphoscoliosis and severe obesity.
Patients who have had a cholecystectomy should be treated with caution. The contraction of the sphincter of Oddi can cause symptoms resembling those of myocardial infarction or intensify the symptoms in patients with pancreatitis.
Codeine should be used with caution in patients with convulsive disorders.
Extensive use of analgesics to relieve headaches or migraines, especially at high doses, may induce headaches that must not be treated with increased doses of the drug. In such cases the analgesic should not continue to be taken without medical advice.
Monitoring after prolonged use should include blood count, liver function and renal function.
Codeine should only be used after careful risk-benefit assessment in case of:
Opioid dependence.
Chronic constipation.
Conditions with elevated intracranial pressure and head trauma. Codeine can increase the pressure of cerebrospinal fluid and may increase the respiratory depressant effect. Like other narcotics, it causes adverse reactions that can obscure the clinical course of patients with head injury.
Impaired consciousness.
Compromised respiratory function (due to emphysema, kyphoscoliosis, severe obesity) and chronic obstructive airway disease.
Doxylamine must be administered with caution in patients with:
urinary retention;
susceptibility to angle closure glaucoma.

Hazardous and harmful use.

Dolased contains the opioid codeine and is a potential drug of abuse, misuse and addiction. Addiction can occur in patients appropriately prescribed Dolased at recommended doses.
The risk of addiction is increased in patients with a personal or family history of substance abuse (including alcohol and prescription and illicit drugs) or mental illness. The risk also increases the longer the drug is used and with higher doses. Patients should be assessed for their risks for opioid abuse or addiction prior to being prescribed Dolased.
All patients receiving opioids should be routinely monitored for signs of misuse and abuse. Opioids are sought by people with addiction and may be subject to diversion. Strategies to reduce these risks include prescribing the drug in the smallest appropriate quantity and advising the patient on the safe storage and proper disposal of any unused drug (see Section 6.4 Special Precautions for Storage; Section 6.6 Special Precautions for Disposal). Caution patients that abuse of oral or transdermal forms of opioids by parenteral administration can result in serious adverse events, which may be fatal.
Patients should be advised not to share Dolased with anyone else.

Respiratory depression.

Serious, life-threatening or fatal respiratory depression can occur with the use of opioids even when used as recommended. It can occur at any time during the use of Dolased but the risk is greatest during initiation of therapy or following an increase in dose. Patients should be monitored closely for respiratory depression at these times.
The risk of life-threatening respiratory depression is also higher in elderly, frail, or debilitated patients, in patients with hepatic and renal impairment (see Use in hepatic impairment and Use in renal impairment) and in patients with existing impairment of respiratory function (e.g. chronic obstructive pulmonary disease; asthma). Opioids should be used with caution and with close monitoring in these patients (see Section 4.2 Dose and Method of Administration). The use of opioids is contraindicated in patients with severe respiratory disease, acute respiratory disease and respiratory depression (see Section 4.3 Contraindications).
The risk of respiratory depression is greater with the use of high doses of opioids, especially high potency and modified release formulations, and in opioid naïve patients. Initiation of opioid treatment should be at the lower end of the dosage recommendations with careful titration of doses to achieve effective pain relief. Careful calculation of equianalgesic doses is required when changing opioids or switching from immediate release to modified release formulations, (see Section 4.2 Dose and Method of Administration), together with consideration of pharmacological differences between opioids. Consider starting the new opioid at a reduced dose to account for individual variation in response.

Risks from concomitant use of benzodiazepines or other CNS depressants, including alcohol.

Concomitant use of opioids and benzodiazepines or other CNS depressants, including alcohol, may result in sedation, respiratory depression, coma and death. Because of these risks, concomitant prescribing of Dolased with CNS depressant medicines, such as other opioid analgesics, benzodiazepines, gabapentinoids, cannabis, sedatives, hypnotics, tricyclic antidepressants, antipsychotics, antihistamines, centrally-active anti-emetics and other CNS depressants, should be reserved for patients for whom other treatment options are not possible. If a decision is made to prescribe Dolased concomitantly with any of the medicines, the lowest effective dose should be used, and the duration of treatment should be as short as possible. Patients should be followed closely for signs and symptoms of respiratory depression and sedation. Patients and their caregivers should be made aware of these symptoms. Patients and their caregivers should also be informed of the potential harms of consuming alcohol while taking Dolased.

Use of opioids in chronic (long-term) non-cancer pain (CNCP).

Opioid analgesics have an established role in the treatment of acute pain, cancer pain and palliative and end of life care. Current evidence does not generally support opioid analgesics in improving pain and function for most patients with chronic non-cancer pain. The development of tolerance and physical dependence and risks of adverse effects, including hazardous and harmful use, increase with the length of time a patient takes an opioid. The use of opioids for long-term treatment of CNCP is not recommended.
The use of an opioid to treat CNCP should only be considered after maximised nonpharmacological and non-opioid treatments have been tried and found ineffective, not tolerated or otherwise inadequate to provide sufficient management of pain. Opioids should only be prescribed as a component of comprehensive multidisciplinary and multimodal pain management.
Opioid therapy for CNCP should be initiated as a trial in accordance with clinical guidelines and after a comprehensive biopsychosocial assessment has established a cause for the pain and the appropriateness of opioid therapy for the patient (see Hazardous and harmful use, above). The expected outcome of therapy (pain reduction rather than complete abolition of pain, improved function and quality of life) should be discussed with the patient before commencing opioid treatment, with agreement to discontinue treatment if these objectives are not met.
Owing to the varied response to opioids between individuals, it is recommended that all patients be started at the lowest appropriate dose and titrated to achieve an adequate level of analgesia and functional improvement with minimum adverse reactions. Immediate-release products should not be used to treat chronic pain, but may be used for a short period in opioid-naïve patients to develop a level of tolerance before switching to a modified-release formulation. Careful and regular assessment and monitoring is required to establish the clinical need for ongoing treatment. Discontinue opioid therapy if there is no improvement of pain and/or function during the trial period or if there is any evidence of misuse or abuse. Treatment should only continue if the trial has demonstrated that the pain is opioid responsive and there has been functional improvement. The patient's condition should be reviewed regularly and the dose tapered off slowly if opioid treatment is no longer appropriate (see Ceasing opioids).

Tolerance, dependence and withdrawal.

Neuroadaptation of the opioid receptors to repeated administration of opioids can produce tolerance and physical dependence. Tolerance is the need for increasing doses to maintain analgesia. Tolerance may occur to both the desired and undesired effects of the opioid.
Physical dependence, which can occur after several days to weeks of continued opioid usage, results in withdrawal symptoms if the opioid is ceased abruptly or the dose is significantly reduced. Withdrawal symptoms can also occur following the administration of an opioid antagonist (e.g. naloxone) or partial agonist (e.g. buprenorphine). Withdrawal can result in some or all of the following symptoms: dysphoria, restlessness/agitation, lacrimation, rhinorrhoea, yawning, sweating, chills, myalgia, mydriasis, irritability, anxiety, increasing pain, backache, joint pain, weakness, abdominal cramps, insomnia, nausea, anorexia, vomiting, diarrhoea, increased blood pressure, increased respiratory rate and increased heart rate.
When discontinuing Dolased in a person who may be physically-dependent, the drug should not be ceased abruptly but withdrawn by tapering the dose gradually (see Ceasing opioids; see Section 4.2 Dose and Method of Administration).

Accidental ingestion/exposure.

Accidental ingestion or exposure of Dolased, especially by children, can result in a fatal overdose of codeine. Patients and their caregivers should be given information on safe storage and disposal of unused Dolased (see Section 6.4 Special Precautions for Storage; Section 6.6 Special Precautions for Disposal).

Hyperalgesia.

Hyperalgesia may occur with the use of opioids, particularly at high doses. Hyperalgesia may manifest as an unexplained increase in pain, increased levels of pain with increasing opioid dosages or diffuse sensitivity not associated with the original pain. Hyperalgesia should not be confused with tolerance (see Tolerance, dependence and withdrawal). If opioid induced hyperalgesia is suspected, the dose should be reduced and tapered off if possible. A change to a different opioid may be required.

Ceasing opioids.

Abrupt discontinuation or rapid decreasing of the dose in a person physically dependent on an opioid may result in serious withdrawal symptoms and uncontrolled pain (see Tolerance, dependence and withdrawal). Such symptoms may lead the patient to seek other sources of licit or illicit opioids. Opioids should not be ceased abruptly in a patient who is physically dependent but withdrawn by tapering the dose slowly. Factors to take into account when deciding how to discontinue or decrease therapy include the dose and duration of the opioid the patient has been taking, the type of pain being treated and the physical and psychological attributes of the patient. A multimodal approach to pain management should be in place before initiating an opioid analgesic taper. During tapering, patients require regular review and support to manage any increase in pain, psychological distress and withdrawal symptoms.
There are no standard tapering schedules suitable for all patients and an individualised plan is necessary. In general, tapering should involve a dose reduction of no more than 10 percent to 25 percent every 2 to 4 weeks (see Section 4.2 Dose and Method of Administration). If the patient is experiencing increased pain or serious withdrawal symptoms, it may be necessary to go back to the previous dose until stable before proceeding with a more gradual taper.
When ceasing opioids in a patient who has a suspected opioid use disorder, the need for medication assisted treatment and/or referral to a specialist should be considered.

CYP2D6 metabolism.

Dolased is contraindicated for use in patients who are CYP2D6 ultra-rapid metabolisers.
Codeine is metabolised by the liver enzyme CYP2D6 into morphine, its active metabolite. If a patient has a deficiency or is completely lacking this enzyme an adequate analgesic effect will not be obtained. However, if the patient is an extensive or ultra-rapid metaboliser there is an increased risk of developing side effects of opioid toxicity even at commonly prescribed doses. These patients convert codeine into morphine rapidly resulting in higher than expected serum morphine levels. General symptoms of opioid toxicity include confusion, somnolence, shallow breathing, small pupils, nausea, vomiting, constipation and lack of appetite. In severe cases this may include symptoms of circulatory and respiratory depression, which may be life-threatening and very rarely fatal. Children are particularly susceptible due to their immature airway anatomy. Deaths have been reported in children with rapid metabolism who were given codeine for analgesia post adenotonsillectomy. Morphine can also be ingested by infants through breast milk, causing risk of respiratory depression to infants of rapid metaboliser mothers who take codeine.
The prevalence of codeine ultra-rapid metabolism by CYP2D6 in children is not known, but is assumed to be similar to that reported in adults. The prevalence of ultra-rapid metabolisers is estimated to be 1% in those of Chinese, Japanese and Hispanic descent, 3% in African Americans and 1%-10% in Caucasians. The highest prevalence (16%-28%) occurs in North African, Ethiopian and Arab populations. (Also see Section 4.4 Special Warnings and Precautions for Use, Paediatric use; Section 4.6 Fertility, Pregnancy and Lactation, Use in lactation).

Other precautions.

Dolased should be used with caution or in reduced doses in patients with shock, inflammatory, obstructive bowel disorders or myasthenia gravis.

Use in hepatic impairment.

Administer with caution to patients with hepatic dysfunction.
Hepatotoxicity may develop after the ingestion of a single dose of 10 to 15 g (200 to 250 mg/kg) and a dose of more than 25 g is potentially fatal. Patients may be asymptomatic for several days following the ingestion of large doses of paracetamol and laboratory evidence of hepatotoxicity may be delayed up to one week. Non-fatal damage is usually reversible.

Use in renal impairment.

Administer with caution to patients with renal dysfunction.

Use in the elderly.

Dolased should be given in reduced dosage in elderly patients.
Elderly people may be more sensitive to the effects of this medicinal product, especially respiratory depression. The elderly are more likely to have hypertrophy, prostatic obstruction and age-related renal impairment and may be more susceptible to the undesirable effects due to opioid-induced urinary retention and the respiratory effects of opioid analgesics.

Paediatric use.

Dolased is contraindicated for use in children:
younger than 12 years;
aged between 12 - 18 years in whom respiratory function might be compromised, including post tonsillectomy and/or adenoidectomy for obstructive sleep apnoea. Respiratory depression and death have occurred in some children who received codeine following tonsillectomy and/or adenoidectomy and had evidence of being ultra-rapid metabolisers of codeine due to a CYP2D6 polymorphism. (Also see Section 4.4 Special Warnings and Precautions for Use, CYP2D6 metabolism).

Effects on laboratory tests.

Uric acid and blood glucose.

Intake of paracetamol may affect the laboratory determination of uric acid by phosphotungstic acid and of blood glucose by glucose oxidase-peroxidase.

4.5 Interactions with Other Medicines and Other Forms of Interactions

The concomitant use of opioids with benzodiazepines and/or other CNS depressants (e.g. other opioid analgesics, antitussives, antihypertensives, antihistamines, antipsychotics, antianxiety, gabapentinoids, cannabis, centrally-active anti-emetics, hypnotics, sedatives, tranquillisers), including alcohol, may result in additive CNS depression and increases the risk of sedation, respiratory depression, coma and death (see Section 4.4 Special Warnings and Precautions for Use, Risks from concomitant use of benzodiazepines or other CNS depressants, including alcohol).
The concomitant use of alcohol and opioids increases the risk of sedation, respiratory depression, coma and death because of additive CNS depressant effect. Concomitant use with alcohol is not recommended (see Section 4.4 Special Warnings and Precautions for Use).
Concomitant administration of monoamine oxidase inhibitors (MAOIs) can potentiate the central nervous effects and other side effects of unpredictable severity. Codeine should not be used within 14 days after the discontinuation of MAOI treatment.
A codeine-induced respiratory depression can be potentiated by tricyclic antidepressants.
Concomitant use of codeine with antiperistaltic antidiarrhoeal drugs can increase the risk of severe constipation and CNS depression.
Morphinic agonists-antagonists: concomitant use of codeine with a partial agonist (e.g. buprenorphine) or antagonist (e.g. naltrexone) can precipitate or delay codeine effects.
The risk of paracetamol toxicity may be increased in patients receiving other potentially hepatotoxic drugs or drugs that induce liver microsomal enzymes, such as barbiturates and other antiepileptics (such as phenobarbital, phenytoin, carbamazepine, topiramate), rifampicin and alcohol. The induced metabolism results in an elevated production of the hepatotoxic oxidative metabolite of paracetamol. Hepatotoxicity will occur if this metabolite exceeds the normal glutathione binding capacity.
Paracetamol may increase the risk of bleeding in patients taking warfarin and other antivitamin K. Patients taking paracetamol and antivitamin K should be monitored for appropriate coagulation and bleeding complications.
Paracetamol may considerably slow down the excretion of chloramphenicol, entailing the risk of increased toxicity. When used concurrently with zidovudine, an increased tendency for neutropenia may develop. Combination of Dolased and zidovudine should be avoided.
Concurrent intake of drugs, which delay gastric emptying, such as propantheline, may slow down the uptake of paracetamol, thereby retarding its onset of action. Conversely, drugs, which accelerate gastric emptying, such as metoclopramide or domperidone, may accelerate the absorption rate of paracetamol and its onset of action.
Chelating resin can decrease the intestinal absorption of paracetamol and potentially decrease its efficacy if taken simultaneously. In general, there must be an interval of more than 2 hours between taking the resin and taking paracetamol, if possible.
Co-administration of flucloxacillin with paracetamol may lead to metabolic acidosis, particularly in patients presenting risk factors of glutathione depletion, such as sepsis, malnutrition or chronic alcoholism.

CYP2D6 inhibitors.

Codeine is metabolized by the liver enzyme CYP2D6 to its active metabolite morphine. Medicines that inhibit CYP2D6 activity may reduce the analgesic effect of codeine. Patients taking codeine and moderate to strong CYP2D6 inhibitors (such as fluoxetine, paroxetine, bupropion, cinacalcet, methadone) should be adequately monitored for reduced efficacy and withdrawal signs and symptoms. If necessary, an adjustment of the treatment should be considered.

CYP3A4 inducers.

Medicines that induce CYP3A4 activity may reduce the analgesic effect of codeine. Patients taking codeine and CYP3A4 inducers (such as rifampin) should be adequately monitored for reduced efficacy and withdrawal signs and symptoms. If necessary, an adjustment of the treatment should be considered.

4.6 Fertility, Pregnancy and Lactation

Effects on fertility.

No data is available.
(Category A)
There have been no observations of an increase in the frequency of malformations or other direct or indirect harmful effects on the foetus in pregnant women and women of child-bearing age who have taken those drugs found in Dolased. Codeine may cause respiratory depression and withdrawal syndrome in neonates born to mothers who use codeine during the third trimester of pregnancy. As a precautionary measure, use of Dolased should be avoided during the third trimester of pregnancy and during labour. Dolased should only be used during pregnancy under medical supervision if the potential benefit justifies the potential risk to the foetus. If administered during pregnancy, morphinomimetic properties of codeine should be taken into account.
 Paracetamol and codeine are excreted in breast milk. Very little data are available regarding the appearance of doxylamine succinate in breast milk and its effect on the infant.
Dolased is contraindicated during breastfeeding (also see Section 4.4 Special Warnings and Precautions for Use, CYP2D6 metabolism) due to risk of respiratory depression in the infant.
Analgesic doses excreted in breast milk are generally low. However, infants of breastfeeding mothers taking codeine may have an increased risk of morphine overdose if the mother is an ultrarapid metaboliser of codeine. Codeine is excreted into human breast milk. Codeine is partially metabolised by cytochrome P4502D6 (CYP2D6) into morphine, which is excreted into breast milk. If nursing mothers are CYP2D6 ultra-rapid metabolisers, higher levels of morphine may be present in their breast milk. This may result in symptoms of opioid toxicity in both mother and the breastfed infant. Life-threatening adverse events or neonatal death may occur even at therapeutic doses (also see Section 4.4 Special Warnings and Precautions for Use, CYP2D6 metabolism).
Therefore, Dolased is contraindicated for use during breastfeeding. However, in circumstances where a breastfeeding mother requires codeine therapy, breastfeeding should be suspended and alternative arrangements should be made for feeding the infant for any period during codeine treatment. Breastfeeding mothers should be told how to recognise signs of high morphine levels in themselves and their babies. For example, in a mother, symptoms include extreme sleepiness and trouble caring for the baby. In the baby, symptoms include signs of increased sleepiness (more than usual), difficulty breastfeeding, breathing difficulties, or limpness. Medical advice should be sought immediately.

4.7 Effects on Ability to Drive and Use Machines

Both doxylamine succinate and codeine may cause drowsiness in some patients, therefore patients should be cautioned about operating vehicles or machinery or engaging in activities which require them to be fully alert. Patients should be cautioned to abstain from alcohol.

4.8 Adverse Effects (Undesirable Effects)

Side-effects with Dolased are infrequent. However, among those reported are: anorexia, drowsiness, depression, dizziness, sweating, anaphylactic shock, angioneurotic oedema, angioedema, difficulty in breathing, drop in blood pressure, gastrointestinal discomfort such as nausea and diarrhoea, dry mouth and, on rare occasions, erythema, urticaria, and rash.
Paracetamol may occasionally cause skin reactions and isolated cases of agranulocytosis and thrombocytopenic purpura have been reported. Changes in blood picture (rarely thrombocytopenia, neutropenia, leukopenia, and, in isolated cases, pancytopenia) may occur.
Bronchospasm may be triggered in patients having a tendency of analgesic asthma.
Toxic epidermal necrolysis (TEN), Stevens-Johnson syndrome (SJS), acute generalised exanthematous pustulosis, fixed drug eruption and cytolytic hepatitis, which may lead to acute hepatic failure, have also been reported.
Doxylamine succinate may cause drowsiness in some individuals, as well as paradoxical stimulation, psychomotor impairment, blurred vision, thickened respiratory secretions, gastrointestinal disorders and urinary retention. Constipation and pancreatitis may occur in association with codeine.
Haemolytic anaemia, particularly in patients with underlying glucose-6-phosphate-dehydrogenase deficiency has been reported. Kounis syndrome and bronchospasm have also been reported, as has pyroglutamic acidosis in patients with pre-disposing factors for glutathione depletion.
Adverse effects reported relating specifically to the codeine component are: hypersensitivity, confusional state, dysphoria, euphoria, seizure, headache, somnolence, dizziness, hypotension sedation, miosis, tinnitus, respiratory depression, constipation, vomiting, nausea, dry mouth, pruritus, urinary retention, and fatigue. Long term use also entails the risk of drug dependence. Visuomotor coordination and visual acuity may be adversely affected in a dose-dependent manner at higher doses or in particularly sensitive 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.

4.9 Overdose

Elderly persons, small children, patients with liver disorders, chronic alcohol consumption or chronic malnutrition, as well as patients concomitantly treated with enzyme-inducing drugs are at an increased risk of intoxication, including fatal outcome.
It has been reported that paracetamol may produce symptoms of acute toxicity in adults, following the ingestion of more than 15 g. Hepatotoxicity may develop after the ingestion of a single dose of 10 to 15 g (200 to 250 mg/kg) and a dose of more than 25 g is potentially fatal. 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. Patients may be asymptomatic for several days following ingestion of large doses of paracetamol and laboratory evidence of hepatotoxicity may be delayed for up to one week. Non-fatal hepatic damage is usually reversible. The antidote, N-acetylcysteine, should be administered as early as possible.
Despite lack of significant early symptoms, patients should be referred to hospital urgently for immediate medical attention.
Determinations of the plasma concentration of paracetamol are recommended.
Plasma concentration of paracetamol should be measured at 4 hours or later after ingestion (earlier concentrations are unreliable).
Where paracetamol intoxication is suspected, intravenous administration of SH group donators such as acetylcysteine within the first 10 hours after ingestion is indicated. Although acetylcysteine is most effective if initiated within this period, it can still offer some degree of protection if given as late as 48 hours after ingestion; in this case it is taken for longer.
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 microgram/mL in eight adults whose deaths were attributed primarily 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.

Relating to codeine component.

In general, treatment 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 the opioid antagonist naloxone hydrochloride is an antidote to respiratory depression; naloxone 400 microgram may be administered SC, IM or IV. Reactions associated with doxylamine overdosage may vary from CNS depression to stimulation. Stimulation is particularly likely in children; insomnia, nervousness, euphoria, irritability, tremors, nightmares, hallucinations and convulsions can occur. Atropine-like signs and symptoms such as dry mouth, fixed, dilated pupils, flushing and gastrointestinal symptoms may also occur.
Further measures will depend on the severity, nature and course of clinical symptoms of intoxication and should follow standard intensive care protocols.
For information on the management of overdose, contact the Poisons Information Centre on 13 11 26 (Australia).

5 Pharmacological Properties

5.1 Pharmacodynamic Properties

Mechanism of action.

Paracetamol is an effective analgesic and antipyretic. It produces analgesia through the central rather than a peripheral effect on the nervous system. Paracetamol does not have anti-inflammatory properties and it is often used by patients in whom salicylates and other non-steroidal anti-inflammatory medicines are contraindicated (e.g. gastrointestinal ulcer, dyspepsia, asthma).
Codeine analgesic effect may be due to its conversion to morphine. It binds to receptors in the central nervous system and alters processes affecting perception to pain and the emotional response of pain. Codeine has about one-sixth the analgesic activity of morphine.
Doxylamine succinate, an ethanolamine derivative, is an antihistamine with antimuscarinic and sedative effects.
The combination of paracetamol, codeine and doxylamine can be shown to give an enhanced analgesic effect.

Clinical trials.

No data is available.

5.2 Pharmacokinetic Properties

Absorption.

After oral administration, paracetamol is absorbed rapidly and completely from the small intestine; peak plasma levels occur 10 to 60 minutes after administration.
Paracetamol is uniformly distributed throughout most body fluids; the apparent volume of distribution is 1 to 1.2 L/kg. Paracetamol can cross the placenta and is excreted in milk. Plasma protein binding is negligible at usual therapeutic concentrations but increases with increased concentrations.
Codeine is well absorbed from the gastrointestinal tract and does not interfere with the paracetamol absorption.
Doxylamine is also well absorbed from the gastrointestinal tract. Following oral administration peak plasma levels occur after 2-3 hours.

Metabolism.

Paracetamol is metabolised by the hepatic microsomal enzyme system. In adults, at therapeutic doses, paracetamol is mainly conjugated with glucuronide (45 to 55%) or sulfate (20 to 30%). A minor proportion (less than 20%) is metabolised to catechol derivatives and mercapturic acid compounds via oxidation. Paracetamol is metabolised differently by infants and children compared to adults, the sulfate conjugate being predominant. Paracetamol is excreted in the urine mainly as the glucuronide and sulfate conjugates. Less than 5% is excreted as unchanged paracetamol with 85 to 90% of the administered dose eliminated in the urine within 24 hours of ingestion. The elimination half-life varies from 1 to 3 hours. Food intake delays paracetamol absorption.
Codeine is metabolised by O- and N-demethylation in the liver to morphine and norcodeine and other metabolites including normorphine and hydrocodone. Morphine is the active metabolite of codeine.
Patients who metabolise drugs poorly via CYP2D6 are likely to obtain reduced benefit from codeine due to reduced formation of the active metabolite.
Doxylamine is metabolised by the liver and has a half-life of about 10 hours.

Excretion.

Codeine and its metabolites are excreted almost entirely by the kidney, mainly as conjugates with glucuronic acid. Excretion is almost complete within 24 hours. The plasma half life is between 3 to 4 hours.

5.3 Preclinical Safety Data

Genotoxicity.

No data is available.

Carcinogenicity.

No data is available.

6 Pharmaceutical Particulars

6.1 List of Excipients

Each tablet contains the following inactive ingredients: Compap L, crospovidone, povidone, stearic acid, magnesium stearate self-emulsifying glyceryl monostearate, and lactose monohydrate.

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. Protect from moisture.

6.5 Nature and Contents of Container

Blister packs of 20's and 40's*.
(* Not all pack sizes are 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.


Paracetamol.

Chemical Name: N-(4-hydroxyphenyl)acetamide.
Molecular formula C8H9NO2;
Molecular Weight 151.20.
Characteristics: white odourless crystalline powder.

Codeine phosphate hemihydrate.

Chemical Name: (5R,6S)-7,8-didehydro-4,5α-epoxy-3-methoxy-17-methylmorphinan-6α-ol phosphate hemihydrate.
Molecular formula C18H21NO3.H3PO4.½H2O;
Molecular Weight 406.4.
Characteristics: white crystalline powder or small, colourless crystals.

Doxylamine succinate.

Chemical Name: NN-dimethyl-2-[α-methyl- α-(2-piridyl)benzyloxy]ethylamine hydrogen succinate.
Molecular formula C17H22N2O.C4H6O4;
Molecular Weight 388.5.
Characteristics: white to creamy white crystalline powder with a characteristic odour.

CAS number.

Paracetamol: 103-90-2.
Codeine phosphate hemihydrate: 41444-62-6.
Doxylamine succinate: 562-10-7.

7 Medicine Schedule (Poisons Standard)

Prescription Only Medicine (Schedule 4).

Summary Table of Changes