Consumer medicine information

Dolased Forte

Paracetamol; Codeine phosphate hemihydrate; Doxylamine succinate

BRAND INFORMATION

Brand name

Dolased Forte

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 Forte.

SUMMARY CMI

Dolased Forte

Consumer Medicine Information (CMI) summary

The full CMI on the next page has more details. If you are worried about using this medicine, speak to your doctor or pharmacist.

WARNING: Important safety information is provided in a boxed warning in the full CMI. Read before using this medicine.

1. Why am I using Dolased Forte?

Dolased Forte contains the active ingredients paracetamol, codeine phosphate hemihydrate and doxylamine succinate. Dolased Forte is for the short-term management of severe pain where your doctor decides other treatment options are ineffective, are not recommended, not tolerated, or otherwise inappropriate to manage your pain.

For more information, see Section 1. Why am I using Dolased Forte? in the full CMI.

2. What should I know before I use Dolased Forte?

Do not use if you have ever had an allergic reaction to Dolased Forte or any of the ingredients listed at the end of the CMI.

Talk to your doctor if you have any other medical conditions, take any other medicines, or are pregnant or plan to become pregnant or are breastfeeding.

For more information, see Section 2. What should I know before I use Dolased Forte? in the full CMI.

3. What if I am taking other medicines?

Some medicines may interfere with Dolased Forte and affect how it works.

A list of these medicines is in Section 3. What if I am taking other medicines? in the full CMI.

4. How do I use Dolased Forte?

The usual dose for adults and children between 12 and 18 years is one or two tablets every 4-6 hours as needed for relief.

More instructions can be found in Section 4. How do I use Dolased Forte? in the full CMI.

5. What should I know while using Dolased Forte?

Things you should do
  • Remind any doctor, surgeon, dentist or pharmacist you visit that you are using Dolased Forte.
  • Keep all your appointments, including those for blood tests.
  • Call your doctor straight away if you feel you need to change the dose, take it for longer period of time, or you feel very unwell when you are not taking it and feel better when you are taking it again.
Things you should not do
  • Do not take more than 8 tablets in a 24-hour period.
  • Do not stop taking Dolased Forte or change the dose without checking with your doctor, or use it to treat any other complaints unless your doctor or pharmacist tells you to.
  • Do not give Dolased Forte to anyone else, even if they have the same condition as you.
  • Do not take high doses of Dolased Forte for long periods of time unless your doctor tells you to.
Driving or using machines
  • Do not drive a car, operate machinery, or do anything else that could be dangerous while taking Dolased Forte.
Drinking alcohol
  • Do not drink alcohol while using Dolased Forte.
Looking after your medicine
  • Store in a cool and dry place below 25°C.
  • Protect from light.

For more information, see Section 5. What should I know while using Dolased Forte? in the full CMI.

6. Are there any side effects?

Common side effects include skin rash, constipation, nausea, vomiting, dizziness, drowsiness, sweating, blurred vision. Serious side effects include, wheezing, difficulty breathing or shallow breathing, swelling of the face, lips, tongue or other parts of the body, rash, itching or hives.

For more information, including what to do if you have any side effects, see Section 6. Are there any side effects? in the full CMI.

WARNING:

Limitations of use

Dolased Forte should only be used when your doctor decides that other treatment options are ineffective, not tolerated or otherwise inadequate to provide appropriate management your pain.

Hazardous and harmful use

Dolased Forte contains codeine which may be habit forming. Misuse, abuse, or addiction may lead to overdose and death. Your doctor will assess your risks and monitor your treatment regularly.

Life threatening respiratory depression

Serious, life-threatening or fatal respiratory depression (shallow or difficulty breathing) may occur with the use of Dolased Forte. Your doctor will assess your risks of respiratory depression and monitor your treatment regularly.

Concomitant use of benzodiazepines and other central nervous system (CNS) depressants, including alcohol

Using opioids while taking benzodiazepines (medicines used as sedatives or to treat anxiety), gabapentinoids (medicines used for epilepsy or neuropathic pain), antihistamines, antidepressants, antipsychotics, gabapentinoids (e.g. gabapentin and pregabalin), cannabis or other central nervous system (CNS) depressants, including alcohol, may result in extreme drowsiness and sleepiness, respiratory depression (shallow or difficulty breathing), coma, and death. Your doctor will limit your dosage and duration of use and monitor you regularly. Do not drink alcohol while taking Dolased Forte.



FULL CMI

Dolased Forte

Active ingredients: paracetamol, codeine phosphate and doxylamine succinate

Consumer Medicine Information (CMI)

This leaflet provides important information about using Dolased Forte. You should also speak to your doctor or pharmacist if you would like further information or if you have any concerns or questions about using Dolased Forte.

Where to find information in this leaflet:

1. Why am I using Dolased Forte?
2. What should I know before I use Dolased Forte?
3. What if I am taking other medicines?
4. How do I use Dolased Forte?
5. What should I know while using Dolased Forte?
6. Are there any side effects?
7. Product details

1. Why am I using Dolased Forte?

Dolased Forte contains three active ingredients,

  • paracetamol,
  • codeine phosphate, and
  • doxylamine succinate.

Paracetamol is an analgesic (pain-relieving medicine) and antipyretic (lowers body temperature). Codeine phosphate hemihydrate is a potent analgesic that helps to relieve pain. The body must convert codeine into morphine before it can provide pain relief. Doxylamine succinate is an antihistamine which can help to relieve tension and nausea associated with pain. This may be especially useful in the treatment of tension headache, migraine and period pain.

Dolased Forte is used for the short-term management of severe pain for which other treatment options have failed, are contraindicated, not tolerated or are otherwise inappropriate to provide sufficient management of pain. This may include toothache and other dental pain, pain from injury or surgery, or headache pain.

It is suitable for people who cannot take aspirin for pain relief.

2. What should I know before I use Dolased Forte?

Warnings

Do not use Dolased Forte if:

  • you are allergic to paracetamol, codeine phosphate, doxylamine succinate, or any of the ingredients listed at the end of this leaflet.

Always check the ingredients to make sure you can use this medicine.

  • you have or have had any of the following medical conditions:
    - severe and/or acute respiratory diseases, such as bronchitis, acute asthma, emphysema, acute chronic obstructive pulmonary disease (COPD).
    - other problems with breathing such as, shallow breathing, difficulty breathing, or slow breathing.
    - Glucose-6-phosphate-dehydrogenasedeficiency (an enzyme deficiency that may lead to anaemia)
    - you very rapidly metabolise codeine into morphine.
    - known intolerance to paracetamol.
    - severe liver disease or liver failure
  • you have diarrhoea caused by antibiotics or poisoning.
  • you are in the third trimester of pregnancy or in labour, especially if the baby is premature.
  • you are breastfeeding or planning to breastfeed.
  • you have a history of drug dependence, including alcohol dependence.
  • you are already taking Monoamine Oxidase Inhibitors (MAOIs) such as selegiline or moclobemide, or within 14 days of stopping MAOIs.
  • you have experienced allergy (generalised rash or shortness of breath) to morphine or oxycodone.
  • the person going to take the tablets is under 12 years.
  • you are aged between 12 and 18 years of age and have had your tonsils or adenoids removed to treat sleep apnoea.

Check with your doctor if you:

  • have allergies to
    - any other medicines
    - aspirin or any other non-steroidal anti-inflammatory drugs (NSAIDs)
    - any other substances, such as foods, preservatives or dyes
  • have or have had any medical conditions, especially the following:
    - liver problems
    - kidney problems
    - Gilbert's syndrome
    - heart problems
    - low blood pressure
    - lung problems, difficulty breathing, wheezing, chronic cough, asthma, or other chronic breathing conditions
    - intolerance to pain relieving medicine
    - chronic alcohol use, or if you recently stopped taking alcohol
    - opioid dependence
    - a history of drug and/or alcohol abuse.
    Caution is particularly recommended for use in adolescents and young adults with a history of drug and/or alcohol abuse.
    - low levels of glutathione
    - recent stomach, intestine or urinary tract surgery
    - gall bladder problems or your gall bladder has been removed
    - obstructive and inflammatory bowel disease or other bowel problems
    - chronic constipation
    - multiple sclerosis
    - prostate problems
    - retaining urine
    - problems passing urine
    - underactive thyroid
    - adrenal gland problems such as Addison's disease
    - head injury
    - brain tumour, stroke or other problems with the brain
    - fits or seizures
  • take any medicines for any other condition

During treatment, you may be at risk of developing certain side effects. It is important you understand these risks and how to monitor for them. See additional information under Section 6. Are there any side effects?

Pregnancy and breastfeeding

Check with your doctor if you are pregnant or intend to become pregnant.

Do not take Dolased Forte during the third trimester of pregnancy.

Do not take Dolased Forte during labour, especially if the baby is premature.

Talk to your doctor if you are breastfeeding or intend to breastfeed.

Do not take Dolased Forte if you are breastfeeding or planning to breastfeed.

Use in Children

Do not give Dolased Forte to children under 12 years.

Use in the Elderly

If you are over 65 years of age, talk to your doctor or pharmacist about how much to take.

Elderly patients are more likely to have less effective kidney function due to age. This may increase the risk of side effects.

Addiction

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

Dependence

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

Tolerance

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

Withdrawal

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

3. What if I am taking other medicines?

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

Tell your doctor or pharmacist if you are taking any other medicines, which contain paracetamol, codeine or doxylamine.

Do not take Dolased Forte with Monoamine Oxidase inhibitors (MAOIs), such as selegiline or moclobemide, or within 14 days of stopping MAOIs.

Some medicines may interfere with Dolased Forte including:

  • medicines causing sleepiness or drowsiness, such as sedatives or tranquilisers
  • Benzodiazepines (medicines used as sedatives or to treat anxiety). The use of opioids and benzodiazepines together may increase the risk of drowsiness, difficulties in breathing, coma and may be life-threatening.
  • medicines containing alcohol (ethanol), such as some cough syrups
  • cough suppressants or antitussives
  • medicines used to treat alcohol and/or opioid dependence, such as naltrexone or buprenorphine
  • medicines used to treat depression
  • phenothiazines and antipsychotic agents (medicines used to treat mental disorders)
  • some types of antihistamines
  • aspirin or any other NSAIDs
  • Gabapentinoids (medicines used for epilepsy or neuropathic pain)
  • cannabis
  • medicines used to stop or prevent vomiting (antiemetics), such as metoclopramide or domperidone
  • medicines used to treat diarrhoea, such as kaolin or loperamide
  • medicines used to thin the blood, such as warfarin
  • propantheline (medicine used to treat stomach ulcers)
  • medicines used to treat epilepsy or fits, such as phenytoin
  • other pain relief medication
  • medicines used to treat high blood pressure
  • colestyramine (medicine used to treat bile problems or lower cholesterol)
  • chelating resin
  • chloramphenicol, an antibiotic used to treat ear and eye infections
  • neuromuscular blocking agents such as cisatracurium (medicines used during surgical procedures)
  • flucloxacillin, zidovudine or rifampicin (medicines used to treat infections)

Medicines that may reduce the effect of Dolased Forte include:

  • medicines that inhibit the liver enzyme, CYP 2D6 inhibitors such as fluoxetine, paroxetine, bupropion, cinacalcet, and methadone
  • medicines that increase the activity of the liver enzyme, CYP 3A4 inducers such as rifampicin.

Check with your doctor or pharmacist if you are not sure about what medicines, vitamins or supplements you are taking and if these affect Dolased Forte.

4. How do I use Dolased Forte?

How much to take

  • Adult and children between 12 and 18 years
  • The usual adult dose is one or two tablets every 4 to 6 hours as needed for relief.
  • Do not exceed 8 tablets in a 24 hour period.
  • Dolased Forte must not be used in children under 12 years.
  • Follow the instructions provided and use Dolased Forte until your doctor tells you to stop. Their directions may differ from the information contained in this leaflet.

How to take Dolased Forte

  • Swallow the prescribed dose of Dolased Forte whole with a glass of water. It can be taken with or without food.

If you forget to take Dolased Forte

If you miss your dose at the usual time, take it as soon as you remember. If it is almost time for your next dose, skip the dose you missed and take your next dose when you are meant to.

Remember to wait 4 to 6 hours between doses.

Do not take a double dose to make up for the dose you missed.

If you take too much Dolased Forte

If you think that you have used too much Dolased Forte, you may need urgent medical attention.

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.

5. What should I know while using Dolased Forte?

Things you should do

  • Remind any doctor including surgeons, dentist or pharmacist you visit that you are taking Dolased Forte.
  • Keep all your appointments, including those for blood tests.

Call your doctor straight away if you:

  • feel you need to take the medicine for longer periods of time
  • feel you need to take more than the prescribed dose
  • feel very unwell when you stop taking the medicine but feel better when you start taking the medicine again.

Things you should not do

  • Do not stop using this medicine suddenly, or change the dose, without checking with your doctor.
  • Do not take high doses of the medicine for long periods of time unless your doctor tells you to.
  • Do not take Dolased Forte to treat any other conditions unless your doctor tells you to.
  • Do not give your medicine to anyone else, even if they have the same condition as you.

Driving or using machines

Be careful before you drive or use any machines or tools until you know how Dolased Forte affects you.

Dolased Forte may cause dizziness, drowsiness, affect eyesight, or hand-eye coordination in some people. Do not drive a car, operate machinery, or do anything else that could be dangerous while taking Dolased Forte.

Drinking alcohol

Tell your doctor if you drink alcohol.

Alcohol and codeine taken together may increase the risk of sedation, respiratory problems, coma or may be life-threatening.

Do not drink alcohol while you are taking Dolased Forte.

Looking after your medicine

Follow the instructions in the carton on how to take care of your medicine properly.

Keep your tablets in the pack until it is time to take them.

Store it in a cool dry dark place where the temperature stays below 25°C, away from moisture, heat or sunlight; do not store it:

  • in the bathroom or near a sink, or
  • in the car or on window sills.

Keep it where young children cannot reach it.

Getting rid of any unwanted medicine

If you no longer need to use this medicine or it is out of date, take it to any pharmacy for safe disposal.

Do not use this medicine after the expiry date.

6. Are there any side effects?

All medicines can have side effects. If you do experience any side effects, most of them are minor and temporary. However, some side effects may need medical attention.

Do not be alarmed by this list of possible side effects. You may not experience any of them. See the information below and, if you need to, ask your doctor or pharmacist if you have any further questions about side effects.

Less serious side effects

Less serious side effectsWhat to do
Skin related:
  • skin rash
  • sweating
Gastrointestinal related:
  • constipation
  • nausea
  • vomiting
General:
  • blurred vision
  • drowsiness
Head and neurology related:
  • increased sensitivity to pain or increased levels of pain
Speak to your doctor if you have any of these less serious side effects and they worry you.

Serious side effects

Serious side effectsWhat to do
Heart related:
  • irregular heartbeat
Head and neurology related:
  • unusual or extreme mood swings
  • headache
  • dizziness, light-headedness
Liver related:
  • Hepatitis (symptoms include loss of appetite, itching, yellowing of the skin and eyes, light coloured bowel motions, dark coloured urine)
General:
  • flushing of the face
  • shortness of breath
  • slow or shallow breathing
  • mouth ulcer, fever and sore throat
  • stomach pain
  • painful red areas with blisters and peeling layers of skin which may be accompanied by fever and/or chills
Bleeding related:
  • bleeding, bruising more easily
  • severe blisters and bleeding in the lips, eyes, mouths, nose and genitals
Metabolism related:
  • rapid breathing rapid heart rate and changes in consciousness caused by pyroglutamic acidosis (an accumulation of pyroglutamic acid due to low levels of a protein called glutathione).
Allergic reactions:
  • swelling of the face, lips, tongue or other parts of the body
  • wheezing, difficulty breathing or shallow breathing
  • rash, itching or hives on the skin.
Call your doctor straight away, or go straight to the Emergency Department at your nearest hospital if you notice any of these very serious side effects.

Tell your doctor or pharmacist if you notice anything else that may be making you feel unwell.

Other side effects not listed here may occur in some people.

Reporting side effects

After you have received medical advice for any side effects you experience, you can report side effects to the Therapeutic Goods Administration online at www.tga.gov.au/reporting-problems. By reporting side effects, you can help provide more information on the safety of this medicine.

Always make sure you speak to your doctor or pharmacist before you decide to stop taking any of your medicines.

7. Product details

This medicine is only available with a doctor's prescription.

What Dolased Forte contains

Active ingredient
(main ingredient)		paracetamol 450 mg
codeine phosphate 30 mg
doxylamine succinate 5 mg
Other ingredients
(inactive ingredients)		crospovidone
glyceryl monostearate
lactose monohydrate
magnesium stearate
pregelatinised maize starch
povidone
stearic acid

Dolased Forte does not contain tartrazine or any other azo dyes.

Do not take this medicine if you are allergic to any of these ingredients.

What Dolased Forte looks like

Dolased Forte is a round, white tablet with “T” on one side of a break line. Dolased Forte is available in a blister pack of 2, 20 or 40 tablets (AUST R 203987).

Not all pack sizes may be marketed.

Who distributes Dolased Forte

Aspen Pharmacare Australia Pty Ltd
34-36 Chandos St
St Leonards NSW 2065
Australia
www.aspenpharma.com.au

This leaflet was prepared in June 2023.

Published by MIMS August 2023

BRAND INFORMATION

Brand name

Dolased Forte

Active ingredient

Paracetamol; Codeine phosphate hemihydrate; Doxylamine succinate

Schedule

S4

 

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

4.1 Therapeutic Indications

Dolased Forte is indicated for the short-term management of severe pain for which other treatment options have failed, are contraindicated, not tolerated or are otherwise inappropriate to provide sufficient management of pain.

4.2 Dose and Method of Administration

Adults and children 12 years of age and older.

One or two tablets every 4 to 6 hours as needed for relief. Do not exceed 8 tablets in a 24 hour period.
Dolased Forte is contraindicated for use in patients who are:
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. (Also see Section 4.3 Contraindications; Section 4.4 Special Warnings and Precautions for Use, Paediatric use, CYP2D6 metabolism.)
Dolased Forte is suitable for individuals who cannot tolerate aspirin.

4.3 Contraindications

Dolased Forte should not be given to patients with a known hypersensitivity to paracetamol, codeine, doxylamine succinate or any of the excipients listed under Section 6.1 List of Excipients.
It must not be used in patients with known glucose-6-phosphate-dehydrogenase deficiency, severe respiratory disease, acute respiratory disease and respiratory depression/insufficiency, for example acute asthma, acute exacerbations of chronic obstructive pulmonary disease since codeine may exacerbate the condition.
Concomitant treatment with monoamine inhibitors (MAOIs) or treatment within 14 days of stopping MAOIs is contraindicated.
Paracetamol should not be used in patients with a history of intolerance to the drug.
Paracetamol should not be used in patients with severe hepatocellular insufficiency.
Due to codeine's structural similarity to morphine and oxycodone, patients experiencing systemic allergy (generalised rash, shortness of breath) to these drugs should not receive codeine.
Codeine is contraindicated in patients with diarrhoea caused by poisoning, until the toxic substance has been eliminated from the gastrointestinal tract, or diarrhoea associated with pseudomembranous colitis caused by antibiotic administration since codeine may slow the elimination of the toxic material or antibiotic.
Codeine is contraindicated in the event of impending childbirth or in case of risk of premature birth (see Section 4.6 Fertility, Pregnancy and Lactation, Use in pregnancy).
Dolased Forte is contraindicated during breast-feeding (see Section 4.6 Fertility, Pregnancy and Lactation, Use in lactation).
Paracetamol should not be used in patients with active alcoholism as chronic excessive alcohol ingestion predisposes patients to paracetamol hepatotoxicity.
Dolased Forte 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, 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).

4.4 Special Warnings and Precautions for Use

To avoid the risk of overdose, check that paracetamol is absent from the composition of other medicinal products taken concomitantly.
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 with caution in patients with.

Chronic alcohol use including recent cessation of alcohol intake; low glutathione reserves; Gilbert's syndrome.
Codeine should be used with caution in patients with CNS depression or decreased respiratory reserve e.g. in emphysema, kyphoscoliosis, hypoxia, hypercapnia or even severe obesity or cor pulmonale, or chronic obstructive pulmonary disease. Codeine should be administered with caution in patients with hypothyroidism, adrenocortical insufficiency (e.g. Addisons's disease), shock, myxoedema, acute alcohol intoxication or delirium tremens since codeine may exacerbate the symptoms or increase the risk of respiratory and/or CNS depression.
Codeine should be administered with caution in patients with impaired cardiac, hepatic or renal function, hypotension, hyperthyroidism, benign prostatic hyperplasia, urethral stenosis, chronic colitis ulcerative, gall bladder conditions, multiple sclerosis, hypothyroidism, adrenocortical insufficiency (e.g. Addison's disease), shock, myxedema, acute alcohol intoxication or delirium tremens since codeine may exacerbate the symptoms or increase the risk of respiratory and/or CNS depression.
Codeine should be administered with great caution in patients with head injury, brain tumour or increased intracranial pressure since codeine may increase the risk of respiratory depression and further elevate intracranial pressure. In addition codeine can produce side effects such as confusion, miosis, vomiting.
These are important signs in following the clinical course of patients with head injuries.
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 with careful risk-benefit assessment and great caution 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.
Paracetamol should not be used in patients with active alcoholism as chronic excessive alcohol ingestion predisposes patients to paracetamol hepatotoxicity.
Codeine should be administered with caution in patients with acute abdominal conditions since codeine may obscure the diagnosis or the course of the disease.
Codeine should be administered with caution in patients with severe inflammatory bowel disease (risk of toxic megacolon may be increased, especially with repeated dosing). Dolased Forte should also be used with caution in patients who have had recent gastrointestinal tract surgery.
Codeine should be administered with caution in patients with a history of convulsive disorders (convulsions may be induced or exacerbated by codeine).
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 administered with caution in patients with a history of convulsive disorders (convulsions may be induced or exacerbated by codeine).
Codeine should be administered with caution in patients with prostatic hypertrophy, urethral structure or recent urinary tract surgery since codeine may cause urinary retention.
Codeine should be used with caution in elderly or debilitated patients because of the danger of respiratory or cardiac depression.
Patients with known analgesic intolerance or known bronchial asthma must only use Dolased Forte after having consulted a physician (hypersensitivity reactions including bronchospasm are possible).

Hazardous and harmful use.

Dolased Forte contains the opioid codeine and is a potential drug of abuse, misuse and addiction. Addiction can occur in patients appropriately prescribed Dolased Forte 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 Forte.
There have been reports of drug abuse with codeine, including cases in children and adolescents. Caution is particularly recommended for use in children, adolescents, young adults and in patients with a history of drug and/or alcohol abuse (see Section 4.4 Special Warnings and Precautions for Use, Paediatric use).
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 Forte 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 Forte 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, 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 Forte 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 Forte 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 Forte.

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 Forte 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 Forte, 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 Forte (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.
Doxylamine succinate must be administered with caution in patients with:
bladder neck obstruction, symptomatic prostatic hypertrophy or urinary retention;
susceptibility to angle closure glaucoma;
gastrointestinal disease, such as pyloroduodenal obstruction or stenosing peptic ulcer;
benign prostatic hyperplasia.
Doxylamine shares the toxic potentials of other antihistamines, and the usual precautions of antihistamine therapy should be observed.
This medication may be dangerous when used in large amounts or for long periods.
See Section 4.5 Interactions with Other Medicines and Other Forms of Interactions for additional information.

CYP2D6 metabolism.

Dolased Forte 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; Section 4.6, Use in lactation.)

Use in hepatic impairment.

Dolased Forte should be administered with caution to patients with hepatic dysfunction as it contains paracetamol and codeine.
Paracetamol should be used with caution in patients: with impaired hepatic function.
Dolased Forte should be also be administered with caution to patients with viral hepatitis, and patients taking other drugs which affect the liver. Hepatotoxicity may occur with paracetamol even at therapeutic doses, after short treatment duration and in patients without pre-existing liver dysfunction. In view of the increased risk of hepatotoxicity, the benefit should be weighed against the risk when administering Dolased Forte to patients with viral hepatitis or pre-existing hepatic disease. In such patients, hepatic function determinations may be required at periodic intervals during high dose or long-term therapy.
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. 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. There have been reports of kidney damage, disturbances in clotting mechanisms, metabolic acidosis, hypoglycaemia, agranulocytosis, thrombocytopaenia, methaemoglobinaemia and myocardial necrosis.

Use in renal impairment.

Dolased Forte should be administered with caution to patients with renal dysfunction as it contains paracetamol and codeine.

Use in the elderly.

Elderly people may be more sensitive to the effects of this medicinal product. 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. Dose reduction may be required.
Codeine should be used with caution in elderly or debilitated patients because of the danger of respiratory or cardiac depression.

Paediatric use.

Dolased Forte 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.

Plasma amylase and lipase activity.

Codeine may cause increased biliary tract pressure, thus increasing plasma amylase and/or lipase concentrations.

Gastric emptying studies.

Gastric emptying is delayed by codeine so gastric emptying studies will not be valid.

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

Salicylates and NSAIDs.

Prolonged concurrent use of paracetamol and salicylates or nonsteroidal anti-inflammatory drugs may increase the risk of adverse renal effects.

Coumarins.

Repeated high doses of paracetamol increase the risk of bleeding in patients taking warfarin and other coumarin derivatives (antivitamin K). Monitoring of coagulation and bleeding complications is required.

Chloramphenicol.

Paracetamol may slow down the excretion of chloramphenicol, entailing the risk of increased toxicity.

Diflunisal.

Diflunisal may increase the plasma concentrations of paracetamol by 50%.

Anticholinergics.

Concomitant use of codeine and anticholinergic agents may increase the risk of severe constipation and/or urinary retention. Drugs, which decrease gastric emptying, may decrease the absorption of paracetamol.

Cholestyramine.

Cholestyramine reduces the absorption of paracetamol if given within one hour of paracetamol administration.

Chelating resin.

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.

Propantheline.

Decreases gastric emptying which may decrease the absorption of paracetamol.

Rifampicin.

Concomitant use may increase the likelihood of paracetamol toxicity (see Hepatotoxic drugs and liver microsomal enzyme inducers below).

Flucloxacillin.

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.

Alcohol.

Codeine may potentiate the effects of alcohol and increase the likelihood of paracetamol toxicity (see Hepatotoxic drugs and liver microsomal enzyme inducers below).
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).

Metoclopramide.

Codeine may antagonise the effects of metoclopramide on gastrointestinal motility. Paracetamol absorption is increased by drugs which increase gastric emptying.

Domperidone.

The absorption rate of paracetamol may be increased by domperidone.

Codeine and opioid analgesics.

Concurrent use of codeine and other opioid agonists is usually inappropriate as additive CNS depression, respiratory depressant and hypotensive effects may occur. Narcotic analgesics may decrease gastric emptying and therefore decrease the absorption of paracetamol.

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.

Hepatotoxic drugs and liver microsomal enzyme inducers.

The risk paracetamol toxicity may be increased in patients receiving other potentially hepatotoxic drugs or drugs that induce liver microsomal enzymes, such as antiepileptics (such as phenobarbital, phenytoin, carbamazepine, topiramate), alcohol, barbiturates and rifampicin. 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.

Zidovudine.

When used concurrently with zidovudine, an increased tendency for neutropenia may develop. Combination of Dolased Forte and zidovudine should be avoided.

Antiperistaltic antidiarrhoeals (including kaolin, pectin, loperamide).

Concurrent use of these agents with codeine may increase the risk of severe constipation and CNS depression.

Tranquillisers, sedatives, hypnotics, general anaesthetics and CNS depressants.

Codeine may potentiate the effects of these drugs. Concomitant use of tranquillisers or sedatives may enhance the potential respiratory depressant effects of codeine. (See Section 4.4 Special Warnings and Precautions for Use, Risks from concomitant use of benzodiazepines or other CNS depressants, including alcohol.)

Benzodiazepines.

The concomitant use of benzodiazepines and opioids increases the risk of sedation, respiratory depression, coma and death because of additive CNS depressant effect. Limit dosage and duration of concomitant use of benzodiazepines and opioids (see Section 4.4 Special Warnings and Precautions for Use).

Monoamine oxidase inhibitors.

Nonselective MAOIs intensify the effects of opioid drugs, which can cause anxiety, confusion and significant respiratory depression and can potentiate the central nervous effects and other side effects of unpredictable severity. Severe and sometimes fatal reactions have occurred in patients concurrently administered MAO inhibitors and pethidine. Codeine should not be given to patients taking nonselective MAOIs or within 14 days of stopping such treatment. As it is unknown whether there is an interaction between the selective MAOIs (reversible inhibitors of monoamine oxidase A) and codeine, caution is advised with this drug combination.

Tricyclic antidepressants.

A codeine-induced respiratory depression can be potentiated by tricyclic antidepressants (see Section 4.4 Special Warnings and Precautions for Use, Risks from concomitant use of benzodiazepines or other CNS depressants, including alcohol).

Antihypertensives.

Hypotensive effects of antihypertensive agents may be potentiated when used concurrently with codeine and lead to orthostatic hypotension.

Neuromuscular blocking agents.

Codeine may enhance the effects of neuromuscular blocking agents resulting in increased respiratory depression.
Patients receiving other narcotic analgesics, antitussives, antihypertensives, antihistamines, antipsychotics, antianxiety agents, gabapentinoids, cannabis, centrally-active anti-emetics or other CNS depressants (including alcohol) concomitantly with Dolased Forte may experience additive CNS depression (see Section 4.4 Special Warnings and Precautions for Use, Risks from concomitant use of benzodiazepines or other CNS depressants, including alcohol).

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 quinidine, 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.

Doxylamine and alcohol.

Doxylamine succinate may cause drowsiness in some patients, avoid alcohol.

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 childbearing age who have taken those drugs found in Dolased Forte.
However, prolonged high dose use of codeine prior to delivery may prolong codeine withdrawal symptoms in the neonate.
Regular use during pregnancy may cause physical dependence in the foetus, leading to withdrawal symptoms in the neonate. Administration of codeine during labour may cause respiratory depression in the newborn infant. 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 Forte should be avoided during the third trimester of pregnancy and during labour. Codeine is contraindicated in the event of impending childbirth or in case of risk of premature birth (see Section 4.3 Contraindications). Dolased Forte 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.
 Dolased Forte is contraindicated during breast-feeding (also see Section 4.4 Special Warnings and Precautions for Use, CYP2D6 metabolism) due to risk of respiratory depression in the infant.
Codeine, doxylamine and paracetamol are excreted in breast milk.
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 metabolized by cytochrome P450 2D6 (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 breast-fed 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 Forte 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.
Breast feeding 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

Dolased Forte may cause drowsiness, disturbances of visuomotor coordination and visual acuity and/or dizziness. Due to the preparation's sedative action, psychomotor impairment impacting the mental and/or physical abilities required for the performance of potentially hazardous activities may occur. Patients treated with this medicine should not drive or operate machinery, or drink alcohol whilst taking this medication.

4.8 Adverse Effects (Undesirable Effects)

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.
Reports of adverse reactions are rare. Although the following reactions have been reported when paracetamol and codeine have been administered:

Haematologic.

Less frequent to rare: agranulocytosis, anaemia, thrombocytopenia.

Genitourinary.

Less frequent to rare: renal failure, uraemia, urinary retention or hesitance.

Hypersensitive.

Less frequent to rare: skin rashes and other allergic reactions, histamine release (hypotension, flushing of the face, tachycardia, breathlessness).

Gastrointestinal.

Common: constipation, nausea, vomiting.

Neurological.

Common: drowsiness, dizziness.
Less frequent to rare: euphoria, dysphoria. At higher doses codeine may cause respiratory depression.

Hepatic.

Very rare: pancreatitis.

Metabolism and nutrition system disorders.

Not known: pyroglutamic acidosis, in patients with pre-disposing factors for glutathione depletion.
Paracetamol has also been associated with dyspepsia, sweating, erythema, urticaria, anaphylactic shock, angioneurotic oedema, angioedema, leukopenia, neutropenia and pancytopenia. Bronchospasms 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. Large doses may produce hepatotoxicity.
Haemolytic anaemia, particularly in patients with underlying glucose-6-phosphate-dehydrogenase deficiency has been reported. Kounis syndrome and bronchospasm have also been reported.
Codeine can cause confusional state, dysphoria, seizure, headache, somnolence, sedation, miosis, tinnitus, dry mouth, pruritus, fatigue, and hypotension. Visuomotor coordination and visual acuity may be adversely affected in a dose-dependent manner at higher doses or in particular sensitive patients. Long term use also entails the risk of drug dependence.
The following reactions have been reported when doxylamine succinate has been administered.

Mild to moderate poisoning.

Somnolence, anticholinergic effects (i.e. mydriasis, flushing, fever, dry mouth, and decreased bowel sounds), tachycardia, mild hypertension, and nausea and vomiting are common after overdose. Agitation, confusion, and hallucinations may develop with moderate poisoning.

Severe poisoning.

Severe effects may include agitated delirium, psychosis, seizures, coma, hypotension, QRS widening, and ventricular dysrhythmias, including torsade de pointes but are generally only reported in adults after very large, deliberate ingestions. Rhabdomyolysis and renal failure may rarely develop in patients with prolonged agitation, coma, or seizures.
Common: mild sedation, dizziness, impaired coordination, and mild anticholinergic effects. Paradoxical excitation can develop in some patients.
Prolonged administration of high doses of Dolased Forte may result in drug dependence.

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

5.1 Pharmacodynamic Properties

Mechanism of action.

Codeine is a potent analgesic. Paracetamol is an analgesic and antipyretic. Doxylamine succinate has calmative and antinauseant properties which can be useful in relieving tension and nausea associated with pain.

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 30 to 120 minutes after administration. Food intake delays paracetamol absorption. Codeine has about one-sixth of morphine's analgesic activity. It is well absorbed from the gastrointestinal tract and does not interfere with paracetamol absorption. Doxylamine succinate is readily absorbed from the gastrointestinal tract. Following oral administration of a single 25 mg dose of doxylamine succinate in healthy adults, mean peak plasma concentrations of about 100 nanogram/mL occur within 2-3 hours after administration.

Distribution.

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 increasing concentrations. Codeine is distributed into milk.

Metabolism.

Paracetamol is metabolised by the hepatic microsomal enzyme system. In adults at therapeutic doses, paracetamol is mainly conjugated with glucuronide (45-55%) or sulfate (20-30%). 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. Patients who metabolise drugs poorly via CYP2D6 are likely to obtain reduced benefit from codeine due to reduced formation of the active metabolite.
Codeine is metabolised in the liver to morphine and norcodeine.

Excretion.

Paracetamol is excreted in the urine mainly as the glucuronide and sulphate conjugates. Less than 5% is excreted as unchanged paracetamol with 85-90% of the administered dose eliminated in the urine within 24 hours of ingestion. The elimination half-life varies from 1 to 4 hours.
Codeine, morphine and norcodeine are excreted in the urine, partly as conjugates with glucuronic acid. Excretion is almost complete within 24 hours.
Doxylamine has an elimination half-life of about 10 hours in healthy adults. In humans 60-80% of doxylamine given has been recovered has been recovered in urine at 24 hours postdose.

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

6.1 List of Excipients

Other ingredients are pregelatinised maize starch, crospovidone, lactose, povidone, glyceryl monostearate, stearic acid and magnesium stearate.

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

Storage below 25°C, protect from light.

6.5 Nature and Contents of Container

Blister packed white tablets in cartons of 2, 20 and 40.

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

Paracetamol.

Chemical Name: N-(4-hydroxyphenyl)acetamide.

Chemical structure.


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.


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.


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