Consumer medicine information

Mydol 15

Paracetamol; Codeine phosphate hemihydrate

BRAND INFORMATION

Brand name

Mydol 15

Active ingredient

Paracetamol; Codeine phosphate hemihydrate

Schedule

S4

 

Consumer medicine information (CMI) leaflet

Please read this leaflet carefully before you start using Mydol 15.

What is in this CMI

This CMI answers some common questions about MYDOL 15. It does not contain all the available information. It does not take the place of talking to your doctor.

All medicines have risks and benefits. Your doctor has weighed the risks of you taking MYDOL 15 against the benefits this medicine is expected to have for you.

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

What are MYDOL 15 used for

This medicine may be addictive if taken for more than a few days at at a time.

MYDOL 15 are for the temporary relief of acute moderate pain.

MYDOL 15 contain paracetamol and codeine. Paracetamol and codeine work together to stop the pain messages from getting through to the brain.

Paracetamol also acts in the brain to reduce fever.

Your doctor may have given you this medicine for another use.

If you want more information, ask your doctor.

Before you take MYDOL 15

When you must not take it

You should not take MYDOL 15 if you are allergic to paracetamol or codeine or any of the ingredients listed under "Product Description". The symptoms of an allergic reaction may include a rash, asthma attack or hay fever.

Do not take this medicine if you have any of the following conditions:

  • acute breathing difficulties such as bronchitis, unstable asthma or emphysema
  • chronic constipation
  • diarrhoea caused by antibiotics or poisoning

Do not take this medicine if you regularly drink large quantities of alcohol.

Do not take codeine during labour, especially if the baby is premature. The medicine may produce withdrawal effects in the newborn baby.

Ask your doctor about taking MYDOL 15 if you are breastfeeding. A small amount of codeine passes into the breast milk. It may cause breathing problems in newborn infants.

Do not use MYDOL 15 if you are breastfeeding or planning on breastfeeding. A small amount of codeine passes into the breast milk. It may cause breathing problems in newborn infants.

MYDOL 15 may be used during pregnancy. However, ask your doctor about the risks and benefits of taking MYDOL 15 while you are pregnant.

Do not take MYDOL 15 during labour, especially if the baby is premature. The medicine may produce withdrawal effects in the newborn baby.

Do not use MYDOL15 if you are breast feeding or planning to breast feed. This medicine passes into breast milk and may affect the baby.

Do not use MYDOL 15 in children under 12 years.

Ask your doctor or pharmacist about taking MYDOL 15 if you are over 65 years of age and have kidney or respiratory problems.

Do not use it after the expiry date (EXP) printed on the pack. If you take it after the expiry date it may have no effect at all, or worse, have an entirely unexpected effect.

Do not use MYDOL 15 if the packaging is torn or shows signs of tampering.

Before you start to take it

Do not take MYDOL 15 with other medicines containing paracetamol or codeine, unless advised to do so by a doctor or pharmacist.

You must tell your doctor if:

  • You have allergies to any ingredients listed under "Product Description" at the end of this leaflet.
  • You have any of these conditions:
    - Lung, Liver or kidney problems
    - Difficulty breathing, wheezing, chronic cough, asthma or other chronic breathing conditions
    - You drink large quantities of alcohol.
    - You have a history of drug or alcohol abuse
    - Recent surgery on the stomach or intestines
    - Head injury
    - Enlarged prostate
    - Low blood pressure
    - Underactive thyroid

You should tell your pharmacist or doctor if you are using any other medicines including any of the following medicines:

  • Any medicines causing sleepiness
  • Tranquillisers (medicines for anxiety and nerves)
  • Medicines which thin the blood (e.g. warfarin)
  • Medicines to treat epilepsy.
  • Metoclopramide, a medicine used to control nausea and vomiting
  • Chloramphenicol, an antibiotic used to treat ear and eye infections.
  • Medicines used to relieve stomach cramps or spasms
  • Medicines used to prevent travel sickness
  • Medicines used to treat Parkinson's disease
  • Medicines used to treat high blood pressure
  • Medicines for diarrhoea such as kaolin, pectin and loperamide
  • Monoamine oxidase inhibitors, medicines used to treat depression, if taken within the last 14 days
  • Quinidine, a medicine used to treat abnormal or irregular heart beat
  • Phenothiazines and antipsychotic agents, medicines used to treat mental disorders
  • Other opioids, used to treat pain or suppress coughs
  • Alcohol
  • If you are an Ultra rapid metaboliser of CYP2D6
  • If you are aged below 18 years of age and have had your tonsils or adenoids removed to treat sleep apnoea.

These medicines may be affected by MYDOL 15 or affect how well MYDOL 15 work.

Your doctor or pharmacist can tell you what to do if you are taking any of these medicines.

You should also tell your pharmacist or doctor about any other medicines that you have bought without a prescription from either your pharmacy, supermarket or health food shop.

If you have not told your doctor about any of these things, tell him/her before you take any MYDOL 15

How to take MYDOL 15

The label on your pack of MYDOL 15 will tell you how to take your medicine and how often. If you are unsure about the directions ask your doctor or pharmacist.

How much to take

The usual doses of MYDOL 15 are:

Adults and children over 2 years: 2 tablets.

This dosage may be repeated in 4-6 hours if necessary. You should not take more than 8 tablets in a 24 hour period.

MYDOL 15 are not recommended for children under 12 years.

How long to take it

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

Children aged over 12 years: Do not take this medicine for longer than 48 hours at a time, unless advised to by a doctor.

Keep the recommended dose. If MYDOL 15 are not adequately controlling your pain, do not increase the dose. Please see your doctor.

How to take it

Swallow tablets whole with a little water or other liquid.

The directions given to you by your pharmacist or doctor may be different from the information in this leaflet. If you are unsure what dose to take ask your pharmacist or doctor.

If you forget to take it

If you miss a dose, 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.

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

If you have trouble remembering when to take your medicine, ask your pharmacist for some hints.

If you take too much (Overdose)

Immediately telephone your doctor or Poisons Information Centre (telephone 13 11 26) for advice or go to Accident and Emergency at your nearest hospital, if you think that you or anyone else may have taken too much MYDOL 15.

Do this even if there are no signs of discomfort or poisoning. You may need urgent medical attention.

Keep telephone numbers of these places handy.

If you take too many tablets you may feel nauseous, light headed, dizzy or drowsy.

While you are taking MYDOL 15

Things you must do

Take MYDOL 15 exactly as your doctor has told you to.

Tell all your doctors, dentists and pharmacists that you are taking MYDOL 15.

Tell your doctor if you become pregnant while taking MYDOL 15.

Things you must NOT do

Do not use this medicine to treat any other complaint unless your doctor or pharmacist says it is safe. Do not give this medicine to anyone else even if they have the same symptoms as you.

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

Children aged over 12 years: Do not take this medicine for longer than 48 hours at a time, unless advised to by a doctor.

Do not take more than the recommended dose unless your doctor tells you to.

Things to be careful of

MYDOL 15 may cause dizziness or drowsiness in some people, especially after the first dose.

If affected do not drive a car, operate machinery or do anything else that could be dangerous if you are dizzy or drowsy. Children should not ride bikes if affected and should be supervised to avoid potential harm. Do not drink alcohol.

Drinking alcohol increases the likelihood of becoming drowsy.

MYDOL 15 may be habit forming if taken in high doses for extended periods of time. Too much paracetamol may cause delayed, serious liver damage. Please ask your doctor or pharmacist if you are concerned about this.

Please ask your doctor or pharmacist if you are concerned about this.

About 8% of people are poor metabolisers of codeine. MYDOL 15 may not work as well if you are one of those people.

Side Effects

Tell your doctor as soon as possible if you do not feel well while taking MYDOL 15.

Like other medicines, MYDOL 15 can cause some side effects. If they occur, they are most likely minor and temporary. However, sometimes they are serious and need medical treatment.

Ask your doctor to answer any questions you may have.

Tell your doctor if you notice any of the following and they worry you:

Stomach problems such as:

  • Nausea
  • Vomiting
  • Stomach pain
  • Constipation

If you are taking MYDOL 15 regularly, you may also need to take laxatives to prevent constipation.

Difficulty thinking or working because of:

  • Dizziness
  • Drowsiness

Be careful driving or operating machinery until you know how MYDOL 15 affect you.

The above list includes the more common side effects of your medicine. They are usually mild.

Tell your doctor as soon as possible if you notice any of the following:

  • Cough suppression
  • Unusual or extreme mood swings
  • Flushing of the face
  • Fast heart beat

The above list includes serious side effects that may require medical attention. Serious side effects are rare for low doses of this medicine when used for a short period of time.

If any of the following happen, tell your doctor immediately or go to Accident and Emergency at your nearest hospital:

  • Shortness of breath
  • Wheezing or difficulty breathing
  • Swelling of the face, lips, tongue or other parts of the body
  • Rash, itching or hives on the skin

The above list includes very serious side effects. You may need urgent medical attention or hospitalisation.

If you believe MYDOL 15 are not working well for you, do not increase the dose. Please see your pharmacist or doctor.

Some people may get other side effects not listed above.

Tell your doctor if you notice anything else that is making you feel unwell.

After taking MYDOL 15

Storage

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

If you take the tablets out of the box or the blister pack they will not keep well.

Keep MYDOL 15 in a cool dry place where the temperature stays below 30°C.

Heat and dampness can destroy some medicines. Do not leave MYDOL 15 in the car on hot days.

Do not store MYDOL 15 or any other medicine in the bathroom or near a sink.

Keep MYDOL 15 where young 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 tells you to stop taking the tablets, ask your pharmacist what to do with any tablets that are left over.

This is not all the information that is available on MYDOL 15. If you have any more questions or are not sure about anything, ask your doctor or pharmacist.

Product Description

MYDOL 15 (AUST R 188381) come as white to off white capsule shaped uncoated tablets, plain on one side and breakline on the other side.

It is available in pack of 10 tablets, 12 tablets, 24 tablets, 30 tablets, and 40 tablets.

Active ingredients:

Each tablet contains:
Paracetamol 500 mg
Codeine Phosphate Hemihydrate 15 mg

Other ingredients:

Starch - Potato, Lactose monohydrate, Povidone, Docusate Sodium, Silica - colloidal anhydrous, Magnesium Stearate.

MYDOL 15 do not contain any gluten, sucrose, tartrazine or any azo dyes.

Name and Address of the sponsor

MYDOL 15 are supplied in Australia by:

Pharmacor Pty Ltd
Suite 803, Tower A, The Zenith,
821 Pacific Highway,
Chatswood NSW 2067
Australia
Web: www.pharmacor.com.au
Phone: 1300 138 805

This leaflet was prepared in October 2020

Published by MIMS January 2021

BRAND INFORMATION

Brand name

Mydol 15

Active ingredient

Paracetamol; Codeine phosphate hemihydrate

Schedule

S4

 

1 Name of Medicine

Paracetamol and codeine phosphate hemihydrate.

2 Qualitative and Quantitative Composition

Each tablet contains paracetamol 500 mg and codeine phosphate hemihydrate 15 mg.

Excipient with known effect.

Sugars as lactose monohydrate.
For the full list of excipients, see Section 6.1 List of Excipients.

3 Pharmaceutical Form

Mydol 15 tablets are white to off white capsule shaped uncoated tablets, plain on one side and breakline on the other side.

4 Clinical Particulars

4.1 Therapeutic Indications

For the temporary relief of acute moderate pain.

4.2 Dose and Method of Administration

Adults and children over 12 years.

2 tablets four times a day if required (maximum 8 tablets in 24 hours).
Mydol 15 tablets are contraindicated for use in patients who are:
below 12 years of age;
aged between 12 - 18 years in whom respiratory function might be compromised, including post tonsillectomy and/or adenoidectomy for obstructive sleep apnoea (see Section 4.3 Contraindications; Section 4.4 Special Warnings and Precautions for Use, Paediatric use).

4.3 Contraindications

Hypersensitivity to paracetamol or codeine or other ingredients (see Section 6.1 List of Excipients).
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.
Paracetamol should not be used in patients with active alcoholism as chronic excessive alcohol ingestion predisposes patients to paracetamol hepatotoxicity.
Mydol 15 tablets are also contraindicated for use in patients:
With known glucose-6-phosphate-dehydrogenase deficiency or severe respiratory disease, acute respiratory disease and respiratory depression, for example acute asthma, acute exacerbations of chronic obstructive pulmonary disease since codeine may exacerbate the condition.;
With chronic constipation;
In the event of impending childbirth or in case of risk of premature birth (see Section 4.6 Fertility, Pregnancy and Lactation);
In patients who are CYP2D6 ultra rapid metabolisers (see Section 4.4 Special Warnings and Precautions for Use, CYP2D6 metabolism);
In children younger than 12 years of age (see Section 4.4 Special Warnings and Precautions for Use, Paediatric use);
In patients aged between 12-18 years of age in whom respiratory function may be compromised, including post tonsillectomy, and/or adenoidectomy for obstructive sleep apnoea due to an increased risk of developing serious life-threatening adverse reactions (see Section 4.4 Special Warnings and Precautions for Use, Paediatric use);
During breastfeeding (see Section 4.6 Fertility, Pregnancy and Lactation, Use in lactation).

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. In view of the increased risk of hepatotoxicity, the benefit should be weighed against the risk when administering Mydol 15 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.
To avoid the risk of overdose:
Check that paracetamol is absent from the composition of other medicinal products taken concomitantly.
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 may exacerbate respiratory impairment and CNS depression.
Codeine should be administered with caution in patients with impaired cardiac, hepatic or renal function, hypotension, benign prostatic hyperplasia, urethral stenosis, chronic colitis ulcerative, gallbladder 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 and vomiting which 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 after careful risk-benefit assessment in case of:
Opioid dependence.
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.
Patients with known analgesic intolerance or known bronchial asthma must only use Mydol 15 after having consulted a physician (hypersensitivity reactions including bronchospasm possible). Caution is advised in patients with underlying sensitivity to aspirin and/or to non-steroidal antiinflammatory 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. Patients should be advised of the signs and symptoms and monitored closely for skin reactions. If symptoms or signs of SJS and TEN (e.g. progressive skin rash often with blisters or mucosal lesions) occur, patients should stop paracetamol treatment immediately and seek medical advice.
Paracetamol should be used upon medical advice in patients with:
Mild to moderate hepatocellular insufficiency (see Section 4.4 Special Warnings and Precautions For Use, Use in hepatic impairment);
Severe renal insufficiency (see Section 4.4 Special Warnings and Precautions For Use, Use in renal impairment);
Low glutathione reserves;
Gilbert's syndrome.
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). Mydol 15 should also be used with caution in patients who have had recent gastrointestinal tract surgery.
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.
Codeine should be administered with caution in patients taking Monoamine Oxidase Inhibitors (MAOIs) (see Section 4.5 Interactions with Other Medicines and Other Forms of Interactions).

High anion gap metabolic acidosis.

Cases of high anion gap metabolic acidosis (HAGMA) due to pyroglutamic acidosis have been reported in patients with severe illness such as severe renal impairment and sepsis, or patients with malnutrition and other sources of glutathione deficiency (e.g. chronic alcoholism) who were treated with paracetamol at therapeutic dose for a prolonged period or a combination of paracetamol and flucloxacillin. If HAGMA due to pyroglutamic acidosis is suspected, prompt discontinuation of paracetamol and close monitoring is recommended. The measurement of urinary 5-oxoproline may be useful to identify pyroglutamic acidosis as underlying cause of HAGMA in patients with multiple risk factors.

CYP2D6 metabolism.

Mydol 15 tablets are contraindicated for use in patients who are CYP2D6 ultrarapid 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 in infants of rapid metaboliser mothers who take codeine.
The prevalence of codeine ultra-metabolism by CYP2D6 in children is not known, but it 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. See Section 4.4 Special Warnings and Precautions for Use, Paediatric use; Section 4.6 Fertility, Pregnancy and Lactation, Use in lactation.

Hazardous and harmful use.

Mydol 15 contains the opioid codeine and is a potential drug of abuse, misuse and addiction. Addiction can occur in patients appropriately prescribed Mydol 15 at recommended dose.
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 Mydol 15.
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 and 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 Mydol 15 with anyone else.

Respiratory depression.

Serious, life-threatening or fatal respiratory depression occur with the use of opioids even when used as recommended. It can occur anytime during the use of Mydol 15 but the risk is greatest during initiation of therapy 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 renal and hepatic 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 Mydol 15 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 Mydol 15 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 Mydol 15.

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 non-pharmacological 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 Mydol 15 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 Mydol 15, 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 Mydol 15 (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.

Use in hepatic impairment.

Mydol 15 tablets should be administered with caution to patients with hepatic dysfunction, hepatitis, and to patients taking other drugs which affect the liver.

Use in renal impairment.

Mydol 15 tablets should be administered with caution to patients with renal dysfunction.

Use in elderly.

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. Dose reduction may be required.

Paediatric use.

Mydol 15 tablets are 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-metabolisers of codeine due to CYP2D6 polymorphism. 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

Paracetamol excretion may be affected and plasma concentrations altered when given with probenecid.

Salicylates and NSAIDs.

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

Anticoagulant (coumarins).

Paracetamol may increase the risk of bleeding in patients taking warfarin and other Vitamin K antagonist. Patients should be monitored for appropriate coagulation and bleeding complications.

Chloramphenicol.

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

Diflunisal.

Diflunisal may increase the plasma concentrations of paracetamol.

Cholestyramine.

Cholestyramine reduces the absorption of paracetamol if given within 1 hour of paracetamol.

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.

Alcohol.

Codeine may potentiate the effects of 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).

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.

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.

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.

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. 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).

Hepatotoxic drugs and liver microsomal enzyme inducers.

The risk of 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) barbiturates, rifampicin and alcohol.

Zidovudine.

When used concurrently with zidovudine, an increased tendency for neutropenia or hepatotoxicity may develop. Combination of Mydol 15 and zidovudine should be avoided. If chronic paracetamol and zidovudine are to be given concurrently, monitor white blood cell count and liver function tests, especially in malnourished patients.

CNS depressants.

Chloral hydrate.

Centrally acting muscle relaxants.


Anticholinergics.

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

Antihypertensives.

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

Antiperistaltic antidiarrhoeals (e.g. kaolin, pectin and loperamide).

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

Monoamine oxidase inhibitors (MAOIs).

Non-selective MAOI's intensify the effects of opioid drugs, which can cause anxiety, confusion and significant respiratory depression 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 MAOI's or within two weeks of stopping such treatment. As it is unknown whether there is an interaction between the selective MAOI's (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.

Neuromuscular blocking agents.

Codeine may enhance the effects of neuromuscular blocking agents resulting in increased respiratory depression.

Opioid analgesics.

Concurrent use of codeine and other opioid receptor agonists is usually inappropriate as additive CNS depression, respiratory depression and hypotensive effects may occur. Narcotic analgesics may decrease gastric emptying and therefore decrease the absorption of paracetamol.
Patients receiving other narcotic analgesics, antitussives, antihypertensives, antihistamines, antipsychotics, antianxiety agents or other CNS depressants (including gabapentinoids, cannabis, centrally-active anti-emetics, alcohol) concomitantly with this codeine-containing medicine may exhibit additive CNS depression (see Section 4.4 Special Warnings and Precautions For Use).

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.
Caution should be taken when paracetamol is used concomitantly with flucloxacillin as concurrent intake has been associated with high anion gap metabolic acidosis due to pyroglutamic acidosis, especially in patients with risks factors (see Section 4.4).

4.6 Fertility, Pregnancy and Lactation

Effects on fertility.

See Section 5.3 Preclinical Safety Data, Carcinogenicity.
(Category A)
Paracetamol crosses the placenta, however problems in humans have not been documented. Opioid analgesics cross the placenta. 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 Mydol 15 should be avoided during the third trimester of pregnancy and during labour.
 Mydol 15 tablets are contraindicated during breastfeeding (see Section 4.4 Special Warnings and Precautions for Use, CYP2D6 metabolism) due to risk of respiratory depression in the infant. Paracetamol is excreted in breast milk. Maternal ingestion of paracetamol in recommended doses does not appear to present a risk to breastfed infants. If Mydol 15 is administered to a nursing mother, alternative arrangements should be made for feeding the infant.
Analgesic doses excreted in breast milk are generally low. However, infants of breast feeding mothers taking codeine may have 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 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 breastfed infant. Life-threatening adverse events or neonatal death may occur even at therapeutic doses (see Section 4.4 Special Warnings and Precautions for Use, CYP2D6 metabolism).
Therefore, Mydol 15 tablets are 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 recognize 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

Mydol 15 may cause drowsiness, disturbances of visuomotor coordination and visual acuity and/or dizziness. Due to the preparation's sedative action, impairment of the mental and/or physical abilities required for the performance of potentially hazardous activities may occur. Hence, children engaging in bike riding and other hazardous activities should be supervised to avoid potential harm.
Adults should not drive, operate machinery or drink alcohol while taking this medication.

4.8 Adverse Effects (Undesirable Effects)

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, cough supression (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 nutritional system disorder.

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, 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 (see Section 4.4 Special Warnings and Precautions for Use), cytolytic hepatitis, which may lead to acute hepatic failure, have also been reported.
Haemolytic anaemia in particular in patients with underlying glucose 6-phosphate-dehydrogenase deficiency has been reported. Kounis syndrome and bronchospasm have also been reported.
Codeine has also been associated with confusional state, dysphoria, seizure, headache, somnolence, sedation, miosis, tinnitus, dry mouth, pruritus, fatigue, 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.
High anion gap metabolic acidosis with frequency "not known" (cannot be estimated from the available data).
Description of selected adverse reactions.
High anion gap metabolic acidosis.
Cases of high anion gap metabolic acidosis due to pyroglutamic acidosis have been observed in patients with risk factors using paracetamol (see Section 4.4). Pyroglutamic acidosis may occur as a consequence of low glutathione levels in these patients.

Reporting suspected adverse effects.

Reporting suspected adverse reactions after registration of the medicinal product is important. It allows continued monitoring of the benefit-risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions at www.tga.gov.au/reporting-problems.

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.

Symptoms.

Toxic symptoms include vomiting, abdominal pain, hypotension, sweating, central stimulation with exhilaration and convulsions in children, drowsiness, respiratory depression, cyanosis and coma. 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. The most serious adverse effect of acute overdosage of paracetamol is a dose dependent, potentially fatal hepatic necrosis.
In adults, hepatotoxicity may occur after ingestion of a single dose of paracetamol 10 to 15 g (30 tablets); a dose of 25 g (50 tablets) or more is potentially fatal.
Symptoms during the first two days of acute poisoning by paracetamol do not reflect the potential seriousness of the intoxication. Major manifestations of liver failure, such as jaundice, hypoglycaemia and metabolic acidosis, may take at least three days to develop.
In an evaluation of codeine intoxication in children, symptoms seen included: sedation, rash, miosis, vomiting, itching, ataxia and swelling of the skin. Respiratory failure may occur.
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.

For information on the management of overdose, contact the Poisons Information Centre on 131126 (Australia).
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.
Where paracetamol intoxication is suspected, intravenous administration of SH group donators such as acetylcysteine is indicated. For dosage instructions refer to the acetylcysteine IV product information.
For codeine intoxication, naloxone is the treatment of choice. For dosage instructions, refer to the naloxone product information.
Further measures will depend on the severity, nature and course of clinical symptoms of intoxication and should follow standard intensive care protocols.

5 Pharmacological Properties

5.1 Pharmacodynamic Properties

Mechanism of action.

Paracetamol's analgesic mechanism of action has not been fully elucidated, but may involve blocking impulse generation at the bradykinin sensitive chemoreceptors that evoke pain.
The antipyretic effect of paracetamol rises from its ability to block the action of prostaglandin synthetase and so prevent the synthesis of prostaglandins in response to the pyrogen stimulus in the region of the anterior hypothalamus.
Codeine acts centrally. It produces analgesia by dulling the response to painful stimuli at several loci in the central nervous system. This causes an alteration in the sensation and affective response of pain.
There is evidence to suggest that a combination of paracetamol with codeine is superior in analgesic action to either drug administered alone.

Clinical trials.

No data 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.

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.

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.
Patients who metabolise drugs poorly via CYP2D6 are likely to obtain reduced benefit from codeine due to reduced formation of the active metabolite. This may be the case in about 8% of patients.

Excretion.

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 one to four hours.
It is metabolised in the liver to morphine and norcodeine which, with codeine, are excreted in the urine, partly as conjugates with glucuronic acid. Excretion is almost complete within 24 hours.

5.3 Preclinical Safety Data

Genotoxicity.

No data 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

Excipients.

Starch - potato, lactose monohydrate, povidone, docusate sodium, silica - colloidal anhydrous, 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

Store below 30°C.

6.5 Nature and Contents of Container

Mydol 15 (AUST R No. 188381) is presented in PVC/PVDC/Al blister pack sizes of 10 tablets, 12 tablets, 24 tablets, 30 tablets, and 40 tablets.

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 is a white or almost white crystalline powder. It is sparingly soluble in water, freely soluble in alcohol, very slightly soluble in methylene chloride.
Codeine phosphate hemihydrate is a white or almost white, crystalline powder or small, colourless crystals. It is freely soluble in water, slightly soluble or very slightly soluble in ethanol (96%). Codeine phosphate hemihydrate is a cough suppressant and an analgesic.

Chemical structure.

Paracetamol.


Molecular Formula: C8H9NO2.
Molecular weight: 151.2.

Codeine phosphate hemihydrate.


Molecular Formula: C18H21NO3, H3PO4, ½H2O.
Molecular weight: 406.4.

CAS number.

Paracetamol: 103-90-2.
Codeine phosphate hemihydrate: 1444-62-6.

7 Medicine Schedule (Poisons Standard)

Prescription Only Medicine (S4).

Summary Table of Changes