Consumer medicine information

Aspen Codeine Tablets

Codeine phosphate hemihydrate

BRAND INFORMATION

Brand name

Aspen Codeine

Active ingredient

Codeine phosphate hemihydrate

Schedule

S8

 

Consumer medicine information (CMI) leaflet

Please read this leaflet carefully before you start using Aspen Codeine Tablets.

What is in this leaflet

This leaflet answers some common questions about Aspen Codeine tablets.

It does not contain all of the available information about Aspen Codeine tablets.

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

All medicines have risks and benefits. Your doctor has weighed the risks of you taking Aspen Codeine tablets against the benefits he/she expect it will have.

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

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

What is Aspen Codeine tablets

The name of your medicine is Aspen Codeine tablets.

The active ingredient is called codeine phosphate hemihydrate.

Codeine phosphate hemihydrate belongs to a group of medicines called analgesics, which are used to block pain. It is an opioid analgesic, and it acts by blocking pain and your emotional response to pain.

What Aspen Codeine tablets is used for

Aspen Codeine tablets is used for the treatment of mild to moderate pain.

Your doctor, however, may have prescribed Aspen Codeine tablets for another purpose.

Ask your doctor if you have any questions about why Aspen Codeine tablets has been prescribed for you.

If you have any concerns, you should discuss this with your doctor.

Aspen Codeine tablets is available only with a doctor’s prescription.

Before you take Aspen Codeine tablets

When you must not take it

Do not take Aspen Codeine tablets if you are allergic to:

  • Aspen Codeine or any of the ingredients listed at the end of this leaflet.
  • Morphine
  • Oxycodone

Some of the symptoms of an allergic reaction to Aspen Codeine tablets may include red, itchy skin rashes; difficulty breathing; faintness; hay fever and swelling of the face or throat.

Aspen Codeine tablets should not be taken if you are experiencing breathing difficulties such as asthma, bronchitis or emphysema.

Do not take Aspen Codeine tablets if you have had recent biliary tract surgery.

Do not take Aspen Codeine tablets if you have recently ingested a large amount of alcoholic beverages.

Do not take Aspen Codeine tablets if you recently have had a head injury or conditions that raise the pressure within your head.

Do not use Aspen Codeine tablets if you are suffering from diarrhoea caused by poisoning or antibiotics.

Do not take Aspen Codeine tablets if you have been taking monoamine oxidase inhibitors (medicines for treating depression or mood swings, such as phenelzine, tranylcypromine or moclobemide) within the last ten days.

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

Do not purchase or use Aspen Codeine tablets if the packaging is torn or shows signs of tampering. The tablets should not be taken if they show visible signs of deterioration.

Do not give it to children under the age of 12 years unless your doctor has prescribed it for them.

Like all medicines Aspen Codeine tablets should not be used during pregnancy without first consulting your doctor.

Aspen Codeine tablets is distributed to the breast milk so it is not recommended for nursing mothers.

Elderly patients are more likely to have less effective kidney function due to age. This may increase the risk of side effects. You should discuss how much Aspen Codeine tablets to take with your doctor or pharmacist.

Before you start to take it

You must tell your doctor if you are:

Allergic to any other medicines or any foods, dyes or preservatives.

You have any other medical conditions/ health problems including:

  • A breathing disorder, lung disease or a history of asthma
  • Heart disease
  • Liver disease, hepatitis
  • Kidney disease or difficulty urinating
  • Depression
  • An underactive thyroid gland
  • Addison’s disease (low activity of the adrenal glands)
  • Inflammatory bowel disease or other gastro-intestinal problems
  • Diarrhoea
  • Gallbladder disease or gallstones
  • A prostate disorder

You are a heavy drinker or drug user

You have had a recent head injury

You have recent biliary tract surgery

You are about to have surgery under a general anaesthetic

You are pregnant or intend to become pregnant

You are breastfeeding or intend to breastfeed

Your doctor will discuss the risks and benefits of using Aspen Codeine tablets during pregnancy or when breastfeeding.

If you have not told your doctor about any of the above, tell them before you take any Aspen Codeine tablets.

Taking other medicines

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

Some medicines may interfere with Aspen Codeine tablets.

These include:

  • Medicines to help you sleep or relieve anxiety
  • Anticholinergics, medicines to treat muscle spasms
  • Medicines used to treat diarrhoea
  • Medication for epilepsy
  • Medicines used to treat high blood pressure
  • Diuretics or fluid tablets
  • Other opioid analgesics used to block pain
  • Antihistamines (medicines used to treat allergies such as hay fever, insect bites and some cold remedies)
  • Monoamine oxidase inhibitors (medicines for treating depression) taken within the last 10 days
  • Metoclopramide, a medicine used to relieve nausea and vomiting
  • Antidepressant medicines used to treat depression
  • Naloxone or Naltrexone, medicines used to counteract the effects of opioid analgesics.
  • Medicines used to relax muscles
  • Quinidine (a medicine used to treat abnormal or irregular heart beat)
  • Cimetidine (a medicine used to treat reflux or stomach ulcer)

The above medicines may reduce the effectiveness of Aspen Codeine tablets, reduce their own effectiveness and/ or react with Aspen Codeine tablets resulting in untoward or sometimes dangerous side effects.

This list is not exhaustive. Your doctor or pharmacist has more information on medicines to be careful with or avoid while taking Aspen Codeine tablets.

How to take Aspen Codeine tablets

How much to take
The recommended dose of Aspen Codeine tablets is:

Adults: 1 to 2 tablets every four to six hours.

How to take it
The tablets should be swallowed whole with a glass of water.

How long to take it

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

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

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

If you forget to take it

Take you dose as soon as you remember and then go back to taking it as you would normally.

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

If you are unsure about whether to take your next dose, speak to your doctor or pharmacist.

Do not try to make up for missed doses by taking more than one dose at a time. This may increase the chance of you getting an unwanted effect.

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

If you take too much (Overdose):

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

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

If you think you or someone else may have used too much Aspen Codeine tablets you should immediately:

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

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

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

While you are using Aspen Codeine tablets

Things you must do:

Use Aspen Codeine tablets exactly as directed or as prescribed by your doctor.

Tell your doctor if you feel Aspen Codeine tablets is not helping your condition.

Visit your doctor regularly, as your doctor needs to check your progress and see whether you need to keep taking Aspen Codeine tablets.

Always discuss with your doctor any problems or difficulties during or after taking Aspen Codeine tablets.

You should tell any other doctors or dentists treating you that you are taking Aspen Codeine tablets.

Things you must not do:

Do not take any other medicines while you are taking Aspen Codeine tablets without first telling your doctor.

Do not drive or operate machinery until you know how Aspen Codeine tablets affects you.

Aspen Codeine tablets may cause dizziness in some people and therefore may affect alertness. Make sure you know how you react to Aspen Codeine tablets before you drive a car, operate machinery, or do anything else that could be dangerous if you are dizzy or have blurred vision.

Do not give this medicine to anyone else, even if his or her symptoms seem similar to yours.

Things to be careful of:

Be careful drinking alcohol while taking Aspen Codeine tablets. If you drink alcohol, it could make some of the unwanted side effects of Aspen Codeine tablets worse.

Your doctor may suggest that you avoid alcohol completely or reduce the amount of alcohol you drink while you are taking Aspen Codeine tablets.

Some people may experience side effects such as nausea, vomiting, constipation, drowsiness, dizziness, which may further affect the risk when driving or using dangerous machinery.

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

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

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

Side effects

Tell your doctor or pharmacist as soon as possible if you do not feel well while you are taking Aspen Codeine tablets.

Aspen Codeine tablets helps most people in the treatment of mild to moderate pain. However it may have unwanted side effects in some people, especially in elderly patients or those with underlying disorders.

All medicines have side effects. Sometimes they are serious, most of the time they are not. You may need medical treatment if you get some of the side effects.

Ask your doctor or pharmacist any questions you may have.

Common Side Effects:

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

  • stomach cramps
  • dry mouth
  • loss of appetite
  • constipation
  • nausea (feeling sick)
  • vomiting
  • dizziness
  • drowsiness
  • feeling faint
  • excitability
  • skin rashes
  • unable to sleep
  • unusual dreams

Some side effects are potentially serious.

Contact your doctor immediately if you notice any of the following side effects:

  • itchy, raised or red skin rash
  • swelling of face
  • muscle stiffness
  • breathing difficulties
  • heartbeat irregularities
  • blurred or double vision
  • difficulty in urinating (passing water)

Some people may get other side effects of Aspen Codeine tablets that are not listed in this leaflet.

Check with your doctor as soon as possible if you have any problems while taking Aspen Codeine tablets even if you do not think the problems are connected with the medicine or are not listed in this leaflet.

After using Aspen Codeine tablets

Storage

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

Keep Aspen Codeine tablets in a cool dry place where the temperature stays below 30°C and protect from light.

Do not store it, or any other medicines, in a bathroom or near a sink.

Do not leave it in the car or on windowsills.

Heat and dampness can destroy some medicines.

Do not take Aspen Codeine tablets if the tablets do not look quite right.

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

Disposal

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.

Product description

What it looks like

Aspen Codeine tablet is a white unscored tablet that is available in blister packs of 10, 20 and 100 tablets.

Ingredients

Each Aspen Codeine tablet contains 30 mg of Codeine phosphate hemihydrate.

Aspen Codeine tablets also contain the following excipients:

maize starch, lactose monohydrate, and magnesium stearate.

Sponsor

Aspen Pharma Pty Ltd
34-36 Chandos St
St Leonards NSW 2065

The Australian Registration Number for Aspen Codeine tablets is: AUST R 276146.

This leaflet was prepared in July 2020.

Published by MIMS September 2020

BRAND INFORMATION

Brand name

Aspen Codeine

Active ingredient

Codeine phosphate hemihydrate

Schedule

S8

 

1 Name of Medicine

Codeine phosphate hemihydrate.

2 Qualitative and Quantitative Composition

Excipient with known effect.

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

3 Pharmaceutical Form

Plain white round biconvex tablets containing 30 mg of codeine phosphate hemihydrate.

4 Clinical Particulars

4.1 Therapeutic Indications

Aspen Codeine tablets are 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

Initial dosing requirements will depend on medical and analgesic history of the patient, patient's age, weight and severity of pain. It may need to be reduced in patients who are elderly or debilitated.

Adults.

30 to 60 mg every four to six hours (usual dose 30 mg).

Note.

If 60 mg of codeine every four to six hours fails to relieve pain, larger doses rarely succeed and may give rise to restlessness and excitement.

Children.

Aspen Codeine tablets are 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. (See Section 4.3 Contraindications; Section 4.4 Special Warnings and Precautions for Use, Paediatric use, CYP2D6 metabolism.)

4.3 Contraindications

Aspen Codeine tablets are contraindicated in patients with hypersensitivity to any ingredient. 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 respiratory depression (e.g. acute asthma, acute exacerbations of chronic pulmonary disease), especially in the presence of cyanosis and excessive bronchial secretion, and after operations on the biliary tract.
Codeine is contraindicated for use in patients with severe respiratory disease and acute respiratory disease.
Codeine is contraindicated in the presence of acute alcoholism, head injuries, and conditions in which intracranial pressure is raised.
Codeine should not be given during an attack of bronchial asthma or in heart failure secondary to chronic lung disease.
Administration is contraindicated in patients taking monoamine oxidase inhibitors (MAOIs) or within ten days of stopping such treatment.
Like all opioid analgesics, Aspen Codeine tablets are contraindicated for use in patients with diarrhoea caused by pseudomembranous colitis or poisoning until the causative organism or toxic material has been excluded from the gastrointestinal tract. This is because opioid analgesics may slow elimination of the causative agent, thereby worsening and/or prolonging the diarrhoea.
Aspen Codeine tablets are 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 Fertility, Pregnancy and Lactation, Use in lactation).

4.4 Special Warnings and Precautions for Use

Hazardous and harmful use.

Aspen Codeine tablets contains the opioid codeine and is a potential drug of abuse, misuse and addiction. Addiction can occur in patients appropriately prescribed Aspen Codeine tablets 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 Aspen Codeine tablets.
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 Aspen Codeine tablets 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 Aspen Codeine tablets 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 existing impairment of respiratory function (e.g. chronic obstructive pulmonary disease; asthma), in patients with hepatic impairment (see Use in hepatic impairment) and in patients with renal impairment (see Use in renal impairment). 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, 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 Aspen Codeine tablets 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 Aspen Codeine tablets 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 Aspen Codeine tablets.

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 Aspen Codeine tablets 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 Aspen Codeine tablets, especially by children, can result in a fatal overdose of [opioid]. Patients and their caregivers should be given information on safe storage and disposal of unused Aspen Codeine tablets (see Section 6.4 Special Precautions for Storage; Section 6.6 Special Precautions for Disposal).

Hyperalgesia.

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

Ceasing opioids.

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

CYP2D6 metabolism.

Aspen Codeine tablets are 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. (See Paediatric use; see Section 4.6 Fertility, Pregnancy and Lactation, Use in lactation.)
Alarming and atypical effects sometimes occur in the elderly and the dosage should be reduced in elderly and debilitated patients. It should be given with extreme caution to patients with hypothyroidism, adrenocortical insufficiency (e.g. Addison's disease), shock, myxedema, acute alcohol intoxication and delirium tremens since codeine may exacerbate the symptoms or increase the risk of respiratory and/or CNS depression.
Physical and/or psychological dependence may occur following prolonged administration of codeine. Tolerance may also develop following prolonged administration. Codeine produces less euphoria and sedation than morphine and is not a completely satisfactory substitute for morphine in morphine addicts. Withdrawal symptoms develop more slowly than with morphine and are milder.
Diagnosis or clinical course of acute abdominal conditions may be obscured by use of analgesics. As opioids may alter gastric motility they should be used with caution for patients who have recently had gastrointestinal tract surgery. In severe inflammatory bowel disease the risk of toxic megacolon may be increased by opioid use, especially with repeated dosing.
Codeine must be used with extreme caution in patients with decreased respiratory reserve (e.g. in emphysema, kyphoscoliosis, hypoxia, hypercapnia or even severe obesity), cor pulmonale, or chronic obstructive pulmonary disease, since codeine may exacerbate respiratory impairment.
Caution should be exercised when administering codeine and other opioid analgesics to patients with a history of cardiac arrhythmias or convulsions. These conditions may be induced or exacerbated by opioids.
Opioids may cause biliary contraction, thus should be used with caution where there is underlying gallbladder disease or gallstones.
Codeine should be administered with great caution if at all in patients with CNS depression, since codeine may exacerbate the condition.

Use in hepatic impairment.

Codeine is metabolised by the liver and should be used with caution in patients with hepatic disease, since increased bioavailability after oral administration or cumulative effects may occur.

Use in renal impairment.

Opioid use may lead to urinary retention, thus such medicaments should be used with caution in patients with prostatic hypertrophy or obstruction, urethral stricture or who have had recent urinary tract surgery. Opioids and their metabolites are excreted primarily via the kidneys. Because of this there is an increased risk of adverse effects in patients with renal function impairment.

Use in the elderly.

The elderly are more likely to have age-related renal impairment and may be more susceptible to the respiratory effects of opioid analgesics. Dose reduction may be required.

Paediatric use.

Aspen Codeine 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-rapid metabolisers of codeine due to a CYP2D6 polymorphism.
(See Section 4.4 Special Warnings and Precautions for Use, CYP2D6 metabolism.)

Effects on laboratory tests.

Gastric emptying studies.

Opioid analgesics delay gastric emptying, thereby invalidating test results.

Hepatobiliary imaging using technetium Tc 99m disofenin.

Delivery of technetium Tc 99m disofenin to the small bowel may be prevented because opioid analgesics may cause constriction of the sphincter of Oddi and increased biliary tract pressure. These actions result in delayed visualisation and thus resemble obstruction of the common bile duct.

Cerebrospinal fluid (CSF) pressure.

Cerebrospinal fluid pressure may be increased. This effect is secondary to respiratory depression-induced carbon dioxide retention.

Plasma amylase activity and plasma lipase activity.

These may be increased because opioid analgesics can cause contractions of the sphincter of Oddi and increased biliary tract pressure. The diagnostic utility of determinations of these enzymes may be compromised for up to 24 hours after the medication has been given.

4.5 Interactions with Other Medicines and Other Forms of Interactions

Also see Section 4.4 Special Warnings and Precautions for Use, Risks from concomitant use of benzodiazepines or other CNS depressants, including alcohol.

CNS depressants.

Concurrent use with opioid analgesics may result in increased CNS depressant and hypotensive effects. Caution is recommended and one or both agents should be reduced.

Barbiturate anaesthetics.

Codeine may potentiate the effects of barbiturate anaesthetics.

Tranquillisers, sedatives and hypnotics.

Codeine may potentiate the effects of these drugs.

Opioid analgesics.

Codeine may potentiate the effects of opioid agonists.

Alcohol.

Codeine may potentiate the effects of alcohol and the likelihood of toxicity may be increased by its concomitant use.

Barbiturates and antiepileptic medications.

The likelihood of toxicity may be increased by the concomitant use of enzyme inducing agents such as alcohol, barbiturates or antiepileptic drugs.

Anticholinergics.

Concurrent use with opioid analgesics may result in increased risk of severe constipation, which may lead to paralytic ileus and/or urinary retention.

Antidiarrhoeals, antiperistaltic (including kaolin, pectin, loperamide).

Concurrent use of these agents with codeine may result in an increased risk of severe constipation.

Antihypertensives, diuretics and other hypotension-producing medications.

The hypotensive effects of these medications may be potentiated by concurrent use of opioid analgesics, leading to an increased risk of orthostatic hypotension. Patients should be monitored during concurrent use.

Buprenorphine.

Buprenorphine is a partial mu-receptor agonist with high affinity for, and a slow rate of dissociation from, the mu receptor; if administered prior to another opioid agonist it may reduce the therapeutic effects of the other opioid. Buprenorphine also antagonises the respiratory depressant effects of large doses of previously administered mu-receptor agonists; however, additive respiratory depression may occur if buprenorphine is administered in conjunction with low doses of other mu-receptor agonists or with kappa-receptor agonists.

Hydroxyzine.

Concurrent use of opioid analgesics may result in increased analgesia as well as increased CNS depressant and hypotensive effects.

Metoclopramide.

Opioid analgesics may antagonize the effects of metoclopramide or gastrointestinal motility.

Monoamine oxidase inhibitors (MAOIs).

Nonselective MAOIs intensify the effects of opioid drugs which can cause anxiety, confusion and significant respiratory depression. Severe and sometimes fatal reactions have occurred in patients concurrently administered MAO inhibitors and pethidine. Codeine should not be given to patients taking non-selective MAOIs or within 10 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.

Naloxone.

Naloxone antagonises the analgesic, CNS, and respiratory depressant effects of opioid analgesics. Because naloxone may precipitate withdrawal symptoms in physically dependent patients, dosage of naloxone should be carefully titrated when used to treat opioid overdosage in dependent patients.

Naltrexone.

Administration of naltrexone to a patient physically dependent on opioid drugs will precipitate withdrawal symptoms: symptoms may appear within 5 minutes of naltrexone administration, persist for up to 48 hours, and be difficult to reverse. Naltrexone blocks the therapeutic effects of opioids (i.e. analgesic, antidiarrhoeal and antitussive): naltrexone therapy should not be initiated in patients receiving these agents for therapeutic purposes; also, patients receiving naltrexone should be advised to use alternative medications when necessary. Administration of increased doses of opioids to override naltrexone blockade of opioid receptors may result in increased and prolonged respiratory depression and collapse. Naltrexone should be discontinued several days prior to elective surgery if administration of an opioid prior to, during or following surgery is unavoidable. The efficacy of naltrexone in antagonising opioid effects not mediated via opioid receptors (i.e. those that may be caused by histamine release such as facial swelling, itching, generalised erythema, hives, and to some extent, hypotension) has not been fully determined; naltrexone may not antagonise these effects completely.

Neuromuscular blocking agents and drugs with similar activity.

Respiratory depressant effects of neuromuscular blockade may be additive to central respiratory depressant effects of opioid analgesics. Increased or prolonged respiratory depression (apnoea) or paralysis may occur but it is of minor clinical significance if the patient is being mechanically ventilated. However, caution and careful monitoring of the patient are recommended during and following concurrent or sequential use, especially if there is a possibility of incomplete reversal of neuromuscular blockade postoperatively.

Quinidine.

Quinidine interferes with the metabolism of codeine to morphine lowering the analgesic effect of codeine.

Cimetidine.

Cimetidine may reduce the metabolism of codeine, enhancing the possibility of codeine toxicity.

Tricyclic antidepressants.

Concurrent use of codeine and tricyclic antidepressants possessing CNS depression effects may result in a potentiation of the CNS depression and increased sedation. Concurrent use of codeine and tricyclic antidepressants with anticholinergic effects may result in an increased risk of severe constipation and/or urinary retention.

4.6 Fertility, Pregnancy and Lactation

Effects on fertility.

Adequate studies in animals have not been performed to determine whether Aspen Codeine tablets have potential to impair fertility.
(Category A)
Opioid analgesics cross the placenta. Regular use during pregnancy may cause physical dependence in the foetus, leading to withdrawal symptoms in the neonate. Although teratogenic effects in humans have not been documented, controlled studies have not been done. Studies in animals have shown codeine (single dose of 100 mg per kg) to cause delayed ossification in mice and (in doses of 120 mg per kg) increased resorptions in rats. The use of codeine may prolong labour. Administration of codeine during labour may cause respiratory depression in the newborn infant.
 Aspen Codeine 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.
Analgesic doses excreted in breast milk are generally low. However, infants of breastfeeding mothers taking codeine may have an increased risk of morphine overdose if the mother is an ultrarapid metaboliser of codeine. Codeine is excreted into human breast milk. Codeine is partially metabolised by cytochrome P4502D6 (CYP2D6) into morphine, which is excreted into breast milk If nursing mothers are CYP2D6 ultra-rapid metabolisers, higher levels of morphine may be present in their breast milk. This may result in symptoms of opioid toxicity in both mother and the breastfed infant. Life-threatening adverse events or neonatal death may occur even at therapeutic doses (see Section 4.4 Special Warnings and Precautions for Use, CYP2D6 metabolism).
Therefore, Aspen Codeine 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. Breastfeeding mothers should be told how to recognise signs of high morphine levels in themselves and their babies. For example, in a mother, symptoms include extreme sleepiness and trouble caring for the baby. In the baby, symptoms include signs of increased sleepiness (more than usual), difficulty breastfeeding, breathing difficulties, or limpness. Medical advice should be sought immediately.

4.7 Effects on Ability to Drive and Use Machines

Codeine may impair the psychological and/or physical abilities needed for certain potentially hazardous activities such as driving a car or operating machinery. Patients should be cautioned accordingly.

4.8 Adverse Effects (Undesirable Effects)

Gastrointestinal.

Uncommon: constipation, dry mouth, loss of appetite, nausea, vomiting, paralytic ileus, toxic megacolon, anorexia, stomach cramps.

CNS.

Common: drowsiness.
Uncommon: headache, dizziness, lightheadedness, feeling faint, CNS stimulation, euphoria, dysphoria, unusual dreams, hallucinations, insomnia, disorientation.

Hypersensitivity.

Uncommon: skin rashes, itching, swelling of face, histamine release.

Musculoskeletal.

Uncommon: muscle rigidity.

Respiratory.

Uncommon: bronchospasm, laryngospasm, respiratory depression.

Cardiovascular.

Uncommon: heartbeat irregularities, blood pressure changes, syncope.

Genitourinary.

Uncommon: urinary retention or hesitance, ureteric spasm, reduced libido and/or potency.

Endocrine.

Uncommon: antidiuretic effect.

Ocular.

Uncommon: miosis, blurred or double vision.
Signs and symptoms of withdrawal when chronic administration of codeine is discontinued or opioid antagonists are administered include the following: diarrhoea, sweating, vomiting, insomnia, agitation, tremor.

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

Symptoms.

Poisoning with codeine produces central stimulation with exhilaration and, in children, convulsions, followed by vomiting, drowsiness, respiratory depression and cyanosis, and coma. Further symptoms of overdosage include cold or clammy skin, miosis, skeletal muscle flacidity, hypotension and bradycardia. Severe overdosage may result in apnea, circulatory collapse, cardiac arrest, respiratory arrest, and death.

Treatment.

The first step should be to establish adequate respiratory exchange by provision of a patent airway and controlled or assisted ventilation. Naloxone hydrochloride is given subcutaneously, intramuscularly or intravenously, with a usual adult dose of 0.4-2 mg repeated at intervals of two to three minutes if necessary. Intravenous administration is the preferred route for naloxone to achieve the most rapid onset of action and is recommended in emergency situations.
If no response is observed after 10 mg of naloxone hydrochloride has been administered the diagnosis of opioid-induced toxicity should be questioned. Children may receive an initial dose of 0.01 mg/kg; if this dose does not produce the desired degree of response, a subsequent dose of 0.1 mg/kg may be administered. Since the duration of action of codeine may be longer than that of naloxone, the patient should be kept under surveillance, and doses of naloxone repeated as needed.
For information on the management of overdose, contact the Poisons Information Centre on 13 11 26 (Australia).

5 Pharmacological Properties

5.1 Pharmacodynamic Properties

Mechanism of action.

Codeine phosphate hemihydrate is an opioid analgesic that binds with stereospecific receptors at many sites within the CNS to alter processes affecting both the perceptions of pain and the emotional response to pain. There are multiple sub-types of opioid receptors, each mediating various therapeutic and/or side effects of drugs. Its analgesic effect is thought to be due to its partial metabolic conversion to morphine. Codeine has about one-sixth the analgesic activity of morphine.

Clinical trials.

No data available.

5.2 Pharmacokinetic Properties

Absorption.

Codeine is well absorbed after administration by mouth or injection. Codeine is absorbed from the GI tract. Following oral administration, onset of action occurs in 15 to 30 minutes and analgesia is maintained for 4 to 6 hours. Peak antitussive effects usually occur within 1 to 2 hours and antitussive activity may persist for 4 hours.

Distribution.

Codeine is rapidly distributed to skeletal muscle, kidneys, liver, gastrointestinal tract, lungs, spleen and brain. It readily crosses the placenta, and is distributed in low levels into the breast milk.

Metabolism.

Codeine is metabolised in the liver. The major metabolic pathway involves glucuronidation of codeine to codeine-6-glucuronide. Codeine can also undergo O- and N-demethylation catalysed by CYP2D6 and CYP3A4 respectively. Patients who metabolise drugs poorly via CYP2D6 are likely to obtain reduced benefit from codeine due to reduced formation of the active metabolite. About 10% of an administered dose of codeine is converted by O-demethylation to morphine which subsequently undergoes glucuronidation to morphine-3 or morphine-6 glucuronide, or N-demethylation to normorphine. Approximately 5% to 10% of the Caucasian population cannot convert codeine to morphine, as they are deficient in the CYP2D6 enzyme. Codeine is also converted by N-demethylation to norcodeine which subsequently undergoes glucuronidation to norcodeine glucuronide, or O-demethylation to normorphine.

Excretion.

Codeine is excreted mainly in the kidneys as its metabolite codeine-6-glucuronide. 5-15% is excreted unchanged and approximately 10% is excreted as unchanged or conjugated morphine. The plasma half-life of codeine is 2 to 4 hours. Only traces of codeine and its metabolites are found in the faeces.

5.3 Preclinical Safety Data

Genotoxicity.

Adequate studies in animals have not been conducted to determine whether Aspen Codeine have potential for mutagenesis.

Carcinogenicity.

Adequate studies in animals have not been conducted to determine whether Aspen Codeine have potential for carcinogenesis.

6 Pharmaceutical Particulars

6.1 List of Excipients

Aspen Codeine tablets contain the following excipients: maize starch, lactose monohydrate 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

Store below 30°C. Protect from light.

6.5 Nature and Contents of Container

PVC/Al blister packs of 10, 100 and 20 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

Chemical structure.

Codeine phosphate hemihydrate is a small, colourless, odourless crystal or a white, odourless crystalline powder. Codeine phosphate hemihydrate is soluble in 4 parts of water, slightly soluble in ethanol (96%), practically insoluble in chloroform and ether.
Codeine phosphate hemihydrate is (5R,6S)-7,8-didehydro-4,5-epoxy-3-methoxy-N- methylmorphinan-6-ol dihydrogen orthophosphate hemihydrate.
It has the following chemical structure:
The molecular formula is C18H21NO3,H3PO4,1/2H2O. The molecular weight is 406.40.

CAS number.

41444-62-6.

7 Medicine Schedule (Poisons Standard)

Controlled Drug (S8).

Summary Table of Changes