Consumer medicine information

Panamax Co

Codeine phosphate hemihydrate; Paracetamol

BRAND INFORMATION

Brand name

Panamax Co Tablets

Active ingredient

Codeine phosphate hemihydrate; Paracetamol

Schedule

S4

 

Consumer medicine information (CMI) leaflet

Please read this leaflet carefully before you start using Panamax Co.

What is in this leaflet

This leaflet answers some common questions about Panamax Co tablets.

It does not contain all the available information. It does not take the place of talking to your doctor or pharmacist.

All medicines have risks and benefits. Your doctor or pharmacist has weighed the risks of you taking this medicine against the benefits they expect it will have for you.

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

Keep this information with the tablets.

You may want to read it again.

What Panamax Co is used for

Panamax Co is a type of analgesic intended for short term use to relieve moderate pain.

Paracetamol and codeine work together to stop the pain messages from getting through to the brain.

Before you take Panamax Co tablets

When you must not take it

Do not take Panamax Co if you have an allergy to paracetamol or codeine or any of the ingredients listed at the end of this leaflet.

Some of the symptoms of an allergic reaction may include:

  • 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

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

  • acute breathing difficulties such as bronchitis, unstable asthma, or emphysema
  • liver failure
  • chronic constipation
  • diarrhoea caused by antibiotics or poisoning
  • glucose-6-phosphate-dehydrogenase deficiency (an enzyme deficiency)
  • known ultra-rapid metaboliser of CYP 2D6 (a fast metaboliser of codeine by the CYP 2D6 enzyme)

Do not take codeine if you have alcohol dependence.

Do not give Panamax Co to children under 12 years.

Do not give Panamax Co to children aged between 12-18 years who have undergone tonsillectomy and/or adenoidectomy to treat sleep apnoea.

Do not take Panamax Co during the third trimester of pregnancy.

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

This medicine may produce withdrawal effects in the newborn baby.

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

Panamax Co passes into breast milk and there is a possibility your baby may be affected.

Do not use Panamax Co after the expiry date (EXP) printed on the pack.

If you take it after the expiry date has passed, it may not work (as well).

Do not use Panamax Co if the packaging is torn or shows signs of tampering.

If it has expired or is damaged, return it to your pharmacist for disposal.

If you are not sure whether you should start taking Panamax Co, talk to your doctor or pharmacist.

Before you start to take it

Tell your doctor or pharmacist if you have allergies to aspirin, other NSAIDs, any other medicines, foods, preservatives or dyes.

Tell your doctor or pharmacist if you have or have had any of the following medical conditions:

  • difficulty breathing, wheezing, chronic cough, asthma, or other chronic breathing conditions
  • compromised respiratory function (due to emphysema, kyphoscoliosis or obesity)
  • known analgesic intolerance
  • a history of drug dependence, including alcohol dependence
  • pre-existing opioid dependence
  • chronic alcohol use including recent cessation of alcohol intake
  • low glutathione reserves
  • Gilbert's syndrome
  • recent surgery on the stomach, intestine or urinary tract
  • chronic constipation
  • head injury or trauma
  • prostate problems
  • heart, liver or kidney problems
  • urinary, bowel or gallbladder conditions
  • Addison's disease
  • Multiple sclerosis
  • low blood pressure
  • underactive thyroid
  • are under 18 and have undergone adenoidectomy and/or tonsillectomy
  • if you know you are a CYP 2D6 ultra-rapid metaboliser
  • convulsions, fits or seizures

Tell your doctor or pharmacist if you plan to have surgery.

Tell your doctor or pharmacist if you take sedatives (medicines used to help you relax or sleep).

Tell your doctor or pharmacist if you are pregnant or intend to become pregnant.

Your doctor or pharmacist will discuss the risks and benefits of taking it during pregnancy.

If you have not told your doctor or pharmacist about any of the above, tell them before start taking Panamax Co.

Taking other medicines

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

Some medicines and Panamax Co may interfere with each other. These include:

  • medicines used to help you relax, sleep or relieve anxiety, such as barbiturates and sedatives
  • benzodiazepines (medicines used as sedatives or to treat anxiety)
  • medicines containing alcohol (ethanol), e.g. some cough syrups
  • medicines which thin the blood
  • medicines to treat epilepsy or fits
  • metoclopramide or domperidone, medicines used to control nausea and vomiting
  • propantheline, a drug used to relieve stomach cramps or spasms
  • medicines used to prevent travel sickness and to treat Parkinson's disease
  • medicines used to treat high blood pressure
  • medicines for diarrhoea, such as kaolin, pectin, and loperamide
  • medicines used to treat depression
  • monoamine oxidase inhibitors, medicines used to treat depression, taken within the last 14 days
  • other opioid analgesics used to treat pain
  • quinidine, a medicine used to treat abnormal or irregular heart beat
  • phenothiazines and antipsychotic agents, medicines used to treat mental disorders
  • chloramphenicol, an antibiotic used to treat ear and eye infections
  • flucloxacillin, zidovudine or rifampicin, drugs used to treat infections
  • chelating resin
  • buprenorphine
  • naltrexone

These medicines may be affected by Panamax Co or may affect how well Panamax Co works. You may need different amounts of your medicines, or you may need to take different medicines.

Your doctor or pharmacist will have more information on medicines to be careful with or avoid while taking this medicine.

If you have not told your doctor or pharmacist about any of these things, tell him/her before you take any Panamax Co.

How to take Panamax Co

Follow all directions given to you by your doctor or pharmacist carefully.

They may differ from the information contained in this leaflet.

How much to take

The label on your pack of Panamax Co will tell you how to take your medicine and how often.

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

The usual dose of Panamax Co is:

Adults:
1 to 2 tablets.
This dosage may be repeated every 4 - 6 hours if necessary.

You should not take more than 8 tablets in 24 hours.

Do not give Panamax Co to children under 12 years.

Do not take more than the recommended dose.

Talk to your doctor or pharmacist about pain control if Panamax Co is not helping.

If your body cannot metabolise codeine properly, you may be getting reduced benefit from the medicine.

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

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

How long to take it

Adults:

Only take Panamax Co for a few days at a time unless your doctor tells you to take it longer.

Children:

Only give Panamax Co to children for up to 48 hours unless a doctor has told you to give it longer.

How to take it

Swallow tablets with a little water or other liquid.

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 has taken too much Panamax Co.

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, lightheaded, dizzy or drowsy.

While you are taking it

Things you must do

Tell all the doctors, dentists and pharmacists who are treating you that you are taking Panamax Co.

Talk to your doctor or pharmacist if your symptoms don't improve.

Your pharmacist or doctor will assess your condition and decide if you should continue to take the medicine.

If you are about to be started on any new medicine, tell your doctor and pharmacist that you are taking Panamax Co.

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

Things you must not do

Children:

Do not give Panamax Co for more than 48 hours unless a doctor has told you to.

Adults:

Do not take for more than a few days at a time unless your doctor tells you to.

Do not drink alcohol while taking Panamax Co.

Drinking alcohol while taking paracetamol (which is contained in Panamax Co) may increase the risk of liver side effects.

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

Do not take Panamax Co to treat any other complaints unless your doctor or pharmacist tells you to.

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

Things to be careful of

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

This medicine may cause dizziness or light-headedness in some people.

Be careful if you are elderly, unwell or taking other medicines.

Some people may experience side effects such as drowsiness, confusion, dizziness and unsteadiness, which may increase the risk of a fall.

Side Effects

Tell your doctor or pharmacist as soon as possible if you do not feel well while taking Panamax Co.

This medicine helps most people with pain and fever, but it may have unwanted side effects in a few people. All medicines can have side effects. Sometimes they are serious, most of the time they are not. You may need medical attention if you get some of the side effects.

Do not be alarmed by the following list of side effects.

You may not experience any of them.

Ask your doctor or pharmacist to answer any questions you may have.

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

  • nausea
  • vomiting
  • stomach pain
  • constipation
  • dizziness
  • drowsiness

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:

  • shallow breathing or shortness of breath
  • unusual or extreme mood swings
  • dizziness, light-headedness
  • flushing of the face
  • fast heart beat
  • sweating
  • painful red areas with blisters and peeling layers of skin which may be accompanied by fever and/or chills
  • loss of appetite, itching, yellowing of the skin and eyes, light coloured bowel motions, dark coloured urine.

The above list includes serious side effects that may require medical attention. These side effects are rare.

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

  • wheezing or difficulty breathing
  • swelling of the face, lips, tongue or other parts of the body
  • severe blisters and bleeding in the lips, eyes, mouth, nose and genitals
  • skin rashes

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

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

Other side effects not listed above may also occur in some people.

After taking Panamax Co

Storage

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

Keep Panamax Co in a cool, dry place where the temperature stays below 25°C.

Do not store Panamax Co or any other medicine in the bathroom or near a sink. Do not leave it on a window sill or in the car. Heat and dampness can destroy some medicines.

Keep Panamax Co 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

Ask your pharmacist what to do with any tablets left over, or if the expiry date has passed.

Product Description

What it looks like

Panamax Co comes as a white tablet marked 'PANAMAX CO'.

Panamax Co tablets are supplied in packs of 40 & 50 tablets. The 50 pack size is available on prescription only.

Ingredients

Active Ingredient:
Panamax Co tablets contain 500 mg of paracetamol and 8 mg of codeine phosphate hemihydrate

Inactive Ingredients:

  • Starch-maize
  • Starch- soluble maize
  • Cellulose- microcrystalline
  • Talc-purified
  • Stearic acid
  • Povidone
  • Magnesium stearate
  • Potassium sorbate

Panamax Co does not contain gluten, lactose, sucrose, tartrazine or any azo dyes.

Manufacturer

Panamax Co tablets are supplied by:

sanofi-aventis australia pty ltd
12-24 Talavera Road
Macquarie Park NSW 2113

AUST R 62661

This leaflet was prepared in September 2017

panamax-co-ccsiv1-cmiv13-26sept17

BRAND INFORMATION

Brand name

Panamax Co Tablets

Active ingredient

Codeine phosphate hemihydrate; Paracetamol

Schedule

S4

 

1 Name of Medicine

Paracetamol and codeine phosphate hemihydrate.

6.7 Physicochemical Properties

Chemical structure.


Paracetamol. MW: 151.17.
Codeine phosphate hemihydrate. MW: 406.37.

CAS number.

CAS: 103-90-2 (paracetamol). CAS: 41444-62-6 (codeine phosphate hemihydrate).

2 Qualitative and Quantitative Composition

Each tablet contains: paracetamol 500 mg, codeine phosphate hemihydrate 8 mg.

Excipients with known effect.

Potassium sorbate.
For the full list of excipients, see Section 6.1 List of Excipients.

3 Pharmaceutical Form

Tablets (white, scored, marked PANAMAX CO).

5 Pharmacological Properties

5.1 Pharmacodynamic Properties

Mechanism of action.

Analgesic and antipyretic.
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 (45-55%) or sulfate (20-30%). A minor proportion (less than 20%) is metabolised to catechol derivatives, and mercapturic acid compounds via oxidation. Paracetamol is metabolised differently by infants and children compared to adults, the sulfate conjugate being predominant. Patients who metabolise drugs poorly via CYP2D6 are likely to obtain reduced benefit from codeine due to reduced formation of the active metabolite.

Excretion.

Paracetamol is excreted in the urine mainly as the glucuronide and sulfate conjugates. Less than 5% is excreted as unchanged paracetamol with 85-90% of the administered dose eliminated in the urine within 24 hours of ingestion. The elimination half-life varies from 1 to 4 hours.
Codeine 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.

No data available.

4 Clinical Particulars

4.1 Therapeutic Indications

For the relief of acute moderate pain.

4.3 Contraindications

Panamax Co must not be used in patients with known hypersensitivity to paracetamol, codeine or any of the excipients used in this product. It must not be used in patients with known glucose-6-phosphate-dehydrogenase deficiency, patients with severe hepatocellular insufficiency, or pre-existing respiratory depression, for example acute asthma, acute exacerbations of chronic obstructive pulmonary disease since codeine may exacerbate the condition.
Panamax Co is contraindicated for use in patients who are:
CYP2D6 ultra-rapid metabolisers (see Section 4.4 Special Warnings and Precautions for Use, CYP2D6 metabolism);
younger than 12 years (see Section 4.4 Special Warnings and Precautions for Use, Paediatric use);
aged between 12-18 years in whom respiratory function might be compromised including post tonsillectomy and/or adenoidectomy to treat 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);
breast-feeding (see Section 4.6 Fertility, Pregnancy and Lactation, Use in lactation).
Codeine is contraindicated in the event of impending childbirth or in case of risk of premature birth.

4.4 Special Warnings and Precautions for Use

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

To avoid the risk of overdose.

Check that paracetamol is absent from the composition of other medicinal products taken concomitantly.
Caution is advised in patients with underlying sensitivity to aspirin and/or to nonsteroidal anti-inflammatory drugs (NSAIDs).

Severe cutaneous adverse reactions (SCARs).

Life threatening cutaneous reactions Stevens-Johnson syndrome (SJS), and Toxic Epidermal Necrolysis (TEN) have been reported with the use of paracetamol. 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 the following.

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); chronic alcohol use including recent cessation of alcohol intake; low glutathione reserves; Gilbert's syndrome.
Codeine must be administered with caution in certain patients such as those who present with impaired cardiac, hepatic or renal function, hypotension, benign prostatic hyperplasia, urethral stenosis, adrenal insufficiency (Addison's disease), hypothyroidism, multiple sclerosis, chronic colitis ulcerative, gallbladder conditions and diseases that present with reduced respiratory capacity such as emphysema, kyphoscoliosis and severe obesity.
Patients who have had a cholecystectomy should be treated with caution. The contraction of the sphincter of Oddi can cause symptoms resembling those of myocardial infarction or intensify the symptoms in patients with pancreatitis.
Codeine should be used with caution in patients with convulsive disorders.
Extensive use of analgesics to relieve headaches or migraines, especially at high doses, may induce headaches that must not be treated with increased doses of the drug. In such cases the analgesic should not continue to be taken without medical advice.
Codeine, consumed in higher doses and over a prolonged period, may cause addiction.
Codeine has a primary potential for dependence. Tolerance, psychological and physical dependence develop with prolonged use of high doses with withdrawal symptoms after sudden discontinuation of the drug. Cross-tolerance with other opioids exists. Rapid relapses can be expected in patients with pre-existing opiate dependence (including those in remission).
Administration must be discontinued gradually after prolonged treatments.
Monitoring after prolonged use should include blood count, liver function and renal function.
Codeine should only be used after careful risk-benefit assessment in case of:
Opioid dependence.
Chronic constipation.
Conditions with elevated intracranial pressure and head trauma. Codeine can increase the pressure of cerebrospinal fluid and may increase the respiratory depressant effect. Like other narcotics, it causes adverse reactions that can obscure the clinical course of patients with head injury.
Impaired consciousness.
Compromised respiratory function (due to emphysema, kyphoscoliosis, severe obesity) and chronic obstructive airway disease.
Codeine should be used with caution in patients with CNS depression or decreased respiratory reserve. Prolonged use of high doses of codeine may produce dependence.
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).
Patients with known analgesic intolerance or known bronchial asthma must only use Panamax Co after having consulted a physician (hypersensitivity reactions including bronchospasm possible).

CYP2D6 metabolism.

Panamax Co is contraindicated for use in patients who are CYP2D6 ultra-rapid metabolisers.
Codeine is metabolised by the liver enzyme CYP2D6 into morphine, its active metabolite. If a patient has a deficiency or is completely lacking this enzyme an adequate analgesic effect will not be obtained.
However, if the patient is an extensive or ultra-rapid metaboliser, there is an increased risk of developing 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 CYP 2D6 in children is not known, but is assumed to be similar to that reported in adults. The prevalence of ultra-rapid metabolisers differs according to racial and ethnic group. It 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.)
Codeine is not recommended for use in children in whom respiratory function might be compromised.

Risks from concomitant use of opioids and benzodiazepines.

Concomitant use of opioids, including codeine, with benzodiazepines may result in sedation, respiratory depression, coma and death. Because of these risks, reserve concomitant prescribing of opioids and benzodiazepines for use in patients for whom alternative treatment options are inadequate.
If a decision is made to prescribe codeine concomitantly with benzodiazepines, prescribe the lowest effective dosages and minimum durations of concomitant use, and follow patients closely for signs and symptoms of sedation and respiratory depression (see Section 4.5 Interactions with Other Medicines and Other Forms of Interactions).
Patients should be advised to first consult their healthcare professional before taking codeine if they are taking a benzodiazepine (see Section 4.5 Interactions with Other Medicines and Other Forms of Interactions).

Risks from concomitant use of opioids and alcohol.

Concomitant use of opioids, including codeine, with alcohol may result in sedation, respiratory depression, coma and death. Concomitant use with alcohol is not recommended (see Section 4.5 Interactions with Other Medicines and Other Forms of Interactions).

Use in hepatic impairment.

Panamax Co should be administered with caution to patients with hepatic dysfunction.

Use in renal impairment.

Panamax Co should be administered with caution to patients with renal dysfunction.

Use in the elderly.

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

Paediatric use.

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

Effects on laboratory tests.

Uric acid and blood glucose.

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

4.5 Interactions with Other Medicines and Other Forms of Interactions

Paracetamol may increase the risk of bleeding in patients taking warfarin and other antivitamin K. Anticoagulant dosage may require reduction and patients should be monitored for appropriate coagulation and bleeding complications.
Paracetamol absorption is increased by drugs which increase gastric emptying, e.g. metoclopramide or domperidone, and decreased by drugs which decrease gastric emptying, e.g. propantheline, antidepressants with anticholinergic properties, narcotic analgesics. Paracetamol may increase chloramphenicol concentrations. 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), hypnotics, rifampicin and alcohol.
When used concurrently with zidovudine, an increased tendency for neutropenia may develop. Combination of Panamax Co and zidovudine should be avoided.
Chelating resin can decrease the intestinal absorption of paracetamol and potentially decrease its efficacy if taken simultaneously. In general, there must be an interval of more than 2 hours between taking the resin and taking paracetamol, if possible.
Co-administration of flucloxacillin with paracetamol may lead to metabolic acidosis, particularly in patients presenting risk factors of glutathione depletion, such as sepsis, malnutrition or chronic alcoholism.
Concurrent administration of sedatives or tranquillisers may enhance the potential respiratory depressant effects of codeine.
Patients receiving other narcotic analgesics, antitussives, antihypertensives, antihistamines, antipsychotics, antianxiety agents or other CNS depressants (including alcohol) concomitantly with this codeine-containing drug may exhibit additive CNS depression.
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).
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).
A codeine-induced respiratory depression can be potentiated by tricyclic antidepressants.
Concomitant administration of monoamine oxidase inhibitors (MAOIs) can potentiate the central nervous effects and other side effects of unpredictable severity. Codeine should not be used within two weeks after the discontinuation of MAOI treatment.
Concomitant use of codeine with antiperistaltic antidiarrhoeal drugs can increase the risk of severe constipation and CNS depression.

Morphinic agonists-antagonists.

Concomitant use of codeine with a partial agonist (e.g. buprenorphine) or antagonist (e.g. naltrexone) can precipitate or delay codeine effects.

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.

4.6 Fertility, Pregnancy and Lactation

Effects on fertility.

No data available.
(Category A)
There are no indications of a connection between the occurrences of malformations in newborn infants and the use of paracetamol within the recommended dose range during the first four months of pregnancy. During pregnancy, however, the patient is requested to use Panamax Co only after a thorough assessment of possible risks and benefits by the physician. If Panamax Co is administered during pregnancy, morphinomimetic properties of codeine should be taken into account. 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 Panamax Co should be avoided during the third trimester of pregnancy and during labour.
Panamax Co is contraindicated during breast-feeding (see Section 4.3 Contraindications; Section 4.4 Special Warnings and Precautions for Use, CYP2D6 metabolism) due to risk of respiratory depression in the infant. Paracetamol and codeine is excreted into human breast milk. Analgesic doses excreted in breast milk are generally low. However, infants of breastfeeding mothers taking codeine may have an increased risk of morphine overdose if the mother is an ultra-rapid metaboliser of codeine. Codeine is excreted into human breast milk. Codeine is partially metabolized by cytochrome P450 2D6 (CYP2D6) into morphine, which is excreted into breast milk. If nursing mothers are CYP2D6 ultrarapid metabolisers, higher levels of morphine may be present in their breast milk. This may result in symptoms of opioid toxicity in both mother and the breast-fed infant. Life-threatening adverse events or neonatal death may occur even at therapeutic doses (see Section 4.4 Special Warnings and Precautions for Use, CYP2D6 metabolism).
Therefore, Panamax Co is contraindicated for use during breastfeeding. However, in circumstances where a breastfeeding mother requires codeine therapy, breastfeeding should be suspended and alternative arrangements should be made for feeding the infant for any period during codeine treatment. Breastfeeding mothers should be told how to recognise signs of high morphine levels in themselves and their babies. For example, in a mother, symptoms include extreme sleepiness and trouble caring for the baby. In the baby, symptoms include signs of increased sleepiness (more than usual), difficulty breastfeeding, breathing difficulties or limpness. Medical advice should be sought immediately.

4.8 Adverse Effects (Undesirable Effects)

Paracetamol.

Reports of adverse reactions are rare. Although the following reactions have been reported, a causal relationship to the administration of paracetamol has been neither confirmed nor refuted: dyspepsia, sweating, erythema, urticaria, anaphylactic shock, angioneurotic oedema, difficulty breathing, drop in blood pressure, nausea, allergic reactions such as skin rashes and haematological reactions, including thrombocytopenia, leukopenia, neutropenia, agranulocytosis and pancytopenia. Bronchospasm may be triggered in patients having a tendency of analgesic asthma. Toxic epidermal necrolysis (TEN), Stevens-Johnson syndrome (SJS), acute generalised exanthematous pustulosis, fixed drug eruption (see Section 4.4 Special Warnings and Precautions for Use) and cytolytic hepatitis, which may lead to acute hepatic failure, have also been reported.
Haemolytic anaemia, particularly in patients with underlying glucose 6-phosphate-dehydrogenase deficiency has been reported. Kounis syndrome and bronchospasm have also been reported.

Codeine.

Nausea and vomiting, constipation, dizziness and drowsiness have been reported at therapeutic doses. Very rarely, skin rashes may occur in patients hypersensitive to codeine. There have also been very rare reports of pancreatitis. Other adverse reactions reported to be associated with codeine include: confusional state, dysphoria, euphoria, seizure, headache, somnolence, fatigue, hypotension, sedation, respiratory depression, dry mouth, pruritus, miosis, tinnitus and urinary retention. Visuomotor coordination and visual acuity may be adverse affected in a dose-dependent manner at higher doses or in particularly sensitive patients. Long term use also entails the risk of drug dependence.

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.

4.2 Dose and Method of Administration

Adults and children 12 years of age and older.

1 to 2 tablets (maximum 8 tablets per day).
To be taken with water; repeat every 4-6 hours if necessary.
Use in children under 12 years is contraindicated.

4.7 Effects on Ability to Drive and Use Machines

Panamax Co may cause drowsiness, disturbances of visuomotor coordination and visual acuity. 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 whilst taking this medication.

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 10 to 15 g (30 tablets) of paracetamol; 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.
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.

Despite lack of significant early symptoms, patients should be referred to hospital urgently for immediate medical attention.
Consists primarily of management of paracetamol toxicity; naloxone is the treatment of choice for codeine intoxication.
Determinations of the plasma concentration of paracetamol are recommended.
Plasma concentration of paracetamol should be measured at 4 hours or later after ingestion (earlier concentrations are unreliable).
Where paracetamol intoxication is suspected, intravenous administration of SH group donators such as acetylcysteine within the first 10 hours after ingestion is indicated. Although acetylcysteine is most effective if initiated within this period, it can still offer some degree of protection if given as late as 48 hours after ingestion; in this case it is taken for longer.
In cases of overdosage, methods of reducing the absorption of ingested drug are important.
Gastric lavage is essential even if several hours have elapsed. Prompt administration of 50 g activated charcoal and 500 mL iced mannitol 20% by mouth may reduce absorption.
If the history suggests that 15 g paracetamol or more has been ingested, administer one of the following antidotes:

Acetylcysteine 20% i.v.

Administer 20% acetylcysteine (Parvolex, David Bull) immediately without waiting for positive urine test or plasma level results: initial dose 150 mg/kg over 15 minutes, followed by continuous infusion of 50 mg/kg in 500 mL 5% glucose over 4 hours and 100 mg/kg in 1 L 5% glucose over 16 hours or;

Oral methionine.

2.5 g immediately followed by three further doses of 2.5 g at four hourly intervals. For a 3 year old child, 1 g methionine 4-hourly for four doses has been used.
If more than ten hours have elapsed since the overdosage was taken, the antidote may be ineffective.

Relating to codeine component.

In general, treatment should be symptomatic: re-establish adequate respiratory exchange by ensuring a clear airway and using mechanical ventilation. When treatment for paracetamol toxicity has been initiated the opioid antagonist naloxone hydrochloride is an antidote to respiratory depression; naloxone 400 microgram may be administered SC, IM or IV; IV may be repeated at intervals of 2 to 3 minutes if necessary. Assisted respiration may be required.
Further measures will depend on the severity, nature and course of clinical symptoms of intoxication and should follow standard intensive care protocols.
For information on the management of overdose contact the Poisons Information Centre on 131126 (Australia).

7 Medicine Schedule (Poisons Standard)

S4.

6 Pharmaceutical Particulars

6.1 List of Excipients

Other ingredients are maize starch, povidone, potassium sorbate, microcrystalline cellulose, stearic acid, magnesium stearate, purified talc and pregelatinised maize starch.

6.2 Incompatibilities

Incompatibilities were either not assessed or not identified as part of the registration of this medicine.

6.3 Shelf Life

In Australia, information on the shelf life can be found on the public summary of the Australian Register of Therapeutic Goods (ARTG). The expiry date can be found on the packaging.

6.4 Special Precautions for Storage

Store below 25°C.

6.5 Nature and Contents of Container

Tablets, 40s.

6.6 Special Precautions for Disposal

In Australia, any unused medicine or waste material should be disposed of by taking to your local pharmacy.

Summary Table of Changes