FULL CMI

CODRAL Original Day & Night + Dry Cough

Active ingredient(s): Paracetamol and Pseudoephedrine hydrochloride, Dextromethorphan hydrobromide monohydrate and Chlorphenamine maleate

Consumer Medicine Information (CMI)

This leaflet provides important information about using CODRAL Original Day & Night + Dry Cough. You should also speak to your doctor or pharmacist if you would like further information or if you have any concerns or questions about using CODRAL Original Day & Night + Dry Cough.

Where to find information in this leaflet:

1. Why am I using CODRAL Original Day & Night + Dry Cough?
2. What should I know before I use CODRAL Original Day & Night + Dry Cough?
3. What if I am taking other medicines?
4. How do I use CODRAL Original Day & Night + Dry Cough?
5. What should I know while using CODRAL Original Day & Night + Dry Cough?
6. Are there any side effects?
7. Product details

1. Why am I using CODRAL Original Day & Night + Dry Cough?

CODRAL Original Day & Night + Dry Cough contains the active ingredients Paracetamol and Pseudoephedrine hydrochloride, Dextromethorphan hydrobromide monohydrate and Chlorphenamine maleate. Paracetamol is an analgesic. It works to stop the pain messages from getting through to the brain. It also acts in the brain to reduce fever. Pseudoephedrine hydrochloride belongs to a group of medicines called sympathomimetic decongestants. It works by reducing congestion in the upper respiratory tract, including the nose, nasal passages and sinuses, and making it easier to breathe. Dextromethorphan is a cough suppressant that acts on the cough centre in the brain to suppress a dry cough. Chlorphenamine belongs to a group of medicines called 'antihistamines'. Antihistamines help reduce allergic symptoms by preventing the effects of a substance called histamine. Histamine is produced by the body in response to foreign substances that the body is allergic to.

CODRAL Original Day & Night + Dry Cough is used for the temporary relief from the symptoms of cold and flu. 'Day' capsules temporarily relieve headaches, body aches and pains, blocked nose, fever and dry irritated coughs without causing drowsiness. 'Night' capsules temporarily relieve headaches, body aches and pains, blocked nose, fever and dry irritated coughs and a runny nose.

2. What should I know before I use CODRAL Original Day & Night + Dry Cough?

Warnings

Do not use CODRAL Original Day & Night + Dry Cough if:

• you are allergic to Paracetamol, Pseudoephedrine hydrochloride, Dextromethorphan hydrobromide monohydrate, Chlorphenamine maleate or other antihistamines, or any of the ingredients listed at the end of this leaflet.
  Always check the ingredients to make sure you can use this medicine.
• you are younger than 12 years
• have very high blood pressure
• have severe coronary artery disease (heart disease caused by poor blood flow or narrowing of the blood vessels of the heart)
• have taken other products containing paracetamol
• have taken antihistamines
• have taken monoamine oxidase inhibitors, medicines used to treat depression, in the last 14 days.

Check with your doctor or pharmacist if you:

• have any other medical conditions
  - respiratory conditions (such as asthma, chronic obstructive airway disease, chronic cough, excessive secretions or pneumonia)
  - high blood pressure
  - overactive thyroid gland
  - diabetes
  - heart disease and poor blood flow in the blood vessels of the heart
  - glaucoma (high pressure in the eyes)
  - prostate problems
  - bladder problems
  - liver or kidney disease
  - alcohol dependence
  - epilepsy
• take sedatives
• take any medicines for any other condition

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

Pregnancy and breastfeeding

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

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

Small amounts of pseudoephedrine pass into the breast milk. Your pharmacist or doctor will discuss the potential benefits and risks of taking the medicine if you are breastfeeding.

3. What if I am taking other medicines?

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

Some medicines may interfere with CODRAL Original Day & Night + Dry Cough and affect how it works.

These include

• medicines used to treat depression especially monoamine oxidase inhibitors and tricyclic antidepressants
• medicines used to treat heart conditions
• medicines used to treat high blood pressure
• medicines used to treat urinary tract infections and bladder problems
• quinidine and amiodarone, medicines used to treat abnormal or irregular heart beat
• medicines used to treat behavioral disorders
• phenylephrine, a medicine used to treat congestion
• appetite suppressants
• warfarin, a medicine used to prevent blood clots
• metoclopramide, a medicine used to control nausea and vomiting
• medicines used to treat epilepsy or fits
• chloramphenicol, an antibiotic used to treat ear and eye infections
• alcohol
• medicines used to help you sleep or relax (sedatives and hypnotics)
• opioid analgesics, medicines used to treat pain
• flucloxacillin, an antibiotic used to treat skin infections.

You may need different amounts of your medicines, or you may need to take different medicines.

Check with your doctor or pharmacist if you are not sure about what medicines, vitamins or supplements you are taking and if these affect CODRAL Original Day & Night + Dry Cough.

4. How do I use CODRAL Original Day & Night + Dry Cough?

How much to take

• The recommended dose of CODRAL Day & Night + Dry Cough for adults and children over 12 years is
  Day time: 2 Day capsules every 4-6 hours
  Night time: 2 Night capsules at night time as necessary
• Follow the instructions provided with the medicine.
• Do not exceed 6 day capsules and 2 night capsules in 24 hours.
• Do not exceed the recommended dosage.

When to take CODRAL Original Day & Night + Dry Cough

• Day capsules should be used every 4 to 6 hours as necessary.
• Night capsules should be taken at night time as necessary.

How to take CODRAL Original Day & Night + Dry Cough

• Swallow the tablets whole.
• Do not use for more than a few days at a time except on medical advice.
• Follow all directions given to you by your pharmacist or doctor carefully. This may differ from the information contained in this leaflet.
• If you forget to take it and it is almost time for your next dose, skip the dose you missed and take your next dose when you are meant to. Otherwise, you may take a dose as soon as you remember if you think you need it. Do not take a double dose to make up for the dose that you missed.
• If you do not understand the instructions on the pack, ask your pharmacist or doctor for help.

If you use too much CODRAL Original Day & Night + Dry Cough

If you think that you have used too much CODRAL Original Day & Night + Dry Cough, you may need urgent medical attention.

You should immediately:

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

You should do this even if there are no signs of discomfort or poisoning.

5. What should I know while using CODRAL Original Day & Night + Dry Cough?

Things you should do

Stop use and talk to your doctor or pharmacist if your symptoms persist, worsen, or if new symptoms occur. Your doctor or pharmacist will assess your condition and decide if you should continue to take the medicine.

Remind any doctor, dentist or pharmacist you visit that you are using CODRAL Original Day & Night + Dry Cough.

Things you should not do

• Do not take CODRAL Original Day & Night + Dry Cough to treat any other complaints unless your pharmacist or doctor tells you to.
• Do not give your medicine to anyone else, even if they have the same condition as you.
• Do not take more than the recommended dose unless your pharmacist or doctor tells you to.

Driving or using machines

Be careful before you drive or use any machines or tools until you know how CODRAL Original Day & Night + Dry Cough affects you.

CODRAL Original Day & Night + Dry Cough may cause dizziness in some people.

If this happens, do not drive or operate machinery.

Drinking alcohol

Tell your doctor or pharmacist if you drink alcohol.

Do not drink alcohol while taking CODRAL Original Day & Night + Dry Cough. The sedative effects of alcohol may be increased.

Looking after your medicine

• Keep your medicine in the original pack until it is time to take.
• Keep your medicine in a cool dry place where the temperature stays below 25°C.

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

Store it in a cool dry place away from moisture, heat or sunlight; for example, do not store it:

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

Keep it where young children cannot reach it.

Getting rid of any unwanted medicine

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

Do not use this medicine after the expiry date.

6. Are there any side effects?

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

See the information below and, if you need to, ask your doctor or pharmacist if you have any further questions.

Less serious side effects

Serious side effects

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

Other side effects not listed here may occur in some people. Children and people over 65 years if age may have an increased chance of getting side effects.

Reporting side effects

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

7. Product details

This medicine is available over-the-counter without a doctor's prescription.

What CODRAL Original Day & Night + Dry Cough contains

Day Capsules

Night Capsules

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

What CODRAL Original Day & Night + Dry Cough looks like

Day capsules are blue green/white opaque hard gelatin capsules, printed "Day" in black.

Night capsules are reddish orange/white opaque hard gelatin capsules, printed "Night" in black.

(Aust R 73421).

Who distributes CODRAL Original Day & Night + Dry Cough

Johnson & Johnson Pacific
45 Jones Street
Ultimo NSW 2007
Australia
Phone: 1800 029979

This leaflet was prepared in February 2022.

Published by MIMS June 2022

1 Name of Medicine

Paracetamol, pseudoephedrine hydrochloride, dextromethorphan hydrobromide monohydrate, chlorphenamine maleate.

2 Qualitative and Quantitative Composition

Codral Original Day & Night + Dry Cough capsules contain two separate formulations: day capsules and night capsules.
Each day capsule contains paracetamol 500 mg, pseudoephedrine hydrochloride 30 mg, dextromethorphan hydrobromide monohydrate 10 mg.
Each night capsule contains paracetamol 500 mg, chlorphenamine maleate 2 mg, dextromethorphan hydrobromide monohydrate 10 mg.
Day and Night capsules also contain lactose.
For the full list of excipients, see Section 6.1 List of Excipients.

3 Pharmaceutical Form

The day capsules are blue green/white opaque hard gelatin with 'Day' printed in black.
The night capsules are reddish orange/white opaque hard gelatin with 'Night' printed in black.

4 Clinical Particulars

4.1 Therapeutic Indications

Codral Original Day & Night + Dry Cough provide temporary relief of cold and flu symptoms. The day capsules temporarily relieve headache, body aches and pains, blocked nose, fever and dry irritated coughs without causing drowsiness. The night capsules temporarily relieve headache, body aches and pains, blocked nose, fever and dry irritated coughs and a runny nose.

4.2 Dose and Method of Administration

The recommended dosage of Codral Original Day & Night + Dry Cough capsules for adults and children over 12 years is:
Day dosage: take one or two green capsules in the morning, at midday and in the afternoon as required.
Night dosage: take one or two red capsules at bedtime as required.
Each dose should be taken at least 4 to 6 hours apart. Do not exceed four doses in 24 hours.

Use in adults.

Use in children.

4.3 Contraindications

Paracetamol is contraindicated for use in patients with known hypersensitivity or idiosyncratic reaction to paracetamol (or any of the other ingredients in the product).
Pseudoephedrine is contraindicated for use in patients:
with known hypersensitivity or idiosyncratic reaction to pseudoephedrine (or any of the other ingredients in the product);
with severe hypertension or coronary artery disease;
taking monoamine oxidase inhibitors (MAOIs) or who have taken MAOIs within the previous 14 days.
Dextromethorphan is contraindicated for use in patients:
with known hypersensitivity or idiosyncratic reaction to dextromethorphan (or any of the other ingredients in the product);
taking monoamine oxidase inhibitors (MAOIs) or who have taken MAOIs within the previous 14 days.
Chlorphenamine is contraindicated for use in patients with:
a history of hypersensitivity to the substance or substances of similar chemical structure (or any of the other ingredients in the product);
narrow-angle glaucoma;
stenosing peptic ulcer;
symptomatic prostatic hypertrophy;
bladder neck obstruction;
pyloroduodenal obstruction.
Chlorphenamine is contraindicated for use in:
newborns or premature infants;
lactating women;
patients taking monoamine oxidase inhibitors (MAOIs).

4.4 Special Warnings and Precautions for Use

Identified precautions.

Use in hepatic impairment.

Use in renal impairment.

Use in the elderly.

Paediatric use.

Effects on laboratory tests.

4.5 Interactions with Other Medicines and Other Forms of Interactions

The following interactions with paracetamol have been noted:
anticoagulant drugs (warfarin) - dosage may require reduction if paracetamol and anticoagulants are taken for a prolonged period of time;
paracetamol absorption is increased by substances that increase gastric emptying, e.g. metoclopramide;
paracetamol absorption is decreased by substances that decrease gastric emptying, e.g. propantheline, antidepressants with anticholinergic properties, and 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 alcohol and anticonvulsant agents;
paracetamol excretion may be affected and plasma concentrations altered when given with probenecid;
colestyramine reduces the absorption of paracetamol if given within 1 hour of paracetamol;
high anion gap metabolic acidosis from pyroglutamic acid (5-oxoprolinemia) has been reported with concomitant use of therapeutic doses of paracetamol and flucloxacillin. Patients reported to be most at risk are elderly females with underlying disease such as sepsis, renal function abnormality, and malnutrition.
The following interactions with pseudoephedrine have been noted:
antidepressant medication, e.g. tricyclic antidepressants and monoamine oxidase inhibitors (MAOIs), may cause a serious increase in blood pressure or hypertensive crisis;
other sympathomimetic agents, such as decongestants, appetite suppressants and amphetamine-like psychostimulants, may cause an increase in blood pressure and additive effects;
methyldopa and β-blockers may cause an increase in blood pressure;
urinary acidifiers enhance elimination of pseudoephedrine;
urinary alkalinisers decrease elimination of pseudoephedrine.
The following interactions with dextromethorphan have been noted:
Dextromethorphan should not be used in patients taking monoamine oxidase inhibitors (MAOIs) or who have taken MAOIs within the previous 14 days. The use of dextromethorphan with, or within two weeks of taking, MAOIs may increase the risk of serious side effects such as hypertensive crisis, hyperpyrexia and convulsions.
Dextromethorphan when used with SSRIs (such as fluoxetine) or tricyclic antidepressants (such as clomipramine and imipramine) may result in a "serotonin syndrome" with changes in mental status, hypertension, restlessness, myoclonus, hyper-reflexia, diaphoresis, shivering and tremor.
Serum levels of dextromethorphan may be increased by the concomitant use of inhibitors of cytochrome P450 2D6, such as the antiarrhythmics quinidine and amiodarone, antidepressants such as fluoxetine and paroxetine, or other drugs which inhibit cytochrome P450 2D6 such as haloperidol and thioridazine.
Metoprolol is a CYP2D6 substrate and metabolism of dextromethorphan has been shown to be prolonged when the two drugs are administered concomitantly.
Isavuconazole is a moderate inhibitor of CYP3A4 and a mild inducer of CYP2B6. When administered concomitantly with dextromethorphan, the AUC and C_max of dextromethorphan has been observed to increase by 18% and 17%, respectively.
Concomitant use of dextromethorphan with SSRI agents may lead to Serotonin Syndrome.
Concomitant use of dextromethorphan and other CNS depressants (e.g. alcohol, narcotic analgesics and tranquillizers) may increase the CNS depressant effects of these drugs.
The following interactions with chlorphenamine have been noted:
CNS depressants (alcohol, sedatives, opioid analgesics, hypnotics) may cause an increase in sedation effects;
monoamine oxidase inhibitors (MAOIs) and tricyclic antidepressants (TCAs) may prolong and intensify the anticholinergic and CNS depressive effects;
when taken concomitantly with phenytoin may cause a decrease in phenytoin elimination.

4.6 Fertility, Pregnancy and Lactation

Effects on fertility.

4.7 Effects on Ability to Drive and Use Machines

Chlorphenamine may cause drowsiness and may increase the effects of alcohol. Drowsiness may continue the following day. Those affected should not drive or operate machinery; alcohol should be avoided.

4.8 Adverse Effects (Undesirable Effects)

Side effects of paracetamol are rare and usually mild, although haematological reactions have been reported. Skin rashes and hypersensitivity reactions occur occasionally. Overdosage with paracetamol if left untreated can result in severe, sometimes fatal liver damage and, rarely, acute renal tubular necrosis.
Adverse effects of pseudoephedrine include:
cardiovascular stimulation: elevated blood pressure, tachycardia or arrhythmias;
CNS stimulation: restlessness, insomnia, anxiety, tremors and (rarely) hallucinations;
skin rashes and urinary retention.
Children and the elderly are more likely to experience adverse effects than other age groups.
Side effects with usual doses of dextromethorphan are uncommon but may include mild drowsiness, fatigue, dystonias, dizziness and gastrointestinal disturbances (nausea or vomiting, stomach discomfort, or constipation).
Side effects that may occur with high doses (overdosage) of dextromethorphan include excitation, confusion, psychosis, nervousness, irritability, restlessness, "serotonin syndrome", severe nausea and vomiting, and respiratory depression.

Central nervous system (CNS) effects.

Anticholinergic effects.

Post-marketing data.

4.9 Overdose

If an overdose is taken or suspected, immediately contact the Poisons Information Centre (in Australia, call 13 11 26; in New Zealand call 0800 764 766) for advice, or go to a hospital straight away even if you feel well because of the risk of delayed, serious liver damage.
Overdosage with paracetamol if left untreated can result in severe, sometimes fatal liver damage, and rarely, acute renal tubular necrosis.

5 Pharmacological Properties

5.1 Pharmacodynamic Properties

Mechanism of action.

Clinical trials.

5.2 Pharmacokinetic Properties

Paracetamol is readily absorbed from the gastrointestinal tract with peak plasma concentrations occurring about 10 to 60 minutes after oral administration. Paracetamol is distributed into most body tissues. Plasma protein binding is negligible at usual therapeutic doses but increases with increasing doses. The elimination half-life varies from about 1 to 3 hours.
Paracetamol is metabolised extensively in the liver and excreted in the urine mainly as inactive glucuronide and sulfate conjugates. Less than 5% is excreted unchanged. The metabolites of paracetamol include a minor hydroxylated intermediate which has hepatotoxic activity. This intermediate metabolite is detoxified by conjugation with glutathione; however, it can accumulate following paracetamol overdosage (more than 150 mg/kg or 10 g total paracetamol ingested) and if left untreated can cause irreversible liver damage.
Paracetamol is metabolised differently by premature infants, newborns, infants and young children compared to adults, the sulfate conjugate being predominant.
Pseudoephedrine is readily absorbed from the gastrointestinal tract. It is largely excreted unchanged in the urine together with small amounts of its hepatic metabolite. It has a half-life of about 5-8 hours; elimination is enhanced and half-life reduced accordingly in acid urine. Small amounts are distributed into breast milk.
Dextromethorphan is well absorbed from the gastrointestinal tract after oral administration. It is metabolised in the liver, exhibiting polymorphic metabolism involving the cytochrome P450 isoenzyme (CYP2D6). It is excreted in the urine as unchanged dextromethorphan and demethylated metabolites, including dextrorphan, which has some cough suppressant activity. The plasma elimination half-life of dextromethorphan is 1.2 to 3.9 hours. However, the rate of metabolism varies between individuals according to phenotype (extensive v poor metabolisers), with half-life being as long as 45 hours in patients who are poor metabolisers.
Chlorpheniramine maleate is absorbed relatively slowly from the gastrointestinal tract, with peak plasma concentrations occurring about 2.5 to 6 hours after oral administration. Chlorpheniramine appears to undergo considerable first-pass metabolism. Bioavailability is low, values of 25 to 50% having been reported. About 70% of chlorpheniramine in the circulation is bound to plasma proteins. There is wide inter-individual variation in the pharmacokinetics of chlorpheniramine; half-life values ranging from 2 to 43 hours have been reported. Chlorpheniramine is widely distributed in the body and enters the central nervous system (CNS).
Chlorpheniramine is metabolised extensively. Metabolites include desmethyl- and didesmethylchlorpheniramine. Unchanged drug and metabolites are excreted primarily in the urine; excretion is dependent on urinary pH and flow rate. Only trace amounts have been found in the faeces.
A duration of action of 4 to 6 hours has been reported; this is shorter than may be predicted from pharmacokinetic parameters.
More rapid and extensive absorption, faster clearance, and a shorter half-life have been reported in children compared to adults.

5.3 Preclinical Safety Data

Genotoxicity.

Carcinogenicity.

6 Pharmaceutical Particulars

6.1 List of Excipients

Each day capsule contains the following excipients: allura red AC, brilliant blue FCF, gelatin, lactose, magnesium stearate, quinoline yellow, colloidal anhydrous silica, silicon dioxide, sodium lauryl sulfate, purified talc, titanium dioxide, Opacode Black A-10259.
Each night capsule contains the following excipients: allura red AC, brilliant blue FCF, gelatin, lactose, magnesium stearate, colloidal anhydrous silica, silicon dioxide, sodium lauryl sulfate, purified talc, titanium dioxide, Opacode Black A-10259.

6.2 Incompatibilities

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

6.3 Shelf Life

36 months.

6.4 Special Precautions for Storage

Store below 25°C.

6.5 Nature and Contents of Container

Blister packs of 24 capsules (18 Day capsules, 6 Night capsules).

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.

CAS number.

7 Medicine Schedule (Poisons Standard)

Schedule 3.

Summary Table of Changes