Mersyndol^® DayStrength

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

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

Mersyndol DayStrength contains the active ingredients paracetamol and codeine phosphate hemihydrate. Mersyndol DayStrength is used to relieve acute moderate pain and fever.

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

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

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

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

Some medicines may interfere with Mersyndol DayStrength and affect how it works.

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

Adults and children 12 years or over:

• One or two tablets every 3 to 4 hours as needed for relief. Do not take more than 8 caplets in 24 hour period
• More instructions can be found in Section 4. How do I use Mersyndol DayStrength? in the full CMI.

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

Mersyndol DayStrength may be habit forming if taken frequently or over long periods. Tell your doctor or pharmacist if you notice any of the following and they worry you: nausea or vomiting; drowsiness or dizziness; constipation; stomach pain; skin rashes; sweating. For more information, including what to do if you have any side effects, see Section 6. Are there any side effects? in the full CMI.

1 Name of Medicine

Paracetamol, codeine phosphate hemihydrate.

2 Qualitative and Quantitative Composition

Mersyndol DayStrength contains paracetamol 500 mg and codeine phosphate hemihydrate 9.6 mg.
Mersyndol DayStrength is aspirin-free.
For the full list of excipients, see Section 6.1 List of Excipients.

3 Pharmaceutical Form

The caplets are yellow, capsule-shaped tablets with 'Mersyndol' on one side and 'DS' and a breakline on the other.

4 Clinical Particulars

4.1 Therapeutic Indications

For the relief of acute moderate pain and fever.

4.2 Dose and Method of Administration

Adults and children 12 years of age and older.

4.3 Contraindications

Mersyndol DayStrength is contraindicated in patients:
with known hypersensitivity to paracetamol, codeine or any of the excipients used in this product;
with severe respiratory disease, acute respiratory disease and respiratory depression for example an acute asthma attack;
with glucose-6-phosphate-dehydrogenase deficiency;
with severely impaired liver or renal function;
with diarrhoea caused by pseudomembranous colitis or poisoning (until the causative organism or toxin has been eliminated from the gastrointestinal tract, since codeine may slow down the elimination, thereby prolonging the diarrhoea);
with chronic constipation;
with active alcoholism;
during labour when delivery of a premature infant is anticipated as it may produce codeine withdrawal symptoms in neonate;
during breast-feeding (see Section 4.6 Fertility, Pregnancy and Lactation, Use in lactation);
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);
who are CYP 2D6 ultra-rapid metabolisers (see Section 4.4 Special Warnings and Precautions for Use, CYP2D6 metabolism).
Mersyndol DayStrength is contraindicated for use in patients younger than 12 years (see Section 4.4 Special Warnings and Precautions for Use, Paediatric use).

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. This medication may be dangerous when used in large amounts or for long periods. Hepatotoxicity may develop following a dose of 10 g of paracetamol and hepatic failure is known to occur occasionally with the long term use of paracetamol.

To avoid the risk of overdose.

Severe cutaneous adverse reactions (SCARs).

CYP2D6 metabolism.

Hazardous and harmful use.

Respiratory depression.

Risks from concomitant use of benzodiazepines or other CNS depressants, including alcohol.

Use of opioids in chronic (long-term) non-cancer pain (CNCP).

Tolerance, dependence and withdrawal.

Accidental ingestion/exposure.

Hyperalgesia.

Ceasing opioids.

Use in hepatic impairment.

Use in renal impairment.

Use in the elderly.

Paediatric use.

Effects on laboratory tests.

Uric acid and blood glucose.

4.5 Interactions with Other Medicines and Other Forms of Interactions

Patients receiving other opioid analgesics, antitussives, antihypertensives, antihistamines, antipsychotics, antianxiety or other CNS depressants e.g. gabapentinoids, cannabis, centrally-active anti-emetics, hypnotics, sedatives, tranquillisers, including alcohol, may exhibit an additive CNS depression and increases the risk of sedation, respiratory depression, coma and death (see Section 4.4 Special Warnings and Precautions for Use, Risks from concomitant use of benzodiazepines or other CNS depressants, including alcohol).
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.
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).
Concurrent administration or use within 14 days of ceasing monoamine oxidase inhibitors (MAOIs) may enhance the potential respiratory depressant effects of codeine and other side effects of unpredictable severity.
A codeine-induced respiratory depression can be potentiated by tricyclic antidepressants.
Codeine may increase the hypotensive effects of antihypertensive agents.
Other potential interactions with codeine include anticholinergic agents or antidiarrhoeal agents (due to the risk of severe constipation and CNS depression); metoclopramide (as codeine may antagonise the effects of this medicine on gastrointestinal motility); and drugs that can inhibit CYP2D6 such as quinidine, phenothiazines and antipsychotic agents as they can interfere with the metabolism of codeine to morphine, reducing the analgesic effect of codeine.
The risk of paracetamol toxicity may be increased in patients receiving other potentially hepatotoxic drugs or drugs that induce liver microsomal enzymes, such as barbiturates and other antiepileptics (such as phenobarbital, phenytoin, carbamazepine, topiramate), rifampicin and alcohol.
Paracetamol may increase the risk of bleeding in patients taking warfarin and antivitamin K. Patients taking paracetamol and antivitamin K should be monitored for appropriate coagulation and bleeding complications.
Paracetamol may considerably slow down the excretion of chloramphenicol, entailing the risk of increased toxicity. When used concurrently with zidovudine, an increased tendency for neutropenia may develop. Combination of Mersyndol DayStrength and zidovudine should be avoided.
Concurrent intake of drugs, which delay gastric emptying, such as propantheline, may slow down the uptake of paracetamol, thereby retarding its onset of action. Conversely, drugs, which accelerate gastric emptying, such as metoclopramide or domperidone, may accelerate the absorption rate of paracetamol and its onset of action.
Cholestyramine reduces the absorption of paracetamol if given within 1 hour of paracetamol. Paracetamol excretion may be affected and plasma concentrations altered when given with probenecid.
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.

CYP2D6 inhibitors.

CYP3A4 inducers.

4.6 Fertility, Pregnancy and Lactation

Effects on fertility.

4.7 Effects on Ability to Drive and Use Machines

The codeine in Mersyndol DayStrength may cause drowsiness, disturbances of visuomotor coordination and visual acuity, impairing the mental and or physical ability required for the performance of potentially dangerous tasks. Those affected should not drive or operate machinery or engage in activities which require them to be alert.

4.8 Adverse Effects (Undesirable Effects)

Reports of adverse reactions with paracetamol are rare. Dyspepsia, nausea, sweating, anaphylactic shock, angioneurotic oedema, difficulty in breathing, erythema, urticaria, skin rashes, drop in blood pressure, allergic and haematological reactions (thrombocytopenia, neutropenia, leukopenia, anaemia, agranulocytosis and pancytopenia) have been reported. A causal relationship to the administration of paracetamol has not been confirmed. Toxic epidermal necrolysis (TEN), Stevens-Johnson syndrome (SJS), acute generalised exanthematous pustulosis, fixed drug eruption and cytolytic hepatitis, which may lead to acute hepatic failure, have also been reported.
Bronchospasm may be triggered in patients having a tendency of analgesic asthma.
Constipation, dry mouth, nausea and vomiting, dizziness, hypotension and drowsiness may occur in association with codeine. Other side effects are rare, especially at dosage levels provided with Mersyndol DayStrength. These include cough suppression, respiratory depression, confusional state, seizure, headache, somnolence, fatigue, sedation, euphoria, dysphoria, skin rashes, pruritus, histamine release (hypotension, flushing of the face, tachycardia, breathlessness) and other allergic reactions. Long term use also entails the risk of drug dependence.
Tinnitus and miosis have been associated with codeine use. Visuomotor coordination and visual acuity may be adverse affected in a dose-dependent manner at higher doses or in particularly sensitive patients.
Very rarely, skin rashes may occur in patients hypersensitive to codeine. Pancreatitis has been reported very rarely.
Renal failure, uraemia, urinary retention or hesitance have been reported less frequently to rarely when both paracetamol and codeine have been administered.
Haemolytic anaemia, particularly in patients with underlying glucose 6-phosphate-dehydrogenase deficiency has been reported. Kounis syndrome and bronchospasm have also been reported.

Reporting suspected adverse effects.

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.
It has been reported that paracetamol may produce symptoms of acute toxicity in adults, following the ingestion of more than 15 g. Hepatotoxicity may develop after the ingestion of a single dose of 10 to 15 g (200 to 250 mg/kg) and a dose of more than 25 g is potentially fatal. 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. Patients may be asymptomatic for several days following ingestion of large doses of paracetamol and laboratory evidence of hepatotoxicity may be delayed for up to one week. Non-fatal hepatic damage is usually reversible. The antidote, N-acetylcysteine, should be administered as early as possible.
Despite lack of significant early symptoms, patients should be referred to hospital urgently for immediate medical attention.
Determinations of the plasma concentration of paracetamol are recommended.
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 an evaluation of codeine intoxication in children, symptoms ranked by decreasing order of frequency included sedation, rash, miosis, vomiting, itching, ataxia and swelling of the skin. Respiratory failure may occur. Blood concentrations of codeine ranged from 1.4 to 5.6 microgram/mL in eight adults whose deaths were attributed primarily to codeine overdosage.
The ingestion of very high doses of codeine can cause initial excitation, anxiety, insomnia followed by drowsiness in certain cases, areflexia progressing to stupor or coma, headache, miosis, alterations in blood pressure, arrhythmias, dry mouth, hypersensitivity reactions, cold clammy skin, bradycardia, tachycardia, convulsions, gastrointestinal disorders, nausea, vomiting and respiratory depression.
Severe intoxication can lead to apnoea, circulatory collapse, cardiac arrest and death.

Relating to codeine component.

5 Pharmacological Properties

5.1 Pharmacodynamic Properties

Mechanism of action.

Clinical trials.

5.2 Pharmacokinetic Properties

Absorption.

Distribution.

Metabolism.

Excretion.

5.3 Preclinical Safety Data

Genotoxicity.

Carcinogenicity.

6 Pharmaceutical Particulars

6.1 List of Excipients

Mersyndol DayStrength also contains Compap L, sodium starch glycollate, purified talc, magnesium stearate and quinoline yellow (CI 47005).

6.2 Incompatibilities

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

6.3 Shelf Life

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

6.4 Special Precautions for Storage

Store below 30°C.

6.5 Nature and Contents of Container

Mersyndol DayStrength is available as caplets of 24*, 36*, or 40*, each containing paracetamol 500 mg and codeine phosphate hemihydrate 9.6 mg.
* Pack sizes not marketed.

6.6 Special Precautions for Disposal

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

6.7 Physicochemical Properties

Paracetamol is an odourless, crystalline powder or crystals with a bitter taste. Codeine phosphate hemihydrate is an odourless, crystalline powder or small colourless crystals with a bitter taste.

Chemical structure.

CAS number.

7 Medicine Schedule (Poisons Standard)

Prescription Only Medicine (Schedule 4).

Summary Table of Changes