Consumer medicine information

MersynoNight Night Time Pain Relief

Paracetamol; Diphenhydramine hydrochloride

BRAND INFORMATION

Brand name

MersynoNight Night Time Pain Relief

Active ingredient

Paracetamol; Diphenhydramine hydrochloride

Schedule

What is in this leaflet

This leaflet answers some common questions about MersynoNight Night Time Pain Relief. 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 using MersynoNight Night Time Pain Relief against the benefits it is expected to have for you.

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 MersynoNight Night Time Pain Relief is used for

MersynoNight Night Time Pain Relief is used to give temporary relief of pain when associated with sleeping difficulty.

It is useful for headache, migraine, backache, arthritis, rheumatic and muscle pain, neuralgia, toothache or period pain.

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.

Diphenhydramine hydrochloride is an antihistamine that helps you sleep.

Ask your doctor or pharmacist if you have any questions about why this medicine has been prescribed for you.

Your pharmacist or doctor may have given you this for another reason.

This medicine is only available from your pharmacist.

Before you use MersynoNight Night Time Pain Relief

When you must not use it

Do not take MersynoNight Night Time Pain Relief if you have an allergy to:

any medicine containing paracetamol or diphenhydramine hydrochloride
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 MersynoNight Night Time Pain Relief if you have or had any of the following medical conditions:

glaucoma (high pressure in the eyes)
stomach or duodenal ulcer or other stomach problems
prostate problems
bladder problems

Do not take MersynoNight Night Time Pain Relief:

if you are taking monoamine oxidase inhibitors (MAOIs), a type of
medicine used to treat depression.
if you have taken other medicine containing paracetamol in the last 4 hours.
if you are breastfeeding or plan to breastfeed. It passes into the breast milk and there is a possibility that the baby may be affected.

Do not give MersynoNight Night Time Pain Relief:

to newborn or premature babies.
to children under 12 years of age.

Do not take this medicine after the expiry date (EXP) printed on the pack.

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

Do not take this medicine 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 this medicine, talk to your doctor.

Before you start to use it

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

Liver or kidney disease
Epilepsy
Myasthenia gravis (a muscle dysfunction)
Prostate gland enlargement or difficulty urinating
Glaucoma
Asthma
Bronchitis or chronic lung disease
Underweight or malnourished
You regularly drink alcohol; you may need to avoid using this product altogether or limit the amount of paracetamol you take
You have a severe infection as this may increase the risk of metabolic acidosis. Signs of metabolic acidosis include deep rapid difficult breathing, nausea or vomiting. Loss of appetite. Contact a doctor immediately if you get a combination of these symptoms

Tell your pharmacist or doctor if you take sedatives.

Tell your doctor if you are pregnant or plan to become pregnant. Your pharmacist or doctor will discuss the benefits and possible risks of taking the medicine during pregnancy.

If you have not told your pharmacist or doctor about any of the above, tell him/her before you start taking MersynoNight Night Time Pain Relief.

Taking other medicines

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

Some medicines and MersynoNight Night Time Pain Relief may interfere with each other.

These include:

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
Probenecid
Cholestyramine
Medicines used to treat depression, especially monoamine oxidase inhibitors and tricyclic antidepressants
Medicines used to help you sleep or relax (sedatives and hypnotics)
Opioid analgesics, medicines used to treat pain
Other antihistamine medicines including cough and cold medicines and those you use on your skin.
Medicines which make you drowsy or give you a dry mouth (sometimes called anticholinergics). Taking such medicines while you are taking this medicine may increase the chances of side effects.

These medicines may be affected by MersynoNight Night Time Pain Relief or may affect how well it works. You may need different amounts of your medicines, or you may need to take different medicines.

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

This product contains paracetamol. If you are taking any other medicine containing paracetamol, you must make sure you do not take more than 4000mg paracetamol (including this product) in any 24 hour period.

If in doubt, consult your doctor or pharmacist.

How to USE MersynoNight Night Time Pain Relief

Follow all directions given to you by your doctor or pharmacist carefully. They may differ from the information contained in this leaflet.

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

How much to use

Take one or two tablets.

Do not take more than the stated dose.

If you are over 65 years of age, talk to your pharmacist or doctor about how much to use. Elderly patients are more likely to have side effects from taking this medicine. Carers should be aware that this medicine should not be given to elderly patients with confusion.

How to use it

Take with water or other fluid. Take the tablets at bedtime.

How long to use it for

Adults should not take this medicine for more than a few days at a time unless your doctor tells you to take it for longer.

Children aged 12 to 17 years should not take this medicine for more than 48 hours unless on the advice of a doctor.

Children under 12 years of age should not be given MersynoNight Night Time Pain Relief.

If you forget to use it

If you forget to take MersynoNight Night Time Pain Relief at bedtime, you may take it through the night.

Do not take a second dose.

If you are not sure what to do, ask your doctor or pharmacist.

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

If you take too much (overdose)

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

While you are using MersynoNight Night Time Pain Relief

Things you must do

Talk to your pharmacist or doctor if your symptoms do not improve. Your pharmacist or doctor will assess your condition and decide if you should continue to take the medicine.

Use MersynoNight Night Time Pain Relief exactly as your pharmacist or doctor has told you to.

Tell all your doctors, dentists and pharmacists that you are using MersynoNight Night Time Pain Relief.

Things you must not do

Children 12 to 17 years:
Do not give paracetamol 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 use this medicine 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 stated dose unless your doctor tells you to.

Do not drink alcohol while taking MersynoNight Night Time Pain Relief. The sedation effects of alcohol may be increased.

Things to be careful of

This product may cause dizziness, drowsiness, difficulty concentrating or blurred vision.

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

Please see your doctor if your symptoms do not improve.

Keep out of sight and reach of children.

This medicine may cause sleepiness in some people.

If this happens, do not drive or operate machinery.

Side effects

Tell your doctor or pharmacist as soon as possible if you do not feel well while you are taking MersynoNight Night Time Pain Relief.

This medicine helps most people with pain when associated with sleeping difficulty, 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 lists of side effects. You may not experience any of them.

Tell 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 or dyspepsia
drowsiness or sleepiness
dry mouth, nose and throat
constipation
nervousness and irritability
anxiety
hallucinations
twitching or jerking muscles
fast heart beat
tiredness
dizziness
difficulty concentrating
unsteadiness

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:

difficult or painful urination
seizures (fits)

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:

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
previous breathing problems with aspirin or non-steroidal anti-inflammatories, and you experience a similar reaction with this product.
unexplained bruising or bleeding

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 or pharmacist if you notice anything that is making you feel unwell.

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

After using MersynoNight Night Time Pain Relief

Storage

Keep your medicine in the original pack until it is time to take it. If you keep the tablets out of their packaging, they may not keep well.

Keep your medicine in a cool dry place where the temperature stays below 25°C. Protect from moisture.

Do not store MersynoNight Night Time Pain Relief 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 it 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.

Disposal

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

Product description

What it looks like

MersynoNight Night Time Pain Relief is a blue, capsule shaped, film coated tablet debossed with "PD5" on one side and plain on the other side, supplied in blister packs of 20 tablets.

Ingredients

Each MersynoNight Night Time Pain Relief tablet contains 500 mg paracetamol and 25 mg diphenhydramine hydrochloride as active ingredients.

It also contains:

Maize starch
Potassium sorbate
Povidone
Croscarmellose sodium
Purified talc
Stearic acid
Opadry complete film coating system 03F505035 Blue

Supplier

Sanofi Consumer Healthcare
87 Yarraman Place Virgina QLD 4014
Australia

AUST R 301428

This leaflet was prepared: 28 March 2018

™ = Trademark

Published by MIMS February 2019

BRAND INFORMATION

Brand name

MersynoNight Night Time Pain Relief

Active ingredient

Paracetamol; Diphenhydramine hydrochloride

Schedule

1 Name of Medicine

Paracetamol.
Diphenhydramine hydrochloride.

2 Qualitative and Quantitative Composition

Paracetamol 500 mg, diphenhydramine hydrochloride 25 mg.
For the full list of excipients, see Section 6.1 List of Excipients.

3 Pharmaceutical Form

Film coated tablets.
Blue colour, capsule shaped film coated tablet debossed with "PD5" on one side and plain on the other side.

4 Clinical Particulars

4.1 Therapeutic Indications

For the temporary relief of pain when associated with sleeping difficulty, for example: headache, migraine, backache, arthritis, rheumatic and muscle pain, neuralgia, toothache or period pain. Relief of fever.

4.2 Dose and Method of Administration

Dosage.

Adults and children over 12 years.

Take 1-2 tablets with water or other fluid only at bedtime. Maximum of two tablets in 24 hours. Do not exceed the stated dose.
Do not use in children under 12 years of age.
Other products containing paracetamol may be taken during the day but the total daily dose of paracetamol must not exceed 4,000 mg in any 24 hour period. Allow at least four hours between taking any paracetamol containing product and MersynoNight Night Time Pain Relief tablets.
For adults, paracetamol should not be taken for more than a few days at a time except on medical advice.
For children, paracetamol should not be taken for more than 48 hours except on medical advice.

Method of administration.

For oral use.

4.3 Contraindications

Not for use in children 12 years of age and younger.
Not for use for anyone with hypersensitivity to paracetamol, diphenhydramine hydrochloride or to any of the excipients.
Severe hepatocellular insufficiency.
Caution should be exercised in patients with the following: narrow angle glaucoma, stenosing peptic ulcer, symptomatic prostatic hypertrophy, bladder neck obstruction, pyloroduodenal obstruction.
Diphenhydramine is contraindicated for use in the following: newborns or premature infants, lactating women, patients taking monoamine oxidase inhibitors (MAOIs).
See Section 4.5 for additional information.

4.4 Special Warnings and Precautions for Use

Contains paracetamol. Do not use with any other paracetamol containing products. The concomitant use with other products containing paracetamol may lead to overdose.

To avoid the risk of overdose.

Check that paracetamol is absent from the composition of other medicinal products taken concomitantly.

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 this product. 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 immediately stop MersynoNight Night Time Pain Relief treatment and seek medical advice.
Caution is advised in patients with underlying sensitivity to aspirin and/or to non-steroidal anti-inflammatory drugs (NSAIDs).
MersynoNight Night Time Pain Relief should be used only upon medical advice in patients with:
depleted glutathione states such as sepsis, as the use of paracetamol may increase the risk of metabolic acidosis;
glucose-6-phosphate-dehydrogenase deficiency;
Gilbert's syndrome;
concurrent use of drugs which cause sedation such as tranquilizers, hypnotics and anxiolytics as diphenhydramine may cause an increase in sedative effects. See Section 4.5 for additional information.
Caution should be exercised in patients with epilepsy or seizure disorders, myasthenia gravis, prostatic hypertrophy, urinary retention, asthma, bronchitis and chronic obstructive pulmonary disease (COPD), moderate to severe hepatic impairment and moderate to severe renal impairment.
Diphenhydramine hydrochloride 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. The potential for abuse and dependence is low. Cases of abuse and dependence have been reported in patients having psychotic disorders or those with a history of abuse and/or dependence.
Do not take for more than 3 days without consulting a doctor. If symptoms persist, medical advice must be sought.
Keep out of sight and reach of children.
Use with caution with: drugs with antimuscarinic properties, e.g. atropine, tricyclic antidepressants; monoamine oxidase inhibitors (MAOIs) or within 2 weeks of stopping an MAOI. See Section 4.5 for additional information.
See Section 4.5 for additional information.

Use in hepatic impairment.

MersynoNight Night Time Pain Relief should be used with care in patients with: impaired hepatic function, mild-to-moderate hepatocellular insufficiency.
Underlying liver disease increases the risk of paracetamol related liver damage. Patients who have been diagnosed with liver impairment must seek medical advice before taking this medication.
Paracetamol overdose may cause liver failure which can lead to liver transplant or death.
Cases of hepatic dysfunction/failure have been reported in patients with low glutathione reserves, such as those who are severely malnourished, anorexic have a low body mass index or are chronic heavy users of alcohol. MersynoNight Night Time Pain Relief should be used only upon medical advice in patients with chronic alcohol use including recent cessation of alcohol intake.
Hepatotoxicity may occur with paracetamol even at therapeutic doses, after short treatment duration and in patients without pre-existing liver dysfunction.

Use in renal impairment.

MersynoNight Night Time Pain Relief should be used with care in patients with: impaired renal function, severe renal insufficiency.
Patients who have been diagnosed with kidney impairment must seek medical advice before taking this medication.

Use in the elderly.

The elderly may experience paradoxical excitation with diphenhydramine. The elderly are more likely to have central nervous system (CNS) depressive side effects including confusion (see Section 4.3). Should not be taken by elderly patients with confusion and paradoxical excitation in the elderly.

Paediatric use.

Children may experience paradoxical excitation with diphenhydramine.
MersynoNight Night Time Pain Relief tablets are not recommended for use in children under 12 years of age.

Effects on laboratory tests.

No data available.

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 may increase the risk of bleeding in patients taking warfarin and other antivitamin K. Patients taking paracetamol and antivitamin K should be monitored for appropriate coagulation and bleeding complications.
Coadministration 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.
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.
Paracetamol absorption is increased by substances that increase gastric emptying, e.g. metoclopramide or domperidone.
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 antiepileptics (such as phenobarbital, phenytoin, carbamazepine, topiramate), rifampicin and alcohol. The induced metabolism results in an elevated production of the hepatotoxic oxidative metabolite of paracetamol. Hepatotoxicity will occur if this metabolite exceeds the normal glutathione binding capacity.
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.
The following interactions with diphenhydramine hydrochloride have been noted.
Central nervous system (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.
Diphenhydramine is an inhibitor of the cytochrome P450 isoenzyme CYP2D6. Therefore, there may be a potential for interaction with drugs that are primarily metabolised by CYP2D6, such as metoprolol and venlafaxine.
Avoid use with other antihistamine containing preparations including topical preparations and cough and cold medicines.
As diphenhydramine has some anticholinergic activity, the effects of some anticholinergic drugs may be potentiated. This may result in tachycardia, dry mouth, blurred vision, gastrointestinal disturbances, urinary retention and headaches.

4.6 Fertility, Pregnancy and Lactation

Effects on fertility.

No data available.
(Category A)
Both paracetamol and diphenhydramine have been taken by a large number of pregnant women and women of childbearing age without any proven increase in the frequency of malformations or other direct or indirect harmful effects on the foetus having been observed. No feto/neonatal toxicity has been observed. Paracetamol can be used during pregnancy if clinically needed however it should be used at the lowest effective dose for the shortest possible time and at the lowest possible frequency.
This product is not to be used during pregnancy without medical advice.
Use of sedating antihistamines during the third trimester may result in reactions in the newborn or premature neonates.
MersynoNight Night Time Pain Relief tablets should not be used whilst breastfeeding.
Paracetamol is excreted in small amounts (< 0.2%) in breast milk but not at a clinically significant amount. Maternal ingestion of paracetamol in usual analgesic doses does not appear to present a risk to the breastfed infant.
Diphenhydramine is excreted in breast milk. Therefore it is not recommended for breastfeeding mothers unless the potential benefits to the patient are weighed against the possible risk to the infant.

4.7 Effects on Ability to Drive and Use Machines

MersynoNight Night Time Pain Relief tablets may cause drowsiness, dizziness, blurred vision, cognitive and psychomotor impairment which can seriously affect the patient's ability to drive or operate machinery. If affected, do not drive or operate machinery.

4.8 Adverse Effects (Undesirable Effects)

Paracetamol.

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 events from historical clinical trial data are both infrequent and from small patient exposure. Accordingly, events reported from extensive postmarketing experience at therapeutic/ labelled dose and considered attributable are listed below by system organ class and frequency.
As the adverse reactions identified from postmarketing use are reported voluntarily from a population of uncertain size, the frequency is not known but likely to be very rare.

Blood and lymphatic system disorders.

Very rare: thrombocytopenia, neutropenia, leukopenia. Not known: agranulocytosis, haemolytic anaemia in particular in patients with underlying glucose 6-phosphate-dehydrogenase deficiency.

Immune system disorders.

Not known: hypersensitivity* such as anaphylactic shock, angioedema.
*Cutaneous hypersensitivity reactions including skin rashes and Stevens-Johnson syndrome.

Respiratory, thoracic and mediastinal disorders.

Bronchospasm in patients sensitive to aspirin and other NSAIDs.

Metabolism and nutrition system disorders.

Not known: pyroglutamic acidosis, in patients with pre-disposing factors for glutathione depletion.

Hepatobiliary disorders.

Hepatic dysfunction. Not known: cytolytic hepatitis, which may lead to acute hepatic failure.

Skin and subcutaneous disorders.

Very rare: erythema, urticaria, rash. Not known: toxic epidermal necrolysis (TEN), Stevens-Johnson syndrome (SJS), acute generalised exanthematous pustulosis, fixed drug eruption.

Diphenhydramine.

Central nervous system (CNS) effects.

CNS depressive effects of diphenhydramine hydrochloride include sedation and impaired performance (impaired driving performance, poor work performance, incoordination, reduced motor skills and impaired information processing). Performance may be impaired in the absence of sedation and may persist the morning after a night time dose.
CNS stimulatory effects of diphenhydramine may include anxiety, hallucinations, appetite stimulation, muscle dyskinesias and activation of epileptogenic foci.
High doses of diphenhydramine may cause nervousness, tremor, insomnia, agitation and irritability.

Anticholinergic effects.

Side effects of diphenhydramine associated with cholinergic blockage include dryness of the eyes, mouth and nose, blurred vision, urinary hesitancy and retention, constipation and tachycardia.
Adverse reactions that have been observed in clinical trials and which are considered to be common or very common are listed below. The frequency of other adverse reactions identified during postmarketing use is not known but these reactions are likely to be uncommon or rare.

General disorders and administration site conditions.

Common (1/10-1/100): fatigue.

Immune system disorders.

Not known: hypersensitivity reaction including rash, urticaria, dyspnoea and angioedema.

Psychiatric disorders.

Not known: confusion, paradoxical excitation (e.g. increased energy, restlessness, nervousness).
The elderly are more prone to confusion and paradoxical excitation.

Nervous system disorders.

Common (1/10-1/100): sedation, drowsiness, disturbance in attention, unsteadiness, dizziness. Not known: convulsions, headache, paraesthesia, dyskinesias.

Eye disorders.

Not known: blurred vision.

Cardiac disorders.

Not known: tachycardia, palpitations.

Respiratory, thoracic and mediastinal disorders.

Not known: thickening of bronchial secretions, bronchospasm.

Gastrointestinal disorders.

Common (1/10-1/100): dry mouth. Not known: gastrointestinal disturbance including nausea, vomiting.

Musculoskeletal and connective tissue disorders.

Not known: muscle twitching.

Renal and urinary disorders.

Not known: urinary difficulty, urinary retention.

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 (Australia).

4.9 Overdose

If an overdose is taken or suspected, immediately contact the Poisons Information Centre (in Australia, call 131 126) for advice, or go to a hospital straight away even if you feel well because of the risk of delayed, serious liver damage.
Paracetamol overdose may cause liver failure which can lead to liver transplant or death.
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.

Signs and symptoms.

Nausea, vomiting, anorexia, pallor, 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 can appear 12 to 48 hours after acute overdosage.
It can also lead to pancreatitis, acute renal failure and pancytopenia.
Diphenhydramine overdose is likely to result in effects similar to those listed under Adverse Effects (Undesirable Effects). Additional symptoms may include mydriasis, fever, flushing, agitation, tremor, dystonic reactions, hallucinations and ECG changes. Large overdose may cause rhabdomyolysis, convulsions, delirium, toxic psychosis, arrhythmias, coma and cardiovascular collapse.
Prolonged QTc, wide complex tachycardia which may lead to ventricular tachycardia including Torsades de Pointes have been reported in acute overdoses of more than 500 mg in adults. Fatal outcomes have been reported rarely with diphenhydramine overdose.

Treatment.

Paracetamol.

Immediate medical management is required in the event of overdose, even if symptoms of overdose are not present. Despite a lack of significant early symptoms, patients should be referred to hospital urgently for immediate medical attention. Treatment involves gastric aspiration and lavage, preferably within 4 hours of ingestion. 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 N-acetylcysteine within the first 10 hours after ingestion is indicated or methionine may be required. Although N-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.
Further measures will depend on the severity, nature and course of clinical symptoms of paracetamol intoxication and should follow standard intensive care protocols.

Diphenhydramine.

Treatment should be supportive and directed towards specific symptoms. Convulsions and marked CNS stimulation should be treated with parenteral diazepam.

5 Pharmacological Properties

5.1 Pharmacodynamic Properties

Mechanism of action, paracetamol.

Paracetamol is a p-aminophenol derivative that exhibits analgesic and antipyretic activity. It does not possess anti-inflammatory activity. Paracetamol is thought to produce analgesia through a central inhibition of prostaglandin synthesis.
The lack of peripheral prostaglandin inhibition confers important pharmacological properties such as the maintenance of the protective prostaglandins within the gastrointestinal tract. Paracetamol is, therefore, particularly suitable for patients with a history of disease or on concomitant medication, where peripheral prostaglandin inhibition would be undesirable (such as, for example, those with a history of gastrointestinal bleeding or the elderly).

Mechanism of action, diphenhydramine hydrochloride.

Diphenhydramine hydrochloride competes with histamine at central and peripheral histamine-receptor sites, preventing the histamine1-receptor interaction and subsequent mediator release.
Diphenhydramine is a highly lipophilic molecule that readily crosses the blood brain barrier.
Diphenhydramine is highly selective for histamine1-receptors but has little effect on histamine2 or histamine3-receptors. Diphenhydramine also activates 5-hydroxytryptamine (serotonin) and α-adrenergic receptors and blocks cholinergic receptors.
Diphenhydramine is effective in reducing sleep onset (i.e. time to fall asleep) and increasing the depth and quality of sleep.

Clinical trials.

Not Applicable.

5.2 Pharmacokinetic Properties

Absorption.

Paracetamol is readily absorbed from the gastrointestinal tract with peak plasma concentrations occurring about 10 to 60 minutes after oral administration.
Diphenhydramine hydrochloride is well absorbed from the gastrointestinal tract, although high first-pass metabolism appears to affect systemic availability. Peak plasma concentrations are achieved about 1 to 4 hours after oral administration. The sedative effect also appears to be maximal within 1-3 hours after administration of a single dose. It is positively correlated with the plasma drug concentration.

Distribution.

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.
Diphenhydramine is widely distributed throughout the body, including the CNS. It crosses the placenta and has been detected in breast milk. Diphenhydramine is highly (approx. 80-85%) bound to plasma proteins.

Metabolism.

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.
Diphenhydramine - metabolism is extensive, mainly in the liver. Multiple cytochrome P450 enzymes contribute to the metabolism of diphenhydramine, including CYP2D6. The drug is metabolised principally to diphenylmethoxyacetic acid and is also dealkylated. It undergoes first-pass metabolism in the liver and only about 40-60% of an oral dose reaches systematic circulation as unchanged diphenhydramine. The metabolites are conjugated with glycine and glutamine and excreted in urine.

Excretion.

Diphenhydramine is excreted mainly in the urine as metabolites; little (about 1%) is excreted as unchanged substance. The elimination half-life has been reported to range from 2.4 to 9.3 hours in healthy adults. The terminal elimination half-life is prolonged in liver cirrhosis.

5.3 Preclinical Safety Data

Genotoxicity.

No data available.

Carcinogenicity.

No data available.

6 Pharmaceutical Particulars

6.1 List of Excipients

Maize starch, potassium sorbate, povidone, croscarmellose sodium, purified talc, stearic acid, Opadry complete film coating system 03F505035 Blue.

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. Protect from moisture.

6.5 Nature and Contents of Container

Container type.

PVC/Al blister.

Pack sizes.

Packs of 4, 10, 12 or 20 tablets.

Note.

Not all pack sizes may be available.

6.6 Special Precautions for Disposal

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

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Consumer medicine information

MersynoNight Night Time Pain Relief

Paracetamol; Diphenhydramine hydrochloride

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BRAND INFORMATION

MersynoNight Night Time Pain Relief Tablets