Consumer medicine information

Chemists' Own Night Pain Relief

Paracetamol; Diphenhydramine hydrochloride

BRAND INFORMATION

Brand name

Chemists' Own Night Pain Relief

Active ingredient

Paracetamol; Diphenhydramine hydrochloride

Schedule

FULL CMI

CHEMISTS' OWN NIGHT PAIN RELIEF

Active ingredient(s): paracetamol & diphenhydramine hydrochloride

Consumer Medicine Information (CMI)

This leaflet provides important information about using CHEMISTS' OWN NIGHT PAIN RELIEF. 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 CHEMISTS' OWN NIGHT PAIN RELIEF.

Where to find information in this leaflet:

1. Why am I using CHEMISTS' OWN NIGHT PAIN RELIEF?
2. What should I know before I use CHEMISTS' OWN NIGHT PAIN RELIEF?
3. What if I am taking other medicines?
4. How do I use CHEMISTS' OWN NIGHT PAIN RELIEF?
5. What should I know while using CHEMISTS' OWN NIGHT PAIN RELIEF?
6. Are there any side effects?
7. Product details

1. Why am I using CHEMISTS' OWN NIGHT PAIN RELIEF?

CHEMISTS' OWN NIGHT PAIN RELIEF contains the active ingredients paracetamol and diphenhydramine hydrochloride.

Paracetamol is an analgesic which works to stop the pain messages getting through to the brain. It also acts in the brain to reduce fever.

Diphenhydramine hydrochloride is an antihistamine that helps you sleep.

CHEMISTS' OWN NIGHT 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 muscular pain, neuralgia, toothache, and period pain. It reduces fever.

2. What should I know before I use CHEMISTS' OWN NIGHT PAIN RELIEF?

Warnings

Do not use CHEMISTS' OWN NIGHT PAIN RELIEF if:

you are allergic to paracetamol, diphenhydramine, 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 have 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
- Liver failure
You are taking monoamine oxidase inhibitors (MAOIs), a type of medicine used to treat depression
You have taken other medicines containing paracetamol in the last 4 hours
You are breastfeeding or plan to breastfeed

Do not give CHEMISTS' OWN NIGHT PAIN RELIEF:

To newborn or premature babies
To children under 12 years of age

Check with your doctor or pharmacist 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
You are 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 doctor or pharmacist if you take sedatives.

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.

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.

Do not use if you are breastfeeding or intend to breastfeed.

This medicine passes into the breast milk and there is a possibility that the baby may be affected.

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 CHEMISTS' OWN NIGHT PAIN RELIEF and affect how it works.

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 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 CHEMISTS' OWN NIGHT PAIN RELIEF or may affect how well it works.

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

Check with your doctor or pharmacist if you are not sure about what medicines, vitamins or supplements you are taking and if these affect CHEMISTS' OWN NIGHT PAIN RELIEF.

4. How do I use CHEMISTS' OWN NIGHT PAIN RELIEF?

How much to take / use

Take one or two tablets. Do not take more than the stated dose.
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 be given this medicine for more than 48 hours unless on the advice of a doctor.
Children under 12 should not be given this medicine.
If you are over 65 years of age, talk to your doctor or pharmacist 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.

When to take / use CHEMISTS' OWN NIGHT PAIN RELIEF

Take the tablets at bedtime.

How to take

Take with water or other fluid

If you forget to use CHEMISTS' OWN NIGHT PAIN RELIEF

CHEMISTS' OWN NIGHT PAIN RELIEF should be used at the same time each day. If you miss your dose at the usual time, you may take it through the night.

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

If you use too much CHEMISTS' OWN NIGHT PAIN RELIEF

If you think that you have used too much CHEMISTS' OWN NIGHT PAIN RELIEF, 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 CHEMISTS' OWN NIGHT PAIN RELIEF?

Things you should do

Talk to your doctor or pharmacist if your symptoms do not improve.

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

Use CHEMISTS' OWN NIGHT PAIN RELIEF exactly as your pharmacist or doctor has told you to.

Remind any doctor, dentist or pharmacist you visit that you are using CHEMISTS' OWN NIGHT PAIN RELIEF.

Things you should not do:

Children 12 – 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 doctor or pharmacist tells you to.
Do not give this 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.

Driving or using machines

Be careful before you drive or use any machines or tools until you know how CHEMISTS' OWN NIGHT PAIN RELIEF affects you.

CHEMISTS' OWN NIGHT PAIN RELIEF may cause dizziness, drowsiness, difficulty concentrating or blurred vision in some people. If affected, do not drive or operate machinery.

CHEMISTS' OWN NIGHT PAIN RELIEF may also cause sleepiness in some people. If affected, do not drive or operate machinery.

Drinking alcohol

Do not drink alcohol while taking CHEMISTS' OWN NIGHT PAIN RELIEF.

The sedation effects of alcohol may be increased.

Looking after your medicine

Keep your medicine in the original pack until it is time to take it. If you take your tablets out of the packaging, they not keep as well.
Store below 25°C, Protect from moisture.

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 about side effects.

Less serious side effects

Less serious side effects	What to do
Nausea or dyspepsia Drowsiness or sleepiness Dry mouth, nose and throat Constipation Nervousness and irritability Anxiety Hallucinations Twitching or jerking muscles Fast heartbeat Tiredness Dizziness Difficulty concentrating Unsteadiness	Speak to your doctor or pharmacist if you have any of these less serious side effects and they worry you.

Serious side effects

Serious side effects	What to do
Difficult or painful urination Seizures (fits) 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 breathing	Call your doctor straight away, or go straight to the Emergency Department at your nearest hospital if you notice any of these 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.

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 CHEMISTS' OWN NIGHT PAIN RELIEF contains

Active ingredient (main ingredient)	Paracetamol 500 mg Diphenhydramine hydrochloride 25 mg
Other ingredients (inactive ingredients)	Maize starch Potassium sorbate Povidone Croscarmellose sodium Purified talc Stearic acid Opadry complete film coating system 03F505035 Blue
Potential allergens	Sorbates

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

What CHEMISTS' OWN NIGHT PAIN RELIEF looks like

CHEMISTS' OWN NIGHT PAIN RELIEF is a blue, capsule shaped, film coated tablet debossed with “PD5” on one side and plain on the other side (AUST R 291323).

Supplied in blister packs of 20 tablets.

Who distributes CHEMISTS' OWN NIGHT PAIN RELIEF

Arrotex Pharmaceuticals Pty Ltd
15-17 Chapel Street
Cremorne VIC 3121
www.arrotex.com.au

This leaflet was prepared in April 2024.

Published by MIMS June 2024

BRAND INFORMATION

Brand name

Chemists' Own Night Pain Relief

Active ingredient

Paracetamol; Diphenhydramine hydrochloride

Schedule

1 Name of Medicine

Paracetamol and 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

Paracetamol and diphenhydramine 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

Adults and children over 12 years.

Take 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 paracetamol/ diphenhydramine 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.

4.3 Contraindications

Do not use in:
Infants or children under 12 years of age.
Breastfeeding women.
Patients taking monoamine oxidase inhibitors (MAOIs) - see Section 4.5 Interactions with Other Medicines and Other Forms of Interactions for additional information.
Patients with hypersensitivity to paracetamol, diphenhydramine hydrochloride or to any of the excipients.
Patients with severe hepatocellular insufficiency.
Patients with the following conditions:
Narrow angle glaucoma.
Stenosing peptic ulcer.
Symptomatic prostatic hypertrophy.
Bladder neck obstruction.
Pyloroduodenal obstruction.

4.4 Special Warnings and Precautions for Use

Contains paracetamol. The total daily dose of paracetamol must not exceed 4000 mg in any 24 hour period. The concomitant use with other products containing paracetamol may lead to overdose.

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 paracetamol and diphenhydramine hydrochloride treatment and seek medical advice.
Caution is advised in patients with underlying sensitivity to aspirin and/or to non-steroidal anti-inflammatory drugs (NSAIDs).
Paracetamol and diphenhydramine hydrochloride 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 Interactions with Other Medicines and Other Forms of Interactions for additional information.

Use in hepatic impairment.

Paracetamol and diphenhydramine hydrochloride should be used with care in patients with impaired hepatic function and 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 depleted glutathione levels, such as those who are severely malnourished, anorexic have a low body mass index or are chronic heavy users of alcohol. Paracetamol and diphenhydramine hydrochloride 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.

Paracetamol and diphenhydramine hydrochloride should be used with care in patients with impaired renal function and severe renal function. 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 Contraindications; Section 4.8 Adverse Effects (Undesirable Effects)). Should not be taken by elderly patients with confusion and paradoxical excitation in the elderly.

Paediatric use.

Children may experience paradoxical excitation with diphenhydramine.
Paracetamol/ diphenhydramine tablets should not be used 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.
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.
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.
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.
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

(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.
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.
Paracetamol/ diphenhydramine tablets should not be used whilst breastfeeding. Paracetamol is excreted in small amounts (< 0.2%) in breast milk. 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

Paracetamol/ diphenhydramine 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-deshydrogenase deficiency.

Immune system disorders.

Not known: anaphylaxis, cutaneous hypersensitivity reactions including skin rashes, angioedema and Stevens-Johnson syndrome.

Respiratory, thoracic and mediastinal disorders.

Bronchospasm in patients sensitive to aspirin and other NSAIDs.

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 http://www.tga.gov.au/reporting-problems.

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 reactions. 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 Torsade de Pointe 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.
For information on the management of overdose, contact the Poison Information Centre on 131126 (Australia).

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).

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.

No data available.

5.2 Pharmacokinetic Properties

Paracetamol.

Absorption.

Paracetamol is readily absorbed from the gastrointestinal tract with peak plasma concentrations occurring about 10 to 60 minutes after oral administration.

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.

Metabolism.

Paracetamol is metabolised extensively in the liver.
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.

Excretion.

Paracetamol is excreted in the urine mainly as inactive glucuronide and sulfate conjugates. Less than 5% is excreted unchanged.

Diphenhydramine hydrochloride.

Absorption.

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.

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.

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 diphenylmetoxyacetic 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.

Excretion.

The metabolites are conjugated with glycine and glutamine and excreted in urine. 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

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

PVC/PVDC/Al blister 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

Chemists' Own Night Pain Relief

Paracetamol; Diphenhydramine hydrochloride

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BRAND INFORMATION

Chemists' Own Night Pain Relief Tablets