SUMMARY OF PRODUCT CHARACTERISTICS

1    NAME OF THE MEDICINAL PRODUCT

Panadol Night or Panadol NightPain

2    QUALITATIVE AND QUANTITATIVE COMPOSITION

Each tablet contains Paracetamol Ph Eur 500.0mg and Diphenhydramine hydrochloride Ph Eur 25.0mg

Also contains lactose monohydrate.

3    PHARMACEUTICAL FORM

Film-coated tablets

Blue film coated capsule shaped tablets embossed ‘PM’ on one face

4    CLINICAL PARTICULARS

4.1    Therapeutic indications

For the short term treatment of bedtime pain, for example rheumatic and muscle pain, backache, neuralgia, toothache, migraine, headache and period pain which is causing difficulty in getting to sleep.

4.2    Posology and method of administration

Oral administration only

Do not exceed the stated dose or frequency of dosing

Children: Not recommended for children under 12 years of age except on medical advice.

Adults and Elderly: 2 tablets to be taken 20 minutes before bedtime.

Maximum daily dose: Two tablets (1000mg paracetamol, 50mg diphenhydramine hydrochloride) in 24 hours. Other products containing paracetamol may be taken for daytime pain relief but at a reduced maximum dose of 6 tablets in 24 hours. The dose should not be repeated more frequently than every four hours.

Patients should not take the tablets for more than 7 consecutive nights without consulting their doctor.

4.3 Contraindications

Hypersensitivity to paracetamol, diphenhydramine hydrochloride or other constituents. Porphyria. Antihistamines are contraindicated in premature infants or neonates who have increased susceptibility to antimuscarinic effects.

4.4 Special warnings and precautions for use

Antihistamines should be used with caution in conditions such as epilepsy or seizure disorders, prostatic hypertrophy, narrow-angle glaucoma, urinary retention, pyloroduodenal obstruction, asthma, bronchitis, chronic obstructive pulmonary disease (COPD) or myasthenia gravis. Patients with renal or hepatic impairment should consult their doctor before using this medicine. The hazard of overdose is greater in those with non-cirrhotic alcoholic liver disease.

Avoid use of other antihistamine-containing preparations, including topical antihistamine and cough and cold medicines.

Patients should be advised to consult their doctor if their headaches become persistent.

Patients should be advised not to take other paracetamol containing products, other drugs with sedating properties, or alcohol concurrently.

May cause drowsiness.

Keep out of the reach and sight of children.

If symptoms persist for more than 7 days medical advice should be sought.

Use with caution in the elderly as they may be more susceptible to adverse effects. Avoid use in elderly with confusion.

Patients with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption should not take this medicine.

Pack Label:

Immediate medical advice should be sought in the event of an overdose, even if you feel well. Do not take with any other paracetamol-containing products.

Patient Information Leaflet:

Immediate medical advice should be sought in the event of an overdose, even if you feel well, because of the risk of delayed, serious liver damage.

4.5 Interaction with other medicinal products and other forms of interaction Paracetamol

The speed of absorption of paracetamol may be increased by metoclopramide or domperidone and absorption reduced by colestyramine. The anticoagulant effect of warfarin and other coumarins may be enhanced by prolonged regular daily use of paracetamol with increased risk of bleeding; occasional doses have no significant effect.

Diphenhydramine

Diphenhydramine hydrochloride may potentiate the sedative action of alcohol and other central nervous system depressants (e.g. tranquilizers, hypnotics and anxiolytics).

Monoamine Oxidase inhibitors (MAOIs) may prolong and intensify the antimuscarinic effects of diphenhydramine. The product should be used with caution with MAOIs or within 2 weeks of stopping an MAOI.

As diphenhydramine has antimuscarinic activity the effects of some anticholinergic drugs (e.g. atropine and tricyclic antidepressants) may be potentiated therefore medical advice should be sought before taking diphenhydramine with such medicines.

Diphenhydramine s an inhibitor of the cytochrome p450 isoenzyme CYP2D6. Therefore, there may be a potential for interaction with drugs that are primarily metabolized by CYP2D6, such as metoprolol and venlafaxine.

4.6 Fertility, pregnancy and lactation Pregnancy

This product should not be used during pregnancy without medical advice.

Human and animal studies with paracetamol have not identified any risk to pregnancy or embryo-foetal development.

There are no adequate data from the use of diphenhydramine in pregnant women. Animal studies are insufficient with respects to pregnancy. The potential risk for humans is unknown. Use of sedating antihistamines during the third trimester may result in reactions in the newborn or premature neonates.

Lactation

This product should not be used whilst breast feeding without medical advice.

Human studies with paracetamol have not identified any risk to lactation or the breast-fed offspring. Paracetamol crosses the placental barrier and is excreted in breast milk.

Diphenhydramine has been detected in breast milk, but the effects of this on breast-fed infants are unknown.

4.7 Effects on ability to drive and use machines

May cause drowsiness, dizziness, blurred vision, cognitive and psychomotor impairment, which can seriously affect patients’ ability to drive and use machinery. If affected they should not drive or operate machinery.

4.8 Undesirable effects

Adverse events from historical clinical trials data are both infrequent and from small patient exposure. Accordingly, events reported from extensive postmarketing experience at therapeutic/labeled dose and considered attributable are tabulated below by System Organ Class and frequency. The following convention has been utilized for the classification of undesirable effects: very common (>1/10), common (>1/100, <1/10), uncommon (>1/1000, <1/100), rare (>1/10.000, <1/1000), very rare (<1/10,000), not known (cannot be estimated from available data).

Paracetamol

As the adverse reactions identified from post-marketing use are reported voluntarily from a population of uncertain size, the frequency is not known.

Body System	Undesirable effect
Blood and lymphatic system disorders	Thrombocytopenia Agranulocytosis
Immune system disorders	Anaphylaxis Cutaneous hypersensitivity reactions including skin rashes, angiodema and Steven Johnson syndrome/toxic epidermal necrolysis
Respiratory, thoracic and mediastinal disorders	Bronchospasm*
Hepatobiliary disorders	Hepatic dysfunction

*There have been case of bronchospasm with paracetamol, but there are more likely in asthmatics sensitive to aspirin or other NSAIDs.

Diphenhydramine

Adverse reactions which have been observed in clinical trials and which are considered to be common or very common are listed below by MedDRA System Organ Class. The frequency of other adverse reactions identified during post-marketing use is unknown, but these reactions are likely to be uncommon or rare.

Body System	Undesirable effect
General disorders and administration site conditions	Common: Fatigue
Immune system disorders	Not known: Hypersensitivity reactions including rash, urticaria, dyspnoea and angioedema
Psychiatric disorders	Not known: confusion*, paradoxical excitation* (eg increased energy, restlessness, nervousness) *the elderly are more prone to confusion and paradoxical excitation
Nervous system disorders	Common: 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
Gastrointestinal disorders	Common: 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

4.9 Overdose

Paracetamol

Liver damage is possible in adults who have taken 10g or more of paracetamol. Ingestion of 5g or more of paracetamol may lead to liver damage if the patient has risk factors (see below).

Risk Factors:

If the patient

•    Is on long term treatment with carbamazepine, phenobarbitone, phenytoin, primidone, rifampicin, St John’s Wort or other drugs that induce liver enzymes.

Or

•    Regularly consumes ethanol in excess of recommended amounts.

Or

•    Is likely to be glutathione deplete e.g. eating disorders, cystic fibrosis, HIV infection, starvation, cachexia.

Symptoms

Symptoms of paracetamol overdose in the first 24 hours are pallor, nausea, vomiting, anorexia and abdominal pain. Liver damage may become apparent 12 to 48 hours after ingestion. Abnormalities of glucose metabolism and metabolic acidosis may occur. In severe poisoning, hepatic failure may progress to encephalopathy, haemorrhage, hypoglycaemia, cerebral oedema and death. Acute renal failure with acute tubular necrosis, strongly suggested by loin pain, haematuria and proteinuria, may develop even in the absence of severe liver damage. Cardiac arrhythmias and pancreatitis have been reported.

Management

Immediate treatment is essential in the management of paracetamol overdose. Despite a lack of significant early symptoms, patients should be referred to hospital urgently for immediate medical attention. Symptoms may be limited to nausea or vomiting and may not reflect the severity of overdose or the risk of organ damage. Management should be in accordance with established treatment guidelines, see BNF overdose section.

Treatment with activated charcoal should be considered if the overdose has been taken within 1 hour. Plasma paracetamol concentration should be measured at 4 hours or later after ingestion (earlier concentrations are unreliable). Treatment with N-acetylcysteine may be used up to 24 hours after ingestion of paracetamol, however, the maximum protective effect is obtained up to 8 hours post-ingestion. The effectiveness of the antidote declines sharply after this time. If required the patient should be given intravenous N-acetylcysteine, in line with the established dosage schedule. If vomiting is not a problem, oral methionine may be a suitable alternative for remote areas, outside hospital. Management of patients who present with serious hepatic dysfunction beyond 24h from ingestion should be discussed with the NPIS or a liver unit.

Diphenhydramine

Diphenhydramine overdose is likely to result in effects 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

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

Paracetamol has analgesic and antipyretic effects. It is only a weak inhibitor of prostaglandin biosynthesis, although there is some evidence to suggest that it may be more effective against enzymes in the CNS than those in the periphery. This fact may partly account for its ability to reduce fever (a central action) and to induce analgesia. Diphenhydramine is an ethanolamine class antihistamine that acts predominantly as a competitive but reversible inhibitor of histamine at the H1 receptor sites. However, like most H1 antihistamines it has additional sedative anticholinergic (antimuscarinic) and local anaesthetic properties.

5.2 Pharmacokinetic properties

Paracetamol is rapidly and almost completely absorbed from the gastrointestinal tract. Concentration in plasma generally reaches a peak in 30120 minutes; plasma half-life is 1-4 hours. Paracetamol is relatively uniformly distributed throughout most body fluids. Plasma binding is variable. Excretion is almost exclusively renal in the form of conjugates. Diphenhydramine is well absorbed from the gastrointestinal tract following oral administration. Peak plasma concentrations are achieved in 2 to 3 hours and the effects usually last 4 to 6 hours. Diphenhydramine is extensively metabolised mainly in the liver, and excreted usually as metabolites in the urine.

5.3 Preclinical safety data

None stated

6    PHARMACEUTICAL PARTICULARS

6.1    List of excipients

Tablet cores:

Maize starch Starch pre-gelatinised Potassium sorbate Povidone Purified talc Stearic acid

Film coating:

Hypromellose (E 464)

Titanium dioxide (E 171)

Lactose monohydrate Macrogol 400 Triacetin

Brilliant blue FCF (E 133)

Indigo carmine (E 132)

Carnauba wax

6.2    Incompatibilities

None

6.3    Shelf life

24 months

6.4    Special precautions for storage

The product should be stored below 25°C in a dry place

6.5    Nature and contents of container

White PVDC coated PVC (250pm) and aluminium foil (30pm) child-resistant blister packed into outer cardboard cartons, containing 10 or 20 tablets.

Not all pack sizes may be marketed

6.6 Special precautions for disposal

Not applicable

7    MARKETING AUTHORISATION HOLDER

SmithKline Beecham (SWG) Limited

980 Great West Road

Brentford

Middlesex

TW8 9GS

United Kingdom

Trading as Sterling Health

or as GlaxoSmithKline Consumer Healthcare

Brentford

TW8 9GS

8    MARKETING AUTHORISATION NUMBER(S)

PL 00071/0423

9    DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION

19/01/1996 / 09/06/2005

10    DATE OF REVISION OF THE TEXT

22/09/2011