Blog Massachusetts: Panadol Night

1. Name Of The Medicinal Product

Panadol Night or Panadol NightPain

2. Qualitative And Quantitative Composition

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

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 (1000 mg paracetamol, 50 mg 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. Closed angle glaucoma. Porphyria. Acute asthma. 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, prostatic hypertrophy, glaucoma, urinary retention, pyloroduodenal obstruction, or myasthenia gravis. Care is advised in the administration to patients with severe renal or severe hepatic impairment. The hazard of overdose is greater in those with non-cirrhotic alcoholic liver disease.

Do not exceed the recommended dose.

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 products containing antihistamines, other drugs with sedating properties, or alcohol concurrently.

May cause drowsiness.

Keep out of the reach of children.

If symptoms persist for more than 7 days medical advice should be sought. Antihistamines should be used with caution in the elderly as they may be more susceptible to adverse effects, in those with severe cardiovascular disease and patients with asthma or chronic pulmonary disease.

Patients with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsoprtion 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

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 hydrochloride may enhance the sedative action of central nervous system depressants including alcohol, barbiturates, hypnotics, opioid analgesics, anxiolytic sedatives and neuroleptics. MAOIs may enhance the antimuscarinic effects of antihistamines. Antihistamines may have an additive antimuscarinic action with other antimuscarinic drugs such as atropine and tricyclic antidepressants.

4.6 Pregnancy And Lactation

Epidemiological studies in human pregnancy have shown no ill effects due to paracetamol used in the recommended dosage, but patients should follow the advice of their doctor regarding its use. Paracetamol is excreted in breast milk but not in a clinically significant amount. Available published data do not contraindicate breast feeding. There is inadequate evidence for the safety of diphenhydramine hydrochloride in human pregnancy. Diphenhydramine has been detected in breast milk. Because of the higher risks of antihistamines for infants diphenhydramine is not recommended in nursing mothers.

4.7 Effects On Ability To Drive And Use Machines

Patients should be advised not to drive or operate machinery if affected by drowsiness.

4.8 Undesirable Effects

Adverse effects of paracetamol are rare but hypersensitivity including skin rash may occur. There have been a few reports of blood dyscrasias including thrombocytopenia and agranulocytosis but these were not necessarily causally related to paracetamol. Adverse effects of diphenhydramine hydrochloride may include sedation. Antimuscarinic effects include dry mouth, urinary retention, blurred vision, thickened respiratory tract secretions and chest tightness. In high doses transient bradycardia followed by tachycardia may occur. Other side effects that may occur occasionally are headache, rashes, cross sensitivity to related drugs, photosensitivity, gastrointestinal disturbance and psychomotor impairment. Blood disorders including agranulocytosis, leucopenia, haemolytic anaemia, thrombocytopenia and jaundice though rare have been reported with antihistamines. Paradoxical stimulation may rarely occur especially in high doses or in children.

4.9 Overdose

Liver damage is possible in adults who have taken 10 g or more of paracetamol. Ingestion of 5 g 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.

• Regularly consumes ethanol in excess of recommended amounts.

• 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.

Mild cases of overdose with antihistamines are mainly characterised by prominent anticholinergic effects including dry mouth, headache, nausea, tachycardia and urinary retention. Larger overdoses will have additional antihistamine effects which may depress or stimulate the CNS. In small children, the stimulatory effects predominate and clinical features include hallucinations, ataxia and convulsions. The child may be hot, flushed and have dilated pupils. Cardiorespiratory depression and coma can subsequently develop followed by rapid death. Overdosing diphenhydramine in adults usually results in drowsiness followed by convulsions and coma. Fever and flushing are uncommon. Overdosed patients are best treated by gastric lavage and supportive measures. Administration of activated charcoal may be useful. Convulsions can be controlled with diazepam. Peripheral anticholinergic effects can be controlled with subcutaneous neostigmine.

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 30-120 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

Store below 25°C in a dry place.

6.5 Nature And Contents Of Container

White PVDC coated PVC (250µm) and aluminium foil (30µm) 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 And Other Handling

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

or as SmithKline Beecham International