SUMMARY OF PRODUCT CHARACTERISTICS

1 NAME OF THE MEDICINAL PRODUCT

Boots Pharmacy Cold & Flu Night Capsules Boots Night Cold & Flu Relief Capsules

2. QUALITATIVE AND QUANTITATIVE COMPOSITION

Active ingredient	mg/cap
Paracetamol	500
Pseudoephedrine hydrochloride	30
Pholcodine	5
Diphenhydramine hydrochloride.	12.5

3 PHARMACEUTICAL FORM

Capsule, hard (capsule)

The capsule has a blue cap and purple body printed axially in white ink 'BOOTS' on the cap and '0581' on the body.

4. CLINICAL PARTICULARS

4.1. Therapeutic indications

For the relief of the major night time symptoms of colds and influenza thus aiding restful sleep.

4.2. Posology and method of administration

For oral administration.

Adults and children over 12 years: Two capsules to be taken before bedtime only.

Children under 12 years: Not to be given to children under 12 years of age. Elderly: There is no specific requirement for dosage reduction in the elderly.

Do not use for longer than 7 days unless your doctor agrees.

4.3. Contraindications

Hypersensitivity to the active substances or any of the excipients.

Severe renal impairment.

Cardiovascular disease including hypertension and peripheral vascular disease

Diabetes mellitus

Phaeochromocytoma

Hyperthyroidism

Closed angle glaucoma

Avoid in patients with hyperexcitability, prostatic enlargement or liver failure.

Patients with chronic bronchitis, COPD, bronchiolitis or bronchiectasis due to sputum retention.

Patients taking monoamine oxidase inhibitors (MAOIs) or within 14 days of stopping such treatment (see also section 4.5).

Patients taking beta-blockers - (see section 4.5)

Pholcodine should not be given to subjects in, or at risk of developing respiratory failure.

Diphenhydramine should not be given to patients with asthma, narrow angle glaucoma, prostatic hypertrophy, stenosing peptic ulcer, pyloroduodenal obstruction or bladder neck obstruction and porphyria.

Not to be used in children under the age of 12 years.

4.4 Special warnings and precautions for use

Paracetamol

Label:

Talk to a doctor at once if you take too much of this medicine, even if you feel well. Leaflet or combined label/leaflet:

Talk to a doctor at once if you take too much of this medicine even if you feel well. This is because too much paracetamol can cause delayed, serious liver damage.

Contains paracetamol.

Do not take more medicine than the label tells you to. If you do not get better, talk to your doctor. Warning: May cause drowsiness. If affected do not drive or operate machinery.

Avoid alcoholic drink.

Asthmatics should consult their doctor before using this product.

If symptoms persist, consult your doctor.

Do not take anything else containing paracetamol while taking this medicine.

Do not take with other flu, cold or decongestant products. Keep all medicines out of the sight and reach of children.

Pholcodine

Should be used with caution by patients with liver or renal disease.

Ask a doctor before use if you suffer from a chronic or persistent cough, if you have asthma or are suffering from an acute asthma attack or where cough is accompanied by excessive secretions.

Do not take with any other cough and cold medicine.

Use of pholcodine with alcohol or other CNS depressants may increase the effects on the CNS and cause toxicity in relatively smaller doses.

Pseudoephedrine

If any of the following occur, this medicine should be stopped

Hallucinations

Restlessness

Sleep disturbances

Caution in moderate to severe renal impairment.

Diphenhydramine

Caution is required if administered to patients with hepatic disease, glaucoma and urinary retention, myasthenia gravis or seizure disorders. Tolerance may develop with continuous use.

Side effects are more likely to occur in the elderly.

Information related specifically to the excipients in the formulation (see 6.1).

The colour Ponceau 4R (E124) may cause allergic reactions.

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

Pholcodine

Not to be used in patients taking MAOIs or within 14 days of stopping treatment.

Interaction with neuromuscular blocking agents (anaphylaxis) has been reported.

The reduction in blood pressure caused by antihypertensives may accentuate the hypotensive effects of pholcodine.

Diuretics may have the same effect.

Pholcodine may enhance the sedative effect of central nervous system depressants including alcohol, barbiturates, hypnotics, narcotic analgesics, sedatives and tranquillisers (phenothiazines and tricyclic antidepressants).

Pseudoephedrine

Pseudoephedrine may diminish the antihypertensive effects of hypotensive drugs and increase the possibility of arrhythmias in digitalised patients.

MAOIs and/or reversible inhibitors of monoamine oxidase A (RIMAs): should not be given to patients treated with MAOIs or within 14 days of stopping treatment: increased risk of hypertensive crisis.

Moclobemide: risk of hypertensive crisis.

Antihypertensives (including adrenergic neurone blockers, diuretics & beta-blockers): this medicine may block the hypotensive effects.

Cardiac glycosides: increased risk of dysrhythmias.

Ergot alkaloids (ergotamine & methysergide): increased risk of ertotism.

Appetite suppressants and amphetamine-like psychostimulants: risk of hypertension. Oxytocin: risk of hypertension.

Enhances effects on anticholinergic drugs (such as tricyclic antidepressants).

Paracetamol

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

Diphenhydramine

Diphenhydramine has additive effects with alcohol and other CNS depressants (hypnotics, sedatives, tranquillizers and tricyclic antidepressants) resulting in increased antimuscarinic and sedative effects. Monoamine oxidase (MAO) inhibitors prolong and intensify the anticholinergic effects of Diphenhydramine.

4.6. Fertility, pregnancy and lactation

Pregnancy

This product should not be used in pregnancy.

Epidemiological studies in human pregnancy have shown no ill effects due to paracetamol used in the recommended dosage.

Although there is no evidence to suggest that exposure to diphenydramine during pregnancy is related to major malformations, there are suggestions of an association between diphenhydramine use and inguinal hernia or genitourinary malformations. Accordingly diphenhydramine is considered to be contraindicated during pregnancy.

The safety of pholcodine during pregnancy has not been established, but there is no direct evidence of teratogenicity.

In view of the possible association of foetal abnormalities with first trimester exposure to pseudoephedrine and a possible association between diphenhydramine and foetal malformations, the use of this product, during pregnancy should be avoided.

Lactation

The use of this medicine during lactation is not recommended.

Diphenhydramine is excreted into human breast milk but levels have not been reported. Although the levels are not thought to be high, the drug is considered to be contraindicated during lactation. Paracetamol is excreted in breast milk but not in a clinically significant amount. Amounts of pseudoephedrine secreted into breast milk are considered to be too small to be harmful. There is no information available as to whether pholcodine is excreted in breast milk. The safety of the combined ingredients in this product during lactation has not been established.

4.7    Effects on ability to drive and use machines

The product may cause drowsiness and patients should be warned not to drive or operate machinery.

This medicine can impair cognitive function and can affect a patient’s ability to drive safely. This class of medicine is in the list of drugs included in regulations under 5a of the Road Traffic Act 1988. When prescribing this medicine, patients should be told:

•    The medicine is likely to affect your ability to drive

•    Do not drive until you know how the medicine affects you

•    It is an offence to drive while under the influence of this medicine

•    However, you would not be committing an offence (called a ‘statutory defence’) if:

-The medicine has been prescribed to treat a medical or dental problem and -You have taken it according to the instructions given by the prescriber and in the information provided with the medicine and -It was not affecting your ability to drive safely

4.8    Undesirable effects Diphenhydramine

The following side effects may be associated with the use of diphenhydramine: Cardiovascular disorders: hypotension, palpitations, arrhythmias.

Eye disorders: blurred vision.

Gastrointestinal disorders: dryness of the mouth, gastrointestinal disturbances, nausea.

Immune system disorders: hypersensitivity reactions (including bronchospasm, angioedema and anaphylaxis).

Blood and lymphatic system disorders: thrombocytopaenia, blood disorders. Metabolism and nutrition disorders: liver dysfunction.

Nervous system disorders: drowsiness, dizziness, grogginess, tremors, headache, psychomotor impairment, antimuscarinic effects, extrapyramidal effects, tremors, convulsions, sweating, myalgia, paraesthesia and hair loss.

Psychiatric disorders: nervousness, confusion, depression, sleep disturbances.

Skin and subcutaneous tissue disorders: rash, photosensitivity reactions, hair loss.

Paracetamol

Immune system disorders: adverse effects of paracetamol are rare but anaphylaxis and cutaneous hypersensitivity including skin rash may occur.

Blood and lymphatic system disorders: very rarely there have been reports of blood dyscrasias including thrombocytopaenia and agranulocytosis, but these were not necessarily causally related to paracetamol.

Respiratory, thoracic and mediastinal disorders: bronchospasm has been reported, this is more likely in asthmatics with aspirin or NSAID sensitivity.

Hepatobility disorders: hepatic dysfunction.

Skin and subcutaneous tissue disorders: very rare cases of serious skin reactions have been reported.

Pholcodine

The following side effects may be associated with the use of pholcodine: Gastrointestinal disorders: gastrointestinal disturbances (nausea and constipation), vomiting, diarrhoea, upset stomach, epigastric pain.

Immune system disorders: hypersensitivity reactions and anaphylaxis.

Nervous system disorders: occasional dizziness, excitation, confusion.

Respiratory, thoracic and mediastinal disorders: sputum retention.

Skin and subcutaneous tissue disorders: skin reactions including rash.

Pseudoephedrine

Cardiovascular disorders: tachycardia, palpitations, dry mouth.

Gastrointestinal disorders: nausea and/or vomiting, diarrhoea or constipation, epigastric pain.

Immune system disorders: hypersensitivity reactions, including cross sensitivity. Metabolism and nutrition disorders: anorexia.

Nervous system disorders: dizziness, headache, tinnitus, tremor, anxiety, excitability, irritability, hallucinations, lassitude.

Psychiatric disorders: nightmares, nervousness, insomnia, blurred vision, agitation, restlessness, hallucinations (particularly in children), paranoid delusions, sleep disturbances.

Renal and urinary disorders: dysuria, difficulty in micturition including urinary retention.

Skin and subcutaneous tissue disorders: skin reactions including rash, sweating, allergic dermatitis.

Vascular disorders: hypertension.

Can cause allergic type reactions including asthma. Allergy is more common in those people who are allergic to aspirin. (Ponceau 4R E124 may cause allergic type reactions.)

Reporting of suspected adverse reactions

Reporting suspected adverse reactions after authorisation 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 via the Yellow Card Scheme at www.mhra.gov.uk/vellowcard.

4.9. Overdose

Paracetamol

Symptoms of paracetamol overdosage 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, coma and death. Acute renal failure with acute tubular necrosis may develop even in the absence of severe liver damage. Cardiac arrhythmias and pancreatitis have been reported. Liver damage is possible in adults who have taken 10g or more of paracetamol. It is considered that excess quantities of a toxic metabolite (usually adequately detoxified by glutathione when normal doses of paracetamol are ingested), become irreversibly bound to liver tissue.

Other symptoms of overdosage may include drowsiness, headache, tachycardia, arrhythmias, urinary retention, hallucinations, stupor, coma, hyperreflexia, tremor, excitement and hypertension, dry mouth, disorientation, staggering gait, nystagmus hyperthermia, convulsions and respiratory depression.

Immediate treatment is essential in the management of overdosage.

Patients should be referred to hospital urgently for immediate medical attention and any patient who has ingested the equivalent of 7.5 g or more of paracetamol in the preceding 4 hours should undergo gastric lavage. Administration of oral methionine or intravenous N-acetylcysteine, which may have a beneficial effect up to at least 48 hours after overdosage, may be required. In addition symptomatic and supportive therapy may be necessary including the administration of a beta-blocker if supraventricular tachycardia supervenes and the administration of the specific narcotic antagonist naloxone.

Pholcodine

It is thought to be of low toxicity, but the effects in overdosage will be potentiated by simultaneous ingestion of alcohol and psychotripic drugs.

Symptoms: These include nausea, restlessness, excitement, ataxia and respiratory depression.

Management: Treatment of overdose should be symptomatic and supportive. Gastric lavage may be of use. In addition symptomatic and supportive therapy may be necessary, including the administration of the specific narcotic antagonist naloxone.

Other symptoms of overdosage may include headache, tachycardia, arrhythmias, urinary retention, hallucinations, coma, hyperreflexia, tremor and hypertension. Symptomatic and supportive therapy may be necessary, including the administration of a beta-blocker if supraventricular tachycardia supervenes.

Diphenhydramine

Symptoms: include CNS depression and CNS stimulation.

Management: Should be supportive, and directed towards specific symptoms. Convulsions and marked CNS stimulation should be treated with parenteral diazepam.

Pseudoephedrine

Symptoms: symptoms of overdosage include abdominal discomfort, excitation, confusion, hallucinations, ataxia, irritability, restlessness, palpitations, hypertension, difficulty in micturition and thirst.

Management: in severe overdosage gastric lavage and aspiration should be performed. Symptomatic and supportive measures should be undertaken, particularly with regard to the cardiovascular and respiratory systems. Chlorpromazine may be used to control marked excitement and hallucinations. Severe hypertension may need to be treated with an alpha-adrenoreceptor blocking drug such as phentolamine. A beta-blocker may be required to control cardiac arrhythmias.

5.    PHARMACOLOGICAL PROPERTIES

Pharmacodynamic Properties

Paracetamol has analgesic and antipyretic actions.

Pseudoephedrine is a sympathomimetic agent with both direct and indirect effects on adrenergic receptors.

Pholcodine is a cough suppressant with little analgesic activity.

Diphenhydramine is an antihistamine with anticholinergic properties.

5.2. Pharmacokinetic Properties

Paracetamol is readily absorbed from the gastrointestinal tract with peak plasma concentrations occurring about 30 minutes to 2 hours after oral administration. Paracetamol is distributed into most body tissues. It crosses the placenta and is present in breast milk. Plasma protein binding is negligible at usual therapeutic concentrations. Paracetamol is metabolised predominantly in the liver and excreted in the urine mainly as the glucuronide and sulphate conjugates, with about 10% as glutathione conjugates. Less than 5% is excreted as unchanged paracetamol. The elimination half life varies from about 1 to 4 hours.

Pseudoephedrine is absorbed from the gastrointestinal tract. It is resistant to metabolism and is excreted largely unchanged in the urine. It has a half life of several hours but elimination is enhanced and half life shortened in acid urine.

Pholcodine is rapidly absorbed after oral administration and maximum plasma concentrations are attained at about 4-8 hours. The elimination half life ranges from 32 to 43 hours. The drug has a large volume of distribution and is only 23.5% protein bound. Pholcodine is metabolised in the liver but undergoes little conjugation with glucuronide and sulphate.

Diphenhydramine hydrochloride is well absorbed from the gastrointestinal tract, though high first-pass metabolism appears to affect systemic availability. Peak plasma concentrations are achieved about 1 to 4 hours after administration by mouth. Diphenhydramine is widely distributed throughout the body including the CNS. It crosses the placenta and has been detected in breast milk. Diphenhydramine is highly protein bound. Metabolism is extensive and diphenhydramine is excreted mainly in the urine as metabolites, little being excreted as unchanged drug. Excretion is almost complete within 24 hours of administration.

5.3. Preclinical Safety Data

There are no preclinical data of relevance to the prescriber which are additional to that already included.

6.1 List of excipients

Sodium lauryl sulphate Sodium starch glycollate Magnesium stearate Hard gelatin capsule (size 0)

(containing; Brilliant blue E133, Black iron oxide E172, Titanium dioxide E171, Ponceau 4R E124)

Printing Ink:

(containing; Titanium dioxide (E171), Shellac, Propylene glycol)

6.2. Incompatibilities

Not applicable.

6.3. Shelf Life

18 months.

6.4. Special Precautions for Storage

Do not store above 25°C. Store in the original package.

6 PHARMACEUTICAL PARTICULARS

6.5 Nature and contents of container

A child-resistant push through pack of opaque 250 micron PVC/40gsm PVdC blisters, heat sealed to 35gsm Glassine paper/9 micron soft temper aluminium foil.

Pack sizes: 8/ 10/ 12/ 16/ 20/ 24

6.6. Instruction for Use/Handling