This information is intended for use by health professionals

1. Name of the medicinal product

Day Nurse

2. Qualitative and quantitative composition

Active Ingredient

per 30 ml

Paracetamol

1000 mg

Pseudoephedrine Hydrochloride

60 mg

Pholcodine

10 mg

For excipients, see 6.1

3. Pharmaceutical form

Oral Solution

Clear orange liquid

4. Clinical particulars
4.1 Therapeutic indications

For the relief of the symptoms of colds and influenza.

For oral administration.

4.2 Posology and method of administration

Take during the day.

It is important to shake the bottle for at least 10 seconds before use

Should not used with other paracetamol-containing products, decongestants or cough and cold medicines.

Adults and children 16 years and over

30 ml every four hours

Up to a maximum of 4 doses in 24 hours if needed, or up to a maximum of three doses within any 24 hour period if a night-time paracetamol-containing product is taken before bedtime.

Minimum dosing interval: 4 hours. Do not exceed the stated dose

Children under 16 years

Not to be given to children under sixteen years of age.

Elderly

There is no specific requirement for dosage reduction in the elderly.

4.3 Contraindications

This product is contraindicated in patients with:

• Hypersensitivity to any of the ingredients or excipients.

• Severe hypertension or severe coronary artery disease.,

• Severe renal impairment.

• Hyperexcitability

• With or at risk of developing, respiratory failure (e.g. those with chronic obstructive airways disease or pneumonia) or those with bronchiolitis or bronchiectasis due to sputum retention.

• Who are receiving other sympathomimetics (such as decongestants, appetite suppressants and amphetamine-like psychostimulants).

• Who are receiving Monoamine Oxidase Inhibitors (MAOIs) or for two weeks after stopping a MAOI drug.

4.4 Special warnings and precautions for use

For oral use only.

Always use the measuring cup supplied with the pack.

Should be given with caution to patients with mild to moderate kidney impairment and in those with impaired liver function. The hazard of overdose is greater in those with non-cirrhotic alcoholic liver disease.

There have been rare cases of posterior reversible encephalopathy (PRES)/reversible cerebral vasoconstriction syndrome (RCVS) reported with sympathomimetic drugs, including pseudoephedrine. Symptoms reported included sudden onset of severe headache, nausea, vomiting, and visual disturbances. Most cases improved or resolved within a few days following appropriate treatment. Pseudoephedrine should be discontinued immediately and medical advice sought if signs/symptoms of PRES/RCVS develop.

Caution should also be exercised in patients with cardiovascular disease, arrhythmias, hypertension, hyperthyroidism, prostatic enlargement, diabetes, glaucoma, phaeochromocytoma, or in those with chronic or persistent cough, asthma, or where cough is accompanied by excessive secretions.

Pholcodine may enhance the CNS effects of alcohol and other CNS depressants.

Use with caution in patients taking beta blockers and other antihypertensives,

Patients with rare hereditary problems of fructose intolerance, glucose-galactose malabsorption or sucrose-isomaltase insufficiency should not take this medicine.

Glycerol may cause headache, upset stomach and diarrhoea

This product contains 5 vol% ethanol (alcohol), i.e up to 1.2g per 30ml dose, equivalent to 30ml beer, 12.5ml wine per dose (normally calculated assuming 5% vol and 12% vol ethanol for beer and wine respectively). This could be harmful for those suffering from alcoholism. This should also be taken into consideration in pregnant or breastfeeding women and children and high risk groups such as patients with liver disease or epilepsy.

Contains 28.75mg of sodium per 30ml dose. To be taken into consideration by patients on a controlled sodium diet.

Contains paracetamol.

Warning: Do not exceed stated dose.

Asthmatics should consult their doctor before using this product.

As with all medicines, if your child is currently taking any other medicine consult your doctor or pharmacist before using this product.

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

If symptoms persist, consult your doctor.

Do not take with any other paracetamol-containing products.

Do not take with any other flu, cold or decongestant products.

Keep out of the reach and sight of children.

Severe Skin reactions

Severe skin reactions such as acute generalized exanthematous pustulosis (AGEP) may occur with pseudoephedrine-containing products. This acute pustular eruption may occur within the first 2 days of treatment, with fever, and numerous, small, mostly non-follicular pustules arising on a widespread oedematous erythema and mainly localized on the skin folds, trunk, and upper extremities. Patients should be carefully monitored. If signs and symptoms such as pyrexia, erythema, or many small pustules are observed, administration of Day Nurse should be discontinued and appropriate measures taken if needed.

Label

Immediate medical advice should be sought in the event of an overdose, even if you feel well.

Leaflet or combined Label/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

Should not be given to patients being treated with monoamine oxidase inhibitors or within 14 days of stopping such treatment as this may lead to a hypertensive crisis.

Pholcodinemay enhance the sedative effect of central nervous system depressants including alcohol, barbiturates, hypnotics, narcotic analgesics, sedatives and tranquillisers. Pholcodine may also predispose patients to developing anaphylaxis with neuromuscular blocking agents.

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

Concomitant use of this medication with sympathomimetic agents (such as decongestants, appetite suppressants and amphetamine-like psychostimulants) which interfere with the catabolism of sympathomimetic amines, may occasionally cause a rise in blood pressure.

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.

4.6 Fertility, pregnancy and lactation

Safe use of pseudoephedrine and pholcodine in pregnancy has not been established despite widespread use over many years. Caution should therefore be exercised by balancing the potential benefit of treatment to the mother against any possible hazards to the developing foetus.

In view of the possible association of foetal abnormalities with first trimester exposure to pseudoephedrine, this product should not be used in pregnancy without medical advice .

Pseudoephedrine is secreted into breast milk in small amounts but the effect of this on breast fed infants is unknown. This product should not be used whilst breast-feeding without medical advice.

4.7 Effects on ability to drive and use machines

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

4.8 Undesirable effects

The following convention has been utilised or the classification of undesirable effects: very common (>/=1/10), common (>=1/100. <1/10), uncommon (<=1/1000,<1/100), rare (<=1/10000, <1/1000), very rare (1</10000).

Paracetamol

Adverse events of paracetamol from historical clinical trial data are both infrequent and from small patient exposure. Accordingly, events reported from extensive post-marketing experience at therapeutic/labelled dose and considered attributable are tabulated below by system class. The frequency of these adverse is not known (cannot be estimated from available data).

Body System

Undesirable effect

Frequency

Blood and lymphatic system disorders

Thrombocytopaenia

Very rare

Immune System Disorders

Anaphylaxis

Cutaneous hypersensitivity reactions including skin rashes, angiodema, and Stevens Johnson syndrome

Very rare

Respiratory, thoracic and mediastinal disorders

Bronchospasm in patients sensitive to aspirin and other NSAIDs

Very rare

Hepatobiliary disorders

Hepatic dysfunction

Very rare

Pseudoephedrine

The frequency of reactions identified during post-marketing use is not known.

Body System

Undesirable effect

Frequency

Psychiatric disorders

Nervousness, insomnia

Common

Blurred Vision

Unknown

Agitation, restlessness

Uncommon

Hallucinations (particularly in children)

Rare

Nightmares

Unknown

Nervous System Disorders

Dizziness

Common

Headache, tinnitus, irritability, tremor

Unknown

Cardiac Disorders

Tachycardia, palpitations

Rare

Vascular Disorders

Increased blood pressure*

Rare

Gastrointestinal Disorders

Vomiting, dry mouth, nausea

Common

Diarrhoea or constipation; epigastric pain, anorexia

Unknown

Skin and subcutaneous tissue disorders

Rash, allergic dermatitis**

Rare

Severe skin reactions, including acute generalized exanthematous pustulosis (AGEP), Sweating

Unknown

Renal and Urinary Disorders

Dysuria, urinary retention***

Uncommon

Micturition difficulty

Unknown

*Increases in systolic blood pressure have been observed. At therapeutic doses, the effects of pseudoephedrine on blood pressure are not clinically significant.

**A variety of allergic skin reactions, with or without systemic features such as bronchospasm and angioedema have been reported following use of pseudoephedrine

***Urinary retention is most likely to occur in those with bladder outlet obstruction, such as prostatic hypertrophy.

Pholcodine

The frequency of reactions identified during post-marketing use is not known.

Body System

Undesirable effect

Frequency

Immune System disorders

Hypersensitivity reactions including skin rashes, angioedema, anaphylaxis

Rare

Gastrointestinal Disorders

Nausea vomiting

Common

Respiratory, thoracic and mediastinal disorders

Sputum retention

Unknown

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/yellowcard or search for MHRA Yellow Card in the Google Play or Apple App store.

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

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

Or

b, Regularly consumes ethanol in excess of recommended amounts.

Or

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

Symptoms:

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, 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.

Pseudoephedrine Hydrochloride

Symptoms:

As with other sympathomimetics pseudoephedrine overdose will result in symptoms due to central nervous system and cardiovascular stimulation e.g. excitement, irritability, restlessness, tremor, hallucinations, hypertension, palpitations,arrhythmias and difficulty with micturition. In severe cases, psychosis, convulsions, coma and hypertensive crisis may occur. Serum potassium levels may be low due to extracellular to intracellular shifts in potassium.

Management:

Treatment should consist of standard supportive measures. Beta-blockers should reverse the cardiovascular complications and the hypokalaemia.

Pholcodine

The effects in overdosage will be potentiated by simultaneous ingestion of alcohol and psychotropic drugs.

Symptoms:

Central nervous system depression, including respiratory depression, may develop but is unlikely to be severe unless other sedative agents have been co-ingested, including alcohol, or the overdose is very large. The pupils may be pin-point in size; nausea and vomiting are common. Hypotension and tachycardia are possible but unlikely.

Management:

This should include general symptomatic and supportive measures including a clear airway and monitoring of vital signs until stable. Consider activated charcoal if an adult presents within one hour of ingestion of more than 350 mg or a child more than 5 mg/kg.

Give naloxone if coma or respiratory depression is present. Naloxone is a competitive antagonist and has a short half-life, so large and repeated doses may be required in a seriously poisoned patient. Observe for at least four hours after ingestion, or eight hours if a sustained release preparation has been taken.

5. Pharmacological properties
5.1 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.

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 absobed 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 afetr 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.

5.3 Preclinical safety data

Not applicable.

6. Pharmaceutical particulars
6.1 List of excipients

Acesulfame K

Citric Acid Monohydrate

Sodium Benzoate

Sodium Citrate

Levomenthol

Propylene Glycol

Alcohol 96%

Glycerol

Liquid Sugar

Liquid Glucose

Peach Flavour 17.40.3109

Pear Drop Flavour 17.40.3848

Lime Flavour 17.42.5408

Riboflavin-5-Phosphate Sodium (E101)

Purified water

6.2 Incompatibilities

Not applicable

6.3 Shelf life

36 months

6.4 Special precautions for storage

Do not store above 25°C.

6.5 Nature and contents of container

Bottle of amber polyethylene terephthalate fitted with a child resistant cap closure of polypropylene with expanded polyethylene liner and measuring cup.

Pack size: 210ml, 240ml, 300ml. Not all pack sizes may be marketed.

6.6 Special precautions for disposal and other handling

Not applicable.

7. Marketing authorisation holder

GlaxoSmithKline Consumer Healthcare (UK) Trading Limited

980 Great West Road

Brentford

Middlesex

TW8 9GS

United Kingdom

8. Marketing authorisation number(s)

PL 44673/0075

9. Date of first authorisation/renewal of the authorisation

6 September 2001 / 25 / 02 / 2009

10. Date of revision of the text

08 August 2018