DAY & NIGHT NURSE CAPSULES - summary of medicine characteristics

1 NAME OF THE MEDICINAL PRODUCT

Day & Night Nurse Capsules

2 QUALITATIVE AND QUANTITATIVE COMPOSITION

Day Nurse Capsules

Active Ingredient                                  m­g/cap

Paracetamol

Pseudoephedrine hydrochloride

Pholcodine

Excipients

Sodium (as starch glycollate and lauryl sulphate)

Night Nurse Capsules

Active Ingredient                                  m­g/cap

Paracetamol

Promethazine hydrochloride

Dextromethorphan hydrobromide

Excipients

Lactose (as monohydrate)

For full list of excipients, see section 6.1.

Capsule, hard

The Day capsule has an orange cap and yellow body printed ‘Day Nurse’ in black ink on the cap and the body.

The Night capsule has a green cap and white body printed ‘Night Nurse’ in black ink on the cap and the body.

4.1 Therapeutic indications

For the symptomatic relief of colds, chills and influenza during the day.

For the symptomatic relief of colds, chills and influenza at night.

4.2. Posology and Method of Administration

For oral administration.

Do not exceed the stated dose

Should not be used with other paracetamol-containing products; decongestants antihistamine containing products (including those used on the skin) or cough and cold medicines.

Use the lowest amount needed to achieve benefit for the shortest duration of treatment..

Not to be given to children under 16 years of age

Adults and children aged 16 years and over

Two capsules every four hours, up to a maximum of three

doses in any 24-hour period. Minimum dosing interval: 4 hours

Adults and children aged 16 years and over

Two capsules just before bedtime. Only one dose should be taken at night.

Allow at least 4 hours between taking last dose of Day capsules and the dose of Night capsules.

Elderly

There is no specific requirement for dosage reduction in the elderly. However. the product should not be taken by elderly patients with confusion. The elderly may be more susceptible to adverse effects including confusion and paradoxical excitation with this medicine.

Do not use for longer than 3 days without medical advice.

4.3 Contraindications

This product is contraindicated in patients:

with hypersensitivity to any of the ingredients or excipients

with hyperexcitability.

who are receiving monoamine oxidase inhibitors (MAOIs) or for two weeks after stopping the MAOI drug. with severe hypertension or coronary artery disease

with or at risk of developing, respiratory failure (e.g. those with chronic obstructive airways disease or pneumonia, or during an asthma attack or an exacerbation of asthma).

with severe renal impairment.

with bronchiolitis or bronchiectasis, due to sputum retention.

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

who are taking oxazolidinone class of antibiotics (including linezolid)

who are taking beta-blockers and other antihypertensives

4.4 Special warnings and precautions for use

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.

The concomitant use with other products containing paracetamol may lead to an overdose. Paracetamol overdose may cause liver failure which may require liver transplant or lead to death.

Medical advice must be sought before taking this product in people with:

Hepatic impairment. Underlying liver disease increases the risk of paracetamol-related liver damage.

Glutathione depletion due to metabolic deficiencies

Mild to moderate renal impairment

Chronic or persistant cough, such as occurs with asthma and emphysema, chronic bronchitis or where cough is accompanied by excessive secretions.

Glaucoma

Hypertension or cardiovascular problems including arrhythmia

Prostatic hypertrophy

Urinary retention

Epilepsy

Diabetes

Hyperthyroidism

Phaechromocytoma

Psychosis

Taking tricyclic antidepressants

The product should be discontinued immediately, and medical advice should be sought:

If sudden abdominal pain, rectal bleeding or other symptoms of ischaemic colitis develop as there have been reports of ischaemic colitis with pseudoephedrine.

Medical advice should be sought before taking this product in people taking the following medications (See interactions):

tricyclic antidepressants

selective serotonin reuptake inhibitors (SSRI)

drugs which cause CNS depression, such as antipsychotics, hypnotics and anxiolytics, as concurrent use may cause an increase in sedative effects

drugs with anticholinergic effects (e.g. atropine)

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.

Use with caution:

in patients taking vasoconstrictive agents such as ergot alkaloids

in the elderly, who are more likely to experience anticholinergic adverse effects including confusion and paradoxical excitation. Avoid use in elderly patients with confusion.

when planning surgery. Acute perioperative hypertension may occur if volatile halogenated anaesthetics are used simultaneously with indirect sympathomimetic agents. It is recommended that pseudoephedrine treatment is stopped for several days before anaesthesia.

In patients taking other CNS depressants (including alcohol).

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

Severe cutaneous adverse reactions (SCARs) including acute generalized exanthematous pustulosis (AGEP) may occur with pholcodine-containing products. These can be life-threatening or fatal, have been reported in patients treated with Day Nurse, most likely in the first week. Patients should be advised of the signs and symptoms and monitored closely for skin reactions. If signs and symptoms suggestive of these reactions appear, Day Nurse should be discontinued immediately.

Pseudoephedrine content of this product may result in a positive reaction during antidoping control tests.

Cases of ischaemic optic neuropathy have been reported with pseudoephedrine.

Pseudoephedrine should be discontinued if sudden loss of vision or decreased visual acuity such as scotoma occurs.

Children are more likely to experience paradoxical excitation with sedating antihistamine.

Medical advice should be sought if symptoms persist, or are accompanied by high fever, skin rash or persistent headache.

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

Day Nurse contains less than 1 mmol sodium (23 mg) per dosage unit, that is to say essentially ‚sodium-free‘.

Contains paracetamol.

Do not exceed the stated dose. Alcohol should be avoided.

If symptoms persist, medical advice should be sought.

Should not be used with other paracetamol-containing products; decongestants antihistamine containing products (including those used on the skin) or cough and cold medicines

Keep out of reach and sight of children.

Caution is needed in patients with a history of drug abuse. Pholcodine is an opioid and addiction is observed with opioids as a class.

Cases of dextromethorphan abuse have been reported. Caution is particularly recommended for adolescents and young adults as well as in patients with a history of drug abuse or psychoactive substances.

For all patients, prolonged use of Night Nurse may lead to drug dependence (addiction), even at therapeutic doses. The risks are increased in individuals with current or past history of substance misuse disorder (including alcohol misuse) or mental health disorder (e.g., major depression).

The drug withdrawal syndrome is characterised by some or all of the following: restlessness, lacrimation, rhinorrhoea, yawning, perspiration, chills, myalgia, mydriasis and palpitations. Other symptoms may also develop including irritability, agitation, anxiety, hyperkinesia, tremor, weakness, insomnia, anorexia, abdominal cramps, nausea, vomiting, diarrhoea, increased blood pressure, increased respiratory rate or heart rate.

Dextromethorphan is metabolised by hepatic cytochrome P450 2D6. The activity of this enzyme is genetically determined. About 10% of the general population are poor metabolisers of CYP2D6. Poor metabolisers and patients with concomitant use of CYP2D6 inhibitors may experience exaggerated and/or prolonged effects of dextromethorphan. Caution should therefore be exercised in patients who are slow metabolizers of CYP2D6 or use CYP2D6 inhibitors (see also section 4.5).

Promethazine may interfere with immunologic urine pregnancy tests to produce false positive or negative results

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 and Night Nurse Capsules should be discontinued and appropriate measures taken if needed.

Special label warnings

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

Special leaflet warnings

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

Medical advice should be sought before taking paracetamolpse­udoephedrine- Pholcodine (Day capsules) in combination with these drugs:

Medical advice should be sought before taking paracetamol-promethazine-dextromethorphan (Night capsules) in combination with these drugs:

4.6 Fertility, Pregnancy and lactationPregnancy

The product (both Day and Night Capsules) should not be used during pregnancy without medical advice, and only if the benefits to the mother will outweigh the risks to the foetus. If used, the lowest effective dose and shortest duration of treatment should be considered.

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 during pregnancy without medical advice.

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.

No relevant data are available for products containing dextromethorphan. Human and animal studies with promethazine are insufficient to establish the safety of this drug during pregnancy. It should only be used when considered essential by the doctor

This product (both Day and Night Capsules) should not be used whilst breast feeding without medical advice, and only if the benefits to the mother will outweigh the risks to the infant. If used, the lowest effective dose and shortest duration of treatment should be considered.

Pseudoephedrine is secreted into breast milk in small amounts but the effect of this on breast fed infants is unknown. The safety of pseudoephedrine and pholcodine during lactation has not been established and therefore the product should not be used during this period.

Paracetamol is excreted in breast milk but not in a clinically significant amount.

Promethazine may be excreted in breast milk. It should only be used when considered essential by a doctor.

4.7 Effects on ability to drive and use machines

The day capsule may cause dizziness. Patients should be advised not to drive or operate machinery if affected.

The night capsule may cause drowsiness, dizziness, blurred vision, cognitive and psychomotor impairment which can seriously affect the ability to drive and use machinery. If affected do not drive or operate machinery.

This class of medicine is in the list of drugs included in regulations under 5a of the Road Traffic Act 1988. When taking 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 ‘statutory defence’) if:

o The medicine has been taken to treat a medical or dental problem and

o You have taken it according to the information provided with the medicine and

It was not affecting your ability to drive safely.

4.8 Undesirable effects

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 (ingredient included in Day and Night capsule)

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).

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

Dextromethorphan (ingredient included in Night capsule only)

The following adverse events have been observed in published clinical studies and are likely to represent uncommon adverse reactions to dextromethorphan.

Adverse reaction identified during post-marketing use with dextromethorphan are listed below. The frequency of these reactions is unknown but likely to be very rare.

The frequency of drug dependence and withdrawal reactions is unknown:

Promethazine (ingredient included in Night capsule only)

Adverse reactions which been observed in published clinical studies with promethazine and which are considered to be common or very common are listed below by MedDRA system Organ Class. The frequency of other reactions identified during post-marketing use is not known, but these reactions are likely to be uncommon or rare.

The elderly are more susceptible to anticholinergic effects of promethazine.

Pseudoephedrine (included in Day capsule only)

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

*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 (ingredient included in Day capsule only)

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

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

5   PHARMACOLOGICAL PROPERTIES

5.1 Pharmacodynamic properties

Paracetamol – an analgesic and antipyretic.

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

Pholcodine – an antitussive with little analgesic activity.

Promethazine hydrochloride – an antihistamine with anticholinergic activity.

Dextromethorphan hydrobromide – an antitussive.

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 halflife 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.

Promethazine hydrochloride is readily absorbed from the gastrointestinal tract, but undergoes extensive first pass metabolism in the liver, with only 25% of the oral dose reaching the systemic circulation unchanged. After oral therapy therapeutic effects are identifiable at 15–30 minutes and peak plasma concentrations at 2 to 3 hours. Estimates of terminal half-life in blood plasma are in the range of 4–6 hours. It is extensively plasma protein bound. It is eliminated mainly as metabolites, predominantly by the faecal (via biliary) route, with < 1% of the parent compound and ca. 10% as the sulphoxide metabolite being excreted in the urine over a 72 hour period.

Dextromethorphan hydrobromide is well absorbed from the gastrointestinal tract. It is metabolised in the liver and excreted as demethylated metabolites including dextrorphan, and as a minor proportion of unchanged dextromethorphan. In a small proportion of individuals, metabolism proceeds more slowly and dextromethorphan predominates in blood and urine.

Dextromethorphan undergoes rapid and extensive first-pass metabolism in the liver after oral administration. Genetically controlled O-demethylation (CYD2D6) is the main determinant of dextromethorphan pharmacokinetics in human volunteers.

It appears that there are distinct phenotypes for this oxidation process resulting in highly variable pharmacokinetics between subjects. Unmetabolised dextro-methorphan, together with the three demethylated morphinan metabolites dextrorphan (also known as 3-hydroxy-N-methylmorphinan), 3– hydroxymorphinan and 3-methoxymorphinan have been identified as conjugated products in the urine.

Dextrorphan, which also has antitussive action, is the main metabolite. In some individuals metabolism proceeds more slowly and unchanged dextromethorphan predominates in the blood and urine.

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 excipientsDay Nurse Capsules

Sodium lauryl sulphate Sodium starch glycollate Magnesium stearate (E572) Hard gelatin capsule Quinoline yellow (E104) Allura red (E 129)

Titanium dioxide (E171) Printing Ink:

Shellac

Iron oxide black (E 172) Propylene glycol (E 1520) Ammonium hydroxide (E 527)

Night Nurse Capsules Lactose monohydrate Dimeticone

Colloidal anhydrous silica Gelatin

Patent blue V (E131) Quinoline yellow (E104) Titanium dioxide (E171) Printing Ink:

Shellac

Iron oxide black (E 172) Propylene glycol (E 1520) Ammonium hydroxide (E 527)

6.2 Incompatibilities

Not applicable

6.3 Shelf life

36 months

6.4 Special precautions for storage

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

6.5 Nature and contents of container

Blisters: 250 ^m PVC/60gsm PVDC blister tray with 30 ^m aluminium foil lid.

Each tray holds 6 Day Nurse capsules and 2 Night Nurse capsules.

Pack size: 24 capsules (3 trays) comprising 18 Day Nurse capsules and 6 Night Nurse capsules.

6.6 Special precautions for disposal

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 44673/0068

9 DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION

18/07/2002 / 25/02/2009