4.1. Therapeutic indications

Haleon Day Nurse is indicated in adults and adolescents aged 12 to 18 years. Symptomatic relief of nasal congestion when combined with fever and/or pain such as, sore throat, sinus pain or headache in the common cold or influenza.

4.2. Posology and method of administration

Posology

The lowest dose necessary to achieve efficacy should be used for the shortest duration of treatment.

Adults, including the elderly

Two tablets up to three times daily as required for relief of symptoms.

The dose should not be repeated more frequently than every four hours nor should more than three doses be given in any 24 hour period.

Paediatric Population

Adolescents aged 16 to 18 years old

One to two tablets up to three times daily as required for relief of symptoms.

The dose should not be repeated more frequently than every four hours nor should more than three doses be given in any 24 hour period.

Adolescents aged 12 to 15 years old

One tablet up to three times daily as required for relief of symptoms.

The dose should not be repeated more frequently than every four hours nor should more than three doses be given in any 24 hour period.

Haleon Day Nurse is contraindicated in children aged under 12 years and below (see section 4.3).

Patients with renal impairment

Pseudoephedrine is primarily excreted renally. Pseudoephedrine should not be used by those with severe renal impairment GFR<30mL/min (see section 4.3) and should be used with caution in those with moderate renal impairment GFR 30-59 mL/min (see sections 4.4 and 5.2).

Patients with hepatic impairment

Patients who have been diagnosed with hepatic impairment must seek medical advice before taking this medication. The restrictions related to the use of such combinations in patients with hepatic impairment are primarily a consequence of the paracetamol content of the product (see section 4.4).

Method of administration

For oral use.

Patients should be advised not to use this product for more than 5 days and to seek medical advice if symptoms persist.

Do not exceed the stated dose.

The tablets should be taken with water.

4.3. Contraindications

Hypersensitivity to paracetamol, pseudoephedrine or any of the excipients listed in section 6.1.

Not to be used by patients taking moclobemide or monoamine oxidase inhibitors (MAOIs) or for two weeks after stopping the MAOI drug.

The oxazolidinone class of antibiotics (including furazolidone and linezolid) should not be taken with Haleon Day Nurse (see section 4.5).

Not to be used by patients with the following conditions:

• Severe hypertension or uncontrolled hypertension

• Cardiovascular disease

• Hyperthyroidism

• Prostatic hypertrophy

• Glaucoma

• Severe renal impairment (GFR<30mL/min)

• Severe acute or chronic kidney disease/renal failure

Not to be used by patients currently receiving other sympathomimetics (such as decongestants, tricyclic antidepressants, appetite suppressants and amphetamine-like psychostimulants see section 4.5).

Not to be used by patients taking beta-blockers (see section 4.5).

Paediatric Population

Not to be used by children under 12 years of age.

4.4. Special warnings and precautions for use

Contains paracetamol.

Do not use with any other paracetamol-containing products. The concomitant use with other products containing paracetamol may lead to an overdose. Paracetamol overdose may cause liver failure which may lead to liver transplant or death.

Use with caution in patients with hepatic impairment or mild to moderate renal impairment.

Use with caution in patients with glutathione depletion due to metabolic deficiencies.

Use with caution in patients with psychosis.

Concomitant use of other cold and flu medicines should be avoided.

The hazard of overdose is greater in those with non-cirrhotic alcoholic liver disease.

Use with caution in patients with diabetes mellitus, arrhythmias or phaeochromocytoma.

Use with caution in patients taking antihypertensives or vasoconstrictive agents such as ergot alkaloids (see section 4.5 Interaction with other medicinal products and other forms of interaction).

Use with caution in patients over the age of 60 years. Patients in this age group are at greater risk of adverse reactions due to decreased renal function, and unwanted reactions when using oral sympathomimetic agents.

This product may give rise to insomnia and nervousness.

There have been reports of acute systemic vasoconstrictive events with pseudoephedrine. Significant examples include:

Acute Coronary Syndrome (ACS): Symptoms may include sudden chest pain or discomfort, radiating chest pain, dizziness, sweating and dyspnoea at rest. Pseudoephedrine should be discontinued immediately, and medical advice sought if any symptoms of ACS develop.

Posterior reversible encephalopathy (PRES)/reversible cerebral vasoconstriction syndrome (RCVS): Cases of PRES and RCVS have been reported with the use of pseudoephedrine-containing products (see section 4.8). The risk is increased in patients with severe or uncontrolled hypertension, or with severe or acute or chronic kidney disease/renal failure (see section 4.3). Pseudoephedrine should be discontinued and immediate medical assistance sought if the following symptoms occur: sudden severe headache or thunderclap headache, nausea, vomiting, confusion, seizures and/or visual disturbances. Most reported cases of PRES and RCVS resolved following discontinuation and appropriate treatment.

There have been reports of ischaemic colitis with pseudoephedrine. Pseudoephedrine should be discontinued immediately and medical advice sought if sudden abdominal pain, rectal bleeding or other symptoms of ischaemic colitis develop.

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 Haleon Day Nurse should be discontinued and appropriate measures taken if needed.

Ischaemic optic neuropathy. 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.

Care is advised in the administration of Haleon Day Nurse to patients who will be undergoing general anaesthesia. Acute perioperative hypertension may occur if volatile halogenated anaesthetics are used simultaneously with indirect sympathomimetic agents. It is recommended that pseudoephedrine treatment is stopped 24 hours before anaesthesia.

If you are taking medication, or are under medical care consult your doctor or pharmacist.

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

Cases of high anion gap metabolic acidosis (HAGMA) due to pyroglutamic acidosis have been reported in patients with severe illness such as severe renal impairment and sepsis, or in patients with malnutrition and other sources of glutathione deficiency (e.g. chronic alcoholism), who were treated with paracetamol at therapeutic dose for a prolonged period or a combination of paracetamol and flucloxacillin. If HAGMA due to pyroglutamic acidosis is suspected, prompt discontinuation of paracetamol and close monitoring is recommended. The measurement of urinary 5-oxoproline may be useful to identify pyroglutamic acidosis as underlying cause of HAGMA in patients with multiple risk factors.

Keep all medicines safely out of sight and reach of children.

Hepatotoxicity at therapeutic dose

Cases of paracetamol induced hepatotoxicity, including fatal cases, have been reported in patients taking paracetamol at doses within the therapeutic range. These cases were reported in patients with one or more risk factors for hepatotoxicity including low body weight (<50 kg), renal and hepatic impairment, chronic alcoholism, concomitant intake of hepatotoxic drugs and in acute and chronic malnutrition (low reserves of hepatic glutathione). Paracetamol should be administered with caution to patients with these risk factors. Caution is also advised in patients on concomitant treatment with drugs that induce hepatic enzymes and in conditions which may predispose to glutathione deficiency (see section 4.2 and 4.9).

Doses of paracetamol should be reviewed at clinically appropriate intervals and patients should be monitored for emergence of new risk factors for hepatotoxicity, which may warrant dosage adjustment.

Risks of abuse

Pseudoephedrine carries the risk of abuse. Increased doses may ultimately produce toxicity. Continuous use can lead to tolerance resulting in an increased risk of overdosing. The recommended maximum dose and treatment duration should not be exceeded (see section 4.2).

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

The co-administration of Haleon Day Nurse with tricyclic antidepressants, the antidepressant moclobemide, decongestants, appetite suppressants and amphetamine-like psychostimulants or with monoamine oxidase inhibitors (MAOIs) (or within two weeks of stopping MAOIs) which interfere with the catabolism of sympathomimetic agents, may occasionally cause a rise in blood pressure and may lead to hypertensive crisis in the case of moclobemide or MAOIs.

The oxazolidinone class of antibiotic (including furazolidone and linezolid) are known to cause a dose-related inhibition of monoamine oxidase. Therefore, they should not be taken with Haleon Day Nurse as there is a potential to cause hypertensive crisis (see section 4.3).

Pseudoephedrine may antagonize the effect of certain classes of antihypertensives (e.g., beta-blockers, methyl-dopa, reserpine, debrisoquine, guanethidine) (see sections 4.3 and 4.4).

Pseudoephedrine may interact with halogenated anaesthetics (see section 4.4).

Concomitant administration of vasoconstrictor agents (including ergot derivatives such as bromocriptine, pergolide, lisuride, cabergoline, ergotamine, dihydroergotamine and methylsergide) may cause an increased risk of ergotism (see section 4.4).

The rate of paracetamol absorption may be reduced by colestyramine. The interaction can be avoided by delaying administration of colestyramine by one hour, in order to maintain maximal analgesic effects.

The anticoagulant effect of warfarin and other coumarins may be enhanced by prolonged regular daily use of Haleon Day Nurse with increased risk of bleeding; occasional doses have no significant effect.

Sodium bicarbonate alkalinizes the urine and may reduce the renal elimination of pseudoephedrine, a reduction in dose may be necessary.

The speed of absorption of paracetamol may be increased by metoclopramide or domperidone.

Caution should be taken when paracetamol is used concomitantly with flucloxacillin as concurrent intake has been associated with high anion gap metabolic acidosis due to pyroglutamic acidosis, especially in patients with risks factors (see section 4.4).

4.6. Fertility, pregnancy and lactation

Pregnancy

There are insufficient data from the use of the combination paracetamol and pseudoephedrine in pregnant women. Animal studies are insufficient with respect to reproductive toxicity. Epidemiological studies on neurodevelopment in children exposed to paracetamol in utero show inconclusive results. Haleon Day Nurse is not recommended during pregnancy and in women of childbearing potential not using contraception.

Breastfeeding

Pseudoephedrine is excreted in human milk to such an extent that effects on the breastfed newborns/infants are likely. Haleon Day Nurse should not be used during breastfeeding.

Fertility

There are no relevant data available. See section 5.3.

4.7. Effects on ability to drive and use machines

Dizziness is one of the most frequent adverse effects. Thus, Haleon Day Nurse could have a major influence on the ability to drive and use machines.

4.8. Undesirable effects

Adverse reactions are listed below by system organ class and frequency. Frequencies are defined as: very common (>1/10), common (>1/100 and <1/10), uncommon (>1/1000 and <1/100), rare (>1/10,000 and <1/1000) and very rare (<1/10,000) and not known (cannot be estimated from the available date).

Paracetamol:

System Organ Class

Adverse Reaction

Frequency

Blood and lymphatic system disorders

Blood dyscrasia, including thrombocytopenia and agranulocytosis

Very rare

Immune system disorders

Hypersensitivity*

Rare

Metabolism and nutrition disorders

High anion gap metabolic acidosis

Not known*

Anaphylaxis

Cutaneous hypersensitivity reactions including, among others, Toxic Epidermal Necrolysis, Stevens Johnson syndrome, angioedema and skin rashes.

Very rare

Hepatobiliary disorders

Hepatic dysfunction

Very rare

Respiratory, thoracic and mediastinal disorders

Bronchospasm is more likely in patients sensitive to aspirin or NSAIDs

Very rare

*(cannot be estimated from the available data)

Description of selected adverse reactions:

High anion gap metabolic acidosis: cases of high anion gap metabolic acidosis due to pyroglutamic acidosis have been observed in patients with risk factors using paracetamol (see section 4.4). Pyroglutamic acidosis may occur as a consequence of low glutathione levels in these patients.

Pseudoephedrine:

System Organ Class

Adverse Reaction

Frequency

Psychiatric disorders

Nervousness, insomnia

Common

Agitation, restlessness

Uncommon

Hallucinations (particularly in children)

Rare

Nervous system disorders

Dizziness

Common

Headache, tremor

Not known

Posterior reversible encephalopathy syndrome (PRES) (see section 4.4)

Unknown

Reversible cerebral vasoconstriction syndrome (RCVS) (see section 4.4)

Unknown

Eye disorders

Ischaemic optic neuropathy

Not known

Gastrointestinal disorders

Dry mouth, nausea, vomiting

Common

Ischaemic colitis

Not known

Skin and subcutaneous disorders

Allergic dermatitis*, rash

Rare

Severe skin reactions, including acute generalizes exanthematous pustulosis (AGEP)

Not known

Renal and urinary disorders

Urinary retention**

Dysuria

Uncommon

Cardiac disorders

Minor tachycardia

Uncommon

Palpitations

Rare

Cardiac arrhythmias

Rare

Vascular disorders

Increased blood pressure

Rare

*A variety of allergic skin reactions, with or without systemic features such as bronchospasm, 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.

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/yellowcard

4.9. Overdose

Paracetamol

Liver damage is likely in patients who have taken more than the recommended amounts of paracetamol. It is considered that excess quantities of toxic metabolite become irreversibly bound to liver tissue. Some patients may be at increased risk of liver damage from paracetamol toxicity.

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

Paracetamol overdose may cause liver failure, which may lead to liver transplant and death.

Symptoms of paracetamol overdose usually occur within the first 24 hours and are pallor, nausea, vomiting, anorexia and abdominal pain.

Simultaneously, increased levels of hepatic transaminases (AST, ALT), lactate dehydrogenase and bilirubin are observed together with increased prothrombin time that may appear 12 to 48 hours after administration. Abnormalities of glucose metabolism and metabolic acidosis may occur. Clinical symptoms of liver damage are usually evident initially after 2 days, and reach a maximum after 4 to 6 days.

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. Other non-hepatic symptoms that have been reported following paracetamol overdosage include myocardial abnormalities and pancreatitis.

In severe poisoning, hepatic failure may progress to encephalopathy, haemorrhage, hypoglycaemia, cerebral oedema, and death.

Management

Immediate treatment is essential in the management of paracetamol overdose. Despite a lack of symptoms, seek immediate advice from your Poison Centre and refer patients to hospital urgently for 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.

Paracetamol concentrations in blood should be measured not less than 4 hours after overdose in order to be able to assess the risk of developing liver damage (using the paracetamol overdose nomogram). However, N-acetylcysteine (NAC) treatment should be started immediately when massive overdose is suspected.

The administration of activated charcoal may be beneficial when performed within one hour of the overdose but can be considered for up to four hours after the overdose.

Intravenous (IV) infusion (or oral administration if IV infusion is not possible) of the antidote N-acetylcysteine should be started if possible before the 8th hour. The effectiveness of the antidote declines sharply after this time. N-acetylcysteine can, however, give some degree of protection even after 8 hours, and up to 24 hours, but in these cases prolonged treatment is given. If vomiting is not a problem, oral methionine may be a suitable alternative for remote areas, outside hospital.

Symptomatic treatment should be implemented.

Pseudoephedrine

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.