4.1. Therapeutic indications

For the relief of symptoms associated with the pain and congestion of sinusitis, including relief of aches and pains, headache, nasal congestion and lowering of temperature.

4.2. Posology and method of administration

Route of administration: Oral

Swallow whole with water. Do not chew.

For all indications:

Adults, the elderly and children aged 16 years and over:

Two capsules every 4 to 6 hours when necessary to a maximum of 8 capsules (4 doses) in 24 hours.

Dosage should not be continued for longer than 3 days without consulting a doctor.

Children under 16 years:

Not to be used unless recommended by a doctor.

4.3. Contraindications

Paracetamol: Hypersensitivity to paracetamol or any of the other constituents.

Caffeine: Should be given with care to patients with a history of peptic ulcer.

Phenylephrine Hydrochloride: Severe coronary heart disease and cardiovascular disorders. Hypertension. Hyperthyroidism. Contraindicated in patients currently receiving or within two weeks of stopping therapy with monoamine oxidase inhibitors.

Not to be used in children under the age of 16 years.

Avoid in patients with prostatic enlargement.

4.4. Special warnings and precautions for use

Care is advised in the administration of paracetamol to patients with severe renal or severe hepatic impairment. The hazards of overdose are greater in those with non-cirrhotic alcoholic liver disease.

Use with caution in patients with Raynaud's Phenomenon and diabetes mellitus.

The following warnings will appear on the pack: -

CONTAINS PARACETAMOL

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

Talk to a doctor at once if you take too much of this medicine, even if you feel well. Do not take more medicine than the label tells you to. If you do not get better, talk to your doctor. Keep out of the sight and reach of children.

The Label shall say:

Talk to a doctor at once if you take much of this medicine, even if you feel well.

The Leaflet shall say:

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. Go to your nearest hospital casualty department. Take your medicine and this leaflet with you.

If you are pregnant or breast-feeding, think you may be pregnant or are planning to have a baby, ask your doctor or pharmacist for advice before taking this medicine.

This medicine contains less than 1 mmol sodium (23 mg) per 2 capsules, that is to say essentially 'sodium-free'.

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 or 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.

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

Enzyme-inducing drugs may increase hepatic damage, as does excessive intake of alcohol. The speed of absorption of paracetamol may be increased by metoclopramide or domperidone and absorption reduced by cholestyramine.

These interactions are considered to be of unlikely clinical significance in acute usage at the dosage regimen proposed.

Medical advice should be sought before taking paracetamol-caffeine-phenylephrine in combination with the following drugs:

Monoamine oxidase inhibitors

(including moclobemide)

Hypertensive interactions occur between sympathomimetic amines such as phenylephrine and monoamine Oxidase inhibitors (see contraindications).

Sympathomimetic amines

Concomitant use of phenylephrine with other sympathomimetics amines can increase the risk of cardiovascular side effects (see warnings and precautions).

Beta-blockers and other antihypertensives (including debrisoquine, guanethidine, reserpine, methyldopa)

Phenylephrine may reduce the efficacy of betablocking drugs and antihypertensive drugs. The risk of hypertension and other cardiovascular side effects may be increased (see contraindications).

Tricyclic antidepressants (eg amitriptyline)

May increase the risk of cardiovascular side effects with phenylephrine (see contraindications)

Digoxin and cardiac glycosides

Concomitant use of phenylephrine with digoxin or cardiac glycosides may increase the risk of irregular heartbeat or heart attack

Ergot alkaloids

(ergotamine and methysergide) increased risk of ergotism

Warfarin and other coumarins

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

Paracetamol

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 use of paracetamol with increased risk of bleeding; occasional doses have no significant effect.

Drugs which induce hepatic microsomal enzymes, such as alcohol, barbiturates, monoamine oxidase inhibitors and tricyclic antidepressants, may increase the hepatotoxicity of paracetamol, particularly after overdosage. Contraindicated in patients currently receiving or within two weeks of stopping therapy with monoamine oxidase inhibitors because of a risk of hypertensive crisis.

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 risk factors (see section 4.4)

Phenylephrine Hydrochloride

Phenylephrine may adversely interact with other sympathomimetics, vasodilators and beta blockers.

4.6. Fertility, pregnancy and lactation

Paracetamol

A large amount of data on pregnant women indicate neither malformative, nor feto/neonatal toxicity. Epidemiological studies on neurodevelopment in children exposed to paracetamol in utero show inconclusive results. If clinically needed, paracetamol can be used during pregnancy however it should be used at the lowest effective dose for the shortest possible time and at the lowest possible frequency.

Paracetamol is excreted in breast milk but not in a clinically significant amount. Available published data do not contraindicate breast feeding.

Caffeine

Taken during pregnancy, it appears that the half-life of caffeine is prolonged. This is a possible contributing factor in hyperemesis gravidarum (morning sickness).

Caffeine appears in breast milk. Irritability and poor sleeping pattern in the infant have been reported.

Phenylephrine Hydrochloride

Due to the vasoconstrictive properties of phenylephrine the product should be used with caution in patients with a history of pre-eclampsia. Phenylephrine may reduce placental perfusion and the product should be used in pregnancy only if the benefits outweigh this risk. There is no information on use in lactation.

4.7. Effects on ability to drive and use machines

None known

4.8. Undesirable effects

The frequency of occurrence of undesirable effect is usually classified as follows:

Very common (> 1/10)

Common (> 1/100 to < 1/10)

Uncommon (> 1/1,000 to < 1/100)

Rare (> 1/10,000 to 1/1,000)

Very rare (< 1/10,000)

Not known (incidence cannot be assessed on the basis of the available data).

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. Due to limited clinical trial data, the frequency of these adverse events is not known (cannot be estimated from available data), but post-marketing experience indicates that adverse reactions to paracetamol are rare and serious reactions are very rare.

Paracetamol

Body System

Undesirable effect

Blood and lymphatic system disorders

Thrombocytopenia

Agranulocytosis

These are not necessarily causally related to paracetamol.

Immune system disorders

Anaphylaxis

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

Respiratory, thoracic and mediastinal disorders

Bromchospasm*

Hepatobiliary disorders

Hepatic dysfunction

Metabolism and nutrition disorders

High anion gap metabolic acidosis (Frequency Not Known)

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

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.

Caffeine

Adverse reactions identified through post-marketing use with caffeine are listed below. The frequency of these reactions is unknown.

Central Nervous system

Nervousness and anxiety

Irritability, Restlessness and Excitability

Dizziness

When the recommended paracetamol-caffeine dosing regimen is combined with dietary caffeine intake, the resulting higher dose of caffeine may increase the potential for caffeine-related adverse effects such as insomnia, restlessness, anxiety, irritability, headaches, gastrointestinal disturbances and palpitations.

Phenylephrine

The following adverse events have been observed in clinical trials with phenylephrine and may therefore represent the most commonly occurring adverse events.

Body System

Undesirable effect

Psychiatric disorders

Nervousness

Nervous system disorders

Headache, dizziness, insomnia

Cardiac disorders

Increased blood pressure

Gastrointestinal disorders

Nausea, vomiting, diarrhoea

Adverse reactions identified during post-marketing use are listed below. The frequency of these reactions is unknown.

Eye disorders

Mydriasis, acute angle closure glaucoma, most likely to occur in those with closed angle glaucoma

Cardiac disorders

Tachycardia, palpitations

Skin and subcutaneous disorders

Allergic reactions (e.g. rash, urticaria, allergic dermatitis). Hypersensitivity reactions – including cross-sensitivity with other sympathomimetics may occur

Renal and urinary disorders

Dysuria, urinary retention. This is most likely to occur in those with bladder outlet obstruction, such as prostatic hypertrophy.

Very rare cases of serious skin reactions have been reported.

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 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 British National Formulary (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 24 hours from ingestion should be discussed with the National Poisons Information Service (NPIS) or a liver unit.

CAFFEINE

Doses over 1g are probably necessary to induce toxicity, 2 – 5g to produce severe toxicity and 5 – 10g is likely to be lethal.

Symptoms include: epigastric pain, vomiting, diuresis, tachycardia, CNS stimulation (insomnia, restlessness, excitement, agitation, jitteriness, tremors, convulsions).

No specific antidote is available, reduce or stop dosage and avoid excessive intake of coffee or tea.

PHENYLEPHRINE HYDROCHLORIDE

Severe overdosage may produce hypertension and associated reflex bradycardia. Treatment measures include early gastric lavage and symptomatic and supportive measures. The hypertensive effects may be treated with an alpha-receptor blocking agent (such as phentolamine mesylate 6 – 10 mg) given intravenously, and the bradycardia treated with atropine, preferably only after the pressure has been controlled.