4.1. Therapeutic indications

For the short term symptomatic relief of the symptoms of colds and influenza, including aches and pains, headache, nasal congestion, tickly sore throat and chesty coughs.

4.2. Posology and method of administration

For oral administration.

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

Age

How much

How often (in 24hrs)

Adults, the elderly and children over 16 years

20ml

Up to four times

Children 12-16 years

15ml

Up to four times

• Leave at least 4hrs between doses

• Do not take more than four doses in 24hrs

• Do not give to children under 12 years unless your doctor tells you to

4.3. Contraindications

Patients with known hypersensitivity to paracetamol, phenylephrine hydrochloride, guaifenesin or cetylpyridinium chloride or any of the other ingredients.

Contraindicated during pregnancy.

Avoid in patients with prostatic enlargement.

4.4. Special warnings and precautions for use

Covonia ALL-IN-ONE Chesty Cough, Cold & Flu Relief Oral Solution is not suitable for long term use.

Always use the measuring cup supplied with the pack.

Paracetamol should be used with care in patients with severe renal or hepatic impairment. The hazard of overdose is greater than those with non–cirrhotic alcoholic liver disease.

Do not take with other cold or decongestant medicines or any other paracetamol-containing products.

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

Phenylephrine should be used with care in patients with hyperthyroidism, cardiovascular disease, diabetes mellitus, closed angle glaucoma and hypertension.

Do not exceed the stated dose.

If symptoms persist consult your doctor.

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

Ingredients with specified warnings

This medicine contains Maltitol Liquid and 3.4g sorbitol per 20ml dose. Sorbitol may cause gastrointestinal discomfort and mild laxative effect. Sorbitol is a source of fructose. Patients with rare hereditary problems of fructose intolerance should not take this medicine.

This medicine contains 2880mg of alcohol (ethanol) in each 20ml dose. The amount in 20ml of this medicine is equivalent to 72ml of beer or 29ml of wine. The amount of alcohol in this medicine is not likely to have an effect in adults and adolescents, and its effects in children are not likely to be noticeable. It may have some effects in younger children, for example feeling sleepy. The alcohol in this medicine may alter the effects of other medicines. To be taken into account in those who are breastfeeding, and those who are addicted to alcohol. A dose of 20ml of this medicine administered to an adult weighing 70kg would result in exposure to 41.1mg/kg of ethanol which may cause a rise in blood alcohol concentration (BAC) of about 7.2mg/100ml. Co-administration with medicines containing e.g. propylene glycol or ethanol may lead to accumulation of ethanol and induce adverse effects.

This medicine contains 4300mg propylene glycol per 20ml dose. Not to be taken by those who are breastfeeding or suffer from liver or kidney disease, unless recommended by a doctor.

This medicine contains less than 1 mmol sodium (23 mg) per dose, 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 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.

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

The speed of absorption of paracetamol may be increased by metoclopramide or domperidone; and absorption reduced by colestyramine. The anti-coagulant 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. Alcohol may potentiate the hepatotoxicity of paracetamol.

Phenylephrine may reduce the efficacy of beta-blocking drugs and antihypertensive drugs; the product is contraindicated in such circumstances.

With phenylephrine there is a possibility that an increased risk of arrhythmias may occur in patients receiving cardiac glycosides or tri-cyclic anti-depressants. Phenylephrine interacts with monoamine oxidase inhibitors; it should not therefore, be taken by patients receiving monoamine oxidase inhibitors or within 14 days of stopping such medication.

Guaifenesin may interfere with diagnostic measurements of urinary 5-hydroxyindoleacetic acid or vanillylmandelic acid.

Co-administration with medicines containing e.g. propylene glycol or ethanol may lead to accumulation of ethanol and induce adverse effects, in particular in young children with low or immature metabolic capacity.

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. Pregnancy and lactation

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, but patients should follow the advice of their doctor regarding its use. Paracetamol is excreted in breast milk but not in a clinically significant amount. Available published data do not contraindicate breast feeding.

Phenylephrine should not be taken during pregnancy as it has been reported to cause foetal hypoxia. Excretion in breast milk is reported to be minimal.

Guaifenesin is considered safe for use in lactating women and at normal doses in pregnant women.

4.8. Undesirable effects

Undesirable effects with paracetamol are rare, however, hypersensitivity including skin rashes may occur. Very rare cases of serious skin reactions have been reported.

There have been a few reports of blood dyscrasias including thrombocytopenia and agranulocytosis after regular or excessive ingestion of paracetamol, and of acute pancreatitis after ingestion of above normal dosage.

Undesirable effects are rare with normal doses of phenylephrine, however it can cause the adverse effects typical of sympathomimetics including: hypertension, palpitations (tachycardia), headache, dizziness, vomiting, diarrhoea and insomnia. Urinary retention has also been reported – this is more likely to occur in men with an enlarged prostate (frequency not known).

Metabolism and nutrition disorders

Frequency not known: 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.

Guaifenesin has occasionally been reported to cause gastrointestinal discomfort.

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

Liver damage is possible in adults who have taken 10 g or more of paracetamol. Ingestion of 5 g 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, phenobarbital, phenytoin, primidone, rifampicin, St. John's Wort or other drugs that induce liver enzymes

Or

b) Regularly consumes ethanol in excess of recommended amounts.

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 include 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, coma 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 24 hours from ingestion should be discussed with the NPIS or a liver unit.

The principal features of phenylephrine overdosage are a rise in blood pressure and associated reflex bradycardia. A severe hypertensive response can be countered by administration of an alpha-antagonist and any reflex bradycardia by atropine (but preferably only after the pressure has been controlled by alpha-adrenergic blockade).

Very large doses of guaifenesin may cause nausea and vomiting.