Paracetamol, Phenylephrine Hydrochloride and Ascorbic Acid 1000 mg/10 mg/40 mg – Summary of Product Characteristics (SmPC) for healthcare professionals

1 NAME OF THE MEDICINAL PRODUCT

Paracetamol, Phenylephrine hydrochloride and Ascorbic acid 1000mg/10mg/40mg Powder for Oral Solution

2 QUALITATIVE AND QUANTITATIVE COMPOSITION

Active Constituents mg/6.427g powder

Paracetamol 1000.00

Ascorbic Acid 40.00

Phenylephrine Hydrochloride 10.00

Excipients of known effect

Sucrose

Sodium

3 PHARMACEUTICAL FORM

Powder

4 CLINICAL PARTICULARS

4.1 Therapeutic indications

Short term symptomatic relief of symptoms of influenza, feverishness, chills and colds including headache, sore throat pain, aches and pains, nasal congestion, sinusitis and its associated pain, and acute nasal catarrh.

4.2 Posology and method of administration

Directions for use

Empty contents of sachet into a beaker. Half fill with very hot water. Stir well. Add cold water as necessary and sugar if desired.

Recommended Dose and Dosage Schedule

Adults (including elderly) and children aged 16 years and over:

One sachet to be taken every four to six hours as necessary. Do not exceed four sachets per 24 hours.

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

Not to be given to children under 16 years of age, except on medical advice.

The product should not be used continuously for more than seven days without medical advice.

4.3 Contraindications

Known hypersensitivity to paracetamol or any of the other constituents.

Concomitant use of other sympathomimetic decongestants.

Phaeochromocytoma.

Closed angle glaucoma.

An enlargement of the prostate gland.

Hepatic or severe renal impairment, hypertension, hyperthyroidism, diabetes, and heart disease.

Patients taking tricyclic antidepressants, or beta-blocking drugs and those who are taking or who have taken within the last two weeks monoamine oxidase inhibitors (see section 4.5).

4.4 Special warnings and precautions for use

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

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.

Medical advice should be sought before taking this product in patients with these conditions:

• Occlusive Vascular disease (e.g. Raynaud’s Phenomenon)
• Cardiovascular disease
• Glutathione depletion due to metabolic deficiencies

Use with caution in patients taking the following medications (see interactions).

• digoxin and cardiac glycosides
• ergot alkaloids (e.g. ergotamine and methysergide)

This product should not be used by patients taking other sympathomimetics (such as decongestants, appetite suppressants and amphetamine-like psychostimulants).

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

Contains 4g sucrose per dose. This should be taken into account in patients with diabetes.

This medicinal product contains 131 mg sodium per dose. To be taken into consideration by patients on a controlled sodium diet.

Do not exceed the stated dose.

Patients should be advised not to take other paracetamol-containing or other cold, flu or decongestant products concurrently. Medical advice should be sought if symptoms worsen, persist for more than 7 days, or are accompanied by high fever, skin rash or persistent headache. Keep out of the reach and sight of children.

Consult your doctor if you are taking warfarin.

Special label warnings

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

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

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

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.

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)

Phenylephrine should be used with caution in combination with the following drugs as interactions have been reported.

4.6 Fertility, Pregnancy and lactation

Due to the phenylephrine content this product should not be used in pregnancy or whilst breast-feeding without medical advice. This product should not be used during pregnancy or lactation unless the expected benefit to the mother justifies the potential risk to the foetus or newborn. The lowest effective dose and shortest duration of treatment should be considered. Phenylephrine may be excreted in breast milk

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

Paracetamol

Adverse events 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.

*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

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

Phenylephrine

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

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

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 5 g or more of paracetamol may lead to liver damage if the patient has risk factors (see below).

Risk factors

If the patient

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

Or

1. b) Regularly consumes ethanol in excess of recommended amounts.

Or

1. 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.

Phenylephrine

Symptoms and signs

Phenylephrine overdosage is likely to result in effects similar to those listed under adverse reactions. Additional symptoms may include hypertension and possibly reflux bradycardia. In severe cases confusion, hallucinations, seizures and arrythmias may occur. However, the amount required to produce serious phenylephrine toxicity would be greater than required to cause paracetamol-related toxicity.

Treatment

Treatment should be as clinically appropriate. Severe hypertension may need to be treated with an alpha blocking drug such as phentolamine.

Ascorbic acid

Symptoms and signs

High doses of ascorbic acid (>3000 mg) may cause transient osmotic diarrhoea and gastrointestinal effects such as nausea and abdominal discomfort. Effects of overdose of ascorbic acid would be subsumed by severe liver toxicity caused by paracetamol overdose.

5 PHARMACOLOGICAL PROPERTIES

5.1 Pharmacodynamic properties

ATC Code: N02BE51

Paracetamol: An analgesic and antipyretic.

Ascorbic acid: A common ingredient of cold and influenza combination products included to compensate for Vitamin C losses which may occur in the initial stages of acute viral infections.

Phenylephrine hydrochloride: A sympathomimetic decongestant.

The active ingredients are not known to cause sedation.

5.2 Pharmacokinetic properties

Paracetamol: is readily absorbed from the gastrointestinal tract. It is metabolised in the liver and excreted in the urine, mainly as glucoronide and sulphate conjugates.

Ascorbic Acid: is readily absorbed from the gastrointestinal tract and is widely distributed in the body tissues, 25% bound to plasma proteins. Ascorbic Acid in excess of the body’s needs is eliminated in the urine as metabolites.

Phenylephrine Hydrochloride: is irregularly absorbed from the gastrointestinal tract and undergoes first-pass metabolism by monoamine oxidase in the gut and liver; orally administered phenylephrine thus has reduced bioavailability. It is excreted in the urine almost entirely as the sulphate conjugate.

5.3 Preclinical safety data

Pre-clinical safety data on these active ingredients in the literature have not revealed any pertinent and conclusive findings which are of relevance to the recommended dosage and use of the product and which have not already been mentioned elsewhere in this Summary.

The toxicity of paracetamol has been extensively studied in numerous animal species. Pre-clinical studies in rats and mice have indicated single dose oral LD50 values of 3.7 g/kg and 338 mg/kg, respectively. Chronic toxicity in these species at large multiples of the human therapeutic dose, occurs as degeneration and necrosis of hepatic, renal and lymphoid tissue, and blood count changes. The metabolites believed responsible for these effects have also been demonstrated in man. Paracetamol should not, therefore, be taken for long periods of time, and in excessive doses. At normal therapeutic doses, paracetamol is not associated with genotoxic or carcinogenic risk. There is no evidence of embryo-or foeto-toxicity from paracetamol in animal studies.

6 PHARMACEUTICAL PARTICULARS

6.1 List of excipients

Sucrose

Citric acid anhydrous

Sodium citrate

Maize starch

Sodium cyclamate

Saccharin sodium

Colloidal anhydrous silica

Lemon flavour

Natural curcumin (E100)

6.2 Incompatibilities

None known

6.3 Shelf life

Three years

6.4 Special precautions for storage

Do not store above 25°C

6.5 Nature and contents of container

The product is packed in either laminate sachets comprising paper/polythene/aluminium foil/polythene or child resistant laminate composed of polyethylene terephthalate/polyethylene/aluminium foil/EMAA. Five or ten sachets may be contained in a cardboard carton.

6.6 Special precautions for disposal

Not applicable

7 MARKETING AUTHORISATION HOLDER

Thornton & Ross Ltd.

Linthwaite,

Huddersfield,

HD7 5QH, UK

8 MARKETING AUTHORISATION NUMBER(S)

PL 00240/0625

9 DATE OF FIRST AUTHORISATION/RENEWAL OF THE

AUTHORISATION

16/05/2024

10 DATE OF REVISION OF THE TEXT

27/05/2025