Paracetamol/Guaifenesin/Phenylephrine Hcl Wrafton 1000 Mg/200 Mg/12.2 Mg Powder For Oral Solution
SUMMARY OF PRODUCT CHARACTERISTICS
1 NAME OF THE MEDICINAL PRODUCT
Paracetamol, Guaifenesin, Phenylephrine Hydrochloride 1000 mg/200 mg/12.2 mg powder for oral solution
2 QUALITATIVE AND QUANTITATIVE COMPOSITION
Active Ingredient mg/Sachet
Phenylephrine hydrochloride 12.2
Excipients of known effect:
Sucrose 2000 mg Aspartame (E951) 30 mg
Sodium citrate (E331) 500 mg (contains 117.3 mg sodium) For a full list of excipients, see section 6.1.
3 PHARMACEUTICAL FORM
Powder for oral solution.
Sachets containing the drug product, an off-white powder.
4 CLINICAL PARTICULARS
4.1 Therapeutic indications
For the relief of symptoms associated with colds and flu and the pain and congestion of sinusitis, including aches and pains, headache, blocked nose and sore throat, chills,
lowering of temperature, and to loosen stubborn mucous and provide relief from chesty coughs.
4.2 Posology and method of administration
For oral use after dissolving the contents of the sachet in a standard mug of hot, but not boiling water (250 ml). Allow to cool to a drinkable temperature. Drink all of the yellow solution within 30 minutes.
Adults, including the elderly:
One sachet every four hours as required. Do not take more than 4 sachets (4 doses) in any 24 hour period.
Not to be taken by children or adolescents under 18 years old.
4.3 Contraindications
Hypersensitivity to paracetamol, guaifenesin or phenylephrine or any of the other ingredients.
Hypertension (high blood pressure), hyperthyroidism, diabetes, serious heart disease, cardiovascular disorders or those patients receiving or within two weeks of stopping therapy with monoamine oxidase inhibitors (see Section 4.5).
Those taking tricyclic anti-depressant drugs or beta-blocking drugs (see Section 4.5).
Phaeochromocytoma.
Prostatic enlargement or urinary retention.
Use in patients with closed angle glaucoma, including closed angle glaucoma.
Hepatic and renal impairment.
Use in patients who are currently receiving other sympathomimetic drugs (see Section 4.5).
4.4 Special warnings and precautions for use
The physician or pharmacist should check that sympathomimetic-containing preparations are not simultaneously administered by several routes i.e. orally and topically (nasal, aural and eye preparations).
Care is advised in the administration of paracetamol to patients with severe renal or hepatic impairment. The hazards of overdose are greater in those with non-cirrhotic alcoholic liver disease.
Patients suffering from chronic cough or asthma should consult a physician before taking this product.
Patients should stop using the product and consult a health care professional if cough lasts for more than 5 days or comes back, or is accompanied by a fever, rash or persistent headache.
Do not take with a cough suppressant.
Medical advice should be sought before taking this product in patients with these conditions:
An enlargement of the prostate gland
Occlusive vascular disease (e.g. Raynaud's Phenomenon)
Cardiovascular disease
This product should not be used by patients taking other sympathomimetics (such as decongestants, appetite suppressants and amphetamine-like psychostimulants).
Concomitant use of other paracetamol-containing products should be avoided. If symptoms persist consult your doctor.
Use with caution in patients with diabetes mellitus.
Patients with prostatic hypertrophy may have increased difficulty with micturition.
Sympathomimetic-containing products should be used with great care in patients suffering from angina.
Sympathomimetic-containing products may act as cerebral stimulants giving rise to insomnia, nervousness, hyperpyrexia, tremor and epileptiform convulsions.
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 a source of phenylalanine equivalent to 17 mg per sachet. May be harmful to people with phenylketonuria.
This medicinal product contains 117 mg of sodium per dose. To be taken into consideration by patients on a controlled sodium diet.
Long term use of the product is not recommended. Do not take with alcohol.
Special label warnings
If you are taking medication or are under medical care, consult your doctor before using this medicine. Do not take with other cold, flu or decongestant products.
Do not exceed the stated dose.
If symptoms persist or worsen, consult your doctor.
Keep all medicines out of the reach and sight of children.
Contains paracetamol. Do not take with any other paracetamol-containing products. Immediate medical advice should be sought in the event of an overdose, even if you feel well.
Special leaflet warnings
Contains paracetamol. Do not take with any other paracetamol-containing products.
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.
If you are taking medication or are under medical care, consult your doctor before using this medicine. Do not take with other cold, flu or decongestant products.
4.5 Interaction with other medicinal products and other forms of interaction
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, although occasional doses have no significant effect.
The hepato-toxicity of paracetamol may be potentiated by excessive intake of alcohol.
Pharmacological interactions involving paracetamol with a number of other drugs have been reported. These are considered to be of unlikely clinical significance in acute use at the dosage regimen proposed.
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.
PHENYLEPHRINE HYDROCHLORIDE
Phenylephrine may adversely interact with other sympathomimetics, vasodilators and beta blockers.
Sympathomimetic-containing products should be used with great care in patients receiving phenothiazines or tricylic antidepressants.
Concurrent use with halogenated anaesthetic agents such as chloroform, cyclopropane, halothane, enflurane or isoflurane may provoke or worsen ventricular arrhythmias.
Phenylephrine should be used with caution in combination with the following drugs as interactions have been reported:
|
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 sympathomimetic amines can increase the risk of cardiovascular side effects. |
|
Beta-blockers and other antihypertensives (including debrisoquine, guanethidine, reserpine, methyldopa) |
Phenylephrine may reduce the efficacy of beta-blocking drugs and antihypertensive drugs. The risk of hypertension and other cardiovascular side effects may be increased. |
|
Tricyclic antidepressants (e.g. amitriptyline) |
May increase the risk of cardiovascular side effects with phenylephrine. |
|
Phenothiazides used as sedatives |
May potentiate CNS effects. |
|
Ergot alkaloids (ergotamine and methylsergide) |
Increased risk of ergotism |
|
Cardiac glycosides e.g. digitalis |
Increased risk of arrhythmia or heart attack |
Halogenated anaesthetic agents May provoke or worsen ventricular
such as cyclopropane, halothane, arrhythmias
enflurane, isoflurane__
GUAIFENESIN
If urine is collected within 24 hours of a dose of this product a metabolite of guaifenesin may cause a colour interference with laboratory determinations of urinary-5-hydroxyindolacetic acid (5-HIAA) and vanillylmandelic acid (VMA).
4.6 Fertility, pregnancy and lactation
Paracetamol
A large amount of data on pregnant women indicate no malformative nor feto/neonatal toxicity of paracetamol. Paracetamol can be used during pregnancy if clinically needed however it should be used at the lowest effective dose for the shortest possible time and at the lowest possible frequency.
Guaifenesin
There are no or limited amount of data from the use of guaifenesin in pregnant women.
Phenylephrine Hydrochloride
Based on human experience phenylephrine hydrochloride causes congenital malformations when administered during pregnancy. It has also been shown to have possible associations with fetal hypoxia. Phenylephrine should not be used during pregnancy unless the clinical condition of the woman requires treatment.
Breast-feeding
Paracetamol
Paracetamol / metabolites are excreted in human milk, but at therapeutic doses of the product no effects on the breastfed newborns/infants are anticipated.
Guaifenesin
There are no or limited amount of data from the use of guaifenesin in pregnant women.
Phenylephrine Hydrochloride
There is insufficient information on the excretion of Phenylephrine Hydrochloride/metabolite excreted in human milk.
Fertility
There are no or limited amount of data regarding the use of paracetamol, guaifenesin or phenylephrine hydrochloride and its impact on fertility.
4.7 Effects on ability to drive and use machines
None known.
Patients should be advised not to drive or operate machinery if affected by dizziness.
4.8 Undesirable effects
The active ingredients are usually well tolerated in normal use.
PARACETAMOL
Blood and lymphatic system disorders Frequency unknown
Agranulocytosis; Blood disorders; Thrombocytopenia
Hepatobiliary disorders Frequency unknown Hepatic function abnormal
Immune system disorders
Frequency unknown
Anaphylactic reaction; Hypersensitivity
Respiratory, thoracic and mediastinal disorders
Frequency unknown
Bronchospasm
Skin and subcutaneous tissue disorders Frequency unknown
Angioedema; Dermatitis allergic; Rash; Stevens Johnson syndrome GUAIFENESIN
Gastrointestinal disorders Frequency unknown
Abdominal discomfort, nausea and vomiting
Immune system disorders Frequency unknown Hypersensitivity
PHENYLEPHRINE HYDROCHLORIDE
Cardiac disorders Frequency unknown
Arrhythmia; Palpitations; Bradycardia; Tachycardia
Eye disorders
Frequency unknown
Angle closure glaucoma; Mydriasis
Gastrointestinal disorders Frequency unknown Nausea; Vomiting; Diarrhoea
General disorders and administration site condition
Frequency unknown
Irritability
Immune system disorders
Frequency unknown Hypersensitivity
Investigations Frequency unknown Cross sensitivity reaction
Nervous system disorders Frequency unknown
Dizziness; Headache; Paraesthesia; Tremor
Psychiatric disorders Frequency unknown
Anxiety; Agitation; Hallucination; Insomnia; Nervousness; Restlessness
Renal and urinary disorders Frequency unknown Dysuria; Urinary retention
Skin and subcutaneous tissue disorders
Frequency unknown
Dermatitis allergic; Rash; Urticaria
Vascular disorders
Frequency unknown
Peripheral coldness; Hypertension
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 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. 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 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 one hour. Plasma paracetamol concentration should be measured at four 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 eight 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.
GUAIFENESIN
Gastrointestinal discomfort has occasionally been reported with Guaifenesin.
Very large doses of guaifenesin can cause nausea and vomiting. Vomiting should be treated by fluid replacement and monitoring of electrolytes.
PHENYLEPHRINE HYDROCHLORIDE
Phenylephrine hydrochloride may elevate blood pressure with headache, vomiting and rarely palpitations, tachycardia or reflex bradycardia, tingling and coolness of the skin. There have been rare reports of allergic reactions.
Symptoms of overdosage include irritability, palpitations, hypertension, difficulty in micturition, nausea, vomiting, thirst and convulsions.
Severe overdosage of phenylephrine may produce hypertension and associated reflex bradycardia, haemodynamic changes and cardiovascular collapse with respiratory depression.
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. In severe overdosage gastric lavage and aspiration should be performed. Symptomatic and supportive measures should be undertaken, particularly with regard to cardiovascular and respiratory systems. Convulsions should be controlled with intravenous diazepam. Chlorpromazine may be used to control marked excitement and hallucinations. Severe hypertension may need to be treated with an alpha-adrenoreceptor blocking drug, such as phentolamine. A beta blocker may be required to control cardiac arrhythmias.
5 PHARMACOLOGICAL PROPERTIES
5.1 Pharmacodynamic properties
Pharmacotherapeutic Group: Paracetamol, combination excluding
psycholeptics.
N02BE51
ATC code:
PARACETAMOL
Analgesic:
The mechanism of analgesic action has not been fully determined. Paracetamol may act predominantly by inhibiting a prostaglandin synthesis in the central nervous system (CNS) and to a lesser extent through a peripheral action by blocking pain-impulse generation. The peripheral action may also be due to inhibition of prostaglandin synthesis or to inhibition of the synthesis or actions of other substances that sensitise pain receptors to mechanical or chemical stimulation.
Antipyretic:
Paracetamol probably produces antipyresis by acting on the hypothalamic heatregulating centre to produce peripheral vasodilation resulting in increased blood flow through the skin, sweating and heat loss. The central action probably involves inhibition of prostaglandin synthesis in the hypothalamus.
GUAIFENESIN
Guaifenesin is a well known expectorant. Such expectorants are known to increase the volume of secretions in the respiratory tract and therefore to facilitate their removal by
cilary action and coughing.
PHENYLEPHRINE HYDROCHLORIDE
Sympathomimetic amines, such as phenylephrine, act on alpha-adrenergic receptors of the respiratory tract to produce vasoconstriction, which temporarily reduces the swelling associated with inflammation of the mucous membranes lining the nasal and sinus passages. This allows the free drainage of the sinusoidal fluid from the sinuses.
In addition to reducing mucosal lining swelling, decongestants also suppress the production of mucous, therefore preventing a build up of fluid within the cavities which could otherwise lead to pressure and pain.
5.2 Pharmacokinetic properties
PARACETAMOL
Absorption and Fate
Paracetamol is rapidly absorbed from the gastro-intestinal tract with peak plasma concentrations occurring between 10 and 120 minutes after oral administration. It is metabolised in the liver and excreted in the urine mainly as the glucuronide and sulphate conjugates. Less than 5% is excreted as unchanged paracetamol. The elimination half-life varies from about 1 to 4 hours.
Plasma-protein binding is negligible at usual therapeutic concentrations but increases with increasing concentrations.
A minor hydroxylated metabolite which is usually produced in very small amounts by mixed-function oxidases in the liver and which is usually detoxified by conjugation with liver glutathione may accumulate following paracetamol overdose and cause liver damage.
GUAIFENESIN
Guaifenesin is rapidly absorbed after oral administration. It is rapidly metabolised by oxidation to ^-(2 methoxy-phenoxy)lactic acid, which is excreted in the urine.
PHENYLEPHRINE HYDROCHLORIDE
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
There are no preclinical data of relevance to the prescriber additional to that already covered in other sections of the SPC.
6 PHARMACEUTICAL PARTICULARS
6.1 List of excipients
Sucrose
Citric acid anhydrous Tartaric acid Sodium citrate Acesulfame potassium E950 Aspartame E951
Powdered menthol flavour (containing natural menthol, corn maltodextrin and arabic gum)
Lemon flavours (containing lemon concentrate juice, lemon essential oil, lime essential oil, natural citral, natural citronellol, natural linalool, corn/maize maltodextrin, corn modified starch E1450, silicon dioxide, arabic gum, sucrose, glyceryl triacetate E1518, alpha-tocopherol E307 and butylated hydroxyanisole E320)
Quinoline yellow E104.
Incompatibilities
6.2
None known.
6.3 Shelf life
36 months.
Shelf life after reconstitution: 30 minutes.
6.4 Special precautions for storage
Do not store above 25 °C.
6.5 Nature and contents of container
Pack sizes of five and ten sachets are available.
The sachet laminate comprises:
Ionomer (product contact layer)/aluminium foil /low density polyethylene/bleached paper (outer layer).
6.6 Special precautions for disposal
No special requirements for disposal.
Any unused product or waste material should be disposed of in accordance with local requirements.
7 MARKETING AUTHORISATION HOLDER
Wrafton Laboratories Limited Braunton
Devon EX33 2DL
8 MARKETING AUTHORISATION NUMBER(S)
PL 12063/0131
9 DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION
29/09/2015
10 DATE OF REVISION OF THE TEXT
29/09/2015