Theraflu Cold And Cough Syrup
SUMMARY OF PRODUCT CHARACTERISTICS
1 NAME OF THE MEDICINAL PRODUCT
Theraflu Cold and Cough Syrup
Paracetamol 500 mg/30 ml, Phenylephrine hydrochloride 10 mg/30ml, Guaifenesin 200 mg/30 ml
2 QUALITATIVE AND QUANTITATIVE COMPOSITION
Each 30 ml dose contains paracetamol 500 mg, phenylephrine hydrochloride 10 mg and guaifenesin 200 mg.
Excipients with known effect: each dose also contains maltitol liquid (E965) 9.5 g, sodium benzoate, sodium citrate, disodium edetate (total sodium 15.68 mg), propylene glycol 5.4 g, ethanol anhydrous 2.4 g (10.15 % v/v), potassium 17.27 mg and Sunset yellow (E110).
For the full list of excipients, see section 6.1.
3 PHARMACEUTICAL FORM
Syrup.
Clear, orange to dark orange syrup with a characteristic citrus odour.
4 CLINICAL PARTICULARS
4.1 Therapeutic indications
Short term relief of the symptoms of colds, chills and influenza, including mild to moderate pain, fever, nasal congestion, with an expectorant effect on a chesty cough.
Theraflu Cold and Cough is only indicated in adults.
4.2 Posology and method of administration Posology
Adults
One 30 ml measured dose. Repeat every four to six hours as needed. No more than four doses should be taken in 24 hours. Treatment duration should not exceed three days.
Patients should seek medical advice if symptoms persist for more than 3 days or worsen, or if coughing is accompanied by high fever, skin rash or persistent headache.
Paediatric population
This product should not be used in children and adolescents below 18 years of age. Patients with hepatic insufficiency
In patients with impaired hepatic function or Gilbert’s syndrome, the dose must be reduced or the dosing interval prolonged.
Patients with severe renal insufficiency
This medicine should be used with caution and medical supervision in patients with severe renal insufficiency. In these patients, the dosing interval should be prolonged up to 8 hours.
Method of administration
For oral use.
The measuring cup should be filled up to the 30 ml mark. After each use the measuring cup should be washed and dried.
4.3 Contraindications
Hypersensitivity to the active substances or to any of the excipients listed in section 6.1
Heart disease, hypertension Diabetes Hyperthyroidism Closed angle glaucoma Phaeochromocytoma
Patients who are taking or have taken monoamine oxidase inhibitors (MAOIs) within the last two weeks (see section 4.5)
Patients taking tricyclic antidepressants (see section 4.5)
Patients taking beta-blocking drugs (see section 4.5)
Patients taking other sympathomimetic drugs such as decongestants, appetite suppressants and amphetamine-like psychostimulants (see section 4.5).
4.4 Special warnings and precautions for use
Patients should NOT take any other paracetamol-containing products concurrently due to the risk of severe liver damage in case of overdose.
Patients should not take other cough, cold or decongestant products concurrently.
Patients suffering from chronic cough or asthma should consult a physician before taking this product.
Alcoholic beverages should be avoided while taking this medicine. Paracetamol should be given with caution to patients with alcohol dependence (see section 4.5). The hazards of overdose are greater in those with non-cirrhotic alcoholic liver disease.
Caution is advised in the administration of paracetamol to patients with mild and moderate renal insufficiency, mild to moderate hepatocellular insufficiency (including Gilbert’s syndrome), severe hepatic insufficiency (Child-Pugh >9), acute hepatitis, concomitant treatment with medicinal products affecting hepatic functions, glucose-6- phosphatedehydrogenase deficiency, haemolytic anaemia, dehydration, alcohol abuse and chronic malnutrition.
This medicine should be used with caution in patients with:
• Cardiovascular disease
• Prostatic hypertrophy, as they may be susceptible to urinary retention and dysuria
• Occlusive vascular disease (e.g. Raynaud's Phenomenon)
• Chronic cough, asthma, or emphysema.
This medicine should be used with caution and medical supervision in patients with severe renal insufficiency.
This medicine should only be taken if all of the following symptoms (pain and/or fever, nasal congestion and chesty cough) are present. It should be used for no more than three days. Patients should seek medical advice if symptoms persist for more than 3 days, worsen, or if coughing is accompanied by high fever, skin rash or persistent headache.
Paediatric population
This product should not be used in children below 18 years of age.
Information concerning excipients This medicinal product contains:
• Maltitol liquid (E965) 9.5 g per 30 ml dose. Patients with rare hereditary problems of fructose intolerance should not take this medicine. May have a mild laxative effect
• Ethanol. This medicinal product contains 10.15 % v/v ethanol (alcohol), i.e.
2.4 g of ethanol per 30 ml dose , equivalent to 61 ml beer or 26 ml wine. Harmful for those suffering from alcoholism To be taken into account in pregnant or breast-feeding women and high-risk groups such as patients with liver disease, or epilepsy
• Propylene glycol 5.4 g per 30 ml dose. It may cause alcohol-like symptoms
• Sodium 0.68 mmol (or 15 mg) per 30 ml dose. To be taken into consideration by patients on a controlled or low sodium diet
• Potassium 17.27 mg per 30 ml dose. To be taken into consideration by patients with reduced kidney function or patients on a controlled potassium diet
• Sunset yellow (E110), an azo colouring agent. It may cause allergic reactions.
4.5 Interaction with other medicinal products and other forms of interaction Paracetamol
The anticoagulant effect of warfarin and other coumarins may be enhanced by prolonged regular use of paracetamol, with increased risk of bleeding. Occasional use of paracetamol has no significant effect.
Metoclopramide or domperidone may increase the rate of absorption of paracetamol.
The half-life of chloramphenicol may be prolonged by paracetamol. However, topical chloramphenicol may be used concomitantly when used to treat eye infections.
Paracetamol may decrease the bioavailability of lamotrigine, with possible reduction of its effect, due to a possible induction of its metabolism in the liver.
Cholestyramine may reduce the absorption of paracetamol. Cholestyramine should not be given within one hour following paracetamol intake.
Regular use of paracetamol simultaneously with zidovudine may cause neutropenia and increases the risk of liver damage.
Salicylates/salicylamide may prolong the elimination half-life of paracetamol.
The gout treatment probenecid reduces the clearance of paracetamol, so the dose of paracetamol may be reduced in case of concomitant treatment.
Hepatotoxic substances may increase the possibility of paracetamol accumulation and overdose. The risk of hepatotoxicity of paracetamol may be increased by drugs which induce liver microsomal enzymes such as barbiturates, tricyclic antidepressants, antiepileptics (i.e., phenytoin, phenobarbital and carbamazepine), tuberculosis treatments s(i.e., rifampicine and isoniazid) and excessive alcohol intake.
Paracetamol may affect phosphotungstate uric acid tests.
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.
Phenylephrine
Phenylephrine may potentiate the action of monoamine oxidase inhibitors (MAOIs, including moclobemide and brofaromine) and may induce hypertensive interactions. Use is contraindicated in patients who are taking or have taken MAOIs within the past two weeks (see section 4.3).
Concomitant use of phenylephrine with other sympathomimetic agents or tricyclic antidepressants (e.g. amitriptyline) can increase the risk of cardiovascular side effects (see section 4.3).
Phenylephrine may reduce the efficacy of beta-blockers (see section 4.3) and other antihypertensive drugs (e.g. debrisoquine, guanethidine, reserpine, methyldopa). The risk of hypertension and other cardiovascular side effects may be increased.
Concomitant use of phenylephrine with digoxin and cardiac glycosides may increase the risk of irregular heartbeat or heart attack.
Concomitant use with ergot alkaloids (ergotamine and methylsergide) may increase risk of ergotism.
Concomitant use with halogenated anaesthetic agents such as cyclopropane, halothane, enflurane, isoflurane may provoke or worsen ventricular arrhythmias
Guaifenesin
The administration of guaifenesin may falsely elevate the VMA test (Vanillymandelic acid) if urine is collected within 24 hours of a dose of Theraflu Cold and Cough.
4.6 Fertility, pregnancy and lactation
Pregnancy
The effects of this product during pregnancy have not been fully investigated.
Epidemiological studies in human pregnancy have shown no ill effects due to paracetamol used in the recommended dosage, but patients should follow the advice of their doctor regarding its use.
There are limited data on the use of phenylephrine in pregnant women. Vasoconstriction of uterine vessels and reduced uterine blood flow associated with use of phenylephrine may result in fetal hypoxia. Use of phenylephrine should be avoided during pregnancy.
The safety of guaifenesin in pregnancy has not been fully established.
In the current status of knowledge, Theraflu Cold and Cough should be avoided during pregnancy.
Breast-feeding
The effects of this product during breastfeeding have not been specificaly investigated.
Paracetamol is excreted in breast milk but not in a clinically significant amount. Available published data do not contraindicate breast feeding.
There are no data available on whether phenylephrine is released into breast milk. Use of phenylephrine should be avoided by lactating women.
The safety of guaifenesin in lactation has not been fully established.
In the current status of knowledge, Theraflu Cold and Cough should not be used during breastfeeding.
Fertility
The effects of this product on fertility have not been specifically investigated.
Preclinical studies with paracetamol do not indicate special hazard to fertility at therapeutically relevant doses. There are no adequate reproductive toxicology studies with phenylephrine and guaifenesin.
4.7 Effects on ability to drive and use machines
No studies on the effects on the ability to drive and use machines have been performed. If affected by dizziness, patients should be advised not to drive or operate machinery.
4.8 Undesirable effects
Adverse reactions are listed below by system organ class and frequency, using the following convention: 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), including isolated reports and unknown (cannot be estimated from the available data).
Adverse events from historical clinical trial data are both infrequent and from limited patient exposure. Events reported from extensive post-marketing experience at therapeutic/labelled dose and considered attributable are tabulated below by MedDRA System Organ Class.
PARACETAMOL
Due to limited clinical trial data, the frequency of these adverse events is unknown (cannot be estimated from available data), but post-marketing experience indicates that adverse reactions to paracetamol are rare (>1/10,000 to <1/1,000) and serious reactions are very rare (<1/10,000).
|
System Organ Class |
Undesirable effect |
|
Blood and lymphatic system disorders |
Thrombocytopenia*, agranulocytosis*, leucopenia*, pancytopenia* |
|
Immune system disorders |
Anaphylaxis Cutaneous hypersensitivity reactions including skin rashes, angiodema and Stevens Johnson syndrome, toxic epidermal necrolysis |
|
Respiratory, thoracic and mediastinal disorders |
Bronchospasm** |
|
Hepatobiliary disorders |
Hepatic enzyme increased |
|
Skin and subcutaneous tissue disorders |
Rash, pruritus, erythema, urticaria, allergic dermatitis Very rare cases of serious skin reactions have been reported |
*These are not necessarily causally related to paracetamol
**There have been cases of bronchospasm with paracetamol, but these are more likely in asthmatics sensitive to aspirin or other NSAIDs patients
PHENYLEPHRINE HYDROCHLORIDE
The following adverse events have been observed in clinical trials and post-market experience with phenylephrine and may therefore represent the most commonly occurring adverse events though actual frequencies are unknown but likely to be rare or very rare.
|
Body System |
Undesirable effect |
|
Psychiatric disorders |
Nervousness, irritability, restlessness, confusional state |
|
Nervous system disorders |
Headache, dizziness, insomnia |
|
Vascular disorders |
Hypertension |
|
Gastrointestinal disorders |
Nausea, vomiting, diarrhoea |
|
Cardiac disorders |
Tachycardia, palpitations |
|
Eye disorders |
Mydriasis, acute angle closure glaucoma, most likely to occur in those with closed angle glaucoma |
GUAIFENESIN
The frequency of these adverse events is unknown but considered likely to be rare or very rare.
|
Body System |
Undesirable effect |
|
Immune system disorders |
Hypersensitivity including skin rashes, urticaria, anaphylactic |
|
reactions, angioedema | |
|
Respiratory, thoracic and mediastinal disorders |
Dyspnoea* |
|
Gastrointestinal disorders |
Nausea, vomiting, abdominal discomfort, diarrhoea |
* Dyspnoea has been reported in association with other symptoms of hypersensitivity
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
Taking more than the recommended dose can cause serious health problems. Quick medical attention is critical even if signs or symptoms have not been noticed.
Paracetamol
Patients should NOT take any other paracetamol-containing products concurrently due to the risk of severe liver damage in case of overdose.
In acute overdose, paracetamol may exert a hepatotoxic effect or even cause necrosis of the liver. Overdose of paracetamol, including high total dose levels reached over a prolonged period, may cause nephropathy with irreversible liver failure.
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).
Symptoms of paracetamol overdose in the first 24 hours are pallor, nausea, vomiting, and anorexia. Abdominal pain may be the first indication of liver damage, which is not usually apparent for 24 to 48 hours and sometimes may be delayed for up to 4 to 6 days after ingestion. Liver damage is generally at a maximum 72 to 96 hours after ingestion. Abnormalities of glucose metabolism and metabolic acidosis may occur.
In severe poisoning, hepatic failure may progress to encephalopathy, haemorrhage, hypoglycemia, cerebral edema, and death. Acute renal failure with acute tubular necrosis may develop even in the absence of severe liver damage. Cardiac arrhythmias and pancreatitis have been reported.
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 48 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 local National Poison Center or a liver unit.
Additional information on special populations
There is a risk of poisoning, particularly in elderly patients, young children, in patients with liver disease, in case of chronic alcoholismor in patients with chronic malnutrition. Overdosing may be fatal in these cases.
Risk is higher if the patient:
• is on long term treatment with carbamazepine, phenobarbitone, phenytoin, primidone, rifampicin, St John’s Wort or other drugs that induce liver enzymes,
• regularly consumes ethanol in excess of recommended amounts,
• is likely to be glutathione deplete e.g. eating disorders, cystic fibrosis, HIV infection, starvation, cachexia.
Phenylephrine
Symptoms of the sympathomimetic effect of phenylephrine include haemodynamic changes and cardiovascular collapse with respiratory depression such as sleepiness, which may be followed by agitation (especially in children); visual disturbances, rash, nausea, vomiting, persistent headaches, nervousness, dizziness, sleeplessness, circulatory disorders, coma, convulsions, hypertension and bradycardia.
Treatment includes early gastric lavage and symptomatic and supportive measures. Hypertensive effects may be treated with an i.v. alpha-receptor blocking agent. In case of convulsions diazepam may be administered.
Guaifenesin
Gastrointestinal discomfort, nausea and vomiting have occasionally been reported with guaifenesin, particularly in very large doses. Patient may also experience drowsiness. Urinary calculi have been reported in patients consuming large quantities of preparation containing guaifenesin in combination with ephedrine. Any absorbed guaifenesin is however, rapidly metabolized and excreted in the urine. Patient should be treated symptomatically.
5 PHARMACOLOGICAL PROPERTIES
5.1 Pharmacodynamic properties
Pharmacotherapeutic group: paracetamol, combinations excl. psycholeptics.
ATC code: N02BE51
Paracetamol has both analgesic and antipyretic activity which is mediated principally through its inhibition of prostaglandin synthesis in the central nervous system.
Phenylephrine hydrochloride mainly acts directly on adrenergic receptors. It has predominantly a-adrenergic activity and is without significant stimulating effects on the central nervous system at usual doses. It has recognised nasal decongestant activity and acts by vasoconstriction to reduce oedema and swelling of the nasal mucosa.
Guaifenesin is an expectorant which alleviates cough discomfort by increasing the volume and decreasing the viscosity of bronchial secretions. This facilitates removal of mucus and reduces irritation to the bronchial tissue. It therefore changes an unproductive cough to a cough that is more productive and less frequent.
The active ingredients are not known to cause sedation.
5.2 Pharmacokinetic properties Paracetamol
Paracetamol is rapidly and almost completely absorbed from the gastrointestinal tract. Plasma concentrations of paracetamol in Theraflu Cold and Cough syrup are measured from 5 minutes post-intake, with peak plasma concentrations occurring between 20 to 60 minutes following oral dosing (the median Tmax 40 minutes). Paracetamol is primarily metabolised in the liver via three pathways: glucuronidation, sulphation and oxidation. It is excreted in the urine, mainly as the glucuronide and sulphate conjugates. The mean elimination half-life of paracetamol in Theraflu Cold and Cough syrup is approximately 5 hours.
Phenylephrine
Phenylephrine is absorbed from the gastrointestinal tract and undergoes firstpass metabolism by monoamine oxidase in the gut and liver; orally administered phenylephrine thus has reduced bioavailability. Peak plasma concentrations of unconjugated phenylephrine in Theraflu Cold and Cough syrup occurred between 10 and 40 minutes following oral dosing (median Tmax 30 minutes). Phenylephrine is excreted in the urine almost entirely as the sulphate conjugate. The mean elimination half-life of phenylephrine in Theraflu Cold and Cough syrup is approximately 4 hours.
Guaifenesin
Following oral administration, guaifenesin is rapidly and completely absorbed from the gastro-intestinal tract. Peak plasma concentrations of guaifenesin in Theraflu Cold and Cough syrup occurred between 15 and 40 minutes (median Tmax 30 minutes). Guaifenesin is metabolised mainly into beta-(2-methoxyphenoxy) lactic acid. Guaifenesin is excreted rapidly and almost completely through the kidneys. 81% and 95% of an administered dose appear in the urine within 4 and 24 hours respectively. The mean elimination half-life of guaifenesin in Theraflu Cold and Cough syrup is approximately one hour.
5.3 Preclinical safety data
Preclinical 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 in the product and which have not already been mentioned elsewhere in this Summary.
6 PHARMACEUTICAL PARTICULARS
6.1 List of excipients
Maltitol liquid (E965)
Flavour 316282 (propylene glycol, artificial and natural flavors)
Orange Flavour Natural (propylene glycol, ethyl alcohol and natural flavors) Propylene glycol
Ethanol 96%
Acesulfame potassium (E950) Citric acid, anhydrous Sodium benzoate (E211) Disodium edetate Sodium citrate Sunset Yellow (E110)
Purified water
6.2 Incompatibilities
Not applicable.
6.3 Shelf life
2 years.In-use shelf-life after first opening: 6 months
6.4 Special precautions for storage
Store below 25°C.
6.5 Nature and contents of container
Polyethylene terephtalate (PET) bottle with a polypropylene (PP) child resistant cap including a low density polyethylene (LDPE) liner. Content 240 ml.
A polypropylene measuring cup capable of dosing 30 ml is provided.
6.6 Special precautions for disposal
Any unused medicinal product or waste material should be disposed of in accordance
with local requirements.
7 MARKETING AUTHORISATION HOLDER
Novartis Consumer Health UK Ltd Park View, Riverside Way Watchmoor Park Camberley, Surrey GU15 3YL United Kingdom
8 MARKETING AUTHORISATION NUMBER(S)
PL 00030/0469
9 DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION
20/10/2014
10 DATE OF REVISION OF THE TEXT
20/10/2014