Flurest N  is a combination of an analgesic (paracetamol), a nasal decongestant (phenylephrine hydrochloride) and an antihistamine (chlorpheniramine maleate) for the treatment of symptoms of colds and influenza.

Composition

Each Flurest N tablet contains the following active ingredients:

500 mg Paracetamol.

5 mg Phenylephrine HCL.

2 mg Chlorpheniramine maleate.

Excipients: Maize starch, Povidone K25, Potassium sorbate, Pregelatinized starch, Sodium lauryl sulphate, Microcrystalline cellulose, Stearic acid, Purified talc.

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Indications

For the relief of the symptoms of the common cold and influenza such as: fever, muscle ache, nasal congestion, sinus congestion, headache and sinus pain, sneezing, itchy and watery eyes.

Flurest ™ N tablets- gsk

Dosage and Administration

For oral administration only.

Do not exceed the stated dose or frequency of dosing.

Should not be used with other products containing paracetamol, decongestants

or antihistamines, including cough and cold preparations. (see Warnings and

Precautions).

Adults (including the elderly) and children aged 12 years and over: Take 1 to

2 tablets every 4 to 6 hours as needed.

Maximum daily dose: Eight tablets in 24 hours.

Maximum duration of continued use without medical advice: 7 days Minimum

dosing interval: 4 hours.

Children under 12 years: Not recommended for children under the age of 12 years.

Children: Not recommended for children under the age of 12 years. Note: Multiple active ingredient cough and cold products containing phenylephrine and/or chlorpheniramine should not be used OTC in children below 6 years of age.

Elderly: The elderly are more prone to adverse effects with chlorpheniramine (see

Warnings and Precautions).

Renai Impairment:  Patients who have been diagnosed with kidney impairment must seek

medical advice before taking Flurest N tablets. The restrictions related to the use

of this product in patients with renal impairment are primarily a consequence of

the paracetamol and chlorpheniramine content of the drug (see Warnings and

Precautions).

Hepatic Impairment: Patients who have been diagnosed with liver impairment must seek medical advice before taking this medication. The restrictions related to the use of this product in patients with renal impairment are primarily a consequence of the paracetamol and chlorpheniramine content of the drug (see Warnings and Precautions).

Contraindications

This product is contraindicated in patients:

with a previous history of hypersensitivity to paracetamol phenylephrine,

chlorpheniramine, antihistamines or to any of the product constituents.

who are receiving Monoamine Oxidase Inhibitors (MAOIs), or for two weeks after stopping a MAOI drug (see Interactions).

Warnings and Precautions

Caution should be exercised in patients with kidney impairment and in those with hepatic impairment due to the paracetamol and chlorpheniramine content of the product. Underlying liver disease increases the risk of paracetamol-related liver damage.

Caution should be exercised in patients with cardiovascular disease, hypertension,diabetes, hyperthyroidism, prostatic enlargement, raised intraocular pressure (i.e.glaucoma), pheochromocytoma, occlusive vascular disease (e.g. Raynaud’s Phenomenon), epilepsy, bronchitis, bronchiectasis and bronchial asthma.

The anticholinergic properties of chlorpheniramine may cause drowsiness,dizziness, blurred vision and psychomotor impairment in some patients which may seriously affect ability to drive and use machinery.

Chlorpheniramine may increase the effects of alcohol and therefore concurrent use should be avoided (see Interactions).

Concurrent use with drugs which cause sedation, such as anxiolytics and hypnotics may cause an increase in sedative effect, therefore medical advice

should be sought before taking chlorpheniramine concurrently with these medicines (see Interactions).

Phenylephrine should be used with caution in patients taking beta-blockers or other antihypertensives (see Interactions).

Phenylephrine should be used with caution in patients taking tricyclic antidepressants (see interactions).

Flurest N tablets should not be used by patients taking other sympathomimetics (such as decongestants, appetite suppressants and amphetamine-like psychostimulants (see Interactions).

 

Flurest N tablets should not be used with other anti-histamine containing products, including antihistamine containing cough and cold preparations.

Children and the elderly are more likely to experience neurological anticholinergic effects and paradoxical excitation (e.g. increased energy, restlessness, nervousness).

If symptoms persist for more than 7 days, medical advice must be sought.

Keep out of sight and reach of children.

Interactions

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

Hypertensive interactions occur between sympathomimetic amines such as

phenylephrine and monoamine oxidase inhibitors (see Contraindications). 

The anticholinergic effects of chlorpheniramine are intensified by monoamine oxidase inhibitors (see Contraindications).

Concomitant use of phenylephrine with other sympathomimetic amines increase the risk of cardiovascular side effects (see Warnings and Precautions).

Phenylephrine may reduce the efficacy of beta blocking drugs and antihypertensive drugs (e.g. beta blockers, methyl-dopa, reserpine, debrisoquine, guanethidine). The risk of hypertension and other cardiovascular side effects may be increased. [see Warnings and Precautions].

Tricyclic antidepressants (e.g. amitriptyline) may increase the risk of cardiovascular side effects with phenylephrine (see Warnings and Precautions).

Phenylephrine used in combination with digoxin or cardiac glycosides may increase the risk of irregular heartbeat or heart attack.

Concurrent use of chlorpheniramine and hypnotics or anxiolytics may potentiate drowsiness. Concurrent use of alcohol may have a similar effect (see Warnings and Precautions).

Chlorpheniramine inhibits phenytoin metabolism and can lead to phenytoin toxicity.

Pregnancy and Lactation

Fertility: No relevant data available.

Pregnancy: Flurest N tablets should not be used during pregnancy. Human and animal studies with paracetamol have not identified any risk to pregnancy or embryo-foetal development.No relevant data available for products containing phenylephrine. There are no adequate data from the use of chlorpheniramine in pregnant women. The potential risk for humans is unknown. Chlorpheniramine use during the third trimester may result in reactions in the newborn or premature neonates.

Lactation: Flurest N tablets should not be used whilst breast feeding without medical advice. Phenylephrine is excreted in breast milk. Chiorpheniramne maleate and other antihistamines may inhibit lactation and may be secreted in breast milk.

N.B. Flurest N tablets  may cause drowsiness, dizziness, blurred vision and psychomotor

impairment in some patients which may seriously affect ability to drive and use machinery (see Warnings and Precautions).

Adverse Reactions

Blood and lymphatic system disorders- Very rare: Thrombocytopenia.

Immune System disorders-Very rare: Cutaneous hypersensitivity reactions including skin rashes, angioedema, and Stevens Johnson syndrome.

Respiratory, thoracic and mediastinal disorders Very rare: Bronchospasm in patients sensitive to aspirin and other NSAlDs.

Hepatobiliary disorders- Very rare: Hepatic dysfunction

Phenylephrine adverse events

The following adverse events have been observed in clinical trials with phenylephrine and may therefore represent the most commonly occurring adverse events. Adverse events are listed below by MedDRA system class:

Psychiatric disorders: Nervousness

Nervous System Disorders: Headache, Dizziness, Insomnia

Vascular disorders: Increased blood pressure

Gastrointestinal Disorders: Vomiting, nausea

Adverse reactions identified during post-marketing use are listed below. As these

reactions are reported voluntarily from a population of uncertain size, the

frequency of these reactions is unknown but considered likely to be rare

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)

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

Chlorpheniramine adverse effects

immune system disorders: Unknown: Allergic reactions, angioedema, anaphylactic

reactions

Metabolism and nutritional disorders- Unknown: Anorexia

Psychiatric disorders: Confusion, excitation, irritability, nightmares.

Nervous system disorders: Sedation, somnolence,Disturbance in attention, abnormal coordination, dizziness, headache

Eye disorders: Blurred vision

Vascular disorders:Hypotension

Respiratory, thoracic and mediastinal disorders: Thickening of bronchial secretions

Gastrointestinal disorders: Nausea, dry mouth, vomiting, abdominal pain, diarrhoea, dyspepsia

Skin and subcutaneous disorders:  Exfoliative dermatitis, rash, urticaria, photosensitivity

Musculoskeletal and connective tissue disorders:  Muscle twitching, muscle weakness

Renal and urinary disorders: Urinary retention

General disorders:  Fatigue, Chest tightness

N.B.Children and the eiderly are more susceptible to neurological anticholinergic effects and paradoxical excitation (e.g. increased energy, restlessness, nervousness).

Overdosage

Paracetamol Overdose Symptoms and signs

Paracetamol overdose may cause liver failure.Treatment: Immediate medical management is required in the event of overdose, even if symptoms of overdose are not present. Administration of N-acetyl cysteine or methionine may be required.

Phenylephrine Overdose Symptoms and signs

Phenylephrine overdose is likely to result in effects similar to those listed under

adverse reactions. Additional symptoms may include irritability, restlessness,

hypertension, and possibly reflux bradycardia. In severe cases confusion, hallucinations, seizures and arrhythmias may occur. However the amount required to produce serious phenylephrine toxicity would be greater than required to cause paracetamol-related liver toxicity.

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

Chlorpheniramine Overdose Symptoms and signs

Chlorpheniramine overdose is likely to result in effects similar to those listed under adverse

Reactions. Additional symptoms may include paradoxical excitation, toxic psychosis,

convulsions, apnoea, dystonic reactions and cardiovascular collapse including arrhythmias.

Treatment of chlorpheniramine toxicity: Treatment should be supportive and directed towards specific symptoms. Convulsions and marked CNS stimulation should be treated with parenteral diazepam.

Clinical Pharmacology 

Flurest N  is a combination of an analgesic (paracetamol), a nasal decongestant (phenylephrine hydrochloride) and an antihistamine (chlorpheniramine maleate) for the treatment of symptoms of colds and influenza.

Pharmacotherapeutic group: Nasal decongestant for systemic use, sympathomimetics, combinations.

Mechanism of Action: Paracetamol is an analgesic and antipyretic. Its mechanism of action is believed to include inhibition of prostaglandin synthesis primarily within the central nervous system. Phenylephrine hydrochloride is a sympathomimetic agent with mainly direct effects on adrenergic receptors (predominantly alpha-adrenergic activity) producing nasal decongestant. Chlorpheniramine maleate is potent antihistamine (H1-antagonist). Antihistamines diminish or abolish the actions of histamine in the body by competitive reversible blockade of histamine H1-receptor sites on tissues. Chlorpheniramine also has anticholinergic activity.

Pharmacodynamic Effects

Paracetamol: The lack of peripheral prostaglandin inhibition confers important pharmacological properties such as the maintenance of the protective prostaglandins within the gastrointestinal tract. Paracetamol is, therefore, particularly suitable for patients with a history of disease or on concomitant mediation, where peripheral prostaglandin inhibition would be undesirable (such as, for example, those with a history of gastrointestinal bleeding or the elderly).

Phenylephrine hydrochloride: Phenylephrine hydrochloride is a sympathomimetic agent with mainly direct effects on adrenergic receptors (predominantly alpha-adrenergic activity) producing nasal decongestant.

Chiorpheniramine maleate: .Antihistamines act to prevent the release of histamine,prostaglandins and leukotrienes, and have been shown to prevent the migration of inflammatory mediators. The actions of chlorpheniramine include inhibition of histamine on smooth muscle, capillary permeability and hence reduction of oedema and wheal in hypersensitivity reactions such as allergy and anaphylaxis.

Pharmacokinetics

Paracetamol is rapidly and almost completely absorbed from the gastrointestinal tract. Binding to the plasma proteins is minimal at therapeutic concentrations. Paracetamol is metabolised in the liver and excreted in the urine mainly as glucuronide and sulphate conjugates. Less than 5% is excreted as unmodified paracetamol.

Phenylephrine hydrochloride is irregularly absorbed from the gastrointestinal tract. It undergoes first-pass metabolism by monoamine oxidases in the gut and liver; orally administered pher /lephrine thus has reduced bioavailability. It is excreted in the urine almost entirely as the sulphate conjugate.

Chlorpheniremine maleate is well absorbed from the gastro-intestinal tract, following oral administration.. The effects develop within 30 minutes, are maximal within 1 to 2 hours and last 4 to 6 hours. The plasma half-life has been estimated to be 12 to 15 hours. Chlorpheniramine is metabolised to the monodesmethyl and didesmethyl derivatives. About 22% of an oral dose is excreted unchanged in the urine. Only trace amounts have been found in the faeces.

Patient Information Leaflet

Flurest Patient Information Leaflet

Manufactured by: GlaxoSmithKline Egypt.