FLUDREX is particularly effective against the symptoms of cold and flu. It contains the full

recommended dose of Paracetamol to ease aches, pains and lower body temperature. There is Pseudoephedrine HCl to clear a stuffy nose. Also caffeine is added in tablets as a mild stimulant during illness. Chlorpheniramine maleate is an antihistamine of short duration of action with less sedative effect than other antihistamines.

FLUDREX is used for:

• Relieving nasal congestion and rhinorrhoea.

• Lowering temperature due to common cold & flu.

• Relieving pain and headache.

The usual dose is as follows, to be taken orally:

 For patients 12 years old and above, the usual adult dose is one FLUDREX tablet 3 times daily (every 8 hours) or according to physician’s prescription.

Maximum dose 8 tablets in 24 hours.

Do not exceed the stated dose.

• It should not be given for children lesser than 6 years old because there is no evidence that it works and can cause side effects, such as allergic reactions, effects on sleep or hallucinations. • Hypersensitivity to any component of FLUDREX preparations. • In patients taking Monoamine Oxidase Inhibitors (MAOIs).

Fludrex tablets  should be use with caution in the following cases:

•         For children from 6-12 years.

•         Should not be taken with other preparation containing Paracetamol.

•         Systemic decongestants should be used with caution in patients with diabetes, hypertension, hyperthyroidism and ischaemic heart disease.

•         Should be used with caution in case of epilepsy, prostatic hypertrophy, urinary retention, glaucoma and hepatic diseases.

•         Caffeine: Should be given with care to patients with a history of peptic ulcer

Do not exceed the stated dose.

•         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.

•         Should not be given to patients being treated with monoamine oxidase inhibitors or within 14 days of stopping such treatment.

•         Pseudoephedrine may enhance the effects of anticholinergic drugs such as tricyclic antidepressants.

•         Pseudoephedrine may increase the possibility of arrhythmias in digitalised patients.

•         Pseudoephedrine may increase the vasoconstrictor effects of ergot alkaloids.

•         Chlorphenamine may have an additive effect when used concurrently with hypnotics and anxiolytics causing potentiation of drowsiness.

Caffeine undergoes extensive metabolism by hepatic microsomal cytochrome P450, factors known to alter the activity of this enzyme system may influence caffeine clearance. Thus, caffeine elimination is enhanced in cigarette smokers and inhibited by cimetidine, disulfiram, and oral contraceptive steroids.

•         Like most medicines, it should not be used during pregnancy unless the potential benefit of treatment to the mother outweighs any possible risk to the developing foetus.

•         The use of the product during pregnancy should be avoided.

Small amounts of antihistamines are excreted in breast milk. Use by nursing mothers is not recommended because of the risks of adverse effects in the infant.

Chlorphenamine may cause drowsiness, dizziness, blurred vision and psychomotor impairment, which can seriously hamper the patient's ability to drive and use machinery.

The following side effects may occur during the treatment: somnolence, insomnia, dizziness, allergic skin rashes, palpitations and gastrointestinal disturbances. Paracetamol : Thrombocytopenia, Agranulocytosis, Bronchospasm, Hepatic dysfunction.

Pseudoephedrine: serious adverse effects associated with the use of pseudoephedrine are extremely rare. Symptoms of central nervous system excitation may occur including sleep disturbance and, rarely hallucinations. Skin rashes with or without irritation and tachycardia have occasionally been reported with pseudoephedrine. Urinary retention has been reported in men receiving pseudoephedrine; prostatic enlargement could have been a predisposing factor.

Chlorphenamine maleate: Sedation varying from slight drowsiness to deep sleep. Inability to concentrate, lassitude, blurred vision, GI disturbances such as nausea, vomiting and diarrhoea may occasionally occur. Urinary retention, headaches, dryness of the mouth. Dizziness, palpitation, tachycardia, arrhythmias, hypotension, tightness of the chest, abdominal pain, dyspepsia, anorexia, hepatic including jaundice, thickening of the bronchial secretions, haemolytic anaemia and other blood dyscrasias infrequently occur.

Caffeine: The most commonly reported adverse events following dosing with caffeine are GI irritation and CNS stimulation. Adverse CNS effects include insomnia, restlessness, nervousness and mild delirium; adverse GI effects include nausea, vomiting and gastric irritation.

 In massive over dosage exceeding 10 g of paracetamol may cause liver damage. Early symptoms may include pallor, nausea, vomiting, (diaphoresis) and general malaise.

• Clinical and laboratory evidence of liver damage may not be apparent until 48 to 72 hours past ingestion. Overdose should be promptly treated by gastric lavage followed by intravenous N-acetylcysteine or methionine without waiting for the results of plasma paracetamol levels.

• Additional antidote therapy is normally considered in light of further plasma paracetamol levels and the time elapsed since ingestion. In all cases of suspected overdose, prompt medical attention is critical for adults as well as for children, even if you do not notice any signs or symptoms.

Mode of Action of each ingredient:

ATC code: NO2BE51

Paracetamol : based on the inhibition of prostaglandin biosynthesis.

Pseudoephedrine: has direct and indirect sympathomimetic activity and is an effective upper respiratory decongestant. Pseudoephedrine is less potent than ephedrine in producing both tachycardia and elevation of systolic blood pressure and is also less potent in causing stimulation of the central nervous system. Pseudoephedrine produces its decongestant effect within 30 minutes, persisting for at least 4 hours.

Chlorphenamine maleate: 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. Chlorphenamine also has anticholinergic activity. 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 chlorphenamine include inhibition of histamine on smooth muscle, capillary permeability and hence reduction of oedema and wheal in hypersensitivity reactions such as allergy and anaphylaxis.

Caffeine: Caffeine is a central nervous system stimulant. It inhibits the enzyme phosphodiesterase and has an antagonistic effect at central adenosine receptors. Its action on the central nervous system is mainly on the higher centres and it produces a condition of wakefulness and increased mental activity.

ABSORPTION

Paracetamol : is rapidly and almost completely absorbed from the gastrointestinal tract.

Pseudoephedrine : the C max of pseudoephedrine was approximately 180 ng/ml with t max occurring at approximately 1.5 hours for the tablets after drug administration.

Chlorphenamine 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.

Caffeine: Caffeine is absorbed readily after oral administration, but absorption from the gastrointestinal tract may be erratic. There is little evidence of accumulation in any particular tissue. Caffeine passes readily into the central nervous system and into saliva. Concentrations have also been detected in breast milk.

DISTRIBUTION

The apparent volume of distribution of pseudoephedrine (Vd/F) was approximately 2.8 l/kg.

METABOLISM AND ELIMINATION

Paracetamol : The concentration in plasma reaches a peak in 30 to 60 minutes and the plasma half-life is 1 - 4 hours after therapeutic doses. Paracetamol is relatively uniformly distributed throughout most body fluids. Binding of the drug to plasma proteins is variable; 20 to 30% may be bound at the concentrations encountered during acute intoxication. Following therapeutic doses 90 - 100% of the drug may be recovered in the urine within the first day. However, practically no paracetamol is excreted unchanged and the bulk is excreted after hepatic conjugation.

Pseudoephedrine: the t½ was approximately 5.5 hours. Pseudoephedrine is partly metabolised in the liver by N-demethylation to norpseudoephedrine, an active metabolite. Pseudoephedrine and its metabolite are excreted in the urine; 55% to 90% of a dose is excreted unchanged. The apparent total body clearance of pseudoephedrine (Cl/F) was approximately 7.5 ml/min/kg. The elimination rate constant (Kel) was approximately 0.13 h-1. The rate of urinary elimination is accelerated when the urine is acidified. Conversely, as the urine pH increases, the rate of urinary elimination is slowed.

Chlorphenamine : is metabolised to the monodesmethyl and didesmethyl derivatives. About 22% of an oral dose is excreted unchanged in the urine.

Caffeine : It is metabolised almost completely and is excreted in the urine as 1-methyluric acid, 1-methylxanthine and other metabolites, with only about 1% unchanged

There is insufficient information available to determine whether some of the active ingredients have mutagenic, carcinogenic, teratogenic potential, or the potential to impair fertility.

Maize starch

Poly vinyl Pyrolidone K30

Sorbitol

Magnesium stearate

Aerosil 200

None reported.

3 years from the manufacturing date. The expiry date refers to the last day of the month

Keep in a safe place, out of the reach and sight of children.

• Store below 25 ºC, Protect from light

PVC-film (Upper part of the blister): Thin white opaque, rigid, glossy film used for blister packing of capsules, obtained in form of rolls.

Aluminium foil for blister-pack (lower part of the blister): A hard Aluminium foil.

No special requirements.