Benylin Four Flu Tablets

For the relief of symptoms associated with colds and flu; including coughing, fever, headache, minor aches and pains and nasal congestion.

Adults, the elderly and children 12 years and older: Two tablets four times daily. Do not exceed 8 tablets in 24 hours.

Children aged 6 to less than 12 years: One tablet four times daily. Do not exceed 4 tablets in 24 hours.

Children under 6 years: Not recommended.

For oral use only.

Hepatic dysfunction Caution should be exercised when administrating BENYLIN FOUR FLU TABLETS to patients with severe hepatic impairment.

Renal dysfunction Caution should be exercised when administering BENYLIN FOUR FLU TABLETS to patients with moderate to severe renal impairment.

• Hypersensitivity to diphenhydramine hydrochloride, pseudoephedrine hydrochloride, paracetamol or to any of the other ingredients in BENYLIN FOUR FLU TABLETS (see section 6.1)
• Most types of cardiovascular disease, including angina and hypertension
• Hyperthyroidism
• Hyperexcitability
• Phaeochromocytoma
• Closed angle glaucoma
• Concomitant use of monoamine oxidase inhibitors (MAOIs), or within 14 days of stopping treatment with this class of medicine. The concomitant use of these medications may cause a rise in blood pressure and/or hypertensive crisis (see section 4.5).
• Severe liver disease.
• Should be avoided in patients undergoing anaesthesia with cyclopropane, halothane, or other halogenated anaesthetics.

BENYLIN FOUR FLU TABLETS contains paracetamol which may be fatal in overdose. In the event of overdosage or suspected overdose and notwithstanding the fact that the person may be asymptomatic, the nearest doctor, hospital or poison centre must be contacted immediately.

Patients with the following conditions should be advised to consult a doctor before using BENYLIN FOUR FLU TABLETS: a respiratory condition, such as emphysema, chronic bronchitis, or acute or chronic bronchial asthma, or prostate hyperplasia with urinary retention.

BENYLIN FOUR FLU TABLETS may cause urinary retention in patients with prostatic hypertrophy.

BENYLIN FOUR FLU TABLETS should not be used continuously for more than ten days; if symptoms persist, irrespective of therapy used, a doctor should be consulted. Dosages in excess of those recommended may cause severe liver or kidney damage.

BENYLIN FOUR FLU TABLETS may lead to drowsiness and impaired concentration, which may be aggravated by simultaneous intake of alcohol or other central nervous system depressant medicines (such as sedatives and tranquilisers). While taking BENYLIN FOUR FLU TABLETS, patients should avoid alcoholic beverages and consult with a health care provider prior to taking with central nervous system depressants.

Chronic alcohol users should ask their doctor whether they should take paracetamol or other analgesics or antipyretics.

BENYLIN FOUR FLU TABLETS should not be taken without consulting a doctor or pharmacist if a patient is presently taking other medicines for depression, psychiatric or emotional conditions or hypertension (see section 4.5).

Not to be taken with any other paracetamol or diphenhydramine-containing products, even ones used on skin.

In infants and children BENYLIN FOUR FLU TABLETS may act as a cerebral stimulant. Symptoms of stimulation include insomnia, nervousness, tachycardia, tremors and convulsions. Large doses may precipitate fits in epileptics. Deepening coma, extrapyramidal effects and photosensitisation of the skin may occur.

Elderly patients are more susceptible to the central nervous system depressant and hypotensive effects.

The positive results of skin tests may be suppressed.

Patients with impaired kidney or liver function should take BENYLIN FOUR FLU TABLETS under medical supervision only.

Serious skin reactions such as acute generalised exanthematous pustulosis (AGEP), Stevens-Johnson syndrome (SJS), and toxic epidermal necrolysis (TEN), have been reported in patients receiving paracetamol. Patients should be informed about the signs of serious skin reactions and the use of BENYLIN FOUR FLU TABLETS should be discontinued at the first appearance of skin rash or any other sign of hypersensitivity.

BENYLIN FOUR FLU TABLETS should not be used by patients with renal disease or diabetes.

Taking more than the recommended dose (overdose) may result in liver damage. In case of overdose, get medical help immediately. Quick medical attention is critical for adults as well as for children even if you do not notice any signs or symptoms.

There have been reports of ischaemic colitis with pseudoephedrine. BENYLIN FOUR FLU TABLETS should be discontinued and medical advice sought if sudden abdominal pain, rectal bleeding or other symptoms of ischaemic colitis develop (see section 4.8).

Severe skin reactions such as acute generalised exanthematous pustulosis (AGEP) have been reported very rarely with pseudoephedrine-containing products, such as BENYLIN FOUR FLU TABLETS. This acute pustular eruption may occur within the first 2 days of treatment, with fever, and numerous, small, mostly non-follicular pustules arising on a widespread oedematous erythema and mainly localised on the skin folds, trunk, and upper extremities. Patients should be carefully monitored. If signs and symptoms such as formation of small pustules occur, with or without pyrexia or erythema, then treatment with BENYLIN FOUR FLU TABLETS should be discontinued and a doctor should be consulted (see section 4.8).

Patients should not use BENYLIN FOUR FLU TABLETS for persistent or chronic cough, such as occurs with asthma, or where cough is accompanied by excessive secretions, unless directed by a doctor.

Warfarin-like compounds For most patients, occasional use of paracetamol generally has little or no effect on the International Normalised Ratio (INR) in patients on chronic warfarin therapy; however, there has been controversy regarding the possibility of paracetamol potentiating the anticoagulant effects of warfarin and other coumarin derivatives. Patients should consult a doctor or pharmacist before use if they are taking warfarin or other coumarin derivatives.

Central nervous system (CNS) depressants (alcohol, sedatives, tranquilisers) Diphenhydramine may potentiate the effects of other CNS depressants such as anti-depressants, minor tranquillisers, neuroleptics, barbiturates and alcohol, and other medicines with anti-cholinergic properties such as tricyclic anti-depressants.

Antihypertensive medicines, sympathomimetic medicines and MAOIs Pseudoephedrine may reverse the effect of antihypertensive medicines which modify sympathetic activity, and concomitant use with other sympathomimetic medicines such as decongestants, tricyclic anti-depressants and appetite suppressants or with monoamine oxidase inhibitors, which interfere with the catabolism of sympathomimetic amines, may cause a rise in blood pressure.

Cardiac glycosides, quinidine and tricyclic anti-depressants An increased risk of dysrhythmias may also occur if sympathomimetic medicines are given to patients receiving cardiac glycosides, quinidine, or tricyclic anti-depressants.

Safety in pregnancy and lactation has not been established.

Diphenhydramine Diphenhydramine crosses the placenta and is excreted into breast milk, but levels have not been reported.

Paracetamol A large amount of data on pregnant women indicate neither malformative, nor feto/neonatal toxicity. Epidemiological studies on neurodevelopment in children exposed to paracetamol in utero show inconclusive results. If clinically needed, paracetamol can be used during pregnancy however it should be used at the lowest effective dose for the shortest possible time and at the lowest possible frequency.

Pseudoephedrine Pseudoephedrine distributes into and is concentrated in breast milk. Up to 0,7 % of a single 60 mg dose of pseudoephedrine may be distributed into breast milk over 24 hours. Pseudoephedrine concentrations in milk are from 2 to 3 fold higher than those in plasma. This milk/plasma medicine concentration profile suggests low protein binding, although no protein plasma binding data in humans are available. Data from a study of lactating mothers taking 60 mg pseudoephedrine every 6 hours suggests that from 2,2 to 6,7 % of the maximum daily dose (240 mg) may be available to the infant from a breastfeeding mother.

BENYLIN FOUR FLU TABLETS can cause side effects such as sedation, drowsiness, dizziness or blurred vision. Patients should be warned not to drive a motor vehicle, operate dangerous machinery, or climb dangerous heights, as impaired decision making could lead to accidents.

Diphenhydramine hydrochloride:

Blood and the lymphatic system disorders: Less frequent: blood dyscrasias (including agranulocytosis, leucopenia and haemolytic anaemia), thrombocytopenia

Immune system disorders: Less frequent: allergic reactions and anaphylaxis

Metabolism and nutrition disorders: Less frequent: anorexia or increased appetite

Psychiatric disorders: Less frequent: euphoria

Nervous system disorders: Frequent: sedation (varying from slight drowsiness to deep sleep), lassitude, dizziness, incoordination, headache

Eye disorders: Less frequent: blurred vision

Ear and labyrinth disorders: Less frequent: tinnitus

Vascular disorders: Less frequent: hypotension

Respiratory, thoracic and mediastinal disorders: Less frequent: tightness of the chest

Gastrointestinal disorders: Less frequent: nausea, vomiting, diarrhoea, constipation, epigastric pain and dryness of the mouth

Musculoskeletal, connective tissue and bone disorders: Less frequent: muscular weakness

Renal and urinary disorders: Less frequent: difficulty in micturition, dysuria

Paracetamol:

Blood and the lymphatic system disorders: Less frequent: neutropenia, pancytopenia, leucopenia, agranulocytosis, thrombocytopenia

Immune system disorders: Less frequent: sensitivity reactions resulting in skin rash*, laryngeal oedema, angioedema and anaphylaxis

* (The rash is usually erythematous or urticarial but sometimes more serious and may be accompanied by fever and mucosal lesions.)

Endocrine disorders: Less frequent: pancreatitis

Pseudoephedrine hydrochloride:

Metabolism and nutrition disorders: Less frequent: altered metabolism (including changes in blood sugar levels)

Frequency unknown: hypokalaemia

Psychiatric disorders: Less frequent: fear, anxiety, restlessness, insomnia, confusion, irritability, and psychotic states

Nervous system disorders: Less frequent: tremor, headache

Cardiac disorders: Less frequent: pulmonary oedema, reflex bradycardia, tachycardia and cardiac dysrhythmias, anginal pain, palpitations, and cardiac arrest

Vascular disorders: Less frequent: hypertension, cerebral haemorrhage, hypotension (with dizziness), fainting, flushing

Diphenhydramine hydrochloride: Overdosage may be fatal especially in infants and children. In infants & children CNS stimulation predominates over CNS depression causing ataxia, excitement, tremors, psychoses, hallucinations and convulsions; hyperpyrexia may also occur. Deepening coma and cardio-respiratory collapse may follow. In adults, CNS depression with drowsiness, coma and convulsions, progressing to respiratory failure or possibly cardiovascular collapse.

Paracetamol: Nausea, vomiting and anorexia. Liver damage which may be fatal, may only appear after a few days. Acute intoxication may cause kidney failure.

Prompt treatment is essential. In the event of an overdosage, consult a doctor immediately, or take the person to a hospital directly. A delay in starting treatment may mean that antidote is given too late to be effective. Evidence of liver damage is often delayed until after the time for effective treatment has lapsed.

Susceptibility to paracetamol toxicity is increased in patients who have taken repeated high doses (greater than 5-10 g/day) of paracetamol for several days, in chronic alcoholism, chronic liver disease, AIDS, malnutrition, and with the use of medicines that induce liver microsomal oxidation such as barbiturates, isoniazid, rifampicin, phenytoin and carbamazepine.

Symptoms of paracetamol overdosage in the first 24 hours include pallor, nausea, vomiting, anorexia and possibly abdominal pain. Mild symptoms during the first two days of acute poisoning, do not reflect the potential seriousness of the overdosage.

Liver damage may become apparent 12 to 48 hours, or later after ingestion, initially by elevation of the serum transaminase and lactic dehydrogenase activity, increased serum bilirubin concentration and prolongation of the prothrombin time. Liver damage may lead to encephalopathy, coma and death.

Acute renal failure with acute tubular necrosis may develop even in the absence of severe liver damage. Abnormalities of glucose metabolism and metabolic acidosis may occur. Cardiac dysrhythmias have been reported.

Treatment for paracetamol overdosage: Any adult person who has had about 7,5 grams of paracetamol (or a child who has had more than 140 mg/kg) within the preceding four hours, should have the stomach emptied by lavage (emesis may be adequate for children) and a single dose of 50 g activated charcoal given via the lavage tube. Ingestion of amounts of paracetamol smaller than this may require treatment in patients susceptible to paracetamol poisoning (see above).

In patients who are stuporous or comatose, endotracheal intubation should precede gastric lavage in order to avoid aspiration. N-acetylcysteine should be administered to all cases of suspected overdose as soon as possible preferably within eight hours of overdosage, although treatment up to 36 hours after ingestion may still be of benefit, especially if more than 150 mg/kg of paracetamol was taken.

An initial dose of 150 mg/kg N-acetylcysteine in 200 mL glucose injection given intravenously over 15 minutes, followed by an infusion of 50 mg/kg in 500 mL glucose injection over the next four hours, and then 100 mg/kg in 1000 mL glucose injection over the next sixteen hours. The volume of intravenous fluid should be modified for children.

Orally (not the treatment of choice): 140 mg/kg as a 5% solution initially, followed by 70 mg/kg every four hours for seventeen doses. N-acetylcysteine is more likely to be effective if administered within 8 hours of overdosage. A plasma paracetamol level should be determined four hours after ingestion in all cases of suspected overdosage. Levels done before four hours, unless high, may be misleading. Patients at risk of liver damage, and hence requiring continued treatment with N-acetylcysteine, can be identified according to their 4-hour plasma paracetamol level. The plasma paracetamol level can be plotted against time since ingestion in the nomogram below. The nomogram should be used only in relation to a single acute ingestion.