Bambec Tablets 10mg

1. Name Of The Medicinal Product

Bambec Tablets 10 mg

2. Qualitative And Quantitative Composition

Each tablet contains 10 mg Bambuterol hydrochloride

For excipients, see Section 6.1

3. Pharmaceutical Form

Tablet

4. Clinical Particulars

4.1 Therapeutic Indications

Management of asthma, bronchospasm and/or reversible airways obstruction.

4.2 Posology And Method Of Administration

Bambec is formulated as a tablet and should be taken once daily, shortly before bedtime. The dose should be individualised.

Adults: The recommended starting doses are 10 mg–20 mg. The 10 mg dose may be increased to 20 mg if necessary after 1–2 weeks, depending on the clinical effect.

In patients who have previously tolerated β₂-agonists well, the recommended starting dose, as well as maintenance dose, is 20 mg.

Children: Until the clinical documentation has been completed, Bambec should not be used in children.

Elderly: Dose adjustment is not required in the elderly.

Significant hepatic dysfunction: Not recommended because of unpredictable conversion to terbutaline.

Moderate to severely impaired renal function (GFR < 50 ml/min): It is recommended that the starting dose of Bambec should be halved in these patients.

4.3 Contraindications

Bambec tablets are contraindicated in patients with a history of hypersensitivity to any of their ingredients. Bambec is presently not recommended for children due to limited clinical data in this age group.

4.4 Special Warnings And Precautions For Use

As terbutaline is excreted mainly via the kidneys, the dose of Bambec should be halved in patients with an impaired renal function (GFR

In patients with liver cirrhosis, and probably in patients with other causes of severely impaired liver function, the daily dose must be individualised, taking into account the possibility that the individual patient could have an impaired ability to metabolise bambuterol to terbutaline. Therefore, from a practical point of view, the direct use of the active metabolite, terbutaline (Bricanyl™), is preferable in these patients.

As for all β₂-agonists, caution should be observed in patients with thyrotoxicosis.

Cardiovascular effects may be seen with sympathomimetic drugs, including Bambec. There is some evidence from post-marketing data and published literature of rare occurrences of myocardial ischaemia associated with beta agonists. Patients with underlying severe heart disease (e.g. ischaemic heart disease, arrhythmia or severe heart failure) who are receiving Bambec should be warned to seek medical advice if they experience chest pain or other symptoms of worsening heart disease. Attention should be paid to assessment of symptoms such as dyspnoea and chest pain, as they may be of either respiratory or cardiac origin.

Although Bambec is not indicated for the treatment of premature labour it should be noted that bambuterol is metabolised to terbutaline and that terbutaline should not be used as a tocolytic agent in patients with pre-existing ischaemic heart disease or those patients with significant risk factors for ischaemic heart disease.

Due to the hyperglycaemic effects of β₂-agonists, additional blood glucose controls are recommended initially in diabetic patients.

Due to the positive inotropic effects of β₂-agonists these drugs should not be used in patients with hypertrophic cardiomyopathy.

β₂-agonists may be arrhythmogenic and this must be considered in the treatment of the individual patient.

Unpredictable inter-individual variation in the metabolism of bambuterol to terbutaline has been shown in subjects with liver cirrhosis. The use of an alternative β₂-agonist is recommended in patients with cirrhosis and other forms of severely impaired liver function.

Potentially serious hypokalaemia may result from β₂-agonist therapy. Particular caution is recommended in acute severe asthma as the associated risk may be augmented by hypoxia. The hypokalaemic effect may be potentiated by concomitant treatments (see section 4.5). It is recommended that serum potassium levels are monitored in such situations.

Asthma patients who require treatment with Bambec must have optimum anti-inflammatory treatment with corticosteroids. The patients must be instructed to continue taking their anti-inflammatory medication after the start of treatment with Bambec, even if the asthma symptoms diminish. If a previously effective dosage regimen no longer gives the same symptomatic relief this suggests that the underlying disease has worsened. The patient should urgently seek further medical advice and a re-evaluation of the asthma treatment must be carried out. Consideration should be given to the requirements for additional therapy (including increased dosages of anti-inflammatory medication). Treatment with Bambec must not be begun or the dose increased during an acute exacerbation of the asthma. Severe exacerbations of asthma should be treated as an emergency in the usual manner.

Bambec tablets contains lactose. Patients with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose galactose malabsorption should not take this medicine.

4.5 Interaction With Other Medicinal Products And Other Forms Of Interaction

Bambuterol prolongs the muscle-relaxing effect of suxamethonium (succinylcholine). A prolongation of the muscle-relaxing effect of suxamethonium of up to 2-fold has been observed in some patients after taking Bambec 20 mg on the evening prior to surgery. The inhibition is dose-dependent and fully reversible after cessation of treatment with bambuterol. This is due to the fact that plasma cholinesterase, which inactivates suxamethonium, is partly inhibited by bambuterol. In extreme situations, the interaction may result in a prolonged apnoea time which may be of clinical importance. This interaction should also be considered with other muscle relaxants, which are metabolised by plasma cholinesterase.

Beta-receptor blocking agents (including eye-drops), especially those which are non-selective, may partly or totally inhibit the effect of beta-stimulants. Therefore, Bambec tablets and non-selective β-blockers should not normally be administered concurrently.

Hypokalemia may result from β₂-agonist therapy and may be potentiated by concomitant treatment with xanthine derivatives, steroids and diuretics (see section 4.4).

Bambec should be used with caution in patients receiving other sympathomimetics.

4.6 Pregnancy And Lactation

Pregnancy

Although no teratogenic effects have been observed in animals after administration of bambuterol, caution is recommended during the first trimester of pregnancy.

Beta-agonists should be used with caution at the end of pregnancy because of the tocolytic effect.

Transient hypoglycaemia has been reported in newborn preterm infants after maternal β₂-agonist treatment.

Lactation

It is unknown whether bambuterol or intermediary metabolites are excreted in human breast milk. Terbutaline, the active metabolite of bambuterol, is excreted in breast milk, but at therapeutic doses of terbutaline no effect on breastfed newborns/infants are anticipated. A decision must be made whether to discontinue breast-feeding or to discontinue Bambec therapy taking into account the benefit of breast-feeding for the child and the benefit of therapy for the woman.

4.7 Effects On Ability To Drive And Use Machines

None stated.

4.8 Undesirable Effects

Most of the adverse reactions are characteristic of sympathomimetic amines. The intensity of the adverse reactions is dose-dependent. Tolerance to these effects has usually developed within 1-2 weeks.

Adverse events are listed below by system organ class and frequency. Frequencies are defined as: very common (

System Organ Class (SOC)	Frequency Classification	Adverse Drug Reaction
Immune system disorders	Not known	Hypersensitivity reactions including Angioedema, Urticaria, Exanthema, Bronchospasm, Hypotension and Collapse.
Metabolism and nutrition disorders	Not known	Hypokalemia Hyperglycaemia
Psychiatric disorders	Very Common	Behavioural Disturbances, such as Restlessness
	Common	Sleep disturbances
	Uncommon	Behavioural Disturbances, such as Agitation
	Not known	Dizziness Hyperactivity
Nervous system disorders	Very common	Tremor, Headache
Cardiac disorders	Common	Palpitations
	Uncommon	Tachycardia Cardiac arrhythmias, e.g. Atrial Fibrillation, Supraventricular tachycardia and Extrasystoles
	Not known	Myocardial ischemia (see section 4.4)
Respiratory, thoracic and mediastinal disorders	Unknown	Paradoxical bronchospasm
Gastrointestinal disorders	Not known	Nausea
Musculoskeletal, connective tissue and bone disorders	Common	Muscle cramps

4.9 Overdose

Symptoms

Overdosing may result in high levels of terbutaline and therefore the same symptoms and signs as recorded after overdosage with Bricanyl: Headache, anxiety, tremor, nausea, tonic muscle cramps, palpitations, tachycardia and cardiac arrhythmias.

A fall in blood pressure sometimes occurs after terbutaline overdosage.

Laboratory findings: Hyperglycaemia and lactic acidosis sometimes occur. High doses of β₂-agonists may cause hypokalemia as a result of redistribution of potassium.

Overdosage with Bambec is likely to cause a considerable inhibition of plasma cholinesterase, that may last for days (see also section 4.5).

Treatment of overdosage

Usually no treatment is required. In particularly severe cases of overdosage, the following measures may be considered on a case-by-case basis: Gastric lavage and activated charcoal.

Determine acid-base balance, blood glucose and electrolytes. Monitor heart rate and rhythm and blood pressure. The preferred antidote for haemodynamically significant cardiac arrhythmias is a cardioselective beta-blocking agent, but beta-blocking drugs should be used with caution in patients with a history of bronchospasm. If the β₂-mediated reduction in peripheral vascular resistance significantly contributes to the fall in blood pressure, a volume expander should be given.

5. Pharmacological Properties

5.1 Pharmacodynamic Properties

Pharmacotherapeutic group: selective β₂-agonists, bambuterol, ATC code: R03C C12.

Bambuterol is an active precursor of the selective β₂-adrenergic agonist terbutaline. Bambuterol is the bis-dimethylcarbamate of terbutaline, and is present in the formulation as a 1:1 racemate.

Pharmacodynamic studies have shown that after oral administration of bambuterol to guinea pigs, a sustained protective effect was achieved against histamine-induced bronchoconstriction. At equipotent doses, the duration of the relaxing activity was more prolonged than after plain terbutaline. Bambuterol, or the monocarbamate ester, did not exert any smooth muscle relaxing properties. The bronchoprotective effects seen after oral administration of bambuterol are related to the generation of terbutaline, as were the secondary effects (effects on other organs).

Pharmacodynamic studies have been conducted in asthmatics and healthy volunteers. The effects observed were bronchodilation, tremor and increases in heart rate. The metabolic effects included a small increase in blood glucose, while the effect on serum potassium was negligible. In short-term studies on lipoprotein metabolism, an increase in HDL cholesterol has been observed. In conclusion, all pharmacodynamic effects observed can be ascribed to the active metabolite terbutaline.

5.2 Pharmacokinetic Properties

On average, 17.5% of an oral dose is absorbed. Approximately 70–90% of the absorption occurs in the first 24 hours.

Bambuterol is metabolised in the liver and terbutaline is formed by both hydrolysis and oxidation. After absorption from the gut, about 2/3 of terbutaline is first-pass metabolised, bambuterol escapes this first-pass metabolism. Of the absorbed amount, about 65% reaches the circulation. Bambuterol therefore has a bioavailability of about 10%.

Protein binding of bambuterol is low, 40–50% at therapeutic concentrations.

The terminal half-life of bambuterol after an oral dose is 9–17 hours.

Studies on the effects on plasma cholinesterase showed that bambuterol inhibited activity, but that this was reversible.

All categories of subjects studied were able to form terbutaline in a predictive way except for liver cirrhotics.

5.3 Preclinical Safety Data

Bambuterol has not revealed any adverse effects which pose a risk to man at therapeutic dosages in the toxicity studies.

Bambuterol is given as a racemate: (-)-bambuterol is responsible for the pharmacodynamic effects via generation of (-)-terbutaline. (+)-bambuterol generates the pharmacodynamic inactive (+)-terbutaline. Both (+) and (-)-bambuterol are equally active as plasma cholinesterase inhibitors. This inhibition is reversible.

The toxicity studies showed that bambuterol has β₂-stimulatory effects, expressed as cardiotoxicity in dogs, and at high doses, observed in the acute toxicity studies, cholinergic effects.

There is no evidence from the preclinical safety data to indicate that bambuterol cannot be used in man for the intended indications with sufficient safety.

6. Pharmaceutical Particulars

6.1 List Of Excipients

Lactose monohydrate; maize starch; povidone; microcrystalline cellulose; magnesium stearate; water, purified.

6.2 Incompatibilities

Not applicable.

6.3 Shelf Life

3 years.

6.4 Special Precautions For Storage

Do not store above 30°C.

6.5 Nature And Contents Of Container

Amber glass bottle with LD-polyethene cap: 7, 14, 28, 30, 56 or 100 tablets.

HDPE container with LD-polyethene cap: 7, 14, 28, 30, 56 or 100 tablets.

HDPE container with polypropylene cap: 7, 14, 28, 30, 56 or 100 tablets.

PVC blisters: 7, 14, 28, 30, 56 or 100 tablets.

6.6 Special Precautions For Disposal And Other Handling

None.

7. Marketing Authorisation Holder

AstraZeneca UK Ltd.,

600 Capability Green,

Luton, LU1 3LU, UK.

8. Marketing Authorisation Number(S)

PL 17901/0103

9. Date Of First Authorisation/Renewal Of The Authorisation

21^st May 2002

10. Date Of Revision Of The Text

21^st March 2011

Baclofen Tablets BP 10mg (Sandoz Limited )

1. Name Of The Medicinal Product

Baclofen Tablets BP 10mg

Spasmolen 10mg

2. Qualitative And Quantitative Composition

Each tablet contains baclofen BP 10mg.

3. Pharmaceutical Form

Tablets.

4. Clinical Particulars

4.1 Therapeutic Indications

Baclofen is indicated for the relief of spasticity of voluntary muscle resulting from such disorders as: multiple sclerosis, other spinal lesions eg: tumours of the spinal cord, syringomyelia, motor neurone disease, transverse myelitis, traumatic partial section of the cord.

Baclofen is also indicated in adults and children for the relief of spasticity of voluntary muscle arising from eg: cerebrovascular accidents, cerebral palsy, meningitis, traumatic head injury.

Patient selection is most important when initiating baclofen therapy; it is likely to be of most benefit in patients whose spasticity constitutes a handicap to activities and/or physiotherapy. Treatment should not be commenced until the spastic state has been stabilised.

4.2 Posology And Method Of Administration

Oral administration.

The possible extent of clinical improvement to the patient should be assessed prior to the initiation of baclofen therapy. Titrated doses should be carefully administered in gradually increasing quantities until the patient's condition is stable (this is particularly important in elderly patients). If the dosage is too high or has been increased too quickly, side effects may ensue, especially in patients who are mobile to minimise muscle weakness in unaffected limbs or where some degree of spasticity is required.

Adults:

The following slowly increasing dosage regimen is suggested, but may be adjusted to suit the patient.

5mg 3 times a day for 3 days.

10mg 3 times a day for 3 days.

15mg 3 times a day for 3 days.

20mg 3 times a day for 3 days.

Doses up to 60mg a day usually provide satisfactory control of symptoms, though careful adjustment according to the requirements of each patient is frequently necessary. Small, more frequent doses of baclofen may prove better in some cases than larger, less frequent doses. If required, the dose may be increased slowly. A maximum daily dose of more than 100mg is not recommended, unless the patient is hospitalised and under close supervision. Once this maximum recommended dose is reached, if the therapeutic effects are not evident in 6 weeks, it may not be of benefit for the patient to continue on baclofen therapy.

Some patients may benefit from the use of baclofen just at night to oppose painful flexor spasm. Also, a single dose about an hour before carrying out tasks like dressing, washing, shaving and physiotherapy will often augment a patient's motility.

Elderly:

The elderly may be more susceptible to side effects, especially when first introducing baclofen. Initially, small doses are advised, with gradual adjustment under careful supervision. The eventual average maximum dose is as for adults, but caution should be exercised especially in patients with impaired renal function (see below).

Children:

Dosages in the range of 0.75 to 2mg/kg body weight should be used. In children over 10 years of age, a maximum daily dosage of 2.5mg/kg body weight may be given. Treatment usually commences with 2.5mg 4 times a day. Dosage should be cautiously raised at approximately 3 day intervals until the child's individual requirements are met.

Maintenance therapy:

Children aged 12 months to 2 years:	10 to 20mg
Children aged 2 to 6 years:	20 to 30mg
Children aged 6 to 10 years:	30 to 60mg.

Patients with Impaired Renal Function:

A low dosage of baclofen should be given, ie approximately 5mg a day, in patients with impaired renal function or who are undergoing chronic haemodialysis.

Patients with Spastic States of Cerebral Origin:

A very cautious dosage schedule should be adopted and patients should be carefully monitored as unwanted effects are more likely to occur in these patients.

4.3 Contraindications

Peptic ulceration and hypersensitivity to baclofen.

4.4 Special Warnings And Precautions For Use

Psychotic disorders, confusional states, schizophrenia, depressive or manic disorders or Parkinson's disease may be worsened by treatment with baclofen. Therefore, patients with these conditions should be kept under close observation and treatment should be administered cautiously.

Epileptic manifestations may be exacerbated with baclofen treatment, but may be used if appropriate supervision and anticonvulsive therapy are maintained.

Baclofen should be used with extreme care in patients already receiving antihypertensive therapy.

Caution should be exercised with baclofen therapy in patients suffering from renal, hepatic or respiratory impairment or who have had a cerebrovascular accident.

Patients with neurogenic disturbances affecting emptying of the bladder may show improvement in their condition whilst taking baclofen. However, patients with pre-existing sphincter hypertonia may suffer with acute urine retention during treatment with baclofen; as a result it should be used cautiously in these patients.

Appropriate laboratory tests should be carried out on patients with hepatic dysfunction or diabetes mellitus to make sure that no drug-induced changes to the underlying diseases have resulted with concomitant baclofen therapy as, rarely, elevated SGOT, alkaline phosphatase and glucose levels in serum have been recorded.

Baclofen therapy should always be gradually discontinued, unless serious adverse effects have occurred, by reducing the dose over a period of 1-2 weeks. Anxiety, confusion, hallucinations, psychosis, mania, paranoia, convulsions, tachycardia, and, as a rebound phenomenon, temporary aggravation of spasticity, have all been reported on abrupt withdrawal.

4.5 Interaction With Other Medicinal Products And Other Forms Of Interaction

There have been reports of hallucinations, agitation and mental confusion with the use of baclofen with levodopa and carbidopa in Parkinson's disease.

Use of tricyclic antidepressants and baclofen may result in the potentiation of the effect of baclofen, resulting in pronounced muscular hypotonia.

Baclofen excretion may be reduced by drugs which produce renal insufficiency, eg ibuprofen, resulting in toxic effects.

Concomitant use of drugs acting on the CNS or alcohol with baclofen may lead to increased sedation.

The risk of respiratory depression is also increased. Careful monitoring of respiratory and cardiovascular functions is essential especially in patients with cardiopulmonary disease and respiratory muscle weakness.

Fentanyl induced analgesia may be extended by pretreatment with baclofen.

Hyperkinetic symptoms in patients receiving lithium may be exacerbated by baclofen.

Antihypertensive therapy may require adjustment as an increased fall in blood pressure may result with concomitant treatment with baclofen.

4.6 Pregnancy And Lactation

Not recommended in pregnancy as fetal malformations have been reported as having occurred in rats but not mice or rabbits. Where treatment is necessary, the benefits for the mother should be carefully considered against the possible risks to the child, particularly in the first trimester when baclofen should only be used if essential. Baclofen is not recommended whilst breast-feeding as it is known to be present in the milk.

4.7 Effects On Ability To Drive And Use Machines

Patients taking baclofen should not take charge of vehicles, other means of transport, or machinery where loss of attention may lead to accidents.

4.8 Undesirable Effects

Undesirable effects occur predominately with initial treatment, with large doses, if the dose is increased too quickly or in the treatment of the elderly. These effects rarely necessitate withdrawal of the medication and are frequently of short duration. Modifying the dosage may lessen or eliminate the effects.

It may be difficult to distinguish between drug-induced undesirable effects and those caused by the diseases being treated.

Gastro-intestinal Tract: Mild gastro-intestinal disturbances such as constipation or diarrhoea may occasionally occur. Dry mouth, nausea and vomiting have also been reported. Should nausea continue despite reduced dosage, baclofen should be taken with food or a milk drink.

Genito-urinary Tract: Increased frequency of micturition, dysuria and enuresis have rarely been reported.

Cardio-respiratory System: Hypotension and cardiovascular or respiratory depression have been reported occasionally.

Central Nervous System: Especially at the beginning of treatment, effects including drowsiness and daytime sedation may occur with occasional reports of lassitude, exhaustion, light-headedness, confusion, dizziness, headache and insomnia.

A lower convulsion threshold and seizures may occur, particularly in patients with epilepsy.

Other neurological effects which have been reported include paraesthesiase, muscle weakness, myalgia, ataxia, tremor, nystagmus and accommodation disorders. Reported psychiatric effects include euphoria, hallucinations, nightmares and depressive states.

Other Unwanted Effects: There have been very rare reports of skin rash, hyperhidrosis, visual disturbance, changes in taste sensation and a deterioration in liver function tests.

Increased spasticity as a contradictory response to the medication has been reported in some patients.

Some patients may experience greater difficulty in walking or coping for themselves as a result of excessive hypotonia. This may be alleviated by altering the dosage schedule.

There have been rare reports of hypothermia.

4.9 Overdose

Symptoms: Primarily, these are signs of central nervous depression: including drowsiness, consciousness impairment, respiratory depression, coma. Also likely are confusion, agitation, hallucinations, eye accommodation disorders, absent pupillary reflex, generalised muscular hypotonia, myoclonia, hyporeflexia or areflexia, convulsions, peripheral vasodilatation, hypotension, bradycardia, nausea, vomiting, diarrhoea, hypersalivation and elevated LDH, SGOT and AP values.

Deterioration in the condition may occur if various substances/drugs acting on the CNS, eg alcohol, tricyclic antidepressants or diazepam, have been taken at the same time.

Treatment: No specific antidote is known.

Removal of the drug from the gastro-intestinal tract should be attempted by inducing vomiting or gastric lavage. Comatose patients need to be intubated prior to gastric lavage. Activated charcoal or, if necessary, a saline aperient may be given. In respiratory depression, artificial respiration and measures to support cardiovascular functions should be applied. Large quantities of fluid should be given, possibly with a diuretic, since baclofen is excreted mainly through the kidneys. If convulsions occur, intravenous diazepam should be administered.

5. Pharmacological Properties

5.1 Pharmacodynamic Properties

Baclofen is an analogue of aminobutyric acid. Its mode of action is not fully understood. It inhibits monosynaptic and polysynaptic transmission at the spinal level and also depresses the CNS.

5.2 Pharmacokinetic Properties

The following mean values were obtained for Baclofen Tablets 10mg in healthy volunteers.

T½ (hours)	3.301
Tmax (hours)	1.549
Cmax (ng/ml)	102
AUC (ng/ml hours)	674

5.3 Preclinical Safety Data

--

6. Pharmaceutical Particulars

6.1 List Of Excipients

Lactose, potato starch, microcrystalline cellulose, sodium starch glycollate and magnesium stearate.

6.2 Incompatibilities

Not known.

6.3 Shelf Life

3 years.

6.4 Special Precautions For Storage

Store in a cool dry place and protect from light.

6.5 Nature And Contents Of Container

Securitainer with polyethylene closure.

Pack sizes: 28, 84, 90 and 100.

6.6 Special Precautions For Disposal And Other Handling

Not applicable.

7. Marketing Authorisation Holder

Sandoz Limited

Frimley Business Park,

Frimley,

Camberley,

Surrey,

GU16 7SR.

United Kingdom

8. Marketing Authorisation Number(S)

PL 04416/0160

9. Date Of First Authorisation/Renewal Of The Authorisation

27 September 1990 / 19 December 2000

10. Date Of Revision Of The Text

November 2010

Balmosa Cream

1. Name Of The Medicinal Product

BALMOSA CREAM

2. Qualitative And Quantitative Composition

Active ingredients:

Menthol BP 2.0% w/w

Camphor BP 4.0% w/w

Methyl Salicylate Ph.Eur. 4.0% w/w

Capsicum Oleoresin BPC 0.035% w/w

3. Pharmaceutical Form

Cream for cutaneous use.

4. Clinical Particulars

4.1 Therapeutic Indications

Analgesic/rubefacient cream for the symptomatic relief of muscular rheumatism, fibrositis, lumbago, sciatica and unbroken chilblains.

4.2 Posology And Method Of Administration

Adults and the elderly:

Apply topically. Massage gently into the affected area as required. Wash hands immediately after use.

Children under 12 years:

Not generally recommended.

4.3 Contraindications

Hypersensitivity to aspirin, other non-steroidal anti-inflammatory drugs, or any of the ingredients listed.

4.4 Special Warnings And Precautions For Use

For external use only.

If skin sensitivity reactions occur, discontinue use. Do not apply to inflamed or broken skin. Avoid contact with the eye and mucous membranes. Do not apply to the nostrils of infants. Do not use with occlusive dressings.

After use avoid exposing the affected area to excessive sunlight.

4.5 Interaction With Other Medicinal Products And Other Forms Of Interaction

None stated.

4.6 Pregnancy And Lactation

With all salicylates there is animal evidence of teratogenicity. Use should be avoided during pregnancy and breast feeding.

4.7 Effects On Ability To Drive And Use Machines

None stated.

4.8 Undesirable Effects

Skin sensitivity reactions are possible although rare. Topical applications of large amounts of Balmosa Cream may result in systemic effects, including hypersensitivity and worsening of asthma.

4.9 Overdose

Overdosage is extremely unlikely from topical use.

5. Pharmacological Properties

5.1 Pharmacodynamic Properties

Capsicum oleoresin is a rubefacient. Camphor exhibits counter-irritant and weak local anaesthetic activity. Menthol and methyl salicylate impart analgesic properties to the formulation.

5.2 Pharmacokinetic Properties

Not applicable

5.3 Preclinical Safety Data

There are no preclinical data of relevance to the prescriber which are additional to that already included in other sections of the SPC.

6. Pharmaceutical Particulars

6.1 List Of Excipients

Methylcellulose

White soft paraffin

Emulsifying wax

Liquid paraffin

Lanolin (anhydrous)

Phenonip

Purified Water

6.2 Incompatibilities

None stated.

6.3 Shelf Life

3 years

6.4 Special Precautions For Storage

Do not store above 25^oC.

6.5 Nature And Contents Of Container

Aluminium tube with a polyethylene cap containing 20g or 40g of the product.

6.6 Special Precautions For Disposal And Other Handling

None stated.

7. Marketing Authorisation Holder

Forest Laboratories UK Limited

Bourne Road

Bexley

Kent DA5 1NX

8. Marketing Authorisation Number(S)

PL 0108/5000R

9. Date Of First Authorisation/Renewal Of The Authorisation

18 March 1983 / 22 May 2003

10. Date Of Revision Of The Text

April 2003.

11. Legal Category

GSL

Balneum Plus Cream (Almirall Limited )

1. Name Of The Medicinal Product

Balneum Plus Cream

2. Qualitative And Quantitative Composition

Active Ingredient Lauromacrogols Urea	Percentage (w/w) 3.0% 5.0%
For full list of excipients, see section 6.1.

3. Pharmaceutical Form

Cream.

A white smooth cream.

4. Clinical Particulars

4.1 Therapeutic Indications

For the treatment of pruritus, eczema, dermatitis, and scaling skin conditions where an antipruritic and/or hydrating effect is required. It may also be used for the continued treatment and follow-up treatment of these skin diseases.

4.2 Posology And Method Of Administration

Adults, the elderly and children: Balneum Plus Cream should be applied to each affected area twice a day. The duration of treatment depends on the clinical response. For external use only.

4.3 Contraindications

Patients with known hypersensitivity to any of the ingredients. It should not be used to treat acute erythroderma, acute inflammatory, oozing or infected skin lesions.

4.4 Special Warnings And Precautions For Use

Balneum Plus Cream may cause irritation if applied to broken or inflamed skin.

4.5 Interaction With Other Medicinal Products And Other Forms Of Interaction

None known.

4.6 Pregnancy And Lactation

For Balneum Plus Cream no clinical data on exposed pregnancies are available.

Animal studies do not indicate direct or indirect harmful effects with respect to pregnancy, embryonal/foetal development, parturition or postnatal development.

There are no specific restrictions concerning its use during pregnancy, but it is not to be used on the breasts immediately prior to breast feeding during lactation.

4.7 Effects On Ability To Drive And Use Machines

None.

4.8 Undesirable Effects

Balneum Plus Cream has been reported to cause a burning sensation, erythema, pruritus or the formation of pustules, aggravation of eczema if applied to inflamed skin areas. Contact allergy has also been reported.

4.9 Overdose

Not applicable

5. Pharmacological Properties

5.1 Pharmacodynamic Properties

Pharmacotherapeutic group: Antipruritics incl. antihistamines, anaesthetics etc.

ATC code: D 04 AX

Urea is a physiological product derived from human protein metabolism. It is found naturally in the skin and when applied topically it can increase the horny layer's capacity to retain water. Balneum Plus Cream has been shown to increase skin hydration and when used as recommended provides hydration for 24 hours.

Patients with eczema and psoriasis have been shown to have decreased levels of urea in their skin. Urea is not allergenic and is well-tolerated at a concentration of 5%.

Lauromacrogols have the properties of a topical anaesthetic and have an antipruritic effect. The local tolerability of lauromacrogols is good.

Balneum Plus Cream has also been shown to increase the lipid content of the epidermis thus soothing and smoothing the skin.

After twice-daily application for 4 weeks to non-infected eczematous lesions, in addition to an improvement in the clinical condition, use of Balneum Plus Cream was associated with a significant reduction in total bacteria and Staph. aureus counts. A reduction in Staph. aureus count (p²) to Day 29 (11.8 organisms/cm²). However, no bactericidal or bacteriostatic effects have been tested for.

5.2 Pharmacokinetic Properties

Little urea is absorbed after topical application. It is mainly excreted in the urine, and to a lesser extent in perspiration.

There is no evidence of systemic availability of lauromacrogols after topical administration.

5.3 Preclinical Safety Data

No specific studies have been performed with Balneum Plus Cream. Urea and lauromacrogols have been used therapeutically for many years in humans. Information from animal studies are unlikely to provide any further relevant information.

6. Pharmaceutical Particulars

6.1 List Of Excipients

Dimethicone

Phenyl dimeticone

Liquid paraffin

Cetylpalmitate

Stearic palmitic acid

Octyldodecanol

Glycerol 85%

Polvsorbate

Carbomer

Trometamol

Benzyl alcohol

Purified water

6.2 Incompatibilities

Not applicable.

6.3 Shelf Life

24 months.

6.4 Special Precautions For Storage

Do not store above 25°C.

6.5 Nature And Contents Of Container

Aluminium tubes with double internal lacquer of epoxy phenol resin and closure made of polyethylene. Content: 10g, 35g, 50g, 75g and 100g.

Plastic pump dispensers. Content: 175g, 180g, 185g, 190g, 200g and 500g.

6.6 Special Precautions For Disposal And Other Handling

No special requirements

7. Marketing Authorisation Holder

Almirall Hermal GmbH

Scholtzstrasse 3

Postfach 1228 Reinbek

Hamburg

D-21465

Germany

8. Marketing Authorisation Number(S)

PL 33016/0010

9. Date Of First Authorisation/Renewal Of The Authorisation

31^st July 1998

10. Date Of Revision Of The Text

06^th October 2010

Beechams All-In-One Tablets

1. Name Of The Medicinal Product

Beechams All-In-One Tablets

2. Qualitative And Quantitative Composition

Each tablet contains paracetamol 250 mg, guaifenesin 100 mg and phenylephrine hydrochloride 5 mg

Contains lactose

For full list of excipients, see section 6.1

3. Pharmaceutical Form

Tablets.

White, film-coated tablets embossed with a 'B' on one side.

4. Clinical Particulars

4.1 Therapeutic Indications

Short term symptomatic relief of colds, chills and influenza including chesty coughs.

4.2 Posology And Method Of Administration

Adults and children 12 years and over

Two tablets. Repeat every four hours as necessary.

Do not take more than 8 tablets in 24 hours.

Not to be given to children under 12 years except on medical advice.

Elderly

The normal adult dose may be taken.

Do not take continuously for more than 5 days without medical advice.

4.3 Contraindications

Known hypersensitivity to any of the ingredients.

Concomitant use of other sympathomimetic decongestants.

Phaeochromocytoma.

Closed angle glaucoma.

Hepatic or severe renal impairment, hypertension, hyperthyroidism, diabetes, heart disease or those taking tricyclic antidepressants or beta-blocking drugs and those patients who are taking or have taken, within the last two weeks, monoamine oxidase inhibitors (see section 4.5).

4.4 Special Warnings And Precautions For Use

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.

Keep out of the reach and sight of children.

Patients with rare hereditary problems of galactose intolerance, the Lapp lactose deficiency or glucose-galactose malabsoption should not take this medicine.

Special label warnings

Do not take with any other paracetamol-containing products. Do not take with other flu, cold or decongestant products.

Immediate medical advice should be sought in the event of an overdose, even if you feel well.

Special leaflet warnings

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.

4.5 Interaction With Other Medicinal Products And Other Forms Of Interaction

The anticoagulant effect of warfarin and other coumarins may be enhanced by prolonged regular use of paracetamol with increased risk of bleeding. The hepato-toxicity of paracetamol may be potentiated by excessive intake of alcohol. The speed of absorption of paracetamol may be increased by metoclopramide or domperidone and absorption reduced by colestyramine. 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.

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.
Ergot alkaloids (ergotamine and methylsergide)	Increased risk of ergotism
Digoxin and cardiac glycosides	Increase the risk of irregular heartbeat or heart attack

If urine is collected within 24 hours of a dose of this product, a metabolite may cause a colour interference with laboratory determinations of 5 hydroxyindoleacetic acid (5-HIAA) and vanillymandelic acid (VMA).

4.6 Pregnancy And Lactation

This product should not be used during pregnancy without medical advice.

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. The safety of guaiphenesin and phenylephrine during pregnancy has not been established.

Paracetamol and phenylephrine are excreted in breast milk but not in a clinically significant amount. This product should not be used in breast feedingwithout medical advice.

4.7 Effects On Ability To Drive And Use Machines

Patients should be advised not to drive or operate machinery if affected by dizziness.

4.8 Undesirable Effects

Adverse events from historical clinical trial data are both infrequent and from small patient exposure. Events reported from extensive post-marketing experience at therapeutic/labelled dose and considered attributable are tabulated below by MedDRA System Organ Class. Due to limited clinical trial data, the frequency of these adverse events is not known (cannot be estimated from available data), but post-marketing experience indicates that adverse reactions to paracetamol are rare and serious reactions are very rare.

Body System	Undesirable effect
Blood and lymphatic system disorders	Thrombocytopenia Agranulocytosis These are not necessarily causally related to paracetamol
Immune system disorders	Anaphylaxis Cutaneous hypersensitivity reactions including skin rashes, angiodema and Stevens Johnson syndrome
Respiratory, thoracic and mediastinal disorders	Bronchospasm in patients sensitive to aspirin and other NSAIDs
Hepatobiliary disorders	Hepatic dysfunction
Gastrointestinal disorders	Acute pancreatitis

The following adverse events have been observed in clinical trials with phenylephrine and may therefore represent the most commonly occurring adverse events.

Body System	Undesirable effect
Psychiatric disorders	Nervousness, irritability, restlessness, and excitability
Nervous system disorders	Headache, dizziness, insomnia
Cardiac disorders	Increased blood pressure
Gastrointestinal disorders	Nausea, Vomiting, diarrhoea

Adverse reactions identified during post-marketing use are listed below. The frequency of these reactions is unknown but 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). Hypersensitivity reactions – including that cross-sensitivity may occur with other sympathomimetics.
Renal and urinary disorders	Dysuria, urinary retention. This is most likely to occur in those with bladder outlet obstruction, such as prostatic hypertrophy.

Guaifenesin

The frequency of these events is unknown but considered likely to be rare .

Body system	Undesirable effect
Immune system disorders	Allergic reactions, angioedema, anaphylactic reactions
Respiratory, thoracic and mediastinal disorders	Dyspnoea*
Gastrointestinal disorders	Nausea, vomiting, abdominal discomfort,
Skin and subcutaneous disorders	Rash, urticaria

4.9 Overdose

Paracetamol

Liver damage is possible in adults who have taken 10g or more of paracetamol. Ingestion of 5g 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, phenobarbitone, 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 in accordance with established treatment guidelines, see BNF overdose section.

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 24 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 24h from ingestion should be discussed with the NPIS or a liver unit.

Phenylephrine

Symptoms and signs

Phenylephrine overdosage is likely to result in effects similar to those listed under advserse reactions. Additional symptoms may include hypertension and possibly reflux bradycardia. In severe cases confusion, hallucinations, seizures and arrythmias may occir. However the amount required to produce serious phenylephrine toxicity would be greater than required to cause paracetamol-related toxicity.

Treatment

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

Guaifenesin

Symptoms and signs

Very large doses of guaifenesin cause nausea and vomiting.

Treatment

Vomiting would be treated by fluid replacement and monitoring of electrolytes if indicated.

5. Pharmacological Properties

5.1 Pharmacodynamic Properties

ATC Code: N02BE 51 Paracetamol combinations excluding psycholeptics.

Paracetamol is an analgesic and antipyretic.

Guaifenesin is an expectorant.

Phenylephrine Hydrochloride is a sympathomimetic decongestant.

The active ingredients are not known to cause sedation.

5.2 Pharmacokinetic Properties

Paracetamol is readily absorbed from the gastrointestinal tract. It is metabolised in the liver and excreted in the urine, mainly as glucuronide and sulphate conjugates.

Guaifenesin is rapidly absorbed after oral administration. It is rapidly metabolised by oxidation to ß-(2 methoxy-phenoxy) lactic acid, which is excreted in the urine.

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 has reduced bioavailability. It is excreted in the urine almost entirely as the sulphate conjugate.

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 of the product and which have not already been mentioned elsewhere in this SPC.

6. Pharmaceutical Particulars

6.1 List Of Excipients

Tablets

Lactose

Microcrystalline cellulose

Maize starch

Stearic acid

Colloidal anhydrous silica

Purified talc

Povidone

Potassium sorbate

Pregelatinised starch

Film coating

Hypromellose E464

Titanium dioxide E171

Polyethylene glycol 4000

Lactose monohydrate

6.2 Incompatibilities

None known.

6.3 Shelf Life

Three years.

6.4 Special Precautions For Storage

Do not store above 25°C

6.5 Nature And Contents Of Container

Blister of 250µm PVC/ 25µm LDPE/ 90gsm PVdC/ 30µm Aluminium foil containing 8, 12 or 16 tablets

6.6 Special Precautions For Disposal And Other Handling

Not applicable.

7. Marketing Authorisation Holder

Beecham Group plc

980 Great West Road

Brentford

Middlesex

TW8 9GS

United Kingdom

Trading as: GlaxoSmithKline Consumer Healthcare, Brentford, TW8 9GS

8. Marketing Authorisation Number(S)

PL 00079/0630

9. Date Of First Authorisation/Renewal Of The Authorisation

3^rd July 2008

10. Date Of Revision Of The Text

14/10/2011

Beechams Ultra All In One Capsules, hard.

1. Name Of The Medicinal Product

Beechams Ultra All In One Capsules, hard.

2. Qualitative And Quantitative Composition

Active Ingredient	mg/Capsule
Paracetamol	500
Guaifenesin	100
Phenylephrine hydrochloride	6.1

For a full list of excipients, see section 6.1.

3. Pharmaceutical Form

Capsule, hard.

Dark blue/dark green hard gelatin capsules 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. Swallow whole with water, do not chew.

Adults, the elderly and children aged 12 years and over:

Two capsules every four hours as required. Do not take more than 8 capsules (4 doses) in any 24 hour period.

Do not give to children under 12 years old.

4.3 Contraindications

Hypersensitivity to any of the ingredients.

Severe heart disease and cardiovascular disorders. Hypertension. Hyperthyroidism. Contraindicated in patients currently receiving or within two weeks of stopping therapy with monoamine oxidase inhibitors.

Use in patients with glaucoma or urinary retention.

Use in patients who are currently receiving other sympathomimetic drugs.

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.

Use with caution in patients with Raynaud's Phenomenon and 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.

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 exceed the stated dose.

If symptoms persist 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.

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.

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.

Sympathomimetic-containing products should be used with caution in patients receiving digitalis, beta-adrenergic blockers, guanethidine, reserpine, methyldopa or anti-hypertensive agents.

Concurrent use with halogenated anaesthetic agents such as chloroform, cyclopropane, halothane, enflurane or isoflurane may provoke or worsen ventricular arrhythmias.

4.6 Pregnancy And Lactation

PARACETAMOL

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.

Paracetamol is excreted in breast milk but not in a clinically significant amount. Available published data do not contraindicate breast feeding.

GUAIFENESIN

The safety of guaifenesin in pregnancy and lactation has not been fully established but this constituent is not thought to be hazardous. However the product should only be used in pregnancy when considered essential by the doctor.

PHENYLEPHRINE HYDROCHLORIDE

Due to the vasconstrictive properties of phenylephrine, the product should be used with caution in patients with a history of pre-eclampsia. Phenylephrine may reduce placental perfusion and the product should be used in pregnancy only if the benefits outweigh this risk. There is no information on use in lactation.

4.7 Effects On Ability To Drive And Use Machines

None known.

4.8 Undesirable Effects

The active ingredients are usually well tolerated in normal use.

PARACETAMOL

Adverse effects of paracetamol are rare but hypersensitivity including skin rashes may occur. There have been reports of blood dyscasias including thrombocytopenia and agranulocytosis, but these were not necessarily causally related to paracetamol.

GUAIFENESIN

Gastrointestinal discomfort has occasionally been reported with guaifenesin.

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.

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 in 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

Very large doses of guaifenesin can cause nausea and vomiting. Vomiting should be treated by fluid replacement and monitoring of electrolytes.

PHENYLEPHRINE HYDROCHLORIDE

Severe overdosage may produce hypertension and associated reflex bradycardia. 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.

5. Pharmacological Properties

5.1 Pharmacodynamic Properties

Pharmacotherapeutic Group: Other analgesics and antipyretics & Other cold combination preparations

ATC code: N02BE51

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 heat-regulating 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 β-(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

Maize starch

Croscarmellose sodium

Sodium laurilsulfate

Magnesium stearate

Talc

Gelatin capsule:

Gelatin

Quinoline yellow E104

Indigo carmine E132

Erythrosine E127

Titanium dioxide E171

6.2 Incompatibilities

None known.

6.3 Shelf Life

24 months

6.4 Special Precautions For Storage

Do not store above 25°C.

6.5 Nature And Contents Of Container

Child Resistant blister comprising 250 micron PVC lidded with 35 gsm paper/9 micron aluminium foil.

Pack sizes of 8 and 16 capsules are available.

6.6 Special Precautions For Disposal And Other Handling

None.

7. Marketing Authorisation Holder

Wrafton Laboratories Limited (T/A Perrigo)

Braunton

Devon

EX33 2DL

8. Marketing Authorisation Number(S)

PL 12063/0082

9. Date Of First Authorisation/Renewal Of The Authorisation

20/01/2009

10. Date Of Revision Of The Text

20/01/2009