4.1. Therapeutic indications

This product is indicated for the symptomatic relief of upper respiratory tract disorders accompanied by productive cough, which are benefited by the combination of a decongestant of the mucous membranes of the upper respiratory tract, especially the nasal mucosa and sinuses, and an expectorant.

4.2. Posology and method of administration

Posology

Adults and children aged 12 years and over:

10 ml syrup every 4 - 6 hours up to 4 times a day.

Maximum daily dose: 40 ml

Children under 12 years:

This product is contraindicated in children under the age of 12 years (see section 4.3).

The elderly:

Normal adult dosage is appropriate, [See Pharmacokinetics in the elderly, section 5.2].

Hepatic dysfunction:

Experience with the use of the product suggests normal adult dosage is appropriate, although it may be prudent to exercise caution in the presence of severe hepatic impairment, [See Pharmacokinetics in the elderly, section 5.2].

Renal dysfunction:

Caution should be exercised when administering this product to patients with moderate to severe renal impairment, particularly if accompanied by cardiovascular disease, [See Pharmacokinetics in Renal Impairment, section 5.2].

Do not exceed the stated dose.

Method of Administration

For oral use

4.3. Contraindications

This product is contraindicated in individuals with known hypersensitivity to the product, or any of the excipients listed in section 6.1.

This product is contraindicated in individuals with cardiovascular disease including hypertension and individuals taking beta blockers (see section 4.5).

This product is contraindicated in individuals who are concomitantly taking other sympathomimetic decongestants.

This product is contraindicated in individuals with diabetes mellitus, closed angle glaucoma, hyperthyroidism, phaeochromocytoma or severe renal impairment.

This product is contraindicated in individuals who are taking, or have taken, monoamine oxidase inhibitors within the preceding 14 days. The concomitant use of pseudoephedrine and this type of product may cause a rise in blood pressure or hypertensive crisis (see Section 4.5).

Not to be used in children under the age of 12 years.

4.4. Special warnings and precautions for use

Patients with thyroid disease who are receiving thyroid hormones should not take pseudoephedrine unless directed by a physician.

Patients with the following conditions should be advised to consult a physician before using this product: difficulty in urination due to enlargement of the prostate; a respiratory condition such as emphysema, chronic bronchitis or acute or chronic bronchial asthma.

This product should be not used for persistent or chronic cough, such as occurs with asthma, or emphysema where cough is accompanied by excessive secretions, unless directed by a physician.

Patients should be advised to consult a physician if their cough lasts for more than 5 days or comes back, or is accompanied by a fever, rash or persistent headache.

Caution should be exercised when using the product in the presence of severe hepatic impairment or moderate to severe renal impairment (particularly if accompanied by cardiovascular disease), [See section 5.2], or occlusive vascular disease.

If any of the following occur, this product should be stopped

- Hallucinations

- Restlessness

- Sleep disturbances

Severe Skin reactions: Severe skin reactions such as acute generalized exanthematous pustulosis (AGEP) may occur with pseudoephedrine-containing products. 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 localized on the skin folds, trunk, and upper extremities. Patients should be carefully monitored. If signs and symptoms such as pyrexia, erythema, or many small pustules are observed, administration of this medicine should be discontinued, and appropriate measures taken if needed.

Ischaemic colitis: Some cases of ischaemic colitis have been reported with pseudoephedrine. Pseudoephedrine should be discontinued, and medical advice sought if sudden abdominal pain, rectal bleeding or other symptoms of ischaemic colitis develop.

There have been rare cases of posterior reversible encephalopathy syndrome (PRES) / reversible cerebral vasoconstriction syndrome (RCVS) reported with sympathomimetic drugs, including pseudoephedrine. Symptoms reported include sudden onset of severe headache, nausea, vomiting, and visual disturbances. Most cases improved or resolved within a few days following appropriate treatment. Pseudoephedrine should be discontinued, and medical advice sought immediately if signs or symptoms of PRES/RCVS develop.

Patients with rare hereditary problems of fructose intolerance, glucose-galactose malabsorption or sucrose-isomaltase insufficiency should not take this medicine.

This product contains Ponceau 4R (E124) red colouring and sunset yellow (E110) which may cause allergic reactions.

This product contains Methyl Hydroxybenzoate (E 218) and Propyl Hydroxybenzoate (E 216) which may cause allergic reactions (possibly delayed).

This medicinal product contains 5 % v/v ethanol (alcohol), which is up to 190 mg per 5 ml, and equal to 5 ml beer or 2 ml wine per 5 ml. Harmful for those suffering from alcoholism. To be taken into account in pregnant or breast-feeding women, children and high-risk groups such as patients with liver disease, or epilepsy.

Not more than 4 doses should be given in any 24 hours.

Do not exceed the stated dose.

Do not take with any other cough and cold medicine.

4.5. Interaction with other medicinal products and other forms of interaction

MAOIs and/or RIMAs: Pseudoephedrine exerts its vasoconstricting properties by stimulating α-adrenergic receptors and displacing noradrenaline from neuronal storage sites. Since monoamine oxidase inhibitors (MAOIs) impede the metabolism of sympathomimetic amines and increase the store of releasable noradrenaline in adrenergic nerve endings, MAOIs may potentiate the pressor effect of pseudoephedrine. This product should not be used in patients taking monoamine inhibitors or within 14 days of stopping treatment as there is an increased risk of hypertensive crisis.

Moclobemide: risk of hypertensive crisis.

Concomitant use of this product with tricyclic antidepressants, sympathomimetic agents (such as decongestants, appetite suppressants and amphetamine-like psychostimulants) may occasionally cause a rise in blood pressure. [See section 4.3].

Antihypertensives: Because of its pseudoephedrine content, this product may partially reverse the hypotensive action of antihypertensive drugs which interfere with sympathetic activity including bretylium, betanidine, guanethidine, debrisoquine, methyldopa, adrenergic neurone blockers and beta blockers, [See section 4.4].

Oxytocin: risk of hypertension.

Cardiac glycosides: increased risk of dysrhythmias.

Ergot alkaloids (ergotamine & methysergide): increased risk of ergotism.

Anticholinergic drugs: enhances effects of anticholinergic drugs (such as tricyclic antidepressants).

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

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

4.6. Fertility, pregnancy and lactation

This product should not be used during pregnancy or lactation unless the potential benefit of treatment to the mother outweighs the possible risks to the developing foetus or nursing infant.

Pregnancy

There are no adequate and well-controlled studies in pregnant women

Breast-feeding

Pseudoephedrine is excreted in breast milk in small amounts but the effect of this on breast-fed infants is not known. It has been estimated that approximately 0.5 to 0.7 % of a single 60 mg dose of pseudoephedrine ingested by a nursing mother will be excreted in the breast milk over 24 hours. 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.

Guaifenesin is excreted in breast milk in small amounts with no effect expected on the infant.

4.7. Effects on ability to drive and use machines

It is not known if this product has an effect on the ability to drive or operate machinery.

4.8. Undesirable effects

Placebo-controlled studies with sufficient adverse event data were not available for the combination of guaifenesin and pseudoephedrine.

Adverse drug reactions identified during clinical trials and post-marketing experience with guaifenesin or pseudoephedrine or combination are listed below by System Organ Class (SOC).

The frequencies are defined according to the following convention:

Very common ≥1/10

Common ≥1/100 and < 1/10

Uncommon ≥1/1,000 and <1/100

Rare ≥1/10,000 and <1/1,000

Very rare <1/10,000

Not known (cannot be estimated from the available data).

ADRs are presented by frequency category based on 1) incidence in adequately designed clinical trials or epidemiology studies, if available, or 2) when incidence cannot be estimated, frequency category is listed as 'Not known'

System Organ Class (SOC)

Adverse Drug Reaction (Preferred Term)

Frequency

Immune System Disorders

Hypersensitivity (Cross-sensitivity may occur with other sympathomimetics)

Not known

Psychiatric Disorders

Insomnia

Nervousness

Anxiety

Euphoric mood

Excitability

Hallucinations

Irritability

Paranoid delusions

Restlessness

Sleep disorder

Common

Common

Not known

Not known

Not known

Not known

Not known

Not known

Not known

Not known

Nervous System Disorders

Headache

Dizziness

Cerebrovascular accident

Posterior reversible encephalopathy syndrome (PRES)/reversible cerebral vasoconstriction syndrome (RCVS)

Psychomotor hyperactivity

Somnolence

Very common

Common

Not known

Not known

Not known

Not known

Cardiac Disorders

Dysrhythmias

Myocardial infarction/myocardial ischaemia

Palpitations

Tachycardia

Not known

Not known

Not known

Not known

Vascular Disorders

Hypertension

Not known

Gastrointestinal Disorders

Dry mouth

Nausea

Abdominal pain

Diarrhoea

Ischaemic colitis

Vomiting

Common

Common

Not known

Not known

Not known

Not known

Skin and Subcutaneous Tissue Disorders

Angioedema

Pruritus

Rash

Severe skin reactions, including acute generalised exanthematous pustulosis (AGEP)

Urticaria

Not known

Not known

Not known

Not known

Not known

Renal and Urinary Disorders

Dysuria

Urinary Retention (in men in whom prostatic enlargement could have been an important predisposing factor)

Not known

Not known

Reporting of suspected adverse reactions:

Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions via the Yellow Card Scheme: www.mhra.gov.uk/yellowcard or search for MHRA Yellow Card in the Google Play or Apple App Store.

4.9. Overdose

Symptoms and signs

The effects of acute toxicity from this product may include drowsiness, irritability, restlessness, tremor, palpitations, convulsions, hypertension, difficulty with micturition, gastro-intestinal discomfort, nausea and vomiting.

Guaifenesin

When taken in excess, guaifenesin may cause renal calculi.

Pseudoephedrine

Overdose may result in:

Hyperglycaemia, hypokalaemia, CNS stimulation, insomnia; irritability, restlessness, anxiety, agitation; confusion, delirium, hallucinations, psychoses, seizures, tremor, intracranial haemorrhage including intracerebral haemorrhage, drowsiness in children, mydriasis, palpitations, tachycardia, reflex bradycardia, supraventricular and ventricular arrhythmias, dysrhythmias, myocardial infarction, hypertension, vomiting, ischaemic bowel infarction, acute renal failure, difficulty in micturition

Management

Necessary measures should be taken to maintain and support respiration and control convulsions. Gastric lavage should be performed if indicated. Catheterisation of the bladder may be necessary. If desired, the elimination of pseudoephedrine can be accelerated by acid diuresis or by dialysis.