This information is intended for use by health professionals

1. Name of the medicinal product

Almus Dry Cough Linctus with Decongestant

Boots Dry Cough & Congestion Relief Oral Solution

2. Qualitative and quantitative composition

Active ingredient

mg/5ml

Pseudoephedrine hydrochloride

Dextromethorphan hydrobromide

30.0

10.0

3. Pharmaceutical form

Oral Solution.

A clear yellow viscous liquid.

4. Clinical particulars
4.1 Therapeutic indications

Cough suppressant for the relief of acute non-productive cough associated with upper respiratory tract infection. Decongestant for the relief of catarrh and blocked sinuses associated with nasal congestion and congestion of mucous membranes of the upper respiratory tract associated with the common cold.

4.2 Posology and method of administration

Adults and children over 12 years: two 5ml spoonfuls to be taken three times a day.

Elderly: the normal adult dose is appropriate in the elderly.

Children 6-12 years: one 5ml spoonful to be taken three times a day.

This medicine is contraindicated in children under 6 years of age (see section 4.3).

Children of 6-12 years of age: not to be used for more than 5 days without the advice of a doctor. Parents and carers should seek medical attention if the child's condition deteriorates during treatment.

Warning: Do not exceed the stated dose.

Keep out of the sight and reach of children.

4.3 Contraindications

Hypersensitivity to the active substances or any of the excipients.

Severe renal impairment

Cardiovascular disease including hypertension and peripheral vascular disease

Diabetes mellitus

Phaeochromocytoma

Hyperthyroidism

Closed angle glaucoma

Prostatic enlargement

Patients with chronic or persistent cough such as occurs with asthma, if you are suffering from an acute asthma attack, or where cough is accompanied by excessive secretions.

Dextromethorphan should not be given to subjects in, or at risk of developing respiratory failure.

Patients taking monoamine oxidase inhibitors (MAOIs) or within 14 days of stopping such treatment (see section 4.5).

Patients taking selective serotonin reuptake inhibitors (SSRIs, see section 4.5).

Beta-blockers – (see section 4.5).

Concomitant use of other sympathomimetic decongestants.

Not to be used in children under the age of 6 years.

4.4 Special warnings and precautions for use

Dextromethorphan

Should be used with caution in patients with liver disease.

Should be used with caution in atopic children due to histamine release.

Do not take with any other cough and cold medicines.

Use of dextromethorphan with alcohol or other CNS depressants may increase the effects on the CNS and cause toxicity in relatively smaller doses.

Drug dependence, tolerance and potential for abuse

For all patients, prolonged use of this product may lead to drug dependence (addiction), even at therapeutic doses. The risks are increased in individuals with current or past history of substance misuse disorder (including alcohol misuse) or mental health disorder (e.g., major depression).

Drug withdrawal syndrome

The drug withdrawal syndrome is characterised by some or all of the following: restlessness, lacrimation, rhinorrhoea, yawning, perspiration, chills, myalgia, mydriasis and palpitations. Other symptoms may also develop including irritability, agitation, anxiety, hyperkinesia, tremor, weakness, insomnia, anorexia, abdominal cramps, nausea, vomiting, diarrhoea, increased blood pressure, increased respiratory rate or heart rate.

Serotonin Syndrome

Serotonergic effects, including the development of a potentially life-threatening serotonin syndrome, have been reported for dextromethorphan with concomitant administration of serotonergic agents, such as selective serotonin re-uptake inhibitors (SSRIs), drugs which impair metabolism of serotonin (including monoamine oxidase inhibitors (MAOIs)) and CYP2D6 inhibitors.

Serotonin syndrome may include mental-status changes, autonomic instability, neuromuscular abnormalities, and/or gastrointestinal symptoms.

If serotonin syndrome is suspected, treatment with Almus Dry Cough Linctus with Decongestant and Boots Dry Cough & Congestion Relief Oral Solution should be discontinued.

Dextromethorphan is metabolised by hepatic cytochrome P450 2D6. The activity of this enzyme is genetically determined. About 10% of the general population are poor metabolisers of CYP2D6. Poor metabolisers and patients with concomitant use of CYP2D6 inhibitors may experience exaggerated and/or prolonged effects of dextromethorphan. Caution should therefore be exercised in patients who are slow metabolisers of CYP2D6 or use CYP2D6 inhibitors (see also section 4.5).

Pseudoephedrine

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 Almus Dry Cough Linctus with Decongestant /

Boots Dry Cough & Congestion Relief Oral Solution should be discontinued and appropriate measures taken if needed.

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

Hallucinations

Restlessness

Sleep disturbances

Caution in moderate to severe renal impairment.

If symptoms persist consult your doctor.

Paediatric population

Serious adverse events may occur in children in case of overdose including neurological disorders. Caregivers should be advised not to exceed the recommended dose.

4.5 Interaction with other medicinal products and other forms of interaction

Dextromethorphan

Not to be used in patients taking monoamine oxidase inhibitors or within 14 days of stopping treatment as there is a risk of serotonin syndrome (pyrexia, hypertension, arrhythmias) when MAOIs are taken in combination with dextromethorphan.

Dextromethorphan might exhibit additive CNS depressant effects when co-administered with alcohol, antihistamines, psychotropics, and other CNS depressant drugs.

CYP2D6 inhibitors

Dextromethorphan is metabolized by CYP2D6 and has an extensive first-pass metabolism. Concomitant use of potent CYP2D6 enzyme inhibitors can increase the dextromethorphan concentrations in the body to levels multifold higher than normal. This increases the patient's risk for toxic effects of dextromethorphan (agitation, confusion, tremor, insomnia, diarrhoea and respiratory depression) and development of serotonin syndrome. Potent CYP2D6 enzyme inhibitors include fluoxetine, paroxetine, quinidine and terbinafine. In concomitant use with quinidine, plasma concentrations of dextromethorphan have increased up to 20-fold, which has increased the CNS adverse effects of the agent. Amiodarone, flecaninde and propafenone, sertraline, bupropion, methadone, cinacalcet, haloperidol, perphenazine and thioridazine also have similar effects on the metabolism of dextromethorphan. If concomitant use of CYP2D6 inhibitors and dextromethorphan is necessary, the patient should be monitored and the dextromethorphan dose may need to be reduced.

Pseudoephedrine

MAOIs and/or RIMAs: should not be given to patients treated with MAOIs or within 14 days of stopping treatment: increased risk of hypertensive crisis.

Moclobemide: risk of hypertensive crisis.

Antihypertensives (including adrenergic neurone blockers & beta-blockers): this medicine may block the hypotensive effects.

Cardiac glycosides: increased risk of dysrhythmias.

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

Appetite suppressants and amphetamine-like psychostimulants: risk of hypertension.

Oxytocin – risk of hypertension.

Enhances the effects of anticholinergic drugs (such as TCAs).

There is an increased risk of arrhythmias if given to patients receiving anticholinergic drugs such as tricyclic antidepressants.

Concomitant use with sympathomimetic agents such as decongestants, tricyclic antidepressants, may occasionally cause a rise in blood pressure.

4.6 Pregnancy and lactation

Pregnancy

There are limited amount of data on the use of pseudoephedrine in pregnant women. The use of pseudoephedrine during the first trimester of pregnancy has been associated with an increased frequency of gastroschisis (a developmental defect in the abdominal wall with intestinal herniation) and of small intestinal atresia (congenital obstruction of small intestine). Due to the vasoconstrictive properties of pseudoephedrine, it may induce a reduction in uteroplacental circulation.

Pseudoephedrine is not recommended in pregnancy.

Breast-feeding

Pseudoephedrine has been detected in human milk with a small percentage of the maternal dose potentially administered to the breastfed infant. Irritability and disturbed sleep have been reported in breastfed infants. Pseudoephedrine may supress lactation.

There is no data on the secretion of dextromethorphan into breast milk and therefore use of this product during lactation should be avoided.

4.7 Effects on ability to drive and use machines

This medicine can impair cognitive function and can affect a patient's ability to drive safely. This class of medicine is in the list of drugs included in regulations under 5a of the Road Traffic Act 1988. When prescribing this medicine, patients should be told:

• The medicine is likely to affect your ability to drive

• Do not drive until you know how the medicine affects you

• It is an offence to drive while under the influence of this medicine

• However, you would not be committing an offence (called a 'statutory defence') if:

- The medicine has been prescribed to treat a medical or dental problem and

- You have taken it according to the instructions given by the prescriber and in the information provided with the medicine and

- It was not affecting your ability to drive safely

4.8 Undesirable effects

Dextromethorphan

The following side effects may be associated with the use of dextromethorphan:

Gastrointestinal disorders: vomiting, gastrointestinal disturbances (nausea and diarrhoea).

Nervous system disorders: drowsiness (occasional), dizziness, convulsions.

Psychiatric disorders: excitation, mental confusion, drug dependence (frequency unknown) (see section 4.4).

Respiratory, thoracic and mediastinal disorders: respiratory depression.

Skin and subcutaneous tissue disorders: skin reactions including rash.

General disorders and administration site conditions: drug withdrawal syndrome (frequency unknown).

Pseudoephedrine

Cardiovascular disorders: tachycardia, palpitations, other cardiac dysrhythmias.

Gastrointestinal disorders: nausea and/or vomiting.

General disorders and administration site conditions: irritability.

Immune system disorders: hypersensitivity reactions, including cross-sensitivity that may occur with other sympathomimetics.

Nervous system disorders: headache, tremor, anxiety, restlessness, excitability, insomnia, hallucinations (particularly in children) and paranoid delusions.

Psychiatric disorders: sleep disturbance.

Renal and urinary disorders: difficulty in micturition including urinary retention.

Skin and subcutaneous tissue disorders: skin reactions including rash. Frequency unknown - Severe skin reactions, including acute generalized exanthematous pustulosis (AGEP).

Vascular disorders: hypertension.

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 at www.mhra.gov.uk/yellowcard or search for MHRA Yellow Card in the Google Play or Apple App Store.

4.9 Overdose

Dextromethorphan

It is thought to be of low toxicity, but the effects in overdosage will be potentiated by simultaneous ingestion of alcohol and psychotropic drugs.

Symptoms and signs:

Dextromethorphan overdose may be associated with nausea, vomiting, dystonia, agitation, confusion, somnolence, stupor, nystagmus, cardiotoxicity (tachycardia, abnormal ECG including QTc prolongation), ataxia, toxic psychosis with visual hallucinations, hyperexcitability.

In the event of massive overdose the following symptoms may be observed: coma, respiratory depression, convulsions.

Management:

-Activated charcoal can be administered to asymptomatic patients who have ingested overdoses of dextromethorphan within the preceding hour.

-For patients who have ingested dextromethorphan and are sedated or comatose, naloxone, in the usual doses for treatment of opioid overdose, can be considered. Benzodiazepines for seizures and benzodiazepines and external cooling measures for hyperthermia from serotonin syndrome can be used.”

Information for children

Naloxone has been used successfully to reverse contral or peripheral opioid effects of dextromethorphan in children (0.01mg/kg body weight).

Pseudoephedrine

Symptoms: Symptoms of overdosage include abdominal discomfort, excitation, confusion, hallucinations, ataxia, irritability, restlessness, palpitations, hypertension, difficulty in micturition and thirst.

Management: In severe overdosage gastric lavage and aspiration should be performed. Symptomatic and supportive measures should be undertaken, particularly with regard to the cardiovascular and respiratory systems. Chlorpromazine may be used to control marked excitement and hallucinations. Severe hypertension may need to be treated with an alpha-adrenoreceptor blocking drug, such as phentolamine. A beta-blocker may be required to control cardiac arrhythmias.

5. Pharmacological properties
5.1 Pharmacodynamic properties

Pseudoephedrine is a sympathomimetic agent with direct and indirect effects on adrenergic receptors. It has alpha and beta adrenergic activity and some stimulant effect on the central nervous system. The sympathomimetic effect of pseudoephedrine produces vasoconstriction which in turn relieves nasal congestion.

Dextromethorphan is a cough suppressant.

5.2 Pharmacokinetic properties

Pseudoephedrine is readily and completely absorbed from the gastrointestinal tract and is largely excreted in the urine unchanged. It has an elimination half-life of 5 to 8 hours but its urinary elimination and hence half-life is pH dependent. Pseudoephedrine is rapidly distributed throughout the body, its volume of distribution being 2 to 3 L/kg bodyweight.

Dextromethorphan is well absorbed from the gastrointestinal tract, metabolised in the liver and excreted as both unchanged drug and demethylated metabolites.

Dextromethorphan undergoes rapid and extensive first-pass metabolism in the liver after oral administration. Genetically controlled O-demethylation (CYD2D6) is the main determinant of dextromethorphan pharmacokinetics in human volunteers.

It appears that there are distinct phenotypes for this oxidation process resulting in highly variable pharmacokinetics between subjects. Unmetabolised dextromethorphan, together with the three demethylated morphinan metabolites dextrorphan (also known as 3-hydroxy-N-methylmorphinan), 3-hydroxymorphinan and 3-methoxymorphinan have been identified as conjugated products in the urine.

Dextrorphan, which also has antitussive action, is the main metabolite. In some individuals metabolism proceeds more slowly and unchanged dextromethorphan predominated in the blood and urine.

5.3 Preclinical safety data

Pseudoephedrine

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

Sodium saccharin

Liquid sugar

Hydroxyethylcellulose

Glycerin

Alcohol 96%

Levomenthol

Domiphen bromide

Pear drop flavour C1353

Peach flavour 17403109

Quinoline yellow 14031

Sodium citrate

Citric acid monohydrate

Purified water

6.2 Incompatibilities

Not applicable

6.3 Shelf life

2 years

6.4 Special precautions for storage

None

6.5 Nature and contents of container

An amber PET bottle with a child resistant plastic cap containing a low density polyethylene wad.

Pack size: 120ml

6.6 Special precautions for disposal and other handling

Not applicable.

7. Marketing authorisation holder

The Boots Company PLC

1 Thane Road West

Nottingham

NG2 3AA

Trading as: BCM

8. Marketing authorisation number(s)

PL 00014/0501

9. Date of first authorisation/renewal of the authorisation

1 July 1996

10. Date of revision of the text

21st April 2020