1 NAME OF THE MEDICINAL PRODUCT

Almus Cold and Flu Day Liquid

Boots Day Cold & Flu Relief Oral Solution

2. QUALITATIVE AND QUANTITATIVE COMPOSITION

Active ingredient

% w/v

3.333

0.200

0.033

Paracetamol Ph Eur

Pseudoephedrine Hydrochloride BP

Pholcodine Ph Eur

3. PHARMACEUTICAL FORM

An Oral Solution

4.1 Therapeutic indications

Combination product for the relief of the symptoms of colds and influenza. Decongestant for the relief of nasal congestion and congestion of mucous membranes of the upper respiratory tract associated with the common cold. Cough suppressant for the relief of acute non-productive cough associated with upper respiratory tract infection. Analgesic for the relief of aches, pains and fever associated with colds and influenza.

4.2 Posology and method of administration

Take during the day.

Adults and children over 16 years: 30ml every four hours, up to a maximum of 4 doses in 24 hours if needed, or up to a maximum of three doses within any 24 hour period if a night liquid is taken before bedtime.

Elderly: There is no specific requirement for dosage reduction in the elderly.

This medicine is contraindicated in children under 16 years of age (see section 4.3).

Warning: Do not exceed the stated dose.

Keep all medicines 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.

Avoid in patients with prostatic enlargement or liver failure.

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

Patients with chronic bronchitis, COPD, bronchiolitis or bronchiectasis due to sputum retention.

Concomitant use of other sympathomimetic decongestants.

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

Beta-blockers – (see section 4.5).

Not to be used in children under the age of 16 years.

4.4 Special warnings and special precautions for use Pholcodine

Should be used with caution by patients with liver or renal disease.

Ask a doctor before use if you suffer from a chronic or persistent cough, if you have asthma or are suffering from an acute asthma attack or where cough is accompanied by excessive secretions.

Severe cutaneous adverse reactions (SCARs) including acute generalized exanthematous pustulosis (AGEP), which can be life-threatening or fatal, have been reported in patients treated with pholcodine-containing products, most likely in the first week. Patients should be advised of the signs and symptoms and monitored closely for skin reactions. If signs and symptoms suggestive of these reactions appear, Almus Cold and Flu Day Liquid/Boots Day Cold & Flu Relief Oral Solution should be withdrawn immediately

Do not take with any other cough and cold medicine.

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

Caution is needed in patients with a history of drug abuse. Pholcodine is an opioid and addiction is observed with opioids as a class.

Pseudoephedrine

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

Restlessness

Sleep disturbances

Caution in moderate to severe renal impairment.

Ischaemic optic neuropathy

Cases of ischaemic optic neuropathy have been reported with pseudoephedrine. Pseudoephedrine should be discontinued if sudden loss of vision or decreased visual acuity such as scotoma occurs.

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.

Paracetamol

Should be given with caution to patients with impaired renal or hepatic function. The hazards of overdose are greater in those with non-cirrhotic alcoholic liver disease.

Contains paracetamol.

Warning: Do not exceed the stated dose.

Do not use this product for longer than 5 days unless your doctor agrees.

If symptoms persist consult your doctor.

Do not take with any other paracetamol-containing products.

Label:

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

Leaflet or combined Label/Leaflet:

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.

May be harmful to people on a low sodium diet. (Sodium)

Warning: this product contains 4.8% by volume of ethanol.

Each 30ml dose contains up to 1.16g of alcohol.

Harmful for those suffering from liver disease, alcoholism, epilepsy, brain injury or disease as well as for pregnant women and children. May modify or increase the effect of other medicines. (Alcohol)

This medicinal product contains 42.75g of sucrose.

When taken according to the dosage recommendations each 30ml dose supplies up to 5.34g of sucrose.

Unsuitable in hereditary fructose intolerance, glucose-galactose malabsorption syndrome or sucrase-isomaltase deficiency. (Sucrose)

This medicinal product contains 14.37g of glucose.

When taken according to the dosage recommendations each dose supplies up to 1.8g of glucose. (Glucose)

Harmful in high doses. Can cause headache, upset stomach and diarrhoea. (Glycerin)

4.5 Interaction with other medicinal products and other forms of interaction

Pholcodine

Not to be used in patients taking MAOIs or within 14 days of stopping treatment.

Interaction with neuromuscular blocking agents (anaphylaxis) has been reported.

The reduction in blood pressure caused by antihypertensives may accentuate the hypotensive effects of pholcodine. Diuretics may have the same effect.

Pholcodine may enhance the sedative effect of central nervous system depressants including alcohol, barbiturates, hypnotics, narcotic analgesics, sedatives and tranquillisers (phenothiazines and tricyclic antidepressants).

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, diuretics & betablockers): 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 effects of anticholinergic drugs (such as TCAs).

Paracetamol

The speed of absorption of paracetamol may be increased by metoclopramide or domperidone and absorption reduced by cholestyramine. The anticoagulant effect of warfarin and other coumarins may be enhanced by prolonged use of paracetamol with increased risk of bleeding; occasional doses have no significant effect.

4.6 Fertility, pregnancy and lactation

Pregnancy

A large amount of data on pregnant women indicate neither malformities, 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

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

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

Pseudoephedrine has been detected in human milk with a small percentage of the maternal dose potentially administered to the breastfed infant. The use of pseudoephedrine should be avoided during breastfeeding as lactation may be suppressed, and irritability and disturbed sleep have been reported in breastfed infants. Pseudoephedrine may suppress lactation.

There is no information available as to whether pholcodine is excreted in breast milk.

The safety of the combined ingredients in this product during lactation has not been established. The use of this medicine during lactation is not recommended.

4.7 Effects on ability to drive and use machines

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

4.8 Undesirable effectsParacetamol

Immune system disorders: Adverse effects of paracetamol are rare but hypersensitivity including skin rash may occur.

Blood and lymphatic system disorders: Very rarely there have been reports of blood dyscrasias including thrombocytopaenia and agranulocytosis, but these were not necessarily causally related to paracetamol.

Skin and subcutaneous tissue disorders: very rare cases of serious skin reactions have been reported.

Pholcodine

The following side effects may be associated with the use of pholcodine: Gastrointestinal disorders: Gastrointestinal disturbances (nausea and constipation), vomiting, diarrhoea, upset stomach, epigastric pain. Immune system disorders: Hypersensitivity reactions and anaphylaxis. Nervous system disorders: Occasional drowsiness, dizziness Psychiatric disorders: Excitation, confusion.

Respiratory, thoracic and mediastinal disorders: Sputum retention.

Skin and subcutaneous tissue disorders: Skin reactions including rash and acute generalized exanthematous pustulosis (AGEP) (see section 4.4) (frequency unknown)

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.

Should be given with caution to patients with impaired renal or hepatic function. The hazards of overdose are greater in those with non-cirrhotic alcoholic liver disease.

Contains paracetamol.

Warning: Do not exceed the stated dose.

Do not use this product for longer than 5 days unless your doctor agrees.

If symptoms persist consult your doctor.

Do not take with any other paracetamol-containing products.

Label:

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

Leaflet or combined Label/Leaflet:

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.

May be harmful to people on a low sodium diet. (Sodium)

Warning: this product contains 4.8% by volume of ethanol.

Each 30ml dose contains up to 1.16g of alcohol.

Harmful for those suffering from liver disease, alcoholism, epilepsy, brain injury or disease as well as for pregnant women and children. May modify or increase the effect of other medicines. (Alcohol)

This medicinal product contains 42.75g of sucrose.

When taken according to the dosage recommendations each 30ml dose supplies up to 5.34g of sucrose.

Unsuitable in hereditary fructose intolerance, glucose-galactose malabsorption syndrome or sucrase-isomaltase deficiency. (Sucrose)

This medicinal product contains 14.37g of glucose.

When taken according to the dosage recommendations each dose supplies up to 1.8g of glucose. (Glucose)

Harmful in high doses. Can cause headache, upset stomach and diarrhoea. (Glycerin)

4.5 Interaction with other medicinal products and other forms of interaction

Pholcodine

Not to be used in patients taking MAOIs or within 14 days of stopping treatment.

Interaction with neuromuscular blocking agents (anaphylaxis) has been reported.

The reduction in blood pressure caused by antihypertensives may accentuate the hypotensive effects of pholcodine. Diuretics may have the same effect.

Pholcodine may enhance the sedative effect of central nervous system depressants including alcohol, barbiturates, hypnotics, narcotic analgesics, sedatives and tranquillisers (phenothiazines and tricyclic antidepressants).

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, diuretics & betablockers): 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 effects of anticholinergic drugs (such as TCAs).

Paracetamol

The speed of absorption of paracetamol may be increased by metoclopramide or domperidone and absorption reduced by cholestyramine. The anticoagulant effect of warfarin and other coumarins may be enhanced by prolonged use of paracetamol with increased risk of bleeding; occasional doses have no significant effect.

4.6 Fertility, pregnancy and lactation

Pregnancy

A large amount of data on pregnant women indicate neither malformities, 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

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

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

Pseudoephedrine has been detected in human milk with a small percentage of the maternal dose potentially administered to the breastfed infant. The use of pseudoephedrine should be avoided during breastfeeding as lactation may be suppressed, and irritability and disturbed sleep have been reported in breastfed infants. Pseudoephedrine may suppress lactation.

There is no information available as to whether pholcodine is excreted in breast milk.

The safety of the combined ingredients in this product during lactation has not been established. The use of this medicine during lactation is not recommended.

4.7 Effects on ability to drive and use machines

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

4.8 Undesirable effectsParacetamol

Immune system disorders: Adverse effects of paracetamol are rare but hypersensitivity including skin rash may occur.

Blood and lymphatic system disorders: Very rarely there have been reports of blood dyscrasias including thrombocytopaenia and agranulocytosis, but these were not necessarily causally related to paracetamol.

Skin and subcutaneous tissue disorders: very rare cases of serious skin reactions have been reported.

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

Immediate treatment is essential in the management of paracetamol overdosage.

Despite a lack of significant early symptoms, patients should be referred to hospital urgently for immediate medical attention and any patient who has ingested the equivalent of 7.5g or more of paracetamol in the preceding 4 hours should undergo gastric lavage.

Ingestion of lower doses equivalent to 5g or more of paracetamol may lead to liver damage if the patient has risk factors. These include if:

They are undergoing long-term treatment with drugs that induce liver enzymes

They regularly consume ethanol in excess of advised amounts

They are likely to be glutathione deplete e.g. as in cystic fibrosis, eating disorders, HIV infection, starvation, cachexia

Administration of oral methionine or intravenous N-acetylcysteine, which may have a beneficial effect up to at least 48 hours after overdose, may be required. In addition symptomatic and general supportive therapy must be available, including the administration of a beta-blocker if supraventricular tachycardia supervenes and the administration of the specific narcotic antagonist naloxone.

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, coma and death. Acute renal failure with acute tubular necrosis may develop even in the absence of severe liver damage. Cardiac arrhythmias and pancreatitis have been reported. Liver damage is possible in adults who have taken 10g or more of paracetamol. It is considered that excess quantities of a toxic metabolite (usually adequately detoxified by glutathione when normal doses of paracetamol are ingested), become irreversibly bound to liver tissue.

Pholcodine

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: These include nausea, drowsiness, restlessness, excitement, ataxia and respiratory depression.

Management: Treatment of overdose should be symptomatic and supportive. Gastric lavage may be of use. In cases of severe poisoning the specific narcotic antagonist nalaxone may be used.

Information for children:

Naloxone has been used successfully to reverse central or peripheral opioid effects in children (0.01mg/kg body weight). Other treatment option is activated charcoal (1g/kg body weight) if more than 4mg/kg has been ingested within 1 hour, provided the airway can be protected.

Other symptoms of overdosage may include headache, tachycardia, urinary retention, hallucinations, coma, hyperreflexia, tremor, hypertension and arrhythmias.

5 PHARMACOLOGICAL PROPERTIES

5.1 Pharmacodynamic properties

Paracetamol has analgesic and antipyretic actions. Pseudoephedrine is a sympathomimetic agent with both direct and indirect effects on adrenergic receptors.

Pholcodine is a cough suppressant with little analgesic activity.

5.2 Pharmacokinetic properties

Paracetamol is readily absorbed from the gastrointestinal tract with peak plasma concentrations occurring about 30 minutes to 2 hours after oral administration. Paracetamol is distributed into most body tissues. It crosses the placenta and is present in breast milk. Plasma protein binding is negligible at usual therapeutic concentrations Paracetamol is metabolised predominantly in the liver and excreted in the urine mainly as the glucuronide and sulphate conjugates, with about 10% as glutathione conjugates. Less than 5% is excreted as unchanged paracetamol. The elimination half life varies from about 1 to 4 hours.

Pseudoephedrine is absorbed from the gastrointestinal tract. It is resistant to metabolism and is excreted largely unchanged in the urine. It has a half life of several hours but elimination is enhanced and half life shortened in acid urine.

Pholcodine is rapidly absorbed after oral administration and maximum plasma concentrations are attained at about 4–8 hours. The elimination half life ranges from 32 to 43 hours. The drug has a large volume of distribution and is only 23.5% protein bound.

Pholcodine is metabolised in the liver but undergoes little conjugation with glucuronide and sulphate.

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.

Paracetamol

Conventional studies using currently accepted standard for the evaluation of toxicity to reproduction and development are not available.

6 PHARMACEUTICAL PARTICULARS

6.1

Acesulfame K

Citric Acid Monohydrate

Sodium Benzoate

Sodium Citrate

Levomenthol

Propylene Glycol

Alcohol 96%

Glycerol

Liquid Sugar

Liquid Glucose

Peach Flavour

Pear drop Flavour

Lime Flavour

Riboflavin-5-Phosphate Sodium (E101)

Purified water

6.2. Incompatibilities

Not applicable

6.3. Shelf Life

36 months

6.4. Special Precautions for Storage

Do not store above 25°C

6.5. Nature and Contents of Container

Bottle of amber polyethylene terephthalate fitted with a child resistant cap closure of polypropylene with expanded polyethylene liner.

Pack size: 210 ml, 240 ml, 300 ml.

6.6. Instruction for Use/Handling

Not applicable.

7. MARKETING AUTHORISATION HOLDER

8.   MARKETING AUTHORISATION NUMBER

9 DATE OF FIRST AUTHORISATION/RENEWAL OF THEAUTHORISATION

25/02/2009