Multi-Action Actifed Dry Coughs
SUMMARY OF PRODUCT CHARACTERISTICS
1 NAME OF THE MEDICINAL PRODUCT
Multi-Action ACTIFED Dry Coughs
2. QUALITATIVE AND QUANTITATIVE COMPOSITION
Multi-Action ACTIFED Dry Coughs contains 1.25 mg triprolidine hydrochloride, 30 mg pseudoephedrine hydrochloride and 10 mg dextromethorphan hydrobromide in each 5 ml.
3. PHARMACEUTICAL FORM
Liquid
4. CLINICAL PARTICULARS
4.1. Therapeutic indications
Multi-Action ACTIFED Dry Coughs is indicated for the symptomatic relief of upper respiratory tract disorders which are benefited by the combination of a nasal decongestant, a histamine Hj-receptor antagonist, and an antitussive.
4.2 Posology and method of administration
Adults and children aged 12 years and over:
Oral. 10 ml every 4 -6 hours up to four times a day
Children under 12 years:
Multi-Action ACTIFED Dry Coughs is contraindicated in children under the age of 12 years (see section 4.3)
The Elderly:
There have been no specific studies of Multi-Action ACTIFED Dry Coughs in the elderly. Experience has indicated that normal adult dosage is appropriate.
Hepatic dysfunction:
Caution should be exercised when administering Multi-Action ACTIFED Dry Coughs to patients with severe hepatic impairment.
Renal dysfunction:
Caution should be exercised when administering Multi-Action ACTIFED Dry Coughs to patients with moderate to severe renal impairment.
Multi-Action ACTIFED Dry Coughs may be diluted 1:1 (1 in 2) or 1:3 (1 in 4) with unpreserved Syrup BP. These dilutions have a shelf life of 4 weeks if stored at 25°C.
Do not exceed the stated dose.
Keep out of the reach and sight of children.
4.3 Contraindications
Multi-Action ACTIFED Dry Coughs is contraindicated in individuals who have previously exhibited intolerance to it or to any of its constituents.
Multi-Action ACTIFED Dry Coughs is contraindicated in patients with severe hypertension or severe coronary artery disease.
Multi-Action ACTIFED Dry Coughs is contraindicated in individuals who are taking, or have taken, monoamine oxidase inhibitors within the preceding two weeks. The concomitant use of pseudoephedrine and this type of product may occasionally cause a rise in blood pressure.
The antibacterial agent, furazolidone, is known to cause a dose-related inhibition of monoamine oxidase. Although there are no reports of hypertensive crises caused by the concurrent administration of Multi-Action ACTIFED Dry Coughs and furazolidone they should not be taken together.
Multi-Action ACTIFED Dry Coughs should not be administered to patients where cough is associated with asthma or where cough is accompanied by excessive secretions.
Dextromethorphan, in common with other centrally acting antitussive agents, should not be given to patients in, or at risk of developing respiratory failure.
Not to be used in children under the age of 12 years.
4.4 Special Warnings and Precautions for Use
Multi-Action ACTIFED Dry Coughs may cause drowsiness, and impair performance in tests of auditory vigilance. Patients should not drive or operate machinery until they have determined their own response.
Although there are no objective data, users of Multi-Action ACTIFED Dry Coughs should avoid the concomitant use of alcohol or other centrally acting sedatives.
Although pseudoephedrine has virtually no pressor effects in patients with normal blood pressure, Multi-Action ACTIFED Dry Coughs should be used with caution in patients taking antihypertensive agents, tricyclic antidepressants, other sympathomimetic agents such as decongestants, appetite suppressants and amfetamine-like psychostimulants.
The effects of a single dose of Multi-Action ACTIFED Dry Coughs on the blood pressure of these patients should be observed before recommending repeated or unsupervised treatment.
As with other sympathomimetic agents, caution should be exercised in patients with hypertension, heart disease, diabetes, hyperthyroidism, elevated intra-ocular pressure or prostatic enlargement.
There have been no specific studies of Multi-Action ACTIFED Dry Coughs in patients with hepatic and/or renal dysfunction Multi-Action ACTIFED Dry Coughs should be used with caution in patients with liver disease.
There have been a few reports of abuse of dextromethorphan but there is no evidence of drug dependence at therapeutic dosages.
Not more than 4 doses should be given in any 24 hours. Do not exceed the stated dose.
The packs carry the following statements
Warning: May cause drowsiness. If affected do not operate machinery.
This medicine can make you feel sleepy. Do not drive while taking this medicine until you know how it makes you feel. See the leaflet inside for more information.
Avoid alcoholic drink.
If you are pregnant or currently taking any other medicine, consult your doctor or pharmacist before taking this product.
If symptoms persist consult your doctor.
4.5.
Interaction with other medicinal products and other forms of interaction
Concomitant use of Multi-Action ACTIFED Dry Coughs with sympathomimetic agents such as decongestants, tricyclic antidepressants, appetite suppressants and amphetamine-like psychostimulants or with monoamine oxidase inhibitors, which interfere with the catabolism of sympathomimetic amines, may occasionally cause a rise in blood pressure, [See Contraindications and Special warnings and precautions for use].
Because of its pseudoephedrine content, Multi-Action ACTIFED Dry Coughs may partially reverse the hypotensive action of drugs which interfere with sympathetic activity including bretylium, betanidine, guanethidine, debrisoquine, methyldopa, alpha- and beta- adrenergic blocking agents, [See Special warnings and precautions for use].
4.6. Pregnancy and lactation
Although pseudoephedrine, triprolidine and dextromethorphan have been in widespread use for many years without apparent ill consequence, there are no specific data on their use during pregnancy. Caution should therefore be exercised by balancing the potential benefit of treatment to the mother against any possible hazards to the developing foetus.
Pseudoephedrine and triprolidine are excreted in breast milk in small amounts but the effect of this on breast-fed infants is not known. It has been estimated that 0.5 to 0.7% of a single dose of pseudoephedrine ingested by a mother will be excreted in the breast milk over 24 hours.
It is not known whether dextromethorphan or its metabolites are excreted in breast milk.
No studies have been conducted in animals to determine whether triprolidine, pseudoephedrine or dextromethorphan have potential to impair fertility. There is no experience of the effect of Multi-Action ACTIFED Dry Coughs on human fertility.
In rats and rabbits, systemic administration of triprolidine up to 75 times the human daily dosage did not produce teratogenic effects.
Systemic administration of pseudoephedrine, up to 50 times the human daily dosage in rats and up to 35 times the human daily dosage in rabbits, did not produce teratogenic effects.
There is insufficient information available to determine whether dextromethorphan has teratogenic potential.
4.7 Effects on Ability to Drive and Use Machines
Triprolidine may cause drowsiness and patients should not drive or operate machinery until they have determined their own response.
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 taking 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 ‘statutory defence’) if:
o The medicine has been taken to treat a medical or dental problem and
o You have taken it according to the information provided with the medicine and
o It was not affecting your ability to drive safely.
Details regarding a new driving offence concerning driving after drugs have been taken in the UK may be found here: https://www.gov.uk/drug-driving-law
4.8 Undesirable effects
Central nervous system depression or excitation may occur, drowsiness being reported most frequently. Sleep disturbance and rarely, hallucinations have been reported.
Skin rashes, with or without irritation, tachycardia, dryness of mouth nose and throat have occasionally been reported. Urinary retention has been reported occasionally in male patients in whom prostatic enlargement could be an important predisposing factor.
Side effects attributed to dextromethorphan are uncommon; occasionally nausea, vomiting or gastro-intestinal disturbance may occur.
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.
4.9. Overdose
The signs of acute toxicity from Multi-Action ACTIFED Dry Coughs may include drowsiness, lethargy, dizziness, ataxia, weakness, hypotonicity, respiratory depression, dryness of the skin and mucous membranes, tachycardia, hypertension, hyperpyrexia, hyperactivity, irritability, convulsions, difficulty with micturition, nausea and vomiting.
Necessary measures should be taken to maintain and support respiration and control convulsions. Gastric lavage may be undertaken if indicated. Catheterisation of the bladder may be necessary. If desired, the elimination of pseudoephedrine can be accelerated by acid diuresis or by dialysis.
Naloxone has been used successfully as a specific antagonist to dextromethorphan toxicity in children.
5. PHARMACOLOGICAL PROPERTIES
5.1. Pharmacodynamic properties
Triprolidine provides symptomatic relief in conditions believed to depend wholly or partially upon the triggered release of histamine. It is a potent competitive histamine H1-receptor antagonist of the pyrrolidone class with mild central nervous system depressant properties which may cause drowsiness. Pseudoephedrine has a direct and indirect sympathomimetic activity and is an effective upper respiratory decongestant. Pseudoephedrine is substantially less potent than ephedrine in producing both tachycardia and elevation of systolic blood pressure and considerably less potent in causing stimulation of the central nervous system. Dextromethorphan has an antitussive action. It controls coughs by depressing the medullary cough centre.
After oral administration of a single dose of 2.5 mg triprolidine to adults, the onset of action as determined by the ability to antagonise histamine-induced weals and flares in the skin is within 1 to 2 hours. Peak effects occur at about 3 hours and, although activity declines thereafter, significant inhibition of histamine-induced weals and flares still occurs 8 hours after the dose. Pseudoephedrine produces its decongestant effect within 30 minutes, persisting for at least 4 hours.
A single oral dose of 10 - 20 mg dextromethorphan produces its antitussive action within 1 hour and lasts for at least 4 hours.
5.2. Pharmacokinetic properties
After the administration of 2.5 mg triprolidine hydrochloride and 60 mg pseudoephedrine hydrochloride to healthy adult volunteers, the peak plasma concentration (Cmax) of triprolidine is approximately 5.5 ng/ml - 6.0 ng/ml occurring at about 1.5 - 2.0 hours (Tmax) after drug administration. Its plasma half-life is approximately 3.2 hours. The Cmax of pseudoephedrine is approximately 180 ng/ml with Tmax approximately 1.5 - 2.0 hours after drug administration. The plasma halflife is approximately 5.5 hours (urine pH maintained between 5.0 - 7.0). The plasma half-life of pseudoephedrine is markedly decreased by acidification of urine and increased by alkalinisation. Genetically controlled O-demethylation is the main determinant of dextromethorphan pharmacokinetics in human volunteers. It appears that there are two distinct phenotypes for this oxidation process resulting in highly variable pharmacokinetics between subjects.
5.3. Preclinical safety data
The active ingredients of Multi-Action ACTIFED Dry Coughs are well-known constituents of medicinal products and their safety profiles are well documented. The results of pre-clinical studies do not add anything of relevance for therapeutic purposes.
6. PHARMACEUTICAL PARTICULARS
6.1.
List of excipients
Sorbitol solution (70 %) Sucrose
Sodium benzoate Methyl hydroxybenzoate Ponceau 4R Ethanol (96%)
Blackberry Flavour AD16554
Levomenthol
Vanillin
Purified water
6.2. Incompatibilities
None known
6.3. Shelf life
36 months
6.4. Special precautions for storage
Do not store above 25°C. Store in the original container to protect from light.
6.5 Nature and contents of container
100 ml amber glass bottles with a 2 piece or a 3 piece plastic child resistant, tamper evident closure fitted with a polyvinylidene chloride (PVDC) faced wad.
A spoon with a 5ml and a 2.5ml measure is supplied with this product.
Instructions for use/handling
6.6.
None applicable.
7 MARKETING AUTHORISATION HOLDER
McNeil Products Limited Foundation Park Roxborough Way Maidenhead Berkshire SL6 3UG United Kingdom
8. MARKETING AUTHORISATION NUMBER(S)
PL 15513/0010
9. DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION
28 October 1998
10 DATE OF REVISION OF THE TEXT
15/07/2015