ACTIFED 60 mg / 2.5 mg Tablets

This variation is being submitted to implement the PRAC recommendations following the outcome of the ibuprofen / pseudoephedrine PSUSA (PSUSA/00001711/201707). These recommendations include updating Sections 4.4 and 4.8 of the Summary of Product Characteristics and to update Section 2 and 4 of the Package Leaflet accordingly

This variation is being submitted to implement the PRAC recommendations following the outcome of the ibuprofen / pseudoephedrine PSUSA (PSUSA/00001711/201707). These recommendations include updating Sections 4.4 and 4.8 of the Summary of Product Characteristics and to update Section 2 and 4 of the Package Leaflet accordingly

PSE V3 CCDS update plus incorporating PSE/Triprolidine PRAC updates.

Changed from:

Each tablet contains 2.5 mg Triprolidine hydrochloride and 60 mg Pseudoephedrine hydrochloride.

to

Each tablet contains 60 mg Pseudoephedrine hydrochloride and 2.5 mg Triprolidine hydrochloride.

Section 4.2

Heading  ‘Posology’ added.

‘Oral’ deleted from dosage sentence for adults and children

Added:

Method of Administration

For oral use

Section 4.3

Added ‘or hypertensive crisis to end of sentence ‘The concomitant use of pseudoephedrine and this type of product may occasionally cause a rise in blood pressure or hypertensive crisis.

Section 4.4

Deleted:

and impair performance in tests of auditory vigilance. Patients should be cautioned about engaging in activities requiring mental alertness, until they have established their own response to the drug.

Patients should be advised that concomitant use of alcohol or other central nervous depressants whilst taking ACTIFED Syrup may produce additional impairment in mental awareness in some individuals.

Patients with prostatic hypertrophy may have increased difficulty with micturition.

Added:

Patients with the following conditions should be advised to consult a physician before using Actifed Syrup: hypertension, coronary heart disease diabetes, thyroid disease; difficulty in urination due to enlargement of the prostate; a respiratory condition such as emphysema, chronic bronchitis, or acute or chronic bronchial asthma; or glaucoma.

Triprolidine may enhance the sedative effects of central nervous system depressants including alcohol, sedatives, and tranquilizers. While taking this Actifed Syrup, patients should be advised to avoid alcoholic beverages and consult a healthcare professional prior to taking with central nervous system depressants.

This medicinal product contains lactose monohydrate

Section 4.5

Added:

Pseudoephedrine exerts its vasoconstricting properties by stimulating adrenergic receptors and displacing norepinephrine from neuronal storage sites. Since MAOIs impede the metabolism of sympathomimetic amines and increase the store of releasable norepinephrine in adrenergic nervous tissue, MAOIs may potentiate the pressor effect of pseudoephedrine. Acute hypertensive crises have been reported in the medical literature with the concomitant use of MAOIs and sympathomimetic amines.

Deleted:

Concomitant use of ACTIFED Syrup with alcohol or other central nervous system depressants may, in some individuals, produce additional impairment in mental alertness.

Following text changed:

From:

Concomitant use of Actifed Syrup with tricyclic antidepressants, other sympathomimetic agents (such as decongestants, appetite suppressants and amphetamine-like psychostimulants) or with monoamine oxidase inhibitors (including furazolidone),which interfere with the catabolism of sympathomimetic amines, may occasionally cause a rise in blood pressure.

To:

Concomitant use of Actifed Syrup with tricyclic antidepressants, other sympathomimetic agents (such as decongestants, appetite suppressants and amphetamine-like psychostimulants) may occasionally cause a rise in blood pressure.

Added:

Triprolidine may enhance the sedative effects of central nervous system depressants, including alcohol, sedatives and tranquilizers.

Section 4.6

‘Fertility’ added to title.

Following text changed:

From:

This product should not be used during pregnancy unless considered essential by a physician.  Although pseudoephedrine and triprolidine 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 approximately 0.5 to 0.7% of a single dose of pseudoephedrine ingested by a nursing mother will be excreted in the breast milk over 24 hours

To:

There are no adequate and well-controlled studies for pseudoephedrine, triprolidine in pregnant or breast-feeding women.

Fertility

There is no information on the effects of ACTIFED tablets on human fertility.

Pregnancy

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

Breast-feeding

Pseudoephedrine distributes into and is concentrated in breast milk. Up to 0.7% of a single 60-mg dose of pseudoephedrine may be distributed into breast milk over 24 hours. Pseudoephedrine concentrations in milk are from 2 to 3 fold higher than those in plasma. This milk/plasma drug concentration profile suggests low protein binding, although no protein plasma binding data in humans are available. 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.

Triprolidine is excreted in breast milk, it has been estimated that approximately 0.06 to 0.2% of a single 2.5 mg dose of triprolidine ingested by a nursing mother will be excreted in the breast-milk over 24 hours.

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

Section 4.8

Following text changed:

From:

This product may act as a cerebral stimulant in children and occasionally adults giving rise to insomnia, nervousness, hyperpyrexia, tremors and epileptiform convulsions. Care should be taken when used in epileptic patients.

Skin rashes, with or without irritation, tachycardia, dryness of mouth, nose and throat, and headache have occasionally been reported.

Urinary retention has been reported occasionally in men receiving pseudoephedrine; prostatic enlargement could have been an important predisposing factor.

To:

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

Adverse drug reactions identified during clinical trials and post-marketing experience with pseudoephedrine, triprolidine or the combination are listed below by System Organ Class (SOC). The frequencies are defined in accordance with current guidance, as:

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’.

ADRs Identified During Post-Marketing Experience with Pseudoephedrine or the Combination of Pseudoephedrine and Triprolidine by Frequency Category Estimated from Clinical Trials or Epidemiology Studies

^† Adverse events reported by ≥1% of subjects in randomised, placebo-controlled trials with single-ingredients pseudoephedrine

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 HPRA Pharmacovigilance, Earlsfort Terrace, IRL - Dublin 2; Tel: +353 1 6764971; Fax: +353 1 6762517. Website: www.hpra.ie; E-mail:medsafety@hpra.ie.

Section 4.9

Symptoms and signs

The effects of acute toxicity from ACTIFED Syrup may include drowsiness, incoordination, weakness, irritability, palpitations, hypertension, convulsions and difficulty with micturition.

Treatment

The treatment of overdosage is likely to be symptomatic and supportive.  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.Alpha-adrenergic blockade may be required to treat hypertensive crises and beta-adrenergic blockade for the control of supra-ventricular dysrhythmias. 

If desired, the elimination of pseudoephedrine can be accelerated by acid diuresis or by dialysis.

Change to:

Symptoms

The effects of acute toxicity from ACTIFED Syrup may include drowsiness, incoordination, weakness, irritability, palpitations, hypertension, convulsions and difficulty with micturition.

Pseudoephedrine

Overdosage may result in nausea, vomiting, sympathomimetic

symptoms including central nervous system stimulation, insomnia, tremor, mydriasis, anxiety, agitation, hallucinations, seizures, palpitations, tachycardia, hypertension and reflex bradycardia. Other effects may include dysrhythmias, hypertensive crisis, intracerebral haemorrhage, myocardial infarction, psychoses, rhabdomyolysis, hypokalaemia, and ischemic bowel infarction. Drowsiness has been reported with overdose in children.

Triprolidine

Overdosage of an H1 receptor antagonist may result in CNS depression, hyperthermia, anticholinergic syndrome (mydriasis, flushing, fever, dry mouth, urinary retention, decreased bowel sounds), tachycardia, hypotension, hypertension, nausea, vomiting, agitation, confusion, hallucinations, psychosis, seizures, or dysrhythmias. Rhabdomyolysis and renal failure may rarely develop in patients with prolonged agitation, coma, or seizures

Management

The treatment of overdosage is likely to be symptomatic and supportive.  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.Alpha-adrenergic blockade may be required to treat hypertensive crises and beta-adrenergic blockade for the control of supra-ventricular dysrhythmias. 

            If desired, the elimination of pseudoephedrine can be accelerated by acid diuresis or by dialysis.

Section 5.1

Added:

Pharmacotherapeutic group: Sympathomimetics, pseudoephedrine, combinations

ATC code: R01BA52

Section 6.6

Changed from:

6.6        Instructions for use and handling

No special requirements

To:

6.6        Special precautions for disposal and handling

Any unused product or waste material should be disposed of in accordance with local requirements

To change the MAH from Pfizer Consumer Healthcare, Pottery Road, Dun Laoghaire, Co. Dublin to McNeil Healthcare (Ireland) Limited, Airton Road, Tallaght, Dublin 24, Ireland.