4.1. Therapeutic indications

For the symptomatic relief of upper respiratory tract disorders which are benefited by a combination of a nasal decongestant and histamine H1-receptor antagonist, for example:

Allergic Rhinitis

Vasomotor Rhinitis

The Common Cold and Influenza

4.2. Posology and method of administration

Posology

Adults and children over 12 years

One tablet every 4-6 hours up to 4 times a day. Not more than 4 doses should be given in any 24 hours.

Use in the Elderly

No specific studies have been carried out in the elderly, but triprolidine and pseudoephedrine have been widely used in older people.

Hepatic Dysfunction

Caution should be exercised when administering Multi-Action ACTIFED Tablets to patients with hepatic impairment.

Renal Dysfunction

Caution should be exercised when administering Multi-Action ACTIFED Tablets to patients with moderate renal impairment.

Method of Administration

For oral use.

4.3. Contraindications

Multi-Action ACTIFED is contraindicated in individuals with known hypersensitivity to pseudoephedrine or triprolidine or to any of the excipients listed in section 6.1.

Multi-Action ACTIFED is contraindicated in patients 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 and/or hypertensive crisis (see section 4.5).

Concomitant use of other sympathomimetic decongestants or beta-blockers (see section 4.5).

Cardiovascular disease

Severe hypertension or uncontrolled hypertension

Diabetes mellitus

Phaeochromocytoma

Hyperthyroidism

Closed angle glaucoma

Severe acute or chronic kidney disease/renal failure

4.4. Special warnings and precautions for use

Multi-Action ACTIFED Tablets may cause drowsiness. This product should not be used to sedate a child.

Triprolidine may enhance the sedative effects of central nervous system depressants including alcohol, sedatives and tranquilisers. While taking Multi- Action ACTIFED Tablets, patients should be advised to avoid alcoholic beverages and consult a healthcare professional prior to taking with central nervous system depressants.

Use with caution in prostatic hypertrophy, urinary retention or susceptibility to angle closure.

Patients with thyroid disease who are receiving thyroid hormones are advised to consult a physician before using this product.

Use with caution in 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.

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.

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

Cases of PRES and RCVS have been reported with the use of pseudoephedrine-containing products (see section 4.8). The risk is increased in patients with severe or uncontrolled hypertension, or with severe acute or chronic kidney disease/renal failure (see section 4.3).

Pseudoephedrine should be discontinued and immediate medical assistance sought if the following symptoms occur: sudden severe headache or thunderclap headache, nausea, vomiting, confusion, seizures and/or visual disturbances. Most reported cases of PRES and RCVS resolved following discontinuation and appropriate treatment.

Patients with the following conditions should not use Multi-Action Actifed Tablets unless directed by a physician: acute or chronic asthma, chronic bronchitis or emphysema.

There have been no specific studies of Multi-Action ACTIFED Tablets in patients with hepatic and/or renal dysfunction. Caution should be exercised in the presence of hepatic or moderate to severe renal impairment.

This medicinal product contains lactose monohydrate. Patients with rare hereditary problems of galactose intolerance, total lactase deficiency or glucose-galactose malabsorption should not take this 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 given to patients taking monoamine inhibitors or within 14 days of stopping treatment as there is an increased risk of hypertensive crisis (pseudoephedrine) or serotonin syndrome (triprolidine).

Moclobemide: Risk of hypertensive crisis

Appetite suppressants and amphetamine-like psychostimulants: Concomitant use of this product with sympathomimetic agents, such as decongestants, tricyclic antidepressants, appetite suppressants and amphetamine-like psychostimulants, may cause a rise in blood pressure.

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.

Cardiac glycosides: Increased risk of dysrhythmias

Ergot alkaloids (ergotamine & methysergide): Increased risk of ergotism

Oxytocin: Risk of hypertension

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

Antimuscarinic drugs: May have an additive muscarinic action with other drugs such as atropine and some antidepressants.

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

CNS depressants: Triprolidine may enhance the sedative effects of CNS depressants including barbiturates, hypnotics, opioid analgesics, anxiolytic sedatives, antipsychotics and alcohol.

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 breastfeeding infant.

Pregnancy

There are no adequate and well-controlled studies for pseudoephedrine or triprolidine, or for the combination of pseudoephedrine and triprolidine, in pregnant women.

Breastfeeding

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 0.4 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.

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.

4.7. Effects on ability to drive and use machines

Multi-Action ACTIFED 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.

4.8. Undesirable effects

Placebo-controlled studies with sufficient adverse event data are 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 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

Blood and Lymphatic System Disorders

Blood disorder

Rare

Immune System Disorders

Hypersensitivity – cross-sensitivity may occur with other sympathomimetics

Rare

Psychiatric Disorders

Insomnia

Nervousness

Confusional state

Depression

Sleep disorder

Anxiety

Euphoric mood

Excitability

Hallucinations

Irritability

Paranoid delusions

Restlessness

Common

Common

Rare

Rare

Rare

Not Known

Not Known

Not Known

Not Known

Not Known

Not Known

Not Known

Nervous System Disorders

Headache

Dizziness

Paradoxical stimulation

Psychomotor impairment

Somnolence

Extrapyramidal disorder

Seizure

Tremor

Cerebrovascular accident

Paraesthesia

Posterior reversible encephalopathy syndrome (PRES) (see section 4.4) /reversible cerebral vasoconstriction syndrome (RCVS) (see section 4.4)

Psychomotor hyperactivity

Very common

Common

Common

Common

Common

Rare

Rare

Rare

Not Known

Not Known

Not Known

Not Known

Eye Disorders

Vision blurred

Common

Ischaemic optic neuropathy

Not Known

Cardiac Disorders

Palpitations

Dysrhythmias

Myocardial infarction / myocardial ischaemia

Tachycardia

Rare

Not Known

Not Known

Not Known

Vascular Disorders

Hypotension

Hypertension

Rare

Not Known

Respiratory, Thoracic and Mediastinal Disorders

Increased viscosity of bronchial secretion

Dry throat

Epistaxis

Nasal dryness

Common

Not known

Not known

Not known

Gastrointestinal Disorders

Dry mouth

Gastrointestinal disorder

Nausea

Abdominal discomfort

Ischaemic colitis

Vomiting

Common

Common

Common

Not Known

Not Known

Not Known

Hepatobiliary Disorders

Liver Disorder

Rare

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

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

Dysuria

Common

Not known

General Disorders and Administration Site Conditions

Fatigue

Not known

Reporting of suspected adverse reactions

Reporting suspected adverse reactions after authorization 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

Symptoms

The effects of acute toxicity from Multi-Action ACTIFED may include drowsiness, lethargy, dizziness, ataxia, weakness, hypotonicity, respiratory depression, dryness of the skin and mucous membranes, tachycardia, hypertension, hyperpyrexia, hyperactivity, irritability, seizures, and difficulty with micturition.

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 and difficulty in micturition.

Triprolidine

Overdose 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

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