4.1. Therapeutic indications

This product is indicated for the symptomatic relief of allergic rhinitis.

4.2. Posology and method of administration

Posology

Adults and children 12 years and over:

One capsule as necessary, up to three times a day.

Children under 12 years:

This product is not currently recommended for use in children under 12 years of age.

Elderly:

This product is not currently recommended for use in the elderly.

Hepatic dysfunction:

Caution should be exercised when administering Benadryl Allergy Relief Plus Decongestant Capsules to patients with severe hepatic impairment.

Renal dysfunction:

Caution should be exercised when administering Benadryl Allergy Relief Plus Decongestant Capsules to patients with moderate renal impairment.

Method of administration

For oral use.

4.3. Contraindications

- Hypersensitivity to the active substances, antihistamine triprolidine or to any of the excipients listed in section 6.1. (see Section 4.8)

- Cardiovascular disease including hypertension

- Concomitant use of beta blockers (see section 4.5)

- Concomitant use of other sympathomimetic decongestants.

- Diabetes mellitus

- Phaeochromocytoma

- Closed angle glaucoma

- Hyperthyroidism

- Severe acute or chronic kidney disease/renal failure

The concomitant use of a pseudoephedrine-containing product and monoamine oxidase inhibitors may cause a rise in blood pressure and/or hypertensive crisis. This product is therefore contraindicated in patients who are taking, or have taken, monoamine oxidase inhibitors within the preceding 14 days (see section 4.5).

Renal excretion is the principal route of elimination of acrivastine. Until specific studies have been carried out, this product should not be given to patients with significant renal impairment.

4.4. Special warnings and precautions for use

It is usual to advise patients not to undertake tasks requiring mental alertness whilst under the influence of alcohol or other CNS depressants including sedatives and tranquilizers. Concomitant administration of this product may, in some individuals, produce additional impairment.

Although pseudoephedrine has virtually no pressor effects in patients with normal blood pressure, this product should be used with caution in patients taking antihypertensive agents, tricyclic antidepressants or other sympathomimetic agents such as decongestants, appetite suppressants or amphetamine-like psychostimulants. The effects of a single dose on the blood pressure of these patients should be observed before recommending repeated or unsupervised treatment.

Patients with difficulty in urination and/or enlargement of the prostate, or patients with thyroid disease who are receiving thyroid hormones, decreased kidney function should not take pseudoephedrine unless directed by a physician.

Caution should be exercised when using the product in the presence of severe hepatic impairment or moderate to severe renal impairment, or occlusive vascular disease.

This product may cause drowsiness (see section 4.8).

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.

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.

This medicine contains less than 1 mmol sodium (23mg) per capsule, that is to say essentially “sodium-free”.

4.5. Interaction with other medicinal products and other forms of interaction

Pseudoephedrine

Monoamine oxidase inhibitors (MAOIS)

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 sympathomimetics 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 used in patients taking monoamine inhibitors or within 14 days of stopping treatment as there is a risk of hypertensive crisis.

Concomitant use of pseudoephedrine with tricyclic antidepressants, sympathomimetic agents (such as decongestants, appetite suppressants and amphetamine-like psychostimulants), may cause a rise in blood pressure (see section 4.3).

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 (see section 4.4).

Anticholinergic drugs: enhances effect of anticholinergic drugs (such as tricyclic antidepressants).

Oxytocin: risk of hypertension.

Cardiac glycosides: increased risk of dysrhythmias.

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

Moclobemide: risk of hypertensive crisis.

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

Acrivastine

There are no data to demonstrate an interaction between acrivastine and ketoconazole, erythromycin or grapefruit juice. However, due to known interactions between these compounds and other non-sedating antihistamines, caution is advised.

CNS depressants (alcohol, sedatives, tranquilizers)

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

4.6. Fertility, pregnancy and lactation

Pregnancy

There are no adequate and well-controlled studies in pregnant women.

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

Breastfeeding

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.

No information is available on levels of acrivastine which may appear in human breast milk following administration of this product.

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 60mg 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.

4.7. Effects on ability to drive and use machines

There have been the following side effects with acrivastine: dizziness and somnolence. Caution should be exercised when driving a motor vehicle or operating machinery.

It is recommended that patients are advised not to undertake tasks requiring mental alertness whilst under the influence of alcohol or other CNS depressants. Concomitant administration of this product may, in some patients, produce additional impairment.

4.8. Undesirable effects

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

No adverse drug reactions have been identified during post-marketing experience with the combination product acrivastine/pseudoephedrine.

Adverse drug reactions identified during clinical trials and post-marketing experience with acrivastine or pseudoephedrine as single ingredient products 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'.

System Organ Class (SOC)

Frequency

Adverse Drug Reaction (Preferred Term)

Immune System Disorders

Not Known

Hypersensitivity* (including dyspnoea and face swelling)#

Cross-sensitivity may occur with other sympathomimetics

Psychiatric Disorders

Common

Insomnia*

Nervousness*

Not known

Anxiety*

Euphoric mood*

Excitability*

Hallucinations*

Irritability*

Paranoid delusions*

Restlessness*

Sleep disorder*

Nervous System Disorders

Very common

Headache*

Somnolence#*

Common

Dizziness#*

Not Known

Cerebrovascular accident*

Paraesthesia*

Posterior reversible encephalopathy syndrome (PRES) (see section 4.4)

Reversible cerebral vasoconstriction syndrome (RCVS)* (see section 4.4)

Psychomotor hyperactivity*

Tremor*

Eye Disorders

Not known

Ischaemic optic neuropathy

Cardiac Disorders

Not Known

Dysrhythmias*

Myocardial infarction/myocardial ischaemia*

Palpitations#*

Tachycardia*

Vascular Disorders

Not known

Hypertension*

Gastrointestinal Disorders

Common

Dry mouth*

Nausea*

Not Known

Not Known

Ischaemic colitis*

Vomiting*

Skin and Subcutaneous Tissue Disorders

Not Known

Angioedema*

Pruritus*

Rash#*

Severe skin reactions, including acute generalised exanthematous pustulosis (AGEP)*

Renal and Urinary Disorders

Not Known

Dysuria*

Urinary retention in men* in whom prostatic enlargement could have been an important predisposing factor

# Associated with Acrivastine

* Associated with 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 the Yellow Card Scheme: www.mhra.gov.uk/yellowcard or search for MHRA Yellow Card in the Google Play or Apple App Store.

4.9. Overdose

Acrivastine

When the recommended therapeutic dose has been exceeded, acrivastine has been found to impair the ability to drive. This effect is related to the amount of acrivastine taken beyond the recommended maximum daily dosage.

Pseudoephedrine

Symptoms

Overdose may result in:

Hyperglycaemia, hypokalaemia, CNS stimulation, insomnia, irritability, restlessness, anxiety, agitation, confusion, delirium, hallucinations, psychoses, tremor, seizures, 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, difficulty in micturition.

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.