BENADRYL Plus Capsules

BENADRYL Plus Capsules contain 8 mg acrivastine and 60 mg pseudoephedrine hydrochloride.

Capsules.

BENADRYL Plus Capsules are indicated for the symptomatic relief of allergic rhinitis.

Adults and children 12 years and over:

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

Children under 12 years:

BENADRYL Plus Capsules are not currently recommended for use in children under 12 years of age.

The Elderly:

BENADRYL Plus Capsules are not currently recommended for use in the elderly.

BENADRYL Plus Capsules are contra-indicated in individuals with known hypersensitivity to the product, any of its components or triprolidine.

BENADRYL Plus Capsules are contra-indicated in individuals with known intolerance to the product, any of its components or triprolidine.

BENADRYL Plus Capsules are contra-indicated in patients with severe hypertension or severe coronary artery disease.

The concomitant use of a pseudoephedrine-containing product and monoamine oxidase inhibitors can occasionally cause a rise in blood pressure. BENADRYL Plus Capsules are therefore contra-indicated in patients who are taking, or have taken, monoamine oxidase within the preceding two weeks.

The antibacterial agent furazolidone is known to cause a dose-related inhibition of monoamine oxidase. Although there are no reports of hypertensive crises having occurred, it should not be administered concurrently with BENADRYL Plus Capsules.

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

It is usual to advise patients not to undertake tasks requiring mental alertness whilst under the influence of alcohol or other CNS depressants. Concomitant administration of BENADRYL Plus Capsules may, in some individuals, produce additional impairment.

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

As with other sympathomimetic agents, BENADRYL Plus Capsules should be used with caution in patients with hypertension, heart disease, diabetes, hyperthyroidism, elevated intra-ocular pressure or prostatic enlargement.

Concomitant use of pseudoephedrine with tricyclic antidepressants, other sympathomimetic agents (such as decongestants, appetite suppressants and amfetamine-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 (see Contraindications).

The effect of antihypertensive agents, which interfere with sympathetic activity, may be partially reversed by BENADRYL Plus Capsules, e.g. bretylium, betanidine, guanethidine, debrisoquine, methyldopa, alpha- and beta-adrenergic blocking agents.

No information is available on the effects of administration of BENADRYL Plus Capsules during human pregnancy. BENADRYL Plus Capsules, like most medicines, should not be used during pregnancy unless the potential benefit of treatment to the mother outweighs any possible risk to the developing foetus.

No information is available on levels of acrivastine which may appear in human breast milk following administration of BENADRYL Plus Capsules.

It has been estimated that approximately 0.5 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, but the effect of this on breast-fed infants is not known.

Most patients do not experience drowsiness with BENADRYL Plus Capsules. Nevertheless as there is individual variation in response to all medication, it is recommended that patients are advised not to engage in activities requiring mental alertness, such as driving a car or operating machinery, until they have established their own response to the drug (see Special warnings and precautions for use).

It is recommended that patients are advised not to undertake tasks requiring mental alertness whilst under the influence of alcohol or other C.N.S. depressants. Concomitant administration of BENADRYL Plus Capsules may, in some patients, produce additional impairment.

In clinical trials with BENADRYL Plus Capsules, the incidence of somnolence and dizziness was no greater than that from placebo. Reports of drowsiness directly attributable to BENADRYL Plus Capsules are extremely rare. For the great majority of patients, treatment with BENADRYL Plus Capsules is not associated with clinically significant anticholinergic or sedative side effects.

Serious adverse effects associated with the use of pseudoephedrine are extremely rare. Symptoms of central nervous system excitation may occur including sleep disturbance, and, rarely, hallucinations.

Skin rashes, with or without irritation, have occasionally been reported with pseudoephedrine. Urinary retention has been reported occasionally in men receiving pseudoephedrine; prostatic enlargement could have been an important predisposing factor.

There have been no reported cases of acute overdosage with BENADRYL Plus Capsules. It may be expected that as with other sympathomimetic drugs, the symptoms and signs of overdosage may include irritability, restlessness, tremor, convulsions, palpitations, hypertension and difficulty with micturition.

Patients should receive necessary supportive treatment in the event of overdosage. Gastric lavage should be performed if indicated. If desired, the elimination of pseudoephedrine can be accelerated by acid diuresis or by dialysis.

Acrivastine is a potent, competitive H₁-receptor antagonist that lacks significant anticholinergic effects and has a low potential to penetrate the central nervous system. Acrivastine provides symptomatic relief in conditions believed to depend wholly, or partly, upon the triggered release of histamine.

Pseudoephedrine has direct and indirect sympathomimetic activity and is an effective upper respiratory decongestant. Pseudoephedrine is less potent than ephedrine in producing both tachycardia and elevation of systolic blood pressure and is less potent in causing stimulation of the central nervous system. Pseudoephedrine produces its decongestant effect within 30 minutes, persisting for at least 4 hours.

After oral administration of a single dose of 8 mg acrivastine to adult volunteers, the onset of action, as determined by the ability to antagonise histamine induced weals and flares in the skin, is within 1 hour. Peak effects occur at 2 hours, and although activity declines slowly thereafter, significant inhibition of histamine induced weals and flares still occur 8 hours after dose.

Relief from the histamine-mediated symptoms of allergic rhinitis is apparent within 1 hour of systemic administration of the drug and lasts for up to 8 hours.

After the administration of one BENADRYL Plus Capsule to healthy adult volunteers, the peak plasma concentration (C_max) for acrivastine is approximately 140 ng/ml, occurring at about 1.3 hours (T_max) after drug administration. The plasma half-life is approximately 1.6 hours. The peak plasma concentration for pseudoephedrine is approximately 210 ng/ml, with T_max approximately 2 hours after drug administration. The plasma half-life 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 alkalination. Renal excretion is the principal route of elimination of both acrivastine and pseudoephedrine.

Pre-clinical safety data do not add anything of further significance to the prescriber.

Lactose

Sodium starch glycollate

Magnesium stearate

Gelatin

Titanium dioxide (E171)

Patent Blue V (E131)

None known.

36 months.

Do not store above 25°C.

Store in the original package to protect from moisture.

6 or 12 capsules in PVC/PVDC Aluminium foil blister packs.

6 capsules in polypropylene containers with polyethylene snap-fitting lids.

None known.

McNeil Products Limited

Foundation Park

Roxborough Way

Maidenhead

Berkshire SL6 3UG

United Kingdom

PL 15513/0017

24^th March 1998

14 March 2008