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

Route of administration: Oral.

Adults and children over 12 years:

UNIFED^® Syrup: Take two large 5 ml spoonfuls every 4 – 6 hours, up to 4 times a day.

Children under 12 years:

Children between 6 - 12 years: Should be indicated for use as a second line treatment upon doctor advice, and with duration of use restricted to no more than 5 days.

Children under 6 years of age: should not be used. 

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 Unifed to patients with severe hepatic impairment.

Renal Dysfunction

Caution should be exercised when administering Unifed to patients with moderate to severe renal impairment.

- Unifed is contraindicated in individuals who have previously exhibited intolerance to it or to pseudoephedrine or triprolidine. - Unifed is contraindicated in patients 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. - Unifed is contraindicated in patients with severe hypertension or severe coronary artery disease. - 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 Unifed and furazolidone they should not be taken together. - If the patient is a child aged less than 6 years.

Unifed 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 Unifed should avoid the concomitant use of alcohol or other centrally acting sedatives.

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

As with other sympathomimetic agents Unifed should be used with caution in patients with hypertension, heart disease, diabetes, hyperthyroidism, elevated intraocular pressure and prostatic enlargement.

There have been no specific studies of Unifed in patients with hepatic and/or renal dysfunction. Caution should be exercised in the presence of severe renal or hepatic impairment.

There is insufficient information available to determine whether triprolidine or pseudoephedrine have mutagenic or carcinogenic potential.

Systemic administration of pseudoephedrine in rats, up to 7 times the human daily dosage in females and 35 times the human daily dosage in males, did not impair fertility nor alter foetal morphological development and survival.

No studies have been conducted in animals to determine if triprolidine has the potential to impair fertility.

There is no information on the effects of Unifed on human fertility.

Protect from light

Keep out of the reach of children

Warnings may cause drowsiness. If affected do not drive or operate machinery. Avoid alcoholic drink.

If symptoms persist consult your doctor.

Do not exceed the stated dose.

As with all medicines if you are pregnant, or currently taking any other medicine, consult your doctor or pharmacist before taking this product.

Concomitant use of Unifed 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.

Because of its pseudoephedrine content, Unifed 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.

 

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.

Systemic administration of triprolidine in rats and rabbits up to 75 times the human dose 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.

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 mother will be excreted in the breast-milk over 24 hours.

Triprolidine may cause drowsiness and patients should not drive or operate machinery until they have determined their own response

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 men receiving pseudoephedrine; prostatic enlargement could have been an important predisposing factor.

 

Signs and symptoms

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

Treatment

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.

ATC code: ROIBA52

Pseudoephedrine

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 also less potent in causing stimulation of the central nervous system. Pseudoephedrine produces its decongestant effect within 30 minutes, persisting for at least 4 hours.

Triprolidine

Triprolidine is a potent, competitive H₁-receptor antagonist. Being an alkylamine the drug possesses minimal anticholinergic activity. Triprolidine provides symptomatic relief in conditions believed to depend wholly, or partly, upon the triggered release of histamine. 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 wheals and flares in the skin, was within 1 to 2 hours. Peak effects occurred after 3 hours, and although activity declines thereafter, significant inhibition of histamine-induced wheals and flares still occurred 8 hours after a single dose.

Absorption:

Pseudoephedrine and triprolidine are well absorbed from the gut following oral administration. After the administration of 10 ml Unifed^® Syrup (each containing 2.5 mg triprolidine and 60 mg pseudoephedrine) to healthy adult volunteers, the following pharmacokinetic values were found;

Pseudoephedrine the C_max of pseudoephedrine was approximately 180 ng/ml for with t_max occurring at approximately 2.0 hours for the tablet and 1.5 hours for the syrup after drug administration.

Triprolidine the peak plasma concentration (C_max) of triprolidine was approximately 5.5 ng/ml-6.0 ng/ml, occurring at about 2.0 hours (t_max) for the tablet and 1.5 hours for the syrup after drug administration.

 

Distribution:

The apparent volume of distribution of pseudoephedrine (Vd/F) was approximately 2.8 l/kg. The apparent volume of distribution of triprolidine was approximately 6.5 l/kg for the tablet formulation and 7.5 l/kg for the syrup.

Metabolism and Elimination:

Pseudoephedrine: the t_½ was approximately 5.5 hours. Pseudoephedrine is partly metabolised in the liver by N-demethylation to norpseudoephedrine, an active metabolite. Pseudoephedrine and its metabolite are excreted in the urine; 55% to 90% of a dose is excreted unchanged. The apparent total body clearance of pseudoephedrine (Cl/F) was approximately 7.5 ml/min/kg. The elimination rate constant (K_el) was approximately 0.13 h^-1. The rate of urinary elimination is accelerated when the urine is acidified. Conversely, as the urine pH increases, the rate of urinary elimination is slowed.

Triprolidine: the plasma half-life (t_½) of triprolidine was approximately 3.2 hours. Animal hepatic microsomal enzyme studies have revealed the presence of several triprolidine metabolites with an oxidised product of the toluene methyl group predominating. In man, it has been reported that only about 1% of an administered dose is eliminated as unchanged triprolidine over a 24-hour period. The apparent total body clearance of triprolidine (Cl/F) was approximately 30-37 ml/min/kg. The elimination rate constant (K_el) was approximately 0.26 h^-1.

Pharmacokinetics in Renal Impairment:

Following the administration of a single dose of 8mg acrivastine + 60 mg pseudoephedrine to patients with varying degrees of renal impairment, the Cmax for pseudoephedrine increased approximately 1.5 fold in patients with moderate to severe renal impairment when compared to the Cmax in healthy volunteers. The tmax was not affected by renal impairment. The t½ increased 3 to 12 fold in patients with mild to severe renal impairment respectively, when compared to the t½ in healthy volunteers.

Pharmacokinetics in Hepatic Impairment:

There have been no specific studies of Unifed^®, triprolidine, or pseudoephedrine in hepatic impairment.

Pharmacokinetics in the Elderly:

In elderly volunteers, following the administration of 8 mg acrivastine + 60 mg pseudoephedrine, the t½ for pseudoephedrine was 1.4 fold that seen in healthy volunteers. The apparent Cl/F was 0.8 fold that seen in healthy volunteers, and the Vd/F was essentially unchanged. There have been no specific studies of Unifed^®, triprolidine in the elderly.

        Not Applicable

-       Sorbitol Solution

-       Sucrose

-       Sodium Bonzoate

-       Methylparaben

-       Glycerin

-       Sodium Saccharine

-       Hydroxy Ethyl Cellulose

-       Ariavit Quinoline Yellow

-       Flavors

-       Purified Water

        Not Applicable

2 Years

• Do not store above 30°C
• Protect from light
• Discard the content after one month from first opening.

-       Bottle: amber glass type III soda-lime glass, intended for pharmaceutical uses.

-       Cap: white, cylindrical, polypropylene inner and outer caps, LD polyethylene ring and insert, child resistant.

-       Adhesive label.

-       Outer box.

-       Multi folded leaflet

Pack size:

120 ml syrup

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