Tripofed Expectorant syrup is indicated for the symptomatic relief of upper respiratory tract disorders accompanied by productive cough, which are benefited by the combination of a histamine H₁-receptor antagonist, a decongestant of the mucous membranes of the upper respiratory tract, especially the nasal mucosa and sinuses, and an expectorant.

Adults and children aged 12 years and over:

Oral. 10 ml every 4-6 hours up to 4 times a day

 

Children under 12 years

Tripofed Expectorant is contraindicated in children under the age of 12 years (see section 4.3)

 

Use in the Elderly

No specific studies have been carried out in the elderly. Experience has indicated that normal adult dosage is appropriate.

 

Hepatic Dysfunction

Caution should be exercised when administering Tripofed Expectorant to patients with severe hepatic impairment.

 

Renal Dysfunction

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

Do not exceed the stated dose.

 Tripofed Expectorant is contraindicated in individuals with known hypersensitivity to the product, any of its components, or acrivastine.  Tripofed Expectorant is contraindicated in individuals with severe hypertension or severe coronary artery disease.  Tripofed Expectorant is contraindicated in individuals 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.  Not to be used in children under the age of 12 years.

Although pseudoephedrine has virtually no pressor effects in normotensive patients, Tripofed Expectorant should be used with caution in individuals suffering mild to moderate hypertension.

As with other sympathomimetic agents, Tripofed Expectorant should be used with caution in individuals with heart disease, hyperthyroidism, diabetes, elevated intra-ocular pressure or prostatic enlargement.

Tripofed Expectorant should not be used for persistent or chronic cough, such as occurs with asthma, or where cough is accompanied by excessive secretions, unless directed by a physician.

Tripofed Expectorant may cause drowsiness and impair performance in tests of auditory vigilance. There is individual variation in response to antihistamines.

Caution should be exercised when using the product in the presence of severe hepatic impairment or moderate to severe renal impairment (particularly if accompanied by cardiovascular disease).

 

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 Tripofed Expectorant Syrup should be discontinued and appropriate measures taken if needed.

 

Not more than 4 doses should be given in any 24 hours.

Do not take with any other cough and cold medicine.

Although there are no objective data, users of Tripofed Expectorant should avoid concomitant use of alcohol or other centrally acting sedatives.

·   Concomitant use of Tripofed Expectorant with tricyclic antidepressants, sympathomimetic agents (such as decongestants, appetite suppressants and amfetamine-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, Tripofed Expectorant 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.

·   If urine is collected within 24 hours of a dose of Tripofed Expectorant, a metabolite of guaifenesin may cause a colour interference with laboratory determinations of urinary 5-hydroxyindoleacetic acid (5-HIAA) and vanillylmandelic acid (VMA).

Insufficient information is available on the effects of administration of Tripofed Expectorant during human pregnancy. Like most medicines, it should not be used during pregnancy unless the potential benefit of treatment to the mother outweighs any possible risk 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, following the ingestion of a single dose of Tripofed Expectorant Syrup (2.5 mg triprolidine + 60 mg pseudoephedrine) by a nursing mother, approximately 0.4 to 0.7% of pseudoephedrine and 0.06% to 0.2% triprolidine in the dose will be excreted in the breast milk over 24 hours.

Guaifenesin is excreted in breast milk in small amounts with no effect expected on the infant.

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 this medicine.

Pseudoephedrine - 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 and tachycardia have occasionally been reported with pseudoephedrine. Urinary retention has been reported in men receiving pseudoephedrine; prostatic enlargement could have been a predisposing factor.

Triprolidine - triprolidine may cause drowsiness. Skin rashes, with or without irritation have occasionally been reported. Dryness of the mouth, nose and throat may occur.

Guaifenesin - side effects resulting from guaifenesin administration are very rare.

 

Skin and subcutaneous tissue disorders:

Severe skin reactions, including acute generalized exanthematous pustulosis (AGEP) (Frequency unknown).

 

Adverse Drug Reaction (ADR) Reporting

·   Saudi Arabia:

 

The National Pharmacovigilance and Drug Safety Centre (NPC) § Fax: +966-11-205-7662 § Call NPC at: +966-11-2038222, Ext.: 2317-2356-2353-2354-2334-2340. § Toll free phone: 8002490000 § E-mail:npc.drug@sfda.gov.sa § Website: www.sfda.gov.sa/npc

Signs and symptoms - the effects of acute toxicity from Tripofed Expectorant may include drowsiness, irritability, restlessness, lethargy, dizziness, gastro-intestinal discomfort, nausea, vomiting, difficulty with micturition, dryness of the skin and mucous membranes, ataxia, weakness, hypotonicity, respiratory depression, hyperpyrexia, hyperactivity, convulsions, tremor, tachycardia, palpitations, hypertension.

 

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. Acid diuresis can accelerate the elimination of pseudoephedrine, although the potential therapeutic gain of this procedure is now in dispute. The value of dialysis in overdose is not known, although four hours of haemodialysis removed approximately 20% of the total body load of pseudoephedrine in a combination product containing 60mg pseudoephedrine and 8mg acrivastine.

ATC code: R01BA52

 

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.

 

Guaifenesin

Guaifenesin is though to exert its pharmacological action by stimulating receptors in the gastric mucosa. This increases the output from secretory glands of the gastrointestinal system and reflexly increases the flow of fluids from glands lining the respiratory tract. The result is an increase in volume and decrease in viscosity of bronchial secretions. Other actions may include stimulating vagal nerve endings in bronchial secretory glands and stimulating certain centres in the brain which in turn enhance respiratory fluid flow. Guaifenesin produces its expectorant action within 24 hours.

Absorption

Pseudoephedrine and triprolidine are well absorbed from the gut following oral administration. After the administration of one Pseudoephedrine and triprolidine 10 ml Tripofed Expectorant 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 with t_max occurring at approximately 1.5 hours 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 1.5 hours (t_max) after drug administration.

 

GUAIFENESIN - guaifenesin is well absorbed from the gastro-intestinal tract following oral administration, although limited information is available on its pharmacokinetics. After the administration of 600 mg guaifenesin to healthy volunteers, the C_max was approximately 1.4 μg/ml, with t_max occurring approximately 15 minutes 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 7.5 l/kg. No information is available on the distribution of guaifenesin in humans.

 

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.

 

GUAIFENESIN - guaifenesin appears to undergo both oxidation and demethylation. Following an oral dose of 600 mg guaifenesin to 3 healthy male volunteers, the t_½ was approximately 1 hour and the drug was not detectable in the blood after approximately 8 hours.

 

Pharmacokinetics in renal impairment

Following the administration of a single dose of DUACT CAPSULES (8 mg acrivastine + 60 mg pseudoephedrine) to patients with varying degrees of renal impairment, the C_max for pseudoephedrine increased approximately 1.5 fold in patients with moderate to severe renal impairment when compared to the C_max in healthy volunteers. The t_max was not affected by renal impairment. The t_½ increased 3 to 12 fold in patients with mild to severe renal impairment respectively, when compared to the t_½ in healthy volunteers.

There have been no specific studies of Tripofed Expectorant syrup, triprolidine or guaifenesin in renally impaired patients.

 

Pharmacokinetics in hepatic impairment

There have been no specific studies of Tripofed Expectorant syrup, triprolidine, pseudoephedrine or guaifenesin in hepatic impairment.

 

Pharmacokinetics in the elderly

In elderly volunteers, following the administration of DUACT Capsules (8 mg acrivastine + 60 mg pseudoephedrine), the t_½ 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 Tripofed Expectorant syrup, triprolidine or guaifenesin in the elderly.

There is insufficient information available to determine whether some of the active ingredients have mutagenic, carcinogenic, teratogenic potential, or the potential to impair fertility.

 

Sucrose,

Sodium benzoate,

Saccharine sodium,

Methyl Paraben,

Glycerol,

Cherry flavor,

Banana flavor,

FD&C Yellow No. 6 (Sunset yellow),

purified water

None known.

3 years from the manufacturing date. The expiry date refers to the last day of the month.

§ Keep in a safe place, out of the reach and sight of children.

§ Store below 30° C, protect from light.

§ Use within 2 months after opening.

Tripofed Expectorant syrup is available in an amber colored type III glass bottle size of 100 ml, with child resistant cap.

No special requirements.