Tripofed DM syrup is indicated for the symptomatic relief of upper respiratory tract disorders which are benefited by the combination of a nasal decongestant, a histamine H₁-receptor antagonist, and an antitussive.

Adults and children aged 12 years and over:

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

 

Children under 12 years:

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

 

The Elderly:

There have been no specific studies of Tripofed DM syrup in the elderly. Experience has indicated that normal adult dosage is appropriate.

 

Hepatic dysfunction:

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

 

Renal dysfunction:

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

Do not exceed the stated dose.

Tripofed DM syrup is contraindicated in individuals who have previously exhibited intolerance to it or to any of its constituents. Tripofed DM syrup is contraindicated in patients with severe hypertension or severe coronary artery disease. Tripofed DM syrup 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. 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 Tripofed DM syrup and furazolidone they should not be taken together. Tripofed DM syrup should not be administered to patients where cough is associated with asthma or where cough is accompanied by excessive secretions. Dextromethorphan, in common with other centrally acting antitussive agents, should not be given to patients in, or at risk of developing respiratory failure. Not to be used in children under the age of 12 years.

Tripofed DM syrup 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 Tripofed DM syrup should avoid the concomitant use of alcohol or other centrally acting sedatives.

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

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

Cases of dextromethorphan abuse have been reported. Caution is particularly recommended for adolescents and young adults as well as in patients with a history of drug abuse or psychoactive substances.

Dextromethorphan is metabolised by hepatic cytochrome P450 2D6. The activity of this enzyme is genetically determined. About 10% of the general population are poor metabolisers of CYP2D6. Poor metabolisers and patients with concomitant use of CYP2D6 inhibitors may experience exaggerated and/or prolonged effects of dextromethorphan. Caution should therefore be exercised in patients who are slow metabolizers of CYP2D6 or use CYP2D6 inhibitors (see also section 4.5).

There have been no specific studies of Tripofed DM syrup in patients with hepatic and/or renal dysfunction Tripofed DM syrup should be used with caution in patients with liver disease.

There have been a few reports of abuse of dextromethorphan but there is no evidence of drug dependence at therapeutic dosages.

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

Do not exceed the stated dose.

Warning: May cause drowsiness. If affected do not operate machinery.

This medicine can make you feel sleepy. Do not drive while taking this medicine until you know how it makes you feel. See the leaflet inside for more information.

Avoid alcoholic drink.

If you are pregnant or currently taking any other medicine, consult your doctor or pharmacist before taking this product.

If symptoms persist consult your doctor.

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Concomitant use of Tripofed DM syrup 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, [See Contraindications and Special warnings and precautions for use].

Because of its pseudoephedrine content, Tripofed DM syrup 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, [See Special warnings and precautions for use].

 

CYP2D6 inhibitors

Dextromethorphan is metabolized by CYP2D6 and has an extensive first-pass metabolism. Concomitant use of potent CYP2D6 enzyme inhibitors can increase the dextromethorphan concentrations in the body to levels multifold higher than normal. This increases the patient's risk for toxic effects of dextromethorphan (agitation, confusion, tremor, insomnia, diarrhoea and respiratory depression) and development of serotonin syndrome. Potent CYP2D6 enzyme inhibitors include fluoxetine, paroxetine, quinidine and terbinafine. In concomitant use with quinidine, plasma concentrations of dextromethorphan have increased up to 20-fold, which has increased the CNS adverse effects of the agent. Amiodarone, flecainide and propafenone, sertraline, bupropion, methadone, cinacalcet, haloperidol, perphenazine and thioridazine also have similar effects on the metabolism of dextromethorphan. If concomitant use of CYP2D6 inhibitors and dextromethorphan is necessary, the patient should be monitored and the dextromethorphan dose may need to be reduced.

Although pseudoephedrine, triprolidine and dextromethorphan 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.

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 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.

It is not known whether dextromethorphan or its metabolites are excreted in breast milk.

No studies have been conducted in animals to determine whether triprolidine, pseudoephedrine or dextromethorphan have potential to impair fertility. There is no experience of the effect of Tripofed DM syrup on human fertility.

In rats and rabbits, systemic administration of triprolidine up to 75 times the human daily dosage 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.

There is insufficient information available to determine whether dextromethorphan has teratogenic potential.

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

This medicine can impair cognitive function and can affect a patient's ability to drive safely. When taking this medicine, patients should be told:

§ The medicine is likely to affect your ability to drive

§ Do not drive until you know how the medicine affects you

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 male patients in whom prostatic enlargement could be an important predisposing factor.

Side effects attributed to dextromethorphan are uncommon; occasionally nausea, vomiting or gastro-intestinal disturbance may occur.

 

To report any side effect(s):

·   Saudi Arabia:

The National Pharmacovigilance Centre (NPC): Fax: +966-11-205-7662 SFDA Call Center: 19999 E-mail: npc.drug@sfda.gov.sa Website: https://ade.sfda.gov.sa

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

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.

Naloxone has been used successfully as a specific antagonist to dextromethorphan toxicity in children.

ATC Code of Triprolidine: R06AX07

ATC Code of Dextromethorphan: R05DA09 

Triprolidine provides symptomatic relief in conditions believed to depend wholly or partially upon the triggered release of histamine. It is a potent competitive histamine H₁-receptor antagonist of the pyrrolidine class with mild central nervous system depressant properties which may cause drowsiness. Pseudoephedrine has a direct and indirect sympathomimetic activity and is an effective upper respiratory decongestant. Pseudoephedrine is substantially less potent than ephedrine in producing both tachycardia and elevation of systolic blood pressure and considerably less potent in causing stimulation of the central nervous system. Dextromethorphan has an antitussive action. It controls coughs by depressing the medullary cough centre.

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 weals and flares in the skin is within 1 to 2 hours. Peak effects occur at about 3 hours and, although activity declines thereafter, significant inhibition of histamine-induced weals and flares still occurs 8 hours after the dose. Pseudoephedrine produces its decongestant effect within 30 minutes, persisting for at least 4 hours.

A single oral dose of 10 - 20 mg dextromethorphan produces its antitussive action within 1 hour and lasts for at least 4 hours.

After the administration of 2.5 mg triprolidine hydrochloride and 60 mg pseudoephedrine hydrochloride to healthy adult volunteers, the peak plasma concentration (C_max) of triprolidine is approximately 5.5 ng/ml - 6.0 ng/ml occurring at about 1.5 - 2.0 hours (T_max) after drug administration. Its plasma half-life is approximately 3.2 hours. The C_max of pseudoephedrine is approximately 180 ng/ml with T_max approximately 1.5 - 2.0 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 alkalinisation.

Dextromethorphan undergoes rapid and extensive first-pass metabolism in the liver after oral administration. Genetically controlled O-demethylation (CYD2D6) is the main determinant of dextromethorphan pharmacokinetics in human volunteers.

It appears that there are distinct phenotypes for this oxidation process resulting in highly variable pharmacokinetics between subjects. Unmetabolised dextromethorphan, together with the three demethylated morphinan metabolites dextrorphan (also known as 3-hydroxy-N-methylmorphinan), 3- hydroxymorphinan and 3-methoxymorphinan have been identified as conjugated products in the urine.

Dextrorphan, which also has antitussive action, is the main metabolite. In some individuals metabolism proceeds more slowly and unchanged dextromethorphan predominates in the blood and urine.

The active ingredients of Tripofed DM syrup are well-known constituents of medicinal products and their safety profiles are well documented. The results of pre-clinical studies do not add anything of relevance for therapeutic purposes.

The excipients in each 100 ml are

 

Sucrose	35.000 gm
Sodium benzoate	0.100 gm
Saccharine sodium	0.100 gm
Methyl paraben	0.100 gm
Glycerol	10.000 gm
Cherry flavour	0.010 gm
Banana flavour	0.010 gm
Purified water	To 100 ml

None reported.

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 30º C, protect from light.

Tripofed DM syrup is available in glass bottles size 100 ml.

It is available in an amber colored type III glass bottle size of 100 ml with narrow mouth and provided with child resistant cap.

No special requirements.