Soventus Syrup

Ambroxol Hydrochloride, Terbutaline Sulphate, Guaifenesin & Menthol Syrup

Each 5 ml Contains:

Ambroxol Hydrochloride IP….20 mg

Terbutaline Sulphate IP……….1.25 mg

Guaifenesin IP……………….50 mg

Menthol IP…………………...0.5 mg

Excipients …... …………………. q. s.

Colour Tartrazine Supra

In a flavoured syrup base

Syrup

4.1 Therapeutic indication

For the symptomatic relief of bronchospasm in bronchial asthma & chronic bronchitis.

4.2 Posology and method of administration

Adults (12 years & above) 10 ml (2 teaspoonful) 3 times a day.

Children (6-12 years) 5 - 10 ml (1 - 2 teaspoonful) 3 times a day

Paediatric population

Not recommended for children below 6 years of age.

Hepatic & Renal Insufficiency

Caution should be exercised in patients with moderate to severe renal impairment and liver disease.

4.3 Contraindications

• hypersensitivity to any of the components of the formulation.
• patients with pre-existing ischaemic heart disease or those patients with significant risk factors for ischaemic heart disease.
• patients with gastric ulceration.

4.4 Special warnings and precautions for use

In cases of severe renal failure, an accumulation of metabolites formed in the liver must be considered, and a reduction in the maintenance dose of Ambroxol or an increase in the

dose interval must be performed. In patients with a tendency for peptic ulcers, the use of Ambroxol hydrochloride should be carefully considered.

For Terbutaline, caution should be observed in patients with thyrotoxicosis. Cardiovascular effects may be seen with sympathomimetic drugs, including terbutaline.

Guaifenesin 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. Caution should be exercised in the presence of severe renal or severe hepatic impairment. The concomitant use of cough suppressants is not recommended.

Menthol based cough syrups should not be used in consistent and chronic cough with excessive mucin secretions.

4.5 Drugs interactions

The concomitant use of antitussives along with ambroxol may impair the coughing up of the liquefied bronchial mucous and cause a secretory obstruction.

The administration of ambroxol with antibiotics (amoxicillin, cefuroxime, and erythromycin) increases the concentration of antibiotics in bronchopulmonary secretions and sputum.

Terbutaline and non-selective β-blockers should not be administered concurrently. Terbutaline should be used with caution in patients receiving other sympathomimetics. Terbutaline should be administered with extreme caution to patients being treated with monoamine oxidase inhibitors or tricyclic antidepressants, or within 2 weeks of discontinuation of these agents, since the action of terbutaline on the vascular system may be potentiated.

The concomitant use of menthol cough syrup with warfarin may reduce the therapeutic effects of war farin. Large doses of menthol may affect the felodipine metabolism by inhibiting CYP3A4.

4.6 Use in special populations (such as pregnant women, lactating women, paediatric patients, geriatric patients etc.)

Pregnancy

Since there are no adequate and well-controlled studies of this combination in pregnant women, this medicine should be administered with caution.

Lactation

Terbutaline is secreted into breast milk, but any effect on the infant is unlikely at therapeutic doses. Transient hypoglycaemia has been reported in newborn preterm infants after maternal β-2 agonist treatment. Since Guaifenesin is excreted in breast milk in small amounts, decision must be made to continue with the medicine if benefit of drug outweighs the risks of treatment. It is preferable to avoid use of menthol based cough syrups during pregnancy or lactation.

Geriatric Population

They are more sensitive to the effects of terbutaline; hence a lower dose may be required.

4.7 Effects on ability to drive and use machines

Patients should be cautioned against engaging in activities requiring complete mental alertness, and motor coordination such as operating machinery until their response to Soventus syrup is known.

4.8 Undesirable Effects

The most common adverse reactions with Ambroxol are nausea, oral and pharyngeal hypoesthesia, dyspepsia, dry mouth, abdominal pain and allergic reactions such as skin rash or urticaria can also occur.

Tremor and headache are the most common adverse events observed with Terbutaline administration. Tachycardia, palpitations, muscle spasms and hypokalaemia are few other common adverse reactions observed.

Guaifenesin has occasionally been reported to cause gastro-intestinal discomfort, nausea and vomiting, particularly in very high doses. Allergic reactions, angioedema, anaphylactic reactions, dyspnoea (reported in association with other symptoms of hypersensitivity), nausea, vomiting, abdominal discomfort, rash and urticaria may also occur.

Possible side effects from the use of high doses of Menthol are allergic reactions, facial swelling, throat disorder, nausea, vomiting, vertigo, ataxia, drowsiness, exhaustion and stomach pain.

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 email to:medico@zuventus.com

Website : http://www.zuventus.co.in/safety.aspx

By reporting side effects, you can help provide more information on the safety of this medicine.

4.9 Overdose

Ambroxol: Symptoms largely correspond with the known adverse effects in case of unintentional overdosing and/or medication errors. Symptomatic treatment is recommended if manifestations of poisoning do occur.

Possible symptoms and signs of Terbutaline overdose is headache, anxiety, tremor, nausea, tonic cramp, palpitations, tachycardia, arrhythmia. A fall in blood pressure sometimes occurs. Hypokalaemia, hyperglycaemia and lactic acidosis may also occur in case of drug overdose. Dose can be reduced in mild and moderate cases whereas gastric lavage or administration of activated charcoal can be followed in severe cases.

The effects of acute toxicity from Guaifenesin may include gastrointestinal discomfort, nausea and drowsiness. The drug is, however, rapidly metabolised and excreted in the urine.

Patients should be kept under observation and treated symptomatically.

Menthol is considered to be safe, and cases of menthol overdose are extremely rare. However, when consumed in large quantities in short span of time may cause heartburn, diarrhoea, dizziness, muscle weakness, mouth sores, skin lesions etc. Treatment should consist of gastric lavage and aspiration.

5.1 Pharmacodynamic properties

Ambroxol is a metabolic product of bromhexine and possesses mucokinetic (improvement in mucus transport) and secretolytic (liquifies secretions) properties. It promotes the removal of tenacious secretions in the respiratory tract and reduces mucostasis (arresting the secretion of mucus). The breakdown of acid mucopolysaccharide fibers makes the sputum thinner and less viscous and therefore more easily removed by coughing. Although sputum volume eventually decreases, its viscosity remains low for as long as treatment is maintained.

Terbutaline sulphate is an ethanolamine derivative with bronchodilating and tocolytic properties. It selectively binds to and activates β-2 -adrenergic receptors, leading to intracellular adenyl cyclase activation via a trimeric G protein and subsequent increase in cyclic cAMP production. Increased cAMP levels result in relaxation of bronchial and vascular smooth muscle mediated through the activation of protein kinase A (PKA), which phosphorylates proteins in control of muscle tone. cAMP also inhibits release of intracellular calcium ion, reduces calcium entry into cells and induces the sequestration of intracellular calcium. This helps in the relaxation of airway muscles. Terbutaline sulfate also increases mucociliary clearance and reduces release of inflammatory cell mediators.

Guaifenesin is a glyceryl guaiacolate with expectorant effects. It increases respiratory tract mucus secretions, acts as an irritant to gastric vagal receptors and recruits efferent parasympathetic reflexes that cause glandular exocytosis of a less viscous mucus mixture. This provokes cough which facilitates in flushing out tenacious, congealed mucopurulent material from obstructed small airways and lead to a temporary improvement in dyspnea or breathing. This agent reduces the viscosity of mucus secretion by reducing adhesiveness and surface tension as well as increasing hydration of mucus. Guaifenesin increases the efficiency of the mucociliary mechanism which is important in removing accumulated secretions from the upper and lower respiratory tract.

Guaifenesin is a glyceryl guaiacolate with expectorant effects. It increases respiratory tract mucus secretions, acts as an irritant to gastric vagal receptors and recruits efferent parasympathetic reflexes that cause glandular exocytosis of a less viscous mucus mixture. This provokes cough which facilitates in flushing out tenacious, congealed mucopurulent material from obstructed small airways and lead to a temporary improvement in dyspnea or breathing. This agent reduces the viscosity of mucus secretion by reducing adhesiveness and surface tension as well as increasing hydration of mucus. Guaifenesin increases the efficiency of the mucociliary mechanism which is important in removing accumulated secretions from the upper and lower respiratory tract.

5.2 Pharmacokinetic properties

5.3 Preclinical safety data

Not Available

6.1 Animal Toxicology or Pharmacology

No known animal toxicology data.

Soventus Syrup is a combination of Terbutaline sulphate, Ambroxol hydrochloride and Guaiphenesin. Terbutaline sulphate is a beta-adrenergic agonist bronchodilator available as syrup for oral administration.

Terbutaline sulphate is ±-alpha-[(tert-butylamino) methyl]-3,5-dihydroxybenzyl alcohol sulphate (2:1) (salt).

The empirical formula is (C12H19NO3)2H2SO4 and the structural formula is

Guaiphenesin, a member of methoxybenzenes is an expectorant. The physiologic effect of guaifenesin is by means of decreased respiratory secretion viscosity, and increased respiratory secretions.

Chemical Name: 3-(2-methoxyphenoxy)propane-1,2-diol

Molecular formula: C₁₀H₁₄O₄

Molecular Weight: 198.22 g/mol

Ambroxol hydrochloride is an aromatic amine. A metabolite of Bromhexine that stimulates mucociliary action and clears the air passages in the respiratory tract. It is usually administered as the hydrochloride.

Chemical Name: 4-[(2-amino-3,5-dibromophenyl)methylamino]cyclohexan-1-ol;hydrochloride Molecular Formula: C13H19Br2ClN2O Molecular Weight: 414.56 g/mol

8.1 List of excipients

Disodium Edetate, Sodium Benzoate, Sucralose, Glycerol, Propylene Glycol, Liquid Sorbitol (Non Crystallising), Hydroxyethyl Cellulose, Potassium Sorbate, Colour Tartrazine Supra Soluble , Flavour Ginger RS- 2, Flavour Honey RS 80008, Flavour Lemon RS , Sodium Citrate, Citric Acid Monohydrate.

8.2 Incompatibilities

Not Applicable

8.3 Shelf life

24 MONTHS

8.4 Special precautions for storage

Protect from light.

8.5 Nature and contents of container

1x100ml, PET Bottle

8.6 Special precautions for disposal and other handling

No special requirements for disposal.

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

• Take this medicine in the dose and duration as advised by your doctor.
• Check the label for directions before use.
• Measure it with a measuring cup and take it by mouth. Shake well before use.
• Soventus Syrup may be taken with or without food, but it is better to take it at a fixed time.
• It may cause dizziness and sleepiness. Do not drive or do anything that requires mental focus until you know how it affects you.
• If you are diabetic, monitor your blood glucose regularly while taking this medicine.
• Inform your doctor if you have a history of thyroid or heart disease.
• Stop taking Soventus Syrup and inform your doctor if your cough persists for more than 1 week, tends to recur, or is accompanied by a fever, rash or persistent headache.

18th Oct. 2023