Soventus DC Syrup

Levocloperastine Fendizoate Oral Suspension

Each 5 ml oral suspension contains:

Levocloperastine Fendizoate 35.4 mg (equivalent to 20 mg of Levocloperastine Hydrochloride)

Excipients q.s.

In a flavoured syrup base

Colour: Sunset Yellow FCF

Flavour: Mango

Oral suspension

20mg of Levocloperastine per 5ml

4.1 Therapeutic Indication

For the treatment of non-productive cough in adult patients

4.2 Posology and method of administration

Dose for Adults: 5 ml (20mg) three times daily.

4.3 Contraindications

• Known hypersensitivity to cloperastine or to any of the excipients.
• It should not be used in children under 2 years of age.
• Pregnant or breast-feeding women.
• Known hypersensitivity to antihistaminic agents.
• Patients receiving concomitant treatment with MAO inhibitors.
• Patients with hereditary fructose intolerance, glucose or galactose malabsorption, or sucrose isomaltase deficiency.
• Consumption of Alcohol is strictly contraindicated with Levocloperastine suspension.

4.4 Special warnings and precautions for use

Caution should be observed while prescribing Levocloperastine Fendizoate suspension to adults and children with hypertension, cardiovascular disease, uncontrolled diabetes mellitus, hyperthyroidism, seizures or in patients who are unusually hypersensitive to sympathomimetic amines.

Due to its mild anticholinergic activity, cloperastine should be administered with caution in patients with intraocular hypertension, narrow-angle glaucoma, prostatic hypertrophy, urine retention, hypertension, cardiac arrhythmia, myasthenia gravis, stenosing peptic ulcer or bowel obstruction affecting the oesophagus, intestine or bladder.

Persistent cough.

Caution is recommended in patients with chronic cough such as smoker's cough, pulmonary emphysema or asthma, as it inhibits the cough reflex and could therefore alter expectoration and increase airway resistance.

4.5 Drugs interactions

Levocloperastine Fendizoate suspension should not be concomitantly prescribed with sedatives or tranquilizers. Similarly, other antihistamine drugs should not be prescribed concomitantly.

As it has some antihistaminic activity, cloperastine can enhance the sedative effect of CNS

depressors such as anxiolytics, antipsychotic drugs, barbiturates, hypnotics, narcotics, sedatives, tranquilizers, some analgesics and alcohol.

Also due to this activity, cloperastine, antihistaminic agents and anticholinergic drugs (anti-parkinson's drugs, tricyclic antidepressants, MAO inhibitors, neuroleptic agents) can reciprocally increase their effects.

Expectorants and mucolytic drugs: Inhibition of the cough reflex could give rise to pulmonary obstruction in case of elevated volume or fluidity of bronchial secretions.

4.6 Use in special populations

Animal studies have not shown any evidence of damage to the foetus. In humans, its safety for use in pregnancy and lactation has not been established. Cloperastine should therefore not be used during pregnancy unless a doctor believes that the treatment's potential benefit for the mother exceeds all risks for the developing foetus or infant. As it is unknown whether the drug is excreted in human milk, its use during lactation is not recommended.

4.7 Effects on ability to drive and use machines

Levocloperastine can cause drowsiness, so caution is recommended when driving or using dangerous machinery. If drowsiness is noted at normal doses of cloperastine, do not drive or handle dangerous machinery.

4.8 Undesirable effects

Levocloperastine can produce minor and transient adverse reactions such as Dry mouth, GI effects, exhaustion, fainting, somnolence, sedation, clouding of consciousness, numbness, dizziness, headache, palpitations and allergic reaction.

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: https://www.zuventus.co.in/drug-safety-reporting

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

4.9 Overdose

No cases of overdose have been reported.

Intoxication can occur after ingesting quantities that are much higher than the therapeutic doses.

Overdose could cause symptoms such as drowsiness, anticholinergic symptoms, hallucinations, excitation, ataxia, lack of motor coordination and convulsions. In case of overdose, symptomatic and maintenance treatment is recommended. Vomiting should be induced or stomach lavage should be performed with saline serum.

5.1 Mechanism of action

Levocloperastine is a cough suppressant. Levocloperastine is a novel antitussive agent having dual mechanism of action, it acts on both the central bulbar cough centre and on peripheral receptors in the tracheobronchial tree.

As demonstrated in a number of animal models, Levocloperastine acts at the CNS level by inhibiting the bulbar cough centre. In addition to this primary mechanism of action, peripheral effects related to its antihistamine, anti-serotonergic and smooth muscle-relaxant properties also contribute to the overall efficacy of Levocloperastine in the treatment of cough, bronchospasm and related symptoms.

5.2 Pharmacodynamic properties

The therapeutic efficacy of DL-cloperastine in reducing the intensity and frequency of cough is well established, with efficacy similar to that of codeine and superior to that of dextromethorphan.

In clinical trials, levocloperastine had a faster onset of action and produced greater reductions in the intensity and frequency of cough compared with DL-cloperastine, codeine and levodropropizine.

The antitussive effects (reduction in intensity and frequency of cough) of levocloperastine were observed after the first day of treatment in patients of all ages. In children, levocloperastine reduced night-time awakenings and irritability; in adults, it was also effective in treating ACE inhibitor cough.

Levocloperastine was generally well tolerated. There was no evidence of clinically significant central adverse events, whereas drowsiness, dry mouth and nausea were reported with comparator agents (levodropropizine, codeine, DL-cloperastine).

Levocloperastine represents an effective alternative to currently used antitussive agents with the added advantage of faster onset of action and improved tolerability in all patient groups.

5.3 Pharmacokinetic properties

The product is absorbed from the gastrointestinal tract and mostly excreted in urine.

After administration of 10ml of oral suspension containing levocloperastine fendizoate, peak plasma concentrations of 10 μg/L were reached 2 to 4 hours after administration, with a lag-time of approximately 45 minutes before detection of the drug in the bloodstream, suggesting a gradual and protracted absorption from the intestine.

Oral bioavailability was >40% based on the ratio of area under the plasma concentrationtime curve (AUC) of unmodified drug calculated after oral and intravenous administration, while substantially higher values were obtained in excretion studies conducted with radiolabelling techniques (14C).

The half-life of levocloperastine is 0.80 hours (distribution half-life), 1.68 hours (elimination half-life), and 6.58 hours (terminal elimination half-life). The volumes of distribution (Vd) were found to be 80 ml/kg (terminal) and 57 ml/kg (at steady state), and the protein-bound fraction was high. Total body clearance was 7.5 L/hour.

In preclinical studies, levocloperastine demonstrated antitussive effects similar to those observed with codeine. In acute and repeated-dose toxicity studies, levocloperastine was well tolerated in rodents and dogs, with no clinically significant cardiovascular or gastrointestinal adverse events. The pharmacokinetic behaviour of levocloperastine, best described by a two-compartmental model with absorption phase, is similar to that of the racemic compound DL-cloperastine.

Administration of levocloperastine 1 to 9 mg/kg to guinea pigs dose-dependently inhibited cough induced by citric acid or ammonia vapour, showing an antitussive effect similar to that of codeine. The 50% effective dose (ED50) values for levocloperastine vs codeine were, respectively, 2.6 vs 3.6 mg/kg in the citric acid test, and 2.9 vs 3.1 mg/kg in the ammonia test. Activities of levocloperastine, DL-cloperastine and dextrocloperastine were similar in the citric acid-induced cough model, suggesting that the antitussive efficacy of cloperastine compounds is independent of their enantiomeric structure.

Levocloperastine (as well as dextrocloperastine and DL-cloperastine) exhibited spasmolytic activity in guinea-pigs via its antihistamine properties in vitro (inhibition of histamine-induced contraction in isolated tracheal rings) and in vivo (dose-dependent inhibition of bronchospasm induced by histamine aerosol). Similarly, serotonin-antagonist activity was demonstrated in vitro.

Unlike opioid antitussives, such as codeine, the CNS activity of levocloperastine is highly selective for the cough centre, thus avoiding central adverse effects such as sedation. This attenuation of CNS adverse effects is a differential feature of levocloperastine and is related to its specific stereoisomeric properties, since dextrocloperastine and DL-cloperastine, administered orally or intraperitoneally, induced sedative and stimulant effects of much greater magnitude (by approximately 50%) in tests of CNS function in rodents.

Both acute and repeated-dose toxicity studies found levocloperastine to be well tolerated in rodents and dogs. The 50% lethal dose (LD50) value of levocloperastine could not be calculated because the oral/intraperitoneal doses tested (up to 2000 mg/kg) did not cause death in any of the experimental animals. By comparison, the enantiomer dextrocloperastine was more toxic, with LD50 values of 466 mg/kg in the mouse and 1226 mg/kg in the rat after oral administration, and 155 and 177 mg/kg, respectively, after intraperitoneal administration.

In chronic toxicity studies, levocloperastine at dosages up to 75 mg/kg/day (corresponding to 45 times the therapeutic daily dosage in humans) for 6 months was considered 'safe' in rats and dogs. Mild adverse events (including vomiting, anorexia and transient biochemical/ histological signs of liver and kidney dysfunction) were observed only with dosages of 250 mg/kg/day following 6 months' treatment. Levocloperastine did not show mutagenic or carcinogenic effects in specific in vitro and in vivo studies.

Levocloperastine, the levorotatory isomer of DLcloperastine, is a centrally active, non-opioid antitussive agent with a chemical structure and pharmacological profile distinct from that of the racemate. It is devoid of central antinociceptive activities, does not cause addiction or dependence phenomena, and does not interfere with cardiovascular or gastrointestinal functions.

Cloperastine fendizoate is a N-oxyethylpiperidine. It is functionally related to a benzoate.

Structure of Cloperastine fendizoate

Molecular Formula: C₄₀H₃₈ClNO₅

Molecular Weight: 648.2 g/mol

8.1 Incompatibilities

None known.

8.2 Shelf-life

Refer on the pack.

8.3 Packaging information

A bottle of 100 ml.

8.4 Storage and handing instructions

Store in a cool place. Protect from light. Keep out of reach of children. Shake well before each use.

• You have been prescribed Soventus-DC Oral Suspension for the symptomatic relief of dry cough.
• It is usually taken for a short time, until the symptoms clear up.
• Measure the syrup with a special dose-measuring spoon or cup, not a regular table spoon.
• Drink extra fluids to help loosen the congestion and lubricate your throat while you are taking this medication.
• It should not be administered to patients with chronic cough or where cough is accompanied by excessive secretions.
• Inform your doctor if your cough lasts more than 7 days, comes back, or occurs with fever, rash or headache. These could be signs of a serious condition.

19-09-2024