Levodropropizine & Chlorpheniramine Maleate syrup
Each 5 ml contains:
Levodropropizine IP……………………………….30 mg
Chlorpheniramine Maleate IP……………………..2 mg
Flavoured Base
Colour: Ponceau 4R Supra
Syrup Levodropropizine & Chlorpheniramine (30 mg+2 mg)
For the treatment of non-productive cough.
Adults and children aged 12 years and above
10 ml syrup three times a day with an interval of at least 6 hours
Children aged 6-12 years
5 ml syrup three times a day with an interval of at least 6 hours
Children aged 2-6 years
2.5 ml syrup three times a day with an interval of at least 6 hours.
(The usual dose for levodropropizine is 1 mg to 2 mg per kg of bodyweight)
Patients with known or suspected hypersensitivity to the drug or any of the excipients, during pregnancy and lactation, in patients with severe hepatic failure, in cases such as kartagener's syndrome associated with bronchorrhea and decrease in mucociliary clearance mechanism or ciliary dyskinesia.
It is not recommended to use under 2 years.
It is contraindicated in patients using monoamine oxidase inhibitor (MAOI) within the last 14 days.
It should be used with caution considering the benefit-risk ratio in cases of the severe renal failure (creatinine clearance <35 ml/min.). Cough medicines provide symptomatic treatment and should not be used until the treatment of the underlying pathology is provided and/or precipitating cause is detected. Therefore, Levodropropizine & Chlorpheniramine should not be used in long-term treatments. If there is no significant result after a short-term treatment, the doctor should be consulted.
Do not exceed the recommended dosage. Antihistamines may cause excitability, especially in children. At doses higher than the recommended dose, nervousness, dizziness or sleeplessness may occur.
Chlorpheniramine maleate should be given with caution to patients with epilepsy, severe cardiovascular disorders, liver disorders, glaucoma, urinary retention, prostatic enlargement, pyloroduodenal obstruction, asthma, bronchitis, bronchiectasis, thyrotoxicosis and severe hypertension.
Special care should be taken when using chlorpheniramine maleate in children and the elderly as they are more prone to developing neurological anticholinergic effects.
Warning
May cause drowsiness. If affected, do not drive or operate machinery. Avoid alcoholic drinks.
Although most antihistamines should be avoided by patients with porphyria, chlorpheniramine maleate has been used and is thought to be safe.
As the pharmacokinetic profile of Levodropropizine has not change significantly in elderly patients, dose adjustment or change in time between applications may not be necessary in elderly patients. However, it is clearly known that the sensitivities of elderly patients to many medicines have changed; special attention must be paid when levodropropizin is administered in this group. It should be avoided in the following cases:
Arrhythmia
Epilepsy
Severe hypertension
Cardiovascular disease
Prostate hypertrophy
Liver failure
Glaucoma
Bronchitis, bronchiectasis, asthma
Overactive thyroid dysfunction.
Children and the elderly are more susceptible to neurological anticholinergic side effects and paradoxical excitation (such as increased energy, restlessness, irritability).
The sedative effect increases when alcohol and classical antihistamines (sedative) are used together. Sedative interactions are more limited with non-sedated antihistamines. Topically applied antihistamines (including those administered by inhalation) do not show this type of interaction.
Some other central nervous system depressants such as anxiolytics or hypnotics may potentiate chlorpheniramine maleate and its sedative effects.
Phenytoin metabolism is inhibited by chlorpheniramine maleate, which can cause phenytoin toxicity.
The anticholinergic effects of chlorpheniramine maleate are exacerbated by the use of other anticholinergic drugs such as atropine, tricyclic antidepressants and MAOI.
Clinical studies have not revealed interactions following simultaneous administration of medicines used to treat bronchopulmonary diseases. Patients sensitive to sedative medication should be careful when using these medicines combined with levodropropizine.
Pregnancy
Levodropropizine may cross the placenta and could be harmful to the unborn baby, while the safety of chlorpheniramine in pregnancy is not established and it may cause adverse effects in newborns, especially if used in late pregnancy. Therefore, Tusvia Plus syrup is contraindicated during pregnancy.
Lactation
Levodropropizine and chlorpheniramine pass into breast milk and may affect the breastfed infant. Adverse effects such as sleepiness, reduced muscle tone, and vomiting have been reported in infants exposed to levodropropizine, while chlorpheniramine may also reduce milk production. Therefore, Tusvia Plus syrup is contra-indicated during breast feeding.
Pediatric Patients
It is not recommended to use in children under 2 years.
Geriatric Patients
The dose should be determined with caution in elderly patients.
Drowsiness, dizziness and blurred vision which are the most serious anticholinergic properties of chlorpheniramine may prevent the patient's ability to drive and use machines. It can also cause psychomotor impairment. Very caution should be exercised during the drive and use machines. The patient should be informed about this possibility.
Blood and lymphatic system disorders
Unknown: Hemolytic anemia, blood dyscrasia.
Immune system disorders
Very rare: Hypersensitivity reactions.
Unknown: Allergic reaction, angioedema, anaphylactic reactions.
Metabolism and nutritional disorders
Unknown: Anorexia.
Psychiatric disorders
Very rare: Nervousness, drowsiness, loss of self.
Unknown: Insomnia, Increased excitability*, anxiety, confusion*, irritability*, nightmares*, depression*.
Nervous system disorders
Very common: Sedation, somnolence.
Common: Distractibility, abnormal coordination, dizziness.
Very rare: Fatigue-asthenia, weakness, lethargy, headache, vertigo, tremor, paresthesia.
Tonic-clonic convulsions and petitmal attacks were reported in one case.
Eye disorders
Mydriasis was reported in one case and bilateral loss of vision was reported in another case. In both cases the reaction were resolved after discontinuation of the drug
Unknown: Blurred vision.
Ear and inner ear disorders
Unknown: Tinnitus.
Cardiac disorders
Very rare: Palpitation, tachycardia.
Unknown: Arrhythmia.
Vascular disorders
Very rare: Hypotension.
Atrial bigeminal beat was reported in one case.
Respiratory, thoracic and mediastinal disorders
Unknown: Darkening of bronchial secretions.
Respiratory, thoracic and mediastinal disorders
Very rare: Dyspnea, cough, edema in the respiratory tract.
Unknown: Darkening of bronchial secretions.
Gastrointestinal diseases
Common: Constipation, vomiting, dry mouth.
Very rare: Nausea, heartburn and pain, dyspepsia, diarrhea. Glossitis and aphthous were reported in two cases.
Cholestatic hepatitis was reported in one case and hypoglycemic coma was observed in elderly patients using oral hypoglycemics at the same time.
Hepatobiliary system disorders
Unknown: Hepatitis, jaundice.
Skin and subcutaneous tissue disorders
Very rare: Allergic skin rash, urticaria, erythema, exanthema, itching, angioedema.
Unknown: Exfoliative dermatitis, redness, photosensitivity.
A case of epidermolysis resulting in death has also been reported.
Musculoskeletal and Connective Tissue Disorders
Very rare: Asthenia and weakness in lower extremities.
Unknown: Muscle twitching and muscle weakness.
Kidney and Urinary Tract Disorders
Rare: Urinary retention.
General disorders and administration site conditions
Common: Exhaustion.
Very rare: Allergic and anaphylactic reactions. General malaise. Edema, syncope and asthenia have been reported rarely.
Unknown: Chest pain and tightness.
* Children and the elderly are more susceptible to neurological anticholinergic side effects and paradoxical excitation (such as increased energy, restlessness, irritability).
Reporting of Suspected Adverse Reactions
Reporting suspected adverse reactions after authorization 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@zorvia.com
By reporting side effects, you can help provide more information on the safety of this medicine.
There is limited experience of overdose. Initiate general symptomatic and supportive measures in all cases of overdosages where necessary.
Levodropropizine inhibit the cough reflex by acting on the peripheral receptors and their afferent conductors. Levodropropizine inhibits the C-fibers of the vagus nerves and modulate the sensory neuropeptides production in the respiratory tract, involved in the cough reflex. Levodropropizine has a dose-dependent and short-term local anaesthetic activity. It also has a mild analgesic and an antihistaminic action.
In allergic reactions an allergen interacts with and cross-links surface IgE antibodies on mast cells and basophils. Once the mast cell-antibody-antigen complex is formed, a complex series of events occurs that eventually leads to cell-degranulation and the release of histamine (and other chemical mediators) from the mast cell or basophil. Once released, histamine can react with local or widespread tissues through histamine receptors. Histamine, acting on H1-receptors, produces pruritis, vasodilatation, hypotension, flushing, headache, tachycardia, and bronchoconstriction. Histamine also increases vascular permeability and potentiates pain. Chlorpheniramine maleate binds to the histamine H1 receptor. This blocks the action of endogenous histamine, which subsequently leads to temporary relief of the negative symptoms brought on by histamine.
Levodropropizine is a peripherally acting antitussive working at tracheobronchial level. The peripheral action has been demonstrated in animal studies. Its mechanism provides this drug antitussive properties against cough associated to different lung pathologies, but without relevant central side effects. Levodropropizine inhibits bronchospasms induced by histamine, serotonin and bradykinin. Levodropropizine exerts its antitussive effect through an inhibitory action at the level of the airway sensory nerves involving modulation of sensitive C-fibers and release of neuropeptides.
Chlorpheniramine maleate is a histamine H1 antagonist of the alkylamine class. It competes with histamine for the normal H1-receptor sites on effector cells of the gastrointestinal tract, blood vessels and respiratory tract. It provides effective, temporary relief of sneezing, watery and itchy eyes, and runny nose due to hay fever and other upper respiratory allergies.
Levodropropizine
Absorption: Bioavailability of levodropropizine was found to be greater than 75% after oral administration. Plasma protein binding rate was lower (11-14%).
Distribution: In human, oral levodropropizine was rapidly absorbed and distributed throughout the body.
Biotransformation: There is no data about the specific site of metabolism of levodropropizine either in the liver or in other sites.
Elimination: Plasma elimination half-life of levodropropizine is approximately 1-2 hours. Its excretion is mainly in the urine. Elimination of the active substance is either in the form of both unchanged and conjugated or free levodropropizine or in conjugated p-hydroxy-levodropropizine metabolites. Elimination of the active substance and its metabolites in 48 hours approximates to 35% of the administered dose. Results of the repeat dose studies have demonstrated that 8 days of treatment (3 times a day) did not alter the elimination characteristics of the drug and therefore accumulation or metabolic auto-induction were unlikely.
Chlorpheniramine maleate
Absorption: Chlorphenamine maleate is absorbed relatively slowly from the gastrointestinal tract, peak plasma concentrations occurring about 2.5 to 6 hours after oral doses. Bioavailability is low, values of 25 to 50% having been reported.
Distribution: Chlorphenamine is widely distributed in the body and enters the CNS.
Biotransformation: Chlorphenamine appears to undergo considerable first-pass metabolism. About 70% of chlorphenamine in the circulation is bound to plasma proteins. There is wide inter individual variation in the pharmacokinetics of chlorphenamine; values ranging from 2 to 43 hours have been reported for the half-life. Chlorphenamine maleate is extensively metabolised. Metabolites include desmethyl- and didesmethylchlorphenamine.
Elimination: Unchanged drug and metabolites are excreted primarily in the urine; excretion is dependent on urinary pH and flow rate. Only trace amounts have been found in the faeces. Duration of action of 4 to 6 hours has been reported; this is shorter than may be predicted from pharmacokinetic parameters. More rapid and extensive absorption, faster clearance, and a shorter half-life have been reported in children.
Levodropropizine
Oral acute toxicity is 886.5 mg/kg, 1287 mg/kg and 2492 mg/kg in rats, mice and guinea pigs, respectively. The therapeutic index in the guinea pigs, calculated as LD50/ED50 ratio after oral administration is included between 16 and 53 according to the experimental model of cough induction. Toxicity tests for repeated oral administrations have shown that the daily dose without toxic effect corresponds to 24 mg/kg.
Chlorpheniramine Maleate
The antihistaminic potency of chlorpheniramine is confined mainly to its (+)-isomer. The racemate is similarly or slightly more toxic because of the contribution of (-)-isomer. The toxicity may, therefore, be non- specific, perhaps attributable to local anaesthetic action and the toxic effects (excitation/sedation, coma, convulsions and death) resemble those of other classic H1antihistamines. Toxic doses may cause hypotension attributable to myocardial depression, an effect which is clearer with the (-)-isomer.
The experimental data on the carcinogenicity and mutagenicity of chlorpheniramine indicate lack of these adverse effects, but the racemate and the (+)-isomer have shown some embryotoxicity in fertility tests.
Effective antihistaminic concentrations of chlorpheniramine in vitro are about 1–10 μg/L and oral doses of 0.2–1 mg/kg antagonise histamine-induced bronchospasm in guinea pigs.
TUSVIA PLUS Syrup is a combination of levodropropizine and chlorpheniramine maleate. Levodropropizine has a peripheral tracheobronchial antitussive effect. It has an inhibitory impact on the C-fibers and inhibits neuropeptide secretion. Levodropropizine combined with chlorpheniramine maleate (an antihistamine) helps treat non-productive cough.
Not applicable
Refer on pack
120 ml Bottle
Store at a temperature not exceeding 30°C. Protect from light.