Name of Medicinal Product: RESWAS (Levodropropizine and Chlorpheniramine Maleate Syrup) Dosage Form and Strength: Each 5 mL Syrup contains: Levodropropizine IP 30 mg, Chlorpheniramine Maleate IP 2 mg, Sugar free base q.s., Colour: Quinoline Yellow WS. Therapeutic Indications: Fixed-dose combination of Levodropropizine and Chlorpheniramine maleate is indicated for the treatment of non-productive cough. Posology and Administration: Adults - 10 mL (two teaspoonful) three times a day. Children: 10-20 kg body weight: 3 ml three times a day, 20-30 kg body weight: 5 ml three times a day, 40 kg+ body weight: 10 ml three times a day. Contraindications: Hypersensitivity to Levodropropizine or Chlorpheniramine maleate or structurally related compounds, conditions associated with bronchorrhea and impaired mucociliary clearance (Kartagener's syndrome, ciliary dyskinesia), narrow-angle glaucoma; bladder neck obstruction; symptomatic prostate hypertrophy; during acute asthmatic attacks; stenosing peptic ulcer; pyloroduodenal obstruction. Pregnancy and lactation. Special warnings and precautions for use: Chlorpheniramine is contraindicated in patients who have had treatment with monoamine Oxidase Inhibitors (MAOl's) within the last 14 days as the anticholinergic properties of Chlorpheniramine are intensified by MAOl's. Chlorpheniramine has an anticholinergic effect and should be used with caution in patients with epilepsy, raised intra-ocular pressure including glaucoma, prostatic hypertrophy, severe hypertension, cardiovascular disease, bronchitis, bronchiectasis, asthma, hepatic impairment. Children and the elderly patients are more likely to experience the neurological anticholinergic effects and paradoxical excitation (e.g., increased energy, restlessness, nervousness). The effects of alcohol may be increased and therefore should be avoided. Chlorpheniramine should not be used with other antihistamine containing products such as antihistamine containing cough and cold medicines. The observation that the pharmacokinetic profiles of Levodropropizine are not markedly altered in old subjects suggests that dose adjustments or modifications of the intervals between administrations may not be required in elderly persons. In any case, being evident that the sensitivity to several drugs is altered in old patients, special caution is necessary when administering Levodropropizine to old patients.The effect of the administration of the product to children younger than 24 months has not been studied completely and in any case the drug should be used with caution in such patients. Caution is recommended in patients with severe renal failure (creatinine clearance < 35 ml/min). Caution is also recommended for the concomitant intake of sedative drugs in particularly sensitive subjects. The drug contains 4g of sucrose per dose (10 ml): patients with rare hereditary problems of fructose intolerance, glucose-galactose malabsorption or sucrose isomaltase insufficiency should not take this medicine. This should be taken into account in patients with diabetes mellitus. The drug contains methyl-para-hydroxy benzoate and propyl-para-hydroxy benzoate that are known for the possibility of causing urticaria. Para-hydroxy benzoates may generally cause delayed reactions such as contact dermatitis and rarely immediate reactions with urticaria and bronchospasm. Anti-cough drugs are symptomatic and must be used only when waiting for the diagnosis of the triggering cause and or the effect of the therapy of the underlying pathology. In the absence of information about the effect of the intake of food on drug absorption, it is advisable to take the drug away from meals. Drug Interactions: Alcoholic drinks and certain other central nervous system depressants such as anxiolytics or hypnotics can potentiate the sedative effects of Chlorpheniramine. Phenytoin metabolism is inhibited by Chlorpheniramine and this can cause phenytoin toxicity. The anticholinergic effects of Chlorpheniramine are intensified by the use of other anticholinergic drugs such as atropine, tricyclic antidepressants and MAOI's Animal pharmacology studies have demonstrated that Levodropropizine does not potentiate the pharmacological effect of substances acting on the central nervous system (eg. benzodiazepines, alcohol, phenytoin, imipramine). In animals, the product does not modify the activity of oral anticoagulants, such as warfarin, nor does it interfere with the hypoglycaemic effect of insulin. In human pharmacology studies, the combination with benzodiazepines does not modify the EEG-pattern. Caution is necessary in case of the concomitant intake of sedative drugs in particularly sensitive subjects. Clinical studies do not show any interaction with drugs for the treatment of bronchopulmonary pathologies, such as beta-2-agonists, methylxantines and derivatives, corticosteroids, antibiotics, mucoregulators and antihistamines. Use in Special Populations (such as pregnant women, lactating women, paediatric patients, geriatric patients etc): Do not use in pregnancy unless the physician considers it essential. Small amounts of antihistamines are excreted in breast milk. Use by nursing mothers is not recommended because of the risks of adverse effects in the infant. Antihistamines may inhibit lactation. Effects on Ability to Drive and Use Machines: As with all antihistamines, dizziness, drowsiness, blurred vision and psychomotor impairment may occur. Extreme caution should be advised when driving or operating machinery. Undesirable Effects: Chlorpheniramine maleate: Adverse reactions which have been observed in clinical trials and which are considered to be common (occurring in ≥1% to < 1/10,000) have been observed: Skin and subcutaneous tissue disorders: urticaria, erythema, exanthema, itching, angioedema, skin reactions. Gastrointestinal disorders: gastric and abdominal pain, nausea, vomiting, diarhoea. General disorders: allergic and anaphylactoid reactions, general malaise. Neurological disorders: dizziness, vertigo, tremor, paresthesia. Cardiovascular disorders: palpitations, tachycardia, hypotension. Psychiatric disorders: irritability, sleepiness, depersonalization. Respiratory disorders: dyspnoea, cough, edema of the respiratory tract. Musculoskeletal, connective tissue & bone disorders: asthenia and weakness of lower limbs. The drug contains methyl-para-hydroxy benzoate and propyl-para-hydroxybenzoate, known for the possibility of causing urtic rarely immediate reactions with urticaria and bronchospasm. Overdose: Symptoms and signs: The estimated lethal dose of Chlorpheniramine is 25 - 50mg/kg body weight. Symptoms and signs include sedation, paradoxical excitation of the CNS, toxic psychosis, convulsions, apnoea, anticholinergic effects, dystonic reactions and cardiovascular collapse and arrhythmias. Treatment: Symptomatic and supportive measures giving special attention to cardiac, respiratory, renal and hepatic functions and fluid and electrolyte balance. If overdose occurs by the oral route treat with activated charcoal should be considered, provided there are no contraindications for use and the overdose has been taken recently (within an hour of ingestion). Treat hypotension and arrhythmias vigorously. CNS convulsions may be treated with i.v. diazepam. Haemoperfusion may be used in severe cases. Levodropropizine: No significant side effects have been reported after the administration of a single dose of up to 240 mg of the drug and of up to 120 mg t.i.d. for 8 consecutive days. Only one case of overdose is known in a 3-year-old child treated with a 360 mg daily dose of Levodropropizine. The patient showed severe abdominal pain and vomiting that solved without consequences. In case of overdose with evident clinical signs, immediately set up a symptomatic therapy and adopt the usual emergency measures (gastric lavage, active coal, parenteral liquid, etc.), if needed. PHARMACOLOGICAL PROPERTIES: Mechanism of action: Mechanism of action of Chlorpheniramine ties to the histamine H1 receptor. These obstructs the activity of endogenous histamine, which in this way prompts brief alleviation of the negative indications expedited by histamine. Levodropropizine acts through a mainly peripheral tracheobronchial antitussive effect by inhibition of vagal C fibre and its sensor neuro peptide. Pharmacodynamic properties: Levodropropizine: Evidence has been provided that the antitussive effect is produced at least in part at peripheral levels through inhibition of the afferent pathways involved in the generation of the cough reflex. It is also effective in protecting against bronchospasm induced by histamine, serotonin and bradykinin. Chlorpheniramine maleate: Chlorpheniramine, an H1-receptor blocking anti histamine, relieves histamine induced allergic edema of respiratory mucosa. Pharmacokinetic properties: Levodropropizine is well absorbed after oral administration; the apparent steady-state volume of distribution is approximately 3.4 L/kg in adults and 11-14% is bound to plasma proteins. The drug is metabolized in the liver and is excreted in the urine. In patients with normal renal and hepatic function, the terminal serum half-life of the drug is 2 hours. Chlorpheniramine is well absorbed after oral administration; the apparent steady-state volume of distribution is 2.5-3.2L/kg in adults. It is approximately 70% bound to plasma proteins. The drug is metabolized in the liver and is excreted in the urine. In patients with normal renal and hepatic function, the terminal serum half-life of the drug ranges from 13.2-43 hours. NONCLINICAL PROPERTIES: Animal Toxicology or Pharmacology: Chlorpheniramine: 2-year gavage studies, there was no evidence of carcinogenicity* for F344/Nrats or B6C3F1 mice of either sex administered Chlorpheniramine maleate in deionized water, 5 days per week for 2 years. Chlorpheniramine maleate had a proliferative effect on the thyroid gland of female mice, as shown by the increased incidences of follicular cell cysts and hyperplasia in both low dose and high dose groups. Levodropropizine: Oral acute toxicity is 886.5 mg/kg, 1287 mg/kg and 2492 mg/kg in rats, mice and cavies, respectively. The therapeutic index in the cavy, calculated as DL50/DE50 ratio after oral administration is included between 16 and 53 according to the experimental model of cough induction. Toxicity tests for repeated oral administrations (4-26 weeks) have shown that the daily dose without toxic effect corresponds to 24 mg/kg. Description: Chlorpheniramine is a histamine H1 antagonist used been used in veterinary applications. One of the most widely used of the classical antihistaminic, it generally causes less drowsiness and sedation than promethazine. In allergic reactions, hay fever, rhinitis, urticaria, and asthma. Chemically it is [3-(4- chlorophenyl)-3(pyridin-2-yl) propyl] dimethylamine. Molecular formula is (C H ClN ). Levodropropizine Molecular formula: C13H20N2O2. Chemical Name: (-) - (S)-3- (4-Phenyl-1-piperazinyl)-1,2propanediol. Mechanism of action of Levodropropizine is the levo- rotatory(S)enantiomer of dropropizine, a racemic non-opiate antitussive agent. Pharmaceutical particulars: Incompatibilities - Not applicable. Packaging information - 120ml and 50ml bottle. Shelf-life - 24 Months. Storage and handing instructions: Store in a cool place, protected from light. Keep out of reach of children. Patient Counselling Information: Reswas syrup is used to treat cough. It is a combination of chlorpheniramine and levodropropizine. Both these medicines provide relief for dry cough. Chlorpheniramine is an antiallergic medicine that relieves the symptoms of allergies like irritation in the throat and nose, sneezing, running nose, etc. While levodropropizine is a cough suppressant. Sleepiness is one of the common side effects of Reswas syrup. Avoid driving or handling machinery after taking this syrup. Follow your doctor's instructions or those on the label when consuming the syrup. Shake thoroughly before using. Never take more dose than what is advised. Details of manufacturer: Manufactured in India by: Dr. Reddy's Laboratories Limited, (FTO-12), Plot No. 57, Village Kunjhal, P.O. Barotiwala, Tehsil Baddi, Distt. Solan (H.P.) - 174103. Details of permission or licence number with date M.L. MNB/05/107, 21.08.2023 Date of revision September 2023