Maxtra-P DS Syrup

Paracetamol, Phenylephrine Hydrochloride & Chlorpheniramine Maleate Syrup

Each 5 ml contains :

Paracetamol IP 250 mg

Phenylephrine Hydrochloride IP 5 mg

Chlorpheniramine Maleate IP 2 mg

Excipients q.s.

Colour : Sunset Yellow FCF

In a flavoured syrup base

Syrup, Paracetamol 250 mg, Phenylephrine 5 mg, Chlorpheniramine 2 mg

4.1 Therapeutic Indication

For the treatment of common cold and cough associated with fever

4.2 Posology and method of administration

2 to 5 years of age: 2.5 ml every 4 to 6 hours

6 to 11 years of age: 5 ml every 4 to 6 hours

≥12 years of age: 10 ml every 4 to 6 hours

Or as directed by physician

Method of administration: Oral

4.3 Contraindications

• Hypersensitivity to the active substances or to any of the excipients

• Concomitant use of other sympathomimetic decongestants

• Pheochromocytoma

• Closed angle glaucoma

• An enlargement of the prostate gland

• Hypertensive patients or those who are taking, or have taken in the last two weeks, monoamine oxidase inhibitors, tricyclic antidepressants or beta-blockers

• Hepatic or renal impairment, diabetes, hyperthyroidism and cardiovascular disease

4.4 Special warnings and precautions for use

• Use with caution in patients with Raynaud's phenomenon or diabetes mellitus.

• This medicine 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.

• Care is advised in the administration of paracetamol to patients with severe renal or severe hepatic impairment. The hazard of overdose is greater in those with non-cirrhotic alcoholic liver disease. Patients should be advised not to take other paracetamol-containing products concurrently.

• Special care should be taken when using chlorpheniramine maleate in children and the elderly as they are more prone to developing neurological anticholinergic effects.

• Taking more than daily dose may cause serious liver damage or allergic reactions (eg. Swelling of the face, mouth and throat, difficulty in breathing, itching or rash) Paracetamol, Phenylephrine Hydrochloride & Chlorpheniramine Maleate Syrup

4.5 Drugs interactions

• The anticoagulant effect of warfarin and other coumarins may be enhanced by prolonged regular use of paracetamol with increased risk of bleeding; occasional doses have no significant effect.

• The hepato-toxicity of paracetamol may be potentiated by excessive intake of alcohol.

• The speed of absorption of paracetamol may be increased by metoclopramide or domperidone and absorption reduced by colestyramine.

• Phenylephrine may adversely interact with other sympathomimetics, vasodilators and beta blockers.

• Sympathomimetic-containing products should be used with great care in patients receiving phenothiazines or tricylic antidepressants.

• Sympathomimetic-containing products should be used with caution in patients receiving digitalis, beta-adrenergic blockers, guanethidine, reserpine, methyldopa or anti-hypertensive agents.

• Concurrent use with halogenated anaesthetic agents such as chloroform, cyclopropane, halothane, enflurane or isoflurane may provoke or worsen ventricular arrhythmias.

• This medicine may enhance the sedative effects of alcohol, hypnotics, anxiolytics, sedatives, opioid analgesics and neuroleptics.

• The antimuscarinic effects of chlorpheniramine are enhanced by other antimuscarinic drugs and both antimuscarinic and sedative effects are enhanced by monoamine oxidase inhibitors and tricyclic antidepressant.

4.6 Use in special populations

Pregnancy and lactation There are no adequate controlled studies of chlorpheniramine in pregnant women, Phenylephrine may reduce placental perfusion and this medicine should therefore not be used during pregnancy. Chlorpheniramine may be secreted in breast milk and its use is not recommended in nursing mothers because of the risk of adverse effects, such as unusual excitement or irritability in infants. Chlorpheniramine may also inhibit lactation.

4.7 Effects on ability to drive and use machines

Chlorpheniramine may cause blurred vision, dizzines s, drowsiness and interfere with human performance and therefore may seriously influence the ability to drive and operate machinery.

4.8 Undesirable effects

• Adverse effects of paracetamol are rare but hypersensitivity including skin rashes and Fixed drug eruption (FDE) may occur. There have been reports of blood dyscrasias including thrombocytopenia and agranulocytosis, but these were not necessarily causally related to paracetamol.

• Phenylephrine hydrochloride may elevate blood pressure with headache, vomiting and rarely palpitations, tachycardia or reflex bradycardia, tingling and coolness of the skin. There have been rare reports of allergic reactions.

• Chlorpheniramine may cause drowsiness, which may progress to deep sleep, headache, dizziness, psychomotor impairment, inability to concentrate,lassitude, irritability and antimuscarinic effects such as urinary retention, dry mouth and blurred vision. Gastrointestinal disturbances may occur including abdominal pain, dyspepsia and anorexia. Paradoxical CNS stimulation may occur especially in children or after high doses. Skin rashes including exfoliative dermatitis and photosensitivity reactions and hypersensitivity reactions including urticaria may occur. Other side effects include convulsions, sweating, myalgia, paraesthesia, tinnitus, palpitations, tachycardia, arrhythmias, chest pain, haemolytic anaemia and other blood dyscrasias, extrapyramidal effects, tremor, liver dysfunction, including hepatitis and jaundice, sleep disturbances, including nightmares, depression, hypotension, hair loss, thickening of bronchial secretions and confusional psychosis in the elderly.

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

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

4.9 Overdose

Initiate general symptomatic and supportive measures in all cases of over dosages where necessary

5.1 Mechanism of Action

Paracetamol : Paracetamol has both analgesic and antipyretic activity which is believed to be mediated principally through its inhibition of prostaglandin synthesis within the central nervous system. Phenylephrine : Phenylephrine hydrochloride is an α-1 adrenergic receptor agonist. Chlorpheniramine : Chlorpheniramine antagonises competitively the effects of histamine on H1-receptors and also has weak antimuscarinic and moderate antiserotonin and local anaesthetic actions.

5.2 Pharmacodynamic properties

Paracetamol provides the analgesic and antipyretic actions. Phenylephrine is a post-synaptic α-receptor agonist with low cardioselective β-receptor affinity and minimal central stimulant activity. It is a recognised decongestant and acts by vasoconstriction to reduce oedema and nasal swelling. Chlorpheniramine is an antihistamine drug (H1 receptor antagonist) that also possesses anticholinergic and sedative activity. It prevents released histamine from dilating capillaries and causing edema of the respiratory mucosa

5.3 Pharmacokinetic properties

Paracetamol : Paracetamol is rapidly absorbed from the gastro-intestinal tract with peak plasma concentrations occurring between 10 and 120 minutes after oral administration. It is metabolised in the liver and excreted in the urine mainly as the glucuronide and sulphate conjugates. Less than 5% is excreted as unchanged paracetamol. The elimination half-life varies from about 1 to 4 hours. Phenylephrine : Phenylephrine hydrochloride is irregularly absorbed from the gastrointestinal tract and undergoes first-pass metabolism by monoamine oxidase in the gut and liver; orally administered phenylephrine thus has reduced bioavailability. It is excreted in the urine almost entirely as the sulphate conjugate. Chlorpheniramine : Chlorphenamine is well absorbed from the gastro-intestinal tract, following oral administration. The effects develop within 30 minutes, are maximal within 1 to 2 hours and last 4 to 6 hours. The plasma half-life has been estimated to be 12 to 15 hours. Chlorphenamine is metabolised to the monodesmethyl and didesmethyl derivatives. About 22% of an oral dose is excreted unchanged in the urine.

6.1 Animal Toxicology or Pharmacology

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 1-10µg/L and oral doses of 0.2-1 mg/kg antagonise histamine- induced bronchospasm in guinea pigs.

Preclinical safety data of paracetamol and phenylephrine : None stated

Maxtra-P DS syrup is a combination of analgesic/antipyretic paracetamol, decongestants phenylephrine hydrochloride and anti-allergic chlorpheniramine maleate.

8.1 Incompatibilities

Not applicable.

8.2 Shelf-life

Refer on the pack.

8.3 Packaging information

A bottle of 60 ml.

8.4 Storage and handing instructions

Store at a temperature not exceeding 25°C. Protect from light.

Keep out of reach of children.

• Do not take this medicine, if you are allergic to Paracetamol, Phenylephrine Hydrochloride, Chlorpheniramine Maleate

• Signs of an allergic reaction include a rash, itching or shortness of breath.

• Chlorpheniramine may cause blurred vision, dizziness, drowsiness and interfere with human performance and therefore may seriously influence the ability to drive and operate machinery.

• Advice patient to talk to doctor or pharmacist in case of any side effects. This includes any possible side effects not listed in this leaflet.

• Advice patient to talk to doctor or pharmacist in case of any further questions.