MAXTRA® Tablets

Phenylephrine Hydrochloride / Chlorpheniramine Maleate

Each uncoated tablet contains

Phenylephrine Hydrochloride  10 mg

Chlorpheniramine Maleate  4 mg

Excipients q.s.

Tablet.

10mg/4mg.

4.1 Therapeutic indication

Treatment of cough and cold with nasal congestion.

4.2 Posology and method of administration

The recommended dosage of MAXTRA® for the treatment of cough and cold with nasal congestion in adults and children 12 years of age and older is 1 tablet every 4 to 6 hours and in children 6 to under 12 years of age is ½ tablet every 4 to 6 hours.

4.3 Contraindications

The tablets are contraindicated in patients who are hypersensitive to antihistamines or to any of the tablet ingredients. The anticholinergic properties of chlorphenamine are intensified by monoamine oxidase inhibitors (MAOIs). The tablets are therefore contraindicated in patients who have been treated with MAOIs within the last fourteen days. Avoid in patients with cardiovascular disease, high blood pressure, diabetes mellitus, closed angle glaucoma, hyperthyroidism, prostatic enlargement and phaeochromocytoma. Patients being treated with monoamine oxidase inhibitors or within 14 days of ceasing such treatment

4.4 Special warnings and precautions for use

Chlorphenamine, in common with other drugs having anticholinergic effects, should be used with caution in epilepsy; raised intra-ocular pressure including glaucoma; prostatic hypertrophy; severe hypertension or cardiovascular disease; bronchitis, bronchiectasis or asthma; hepatic impairment; renal impairment. Children and the elderly are more likely to experience the neurological anticholinergic effects and paradoxical excitation (e.g., Increased energy, restlessness, nervousness).

The anticholinergic properties of chlorphenamine may cause drowsiness, dizziness, blurred vision and psychomotor impairment in some patients which may seriously affect ability to drive and use machinery.

The effects of alcohol may be increased and therefore concurrent use should be avoided. Should not be used with other antihistamine containing products, including antihistamine containing cough and cold medicines.

Patients with rare hereditary problems of galactose intolerance, Lapp lactase deficiency or glucose-galactose malabsorption should not take this medicine. This medicine should be used with caution in patients with occlusive vascular disease including Raynaud's Phenomenon.

Do not take for longer than 7 days, unless your doctor agrees.

If symptoms do not go away talk to your doctor.

Keep all medicines out of the reach of children.

Warning: Do not exceed the stated dose.

4.5 Drugs interactions

Should not be given to patients being treated with monoamine oxidase inhibitors or within 14 days of stopping such treatment. May enhance the effects of anticholinergic drugs such as tricyclic antidepressants. May increase the possibility of arrhythmias in digitalised patients. May enhance the cardiovascular effects of other sympathomimetic amines (e.g. decongestants). This medicine should not be taken together with vasodilators, Beta-blockers or enzyme inducers such as alcohol.

Concurrent use with hypnotics or anxiolytics may cause an increase in sedative effects, therefore medical advice should be sought before taking MAXTRA® concurrently with these medicines.

Chlorphenamine inhibits phenytoin metabolism and can lead to phenytoin toxicity.

The anticholinergic effects of chlorphenamine are intensified by MAOIs (see Contraindications).

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

Pregnancy

The safety of this medicine during pregnancy has not been established but in view of a possible association of foetal abnormalities with first trimester exposure to phenylephrine, the use of the product during pregnancy should be avoided. In addition, because phenylephrine may reduce placental perfusion, the product should not be used in patients with a history of pre-eclampsia. Similarly, there are no adequate data from the use of chlorphenamine maleate in pregnant women. The potential risk for humans is unknown. Use during the third trimester may result in reactions in the newborn or premature neonates. Not to be used during pregnancy unless considered essentially by a physician.

Lactation

The safety of this medicine during lactation has not been established. Chlorphenamine maleate and other antihistamine may inhibit lactation and may be secreted in breast milk. Not to be used during lactation unless considered essential by a physician. In view of the lack of data on the use of phenylephrine during lactation, this medicine should not be used during breast feeding.

4.7 Effects on ability to drive and use machines

The anticholinergic properties of chlorphenamine may cause drowsiness, dizziness, blurred vision and psychomotor impairment, which can seriously hamper the patients' ability to drive and use machinery.

4.8 Undesirable effects

Chlorpheniramine Maleate

Specific estimation of the frequency of adverse events for OTC products is inherently difficult (particularly numerator data). Adverse reactions which have been observed in clinical trials and which are considered to be common (occurring in ≥1% to <10% of subjects) or very common (occurring in ≥10% of subjects) are listed below. The frequency of other adverse reactions identified during post-marketing use is unknown.

Blood and lymphatic system disorders:

Unknown: haemolytic anaemia, blood dyscrasias

Immune system disorders:

Unknown: allergic reaction, angioedema, anaphylactic reactions

Metabolism and nutritional disorders:

Unknown: anorexia

Psychiatric disorders:

Unknown: confusion*, excitation*, irritability*, nightmares*, depression

Nervous system disorders*:

Very common: sedation, somnolence

Common: disturbance in attention, abnormal coordination, dizziness headache

Eye Disorders:

Common: blurred vision

Ear and labyrinth disorders:

Unknown: tinnitus

Cardiac disorders:

Unknown: palpitations, tachycardia, arrythmias

Vascular disorders:

Unknown: Hypotension

Respiratory, thoracic and mediastinal disorders:

Unknown: thickening of bronchial secretions

Gastrointestinal disorders:

Common: nausea, dry mouth

Unknown: vomiting, abdominal pain, diarrhoea, dyspepsia

Hepatobiliary disorders:

Unknown: hepatitis, jaundice

Skin and subcutaneous disorders:

Unknown: exfoliative dermatitis, rash, urticaria, photosensitivity

Musculoskeletal and connective tissue disorders:

Unknown: muscle twitching, muscle weakness

Renal and urinary disorders:

Unknown: urinary retention

General disorders and administration site conditions:

Common: fatigue Unknown: chest tightness

*Children and the elderly are more likely to experience the neurological anticholinergic effects and paradoxical excitation (eg. increased energy, restlessness, nervousness).

Phenylephrine hydrochloride

Adverse effects may include tachycardia, cardiac arrhythmias, palpitations, hypertension, nausea, vomiting, headache and occasionally urinary retention in males.

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 at www.zuventus.co.in and click the tab “Safety Reporting” located on the top end of the home page.

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

4.9 Overdose

Chlorpheniramine Maleate

Symptoms and signs

The estimated lethal dose of chlorphenamine is 25 to 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 including arrhythmias.

Treatment

Symptomatic and supportive measures should be provided with special attention to cardiac, respiratory, renal and hepatic functions and fluid and electrolyte balance. If overdosage is by the oral route, treatment with activated charcoal should be considered provided there are no contraindications for use and the overdose has been taken recently (treatment is most effective if given 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.

Phenylephrine hydrochloride

Symptoms of overdosage include irritability, restlessness, palpitations, hypertension, difficulty in micturition, nausea, vomiting, thirst and convulsions. In severe overdosage gastric lavage and aspiration should be performed. Symptomatic and supportive measures should be undertaken, particularly with regard to cardiovascular and respiratory systems. Convulsions should be controlled with intravenous diazepam. Chlorpromazine may be used to control marked excitement and hallucinations. Severe hypertension may need to be treated with an alpha-adrenoreceptor blocking drug, such as phentolamine. A beta blocker may be required to control cardiac arrhythmias.

5.1 Pharmacodynamic properties

Chlorpheniramine Maleate

Chlorphenamine is a potent antihistamine (H1-antagonist).

Antihistamines diminish or abolish the actions of histamine in the body by competitive reversible blockade of histamine H1-receptor sites on tissues. Chlorphenamine also has anticholinergic activity.

Antihistamines act to prevent the release of histamine, prostaglandins and leukotrienes and have been shown to prevent the migration of inflammatory mediators. The actions of chlorphenamine include inhibition of histamine on smooth muscle, capillary permeability and hence reduction of oedema and wheal in hypersensitivity reactions such as allergy and anaphylaxis.

Phenylephrine hydrochloride

Phenylephrine is a sympathomimetic agent with mainly direct effects on adrenergic receptors. It has predominantly alpha adrenergic activity and is without stimulating effects on the central nervous system. The sympathomimetic effect of phenylephrine produces vasoconstriction which in turn relieves nasal congestion.

5.2 Pharmacokinetic properties

Chlorpheniramine Maleate

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. Only trace amounts have been found in the faeces.

Phenylephrine hydrochloride

Phenylephrine is readily absorbed after oral administration but is subject to extensive presystemic metabolism, much of which occurs in the enterocytes. As a consequence, systemic bioavailability is only about 40%. Following oral administration, peak plasma concentrations are achieved in 1-2 hours. The mean plasma half-life is in the range 2-3 hours. Penetration into the brain appears to be minimal.

Following absorption, the drug is extensively metabolised in the liver. Both phenylephrine and its metabolites are excreted in the urine.

The volume of distribution is between 200 and 500 litres, but there are no data on the extent of plasma protein binding.

No additional data of relevance.

MAXTRA® tablet contains phenylephrine hydrochloride (a nasal decongestant) and chlorpheniramine maleate (an antihistamine). Each uncoated tablet contains: Phenylephrine Hydrochloride, IP, 10 mg; Chlorpheniramine Maleate, IP, 4 mg; and Excipients (q.s.)

Chlorpheniramine Maleate

Chlorpheniramine maleate is 2-pyridinepropanamine, g-( as the following chemical structu 4-chlorophenyl)-N,N-dimethyl-, (Z)-2 - butenedioate (1:1) and has the following chemical structure:

Phenylephrine hydrochloride

Phenylephrine is an alpha-1 adrenergic receptor agonist. The chemical name of phenylephrine hydrochloride is (-)-m-hydroxy-α-[(methylamino)methyl]benzyl alcohol hydrochloride, and its structural formula is depicted below:

8.1 Incompatibilities

Not applicable

8.2 Shelf-life

Refer on pack.

8.3 Packaging information

20 Blister strips of 10 tablets in each strip

8.4 Storage and handing instructions

Store below 25°C. Protect from moisture.

Keep out of reach of children.

Caution: Maxtra Tablets may cause drowsiness. Patients on long term therapy should not drive vehicle or operate machinery.

Do Not Use

if you are now taking a prescription monoamine oxadise inhibitor (MAOI) (certain drugs for depression, psychiatric, or emotional conditions, or Parkinson’s disease), or for 2 weeks after stopping the MAOI drug. If you do not know if your prescription drug contains an MAOI, ask a doctor or pharmacist before taking this product.

Ask a doctor before use if you have 

• a breathing problem such as emphysema or chronic bronchitis
• glaucoma
• trouble urinating due to an enlarged prostate gland
• diabetes
• heart disease
• high blood pressure
• thyroid disease

Ask a doctor or pharmacist before use if you are

• taking sedatives or tranquilizers

When using this product

• do not use more than directed
• may cause excitability, especially in children
• may cause drowsiness; alcohol, sedatives or tranquilizers may increase drowsiness
• avoid alcoholic beverages and use caution when driving a motor vehicle or operating machinery

Stop use and ask a doctor if

• nervousness, dizziness, or sleeplessness occur
• symptoms do not improve within 7 days or are accompanied by fever

If pregnant or breast-feeding

ask a health professional before use.