Paracetamol/ Pseudoephedrine/ Chlorpheniramine

Registered South African indications:

• Symptomatic treatment and relief of colds and influenza
• Relief of symptoms of nasal stuffiness, runny nose, sneezing, minor aches and pains, headaches and fever due to the common cold, hayfever or other nasal allergies

This product contains paracetamol which may be fatal in overdose. In the event of overdosage or suspected overdosage and notwithstanding the fact that the person may be asymptomatic, the nearest doctor, hospital or poison control centre must be contacted immediately.

Registered South African contraindications

120/15/2 (mg/5ml)

• Hypersensitivity to the active ingredient or any of the excipients in this combination product
• Pregnancy
• Lactation
• Hyperthyroidism
• Use with great care in patients with cardiovascular disease such as ischaemic heart disease and coronary insufficiency, dysrhythmias, tachycardia or hypertension
• Use with care in patients with diabetes mellitus or closed angle glaucoma, urinary retention and prostatic hypertrophy
• Do not use in children under 2 years of age
• Contraindicated in neonates owing to their increased susceptibility to antimuscarinic effects
• Contraindicated during attacks of asthma
• Severe liver function impairment
• Coadministration with monoamine oxidase inhibitors or within 14 days of their use

160/15/1 (mg/5ml)

• Hypersensitivity to the active ingredient or any of the excipients in this combination product
• Paracetamol should not be used in patients with severe liver disease
• Pseudoephedrine hydrochloride should not be used in patients suffering from any of the following
  • Heart disease (especially coronary insufficiency or arrhythmias)
  • High blood pressure (hypertension)
  • An overactive thyroid gland (hyperthyroidism)
  • Tumour of the adrenal gland (phaeochromocytoma)
  • Raised intraocular pressure (closed-angle glaucoma)
  • Diabetes mellitus
• Pseudoephedrine hydrochloride should be avoided in patients receiving chloroform, cyclopropane, halothane or other halogenated anaesthetics
• Pregnancy
• Breastfeeding
• Coadministration with monoamine oxidase inhibitors or within two weeks of stopping such treatment

Mild to moderate hepatic impairment or renal disease

• Patients with liver or kidney disease should only take paracetamol under the guidance of a doctor

Elderly patients

• Elderly patients are more susceptible to many of the adverse effects including antimuscarinic effects, sedation, and lowering of blood pressure

May impair ability to drive and operate machinery

• This medicine may cause drowsiness and impaired concentration, potentially worsened by alcohol or other nervous system depressants
• Avoid operating vehicles, machinery, or performing tasks where concentration is required

Respiratory conditions and glaucoma

• Patients with persistent respiratory conditions (e.g., emphysema, chronic bronchitis, bronchial asthma) or excessive secretions, or glaucoma should consult a physician before using this product

Persistent or worsening symptoms

• If pain or fever persists or worsens, or new symptoms occur, consult a physician

Serious skin reactions

• Rare but serious skin reactions like acute generalised exanthematous pustulosis (AGEP), Stevens-Johnson syndrome (SJS), and toxic epidermal necrolysis (TEN) have been reported. Discontinue use at the first sign of skin rash or any other sign of hypersensitivity
• Severe skin reactions like acute generalised exanthematous pustulosis (AGEP) have been reported with pseudoephedrine-containing products. Discontinue use and consult a physician at the first sign of such reactions

Other paracetamol products

• Do not use this product in conjunction with any other paracetamol-containing products

Thyroid disease, diabetes, kidney function, and prostate enlargement

• Patients with thyroid disease, diabetes, decreased kidney function, or adults with difficulty in urination due to enlargement of the prostate should not take pseudoephedrine unless directed by a physician

Ischaemic colitis

• Discontinue pseudoephedrine and seek medical advice if symptoms of ischaemic colitis such as sudden abdominal pain, rectal bleeding develop

Alcoholic beverages and CNS depressants

• Avoid alcoholic beverages and CNS depressants while taking this product
• Chlorpheniramine may enhance the sedative effects of CNS depressants including alcohol, sedatives, and tranquilisers

Pancreatitis and allergic reactions

• Paracetamol may cause pancreatitis, allergic reactions in the form of a rash or blood disorders
• Discontinue use if these occur
• The rash usually appears as red areas or allergic wheals and may be accompanied by fever and involvement of the mucous membranes

Epilepsy and pyloroduodenal obstruction

• Caution is advised for patients with epilepsy or pyloroduodenal obstruction

Concurrent use of certain medications

• Care should be taken when using this product with medicines containing tricyclic anti-depressants or atropine

Ototoxic medicines

• The warning signs of damage caused by ototoxic medicines may be masked by chlorpheniramine

Tolerance and dependence

• Tolerance with dependence may occur after continued use of pseudoephedrine

Interaction with other medicines

• The effects of pseudoephedrine hydrochloride may be lessened by medicines containing guanethidine, reserpine, methyldopa, and may be diminished or enhanced by tricyclic antidepressants
• Pseudoephedrine may increase the possibility of irregular heartbeat in patients taking digitalis

Skin tests

• Chlorpheniramine may interfere with the results of skin tests and should be stopped several days before such tests

Contains sucrose

• Not recommended for patients with rare hereditary conditions such as fructose intolerance, glucose-galactose mal-absorption, or sucrase-isomaltase insufficiency
• Sucrose may affect the glycaemic control of patients with diabetes mellitus

Forms avail. in SA and covered in this monograph: syr

South African registered indications and dosages

Symptomatic treatment and relief of colds and influenza

Paracetamol/ Pseudoephedrine/ Chlorpheniramine
120/15/2 (mg/5ml)

• Oral (syr): 15-20ml, 3 times dly

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Do not exceed recommended dose

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Not to be used continuously for longer than 10 days without consultation

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160/15/1 (mg/5ml) is not indicated for use in adults

Forms avail. in SA and covered in this monograph: syr

South African registered indications and dosages

Symptomatic treatment and relief of colds and influenza

Paracetamol/ Pseudoephedrine/ Chlorpheniramine
120/15/2 (mg/5ml)

• Younger than 2 years: Contraindicated
• Between 2-5 years: Oral (syr): 2.5-5ml, 3 times dly
• Between 6-12 years: Oral (syr): 5-10ml, 3 times dly

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Do not exceed recommended dose

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Not to be used continuously for longer than 10 days without consultation

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Relief of symptoms of nasal stuffiness, runny nose, sneezing, minor aches and pains, headaches and fever due to the common cold, hayfever or other nasal allergies

Paracetamol/ Pseudoephedrine/ Chlorpheniramine
160/15/1 (mg/5ml)

• Younger than 2 years: Not recommended for use
• Between 2-5 years: Oral (syr): 5ml, 4-6hrly as needed
• Between 6-11 years: Oral (syr): 10ml, 4-6hrly as needed

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Do not exceed the recommended dosage. Do not exceed 4 doses in 24 hours

Pregnancy

South African recommendations

• Contraindicated
• The safety and efficacy in pregnancy has not been established
• There are no adequate and well-controlled studies in pregnant women for the combination of chlorpheniramine, paracetamol, and pseudoephedrine. It is unknown if chlorpheniramine or its metabolites cross the placenta

Breastfeeding

South African recommendations

• Contraindicated
• The safety and efficacy in lactation has not been established
• There are no adequate and well-controlled studies in breastfeeding women for the combination of chlorpheniramine, paracetamol, and pseudoephedrine. It is unknown if chlorpheniramine or its metabolites are excreted in breast milk

South African recommendations

• Caution; no dose adjustment recommended
  There are no pseudoephedrine pharmacokinetic data available in patients with kidney disease. However, a decrease in renal function may decrease oral clearance because pseudoephedrine is mainly excreted unchanged in urine

South African recommendations

• Mild to moderate: Caution; no dose adjustment recommended
  There are no pseudoephedrine pharmacokinetic data available in patients with liver disease
• Severe: Contraindicated

South African recommendations

• Caution; no dose adjustment recommended
  Elderly patients are more susceptible to many of the adverse effects including antimuscarinic effects, sedation and lowering of blood pressure

Combination products may have additional pharmacological effects not accounted for by the action of the individual ingredients

Chlorpheniramine
Nervous System Disorders

• Sedation
• Dizziness
• Lassitude
• Incoordination
• Tremors¹
• Headache
• Convulsions¹
• Hallucinations¹
• Parathesias

Psychiatric Disorders

• Insomnia¹
• Nervousness¹
• Euphoria¹
• Irritability¹
• Nightmares¹

Respiratory Disorders

• Thickened respiratory tract secretions
• Tightness of the chest

Eye Disorders

• Blurred vision

Cardiac Disorders

• Slowing of the heart beat (at high doses)
• Increased heart rate (following slowing of the heart beat at high doses)
• Irregular heartbeat (following slowing of the heart beat at high doses)

Gastrointestinal Disorders

• Dry mouth
• Diarrhoea
• Epigastric pain
• Nausea and vomiting
• Anorexia
• Disturbances affecting the stomach and intestines resulting in constipation
• Increased gastric reflux

Renal and Urinary Disorders

• Urinary difficulty and retention

Vascular Disorders

• Hypotension

Skin and Subcutaneous Tissue Disorders

• Photosensitivity
• Hypersensitivity reactions, particularly of the skin

Immune, Blood and Lymphatic System Disorders

• Blood disorders
• Cross-sensitivity to related medicines

Ear and Labyrinth Disorders

• Ringing in the ears

Pseudoephedrine
Nervous System Disorders

• Giddiness
• Tremors
• Headache

Cardiac Disorders

• Irregular heartbeat
  - Tachycardia
  - Ventricular dysrhythmia
• Precordial pain
• Palpitations

Gastrointestinal Disorders

• Nausea and vomiting

Metabolism and Nutrition Disorders

• Thirst
• Sweating

Vascular Disorders

• Hypertension

Renal and Urinary Disorders

• Difficulty in urination

Musculoskeletal and Connective Tissue Disorders

• Muscular weakness

Psychiatric Disorders

• Anxiety
• Restlessness

General Disorders

• Inability to sleep

Chlorpheniramine/ Paracetamol/ Pseudoephedrine
Immune System Disorders

• Anaphylactic reaction (Very rare)
• Hypersensitivity (Very rare)

Investigations

• Increased blood pressure (Very rare)
• Increased transaminases (Very rare)

Psychiatric Disorders

• Anxiety (Very rare)
• Euphoric mood (Very rare)
• Hallucination (Very rare)
• Visual hallucination (Very rare)
• Restlessness (Very rare)

Nervous System Disorders

• Cerebrovascular accident (Very rare)
• Headache (Very rare)
• Paraesthesia (Very rare)
• Psychomotor hyperactivity (Very rare)
• Tremor (Very rare)

Cardiac Disorders

• Dysrhythmia (Very rare)
• Myocardial infarction (Very rare)
• Palpitations (Very rare)
• Tachycardia (Very rare)

Gastrointestinal Disorders

• Abdominal pain (Very rare)
• Ischaemic colitis (Very rare)
• Diarrhoea (Very rare)
• Vomiting (Very rare)

Skin and Subcutaneous Tissue Disorders

• Acute generalised exanthematous pustulosis (Very rare)
• Angioedema (Very rare)
• Fixed eruption (Very rare)
• Pruritus (Very rare)
• Rash (Very rare)
• Rash pruritic (Very rare)
• Urticaria (Very rare)

Renal and Urinary Disorders

• Dysuria (Very rare)
• Urinary retention (Very rare)

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¹ Especially in children

Combination products may have additional pharmacological effects not accounted for by the action of the individual ingredients

120/15/2 (mg/5ml)

Paracetamol/ Pseudoephedrine/ Chlorpheniramine

• Monoamine oxidase inhibitors (MAOIs)
• Central nervous system depressants
• Alcohol
• Barbiturates
• Hypnotics
• Narcotic analgesics
• Sedatives
• Tranquillisers
• Ototoxic agents
• Aminoglycoside antibiotics
• Anticholinergic agents
• Atropine
• Tricyclic antidepressants

Pseudoephedrine

• Halothane
• Other halogenated anaesthetics
• Cardiac glycosides
• Tricyclic antidepressants

160/15/1 (mg/5ml)

Paracetamol

• Warfarin-like compounds
• Warfarin
• Other coumarin derivatives

Pseudoephedrine

• Monoamine oxidase inhibitors (MAOIs)
• Guanethidine
• Reserpine
• Methyldopa
• Tricyclic antidepressants
• Digitalis

Chlorpheniramine

• Central nervous system depressants
• Alcohol
• Barbiturates
• Hypnotics
• Analgesics
• Sedatives
• Tranquillisers

Other interactions

• Skin tests (Chlorpheniramine)

None routine

Paracetamol
Paracetamol is a centrally acting, non-opiate, non-salicylate analgesic. Paracetamol is a clinically proven analgesic/antipyretic, and it is thought to produce analgesia by elevation of the pain threshold and antipyresis through action on the hypothalamic heat-regulating center.

Pseudoephedrine
Pseudoephedrine is a sympathomimetic substance that has weak direct agonist activity at α- and β-adrenergic receptors. Its principal mechanism is indirect action on the adrenergic receptor system in which pseudoephedrine displaces norepinephrine from storage vesicles in presynaptic neurons. The displaced norepinephrine is released into the neuronal synapse where it is free to activate the postsynaptic α-adrenergic receptors. Stimulation of α₁-adrenergic receptors located on capacitance blood vessels of the nasal mucosa (postcapillary venules) results in vasoconstriction, decreased blood volume and a decrease in the volume of the nasal mucosa (nasal decongestion). Constricted blood vessels allow less fluid to enter the nose, throat, and sinus linings, which result in decreased inflammation of nasal membranes as well as decreased mucous production. Thus, by constriction of blood vessels, mainly those located in the nasal congestion.

Chlorpheniramine
Chlorpheniramine is an alkylamine and a first generation H₁ antagonist. It is a reversible, competitive inhibitor of histamine binding to the H₁ receptor. The first generation H₁-antagonists relieve histamine-mediated symptoms associated with allergic rhinitis such as sneezing, pruritus, rhinorrhoea, and ocular symptoms. Alkylamine H₁ antagonists are among the most potent H₁ antagonists and are less likely than other H₁ antagonists to produce drowsiness; however, sedation may occur in some patients. Central nervous system stimulation is more common in the alkylamine class of H₁ antagonists. Chlorpheniramine is also a competitive inhibitor of acetylcholine binding to muscarinic receptors. The anticholinergic properties of first generation H₁ antagonists may contribute to the reduced sneezing, rhinorrhoea, and volume of nasal fluid production observed when first generation H₁ antagonists are used to treat the common cold.

COMBINATION PREPARATIONS

Paracetamol/ Pseudoephedrine/ Chlorpheniramine

Syrup (per 5ml) 120mg/15mg/2mg

• Corenza Cold & Flu (Adcock)

Syrup (per 5ml) 120mg/15mg/1mg

• Sinumax Allergy Sinus Ped Liquid (Janssen Pharmaceutica)