Paracetamol/ Pseudoephedrine/ Chlorphenamine

Registered South African indications:

• Symptomatic relief of colds and influenza
• Symptomatic relief of allergic rhinitis (hay fever) and vasomotor rhinitis
• Symptomatic relief of sinus pain, including maxillary, frontal, or facial pain
• Relief of associated malaise, fever, and congestion of the nasal, sinus, and eustachian tube mucosa

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

Registered South African contraindications

Caplet formulation

• 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
• Coadministration with monoamine oxidase inhibitors, or within two weeks of stopping treatment with these medications
• Pseudoephedrine hydrochloride should not be used in patients suffering from 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), and diabetes mellitus
• Pseudoephedrine hydrochloride should be avoided in patients receiving chloroform, cyclopropane, halothane, or other halogenated anaesthetics
• Pregnancy
• Lactation

Tablet formulation

• Hypersensitivity to the active ingredient or any of the excipients in this combination product
• Children under 12 years of age
• Paracetamol should not be used in patients with severe liver and renal disease
• Pseudoephedrine should be avoided in patients undergoing inhalation anaesthesia
• Coadministration with any monoamine oxidase inhibitor (MAOI) for depression or within 14 days of stopping such treatment
• Contraindicated in most types of cardiovascular disease, including angina and hypertension
• Contraindicated in hyperthyroidism, phaeochromocytoma, closed angle glaucoma, and diabetes mellitus

South African recommendations

• Pregnancy (Tablet formulation)
• Breastfeeding (Tablet formulation)
• Mild to moderate renal impairment (Tablet formulation)
• Renal impairment (Caplet formulation)
• Mild to moderate hepatic impairment
• Elderly

Other paracetamol containing products

• Do not use this medicine with any other products containing paracetamol

Duration of use

• Caplets: Do not use continuously for more than 10 days
• Tablets: Do not use continuously for more than 7 days
• Consult a doctor if symptoms persist, worsen, or new symptoms appear

Persistent respiratory conditions such as:

• Emphysema
• Chronic bronchitis
• Bronchial asthma, or where cough is accompanied by excessive secretions

Alcoholic beverages

• Patients should avoid alcoholic beverages and consult a doctor prior to taking with central nervous system depressants

Effects on ability to drive and use machines

• This combination product may cause drowsiness and impaired concentration, which can be worsened by the simultaneous intake of alcohol or other central nervous system depressant agents
• Patients should be advised against driving a motor vehicle, operating dangerous machinery, or climbing heights, as impaired decision-making could lead to accidents

Paracetamol

Excess dosages

• Dosages in excess of those recommended may cause severe liver or kidney damage

Renal and hepatic impairment

• Patients with impaired kidney or liver function should take paracetamol under medical supervision only

Skin reactions

• Serious skin reactions like acute generalised exanthematous pustulosis (AGEP), Stevens Johnson syndrome (SJS), and toxic epidermal necrolysis (TEN) have been reported rarely. Discontinue use at the first sign of rash or hypersensitivity

Coadministration caution

• Consult a doctor before using paracetamol alcohol is consumed regularly

Chlorphenamine maleate

Use with care in the following patients

• Glaucoma
• Urinary retention
• Prostatic hypertrophy
• Pyloroduodenal obstruction
• Epilepsy
• Severe cardiovascular disorders

Elderly patients

• More susceptible to central nervous system depressant and blood pressure lowering effects in elderly patients

Masking precaution

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

May cause drowsiness

• May cause drowsiness and enhance the sedative effect of central nervous system depressants including alcohol, barbiturates, hypnotics, analgesics, sedatives and tranquillisers
• Care should be taken when taking medicines containing tricyclic anti-depressants or atropine together

Pseudoephedrine hydrochloride

Caution in the following patients

• Not recommended for use by patients with liver disease, renal disease, and difficulty in urination

Symptoms of ischaemic colitis

• Discontinue and seek medical advice if symptoms like sudden abdominal pain or rectal bleeding develop

Acute generalised exanthematous pustulosis (AGEP)

• AGEP has been reported with pseudoephedrine-containing medicines. Discontinue use and consult a doctor if symptoms like pustules or fever appear

Forms avail. in SA and covered in this monograph: caplet, tab

South African registered indications and dosages

Short-term relief of symptoms of the common cold, hayfever or other nasal allergies such as minor aches and pains, headache and fever, nasal stuffiness, runny nose, sneezing, itchy and watery eyes

Paracetamol/ Pseudoephedrine/ Chlorphenamine
500/30/2 (mg)

Oral (cap): 2 cap, 6-8hrly; Max: 8 cap/24hrs

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Do not use continuously for more than 10 days

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Symptomatic relief of sinus pain, including maxillary, frontal, or facial pain
Relief of associated malaise, fever, and congestion of the nasal, sinus, and eustachian tube mucosa
Symptomatic relief of allergic rhinitis (hay fever), vasomotor rhinitis, influenza, and the common cold

Paracetamol/ Pseudoephedrine/ Chlorphenamine
500/30/2 (mg)

• Oral (tab): 2 tab, 6-8hrly; Max: 8 tab/24hrs

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Do not use continuously for more than 7 days

---

Caplets and tablets: Do not exceed the recommended dose

Paed. forms avail. in SA and covered in this monograph: caplet, tab

South African registered indications and dosages

Short-term relief of symptoms of the common cold, hayfever or other nasal allergies such as minor aches and pains, headache and fever, nasal stuffiness, runny nose, sneezing, itchy and watery eyes

Paracetamol/ Pseudoephedrine/ Chlorphenamine
500/30/2 (mg)

Caplet formulation

• Younger than 12 years: Not recommended for use
• Older than 12 years: See adult dosage

Symptomatic relief of sinus pain, including maxillary, frontal, or facial pain
Relief of associated malaise, fever, and congestion of the nasal, sinus, and eustachian tube mucosa
Symptomatic relief of allergic rhinitis (hay fever), vasomotor rhinitis, influenza, and the common cold

Paracetamol/ Pseudoephedrine/ Chlorphenamine
500/30/2 (mg)

Tablet formulation

• Younger than 12 years: Contraindicated
• Older than 12 years: See adult dosage

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Do not exceed the recommended dose

Pregnancy

South African recommendations

Caplet formulation

• Contraindicated

Tablet formulation

• Caution
• Safety during pregnancy has not been established

Breastfeeding

South African recommendations

Caplet formulation

• Contraindicated

Tablet formulation

• Caution
• Safety during lactation has not been established

Fertility

South African recommendations

• No information available

South African recommendations

Caplet formulation

• Caution; no dose adjustment recommended
  Patients suffering from kidney disease should take paracetamol only if instructed to do so by a doctor

Tablet formulation

• Mild to moderate: Caution; no dose adjustment recommended
  Use of pseudoephedrine is not recommended in renal disease
  Patients with impaired kidney function should take paracetamol under medical supervision only
• Severe: Contraindicated

South African recommendations

Caplet formulation

• Mild to moderate: Caution; no dose adjustment recommended
  Patients suffering from liver disease should take paracetamol only if instructed to do so by a doctor
• Severe: Contraindicated

Tablet formulation

• Mild to moderate: Caution; no dose adjustment recommended
  Use of pseudoephedrine is not recommended in liver disease
  Patients with impaired liver function should take paracetamol under medical supervision only
• Severe: Contraindicated

South African recommendations

• Caution; no dose adjustment recommended
  Elderly patients are more susceptible to the central nervous system depressant and lowering of blood pressure effects even at dose quantities effective for treatment

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

Paracetamol/ Pseudoephedrine/ Chlorphenamine

Nervous System Disorders

Frequent

• Dizziness
• Somnolence

Gastrointestinal Disorders

Frequent

• Dry mouth

General Disorders and Administration Site Conditions

Frequent

• Asthenia

Paracetamol

Blood and Lymphatic System Disorders

Less frequent

• Neutropenia
• Pancytopenia
• Leucopenia
• Thrombocytopenia

Immune System Disorders

Less frequent

• Sensitivity/allergic reactions resulting in skin rash
• Laryngeal oedema
• Angioedema
• Anaphylaxis

Skin and Subcutaneous Tissue Disorders

Less frequent

• Erythematous rash
• Urticarial rash

Gastrointestinal Disorders

Less frequent

• Mucosal lesions
• Pancreatitis

General Disorders and Administration Site Conditions

Less frequent

• Fever

Pseudoephedrine Hydrochloride

Metabolism and Nutrition Disorders

Less frequent

• Decreased appetite
• Hypokalaemia
• Altered metabolism

Psychiatric Disorders

Frequent

• Fear
• Anxiety
• Insomnia
• Confusion
• Irritability
• Psychotic states

Nervous System Disorders

Frequent

• Restlessness
• Tremor
• Dizziness

Less frequent

• Cerebral haemorrhage
• Headache

Cardiac Disorders

Less frequent

• Pulmonary oedema
• Cardiac dysrhythmias
• Anginal pain
• Palpitations
• Cardiac arrest

Vascular Disorders

Less frequent

• Hypertension
• Reflex bradycardia
• Tachycardia
• Hypotension
• Fainting

Respiratory, Thoracic and Mediastinal Disorders

Less frequent

• Dyspnoea

Gastrointestinal Disorders

Less frequent

• Nausea
• Vomiting
• Hypersalivation

Renal and Urinary Disorders

Less frequent

• Difficulty in micturition
• Urinary retention

General Disorders and Administration Site Conditions

Frequent

• Weakness
• Sweating
• Tolerance with dependence

Investigations

Less frequent

• Changes in blood sugar levels

Chlorphenamine Maleate

Blood and Lymphatic System Disorders

Less frequent

• Agranulocytosis
• Leucopenia
• Haemolytic anaemia
• Thrombocytopenia

Immune System Disorders

Less frequent

• Hypersensitivity reactions such as pruritus or rash

Psychiatric Disorders

Less frequent

• Nervousness
• Euphoria
• Irritability
• Nightmares
• Hallucinations

Nervous System Disorders

Frequent

• Sedation (varying from slight drowsiness to deep sleep)
• Lassitude
• Dizziness
• Incoordination

Less frequent

• Insomnia
• Tremors
• Convulsions
• Headache
• Blurred vision
• Paraesthesias
• Extrapyramidal effects

Ear and Labyrinth Disorders

Less frequent

• Tinnitus

Vascular Disorders

Less frequent

• Hypertension
• Hypotension

Respiratory, Thoracic and Mediastinal Disorders

Less frequent

• Thickened respiratory-tract secretions
• Tightness of the chest

Gastrointestinal Disorders

Less frequent

• Nausea
• Vomiting
• Dry mouth
• Constipation
• Gastric reflux
• Diarrhoea
• Epigastric pain

Musculoskeletal and Connective Tissue Disorders

Less frequent

• Myalgia

Renal and Urinary Disorders

Less frequent

• Urinary difficulty and retention

General Disorders and Administration Site Conditions

Less frequent

• Sweating
• Hair loss

Paracetamol/ Pseudoephedrine/ Chlorphenamine Post-marketing Experience

Immune System Disorders

Frequency unknown

• Anaphylactic reaction
• Hypersensitivity

Psychiatric Disorders

• Anxiety
• Euphoric mood
• Hallucination
• Visual hallucination
• Restlessness

Nervous System Disorders

• Cerebrovascular accident
• Headache
• Paraesthesia
• Psychomotor hyperactivity
• Tremor

Cardiac Disorders

• Dysrhythmia
• Myocardial infarction
• Palpitations
• Tachycardia

Gastrointestinal Disorders

• Abdominal pain
• Colitis ischaemic
• Diarrhoea
• Vomiting

Skin and Subcutaneous Tissue Disorders

• Acute generalised exanthematous pustulosis
• Angioedema
• Fixed eruption
• Pruritus
• Rash
• Pruritic rash
• Urticaria

Renal and Urinary Disorders

• Dysuria
• Urinary retention

Investigations

• Increased blood pressure
• Increased transaminases

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

Paracetamol

• Hepatotoxic agents
• Hepatic enzyme inducers
• Non-steroidal anti-inflammatory drugs
• Zidovudine
• Warfarin-like compounds
• Other coumarin derivatives

Pseudoephedrine Hydrochloride

• Inhalation anaesthetics
• Chloroform
• Cyclopropane
• Enflurane
• Halothane
• Isoflurane
• Methoxyflurane
• Trichloroethylene
• Digitalis glycosides
• Anticholinergics
• Cardiovascular medicines
• Beta-adrenergic blocking agents
• Central nervous system stimulants
• Doxapram
• Sympathomimetic amines
• Monoamine oxidase inhibitors
• Aluminium-hydroxide containing preparations

Chlorphenamine Maleate

• Central nervous system depressants
• Alcohol
• Barbiturates
• Hypnotics
• Opioid analgesics
• Anxiolytic sedatives
• Medicines with anticholinergic properties
• Antipsychotics
• Tricyclic antidepressants
• Monoamine oxidase inhibitors

None routine. Specific cases may require

• Renal function
• Hepatic function

Paracetamol/ pseudoephedrine/ chlorpheniramine has analgesic, anti-pyretic, decongestant and antihistaminic properties.

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.

Chlorphenamine
Chlorphenamine 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. Chlorphenamine 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

Tablet 500mg/30mg/2mg

• Sinutab Sinus Allergy Congestion & Pain (Johnson & Johnson)

Caplet 500mg/30mg/2mg

• Sinumax Allergy Sinus (Janssen)