Chlorphenamine/ Pseudoephedrine/ Aspirin/ Ascorbic Acid

Registered South African indications:

• Symptoms associated with colds and influenza

Chlorphenamine/ pseudoephedrine/ aspirin/ ascorbic acid may predispose to cardiovascular events, gastrointestinal events, or cutaneous reactions which may be fatal

Registered South African contraindications

• Hypersensitivity to the active ingredients or any of the excipients in this combination product
• Hypersensitivity to any other nonsteroidal anti-inflammatory medicine (NSAID)
• Patients with coronary disease, hypertension, cardiovascular disease, heart failure, hyperthyroidism, epilepsy
• Pregnancy
• Breastfeeding
• Patients being treated with monoamine oxidase inhibitors (MAOIs) or within 14 days of stopping such treatment
• Patients with a history of gastrointestinal perforation, ulceration or bleeding (PUBs) related to previous nonsteroidal anti-inflammatory medicines (NSAIDs) including aspirin, as contained in this combination product
• Patients with haemophilia
• Severe renal impairment
• Patients receiving oral anticoagulant therapy
• Patients with active or history of recurrent ulcer/haemorrhage/perforations
• Patients with phenylketonuria
• Children under the age of 16 years

South African recommendations

Renal and hepatic impairment

• Patients suffering from kidney or liver disease should take this combination product under medical supervision

Elderly

• Elderly individuals experience more adverse reactions to NSAIDs, (such as the aspirin in this combination product)
• Especially at risk for gastrointestinal issues like perforation, ulceration, and bleeding (PUBs), which can be fatal

Prolonged use of high doses

• Prolonged use of high doses may lead to anaemia, blood dyscrasias, gastrointestinal haemorrhage, peptic ulceration and renal papillary necrosis

Urinary retention

• Care should be taken in patients with urinary retention

Sensitivity to aspirin

• Use cautiously in individuals with asthma or allergic disorders
• Patients with a history of nasal polyps related to aspirin or those who have sensitivity reactions to aspirin or other NSAIDs should not take this combination product

Drowsiness

• Causes drowsiness and impaired concentration
• The effects may intensify with alcohol or other central nervous system depressants
• Especially at the beginning of treatment, patients should avoid operating machinery, driving, or any activity requiring focus

Reye’s syndrome

• Aspirin, an ingredient in this combination, is linked to Reye’s syndrome, a severe condition in children and teenagers recovering from chickenpox or the flu
• A medical practitioner should be consulted before giving chlorphenamine/ pseudoephedrine/ aspirin/ ascorbic acid to children under 16 years of age, as it is contraindicated in children under 16 years of age and in teenagers with chickenpox and influenza

Cardiovascular disease

• Higher doses and prolonged treatment increase the risk of cardiovascular events
• The combination contains aspirin, which can lead to fluid retention and oedema due to the inhibition of prostaglandin synthesis
• Use with caution in patients with cardiovascular disease such as ischaemic heart disease, dysrhythmia or tachycardia, and occlusive vascular disorders, including arteriosclerosis or aneurysms. Anginal pains may be precipitated in patients with angina pectoris

Diabetes mellitus, closed-angle glaucoma and prostatic hyperplasia

• Use with caution in these patients

Gastrointestinal disease

• The risk of gastrointestinal perforation, ulceration, or bleeding (PUBs) increases with higher doses
• This risk is also higher in patients with a history of ulcers and in elderly individuals
• If gastrointestinal issues like bleeding or ulceration arise while using chlorphenamine/ pseudoephedrine/ aspirin/ ascorbic acid, the treatment should be discontinued
• Patients with a history of gastrointestinal diseases, such as ulcerative colitis, Crohn’s disease, hiatus hernia, gastro-oesophageal reflux disease, and angiodysplasia, should use this medicine with caution, as their condition might worsen
• Precaution is advised for patients with pyloroduodenal obstruction

Surgery

• Chlorphenamine/ pseudoephedrine/ aspirin/ ascorbic acid contains aspirin, which may elevate the risk of bleeding during surgical procedures
• It's not recommended to use neuraxial regional anaesthetic techniques for patients on this medicine, especially if they are also on other medications with anticoagulant effects

Skin reactions

• This medicine has been associated with severe skin reactions, including exfoliative dermatitis, Stevens-Johnson syndrome, and toxic epidermal necrolysis, some of which have been fatal
• If patients show initial signs such as skin rashes, mucosal lesions, or other indicators of hypersensitivity, discontinue promptly

Laboratory tests

• Due to the aspirin content in this combination product, it may have an impact on thyroid function tests

Skin testing

• The combination product has the potential to suppress skin reactions to allergen extracts
• Patients undergoing skin tests should discontinue this medicine several days prior to the test to ensure accurate results

Hyperoxaluria

• Use with caution in patients with hyperoxaluria
• Prolonged use of large doses of vitamin C (ascorbic acid) can lead to increased tolerance

Aspartame

• Contains aspartame, a compound which is broken down in the body to phenylalanine
• Contraindicated for patients with phenylketonuria due to their inability to metabolise phenylalanine

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

South African registered indications and dosages

Symptomatic relief of colds and influenza

Chlorphenamine/ Pseudoephedrine/ Aspirin/ Ascorbic Acid
4/50/600/330 (mg)

• Oral (eft): 1 tab, 8hrly as needed

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Use the lowest effective dose for the shortest possible duration of treatment

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Gastric irritation may be reduced by taking doses after food

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Place one tablet in a glass of warm (or cold if so wished) water and allow to dissolve. Drink all the contents immediately once the whole tablet has dissolved

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Usage beyond 10 days without consulting a doctor is not recommended

Paeds. forms avail. in SA and covered in this monograph: eft

South African registered indications and dosages

Symptomatic relief of colds and influenza

Chlorphenamine/ Pseudoephedrine/ Aspirin/ Ascorbic Acid
4/50/600/330 (mg)

• Younger than 16 years: Contraindicated
• Older than 16 years: See adult dosage

Pregnancy 

South African recommendations

• Contraindicated
• Chlorphenamine/ pseudoephedrine/ aspirin/ ascorbic acid is contraindicated in pregnancy
• Use of NSAIDs, such as aspirin in this combination product, at around 20 weeks of gestation or later in pregnancy may cause a rare but serious foetal renal dysfunction leading to oligohydramnios and, in some cases, neonatal renal impairment
• Complications of prolonged oligohydramnios include limb contractures and delayed lung maturation, which may require invasive procedures such as exchange transfusion or dialysis, in some cases
• Regular use of NSAIDs, such as aspirin in this combination product, during the third trimester of pregnancy, may result in premature closure of the foetal ductus arteriosus in utero, and in persistent pulmonary hypertension of the new-born. The onset of labour may be delayed and its duration increased

Breastfeeding

South African recommendations

• Contraindicated
• Chlorphenamine/ pseudoephedrine/ aspirin/ ascorbic acid is contraindicated in breastfeeding women
• Pseudoephedrine as contained in this combination product is excreted in breast milk

Fertility

• No information available

South African recommendations

• Mild to moderate: Caution; no dose adjustment recommended
  Patients suffering from kidney disease should take this combination product under medical supervision. Care should be taken in patients with urinary retention
• Severe: Contraindicated

South African recommendations

• Caution; no dose adjustment recommended
  Patients suffering from liver disease should take this combination product under medical supervision

South African recommendations

• Caution; no dose adjustment recommended
  The elderly have an increased frequency of adverse reactions to NSAIDs, such as aspirin in this combination product, especially gastrointestinal perforation, ulceration and bleeding (PUBs) which may be fatal

Blood and the Lymphatic System Disorders

Less frequent

• Agranulocytosis
• Thrombocytopenia
• Pancytopenia
• Aplastic anaemia
• Iron-deficiency anaemia (during long-term salicylate therapy)
• Leukopenia
• Haemolytic anaemia

Frequency unknown

• Increased bleeding time
• Decreased platelet adhesiveness
• Hypoprothrombinaemia
• Haemolysis (in patients with G6PD deficiency)

Immune System Disorders

Frequency unknown

• Hypersensitivity reactions
• Urticaria
• Skin eruptions
• Angioedema
• Rhinitis
• Severe, even fatal, paroxysmal bronchospasm and dyspnoea (especially in asthmatics, chronic urticaria or rhinitis)
• Anaphylaxis

Metabolism and Nutrition Disorders

Frequency unknown

• Altered metabolism
• Disturbances of glucose metabolism

Psychiatric Disorders

Frequent

• Anxiety
• Restlessness
• Insomnia

Less frequent

• Hallucinations (particularly in children)

Frequency unknown

• Sleep disturbances
• Confusion
• Fear
• Irritability
• Psychotic states
• Euphoria
• Nervousness

Nervous System Disorders

Frequent

• Central nervous system depression
• Slight drowsiness to deep sleep (including lassitude)
• Dizziness or incoordination
• Headache
• Psychomotor impairment
• Antimuscarinic effects, such as dry mouth, thickened respiratory tract secretions, blurred vision, urinary difficulty or retention, constipation and increased gastric reflux

Less Frequent

• Paradoxical stimulation (especially at high doses, in children and the elderly)

Frequency Unknown

• Facial dyskinesia
• Adverse mental effects (particularly in children)
• Convulsions
• Paraesthesias
• Extrapyramidal effects
• Tremor
• Depression
• Tingling
• Heaviness and weakness of the hands

Eye Disorders

Frequency unknown

• Blurred vision
• Diplopia

Ear and Labyrinth Disorders

Frequency unknown

• Tinnitus
• Hearing loss

Cardiac Disorders

Frequent

• Tachycardia

Less frequent

• Palpitations
• Cardiac dysrhythmias

Frequency unknown

• Bradycardia
• Anginal pain
• Cardiac arrest
• Oedema
• Cardiac failure

Vascular Disorders

Frequency unknown

• Hypotension (accompanied by dizziness, fainting, and flushing)
• Vasoconstriction
• Hypertension
• Cerebral haemorrhage
• Pulmonary oedema

Respiratory, Thoracic and Mediastinal Disorders

Frequency unknown

• Impaired sense of smell
• Dryness of the respiratory passages
• Tightness of the chest
• Dyspnoea

Gastrointestinal Disorders

Frequent

• Gastrointestinal disturbances
• Nausea
• Dyspepsia
• Vomiting

Less frequent

• Major upper gastrointestinal bleeding
• Diarrhoea
• Epigastric pain

Frequency unknown

• Irritation of the gastric mucosa with erosion, ulceration, haematemesis and melaena
• Impaired sense of taste
• Ischaemic colitis
• Loss of appetite
• Epigastric distress
• Constipation
• Dryness of the mouth and throat
• Hypersalivation
• Peptic ulcers
• Perforation or gastrointestinal bleeding (sometimes fatal)
• Flatulence
• Abdominal pain
• Ulcerative stomatitis
• Exacerbation of colitis and Crohn’s disease
• Gastritis

Hepatobiliary Disorders

Frequency unknown

• Hepatotoxicity
• Hepatic injury
• Elevation of aminotransferase values

Skin and Subcutaneous Tissue Disorders

Less frequent

• Skin rashes
• Fixed medicine eruptions

Frequency unknown

• Exfoliative dermatitis
• Sweating
• Hair loss
• Bullous reactions, including Stevens-Johnson syndrome and toxic epidermal necrolysis

Musculoskeletal, Connective Tissue and Bone Disorders

Frequency unknown

• Myalgia

Renal and Urinary Disorders

Less frequent

• Urinary retention
• Analgesic nephropathy

Frequency unknown

• Hyperoxaluria
• Renal calcium oxalate calculi
• Renal impairment
• Difficulty in micturition
• Urinary frequency
• Dysuria

General Disorders and Administrative Site Conditions

Frequency unknown

• Weakness
• Fatigue

• Central nervous system (CNS) depressants
• Barbiturates
• Sedatives
• Hypnotics
• Opioid / narcotic analgesics
• Anxiolytic sedatives
• Tranquillisers
• Antipsychotics
• Other antimuscarinic medicines
• Atropine
• Tricyclic antidepressants
• Monoamine oxidase inhibitors (MAOIs), including reversible monoamine oxidase inhibitors (RIMA)
• Reserpine
• Methyldopa
• Volatile or halogenated anaesthetics
• Digoxin
• Quinidine
• Ergot alkaloids
• Oxytocin
• Non-steroidal anti-inflammatory drugs (NSAIDs), including aspirin
• Corticosteroids
• Warfarin
• Oral antidiabetic preparations
• Sulphonamides
• Anti-platelet medicines
• Selective serotonin reuptake inhibitors (SSRIs)
• Anti-gout preparations
• Probenecid
• Sulphinpyrazone
• Aminoglycoside antibiotics
• Dipyridamole
• Metoclopramide
• Metoprolol
• Carbonic anhydrase inhibitors
• Antacids and adsorbents
• Aluminium hydroxide
• Kaolin
• Sulfonylurea hypoglycaemic medicines
• Zafirlukast
• Methotrexate
• Phenytoin
• Valproate
• Mifepristone
• Calcium channel blockers
• Verapamil
• Spironolactone

Other interactions

• Alcohol
• Gold compounds
• Cutaneous histamine response to allergen extracts

Specific cases may require

• Cardiac function (patients with pre-existing congestive heart failure)
• Blood pressure (patients with pre-existing hypertension)

Chlorphenamine/ pseudoephedrine/ aspirin/ ascorbic acid has analgesic, antipyretic, antihistaminic and decongestant properties.

Chlorphenamine
Chlorphenamine is a potent antihistamine (H1-antagonist) that causes a moderate degree of sedation; it also has antimuscarinic activity. It is a common ingredient of compound preparations for symptomatic treatment of coughs and the common cold.

Pseudoephedrine
Pseudoephedrine is a direct and indirect acting sympathomimetic. It is given orally for the symptomatic relief of nasal congestion and is commonly combined with other ingredients in preparations intended for the relief of cough and cold symptoms.

Aspirin
Aspirin is a salicylate nonsteroidal anti-inflammatory medicine (NSAlD). It has analgesic, anti-inflammatory and antipyretic properties and acts as an inhibitor of the enzyme cyclo-oxygenase, which results in the direct inhibition of the biosynthesis of prostaglandins and thromboxanes from arachidonic acid. Aspirin also inhibits platelet aggregation. It is used for the relief of mild to moderate pain and minor febrile conditions, such as colds or influenza.

Ascorbic acid
Vitamin C (ascorbic acid) contributes to the normal function of the immune system and is an antioxidant for the maintenance of good health.

COMBINATION PREPARATIONS

Chlorphenamine/ Pseudoephedrine/ Aspirin/ Ascorbic Acid

Tablet effervescent 4mg/50mg/600mg/330mg

• Coryx effervescent (Cipla Medpro)