Paracetamol/ Caffeine/ Phenyltoloxamine/ Phenylephrine/ Chlorpheniramine

Registered South African indications:

• Colds and influenza

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

Paracetamol
Contraindications

• Hypersensitivity to active ingredient or any of the excipients in this combination product
• Severe hepatic impairment

Cautions

• Pregnancy
• Renal impairment
• Mild to moderate hepatic impairment

Caffeine
Contraindications

• Hypersensitivity to the active ingredient or any of the excipients in this combination product

Cautions

• Pregnancy
• Breastfeeding
• Renal impairment
• Hepatic impairment
• Anxiety 
• Cardiovascular disease
• History of peptic ulcer
• Gastroesophageal reflux
• History of seizure disorder
• Neonates
• Concommitant use with transcutaneous electrical nerve stimulation

Phenyltoloxamine
Contraindications

• Hypersensitivity to the active ingredient or any of the excipients in this combination product
• Hypersensitivity to other antihistamines, especially ethanolamine-type agents

Cautions

• Pregnancy
• Breastfeeding
• Renal impairment
• Hepatic impairment
• Elderly
• Prostatic hypertrophy
• Urinary retention
• Bladder neck obstruction
• Closed angle glaucoma
• Asthma

Phenylephrine
Contraindications

• Hypersensitivity to the active ingredient or any of the excipients in this combination product
• Cardiovascular disease
• Hypertension
• Diabetes mellitus
• Closed angle glaucoma
• Hyperthyroidism
• Prostatic hypertrophy
• Phaeochromocytoma
• Coadministration with monoamine oxidase inhibitors or within 14 days of use

Cautions

• Pregnancy
• Breastfeeding
• Occlusive vascular disease
• Prolonged use

Chlorpheniramine
Contraindications

• Hypersensitivity to the active ingredient and any of the excipients in this combination product
• Premature infants
• Neonates
• Coadministration with monoamine oxidase inhibitors or within 14 days of their use

Cautions

• Breastfeeding
• Renal impairment
• Hepatic impairment
• Elderly
• Narrow angle glaucoma
• Urinary retention
• Prostatic hypertrophy
• Severe hypertension and cardiovascular disease
• Bronchitis
• Bronchiectasis
• Asthma
• Fructose intolerance
• Epilepsy
• Acute exacerbation of asthma
• Galactose intolerance
• Lapp lactase deficieny
• Glucose-galactose malabsorption
• May impair ability to drive and operate machinery

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

Colds and influenza

Paracetamol/ Caffeine/ Phenyltoloxamine/ Phenylephrine/ Chlorpheniramine
200/30/12.5/5/2 (mg)

• Oral (cap): 1-2 cap, 6-8hrly; Max: 6 doses/24hrs

Not established for use in children below 12 years

Recommendations for this combination product as per highest risk category when comparing individual active ingredients

Pregnancy

• FDA Pregnancy Category Not Rated (Phenyltoloxamine)

Breastfeeding

• Caution; not recommended (Phenyltoloxamine)

Renal Impairment

• Caution; no information available (Phenyltoloxamine)

Hepatic Impairment

• Mild to moderate: Caution; no information available (Phenyltoloxamine)
• Severe: Contraindicated (Paracetamol) 

Elderly

• Caution; dose adjustment recommended (Chlorpheniramine)

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

Paracetamol
Respiratory Disorders

• Bronchospasm

Hepatobiliary Disorders

• Hepatic dysfunction

Immune, Blood and Lymphatic System Disorders

• Anaphylaxis
• Cutaneous hypersensitivity reactions 
• Angioedema
• Stevens Johnson syndrome
• Thrombocytopenia 
• Agranulocytosis
• Methaemoglobinaemia

Caffeine
Central Nervous System Disorders

• Agitation
• Delirium
• Dizziness
• Hallucination
• Headache
• Insomnia
• Irritability
• Psychosis
• Restlessness

Cardiovascular Disorders

• Angina
• Chest pain
• Flushing
• Palpitations
• Sinus tachycardia
• Supraventricular tachycardia
• Vasodilation
• Ventricular arrhythmia

Gastrointestinal Disorders

• Oesophageal motility disorder
• Gastritis

Genitourinary Disorders

• Diuresis

Musculoskeletal Disorders

• Fasciculations

Skin and Subcutaneous Tissue Disorders

• Urticaria

Sensory Disorders

• Increased intraocular pressure
• Miosis

Phenyltoloxamine
Central Nervous System Disorders

• Drowsiness
• Dizzyness
• Euphoria
• Faintness
• Tiredness

Cardiovascular Disorders

• Tachycardia 
• High degree heart block

Immune, Blood and Lymphatic System Disorders

• Haemolytic anemia
• Thrombocytopenia
• Agranulocytosis  

Skin and Subcutaneous Tissue Disorders

• Diaphoresis

Sensory Disorders

• Blurred vision

Phenylephrine
Central Nervous System Disorders

• Headache

Cardiovascular Disorders

• Tachycardia
• Cardiac arrhythmia
• Palpitations
• Hypertension

Gastrointestinal Disorders

• Nausea and vomiting

Genitourinary Disorders

• Urinary retention

Chlorpheniramine
Central Nervous System Disorders

• Sedation
• Seizures
• Disturbances in attention
• Abnormal co-ordination
• Dizziness
• Headache
• Depression
• Nightmares
• Paradoxical stimulation

Cardiovascular Disorders

• Palpitations
• Tachycardia
• Arrhythmias
• Hypotension

Respiratory Disorders

• Thickening of bronchial secretions
• Tight chest

Gastrointestinal Disorders

• Nausea and vomiting
• Dry mouth
• Abdominal pain
• Diarrhoea
• Constipation
• Dyspepsia

Hepatobiliary Disorders

• Hepatitis 
• Jaundice

Genitourinary Disorders

• Urinary retention
• Dysuria

Endocrine and Metabolic Disorders

• Anorexia
• Increased appetite

Musculoskeletal Disorders

• Muscle twitching
• Muscle weakness

Skin and Subcutaneous Tissue Disorders

• Exfoliative dermatitis
• Rash
• Urticaria
• Photosensitivity

Immune, Blood and Lymphatic System Disorders

• Haemolytic anaemia
• Blood dyscrasias
• Allergic reaction
• Angioedema
• Anaphylactic reactions

Sensory Disorders

• Blurred vision
• Tinnitis

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

Paracetamol

• Metoclopramide 
• Domperidone
• Cholestyramine
• Oral anticoagulants
• Chloramphenicol

Caffeine

• Adenosine
• Cocaine
• CYP1A2 inhibitors 
• Linezolid
• Xanthines

Phenyltoloxamine

• No information available

Phenylephrine

• Monoamine oxidase inhibitors
• Anticholinergic agents
• Digoxin
• Sympathomimetic agents
• Tricyclic antidepressants
• Vasodilating agents
• Beta blockers
• CYP450 inducers
• Linezolid
• Alcohol

Chlorpheniramine

• Phenytoin
• Monoamine oxidase inhibitors
• Anticholinergic agents
• Antihistamines
• Central nervous system depressants

None routine. Specific cases may require

• Blood pressure
• Heart rate
• Hepatic function

Paracetamol
Paracetamol increases the pain threshold by inhibiting both isoforms of cyclooxygenase, COX-1, COX-2, and COX-3 enzymes involved in prostaglandin synthesis. It does not inhibit cyclooxygenase in peripheral tissues and, thus, has no peripheral anti-inflammatory affects.

Caffeine
Caffeine is a nonspecific adenosine receptor antagonist and acts as a central nervous system stimulant. 

Phenyltoloxamine
Phenyltoloxamine is an ethanolamine-type antihistamine which possesses typical H1-histamine antagonist properties. It available only in combination preparations for the treatment of coughs, cold, allergies. In addition to antihistaminic activity, it is considered to have analgesic properties. It has been suggested that the analgesic effects of antihistamines are related to modulation serotonergic and histaminergic pathways that may be involved in nociception.

Phenylephrine
Phenylephrine is a sympathomimetic agent which acts directly on adrenoreceptors. It has predominantly alpha adrenergic activity and does not cause stimulation of the central nervous system. It produces vasoconstriction which relieves nasal congestion. 

Chlorpheniramine
Chlorpheniramine acts as a competitive antagonist at H1-receptors. These histamine receptors are present in the respiratory tract, gastrointestinal tract and blood vessels thus allowing chlorpheniramine to perform its role in modulating the immune response and as a decongestant. 

COMBINATION PREPARATIONS

Paracetamol/ Caffeine/ Phenyltoloxamine/ Phenylephrine/ Chlorpheniramine

Capsule 200mg/30mg/12.5mg/5mg/2mg

• Dequa-flu (Pharmacare)