Aspirin/ Paracetamol/ Caffeine

Registered South African indications:

• Pain
• Fever

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

Aspirin
Contraindications 

• Hypersensitivity to the active ingredient or any of the excipients in this combination product
• Pregnancy >30 weeks
• Severe renal impairment
• Severe hepatic impairment
• Peptic ulcer 
• Gastric/intestinal haemorrhage
• Cerebrovascular haemorrhages
• Coagulation disorders 
• Gout
• Coadministration with methotrexate at doses >15mg/week 

Cautions 

• Pregnancy <30 weeks
• Breastfeeding
• Mild to moderate renal impairment
• Mild to moderate hepatic impairment
• Elderly 
• Children < 16 years
• Surgery
• Menorrhagia
• Hypertension
• History of gastric or duodenal ulcer
• Haemorrhagic episodes
• Dehydration
• History of asthma
• History of hay fever
• History of nasal polyps 
• History of chronic respiratory diseases
• Gout 

Paracetamol
Contraindications

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

Cautions

• 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
• Coadministration with transcutaneous  electrical nerve stimulation 

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

Pain - mild to moderate
Fever

Aspirin/ Paracetamol/ Caffeine
453.6/ 324/ 64.8 (mg)

• Oral (pdr): 1 powder, 4hrly; Max: 6 powders/24hrs

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Take after meals

Take with water

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Aspirin/ Paracetamol/ Caffeine
400/ 100/ 30 (mg)

• Oral (tab): 1-2 tab, 4hrly; Max: 4 doses/24hrs

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

Pain - mild to moderate
Fever

Aspirin/ Paracetamol/ Caffeine
453.6/ 324/ 64.8 (mg)

• Younger than 12 years: Oral (pdr): Not established for use
• Older than 12 years: Oral (pdr): See adult dosage

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Take after meals

Take with water

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Aspirin/ Paracetamol/ Caffeine
400/ 100/ 30 (mg)

• Younger than 6 years: Oral (tab): Not established for use
• Between 6-12 years: Oral (tab): 1/2-1 tab, 4hrly; Max: 4 doses/24hrs
• Older than 12 years: Oral (tab): See adult dosage

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

Pregnancy

• <30 weeks: FDA Pregnancy Category C (Aspirin) 
• >30 weeks: FDA Pregnancy Category D (Aspirin)

Breastfeeding

• Caution; not recommended (Aspirin)

Renal Impairment

• Mild to moderate: Caution; no dose adjustment recommended (Aspirin)
• Severe: Contraindicated (Aspirin)

Hepatic Impairment

• Mild to moderate: Caution; no dose adjustment recommended (Aspirin)
• Severe: Contraindicated (Aspirin)

Elderly

• Caution; no dose adjustment recommended (Aspirin)  

Drugs in Sport

• Permitted - No warning

Aspirin
Central Nervous System Disorders

• Intracranial haemorrhage
• Headache
• Vertigo

Cardiovascular  Disorders

• Hemorrhagic vasculitis

Respiratory Disorders

• Rhinitis
• Dyspnoea
• Bronchospasm
• Asthma attacks

Gastrointestinal Disorders

• Dyspepsia
• Severe gastrointestinal haemorrhage
• Nausea and vomiting
• Gastric or duodenal ulcers and perforation
• Diarrhoea

Hepatobiliary Disorders

• Hepatic impairment

Genitourinary Disorders

• Menorrhagia
• Renal impairment
• Salt and water retention

Endocrine and Metabolic Disorders

• Hyperuricaemia

Skin and Subcutaneous Tissue Disorders

• Urticaria
• Steven-Johnsons syndrome
• Lyells syndrome
• Purpura
• Erythema nodosum
• Erythema multiforme

Immune, Blood and Lymphatic System Disorders

• Hypersensitivity reactions
• Angio-oedema
• Allergic oedema
• Anaphylactic reactions including shock 
• Increased bleeding tendencies
• Thrombocytopenia
• Granulocytosis
• Aplastic anaemia
• Epistaxis
• Gingival bleeding
• Iron deficiency anaemia

Sensory Disorders

• Reduced hearing ability
• Tinnitus 

Paracetamol
Respiratory Disorders

• Bronchospasm

Hepatobiliary Disorders

• Hepatic impairment

Immune, Blood and Lymphatic System Disorders

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

Caffeine
Central Nervous System Disorders

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

Gastrointestinal Disorders

• Oesophageal motility disorder (sphincter tone decreased)
• Gastritis

Genitourinary Disorders

• Diuresis

Musculoskeletal Disorders

• Fasciculations

Skin and Subcutaneous Tissue Disorders

• Urticaria

Sensory Disorders

• Increased intraocular pressure
• Miosis

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

Aspirin

• Methotrexate
• Probenecid
• Anticoagulants
• Antiplatelet agents
• Selective serotonin reuptake inhibitors
• Sulphonylureas
• Digoxin
• Lithium
• Antihypertensives
• Diuretics
• Carbonic anhydrase inhibitors
• Corticosteroids
• Non-steroidal anti-inflammatory drugs
• Ciclosporin
• Tacrolimus
• Phenytoin
• Sodium valproate
• Alcohol
• Antacids 

Paracetamol

• Metoclopramide 
• Domperidone
• Colestyramine
• Oral anticoagulants
• Chloramphenicol

Caffeine

• Adenosine
• Cocaine
• CYP1A2 Inhibitors 
• Linezolid 
• Xanthines 

None routine

Aspirin
Acetylsalicylic acid inhibits the cyclooxygenase (COX) enzyme, thereby preventing production of prostaglandins and thromboxanes. 

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.

COMBINATION PREPARATIONS

Aspirin/ Paracetamol/ Caffeine

Tablet 226.8mg/162mg/32.4mg

• Grand-pa (GSK)

Tablet 400mg/100mg/30mg

• Compral (Adcock)

Powder 453.6mg/324mg/64.8mg

• Compral (Adcock)
• Grand-pa (GSK)