Paracetamol/ Caffeine/ Phenyltoloxamine/ Codeine

Registered South African indications:

• Pain
• Colds and influenza

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

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
• Concommitant use with transcutaneous electrical nerve stimulation

Phenyltoxolamine
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

Codeine
Contraindications

• Hypersensitivity to the active ingredient or any of the excipients in this combination product
• Breastfeeding
• Severe hepatic impairment
• Acute respiratory depression
• Obstructive airways disease
• Acute alcoholism
• Raised intracranial pressure or head injury
• Comatose patients
• Conditions where inhibition of peristalsis is to be avoided
• CYP2D6 ultra-rapid metabolisers

Cautions

• Pregnancy
• Renal impairment
• Mild to moderate hepatic impairment
• Elderly 
• Debilitated
• Asthma and decreased respiratory reserve
• Misuse, abuse potential or dependence
• Dependency and addiction with prolonged and continuous use
• Hypotension
• Hypothyroidism
• Prostatic hypertrophy
• Urethral stricture
• Adrenocortical insufficiency
• Inflammatory or obstructive bowel disorders
• Shock
• Convulsive disorders
• Myasthenia gravis
• Children with compromised respiratory function
• Biliary tract disorders
• May impair ability to drive and operate machinery

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

Colds and influenza
Fever
Pain 
- Muscle pain
- Neuralgia
- Dysmenorrhea
- Sinus headaches
- Pain following tooth extraction

Paracetamol/ Caffeine/ Phenyltoxamine/ Codeine
400/32/12/8 (mg)

• Oral (tab): 2 tab, 6-8hrly; Max duration: 10 days

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

Colds and influenza
Fever
Pain 
- Muscle pain
- Neuralgia
- Dysmenorrhea
- Sinus headaches
- Pain following tooth extraction

Paracetamol/ Caffeine/ Phenyltoxamine/ Codeine
400/32/12/8 (mg)

• Younger than 6 years: Not recommended for use
• Between 6-8 years: 1/2 tab, 8hrly; Max duration: 10 days
• Between 9-12 years: 1 tab, 6hrly; Max duration: 10 days
• Older than 12 years: See adult dosage

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

Pregnancy

• FDA Pregnancy Category Not Rated (NR) (Phenyltoloxamine)

Breastfeeding

• Contraindicated (Codeine)

Renal Impairment

• Caution; no information available (Phenyltoloxamine)

Hepatic Impairment

• Mild to moderate: Caution; no information available (Phenyltoxolamine); 
• Severe: Contraindicated (Paracetamol, Codeine)

Elderly

• Caution; no information available (Phenyltoloxamine)

Drugs in Sport

• Permitted - No warning

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 
• Angiodema
• 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 arrhythmis

Gastrointestinal Disorders

• Oesophageal motility disorder
• Gastritis

Genitourinary Disorders

• Diuresis

Musculoskeletal Disorders

• Fasciculations

Skin and Subcutaneous Tissue Disorders

• Urticaria

Sensory Disorders

• Increased intraocular pressure
• Miosis

Phenyltoxolamine
Central Nervous System Disorders

• Drowsiness
• Dizziness
• 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

Codeine
Central Nervous System Disorders

• Dizziness
• Drowsiness
• Mood changes
• Euphoria 
• Dysphoria
• Mental depression
• Restlessness
• Confusion
• Headache
• Raised intracranial pressure
• Hallucinations
• Nightmares
• Vertigo

Cardiovascular Disorders

• Tachycardia
• Palpitations
• Bradycardia 
• Postural hypotension
• Facial flushing 
• Hypotension

Respiratory Disorders

• Dyspnoea
• Respiratory depression

Gastrointestinal Disorders

• Nausea and vomiting
• Constipation
• Dry mouth
• Stomach cramps
• Pancreatitis
• Biliary spasm

Genitourinary System Disorders

• Sexual dysfunction
• Erectile dysfunction
• Decreased potency
• Decreased libido
• Difficulty with micturition
• Urinary retention
• Ureteric spasm
• Dysuria

Endocrine and Metabolic Disorders

• Hyperglycaemia
• Anorexia

Musculoskeletal Disorders

• Uncontrolled muscle movements
• Muscle rigidity 

Skin and Subcutaneous Tissue Disorders 

• Skin rashes
• Urticaria
• Pruritus
• Sweating 
• Facial oedema

Immune System Disorders

• Maculopapular rash
• Fever
• Splenomegaly 
• Lymphadenopathy 

Sensory Disorders

• Blurred or double vision or other changes in vision
• Miosis

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

Paracetamol

• Metoclopramide 
• Domperidone
• Colestyramine
• Oral anticoagulants
• Chloramphenicol

Caffeine

• Adenosine
• Cocaine
• CYP1A2 inhibitors 
• Linezolid
• Xanthines

Phenyltoxolamine

• No information available

Codeine

• Alcohol
• Anaesthetics
• Antiarrhythmic agents
• Central nervous system depressants
• Antihistamines
• Domperidone 
• Metoclopramide
• Cimetidine

None routine

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. 

Phenyltoxolamine
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.

Codeine
Codeine is a centrally acting weak analgesic. It exerts its effect through mu opioid receptors. It resembles morphine in its pharmacodynamic actions although much weaker in its effects.

COMBINATION PREPARATIONS

Paracetamol/ Caffeine/ Phenyltoloxamine/ Codeine

Tablet 400mg/32mg/12mg/8mg

• Suncodin (Winthrop) originator