Paracetamol/ Pseudoephedrine/ Codeine

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

Cautions

• Mild to moderate hepatic impairment
• Renal impairment

Pseudoephedrine
Contraindications

• Hypersensitivity to the active ingredient or any of the excipients in this combination product
• Severe renal impairment
• Cardiovascular disease
• Children younger than 12 years
• Phaeochromocytoma
• Diabetes mellitus
• Hyperthyroidism
• Closed angle glaucoma
• Coadministration with monoamine oxidase inhibitors or within 14 days of their use
• Coadministration with other sympathomimetic decongestants
• Coadministration with beta blockers

Cautions

• Breastfeeding
• Mild to moderate renal impairment
• Severe hepatic impairment
• Elderly
• Enlarged prostate
• Bladder dysfunction
• Seizure disorders

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 the ability to drive and operate machinery

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

Symptomatic relief of colds and influenza
- Mild to moderate pain
- Nasal, sinus and Eustachian tube mucal congestion
- Fever

Paracetamol/ Pseudoephedrine/ Codeine
500/ 30/ 8 (mg)

• Oral (tab): 2 tab, 6-8hrly; Max: 8 tab/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 (NR) (Pseudoephedrine)

Breastfeeding

• Contraindicated (Codeine)

Renal Impairment 

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

Hepatic Impairment

• Mild to moderate: Caution; dose adjustment recommended (Codeine) 
• Severe: Contraindicated (Codeine)

Elderly

• Caution; dose adjustment recommended (Pseudoephedrine, Codeine)

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

Pseudoephedrine
Central Nervous System Disorders

• Hallucinations
• Insomnia
• Anxiety
• Restlessness
• Irritability
• Psychosis
• Headache
• Seizures
• Vertigo
• Ataxia
• Fatigue 
• Tremor

Cardiovascular Disorders

• Tachycardia
• Palpitations
• Arrhythmias
• Hypertension
• Impaired circulation to the extremities

Respiratory Disorders

• Dry throat
• Dry nose
• Dyspnoea
• Nasal congestion
• Pharyngeal oedema
• Thickening of bronchial secretions
• Wheezing

Gastrointestinal Disorders

• Dry mouth
• Nausea and vomiting
• Anorexia
• Constipation
• Diarrhoea
• Ischemic colitis

Genitourinary Disorders

• Urinary retention
• Dysuria

Skin and Subcutaneous Tissue Disorders

• Diaphoresis
• Skin photosensitivity
• Skin rash
• Urticaria

Immune, Blood and Lymphatic System Disorders

• Anaphylaxis
• Agranulocytosis
• Haemolytic anaemia
• Thrombocytopaenia

Sensory Disorders

• Closed angle glaucoma
• Blurred vision
• Diplopia
• Tinnitus

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 micturation
• 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
• Cholestyramine
• Oral anticoagulants
• Chloramphenicol

Pseudoephedrine

• Sympathomimetic agents
• Antihypertensive agents
• Monoamine oxidase inhibitors
• Volatile anaesthetics
• Cardiac glycosides
• Anticholinergic agents
• Antidepressants
• Antipsychotics 
• Doxapram 
• Oxytocin
• Aluminium oxide 

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 effects.

Pseudoephedrine
Pseudoephedrine acts mainly on alpha and also on beta adrenergic receptors. It produces vasoconstriction by acting on the alpha-adrenergic receptors in the mucosa of the respiratory tract. This results in the decongestant properties of pseudoephedrine.

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/ Pseudoephedrine/ Codeine

Tablet 500mg/30mg/8mg

• Sinumax co (Janssen) originator