Paracetamol/ Pseudoephedrine/ Promethazine/ Codeine

Registered South African indications:

• Symptomatic relief of colds and flu associated with cough

Paracetamol/pseudoephedrine/promethazine/codeine contains paracetamol which may be fatal in overdose. In the event of overdosage or suspected overdose and notwithstanding the fact that the person may be asymptomatic, the nearest doctor, hospital, poison control centre must be contacted immediately.

Registered South African contraindications

• Hypersensitivity to the active ingredients or any of the excipients in this combination product
• Severe renal impairment
• Severe hepatic impairment
• Patients receiving monoamine oxidase inhibitor treatment, or within 14 days of such treatment
• Children under 2 years of age
• Breastfeeding
• CYP2D6 ultra-rapid metabolisers who convert codeine into its active metabolite more rapidly and completely than other people. These individuals may experience signs of overdose/toxicity including symptoms such as extreme sleepiness, confusion, or shallow breathing, which may be life threatening
• Acute respiratory depression and obstructive airways disease especially in the presence of cyanosis and excessive bronchial secretion, and after operations on the biliary-tract
• Patients at risk of paralytic ileus
• Convulsive disorders, head injuries, and conditions in which intracranial pressure is raised
• Acute alcoholism
• Should not be given during an attack of bronchial asthma or in heart disease
• The use of promethazine as contained in this combination product may be associated with the sudden infant death syndrome

South African recommendations

• Pregnancy
• Mild to moderate renal impairment
• Mild to moderate hepatic impairment
• Elderly

Glucose and sucrose

• Affects glycaemic control in diabetes
• Not suitable for hereditary fructose intolerance, glucose-galactose malabsorption, sucrase-isomaltase insufficiency

Paracetamol

Continuous use

• Avoid continuous use for over ten days without medical advice

Requires caution in patients with:

• Liver or kidney disease
• Hepatitis
• Alcoholism
• Recovering liver disease patients
• Hyperthyroidism
• Cardiovascular disease such as dysrhythmia or tachycardia
• Occlusive vascular disorders, including arteriosclerosis, hypertension or aneurysms
• Diabetes
• Closed angle glaucoma

Pseudoephedrine hydrochloride

Occlusive vascular disease

• Use cautiously in occlusive vascular disease

Hallucinations

• Discontinue if hallucinations or restlessness occur

Promethazine hydrochloride

• Caution in
  • Glaucoma
  • Respiratory depression (fatalities in children under two)
  • Asthma
  • Bronchitis
  • Bronchiectasis
  • Coronary artery disease
  • Epilepsy
  • Hepatic and renal insufficiency
  • Bladder neck or pyloro-duodenal obstruction
• Avoid in children and adolescents with symptoms of Reye's Syndrome

Masking

• May mask the warning signs of ototoxicity caused by ototoxic medicines e.g. salicylates
• May also delay the early diagnosis of intestinal obstruction or raised intracranial pressure through the suppression of vomiting

Codeine phosphate

Requires caution in patients with: 

• Hypothyroidism
• Adrenocortical insufficiency
• Impaired liver function
• Prostatic hypertrophy
• Shock
• Inflammatory or obstructive bowel disorders
• Myasthenia gravis

Prolonged use

• Risk of dependency and addiction with prolonged use

No specific recommendations for adults are provided

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

South African registered indications and dosages

Paracetamol/ Pseudoephedrine/ Promethazine/ Codeine
120/25/6.5/5 (mg/5ml)

Symptomatic relief of colds and flu associated with cough

• Younger than 2 years: Contraindicated
• Between 2-5 years: Oral (syr): 5ml, 3 times dly
• Between 5-12 years: Oral (syr): 5-10ml, 3 times dly

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Do not exceed the recommended dose

Pregnancy 

South African recommendations

• Caution; not recommended
• Safety in pregnancy has not been established. Do not use in pregnancy

Breastfeeding

South African recommendations

• Contraindicated
• Safety in lactation has not been established
• Paracetamol/pseudoephedrine/promethazine/codeine is contraindicated in breastfeeding mothers

Fertility

South African recommendations

• No information available

South African recommendations

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

South African recommendations

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

South African recommendations

• Caution; no information available

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

Paracetamol

Blood and Lymphatic System Disorders

Less frequent

• Thrombocytopenia
• Agranulocytosis

Unknown frequency

• Leucopenia
• Pancytopenia
• Neutropenia
• Anaemia

Immune System Disorders

Less frequent

• Allergic reactions

Gastrointestinal Disorders

Unknown frequency

• Pancreatitis

Hepato-biliary Disorders

Less frequent

• Hepatitis

Renal and Urinary Disorders

Less frequent

• Renal colic
• Renal failure
• Sterile pyuria

Skin and Subcutaneous Tissue Disorders

Less frequent

• Skin rash (usually erythematous or urticarial)
• Dermatitis

Pseudoephedrine hydrochloride

Metabolism and Nutrition Disorders

Unknown frequency

• Reduced appetite
• Altered metabolism
• Disturbances of glucose metabolism

Psychiatric Disorders

Frequent

• Restlessness
• Insomnia

Unknown frequency

• Fear
• Anxiety
• Confusion
• Irritability
• Psychotic state

Nervous System Disorders

Less frequent

• Tremor

Cardiac Disorders

Less frequent

• Palpitations
• Tachycardia
• Reflex bradycardia
• Cardiac dysrhythmias
• Cardiac arrest
• Dyspnoea

Unknown frequency

• Anginal pain
• Cardiac oedema

Vascular Disorders

Unknown frequency

• Vasoconstriction with resultant hypertension
• Cerebral haemorrhage
• Hypotension with dizziness and flushing

Respiratory, Thoracic and Mediastinal Disorders

Unknown frequency

• Pulmonary oedema

Gastrointestinal Disorders

Less frequent

• Nausea
• Vomiting

Unknown frequency

• Hypersalivation

Skin and Subcutaneous Tissue Disorders

Less frequent

• Sweating

Renal and Urinary Disorders

Less frequent

• Difficulty in micturition
• Urinary retention

General Disorders and Administration Site Conditions

Less frequent

• Weakness
• Fainting

Promethazine hydrochloride

Blood and Lymphatic System Disorders

Less frequent

• Blood dyscrasias
• Haemolytic anaemia

Unknown frequency

• Agranulocytosis

Immune System Disorders

Unknown frequency

• Allergy
• Anaphylaxis

Metabolism and Nutrition Disorders

Less frequent

• Anorexia

Psychiatric Disorders

Unknown frequency

• Depression
• Elation
• Irritability
• Nightmares
• Insomnia
• Nervousness
• Inability to concentrate

Nervous System Disorders

Unknown frequency

• Incoordination
• Tremors
• Muscular weakness
• Sedation
• Tinnitus
• Headache
• Convulsions
• Tingling
• Cerebral stimulation (in infants and children)

Cardiac Disorders

Less frequent

• Tachycardia

Vascular Disorders

Less frequent

• Hypotension
• Dizziness

Respiratory, Thoracic and Mediastinal Disorders

Frequent

• Tightness of chest

Gastrointestinal Disorders

Less frequent

• Dryness of the mouth

Unknown frequency

• Vomiting
• Nausea
• Diarrhoea
• Constipation
• Epigastric pain
• Gastrointestinal disturbances

Musculoskeletal and Connective Tissue Disorders

Unknown frequency

• Muscle twitching
• Heaviness and weakness of hands

Renal and Urinary Disorders

Less frequent

• Difficulty in micturition

General Disorders and Administration Site Conditions

Unknown frequency

• Lassitude

Codeine phosphate

Immune System Disorders

Less frequent

• Urticaria

Psychiatric Disorders

Less frequent

• Restlessness
• Confusion

Unknown frequency

• Changes of mood
• Hallucinations

Nervous System Disorders

Frequent

• Drowsiness

Unknown frequency

• Headache
• Dizziness

Eye Disorders

Less frequent

• Miosis

Unknown frequency

• Raised intracranial pressure

Ear and Labyrinth Disorders

Unknown frequency

• Vertigo

Cardiac Disorders

Less frequent

• Bradycardia
• Palpitations

Unknown frequency

• Tachycardia

Vascular Disorders

Less frequent

• Orthostatic hypotension

Unknown frequency

• Hypothermia

Gastrointestinal Disorders

Frequent

• Constipation

Less frequent

• Nausea
• Vomiting
• Dry mouth

Hepatobiliary Disorders

Less frequent

• Biliary spasm

Skin and Subcutaneous Tissue Disorders

Less frequent

• Sweating
• Facial flushing
• Pruritus

Renal and Urinary Disorders

Less frequent

• Micturition difficulties
• Ureteric spasm

General Disorders and Administration Site Conditions

Unknown frequency

• Hypothermia

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

Paracetamol/ Pseudoephedrine/ Promethazine/ Codeine

• Amphetamine-like psychostimulants
• Oxytocin
• Anticholinergic agents
• Hepatotoxic agents
• Enzyme inducing medicines
• Metoclopramide
• Cholestyramine
• Probenecid

Pseudoephedrine

• Halogenated anaesthetics
• Cardiac glycosides
• Tricyclic antidepressants
• Antihypertensive agents
• Alpha- and beta-blocking medicines

Promethazine

• Atropine
• Tricyclic antidepressants
• Ototoxic agents
• Aminoglycoside antibiotics
• Central nervous system depressants
• Barbiturates
• Hypnotics
• Opioid analgesics
• Anxiolytic sedatives
• Antipsychotics
• Alcohol

Codeine

• Central nervous system depressants
• Anaesthetics
• Hypnotics
• Sedatives
• Phenothiazines
• Mexiletine
• Cisapride
• Metoclopramide
• Domperidone
• Alcohol

Other interactions

• Skin tests (affected by promethazine hydrochloride)

None routine

Paracetamol/ Pseudoephedrine/ Promethazine/ Codeine 
Paracetamol/ pseudoephedrine/ promethazine/ codeine has an analgesic, antipyretic, antihistaminic and antitussive properties.

Paracetamol
Paracetamol has analgesic and antipyretic effects.

Pseudoephedrine
Pseudoephedrine hydrochloride has decongestant properties.

Promethazine
Promethazine has antihistaminic and anticholinergic properties.

Codeine
Codeine is an opioid and metabolised to morphine, which in turn exerts an analgesic effect.

COMBINATION PREPARATIONS

Paracetamol/ Pseudoephedrine/ Promethazine/ Codeine

Syrup (per 5ml) 120mg/25mg/6.5mg/5mg

• Colcaps childrens syrup (Adcock)