Codeine/ Ephedrine/ Promethazine

Registered South African indications: 

• Alleviation of cough

Codeine/ ephedrine/ promethazine may lead to drowsiness and impaired concentration, which may be aggravated by the simultaneous intake of alcohol, or any other central nervous system depressant agents. Patients should be warned not to drive a motor vehicle, operate dangerous machinery or climb dangerous heights, as impaired decision making could lead to accidents.

Registered South African contraindications

• Hypersensitivity to the active ingredient or to any of the excipients in this combination product
• Respiratory depression
• Acute alcoholism
• Head injuries and conditions in which intracranial pressure is raised
• Patients receiving monoamine oxidase inhibitors or within 14 days of their termination
• Premature infants or neonates
• During acute attacks of asthma
• Heart failure secondary to chronic lung disease
• Children under 2 years of age
• Safety in pregnancy has not been established

Additional contraindications for the (9.2/7.0/3.0 (mg/5ml)) syrup

• Diabetes
• Emphysema
• Severe hypertension
• Lactation

South African recommendations

• Breastfeeding (9/7.2/3.6 (mg/5ml) syrup)
• Renal impairment
• Hepatic impairment

Elderly

• Elderly patients are more susceptible to the many adverse effects of promethazine

Excess doses

• Exceeding the prescribed dose, together with prolonged and continuous use of this medication, may lead to dependency and addiction

Ability to drive and use machines

• May lead to drowsiness and impaired concentration, which may be aggravated by the simultaneous intake of alcohol, or any other central nervous system depressant agents
• Patients should be warned not to drive a motor vehicle, operate dangerous machinery or climb dangerous heights, as impaired decision making could lead to accidents

Excipient cautions

• Patients with the rare hereditary conditions such as fructose intolerance, glucose-galactose malabsorption or sucrase-isomaltase insufficiency should not take codeine/ephedrine/promethazine
• Contains glucose and sucrose which may have an effect on the glycaemic control of patients with diabetes mellitus

Codeine Phosphate

Caution or reduced doses are recommended in patients with:

• Hypothyroidism
• Adrenocortical insufficiency
• Impaired kidney or liver function
• Prostatic hypertrophy or shock
• Obstructive bowel disorders
• Myasthenia gravis

Ephedrine Hydrochloride

Caution is recommended in patients with:

• Hyperthyroidism
• Cardiovascular disease
• Occlusive vascular disorders
• Aneurysms
• Diabetes mellitus
• Closed-angle glaucoma

Patients with angina pectoris

• Angina pain may be precipitated in patients with angina pectoris

Patients undergoing anaesthesia

• Ephedrine hydrochloride, as contained in this combination medicine, should be avoided or used with caution in patients undergoing anaesthesia with halogenated anaesthetics and may cause an increased risk of dysrhythmias in patients receiving cardiac glycosides, quinidine or tricyclic antidepressants

Promethazine Hydrochloride

Caution is recommended in patients with:

• Cardiovascular diseases
• Hepatic diseases
• Narrow-angle glaucoma
• Urinary retention
• Prostatic hypertrophy

Potentiation of other medicines

• Promethazine may potentiate the hypotensive effect of some anti-hypertensives

Masking

• It has been suggested that some antihistamines could mask the warning signs of damage caused by ototoxic medicines such as aminoglycoside antibiotics

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

South African registered indications and dosages

Alleviation of cough

Codeine/ Ephedrine/ Promethazine
9/7.2/3.6 (mg/5ml) 

• Oral (syr): 5-10ml, 2-3 times dly

9.2/7.0/3.0 (mg/5ml) 

Oral (syr): 5-10ml, 3 times dly

Paed. forms avail. in SA and covered in this monograph: syr

South African registered indications and dosages

Alleviation of cough

Codeine/ Ephedrine/ Promethazine
9/7.2/3.6 (mg/5ml) 

• Younger than 2 years: Contraindicated
• Between 2-6 years: Oral (syr): 1.25-2.5ml, 2-3 times dly
• Between 7-11 years: Oral (syr): 2.5-5ml, 2-3 times dly
• 12 years and older: Oral (syr): 5-7.5ml, 2-3 times dly

9.2/7.0/3.0 (mg/5ml) 

• Younger than 2 years: Contraindicated
• Older than 2 years: Not recommended for use

Pregnancy

South African recommendations

• Contraindicated
• Safety in pregnancy has not been established

Breastfeeding

South African recommendations

9/7.2/3.6 (mg/5ml) syrup

• Caution
• Safety in lactation has not been established

9.2/7.0/3.0 (mg/5ml) syrup

• Contraindicated
• Not recommended in lactation
• Should not be given to premature infants or neonates under two years, as promethazine has been associated with the sudden infant death syndrome

Fertility

South African recommendations

• No information available

South African recommendations

• Caution; dose adjustment recommended
  Codeine phosphate, as contained in this combination medicine, should be given with caution or in reduced doses to patients with impaired kidney function

South African recommendations

• Caution; dose adjustment recommended
  Codeine phosphate, as contained in this combination medicine, should be given with caution or in reduced doses to patients with impaired liver function and should be used with care in patients with hepatic diseases

South African recommendations

9/7.2/3.6 (mg/5ml) syrup

• Caution; no dose adjustment recommended
  Elderly patients are more susceptible to the many adverse effects of promethazine

9.2/7.0/3.0 (mg/5ml) syrup

• Caution; no information available

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

Codeine Phosphate

Psychiatric Disorders

Less frequent

• Euphoria

Nervous System Disorders

Frequent

• Drowsiness
• Confusion

Less frequent

• Restlessness
• Vertigo (dizziness)
• Mood changes
• Deepening coma with high doses
• Increased intracranial pressure
• Convulsions (particularly in infants and children with high doses)

Eye Disorders

Frequent

• Miosis

Cardiac Disorders

Less frequent

• Bradycardia
• Palpitations

Vascular Disorders

Less frequent

• Circulatory failure
• Hypotension
• Orthostatic hypotension

Respiratory, Thoracic and Mediastinal Disorders

Frequent

• Respiratory depression

Skin and Subcutaneous Tissue Disorders

Less frequent

• Pruritus
• Urticaria
• Sweating

Musculoskeletal, Connective Tissue and Bone Disorders

Less frequent

• Muscle rigidity (reported following high doses)

Renal and Urinary Disorders

Less frequent

• Difficulty in micturition
• Ureteric and biliary spasm
• Anti-diuretic effect

General Disorders and Administrative Site Conditions

Less frequent

• Facial flushing
• Hypothermia

Ephedrine Hydrochloride

Metabolism and Nutrition Disorders

Frequency unknown

• Altered metabolism including disturbances of glucose metabolism

Psychiatric Disorders

Less frequent

• Psychotic states

Nervous System Disorders

Frequent

• Anxiety
• Restlessness
• Insomnia
• Headache

Less frequent

• Tremor
• Fear

Frequency unknown

• Confusion
• Irritability
• Weakness

Cardiac Disorders

Frequent

• Tachycardia
• Palpitations

Less frequent

• Reflex bradycardia
• Cardiac dysrhythmias
• Angina pain
• Cardiac arrest

Frequency unknown

• Dyspnoea

Vascular Disorders

Less frequent

• Vasoconstriction with resultant hypertension
• Hypotension with dizziness and fainting

Gastrointestinal Disorders

Less frequent

• Decrease in appetite
• Nausea and vomiting

Frequency unknown

• Hypersalivation

Skin and Subcutaneous Tissue Disorders

Frequency unknown

• Sweating

Renal and Urinary Disorders

Frequency unknown

• Difficulty in micturition
• Urinary retention

General Disorders and Administrative Site Conditions

Less frequent

• Flushing

Promethazine Hydrochloride

Blood and the Lymphatic System Disorders

Less frequent

• Agranulocytosis
• Leucopenia
• Haemolytic anaemia
• Thrombocytopenia

Psychiatric Disorders

Less frequent

• Depression
• Euphoria
• Confusion

Nervous System Disorders

Frequent

• Sedation
• Headache
• Dizziness
• Lassitude
• Incoordination

Less frequent

• Paradoxical central nervous system stimulation (especially at high doses in children or elderly)

Frequency unknown

• Convulsions
• Extrapyramidal effects
• Tremor
• Sleep disturbances

Eye Disorders

Frequent

• Blurred vision

Ear and Labyrinth Disorders

Less frequent

• Tinnitus

Vascular Disorders

Frequency unknown

• Hypotension

Respiratory, Thoracic and Mediastinal Disorders

Frequent

• Tightness of the chest

Gastrointestinal Disorders

Frequent

• Dryness of the mouth
• Constipation

Less frequent

• Nausea
• Vomiting
• Diarrhoea
• Epigastric pain
• Anorexia or increased appetite

Hepato-Biliary Disorders

Frequency unknown

• Jaundice

Skin and Subcutaneous Tissue Disorders

Less frequent

• Photosensitivity
• Angioedema

Frequency unknown

• Sweating

Musculoskeletal System, Connective Tissue and Bone Disorders

Frequency unknown

• Myalgia

Urinary and Renal Disorders

Frequent

• Difficulty in micturition
• Dysuria

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

Codeine Phosphate

• Central nervous system depressants
• Anaesthetics
• Anxiolytics
• Hypnotics
• Tricyclic antidepressants
• Antipsychotics
• Alcohol

Ephedrine Hydrochloride

• Halogenated anaesthetics
• Cardiac glycosides
• Quinidine
• Tricyclic antidepressants

Promethazine Hydrochloride

• Central nervous system depressants
• Barbiturates
• Hypnotics
• Opioid analgesics
• Anxiolytics
• Sedatives
• Antipsychotics
• Antimuscarinic medicines
• Atropine
• Some antidepressants
• Tricyclic antidepressants
• Monoamine oxidase inhibitors
• Ototoxic agents
• Aminoglycosides
• Anti-hypertensives
• Alcohol

None routine 

Codeine Phosphate
Codeine phosphate is a narcotic analgesic agent.

Ephedrine Hydrochloride
Ephedrine hydrochloride is sympathomimetic with bronchodilator and central nervous system stimulant properties.

Promethazine Hydrochloride
Promethazine hydrochloride is a phenothiazine derivative with antihistamine and sedative properties.

COMBINATION PREPARATIONS

Codeine/ Ephedrine/ Promethazine

Syrup (per 5ml) 9.2mg/7mg/3mg

• Brunacod (iNova Pharmaceuticals) originator

Codeine/ Ephedrine/ Promethazine

Syrup (per 5ml) 9mg/7.2mg/3.6mg

• Dequa-Coff (Pharmacare)
• Lenazine forte (Pharmacare)
• Phensedyl Cough Linctus  (Sanofi)