Paracetamol/ Promethazine/ Codeine

Registered South African indications: 

• Pain
• Fever

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

• Pregnancy
• Renal impairment
• Mild to moderate hepatic impairment

Promethazine
Contraindications

• Hypersensitivity to the active ingredient or any of the excipients in this combination product
• Coma or central nervous system depression
• Children < 2 years
• Coadministration with monoamine oxidase inhibitors or within 14 days of their use

Cautions

• Pregnancy
• Breastfeeding
• Renal impairment
• Hepatic impairment
• Elderly
• Asthma
• Bronchitis
• Bronchiectasis
• Severe coronary artery disease
• Narrow angle glaucoma
• Epilepsy
• Bladder neck obstruction
• Pyloroduodenal obstruction
• Children and adolescents with signs and symptoms of Reye's syndrome
• Ototoxicity
• Intestinal obstruction
• Raised intracranial pressure

Codeine
Contraindications

• Hypersensitivity to the active ingredient or any of the excipients in this combination product
• Breastfeeding
• 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
• Coadministration with CYP2D6 ultra-rapid metabolisers

Cautions

• Pregnancy
• Renal impairment
• 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

Not indicated for use in adults 

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

Pain
Fever

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

• Younger than 2 years: Not established for use
• Between 2-5 years: Oral (syr): 5ml, 8hrly
• Between 6-12 years: Oral (syr): 5-10ml, 8hrly

120/7/5 (mg/5ml)

• Younger than 2 years: Not established for use
• Between 2-5 years: Oral (syr): 5ml, 4hrly
• Between 6-12 years: Oral (syr): 10ml, 4hrly

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

Pregnancy

• Caution (Codeine, Promethazine)
• Refer to the single agent monograph for Codeine
• Refer to the single agent monograph for Promethazine
• Refer to the single agent monograph for Paracetamol

Breastfeeding

• Contraindicated (Codeine)
• Refer to the single agent monograph for Codeine
• Refer to the single agent monograph for Promethazine
• Refer to the single agent monograph for Paracetamol

Renal Impairment

• Caution; dose adjustment recommended (Paracetamol, Codeine)
  No dose adjustment recommendations are available for this combination product
  Refer to the single agent monograph for Paracetamol
  Refer to the single agent monograph for Codeine

Hepatic Impairment

• Mild to moderate: Caution; dose adjustment recommended (Paracetamol)
  No dose adjustment recommendations are available for this combination product
  Refer to the single agent monograph for Paracetamol
• Severe: Contraindicated (Paracetamol)

Elderly

• Caution; dose adjustment recommended (Codeine, Promethazine)
  Refer to the single agent monograph for Codeine
  Refer to the single agent monograph for Promethazine

Porphyria Information

• Not yet classified (NC)

Drugs in Sport

• Permitted - No warnings

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

Promethazine
Central Nervous System Disorders

• Drowsiness
• Dizziness
• Restlessness
• Headaches
• Nightmares
• Tiredness
• Disorientation
• Confusion
• Paradoxial hyperexcitability
• Extrapyramidal side effects
• Tic-like movements of head and face

Cardiovascular Disorders

• Palpitations
• Hypotension
• Arrhythmias

Gastrointestinal Disorders

• Dry mouth
• Anorexia
• Gastric irritation

Hepatobiliary Disorders

• Jaundice

Genitourinary Disorders

• Urinary retention

Skin and Subcutaneous Tissue Disorders

• Pruritis
• Anaphylaxis

Immune, Blood and Lymphatic System Disorders

• Haemolytic anaemia

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 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
• Colestyramine
• Oral anticoagulants
• Chloramphenicol

Promethazine

• Anticholinergic agents
• Tricyclic antidepressants
• Central nervous system depressants
• Monoamine oxidase inhibitors
• Ototoxic agents

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.

Promethazine
Promethazine is a phenothiazine derivative and a potent histamine antagonist with a prolonged action. It has local analgesic actions and some anti-adrenergic and atropine-like effects.  Muscarinic blockade may be responsible for its antiemetic activity. 

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/ Promethazine/ Codeine

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

• Adco-Kiddipayne (Adcock)
• Adco-Salterpyn (Adcock)
• Ban Pain A/F (Pharmacre)
• Dynapayne (Thebe)
• Go-pain (Glenmark)
• Goldgesic (Medicine Dev)
• Infapain Forte (Alliance) originator
• Kid-Eeze (Camox)
• Lentogesic (Adcock)
• Medipyn (Caps Pharmaceuticals)
• Painagon Syrup (Ranbaxy Pharmaceuticals)
• Pynmed (Cipla)
• Stilpane (Pharmacare)
• Stopayne (Adcock)

Syrup (per 5ml) 120/7/5mg

• Tenston (Adcock)