Paracetamol/ Codeine

Registered South African indications: 

• Pain
• Fever

Contraindications

• Hypersensitivity to the active ingredients or any of the excipients in this combination product
• Breastfeeding
• Severe hepatic impairment
• Paediatric patients undergoing tonsillectomy or adenoidectomy for obstructive sleep apnoea syndrome
• CYP2D6 ultra-rapid metabolizers 

Cautions

• Pregnancy
• Renal impairment
• Mild to moderate hepatic impairment
• Elderly
• Children < 12 years 
• Deficiency of CYP2D6 enzyme 
• Children with compromised respiratory function
• May impair ability to drive or operate machinery 

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

Pain - mild to moderate
Fever

Paracetamol/ Codeine
500/8 (mg)

• Oral (tab, eft): 1-2 tab/eft, 4-6hrly; Max: 8 tab/24hrs

500/10 (mg)

• Oral (tab): 1-2 tab, 6hrly

500/20 (mg)

• Oral (tab): 1 tab, 6hrly

Tab: Do not cut/ crush/ chew/ dissolve

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

Pain - mild to moderate
Fever

Paracetamol/ Codeine
500/8 (mg)

• Younger than 6 years: Not established for use
• Between 6-12 years: Oral (tab): 1/2-1 tab, 6hrly
• Older than 12 years: Oral (tab): 1 tab, 4-6hrly

500/8 (mg)

• Younger than 6 years: Not established for use
• Between 6-12 years: Oral (eft): 1 eft, 6hrly; Max: 4 eft/24hrs
• Older than 12 years: Oral (eft): 1 tab, 4-6hrly

500/10 (mg)

• Younger than 7 years: Not established for use
• Between 7-12 years: Oral (tab): 1/2-1 tab, 6hrly
• Older than 12 years: See adult dosage

500/20 (mg)

• Younger than 12 years: Not established for use
• Older than 12 years: See adult dosage

150/4 (mg/5ml)

• Younger than 6 months: Not established for use
• Between 6 months - 1 year: Oral (syr): 2.5ml, 4hrly; Max: 4 doses/24hrs
• Between 1-5 years: Oral (syr): 5ml, 4hrly; Max: 4 doses/24hrs
• Between 6-12 years: Oral (syr): 5-10ml, 4hrly; Max: 4 doses/24hrs

Tab: Do not cut/ crush/ chew/ dissolve

Pregnancy

• Caution
• There is inadequate evidence of the safety of codeine in human pregnancy. Animal studies with codeine do not indicate direct or indirect harmful effects with respect to reproductive toxicity
• There is epidemiological evidence for the safety of paracetamol. Animal studies with paracetamol do not indicate direct or indirect harmful effects with respect to reproductive toxicity. A large amount of data on pregnant women indicate neither malformative, nor feto/neonatal toxicity. Paracetamol can be used during pregnancy if clinically needed however it should be used at the lowest effective dose for the shortest possible time and at the lowest possible frequency
• As a precautionary measure, it is preferable to avoid the use of paracetamol/ codeine during pregnancy

Breastfeeding

• Contraindicated (Codeine)
• Codeine should not be used during breastfeeding. At normal therapeutic doses codeine and its active metabolite may be present in breast milk at very low doses and is unlikely to adversely affect the breastfed infant. However, if the patient is an ultra-rapid metaboliser of CYP2D6, higher levels of the active metabolite, morphine, may be present in breast milk and on very rare occasions may result in symptoms of opioid toxicity in the infant, which may be fatal
• If symptoms of opioid toxicity develop in either the mother or the infant, then all codeine containing medicines should be stopped and alternative non-opioid analgesics prescribed. In severe cases, consideration should be given to prescribing naloxone to reverse these effects
• Paracetamol is excreted in breast milk but not in a clinically significant amount

Renal Impairment

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

Hepatic Impairment

• Mild to moderate: Caution; dose adjustment recommended (Codeine, Paracetamol)
  Refer to single agent monograph for Codeine
  Refer to single agent monograph for Paracetamol
• Severe: Contraindicated (Paracetamol)

Elderly

• Caution; no dose adjustment recommended (Codeine)

Porphyria Information

• Not yet classified (NC)

Drugs in Sport

• Permitted - No warnings

Central Nervous System Disorders

• Dependance
• Withdrawal 

Gastrointestinal Disorders

• Nausea and vomiting
• Constipation
• Dry mouth

Skin and Subcutaneous Tissue Disorders 

• Skin rashes
• Sweating 

Immune, Blood and Lymphatic System Disorders

• Allergic reactions 
• Thrombocytopaenia
• Agranulocytosis  

• Mexiletine
• Metoclopramide 
• Domperidone
• Colestyramine
• Warfarin
• Central nervous system depressants
• Domperidone 
• Metoclopramide

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.

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/ Codeine

Tablet 500mg/8mg 

• Codorol (Medicine Developers)
• Cogesic (Oethmaan Biosims)
• Dino-cod (Pharma Q)
• Dolorol forte (Pharmacare)
• Painamol plus (Be-Tabs)
• Paincodein (Innovata)
• Rocodin (Pharma Q)
• Vari-Cocodamol (LeBasi Pharm)
• Varipan Co (LeBasi Pharm)

Tablet 500mg/10mg 

• Adco-Napacod (Adcock)
• Kodapon (Gulf) 

Tablet 500mg/20mg 

• Empacod (Litha Pharma) originator

Tablet effervescent 500mg/8mg 

• Parafizz co (EFT) (Cipla)

Syrup (per 5ml) 120mg/5mg

• Infapain (Alliance) orginator

Syrup (per 5ml) 150mg/4mg

• Supragesic (Innovata)
• Tensopyn Paed syrup (Cipla Medpro)