Codeine Phosphate

Registered South African indications:

• Pain

Contraindications

• Hypersensitivity to the active ingredient or to any of its excipients
• 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
• Moderate to severe 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
• Seizure disorders
• Myasthenia gravis
• Children with compromised respiratory function
• Biliary tract disorders
• Galactose intolerance
• Lapp lactase deficiency
• Glucose-galactose malabsorption
• May impair ability to drive and operate machinery

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

Pain - moderate

• Oral (tab): 15-60mg, 6hrly; Max: 360mg/24hrs

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Variable metabolism of codeine phosphate may result in unpredictable degrees of effect in different populations

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Discontinuation of therapy: Gradual dose reduction is recommended

Not established for use in children

Pregnancy 

• Caution
• Risk-benefit must be considered because opioid analgesics cross the placenta. Studies in animals have shown opioids to cause delayed ossification in mice and increased resorption in rats. Regular use during pregnancy may cause physical dependence in the foetus, leading to withdrawal symptoms in the neonate. During labour opioids enter the foetal circulation and may cause respiratory depression in the neonate. Respiratory malformation in neonates may be associated with exposure to codeine during pregnancy. Gastric stasis and risk of inhalation pneumonia could occur in the mother during labour. Administration should be avoided during the late stages of labour and during the delivery of a premature infant

Breastfeeding 

• Contraindicated
• Codeine is contraindicated in women 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

Renal Impairment 

• Caution; dose adjustment recommended

GFR (ml/min)	Dose
> 50	No adjustment necessary
10-50	Reduce dose by 25%
< 10	Reduce dose by 50%
CRRT	Reduce dose by 25%, titrate
Haemodialysis	No data available

Hepatic Impairment 

• Mild (Child-Pugh class A): No dose adjustment recommended 
• Moderate to severe (Child-Pugh class B and C): Caution; dose adjustment recommended

Severity	Dose recommendation
Child-Pugh class A	No adjustment necessary
Child-Pugh class B	Initial: 30 mg, Titrate as needed up to 60mg in divided doses;  Max: 180 mg/24hrs
Child-Pugh class C	Reduce recommended daily dose by 50%; Paracetamol-containing preparations are contraindicated

Elderly 

• Caution; no dose adjustment recommended
  Initial lower doses and extended dose intervals may be necessary; Titrate cautiously

Porphyria Information

• Probably not porphyrinogenic (PNP)

Drugs in Sport

• Permitted - No warnings

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 micturition
• 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

• Alcohol
• Anaesthetics
• Antiarrhythmic agents
• Central nervous system depressants
• Antihistamines
• Domperidone 
• Metoclopramide
• Cimetidine

None routine. Specific cases may require

• Hepatic function
• Respiratory function

Codeine phosphate risk in paediatric patients

• Codeine's analgesic effect depends on its conversion to morphine via the hepatic enzyme CYP2D6. In individuals, particularly young children, who are ultrarapid metabolisers due to genetic variance, this conversion is accelerated, resulting in toxic plasma concentrations of morphine
• Acknowledging the documented risk of severe respiratory depression and potential mortality, the use of codeine for analgesia is strongly discouraged in paediatric patients, especially those recovering from tonsillectomy or adenoidectomy

Additional safety precautions

• Codeine may cause drowsiness and impair concentration. Advise patients to take care driving, operating heavy machinery or other dangerous tasks.

Discontinuation of therapy

• Gradual dose reduction is recommended if clinically appropriate. Initially reduce the total daily dose by 50% and for 2 days, followed by a 25% reduction every 2 days thereafter.

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.

Tablet 30mg

• Lennon-Codeine Phosphate (Pharmacare) originator

COMBINATION PREPARATIONS

Codeine/ Paracetamol

Syrup  (per 5ml) 5mg/120mg

• Infapain (Alliance)

Syrup  (per 5ml) 4mg/150mg

• Supragesic Syrup (Innovate)
• Tensopyn Paed syrup (Mirren)

Tablet 8mg/320mg

• Spectrapain (Alliance) originator

Tablet 8mg/500mg

• Cogesic (Medicine Dev)
• Dino-cod (Pharma Q)
• Dolorol forte (Pharmacare) originator
• Painamol plus (Be-tabs)
• Paincodein (Innovata)
• Rocodin (Pharma Q)
• Vari-Cocodamol (LeBasi)

Tablet effervescent 8mg/500mg 

• Parafizz co (Cipla)

Tablet 10mg/500mg

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

Tablet 20mg/500mg

• Emapcod (Takeda)

Ibuprofen/ Codeine

Tablet 200mg/10mg

• Ibucod (Pharmacare)

Paracetamol/ Codeine/ Ibuprofen

Capsule 250mg/10mg/200mg

• Dentopain Forte (Sandoz SA)
• Gen-Payne (Adcock) originator
• Ibupain Forte (Sandoz)
• Myprodol (Adcock) originator

Paracetamol/ Codeine/I buprofen 

Capsule 350mg/10mg/200 mg 

• Mybucod (Pharmacare)
• Mybulen (Pharmacare)

Suspension (per 10ml) 250mg/10mg/200mg

• Mybulen (Pharmacare)
• Myprodol (Adcock) originator

Paracetamol/ Codeine/ Ibuprofen/ Pseudoephedrine

Tablet 125mg/10mg/200mg

• Ibucod (Pharmacare) originator

Paracetamol/ Codeine/ Meprobamate

Capsule 400mg/200mg/8mg  

• Synaleve (Adcock)
• Trinagesic (Adcock) originator

Paracetamol/ Codeine/ Meprobamate

Tablet 500mg/125mg/10mg 

• Meprogesic (Adcock) originator

Paracetamol/ Codeine/ Meprobamate

Capsule 320/150/8mg 

• Stilpane (Pharmacare)

Paracetamol/ Codeine/ Meprobamate/ Caffeine

Capsule 350mg/8mg/150mg/50mg 

• Supragesic (Pharmaceutical Enter)

Paracetamol/ Codeine/ Promethazine

Syrup (per 5ml) 120mg/5mg/6,5mg

• Adco Kiddipayne (Adcock) originator
• Ban Pain A/F (Pharmacare)
• Dynapayne (Thebe)
• Go-pain (Glenmark)
• Infapain forte (Alliance)
• Lentogesic (Adcock)
• Medipyn (Cape Pharma)
• Pynmed pain and fever (Medpro)
• Painagon (Be-tabs)
• Stilpane (Pharmacare)
• Stopayne (Adcock)
• Salterpyn (Adcock)

Paracetamol/ Codeine/ Promethazine

Syrup 120mg/5mg/7mg

• Tenston (Adcock) originator

Paracetamol/ Codeine/ Diphenhydramine

Syrup (per 5ml) 150mg/4mg/10mg

• Medirol-D (Medicine Dev)

Paracetamol/ Codeine/ Caffeine/ Diphenhydramine

Tablet 400mg/10mg/50mg/5mg

• Lenadol (Pharmacare) originator
• Propain (Adcock) originator
• Tensolve (Pharmacare) originator

Paracetamol/ Doxylamine/ Caffeine/Codeine 

Tablet 450mg/5mg/30mg/10mg

• Abflex-4 (Xeragen)
• Doxy Co (Gulf Drug)
• Lenapain (Pharmacare) originator
• Resdol (Akacia)
• Sedapain (Pharmacare) originator
• Sedinol (Pharmacare) originator
• Syndol (Sanofi) originator
• Tensopyn (Mirren)

Paracetamol/ Doxylamine/ Caffeine/ Codeine

Tablet 450mg/5mg/45mg/10mg

• Acurate (Pharmascript)
• Adco-dol (Adcock) originator
• Pynstop (Adcock) originator

Paracetamol/ Doxylamine/ Caffeine/ Codeine

Tablet 450mg/5mg/50mg/10mg 

• Betapyn (Adcock) originator

Paracetamol/ Doxylamine/ Caffeine/ Codeine

Effervescent tablet 450mg/5mg/50mg/10mg 

• Tensopyn (Mirren)

Paracetamol/ Doxylamine/ Caffeine/ Codeine

Tablet 500mg/5mg/30mg/10mg 

• Nomopain (Medicine Dev)
• Pharmadol tablets (Medicine Dev)

Paracetamol/ Caffeine/ Codeine/ Meprobamate

Tablet 320mg/48mg/8mg/150mg

• Spectrapain forte (Alliance) originator
• Stopayne (Adcock) originator

Paracetamol/ Caffeine/ Codeine/ Meprobamate 

Tablet 320mg/32mg/8mg/150mg

• Adco-Payne (Adcock) originator
• Adco-Salterpyn (Adcock) originator
• Antipyn Forte (Garec)
• Fevapar (Xeragen)
• Goldgesic (G D Searle)
• Go-Pain (Glenmark)
• Hopyn (Innovata)
• Megapyn (Compu)
• Medpromol (Sandoz)
• Nucopain (Gulf Drug)
• Pynmed (Medpro)
• Stilpane (Pharmacare) originator

Paracetamol/ Codeine/ Caffeine/ Phenyltoloxamine

Tablets 400mg/8mg/32mg/12mg 

• Suncodin (Winthrop) originator

Codeine/ Meprobamate/ Paracetamol

Capsule 8mg/200mg/400mg 

• Synaleve (Adcock) originator
• Trinagesic (Adcock) originator

Codeine/ Meprobamate/ Paracetamol

Tablet 10mg/125mg/500mg 

• Meprogesic (Adcock) originator

Codeine/ Meprobamate/ Paracetamol/ Caffeine 

Capsule 8mg/150mg/320mg/32mg 

• Dynadol (Thebe)
• Stilpane (Pharmacare) originator
• Vacudol Forte (XIixia) originator

Morphine/ Papaverine/ Codeine

Ampoule  (per ml) 6,72mg/0,6mg/0,52mg

• Omnopon (Bodene)

Morphine/ Papaverine/ Codeine

Ampoule (per ml) 12,44mg/1,2mg/1,04mg 

• Omnopon (Bodene)