Ascorbic Acid/ Paracetamol/ Codeine [Discontinued in SA Market]

Registered South African indications:

• Pain

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

Ascorbic acid
Contraindications

• Hypersensitivity to the active ingredient or any of the excipients in this combination product
• Hyperoxaluria

Cautions

• Pregnancy
• Breastfeeding
• Renal impairment
• Diabetes mellitus
• Glucose-6-phosphate dehydrogenase deficiency
• Haemachromatosis
• High doses 

Paracetamol
Contraindications

• Hypersensitivity to active ingredient or to any of the excipients in this combination product
• Severe hepatic impairment

Cautions

• Pregnancy
• Renal impairment
• Mild to moderate hepatic impairment

Codeine
Contraindications

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

Cautions

• Pregnancy
• Renal impairment
• Mild to moderate 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
• May impair ability to drive and operate machinery

Additional contraindications for this combination product

• Coadministration of monoamine oxidase inhibitors or within 14 days of their use
• After surgery on biliary tract
• Acute bronchial asthma exacerbation
• Cardiac failure secondary to chronic lung disease

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

Pain - mild to moderate

Ascorbic acid/ Paracetamol/ Codeine
50/500/10 (mg)

• Oral (tab): 1-2 tab, 6hrly

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

Pain - mild to moderate

Ascorbic acid/ Paracetamol/ Codeine
50/500/10 (mg)

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

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

Pregnancy

• Caution; not recommended (Codeine)
• Paracetamol
  Epidemiological studies in human pregnancy have shown no ill effects due to paracetamol used in the recommended dosage, but patients should follow the advice of their doctor regarding its use. 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
• Codeine
  As with all medications caution should be exercised during pregnancy, especially in the first trimester. A possible association with respiratory and cardiac malformations has been reported following first trimester exposure to codeine. Regular use of codeine during pregnancy may cause physical dependence in the foetus leading to withdrawal symptoms in the neonate. Administration of codeine during labour may depress respiration in the neonate. Opioid analgesics may cause gastric stasis during labour, increasing the risk of inhalation pneumonia in the mother
• Ascorbic acid
  For ascorbic acid no clinical data on exposed pregnancies are available. Animal studies do not indicate direct or harmful effects with respect to pregnancy, embryonal/foetal development, parturition or postnatal development. Pregnant women should exercise caution

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 breast fed 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 

Renal Impairment

• Caution; dose adjustment recommended (Codeine)

Hepatic Impairment

• Mild to moderate: Caution; dose adjustment recommended (Codeine)
• Severe: Contraindicated (Paracetamol, Codeine)

Elderly

• Caution; dose adjustment recommended (Codeine)

Porphyria Information

• Probably not porphyrinogenic (PNP)

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

Ascorbic acid
Central Nervous System Disorders

• Dizziness
• Fatigue
• Headache

Cardiovascular Disorders

• Flushing

Gastrointestinal Disorders

• Diarrhoea
• Nausea and vomiting
• Flank pain
• Heartburn

Endocrine and Metabolic Disorders

• Hyperoxaluria

Paracetamol
Respiratory Disorders

• Bronchospasm

Hepatobiliary Disorders

• Hepatic dysfunction

Immune, Blood and Lymphatic System Disorders

• Anaphylaxis
• Cutaneous hypersensitivity reactions 
• Angioedema
• Stevens Johnson syndrome
• Thrombocytopenia 
• Agranulocytosis
• Methaemoglobinaemia

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

Ascorbic acid

• Bortezomib
• Fluphenazine
• Desferoxamine
• Copper
• Aluminium
• Aspirin
• Nicotine
• Alcohol
• Appetite suppressants 
• Anticonvulsants
• Iron
• Oral contraceptives 
• Tetracycline 
• Oral anticoagulants 
• Citrate 

Paracetamol

• Metoclopramide 
• Domperidone
• Cholestyramine
• Oral anticoagulants
• Chloramphenicol

Codeine

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

None routine. Specific cases may require

• Hepatic function  
• Respiratory function

Ascorbic acid
Ascorbic acid, a water-soluble vitamin, is essential for formation of collagen and intercellular material, and therefore necessary for the development of cartilage, bone, teeth and for the healing of wounds. It is also essential for the conversion from folic acid to folinic acid, facilitates iron absorption from the gastro-intestinal tract, influences haemoglobin formation and erythrocyte maturation and assists in providing resistance to infections

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

Ascorbic Acid/ Paracetamol/ Codeine

Tablet 50mg/500mg/10mg

• Paracetacod (Adcock)