Paracetamol/ Meprobamate/ Caffeine/ Codeine

Registered South African indications: 

• Pain

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

Meprobamate
Contraindications 

• Hypersensitivity to the active ingredient or any of the excipients in this combination product
• Pregnancy
• Breastfeeding
• Substance abuse
• Acute intermittent porphyria
• Acute pulmonary insufficiency
• Respiratory depression

Cautions 

• Renal impairment
• Hepatic impairment
• Elderly
• Depression
• Suicidal ideation or intent
• Respiratory disease
• Muscle weakness
• Epileptics
• High dosages
• Prolonged use
• Abrupt withdrawal
• May impair ability to drive and operate machinery

Caffeine
Contraindications 

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

Cautions

• Renal impairment
• Hepatic impairment
• Anxiety 
• Cardiovascular disease
• History of peptic ulcer
• Gastroesophageal reflux
• History of seizure disorder
• Neonates 
• Concomitant use of transcutaneous electrical nerve stimulation  

Codeine
Contraindications

• Hypersensitivity to the active ingredient or 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 patients
• Debilitated patients
• 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

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

Pain associated with anxiety 
Pain associated with fever 

Paracetamol/ Meprobamate/ Caffeine/ Codeine
320/150/32/8 (mg)

• Oral (tab): 2 tab, 6-8hrly; Max duration: 5 days

Pain - mild to moderate
Fever 

Paracetamol/ Meprobamate/ Caffeine/ Codeine
200/150/30/10 (mg)

• Oral (tab, cap): 1-2 tab/cap, 6hrly

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

Pain associated with
-Anxiety
-Tension

Paracetamol/ Meprobamate/ Caffeine/ Codeine
200/150/30/10 (mg)

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

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

Pregnancy

• There is no evidence as to drug safety in human pregnancy, nor is there evidence that it is free from hazard. Meprobamate diffuses across the placenta, and should not be used during pregnancy, especially during the first three months, unless there are compelling reasons, and the benefit to the mother is considered to outweigh any potential risks to the developing foetus
• There is inadequate evidence on the use of codeine in human pregnancy. Codeine crosses the placenta and should be used with caution in pregnancy
• Epidemiological studies in human pregnancy, have shown no ill effects due to paracetamol and caffeine use in the recommended dosage, but patients should follow medical advice regarding its use

Breastfeeding

• Contraindicated (Meprobamate, Codeine)
• Meprobamate appears in breast milk at concentrations up to four times those in maternal plasma and may cause drowsiness in the infant. Meprobamate should not be used by patients who are breastfeeding
• Codeine should not be used during breastfeeding. At normal therapeutic doses, codeine and its active metabolites may be present in breast milk at very low doses and are unlikely to adversely affect the breastfed infant. However, if the patient is an ultra-rapid metaboliser of CYP2D6, higher levels of the active metabolites may be present in breast milk and on very rare occasions may result in symptoms of opioid toxicity in the infant and may be fatal  
• Paracetamol and caffeine pass into breast milk in very small amounts which are probably insignificant and considered to be compatible with breastfeeding

Renal Impairment

• Caution; dose adjustment recommended (Meprobamate, Codeine) 

Hepatic Impairment

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

Elderly

• Caution; dose adjustment recommended (Meprobamate, Codeine) 

Porphyria Information

• Porphyrinogenic (P)

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

Meprobamate
Central Nervous System Disorders

• Drowsiness
• Dizziness 
• Ataxia
• Paraesthesia
• Paradoxical excitement

Cardiovascular Disorders

• Hypotension

Gastrointestinal Disorders

• Nausea and vomiting
• Stomatitis
• Proctitis

Skin and Subcutaneous Tissue Disorders

• Skin rashes
• Urticaria
• Itchy maculopapular rashes
• Erythema
• Erythema multiforme
• Exfoliative dermatitis 
• Stevens Johnson syndrome
• Bullous dermatitis

Immune, Blood and Lymphatic System Disorders

• Hypersensitivity reactions 
• Non-thrombocytopenic purpura
• Thrombocytopenia
• Agranulocytosis
• Aplastic anaemia
• Pancytopenia 

Caffeine
Central Nervous System Disorders

• Agitation
• Delirium
• Dizziness
• Hallucination
• Headache
• Insomnia
• Irritability
• Psychosis
• Restlessness

Gastrointestinal Disorders

• Oesophageal motility disorder (sphincter tone decreased)
• Gastritis

Genitourinary Disorders

• Diuresis

Musculoskeletal Disorders

• Fasciculations

Skin and Subcutaneous Tissue Disorders

• Urticaria

Sensory Disorders

• Increased intraocular pressure
• Miosis

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 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

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

Paracetamol

• Metoclopramide 
• Domperidone
• Colestyramine
• Oral anticoagulants
• Chloramphenicol

Meprobamate

• Coumarin anticoagulants
• Systemic steroids
• Phenytoin
• Griseofulvin
• Rifampicin
• Phenothiazines 
• Tricyclic antidepressants
• Central nervous system depressants 

Caffeine

• Adenosine
• Cocaine
• CYP1A2 Inhibitors 
• Xanthines 
• Linezolid 

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.

Meprobamate
Meprobamate is a carbamate with hypnotic, sedative and some muscle relaxant properties. It binds to gamma-amino butyric acid receptors in the central nervous system, including the thalamus and limbic system. 

Caffeine
Caffeine is a nonspecific adenosine receptor antagonist and acts as a central nervous system stimulant.

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.

COMBINATIONS PREPARATIONS

Paracetamol/ Meprobamate/ Caffeine/ Codeine

Tablet 200mg/150mg/30mg/10mg

• Tenston Sa (Adcock)

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

• Adco Salterpyn (Adcock)
• Antipyn forte (Pharmacare)
• Dynapayne (Arya Pharma)
• Goldgesic (Medicine Dev)
• Hopyn (Innovata)
• Megapyn (Pharmacare)
• Nucopain (Gulf)
• Pynmed (Cipla)
• Spectrapain Forte T (Akacia)
• Stilpane (Pharmacare)
• Stopayne (Adcock)

Capsule 200mg/150mg/30mg/10mg

• Tenston Sa (Adcock)

Capsule 320mg/150mg/48mg/8mg

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