Aspirin/ Caffeine/ Codeine/ Meprobamate/ Paracetamol

Registered South African indications:

• Pain 
• Fever

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

Aspirin
Contraindications

• Hypersensitivity to the active ingredient or to any of the excipients in this combination product
• Pregnancy > 30 weeks
• Severe renal impairment
• Severe hepatic impairment
• Peptic ulcer 
• Gastric/intestinal haemorrhage
• Cerebrovascular haemorrhages
• Coagulation disorders 
• Gout
• Coadministration with methotrexate  at doses > 15mg/week 

Cautions

• Pregnancy < 30 weeks
• Breastfeeding
• Impaired renal function
• Impaired hepatic function
• Elderly
• Children < 16 years
• Surgery
• Menorrhagia
• Hypertension
• History of gastric or duodenal ulcer
• Haemorrhagic episodes
• Dehydration
• History of asthma
• History of hay fever
• History of nasal polyps 
• History of chronic respiratory diseases
• Gout 

Caffeine
Contraindications

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

Cautions

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

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

Meprobamate
Contraindications

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

Cautions 

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

Paracetamol
Contraindications

• Hypersensitivity to active ingredient or any of its excipients
• Mild to moderate renal impairment
• Severe hepatic impairment

Cautions

• Renal impairment
• Mild to moderate hepatic impairment

Additional contraindications for this combination product

• Coadministration with monoamine oxidase inhibitors or with 14 days of their use
• Coadministration with oral anticoagulants

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

Pain and fever associated with tension states - mild to moderate

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

• Oral (tab): 1-2 tab, 6hrly

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

Pain and fever associated with tension states - mild to moderate

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

• Younger than 6 years: Not established for use 
• Between 6-12 years: 0.5-1 tab, 6hrly
• Older than 12 years: See adult dosage

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

Pregnancy

• < 30 weeks: Caution; not recommended
  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
• > 30 weeks: Contraindicated
  During the third trimester of pregnancy, all prostaglandin synthesis inhibitors may expose the foetus to: cardiopulmonary toxicity (with premature closure of the ductus arteriosus and pulmonary hypertension); renal dysfunction, which may progress to renal failure with oligo-hydramnios; the mother and the neonate, at the end of pregnancy; possible prolongation of bleeding time, an anti-aggregating effect which may occur even at very low doses; Inhibition of uterine contractions resulting in delayed or prolonged labour

Breastfeeding

• Contraindicated (Codeine) 

Renal Impairment

• Caution; dose adjustment recommended (Codeine, Meprobamate, Paracetamol)
• Severe: Contraindicated (Aspirin) 

Hepatic Impairment

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

Elderly

• Caution; dose adjustment recommended (Codeine, Meprobamate) 

Drugs in Sport

• Permitted - No warning 

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

Aspirin
Central Nervous System Disorders

• Intracranial haemorrhage
• Headache
• Vertigo

Cardiovascular  Disorders

• Hemorrhagic vasculitis

Respiratory Disorders

• Rhinitis
• Dyspnoea
• Bronchospasm
• Asthma attacks

Gastrointestinal Disorders

• Dyspepsia
• Severe gastrointestinal haemorrhage
• Nausea and vomiting
• Gastric or duodenal ulcers and perforation
• Diarrhoea

Hepatobiliary Disorders

• Hepatic insufficiency

Genitourinary Disorders

• Menorrhagia
• Impaired renal function
• Salt and water retention

Endocrine and Metabolic Disorders

• Hyperuricaemia

Skin and Subcutaneous Tissue Disorders

• Urticaria
• Stevens-Johnson syndrome
• Lyells syndrome
• Purpura
• Erythema nodosum
• Erythema multiforme

Immune, Blood and Lymphatic System Disorders

• Hypersensitivity reactions
• Angio-oedema
• Allergic oedema
• Anaphylactic reactions including shock 
• Increased bleeding tendencies
• Thrombocytopenia
• Granulocytosis
• Aplastic anaemia
• Epistaxis
• Gingival bleeding
• Iron deficiency anaemia

Sensory Disorders

• Reduced hearing ability
• Tinnitus

Caffeine
Central Nervous System Disorders

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

Cardiovascular Disorders

• Angina
• Chest pain
• Flushing
• Palpitations
• Sinus tachycardia
• Supraventricular tachycardia
• Vasodilation
• Ventricular arrhythmia

Gastrointestinal Disorders

• Oesophageal motility disorder
• 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 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

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

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

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

Aspirin

• Methotrexate
• Probenecid
• Anticoagulants
• Antiplatelet agents
• Selective serotonin reuptake inhibitors
• Sulphonylureas
• Digoxin
• Lithium
• Antihypertensives
• Diuretics
• Carbonic anhydrase inhibitors
• Corticosteroids
• Non-steroidal anti-inflammatory drugs
• Ciclosporin
• Tacrolimus
• Phenytoin
• Sodium valproate
• Alcohol
• Antacids

Caffeine

• Adenosine
• Cocaine
• CYP1A2 inhibitors 
• Linezolid
• Xanthines

Codeine

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

Meprobamate

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

Paracetamol

• Metoclopramide 
• Domperidone
• Colestyramine
• Oral anticoagulants
• Chloramphenicol

None routine. Specific cases may require

• Hepatic function
• Respiratory function
• Renal function

Aspirin
Acetylsalicylic acid inhibits the cyclooxygenase (COX) enzyme, thereby preventing production of prostaglandins and thromboxanes 

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

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 

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 

COMBINATION PREPARATIONS

Aspirin/ Caffeine/ Codeine/ Meprobamate/ Paracetamol

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

• Tenston (Adcock)