Ammonium Chloride/ Sodium Citrate/ Theophylline/ Etofylline/ Diphenylpyraline Hydrochloride

Registered South African indications:

• Alleviation of cough

Registered South African contraindications

• Hypersensitivity to the active ingredient or any of the excipients in this combination product
• Diabetes
• Alcoholism (rehabilitated alcoholics)
• Severe hypotension
• Peptic ulcer
• Gout
• Renal disease
• Hepatic disease

South African recommendations

Caution in the following patient groups

• Pregnancy
• Breastfeeding
• Elderly

Drowsiness and impaired concentration

• This medicine may cause drowsiness and reduced concentration, especially when combined with alcohol or CNS depressants
• Patients should avoid driving, operating machinery, or engaging in hazardous tasks where impaired concentration could lead to accidents

Risk of theophylline toxicity

• Using this combination cough syrup concurrently with other theophylline-containing preparations can result in toxic theophylline levels. Patients need to be aware of this risk

Sensitivity in children

• Children are especially sensitive to theophylline. Do not administer more frequently than every eight hours

Elderly patients and cardiac disease

• Use theophylline cautiously in the elderly and those with cardiac diseases

Risk for epileptics

• Diphenylpyraline hydrochloride may induce seizures in individuals with epilepsy

Ototoxic drug effects

• Warning signs of damage from ototoxic drugs might be masked
• The metabolism of drugs in the liver could be impacted

Enhanced sedative effects

• Diphenylpyraline hydrochloride can increase the sedative impact of CNS depressants such as alcohol, barbiturates, hypnotics, narcotic analgesics, sedatives, and tranquilizers

Sucrose content and diabetes

• Contains sucrose, which might affect blood sugar control in patients with diabetes mellitus

Theophylline

Smokers and dialysis patients

• Smokers may require increased doses as may patients undergoing routine haemodialysis

Diphenylpyraline Hydrochloride

Patient precautions

• Due to its anticholinergic properties, diphenylpyraline hydrochloride should be used cautiously in patients with conditions like glaucoma and prostatic hypertrophy

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

South African registered indications and dosages

Alleviation of cough

Ammonium Chloride/ Sodium Citrate/ Theophylline/ Etofylline/ Diphenylpyraline Hydrochloride
720/300/100/10/8 (mg/30ml)

• Oral (syr): 15ml, 3 times daily after meals and at bedtime

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

South African registered indications and dosages

Alleviation of cough

Ammonium Chloride/ Sodium Citrate/ Theophylline/ Etofylline/ Diphenylpyraline Hydrochloride
720/300/100/10/8 (mg/30ml)

• Younger than 2 years: No information available
• Between 3-6 years: Oral (syr): 5ml, 3 times daily after meals 
• 7 years and older: Oral (syr): 10ml, 3 times daily after meals

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Children are particularly sensitive to the effects of theophylline and it should not be administered more frequently than every eight hours

Pregnancy

South African recommendations

• Caution
• Safety and/or efficacy has not been established

Breastfeeding

South African recommendations

• Caution
• Safety and/or efficacy has not been established

Fertility

South African recommendations

• No information available

South African recommendations

• Contraindicated

South African recommendations

• Contraindicated

South African recommendations

• Caution; no dose adjustment recommended

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

Theophylline

Gastrointestinal Disorders

Frequency not specified

• Nausea and vomiting
• Gastrointestinal bleeding

Visual Disorders

Frequency not specified

• Changes in vision or visual disturbances

Central Nervous System Disorders

Frequency not specified

• Insomnia
• Headache
• Anxiety
• Confusion
• Restlessness
• Vertigo (dizziness)

Respiratory Disorders

Frequency not specified

• Hyperventilation

Cardiovascular Disorders

Frequency not specified

• Palpitations

Diphenylpyraline Hydrochloride

Gastrointestinal Disorders

Frequency not specified

• Nausea and vomiting
• Diarrhoea
• Constipation
• Epigastric pain
• Dryness of the mouth

Central Nervous System Disorders

Common

• Sedation (ranging from slight drowsiness to deep sleep)
  • Inability to concentrate
  • Lassitude
  • Dizziness
  • Hypotension
  • Muscular weakness
  • Incoordination

Frequency not specified

• Headache
• Elation or depression
• Irritability
• Nightmares
• Anorexia
• Tingling, heaviness, and weakness of the hands
• Symptoms of stimulation (in adults)
  • Insomnia
  • Nervousness
  • Tachycardia
  • Tremors
  • Muscle twitching
  • Convulsions
• May act as a cerebral stimulant (infants and children)

Cardiovascular Disorders

Frequency not specified

• Tightness of the chest

Genitourinary Disorders

Frequency not specified

• Difficulty in micturition

Sensory Disorders

Frequency not specified

• Tinnitus

Allergic Reactions

Frequency not specified

• Allergy
• Anaphylaxis

Blood Disorders

Frequency not specified

• Blood dyscrasias
• Agranulocytosis
• Haemolytic anaemia

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

Theophylline

• Sympathomimetics
• Other xanthines

Other interactions

• Smoking

Diphenylpyraline Hydrochloride

• Anticholinergic agents
• Atropine
• Tricyclic antidepressants
• Central nervous system depressants
• Barbiturates
• Hypnotics
• Narcotic analgesics
• Sedatives
• Tranquilizers

Other interactions

• Alcohol

None routine

Ammonium Chloride
Ammonium chloride is used as an expectorant. It causes irritation of the bronchial mucosa, which results in the production of excess respiratory tract fluid. This allows for easier mucus expulsion due to its decreased viscosity. 

Sodium Citrate
Sodium citrate is metabolised to sodium bicarbonate and acts as a systemic alkalizer.

Theophylline
Theophylline is a phosphodiesterase inhibitor which results in smooth muscle relaxation,  diuresis, cardiac stimulation, cerebral stimulation and skeletal muscle stimulation. Through its ability to bring about smooth muscle relaxation, theophylline acts predominently as a bronchodilator and vasodilator.

Etofylline
Etofylline is a N-7 substituted theophylline derivative which acts similar to other xanthines. The bronchodilating action of xanthines is thought to result from the competitive inhibition of phosphodiesterase, which is the enzyme responsible for the breakdown cyclic AMP in smooth muscle cells. 

Diphenylpyraline Hydrochloride
Diphenylpyraline is an antihistamine, which produces therapeutic anti-allergic effects by binding to histamine H1-receptors.

COMBINATION PREPARATIONS

Ammonium Chloride/ Sodium Citrate/ Theophylline/ Etofylline/ Diphenylpyraline Hydrochloride

Syrup (per 30ml) 720mg/300mg/100mg/10mg/8mg

• Actophlem (Adcock)
• Solphyllex (Adcock)