Ammonium Chloride/ Sodium Citrate/ Theophylline/ Diphenhydramine/ Menthol

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
• Renal function impairment
• Hepatic function impairment
• During an asthma attack
• Patients with peptic ulcer
• Patients with gout
• Patients with severe hypotension
• Pregnancy
• Lactation

South African recommendations

• Elderly

Drowsiness and impaired concentration

• May cause drowsiness and reduced concentration, worsened by simultaneous intake of alcohol or other CNS depressants
• Unsafe to drive a vehicle or be in charge of machinery while using this combination medicine, as impaired decisions could lead to accidents for driving or operating machinery due to potential impaired decision-making

Risk of toxicity with theophylline

• Can lead to elevated levels of theophylline; patients should be informed about this risk

Not suitable for diabetic patients

• Diabetic individuals should not use the combination medicine

Caution in patients with:

• Cardiac failure
• Hypertension
• Peripheral and pulmonary oedema
• Toxaemia of pregnancy

Theophylline

Use in specific patient groups and conditions:

• Alcoholics
• Patients with cor pulmonale
• Acute febrile conditions
• Hypoxia
• Acute pulmonary oedema, or other lung diseases
• Peptic ulceration
• Hyperthyroidism
• Cardiovascular disease and cardiac arrhythmias
• Neonates
• Elderly

Serum concentration monitoring

• Monitoring serum concentrations is recommended, particularly when switching patients from another formulation

Diphenhydramine Hydrochloride

Caution is advised in patients with:

• Urinary retention

Epilepsy

• Large doses of diphenhydramine hydrochloride may precipitate convulsions in epileptics

Conditions exacerbated by atropine

• Use with care in conditions like glaucoma and prostatic hypertrophy, which may worsen with atropine-like effects

Skin allergy tests

• Diphenhydramine hydrochloride may suppress the positive results of skin allergy tests

Coadministration with other medicines

• Diphenhydramine hydrochloride can intensify the sedative properties of central nervous system depressants such as alcohol, barbiturates, hypnotics, narcotic analgesics, sedatives, and tranquilizers
• It may mask warning signs of damage caused by ototoxic agents
• The anticholinergic effects of diphenhydramine hydrochloride may be increased when taken with monoamine oxidase inhibitors
• Effects of agents like atropine and tricyclic antidepressants may be enhanced when used concurrently with diphenhydramine hydrochloride

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

South African registered indications and dosages

Alleviation of cough

Ammonium Chloride/ Sodium Citrate/ Theophylline/ Diphenhydramine/ Menthol
273.86/113.83/56.31/28.15/2.28 (mg/10ml)

• Oral (syr): 10ml, 4hrly

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/ Diphenhydramine/ Menthol
273.86/113.83/56.31/28.15/2.28 (mg/10ml)

• Younger than 6 years: Not recommended for use
• Between 6-12 years: Oral (syr): 2.5-5ml, 4hrly
• Older than 12 years: See adult dosage

Pregnancy

South African recommendations

• Contraindicated
• Safety during pregnancy has not been established

Breastfeeding

South African recommendations

• Contraindicated
• Safety during lactation 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
  Theophylline should be given with caution in the elderly as clearance may be decreased in these patients

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

Ammonium Chloride

Central Nervous System Disorders

• Headache
• Progressive drowsiness
• Mental confusion

Respiratory Disorders

• Hyperventilation

Gastrointestinal Disorders

• Nausea
• Vomiting
• Thirst

Metabolic and Nutritional Disorders

• Hyperchloraemic acidosis
• Hypokalaemia

Sodium Citrate

Metabolic and Nutritional Disorders

• Hypernatraemia
  - Restlessness
  - Weakness
  - Thirst
  - Reduced salivation and tear production
  - Swollen tongue
  - Flushing of the skin
  - Pyrexia
  - Dizziness
  - Headache
  - Oliguria
  - Hypotension
  - Tachycardia
  - Delirium
  - Hyperpnoea
  - Respiratory arrest

Theophylline

Central Nervous System Disorders

• Insomnia
• Headache
• Anxiety
• Restlessness
• Vertigo
• Central nervous system stimulation (especially in children)

Cardiovascular Disorders

• Palpitations

Gastrointestinal Disorders

• Gastric irritation
• Nausea
• Vomiting
• Abdominal pain
• Gastrointestinal bleeding

Diphenhydramine Hydrochloride

Central Nervous System Disorders

• Sedation (ranging from slight drowsiness to deep sleep)
• Inability to concentrate
• Lassitude
• Dizziness
• Incoordination
• Headache
• Elation or depression
• Euphoria
• Extrapyramidal effects
• Irritability
• Nightmares
• Anorexia
• Cerebral stimulation
• Insomnia
• Nervousness
• Tremors
• Convulsions (large doses may precipitate convulsions in epileptics)

Cardiovascular Disorders

• Tachycardia
• Hypotension

Gastrointestinal Disorders

• Nausea
• Vomiting
• Diarrhoea or constipation
• Epigastric pain
• Dryness of the mouth

Genitourinary Disorders

• Difficulty in micturition

Musculoskeletal Disorders

• Muscle twitching
• Muscular weakness

Skin and Subcutaneous Tissue Disorders

• Photosensitisation

Immune, Blood and Lymphatic System Disorders

• Allergic reactions
• Haemolytic anaemia
• Leucopenia

Sensory Disorders

• Blurred vision
• Tinnitus

Others

• Tightness of the chest
• Tingling, weakness, and heaviness of the hands

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

Theophylline

• Sympathomimetics or other xanthines
• Allopurinol
• Cimetidine
• Influenza vaccine
• Propranolol
• Erythromycin
• Phenytoin and some other anticonvulsants

Other interactions

• Cigarette smoking

Diphenhydramine Hydrochloride

• Central nervous system depressants
• Barbiturates
• Hypnotics
• Narcotic analgesics
• Sedatives
• Tranquilizers
• Ototoxic agents
• Monoamine oxidase inhibitors
• Atropine
• Tricyclic antidepressants

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 predominantly as a bronchodilator and vasodilator.

Diphenhydramine Hydrochloride
Diphenhydramine is a histamine H1 antagonist that competes with free histamine for binding at histamine receptors. In addition to its usual anti-allergy actions, it also has significant sedative and antimuscarinic properties.

Menthol
This ingredient has no pharmacological effect.

COMBINATION PREPARATIONS

Ammonium/Citric Acid/ Theophylline/ Diphenhydramine/Menthol

Syrup (per 10ml) 273.86mg/ 113.83mg/ 56.32mg/ 28.15mg/ 2.28mg

• Diatussin (Adcock Ingram)