Aminophylline

Registered South African indications:

• Bronchospasm associated with asthma, bronchitis and emphysema

Contraindications 

• Hypersensitivity to the active ingredient or to any of its excipients
• Hypersensitivity to ethylenediamine, theophyllines, caffeine or theobromine
• Acute porphyria
• Children younger than 6 months
• Coadministration with other xanthine agents

Cautions 

• Pregnancy
• Breastfeeding
• Renal impairment
• Hepatic impairment
• Elderly (>55 years old)
• Children
• History of seizure activity or epilepsy
• Cardiac failure
• Chronic obstructive pulmonary disease
• Chronic alcoholism
• Smokers or those regularly exposed to tobacco smoke
• Undergoing influenza immunisation
• Active influenza infection
• Acute febrile illness
• Hypoxia
• Peptic ulcer disease
• Hyperthyroidism
• Glaucoma
• Diabetes mellitus
• Severe hypoxaemia
• Hypertension
• Compromised cardiac or circulatory function

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

Disease of the cardiovascular system 
- Adjunct in the treatment of pulmonary oedema or paroxysmal nocturnal dyspnoea caused by left ventricular heart failure (example)
Reversible airway obstruction including status asthmaticus and acute bronchospasm

Patients not receiving theophylline products

• IV: Max: 25mg/min up to a dose of 250-500mg (5mg/kg) given slowly

May be given by slow intravenous injection or intravenous infusion in glucose injection or sodium chloride injection. If patients experience acute adverse effects while loading doses are being infused, the infusion may be stopped for 5-10mins or administered at a slower rate

• IV: Approximate maintenance dose as follows:

Patients receiving theophylline products

• Loading dose should be deferred until serum theophylline levels can be determined. Based on expectation that 0.5mg/kg (lean body weight) of theophylline will result in a 1μg/ml increase in serum theophylline concentration
• Maintenance dose as above

Aminophylline has a narrow therapeutic index, therefore cautious dosage determination is essential

Therapeutic serum concentrations of theophylline are considered to range from 10-20μg/ml and >20μg/ml are often associated with toxic effects. A range of 5-15μg/ml may be effective and associated with fewer adverse effects

Dosage should be titrated for each individual and adjusted with caution. Serum theophylline levels should be monitored to ensure that they remain within the therapeutic range. During therapy, patients should be monitored carefully for signs of toxicity

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

Disease of the cardiovascular system 
- Adjunct in the treatment of pulmonary oedema or paroxysmal nocturnal dyspnoea caused by left ventricular heart failure (example)
Reversible airway obstruction including status asthmaticus and acute bronchospasm

Younger than 6 months

• Contraindicated

Older than 6 months

Patients not receiving theophylline products 

• IV: Max: 25mg/min up to a dose of 250-500mg (5mg/kg) given slowly

May be given by slow intravenous injection or intravenous infusion in glucose injection or sodium chloride injection. If patients experience acute adverse effects while loading doses are being infused, the infusion may be stopped for 5-10mins or administered at a slower rate

• IV: Approximate maintenance dose as follows:

Patients receiving theophylline products 

• Loading dose should be deferred until serum theophylline levels can be determined. Based on expectation that 0.5mg/kg (lean body weight) of theophylline will result in a 1μg/ml increase in serum theophylline concentration
• Maintenance dose as above

Aminophylline has a narrow therapeutic index, therefore cautious dosage determination is essential

Therapeutic serum concentrations of theophylline are considered to range from 10-20μg/ml and >20μg/ml are often associated with toxic effects. A range of 5-15μg/ml may be effective and associated with fewer adverse effects

Dosage should be titrated for each individual and adjusted with caution. Serum theophylline levels should be monitored to ensure that they remain within the therapeutic range. During therapy, patients should be monitored carefully for signs of toxicity

Pregnancy

• Caution
• It is not known whether theophyllines can cause foetal harm when administered to pregnant women. Although the safe use of theophylline during pregnancy has not been established relative to the potential risk to the foetus, theophyllines have been used during pregnancy without teratogenicity or other adverse foetal effects
• Because of the risk of uncontrolled asthma, their safety during pregnancy when clearly needed is generally not seriously questioned
• As with other medicines, aminophylline should only be used during pregnancy if considered essential. Theophylline crosses the placenta

Breastfeeding

• Caution; not recommended
• Theophylline is distributed into breast milk and may occasionally induce irritability or other signs of toxicity in breastfeeding infants, and therefore should not be used if the mother is breastfeeding her infant

Fertility

• Animal reproduction studies have not been performed with theophyllines

Renal Impairment

• Caution; no dose adjustment not recommended 

Hepatic Impairment

• Caution; dose adjustment recommended
  Initial: 0.25mg/kg/hr; Max: 507mg/day; however, serum concentrations may indicate a need for higher doses. Monitor theophylline serum concentrations regularly

Elderly

• Caution; dose adjustment recommended
  Maintenance dose: 0.3mg/kg/hr; Max: 507mg/day; however, serum concentrations may indicate a need for higher doses

Porphyria Information

• Probably porphyrinogenic (PRP)

Drugs in Sport

• Permitted - No warnings

Central Nervous System Disorders

• Headache
• Insomnia
• Confusion
• Restlessness
• Hyperventilation
• Anxiety
• Vertigo/dizziness
• Tremor
• Maniacal behaviour (high doses)
• Delirium (high doses)
• Seizures (high doses)

Cardiovascular Disorders

• Palpitations
• Tachycardia
• Cardiac arrhythmias
• Hypotension

Gastrointestinal Disorders

• Nausea and vomiting
• Abdominal pain
• Diarrhoea
• Gastro-oesophageal reflux
• Gastrointestinal bleeding

Endocrine and Metabolic Disorders

• Metabolic disturbances
  - Hypokalaemia
  - Hypophosphataemia
  - Hyponatraemia  
• Hyperthermia (high doses)
• Extreme thirst (high doses)

Skin and Subcutaneous Tissue Disorders

• Rash
• Maculopapular rash
• Erythema
• Pruritus
• Urticaria
• Exfoliative dermatitis

Immune System Disorders

• Hypersensitivity reactions

Sensory Disorders

• Visual disturbances

• Xanthines and xanthine derivatives
• Theophylline  
• Pentoxifylline
• Fluvoxamine
• Cimetidine
• Macrolide antibiotics
• Erythromycin
• Clarithromycin
• Quinolone antibiotics
• Ciprofloxacin
• Norfloxacin
• Fluconazole
• Isoniazid
• Propranolol
• Allopurinol (high doses)
• Oral contraceptives
• Mexiletine
• Propafenone
• Calcium channel blockers
• Diltiazem
• Verapamil
• Disulfiram
• Interferon alfa
• Influenza vaccine
• Methotrexate
• Zafirlukast
• Thyroid hormones
• Rifampicin
• Antiepileptics
• Carbamazepine
• Phenytoin
• Primidone
• Phenobarbitone
• Ritonavir
• Sulfinpyrazone
• Lithium
• Benzodiazepines
• General anaesthetics
• Ketamine
• Halothane
• Pancuronium
• Sympathomimetics
• Ephedrine
• Beta-2 agonists
• Beta-blockers
• Cardiac glycosides
• Adenosine
• Leukotriene antagonists
• Zafirlukast
• Doxapram
• Corticosteroids
• Diuretics

Other

• St John's wort

• Theophylline levels
• Heart rate

Specific cases may require

• Potassium levels
• Respiratory rate
• Arterial or capillary blood gases

Additional observations

• CNS effects

Aminophylline is a soluble derivative of theophylline and is given for its theophylline activity. Aminophylline relaxes smooth muscle and relieves bronchial spasm. It stimulates the myocardium and reduces venous pressure in congestive heart failure, leading to a marked increase in cardiac output. It has stimulant effect on respiration, and also a diuretic action of short duration.

Injection (per ml) 250mg

• Aminophyllin 2Ml (Pharmacare)
• Aminophyllin Iv Fresenius (Fresenius Kabi)

Injection (per 10ml) 250mg

• Aminophyllin 10Ml (Pharmacare)
• Aminophyllin Iv Fresenius (Fresenius Kabi)
• Mylan Aminophylline (SCP Pharma)
• Pharma-Q Theopylline I.V. Injection (Pharma-Q)
• Sabax Aminophylline Iv (Adcock Ingram) originator

Injection (per 2ml) 500mg

• Aminophyllin 10Ml (Pharmacare)