Source: Medicines & Healthcare Products Regulatory Agency (GB) Revision Year: 2015 Publisher: hameln pharmaceuticals ltd, Gloucester, UK
Aminophylline injection should not be used in patients hypersensitive to ethylenediamine or those allergic to the theophyllines, caffeine or theobromine.
Aminophylline should not be administered concomitantly with other xanthine drugs. When therapeutic doses of Aminophylline and/or theophylline are administered simultaneously by more that one route or in more than one preparation, the hazard of serious toxicity is increased.
The use of Aminophylline IV in children under 6 months of age is not recommended.
The use of Aminophylline is contraindicated in patients with acute porphyria.
Intravenous Aminophylline must be administered very slowly to prevent dangerous central nervous system and cardiovascular side-effects due to direct stimulating effect of Aminophylline.
Aminophylline has a narrow therapeutic index and serum levels should be monitored regularly, particularly during initiation of therapy.
Aminophylline injection should be administered cautiously to patients over 55 years of age.
Children are particularly susceptible to the effects of theophylline and care is required when administrating aminophylline to children. There have been reports of seizures in children with theophylline plasma levels within the accepted therapeutic range. Alternative treatment should be considered in patients with a history of seizure activity and, if Aminophylline Injection is used in such patients, they should be carefully observed for possible signs of central stimulation.
Caution is also advised in patients undergoing influenza immunisation or who have active influenza infection or acute febrile illness.
Aminophylline should be given with caution to patients with cardiac failure, chronic obstructive pulmonary disease, renal or hepatic dysfunction and in chronic alcoholism since clearance of Aminophylline is decreased.
Theophylline clearance may be increased in smokers and in those regularly exposed to tobacco smoke.
During regular therapy serum potassium levels must be monitored. This is essential during combination therapy with beta2-agonists, corticosteroids or diuretics, or in the presence of hypoxia.
Aminophylline should be used with caution in patients with peptic ulcer, hyperthyroidism, glaucoma, diabetes mellitus, severe hypoxaemia, hypertension, compromised cardiac or circulatory function and epilepsy, as these conditions may be exacerbated.
Aminophylline should not be administered concurrently with other xanthine medications.
The following drugs may increase plasma theophylline concentrations:
The following drugs may decrease plasma theophylline concentrations:
Xanthines: Concurrent use of other xanthine derivatives, including theophylline and pentoxifylline are contraindicated due to the risk of toxicity.
Lithium: Aminophylline increases the excretion of lithium and may decrease its therapeutic effectiveness.
Benzodiazepines: Theophylline may reduce the effects of benzodiazepines
Quinolones: Increased risk of convulsions.
General anaesthetics: Increased risk of convulsions with ketamine; increased risk of arrhythmias with halothane
Pancuronium: Resistance to neuromuscular block with pancuronium has been reported in patients receiving aminophylline.
Sympathomimetics: Aminophylline may exhibit synergistic toxicity with ephedrine and other sympathomimetics and concurrent use may dispose the patient to cardiac arrhythmias.
Beta2-adrenergic agonists: Increased risk of cardiac arrhythmias (see also hypokalaemia).
Beta-blockers: Antagonism of bronchodilator effects.
Cardiac glycosides: The direct stimulatory effect of Aminophylline on the myocardium may enhance the sensitivity and toxic potential of the cardiac glycosides.
Adenosine: The anti-arrhythmic effect of adenosine is antagonised by theophylline
Leukotriene antagonists: In clinical trials co-administration with theophylline resulted in decreased plasma levels of zafirlukast, by approximately 30%, but with no effect on plasma theophylline levels. However, during post-marketing surveillance, there have been rare cases of patients experiencing increased theophylline levels when co-administered zafirlukast (see above).
Doxapram: Increased CNS stimulation.
The hypokalaemic effects of beta2-adrenergic agonists may be potentiated by concomitant treatment with aminophylline. There is an increased risk of hypokalaemia when theophylline derivatives are given with corticosteroids or diuretics (see 4.4 Special warnings and precautions for use).
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 potential risk to the foetus, theophyllines have been used during pregnancy without teratogenicity or other adverse foetal effect. Because of the risk of uncontrolled asthma, their safety during pregnancy when clearly needed is generally not seriously questioned. As with other drugs, aminophylline should only be used during pregnancy if considered essential by the physician. Theophylline crosses the placenta.
Theophylline is distributed into milk and may occasionally induce irritability or other signs of toxicity in nursing infants, and therefore should not be used if the mother is breast-feeding her infant.
Animal reproduction studies have not been performed with theophyllines.
None known.
Adverse events are usually a consequence of gastrointestinal irritation, stimulation of the central nervous system and effects on the cardiovascular system. Hypotension, arrhythmias and convulsions may follow intravenous injection, particularly if the injection is too rapid, and sudden deaths have been reported. Severe toxicity may occur without preceding milder symptoms (see also 4.9 Overdose).
Immune system disorders: Hypersensitivity reactions (see also Skin and subcutaneous tissue disorders).
Metabolism and nutrition disorders: Metabolic disturbances such as hypokalaemia, hypophosphataemia, and hyponatraemia may occur.
Nervous system/Psychiatric disorders: Headache, insomnia, confusion, restlessness, hyperventilation, anxiety, vertigo/dizziness, tremor. Higher doses may lead to maniacal behaviour, delirium and convulsions.
Eye disorders: Visual disturbances.
Cardiac disorders: Palpitations, tachycardia, cardiac arrhythmias, hypotension.
Gastrointestinal disorders: Nausea, vomiting, abdominal pain, diarrhoea, gastro-oesophageal reflux, gastrointestinal bleeding.
Skin and subcutaneous tissue disorders: Rash, maculo-papular rash, erythema, pruritus, urticaria, exfoliative dermatitis.
General/Administration site reactions: Higher doses may result in hyperthermia and extreme thirst.
Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions via the Yellow Card Scheme at: www.mhra.gov.uk/yellowcard.
Aminophylline injection is not stable in solutions having a pH of substantially less than 8, however, the drug appears to be relatively stable in large volume parenteral solutions over a wide pH range (3.5-8.6) if Aminophylline concentrations do not exceed 40mg per ml. The activity of alkali-sensitive drugs will be reduced by Aminophylline, these drugs should not be added to IV fluids containing Aminophylline.
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