Drug Class Description

Generic Name

Drug Description

Presentation

Indications

Adult Dosage

Aminophylline Injection BP may be given by slow intravenous injection or intravenous infusion in glucose injection or sodium chloride injection. It has also been given by deep intramuscular injection in a dose of 500mg in 2mls of water for injections, but such injections are painful.

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

To minimise adverse effects, IV Aminophylline should be administered slowly, at a rate not exceeding 25mg Aminophylline per minute, up to a dose of 250-500mg (5mg/kg). If patients experience acute adverse effects while loading doses are being infused, the infusion may be stopped for 5-10 minutes or administered at a slower rate.

Approximate IV Aminophylline Dosage: Acute Bronchospasm

n.b. The use of Aminophylline IV in children under 6 months of age is not generally recommended.

Patients not currently receiving theophylline preparations may receive a loading dose of Aminophylline of 6mg/kg and then the above maintenance doses.

In patients who are currently receiving theophylline preparations, the time, route of administration and dosage form of the patient's last dose should be determined where possible and considered in determining a loading dose. Loading doses are based on the expectation that 0.5mg/kg (lean body weight) of theophylline will result in a 1 microgram/ml increase in serum theophylline concentration. Therefore, in patients currently receiving theophylline preparations, the loading dose should be deferred until a serum theophylline concentration can be attained or the clinician must carefully select a dose based on the potential benefits and risks.

Elimination of theophylline in children younger than 6 months of age, especially in neonates, appears to be reduced. Because of this variation in metabolism the use of Aminophylline injection in children under 6 months of age cannot be recommended.

Child Dosage

Contra Indications

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 than 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 generally recommended.

The use of Aminophylline is contra-indicated in patients with acute porphyria.

Special Precautions

To reduce the undesirable stimulating effects of aminophylline on the central nervous and cardiovascular systems, intravenous administration of the drug should be slow and should not exceed a rate of 25 mg/min.

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.

Elderly patients or those with cardiac or hepatic disease should be monitored carefully for signs of theophylline toxicity.

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.

Because the mean half-life of theophylline is shorter in smokers than in non-smokers, the former group may require larger doses of aminophylline.

Care should be taken 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.

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 and compromised cardiac or circulatory function, as these conditions may be exacerbated.

Methylxanthines may increase gastric acidity and care should be taken when they are used in patients with a history of peptic ulceration.

Aminophylline should not be administered concurrently with other xanthine medications.

The label shall contain the following statements:-

Do not store above 25ºC

Keep in outer carton.

If only part used discard the remaining solution.

Discard the ampoule if the contents are discoloured.

Interactions

The following drugs may decrease Aminophylline clearance resulting in increased plasma theophylline concentrationsand the potential for increased toxicity:

• Fluvoxamine

The concomitant use of theophylline and fluvoxamine should usually be avoided. Where this is not possible, patients should have their theophylline dose halved and plasma theophylline should be monitored closely.

• Cimetidine

• Macrolide antibiotics (e.g. erythromycin, clarithromycin)

• Quinolone antibiotics (e.g. ciprofloxacin, norfloxacin)

• Fluconazole

• Isoniazid

• Propranolol

• Allopurinol (high doses e.g. 600 mg daily)

• Oral contraceptives

• Mexiletine, propafenone

• Calcium channel blockers, diltiazem, verapamil

• St John's Wort (Hypericum perforatum)

• Disulfiram

• Interferon alfa, influenza vaccine

• Methotrexate

• Zafirlukast

• Tacrine

• Thiabendazole

• Thyroid hormones

The following drugs may decrease plasma theophylline concentrations:

• Rifampicin

• Antiepileptics (e.g. carbamazepine, phenytoin, primidone, phenobarbitone)

• Ritonavir

• Aminoglutethimide

• Sulphinpyrazone

Other interactions:

• 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.

• Hypokalaemia:

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.

Adverse Reactions

Aminophylline may cause 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.

Psychiatric disorders

Anxiety, insomnia. Higher doses may lead to maniacal behaviour, and delirium.

Nervous system disorders:

Headache, confusion, restlessness, hyperventilation, vertigo/dizziness, tremor. Higher doses may lead to 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 disorders and administration site conditions :

Intramuscular injections are painful, the pain lasting several hours.

Higher doses may result in hyperthermia and extreme thirst.

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