Aminophylline

ADMINISTRATION ROUTES:

IV

ALTERNATIVE NAMES:

Aminophylline (DBL)

ICU INDICATIONS:

1. Management of acute life threatening asthma (particularly in children)

PRESENTATION AND ADMINISTRATION:

IV:

250 mg/10 mL (solution).

For adult administration dilute 500 mg in 500 mL of compatible IV fluid to make a concentration of 1 mg/mL.

Store at room temperature 15-30°C; protect from light

Compatible with: Normal saline, 5% dextrose, 10% dextrose, glucose and sodium chloride, Hartmann’s

Do not mix with other medications – many medications will precipitate if mixed with aminophylline

DOSAGE:

Asthma and COPD:

IV aminophylline is very rarely used for treatment in asthma or COPD in adults in Wellington ICU

Dilute 500 mg in 500 mL of compatible IV fluid (ie 1 mg/mL)

Administer at 0.5 - 1 mg/kg/hr (usually 0 - 40 mL/hr)

Dose adjustment for obesity:

Theophylline does not distribute into fatty tissue. Dosage should be calculated on the basis of lean (ideal) body weight.

Note: Do not use standard dosing for IV infusion if the patient is already on oral theophylline; dosage should be calculated only after determining the serum concentration

DOSAGE IN RENAL FAILURE AND RENAL REPLACEMENT THERAPY:

While dose adjustment in renal failure is possible, dosage is complex and the risk of toxicity is high. Aminophylline should be ceased if the patient develops significant renal impairment.

DOSAGE IN PAEDIATRICS:

Aminophylline Infusion in life-threatening asthma

Children aged 1–9 years:

Add 55 mg/kg of IV aminophylline solution (25 mg/mL) to a 50 mL syringe and make up to 50 mL with 5% dextrose

Dose 1.1 mg/kg/hour

Infuse at 1 mL/hr

Children aged 10–15 years and weight < 35kg:

Add 35 mg/kg of IV aminophylline solution (25 mg/mL) to a 50 mL syringe and make up to 50 mL with 5% dextrose

Dose 0.7 mg/kg/hour

Infuse at 1 mL/hr

Children aged 10-15 years and weight > 35kg:

Draw up neat IV aminophylline solution (25 mg/mL) into a 50 mL syringe

Dose 0.7 mg/kg/hour

Infuse at 0.028 mL/kg/hr

For example, for a 40kg child the infusion rate will be 40 x 0.028 = 1.12 mL/hr

Dose adjustment for obesity:

Theophylline does not distribute into fatty tissue. Dosage should be calculated on the basis of lean (ideal) body weight. Use the 50th percentile of expected weight for age.

Note: Do not use standard dosing for IV infusion if the patient is already on oral theophylline; dosage should be calculated only after determining the serum concentration

CLINICAL PHARMACOLOGY:

Aminophylline is a 2:1 complex of theophylline and ethylenediamine. The activity is of theophylline alone. Theophylline directly relaxes the smooth muscle of the bronchial airway and pulmonary blood vessels, thus acting mainly as a bronchodilator and smooth muscle relaxant. It has also been demonstrated that aminophylline has a potent effect on diaphragmatic contractility in normal persons and may then be capable of reducing fatigability and therapy improve contractility in patients with chronic obstructive airway disease. The exact mode of action remains unclear.

CONTRAINDICATIONS:

1. Hypersensitivity to either aminophylline or ethylenediamine

2. Active peptic ulcer disease

3. Underlying seizure disorders (unless receiving appropriate anticonvulsant medications)

CONTRAINDICATIONS:

1. Hypersensitivity to either aminophylline or ethylenediamine
2. Active peptic ulcer disease
3. Underlying seizure disorders (unless receiving appropriate anticonvulsant medications)

WARNINGS:

In individuals in whom theophylline plasma clearance is reduced for any reason, even conventional doses may result in increased serum levels and potential toxicity. Reduced theophylline clearance has been documented in the following groups:

1. Impaired liver function

2. Patients > 55 years of age, particularly males and those with chronic lung disease

3. Cardiac failure from any cause

4. Sustained high fever

5. Neonates and infants under 1 year of age

6. Patients taking certain drugs (see DRUG INTERACTIONS)

Serious side effects such as ventricular arrhythmias, convulsions or even death may appear as the first sign of toxicity without any previous warning. A serum concentration measurement is the only reliable method of predicting potentially life-threatening toxicity. Theophylline products may cause or worsen arrhythmias and any significant change in rate and/or rhythm warrants measurement of a serum level and consideration of cessation of the drug.

PRECAUTIONS:

General:

See WARNINGS

Laboratory Tests:

Blood specimen collection bottle:

Adults: SST (Yellow) or Plain (Red)

Paediatric and Neonata: 0.4 mL green microtainer

Therapeutic Range: 55-110 micmol/L Neonates: 35-70 micmol/L

Can sample any time after 12 hours of starting infusion

Drug/Laboratory Test Interactions:

Acetazolamide interferes with the HPLC method of assay for theophylline. Interference with the theophylline assay by acetazolamide depends on the solvent used in the extraction; acetazolamide may not interfere with other assay methods for theophylline

IMPORTANT DRUG INTERACTIONS IN ICU:

Aminophylline with:

Allopurinol (high-dose): Increased serum theophylline levels

Ciprofloxacin: Increased serum theophylline levels

Erythromycin: Increased serum theophylline levels

Lithium carbonate: Increased renal excretion of lithium

Oral contraceptives: Increased serum theophylline levels

Phenytoin: Decreased theophylline and phenytoin serum levels Propranolol: Increased serum theophylline levels

Rifampin: Decreased serum theophylline levels

Increased toxicity may be seen with combinations of high dose beta agonists and aminophylline.

ADVERSE REACTIONS:

Body as a Whole:

Irritability, restlessness, insomnia

Cardiovascular System:

Palpitation, tachycardia, extrasystoles, flushing, hypotension, circulatory failure, ventricular arrhythmias

Respiratory System:

Tachypnoea

Digestive System:

Nausea, vomiting, epigastric pain, haematemesis, diarrhoea

Nervous System:

Headaches, reflex hyperexcitability, muscle twitching, clonic and tonic generalised convulsions