Aminophylline
(C,HgN,02)1Β·C2H,(NH2)t.=420.4.
White or slightly yellowish granules or powder, odourless or
with a slight ammoniacal odour. It is a stable mixture or com-
bination, of theophylline and elhylenediamine containing be-
tween 84.0% and 87.4% of anhydrous theophylline and
13.5% to 15.0% of anhydrous ethylenediamine.
Freely soluble in water (the solution may become cloudy in
the presence of carbon dioxide): practically insoluble in alco-
hol and in ether. Solutions are alkaline to litmus and should
not be allowed to come into contact with metals. In moist air
it gradually loses ethylenediamine and absorbs carbon diox-
ide with the liberation of theophylline. Store in airtight con-
tainers. Protect from light.
Incompatibility.
Solutions of aminophylline are alkaline
and if the pH falls below 8 crystals of theophylline will depos-
it. ' Drugs known to be unstable in alkaline solutions should
not be mixed with aminophylline nor should drugs that will
lower the pH below the critical value. The addition of
aminophylline to glucose injection has been reported to raise
the pH by over 4 units to pH 7.7 to 10.45. At this pH insulin
and erythromycin gluceptate are incompatible. Other exam-
ples of drugs incompatible with aminophylline include amio-
darone, benzylpenicillin potassium, cisatracurium,
Dobutamine, tetracycline hydrochloride, verapamil hydro-
Chloride, warfarin sodium, and vitamin B and C injection.
One study has found that although ceftazidime was incompat-
ible with aminophylline in infusion fluids, it was adequately
stable for intermittent Y-site infusion over a 2-hour period.
Infusion fluids containing cefuroxime and aminophylline
have been reported to be stable for up to 4 hours." Solutions
containing ceftriaxone sodium and aminophylline were found
to be generally unstable if stored for 24 hours with degrada-
tion of ceftriaxone and some loss of aminophylline.'
Adverse Effects, Treatment, and Precautions :
As for theophylline,so see theophylline
Pharmacokinetic
Aminophylline, a complex of theophylline with eth-
ylenediamine. readily liberates theophylline in the
body. The pharmacokinetics of aminophylline is similar to theophylline.
Theophylline is rapidly and completely absorbed after oral administration in
solution or immediate-release solid oral dosage form. Theophylline does not
undergo any appreciable presystemic elimination, distributes freely into fat-
free tissues, and is extensively metabolized in the liver.
The pharmacokinetics of theophylline vary widely among similar patients and
cannot be predicted by age, sex, body weight, or other demographic
characteristics. In addition, certain concurrent illnesses and alterations in
normal physiology (See TABLE I) and coadministration of other drugs (see TABLE
II) can significantly alter the pharmacokinetic characteristics of theophylline.
Within-subject variability in metabolism has also been reported in some studies,
especially in acutely ill patients. It is, therefore, recommended that serum
theophylline concentrations be measured frequently in acutely ill patients (eg,
at 24-hour intervals) and periodically in patients receiving long-term therapy
(eg, at 6- to 12-month intervals). More frequent measurements should be made in
the presence of any condition that may significantly alter theophylline
Uses and Administration
Aminophylline has the actions and uses of theophyl-
line and is used similarly as a bronchodi- '
lator in the management of asthma and
chronic obstructive pulmonary disease. It
was formerly used for its diuretic action in heart fail-
ure but has been superseded by more effective drugs.
However, it may have a role in patients
with heart failure and obstructive airways disease
though care is needed in those with increased myo-
cardial excitability. Aminophylline is usually pre-
ferred to theophylline when greater solubility in
water is required, particularly in intravenous formu-
lations.
Aminophylline may be given in the anhydrous form.
or as the dihydrate. Doses appear to be usually ex-
pressed as aminophylline hydrate though some
pharmacopoeias label aminophylline preparations
with respect to their anhydrous aminophylline con-
tent.
As the pharmacokinetics off theophylline are affect-
ed by a number of factors including age, smoking,
disease, diet, and drug interactions, the dose of
aminophylline must be carefully individualised and
serum-theophylline concentrations monitored .
In the management of acute severe bronchospasm,
aminophylline may be administered intravenously
by slow injection or infusion. To reduce adverse ef-
fects, the rate of intravenous administration of ami-
nophylline should not exceed 25 mg per minute, ln
patients who have not been taking aminophylline.
theophylline, or other xanthine-containing medica-
tion. 250 to 500 mg of aminophylline (25 mg per-
mL) may be given by slow intravenous injection
over 20 minutes. When administered by infusion, a
suggested loading dose is 5 mg per kg, given over 20
to 30 minutes, followed by a maintenance dose of
0.5 mg per kg per hour. Older patients and those'
with cor pulmonale. heart failure, or liver disease
may require lower maintenance doses; smokers of-
ten need higher maintenance doses (see Precautions
under Theophylline). A loading dose may not
be considered necessary unless the patient's condi-
tion is deteriorating. Children (also not currently on
xanthine medication) may be given the same load- "
ing dose per kg as adults: suggested maintenance"
doses are 1 mg per kg per hour for children aged 6
months to 9 years and 0.8 mg per kg per Hour for
children aged 10 to 16 years. Some authorities sug-
gest that the maintenance doses should be slightly
higher for the first 12 hours of the infusion in both
adults and children.
Intravenous aminophylline is best avoided in pa-
tients already taking theophylline. aminophylline. or
other xanthine-containing medication but. if consid-
ered necessary, the serum-theophylline concentra-
tion should first be assessed and the initial loading"
dose .should be calculated on the basis that each
0.5 mg per kg of aminophylline will increase serum
theophylline concentration by 1 microgm per mL.
In the treatment of acute bronchospasm that does
not require intravenous therapy, aminophylline has
been given by mouth in conventional dosage forms;
modified-release preparations are not suitable.
Doses used have generally ranged from 100 to
300 mg three or four times daily after food.
In the management of chronic bronchospasm
aminophylline may be given by mouth as conven-
tional or as modified-release preparations. The mod-
ified-release products are generally preferred and a
usual dose is aminophylline hydrate 225 to 450 mg
twice daily by mouth. Therapy should be initiated
with the lower dose and increased as necessary. Eld-
erly patients may require lower doses. Retitration of
the dosage may be required if the patient is changed
from one modified-release preparation to another as
the bioavailability of modified-release aminophyl-
line preparations may vary. Children (over 3 years)
have been given modified-release aminophylline hy-
drate in doses of 12 mg per kg body-weight daily,
increased after I week to 24 mg per kg daily, in 2
divided doses.
Intramuscular administration of aminophylline
causes intense local pain and is not recommended.
Aminophylline has also been used as the hydro-
chloride.
Adminirtratten. RECTAL ADMINISTRATION. Absorption from
aminophylline suppositories is erratic and this dose form has
been associated with toxicity. hence the warnings that suppos-
itories should not be used especially in children. In the UK
suppositories are no longer readily available and one hospital
wishing to use the rectal route for apnoea in premature infants
achieved therapeutic plasma-theophylline concentrations
with a specially formulated rectal gel.'
Methotrexate Neurotoxicity: Aminophylline by intrave-
nous infusion or theophylline by mouth relieved the acute
neurotoxicity of methotrexate in some children' pos-
sibly through an anti-adenosine effect.