DOSESATEXTREMESOFBODY-WEIGHT
▶To avoid excessive dosage in obese patients, dose
should be calculated on the basis of ideal weight for
height.
PHARMACOKINETICS
▶Aminophylline is a stable mixture or combination of
theophylline and ethylenediamine; the
ethylenediamine confers greater solubility in water.
▶Theophylline is metabolised in the liver. The plasma-
theophylline concentration is increased in heart
failure, hepatic impairment, and in viral infections.
The plasma-theophylline concentration is decreased in
smokers, and by alcohol consumption. Differences in
the half-life of aminophylline are important because
the toxic dose is close to the therapeutic dose.lUNLICENSED USEAminophylline injection not licensed for
use in children under 6 months.
PHYLLOCONTIN CONTINUS®FORTE
▶With oral usePhyllocontin Continus®Fortetablets are not
licensed for use in children.
lCAUTIONSArrhythmias following rapid intravenous
injection.cardiac arrhythmias or other cardiac disease.
epilepsy.fever.hypertension.hyperthyroidism.peptic
ulcer.risk of hypokalaemia
lINTERACTIONS→Appendix 1 : aminophylline
lSIDE-EFFECTS
GENERAL SIDE-EFFECTSArrhythmia (more common when
given too rapidly by intravenous injection).headache.
nausea.palpitations.seizure (more common when given
too rapidly by intravenous injection)
SPECIFIC SIDE-EFFECTS
▶With intravenous useAbdominal pain.anxiety.confusion.
delirium.diarrhoea.dizziness.electrolyte imbalance.
gastrointestinal haemorrhage.gastrooesophageal reflux
disease.hyperthermia.hyperventilation.hypotension
(more common when given too rapidly by intravenous
injection).insomnia.mania.metabolic disorder.pain.
skin reactions.tachycardia (more common when given too
rapidly by intravenous injection).thirst.tremor.vertigo.
visual impairment.vomiting
▶With oral useCentral nervous system stimulation.
epigastric discomfort
SIDE-EFFECTS, FURTHER INFORMATIONPotentially serious
hypokalaemia may result from beta 2 -agonist therapy.
Particular caution is required in severe asthma, because
this effect may be potentiated by concomitant treatment
with theophylline and its derivatives, corticosteroids, and
diuretics, and by hypoxia. Plasma-potassium
concentration should therefore be monitored in severe
asthma.
OverdoseTheophylline and related drugs are often
prescribed as modified-release formulations and toxicity
can therefore be delayed. They cause vomiting (which may
be severe and intractable), agitation, restlessness, dilated
pupils, sinus tachycardia, and hyperglycaemia. More
serious effects are haematemesis, convulsions, and
supraventricular and ventricular arrhythmias. Severe
hypokalaemia may develop rapidly.
For specific details on the management of poisoning, see
Theophylline, under Emergency treatment of poisoning
p. 832.
lALLERGY AND CROSS-SENSITIVITYAllergy to
ethylenediamine can cause urticaria, erythema, and
exfoliative dermatitis.
lPREGNANCYNeonatal irritability and apnoea have been
reported. Theophylline can be taken as normal during
pregnancy as it is particularly important that asthma
should be well controlled during pregnancy.lBREAST FEEDINGPresent in milk—irritability in infant
reported; modified-release preparations preferable.
Theophylline can be taken as normal during breast-
feeding.
lHEPATIC IMPAIRMENT
Dose adjustmentsReduce dose.
lMONITORING REQUIREMENTS
▶Aminophylline is monitored therapeutically in terms of
plasma-theophylline concentrations.
▶Measurement of plasma-theophylline concentration may
be helpful and isessentialif a loading dose of intravenous
aminophylline is to be given to patients who are already
taking theophylline, because serious side-effects such as
convulsions and arrhythmias can occasionally precede
other symptoms of toxicity.
▶In most individuals, a plasma-theophylline concentration
of 10 – 20 mg/litre ( 55 – 110 micromol/litre) is required for
satisfactory bronchodilation, although a lower plasma-
theophylline concentration of 5 – 15 mg/litre may be
effective. Adverse effects can occur within the range
10 – 20 mg/litre and both the frequency and severity
increase at concentrations above 20 mg/litre.
▶If aminophylline is given intravenously, a blood sample
should be taken 4 – 6 hours after starting treatment.
▶With oral usePlasma-theophylline concentration is
measured 5 days after starting oral treatment and at least
3 days after any dose adjustment. A blood sample should
usually be taken 4 – 6 hours after an oral dose of a
modified-release preparation (sampling times may vary—
consult local guidelines).
lDIRECTIONS FOR ADMINISTRATION
▶With intravenous useForintravenous injection, givevery
slowlyover at least 20 minutes (with close monitoring).
Forintravenous infusion, dilute to a concentration of
1 mg/mL with Glucose 5 %orSodium Chloride 0. 9 %.
▶With intramuscular useAminophylline is too irritant for
intramuscular use.
lPRESCRIBING AND DISPENSING INFORMATIONPatients
taking oral theophylline or aminophylline should not
normally receive a loading dose of intravenous
aminophylline.
Consider intravenous aminophylline for treatment of
severe and life-threatening acute asthma only after
consultation with senior medical staff.
Modified releaseThe rate of absorption from modified-
release preparations can vary between brands. If a
prescription for a modified-release oral aminophylline
preparation does not specify a brand name, the pharmacist
should contact the prescriber and agree the brand to be
dispensed. Additionally, it is essential that a patient
discharged from hospital should be maintained on the
brand on which that patient was stabilised as an in-
patient.lMEDICINAL FORMS
There can be variation in the licensing of different medicines
containing the same drug. Forms available from special-order
manufacturers include: solution for infusion, suppository
Solution for injection
▶Aminophylline (Non-proprietary)
Aminophylline 25 mg per 1 mlAminophylline 250 mg/ 10 ml solution
for injection ampoules| 10 ampouleP£ 6. 50 DT = £ 6. 50
Modified-release tablet
CAUTIONARY AND ADVISORY LABELS 25
▶Phyllocontin Continus(Napp Pharmaceuticals Ltd)
Aminophylline hydrate 225 mgPhyllocontin Continus 225 mg
tablets| 56 tabletp£ 2. 40 DT = £ 2. 40
Aminophylline hydrate 350 mgPhyllocontin Forte Continus 350 mg
tablets| 56 tabletp£ 4. 22 DT = £ 4. 22168 Airways disease, obstructive BNFC 2018 – 2019
Respiratory system3