page201
3.1.3
Theophylline
Theophylline is a xanthine used as a bronchodilator in
asthma
(see Management
of
Chronic Asthma table,
p.
172) and stable
chronic obstructive pulmonary dis-
ease
, (see p.
171); it is not generally effective in exacer-
bations of chronic obstructive pulmonary disease. Theo-
phylline may have an additive effect
when used in
conjunction with small
doses
of
beta
2
agonists;
the
combination may
increase
the
risk
of
side-effects,
including hypokalaemia (see p.
176).
Theophylline is metabolised in the liver.
The plasma-
theophylline concentration is
increased
in heart failure,
hepatic impairment,
viral
infections,
in the elderly,
and
by drugs that inhibit its metabolism.
The plasma-theo-
phylline concentration is
decreased
in smokers,
by
alcohol
consumption,
and by drugs
that
induce its
metabolism.
For
interactions:
see Appendix 1 (theo-
phylline).
Differences in the half-life of theophylline are important
because the toxic dose is close to the therapeutic dose.
In most individuals, satisfactory bronchodilation is asso-
ciated with a plasma-theophylline concentration of 10–
20 mg/litre (see Note below), although a lower plasma-
theophylline concentration may be effective.
Adverse
effects can occur within the range 10–20 mg/litre and
both the frequency and severity increase at concentra-
tions above 20 mg/litre.
Theophylline is given by injection as aminophylline,
a
mixture of theophylline with ethylenediamine,
which is
20 times more soluble than theophylline alone.
Amino-
phylline injection is
needed rarely for
severe acute
asthma,
see
Management
of
Acute
Asthma
table,
p.
173.
It
must
be given by very slow intravenous
injection (over at least 20 minutes);
it is too irritant for
intramuscular
use.
Measurement
of
plasma-theo-
phylline concentration may be helpful,
and is essential
if
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.
Caffeine is a xanthine derivative used as a respiratory
stimulant
in
neonatal
apnoea
,
see
BNF for Children
section 3.5.1.
THEOPHYLLINE
Indications
reversible airways obstruction,
severe
acute asthma;
see also Management of Chronic
Asthma table p.
172 and Management of Acute
Asthma table p.
173
Cautions
see notes above,
also cardiac disease;
hypertension; hyperthyroidism; peptic ulcer; epilepsy;
elderly;
fever; hypokalaemia risk,
see p.
176;
avoid in
acute porphyria (section 9.8.2);
monitor plasma-
theophylline concentration (see notes above); dose
adjustment may be necessary if smoking started or
stopped during treatment
Hepatic impairment
reduce dose
Pregnancy
neonatal irritability and apnoea have been
reported;
see also p.
170
Breast-feeding
present in milk—irritability in infant
reported;
modified release preparations preferable;
see also p.
170
Side-effects
nausea,
vomiting,
gastric irritation,
diarrhoea;
palpitation,
tachycardia, arrhythmias,
hypotension;
anxiety,
dizziness,
tremor,
headache,
CNS stimulation, insomnia, and convulsions;
over-
dosage: see Emergency Treatment of Poisoning, p.
39
Dose
. See under preparations below
Note
Plasma-theophylline
concentration
for
optimum
response 10–20 mg/litre (55–110 micromol/litre); 4–6
hours after a dose and at least 5 days after starting treatment;
narrow margin between therapeutic and toxic dose, see also
notes above
Modified release
Note
The rate of
absorption from modified-release prepara-
tions can vary between brands. If a prescription for a modified-
release oral theophylline 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.
Nuelin SA
c
(Meda)
SA tablets
, m/r, theophylline 175 mg, net price 60-tab
pack = £3.19.
Label:
21,
25
Dose
175–350 mg every 12 hours;
CHILD 6–12 years 175 mg
every 12 hours
SA 250 tablets
, m/r, scored, theophylline 250 mg, net
price 60-tab pack = £4.46.
Label:
21, 25
Dose
250–500 mg every 12 hours; CHILD 6–12 years 125–250 mg
every 12 hours
Slo-Phyllin
c
(Merck Serono)
Capsules
,
m/r,
theophylline 60 mg (white/clear,
enclosing white pellets),
net price 56-cap pack =
£2.76;
125 mg (brown/clear,
enclosing white pellets),
56-cap pack = £3.48;
250 mg (blue/clear,
enclosing
white pellets),
56-cap pack = £4.34.
Label:
25,
or
counselling,
see below
Dose
250–500 mg every 12 hours;
CHILD 2–6 years 60–120 mg
every 12 hours, 6–12 years 125–250 mg every 12 hours
Counselling
Swallow whole with fluid
or
swallow enclosed gran-
ules with soft food (e.g.
yoghurt)
Uniphyllin Continus
c
(Napp)
Tablets
,
m/r,
scored,
theophylline 200 mg,
net price
56-tab pack = £2.94;
300 mg,
56-tab pack = £4.77;
400 mg,
56-tab pack = £5.32.
Label:
25
Dose
200 mg every 12 hours, increased according to response to
400 mg every 12 hours;
CHILD 2–12 years, 9 mg/kg (up to 200 mg)
every 12 hours;
some children with chronic asthma may require
10–16 mg/kg (max.
400 mg) every 12 hours
Note
May be appropriate to give larger evening or morning dose
to achieve optimum therapeutic effect when symptoms most
severe;
in patients whose night or daytime symptoms persist
despite other therapy,
who are not currently receiving theo-
phylline, total
daily requirement may be added as single evening
or morning dose
AMINOPHYLLINE
Note
Aminophylline is a stable mixture or
combination of
theophylline and ethylenediamine;
the ethylenediamine con-
fers greater solubility in water
Indications
reversible airways obstruction,
severe
acute asthma
Cautions
see under Theophylline
Hepatic impairment
see under Theophylline
Pregnancy
see under Theophylline
Breast-feeding
see under Theophylline
Side-effects
see under Theophylline; also allergy to
ethylenediamine can cause urticaria,
erythema,
and
exfoliative dermatitis;
hypotension,
arrhythmias,
and
convulsions especially if given rapidly by intravenous
injection
Dose
. See under preparations,
below
Note
Plasma-theophylline
concentration
for
optimum
response 10–20 mg/litre (55–110 micromol/litre); measure
plasma-theophylline concentration 4–6 hours after dose by
BNF 61
3.1.3 Theophylline
181
3
Respiratory system