Antimuscarinic bronchodilators

3.1.2 Antimuscarinic bronchodilators

dilution is necessary use only sterile sodium chloride 0.9%

Ipratropium can provide short-term relief in chronic asthma, but short-acting beta agonists act more quickly

Atrovent c (Boehringer Ingelheim) and are preferred. Ipratropium by nebulisation can be

(dry powder for inhalation; for use with added to other standard treatment in life-threatening

Aerocaps c

Atrovent Aerohaler c ), green, ipratropium bromide

Respiratory

asthma or if acute asthma fails to improve with standard

40 micrograms, net price pack of 100 caps with therapy (see Acute Asthma table, p. 150).

Aerohaler c = £14.53; 100 caps = £10.53. Counselling, The aerosol inhalation of ipratropium can be used for

dose

short-term relief in mild chronic obstructive pulmonary Note One Atrovent Aerocap is equivalent to 2 puffs of disease in patients who are not using a long-acting

Atrovent

metered aerosol inhalation

syst

antimuscarinic drug. Its maximal effect occurs 30–60 Aerosol inhalation T, ipratropium bromide 20 micr- ograms/metered inhalation, net price 200-dose unit =

em

minutes after use; its duration of action is 3 to 6 hours and bronchodilation can usually be maintained with

£4.21. Counselling, dose, change to CFC-free inhaler Excipients treatment 3 times a day.

include HFA-134a (a non-CFC propellant)

Nebuliser solution , isotonic, ipratropium bromide Tiotropium, a long-acting antimuscarinic bronchodila-

tor, is effective for the management of chronic obstruc- tive pulmonary disease; it is not suitable for the relief of acute bronchospasm.

necessary use only sterile sodium chloride 0.9% Cautions Antimuscarinic bronchodilators should be Ipratropium Steri-Neb c (IVAX) A

used with caution in patients with prostatic hyperplasia, Nebuliser solution , isotonic, ipratropium bromide bladder outflow obstruction, and those susceptible to angle-closure glaucoma (see below); interactions: Appendix 1 (antimuscarinics)

microgram) = £9.94. If dilution is necessary use only Glaucoma Acute angle-closure glaucoma reported with

sterile sodium chloride 0.9% nebulised ipratropium, particularly when given with

nebulised salbutamol (and possibly other beta ago- A

Respontin c (A&H)

, isotonic, ipratropium bromide nists); care needed to protect patient’s eyes from neb-

Nebuliser solution

ulised drug or from drug powder. Side-effects Dry mouth is the most common side-

microgram) = £5.95. If dilution is necessary use only effect of antimuscarinic bronchodilators; less commonly

sterile sodium chloride 0.9% nausea and headache occur. Constipation, tachycardia,

Compound ipratropium preparations palpitation, paradoxical bronchospasm, urinary reten-

tion, blurred vision, angle-closure glaucoma, and hyper-

Section 3.1.4

sensitivity reactions including rash, urticaria, pruritus, and angioedema occur rarely.

TIOTROPIUM Indications IPRATROPIUM BROMIDE maintenance treatment of chronic

obstructive pulmonary disease Indications reversible airways obstruction, particu-

Cautions see notes above; renal impairment (Appen- larly in chronic obstructive pulmonary disease; rhin-

dix 3); pregnancy (Appendix 4); breast-feeding itis (section 12.2.2)

(Appendix 5)

3.1.3 Theophylline BNF 57 Side-effects see notes above; less commonly taste

vulsions and arrhythmias can occasionally precede disturbance, dysphonia, and dizziness; rarely gastro-

other symptoms of toxicity. intestinal reflux, and epistaxis Dose . See under preparations below

THEOPHYLLINE

A Indications reversible airways obstruction, acute Inhalation powder, hard capsule (for use with

Spiriva c (Boehringer Ingelheim)

severe asthma; see also Management of Chronic and HandiHaler c device), green, tiotropium (as tiotropium

Acute Asthma (p. 149 and p. 150) bromide monohydrate) 18 micrograms, net price 30-

Cautions cardiac disease, hypertension, hyper- cap pack with HandiHaler c device = £37.62, 30-cap

thyroidism; peptic ulcer; epilepsy; elderly; fever; CSM refill = £34.40

advice on hypokalaemia risk, p. 153; avoid in acute Dose by inhalation of powder , ADULT over 18 years, 18 micr-

porphyria (section 9.8.2); monitor plasma-theo- ograms once daily

phylline concentration (see notes above); hepatic Respimat c (solution for inhalation) T, tiotropium (as

impairment (Appendix 2); pregnancy (see p. 148 and tiotropium bromide monohydrate) 2.5 micrograms/

Appendix 4); breast-feeding (see p. 148 and Appendix metered inhalation, net price 60-dose unit = £37.62

5); interactions: Appendix 1 (theophylline) and notes Dose by inhalation , ADULT over 18 years, 5 micrograms (2 puffs)

above

once daily Side-effects tachycardia, palpitation, nausea and Note The Scottish Medicines Consortium has advised (November

other gastro-intestinal disturbances, headache, CNS

tem

2007) that Spiriva Respimat is restricted for use in chronic obstructive pulmonary disease in patients who have poor manual

stimulation, insomnia, arrhythmias, and convulsions

sys

dexterity and difficulty using the Handihaler device especially if given rapidly by intravenous injection; overdosage: see Emergency Treatment of Poisoning, p. 33

atory

Dose . See below

Respir

3.1.3 Theophylline

Note Plasma-theophylline concentration for optimum response 10–20 mg/litre (55–110 micromol/litre); 4–6

3 Theophylline is a bronchodilator used for asthma and hours after a dose and at least 5 days after starting treatment; narrow margin between therapeutic and toxic dose, see also stable chronic obstructive pulmonary disease; it is not

notes above

generally effective in exacerbations of chronic obstruc- tive pulmonary disease. It may have an additive effect

Modified release when used in conjunction with small doses of beta

Note The rate of absorption from modified-release prepara- agonists; the combination may increase the risk of

tions can vary between brands. The Council of the Royal side-effects, including hypokalaemia (for CSM advice

Pharmaceutical Society of Great Britain advises pharmacists that if a general practitioner prescribes a modified-release oral

see p. 153). theophylline preparation without specifying a brand name, the Theophylline is metabolised in the liver; there is con-

pharmacist should contact the prescriber and agree the brand to be dispensed. Additionally, it is essential that a patient

siderable variation in plasma-theophylline concentra- discharged from hospital should be maintained on the brand on tion particularly in smokers, in patients with hepatic

which that patient was stabilised as an in-patient. impairment or heart failure, or if certain drugs are taken concurrently. The plasma-theophylline concentration is

Nuelin SA c (3M) , m/r, theophylline 175 mg, net price 60-tab

SA tablets pack = £3.19. Label: 21, 25

increased in heart failure, cirrhosis, viral infections, in the

elderly, and by drugs that inhibit its metabolism. The Dose 175–350 mg every 12 hours; CHILD 6–12 years 175 mg plasma-theophylline concentration is decreased in smo-

every 12 hours

kers and in chronic alcoholism and by drugs that induce , m/r, scored, theophylline 250 mg, net liver metabolism. For other interactions of theophylline

SA 250 tablets price 60-tab pack = £4.46. Label: 21, 25

see Appendix 1. Dose 250–500 mg every 12 hours; CHILD 6–12 years 125–250 mg Differences in the half-life of theophylline are important

every 12 hours

because its toxic dose is close to the therapeutic dose; Slo-Phyllin c (Merck) particular care is required when introducing or with-

Capsules , m/r, theophylline 60 mg (white/clear, drawing drugs that interact with theophylline. In most

enclosing white pellets), net price 56-cap pack = individuals a plasma-theophylline concentration of

£2.76; 125 mg (brown/clear, enclosing white pellets), between 10–20 mg/litre is required for satisfactory

56-cap pack = £3.48; 250 mg (blue/clear, enclosing bronchodilation, although a plasma-theophylline con-

white pellets), 56-cap pack = £4.34. Label: 25, or centration of 10 mg/litre (or less) may be effective.

counselling, see below Adverse effects can occur within the range 10–20 mg/

Dose 250–500 mg every 12 hours; CHILD 2–6 years 60–120 mg litre and both the frequency and severity increase at

every 12 hours, 6–12 years 125–250 mg every 12 hours concentrations above 20 mg/litre.

Counselling Swallow whole with fluid or swallow enclosed gran- Theophylline is given by injection as aminophylline, a

ules with soft food (e.g. yoghurt) mixture of theophylline with ethylenediamine, which is

Uniphyllin Continus c (Napp)

20 times more soluble than theophylline alone. Amino- Tablets , m/r, scored, theophylline 200 mg, net price phylline injection is needed rarely for severe attacks of

56-tab pack = £3.13; 300 mg, 56-tab pack = £4.77; asthma. It must be given by very slow intravenous

400 mg, 56-tab pack = £5.65. Label: 25 injection (over at least 20 minutes); it is too irritant for

Dose 200 mg every 12 hours, increased according to response to intramuscular use. Measurement of plasma theophylline

400 mg every 12 hours; CHILD 2–12 years, 9 mg/kg (up to 200 mg) concentration may be helpful, and is essential if amino-

every 12 hours; some children with chronic asthma may require phylline is to be given to patients who have been taking 10–16 mg/kg (max. 400 mg) every 12 hours Note May be appropriate to give larger evening or morning dose theophylline, because serious side-effects such as con-

to achieve optimum therapeutic effect when symptoms most

BNF 57

3.1.4 Compound bronchodilator preparations 159

severe; in patients whose night or daytime symptoms persist despite other therapy, who are not currently receiving theo-

3.1.2), so that the dose of each drug can be adjusted. phylline, total daily requirement may be added as single evening

This flexibility is lost with compound bronchodilator or morning dose

preparations. However, a combination product may be appropriate for patients stabilised on individual compo-

AMINOPHYLLINE nents in the same proportion.

Note Aminophylline is a stable mixture or combination of For cautions, contra-indications and side-effects see theophylline and ethylenediamine; the ethylenediamine con-

under individual drugs. fers greater solubility in water Combivent Indications c (Boehringer Ingelheim)

reversible airways obstruction, acute AU

Nebuliser solution , isotonic, ipratropium bromide severe asthma

500 micrograms, salbutamol (as sulphate) 2.5 mg/2.5- Cautions see under Theophylline

mL vial, net price 60 unit-dose vials = £25.08 Side-effects see under Theophylline; also allergy to

Dose bronchospasm in chronic obstructive pulmonary disease, ethylenediamine can cause urticaria, erythema, and

by inhalation of nebulised solution , ADULT and CHILD over 12 exfoliative dermatitis

years, 1 vial (2.5 mL) 3–4 times daily Dose

Glaucoma In addition to other potential side-effects acute angle- closure glaucoma has been reported with nebulised ipratropium—

. See under preparations, below

for details, see p. 157

Note Plasma-theophylline concentration for optimum response 10–20 mg/litre (55–110 micromol/litre); measure c Duovent (Boehringer Ingelheim) AU plasma-theophylline concentration 4–6 hours after dose by

Nebuliser solution , isotonic, fenoterol hydrobromide mouth and at least 5 days after starting oral treatment;

1.25 mg, ipratropium bromide 500 micrograms/4-mL measure plasma-theophylline concentration 4–6 hours after

vial, net price 20 unit-dose vials = £11.00 the start of intravenous infusion; narrow margin between

Dose therapeutic and toxic dose, see also notes above acute severe asthma or acute exacerbation of chronic asthma, by inhalation of nebulised solution , ADULT and CHILD

To avoid excessive dosage in obese patients, dose over 14 years, 1 vial (4 mL); may be repeated up to max. 4 vials in should be calculated on the basis of ideal weight for

24 hours

height Glaucoma In addition to other potential side-effects acute angle- closure glaucoma has been reported with nebulised ipratropium— for details, see p. 157

Aminophylline (Non-proprietary) A Injection , aminophylline 25 mg/mL, net price 10-mL

amp = 72p Brands include Minijet

Aminophylline

Respiratory

Dose acute severe asthma or acute exacerbation of chronic obstructive pulmonary disease not previously treated with theo- phylline, by slow intravenous injection over at least 20 minutes (with close monitoring), 250–500 mg (5 mg/kg), then see below; CHILD

5 mg/kg, then see below

3.1.5 Peak flow meters, inhaler

Acute severe asthma or acute exacerbation of chronic obstructive pulmonary disease, by intravenous infusion (with close monitor-

devices and nebulisers

syst

ing), 500 micrograms/kg/hour, adjusted according to plasma- theophylline concentration; CHILD

em

6 months–9 years 1 mg/kg/

hour, 10–16 years 800 micrograms/kg/hour, adjusted according to plasma-theophylline concentration Note Patients taking oral theophylline or aminophylline should

Peak flow meters

not normally receive intravenous aminophylline unless plasma- Measurement of peak flow is particularly helpful for theophylline concentration is available to guide dosage

patients who are ‘poor perceivers’ and hence slow to Modified release

detect deterioration in their asthma, and for those with Note Advice about modified-release theophylline preparations

moderate or severe asthma. on p. 158 also applies to modified-release aminophylline pre-

Standard-range peak flow meters are suitable for both parations

adults and children; low-range peak flow meters are Phyllocontin Continus c (Napp)

appropriate for severely restricted airflow in adults and Tablets , m/r, yellow, f/c, aminophylline hydrate

children. Patients must be given clear guidelines as to 225 mg, net price 56-tab pack = £2.54. Label: 25

the action they should take if their peak flow falls below Dose ADULT and CHILD body-weight over 40 kg initially 1 tablet

a certain level. Patients can be encouraged to adjust twice daily, increased after 1 week to 2 tablets twice daily according to plasma-theophylline concentration

some of their own treatment (within specified limits) Note Brands of modified-release tablets containing amino-

according to changes in peak flow rate. phylline 225 mg include Norphyllin SR

Standard Range Peak Flow Meter

Forte tablets , m/r, yellow, f/c, aminophylline hydrate Conforms to standard EN 13826 350 mg, net price 56-tab pack = £4.22. Label: 25

MicroPeak , range 60–800 litres/minute, net price = £6.50, Dose initially 1 tablet twice daily, increased after 1 week to 2

replacement mouthpiece = 38p (Micro Medical) tablets twice daily if necessary

Mini-Wright , range 60–800 litres/minute, net price = £6.86, Note Phyllocontin Continus

Forte tablets are for smokers and replacement mouthpiece = 38p (Clement Clarke) other patients with shorter theophylline half-life (see notes above)

Personal Best , range 60–800 litres/minute, net price = £6.48, replacement mouthpiece = 25p (Respironics)

Piko-1 , range 15–999 litres/minute, net price = £9.50,