Smoking: harm reduction. National Institute for Health
and Care Excellence. Public health guidance 45. June 2013.
National Centre for Smoking Cessation and Training.
ANTIDEPRESSANTS › SEROTONIN AND
NORADRENALINE RE-UPTAKE INHIBITORS
Bupropion hydrochloride 08-Jun-2018
To aid smoking cessation in combination with
motivational support in nicotine-dependent patients
▶ Adult: Initially 150 mg daily for 6 days, then 150 mg
twice daily (max. per dose 150 mg), minimum 8 hours
between doses; period of treatment 7–9 weeks, start
treatment 1–2 weeks before target stop date,
discontinue if abstinence not achieved at 7 weeks,
consider maximum 150 mg daily in patients with risk
factors for seizures; maximum 300 mg per day
▶ Elderly: 150 mg daily for 7–9 weeks, start treatment
1–2 weeks before target stop date, discontinue if
abstinence not achieved at 7 weeks; maximum 150 mg
l CONTRA-INDICATIONS Acute alcohol withdrawal . acute
l CAUTIONS Alcohol abuse . diabetes . elderly . history of
head trauma . predisposition to seizures (prescribe only if
benefit clearly outweighs risk)
l INTERACTIONS → Appendix 1: bupropion
avoiding dose at bedtime). nausea . skin reactions .taste
▶ Rare or very rare Angioedema . arthralgia . behaviour
hypotension . seizure . sleep disorders . Stevens-Johnson
syndrome . syncope . urinary disorders
l PREGNANCY Avoid—no information available.
l BREAST FEEDING Present in milk—avoid.
l HEPATIC IMPAIRMENT Manufacturer advises use with
caution—monitor closely for adverse effects; avoid in
498 Substance dependence BNF 78
Dose adjustments Manufacturer advises reduce dose to
150 mg daily in mild to moderate impairment
Dose adjustments Reduce dose to 150 mg daily.
l MONITORING REQUIREMENTS Manufacturer advises
monitor blood pressure before and during treatment.
l PATIENT AND CARER ADVICE Manufacturer advises
patients and carers should be instructed to report any
clinical worsening of depression, suicidal behaviour or
thoughts and unusual changes in behaviour.
Driving and skilled tasks Manufacturer advises patients and
carers should be counselled on the effects on driving and
performance of skilled tasks—increased risk of dizziness
l MEDICINAL FORMS There can be variation in the licensing of
different medicines containing the same drug.
CAUTIONARY AND ADVISORY LABELS 25
▶ Zyban (GlaxoSmithKline UK Ltd)
Bupropion hydrochloride 150 mg Zyban 150mg modified-release
tablets | 60 tablet P £41.76 DT = £41.76
Nicotine replacement therapy in individuals who smoke
fewer than 20 cigarettes each day
▶ Adult: 2 mg as required, chew 1 piece of gum when the
urge to smoke occurs or to prevent cravings, if
attempting smoking cessation, treatment should
continue for 3 months before reducing the dose
▶ BY SUBLINGUAL ADMINISTRATION USING SUBLINGUAL TABLETS
▶ Adult: 1 tablet every 1 hour, increased to 2 tablets every
1 hour if required, if attempting smoking cessation,
treatment should continue for up to 3 months before
reducing the dose; maximum 40 tablets per day
Nicotine replacement therapy in individuals who smoke
more than 20 cigarettes each day or who require more
than 15 pieces of 2-mg strength gum each day
▶ Adult: 4 mg as required, chew 1 piece of gum when the
urge to smoke occurs or to prevent cravings,
individuals should not exceed 15 pieces of 4-mg
strength gum daily, if attempting smoking cessation,
treatment should continue for 3 months before
Nicotine replacement therapy in individuals who smoke
more than 20 cigarettes each day
▶ BY SUBLINGUAL ADMINISTRATION USING SUBLINGUAL TABLETS
▶ Adult: 2 tablets every 1 hour, if attempting smoking
cessation, treatment should continue for up to
3 months before reducing the dose; maximum
▶ BY INHALATION USING INHALATOR
▶ Adult: As required, the cartridges can be used when the
urge to smoke occurs or to prevent cravings,
individuals should not exceed 12 cartridges of the
10-mg strength daily, or 6 cartridges of the 15-mg
▶ Adult: 1 lozenge every 1–2 hours as required, one
lozenge should be used when the urge to smoke occurs,
individuals who smoke less than 20 cigarettes each day
should usually use the lower-strength lozenges;
individuals who smoke more than 20 cigarettes each
day and those who fail to stop smoking with the lowstrength lozenges should use the higher-strength
lozenges; If attempting smoking cessation, treatment
should continue for 6–12 weeks before attempting a
reduction in dose; maximum 15 lozenges per day
▶ BY MOUTH USING OROMUCOSAL SPRAY
▶ Adult: 1–2 sprays as required, individuals can spray in
the mouth when the urge to smoke occurs or to prevent
cravings, individuals should not exceed 2 sprays per
episode (up to 4 sprays every hour); maximum
▶ BY INTRANASAL ADMINISTRATION USING NASAL SPRAY
▶ Adult: 1 spray as required, individuals can spray into
each nostril when the urge to smoke occurs, up to twice
every hour for 16 hours daily, if attempting smoking
cessation, treatment should continue for 8 weeks
before reducing the dose; maximum 64 sprays per day
▶ BY TRANSDERMAL APPLICATION USING PATCHES
▶ Adult: Individuals who smoke more than 10 cigarettes
daily should apply a high-strength patch daily for
6–8 weeks, followed by the medium-strength patch for
2 weeks, and then the low-strength patch for the final
2 weeks; individuals who smoke fewer than
schedule can be used in individuals who are not ready
to quit but want to reduce cigarette consumption
before a quit attempt; if abstinence is not achieved, or
if withdrawal symptoms are experienced, the strength
of the patch used should be maintained or increased
until the patient is stabilised; individuals using the
change to a medium-strength patch for the remainder
of the initial period and then use the low-strength
GENERAL CAUTIONS Diabetes mellitus—blood-glucose
concentration should be monitored closely when initiating
treatment. haemodynamically unstable patients
hospitalised with cerebrovascular accident. haemodynamically unstable patients hospitalised with
myocardial infarction . haemodynamically unstable
patients hospitalised with severe arrhythmias . phaeochromocytoma . uncontrolled hyperthyroidism
▶ When used by inhalation Bronchospastic disease . chronic
throat disease . obstructive lung disease
▶ With intranasal use Bronchial asthma (may exacerbate)
▶ With oral use gastritis (can be aggravated by swallowed
▶ With transdermal use patches should not be placed on
broken skin . patients with skin disorders
CAUTIONS, FURTHER INFORMATION Most warnings for
nicotine replacement therapy also apply to continued
cigarette smoking, but the risk of continued smoking
outweighs any risks of using nicotine preparations.
Specific cautions for individual preparations are usually
related to the local effect of nicotine.
BNF 78 Nicotine dependence 499
nicotine). gastrointestinal disorders . hiccups . increased
risk of infection . mood altered . oral disorders . sleep
▶ With intranasal use Abnormal dreams . asthenia . hypertension . malaise
oedema .tachycardia .taste altered .throat complaints . vascular disorders
▶ With transdermal use Arrhythmias . asthenia . chest
discomfort. dyspnoea . hypertension . malaise . myalgia . paraesthesia
▶ When used by inhalation Dysphagia
▶ With intranasal use Arrhythmias
▶ With oral use Coagulation disorder. platelet disorder
▶ With sublingual use Dysphagia
▶ With transdermal use Abdominal discomfort. angioedema . pain in extremity
▶ When used by inhalation Angioedema . excessive tearing . vision blurred
▶ With sublingual use Excessive tearing . muscle tightness . vision blurred
SIDE-EFFECTS, FURTHER INFORMATION Some systemic
effects occur on initiation of therapy, particularly if the
patient is using high-strength preparations; however, the
patient may confuse side-effects of the nicotinereplacement preparation with nicotine withdrawal
symptoms. Common symptoms of nicotine withdrawal
include malaise, headache, dizziness, sleep disturbance,
coughing, influenza–like symptoms, depression,
irritability, increased appetite, weight gain, restlessness,
anxiety, drowsiness, aphthous ulcers, decreased heart rate,
l PREGNANCY The use of nicotine replacement therapy in
pregnancy is preferable to the continuation of smoking,
but should be used only if smoking cessation without
nicotine replacement fails. Intermittent therapy is
preferable to patches but avoid liquorice-flavoured
nicotine products. Patches are useful, however, if the
patient is experiencing pregnancy-related nausea and
vomiting. If patches are used, they should be removed
l BREAST FEEDING Nicotine is present in milk; however, the
amount to which the infant is exposed is small and less
hazardous than second-hand smoke. Intermittent therapy
l HEPATIC IMPAIRMENT Manufacturer advises caution in
moderate to severe impairment (risk of decreased
l RENAL IMPAIRMENT Use with caution in severe renal
l DIRECTIONS FOR ADMINISTRATION Acidic beverages, such
as coffee or fruit juice, may decrease the absorption of
nicotine through the buccal mucosa and should be avoided
for 15 minutes before the use of oral nicotine replacement
Administration by transdermal patch Patches should be
applied on waking to dry, non-hairy skin on the hip, trunk,
or upper arm and held in position for 10–20 seconds to
ensure adhesion; place next patch on a different area and
avoid using the same site for several days.
Administration by nasal spray Initially 1 spray should be used
in both nostrils but when withdrawing from therapy, the
dose can be gradually reduced to 1 spray in 1 nostril.
Administration by oral spray The oral spray should be
released into the mouth, holding the spray as close to the
mouth as possible and avoiding the lips. The patient
should not inhale while spraying and avoid swallowing for
a few seconds after use. If using the oral spray for the first
time, or if unit not used for 2 or more days, prime the unit
Administration by sublingual tablet Each tablet should be
placed under the tongue and allowed to dissolve.
Administration by lozenge Slowly allow each lozenge to
dissolve in the mouth; periodically move the lozenge from
one side of the mouth to the other. Lozenges last for
10–30 minutes, depending on their size.
Administration by inhalation Insert the cartridge into the
device and draw in air through the mouthpiece; each
session can last for approximately 5 minutes. The amount
of nicotine from 1 puff of the cartridge is less than that
from a cigarette, therefore it is necessary to inhale more
often than when smoking a cigarette. A single 10 mg
cartridge lasts for approximately 20 minutes of intense
use; a single 15 mg cartridge lasts for approximately
Administration by medicated chewing gum Chew the gum until
the taste becomes strong, then rest it between the cheek
and gum; when the taste starts to fade, repeat this process.
One piece of gum lasts for approximately 30 minutes.
l PRESCRIBING AND DISPENSING INFORMATION Flavours of
chewing gum and lozenges may include mint, freshfruit,
freshmint, icy white, or cherry.
l PATIENT AND CARER ADVICE Patient or carers should be
given advice on how to administer nicotine chewing gum,
inhalators, lozenges, sublingual tablets, oral spray, nasal
l MEDICINAL FORMS There can be variation in the licensing of
different medicines containing the same drug.
EXCIPIENTS: May contain Ethanol
▶ Nicorette (McNeil Products Ltd)
Nicotine 500 microgram per 1 actuation Nicorette
500micrograms/dose nasal spray | 10 ml G £16.18 DT = £16.18
▶ Nicorette QuickMist (McNeil Products Ltd)
Nicotine 1 mg per 1 actuation Nicorette QuickMist 1mg/dose
mouthspray freshmint sugar-free | 13.2 ml G £13.03 DT = £13.03
CAUTIONARY AND ADVISORY LABELS 26
▶ Nicorette Microtab (McNeil Products Ltd)
Nicotine (as Nicotine cyclodextrin complex) 2 mg Nicorette
Microtab 2mg sublingual tablets sugar-free | 100 tablet G £15.23
500 Substance dependence BNF 78
Nicotine 7 mg per 24 hour NiQuitin 7mg patches | 7 patch G £9.97 DT = £9.12
Nicotine 14 mg per 24 hour NiQuitin 14mg patches | 7 patch G £9.97 DT = £9.40
Nicotine 21 mg per 24 hour NiQuitin 21mg patches | 7 patch G £9.97 DT = £9.97 | 14 patch G £18.79
▶ NiQuitin Clear (Omega Pharma Ltd)
Nicotine 7 mg per 24 hour NiQuitin Clear 7mg patches | 7 patch G £9.97 DT = £9.12
Nicotine 14 mg per 24 hour NiQuitin Clear 14mg patches | 7 patch G £9.97 DT = £9.40
NiQuitin Pre-Quit Clear 21mg patches | 7 patch G £9.97 DT = £9.97
▶ Nicorette invisi (McNeil Products Ltd)
Nicotine 10 mg per 16 hour Nicorette invisi 10mg/16hours patches
| 7 patch G £10.99 DT = £10.99
Nicotine 15 mg per 16 hour Nicorette invisi 15mg/16hours patches
| 7 patch G £11.10 DT = £11.10
Nicotine 25 mg per 16 hour Nicorette invisi 25mg/16hours patches
| 7 patch G £11.15 DT = £11.15 | 14 patch G £18.28
▶ Nicotinell TTS (GlaxoSmithKline Consumer Healthcare)
Nicotine 7 mg per 24 hour Nicotinell TTS 10 patches | 7 patch G £9.12 DT = £9.12
Nicotine 14 mg per 24 hour Nicotinell TTS 20 patches |
Nicotine 2 mg NiQuitin Fresh Mint 2mg medicated chewing gum
sugar-free | 12 piece G £1.71 sugar-free | 24 piece G £2.85
sugar-free | 96 piece G £8.55 DT = £8.26
Nicotine 4 mg NiQuitin Extra Fresh Mint 4mg medicated chewing
gum sugar-free | 30 piece G £5.16 sugar-free | 100 piece G £11.82 sugar-free | 200 piece G £20.69
NiQuitin Fresh Mint 4mg medicated chewing gum sugar-free |
12 piece G £1.71 sugar-free | 24 piece G £2.85 sugar-free | 96 piece G £8.55 DT = £10.26
▶ Nicorette (McNeil Products Ltd)
Nicotine 2 mg Nicorette Freshmint 2mg medicated chewing gum
sugar-free | 25 piece G £3.52 sugar-free | 105 piece G £10.27 sugar-free | 210 piece G £16.42
Nicorette Fruitfusion 2mg medicated chewing gum sugar-free |
Nicotine 4 mg Nicorette Fruitfusion 4mg medicated chewing gum
sugar-free | 105 piece G £12.57
Nicotine 6 mg Nicorette Fruitfusion 6mg medicated chewing gum
sugar-free | 105 piece G £12.97 DT = £12.97 sugar-free | 210 piece G £20.81 DT = £20.81
▶ Nicorette Icy White (McNeil Products Ltd)
Nicotine 2 mg Nicorette Icy White 2mg medicated chewing gum
sugar-free | 25 piece G £3.52 sugar-free | 105 piece G £10.26 sugar-free | 210 piece G £16.41
Nicotine 4 mg Nicorette Icy White 4mg medicated chewing gum
sugar-free | 105 piece G £12.55
▶ Nicotinell (GlaxoSmithKline Consumer Healthcare)
Nicotine 2 mg Nicotinell Liquorice 2mg medicated chewing gum
sugar-free | 96 piece G £8.26 DT = £8.26
Nicotine 4 mg Nicotinell Liquorice 4mg medicated chewing gum
sugar-free | 96 piece G £10.26 DT = £10.26
Nicotinell Mint 4mg medicated chewing gum sugar-free | 96 piece G £10.26 DT = £10.26
Nicotinell Fruit 4mg medicated chewing gum sugar-free | 96 piece G £10.26 DT = £10.26
EXCIPIENTS: May contain Aspartame
ELECTROLYTES: May contain Sodium
NiQuitin 2mg lozenges original menthol mint sugar-free |
36 lozenge G £5.91 sugar-free | 72 lozenge G £7.40 DT =
NiQuitin Minis Mint 4mg lozenges sugar-free | 20 lozenge G £3.82
sugar-free | 60 lozenge G £10.21
NiQuitin Pre-Quit Mint 4mg lozenges sugar-free | 36 lozenge G £5.91
NiQuitin 4mg lozenges original menthol mint sugar-free |
36 lozenge G £5.91 sugar-free | 72 lozenge G £7.40 DT =
▶ Nicorette (McNeil Products Ltd)
Nicotine 2 mg Nicorette Fruit 2mg lozenges sugar-free | 80 lozenge G £12.05
Nicorette Cools 2mg lozenges sugar-free | 20 lozenge G £3.34
sugar-free | 80 lozenge G £12.05
Nicotine 4 mg Nicorette Cools 4mg lozenges sugar-free | 80 lozenge G £12.17
▶ Nicotinell (GlaxoSmithKline Consumer Healthcare)
Nicotine (as Nicotine bitartrate) 1 mg Nicotinell 1mg lozenges
Nicotine (as Nicotine bitartrate) 2 mg Nicotinell 2mg lozenges
sugar-free | 72 lozenge G £9.41 sugar-free | 96 lozenge G £10.60 sugar-free | 144 lozenge G £15.88
▶ Nicorette (McNeil Products Ltd)
Nicotine 15 mg Nicorette 15mg Inhalator | 4 cartridge G £4.87
DT = £4.87 | 20 cartridge G £17.78 DT = £17.78 | 36 cartridge G £28.28 DT = £28.28
l DRUG ACTION Varenicline is a selective nicotine-receptor
▶ Adult: Initially 500 micrograms once daily for 3 days,
increased to 500 micrograms twice daily for 4 days,
then 1 mg twice daily for 11 weeks; reduced if not
tolerated to 500 micrograms twice daily, usually to be
started 1–2 weeks before target stop date but can be
started up to a maximum of 5 weeks before target stop
date, 12-week course can be repeated in abstinent
individuals to reduce risk of relapse
MHRA/CHM ADVICE: SUICIDAL BEHAVIOUR AND VARENICLINE
Patients should be advised to discontinue treatment and
seek prompt medical advice if they develop agitation,
depressed mood, or suicidal thoughts. Patients with a
history of psychiatric illness should be monitored closely
illness (may exacerbate underlying illness including
depression). predisposition to seizures
BNF 78 Nicotine dependence 501
reactions . sleep disorders . vomiting . weight increased
ideation . sweat changes .thinking abnormal .tinnitus . tremor. urinary disorders
(SCARs). snoring . vaginal discharge . vision disorders
▶ Frequency not known Loss of consciousness
l PREGNANCY Avoid—toxicity in animal studies.
l BREAST FEEDING Avoid—present in milk in animal studies.
Dose adjustments If eGFR less than 30 mL/minute/1.73 m2
initial dose 500 micrograms once daily, increased after
l TREATMENT CESSATION Risk of relapse, irritability,
depression, and insomnia on discontinuation; consider
dose tapering on completion of 12-week course.
Driving and skilled tasks Manufacturer advises patients and
carers should be cautioned on the effects on driving and
performance of skilled tasks—increased risk of dizziness,
somnolence, and transient loss of consciousness.
l NATIONAL FUNDING/ACCESS DECISIONS
▶ Varenicline for smoking cessation (July 2007) NICE TA123
Varenicline (Champix ®) is recommended, within its
licensed indications, as an option for smokers who have
expressed a desire to quit smoking; it should normally be
prescribed only as part of a programme of behavioural
www.nice.org.uk/guidance/ta123
l MEDICINAL FORMS There can be variation in the licensing of
different medicines containing the same drug.
CAUTIONARY AND ADVISORY LABELS 3
Champix 0.5mg/1mg 2 week treatment initiation pack | 25 tablet P £27.30 DT = £27.30
Champix 0.5mg/1mg 4 week treatment initiation pack | 53 tablet P £54.60
Varenicline (as Varenicline tartrate) 500 microgram Champix
0.5mg tablets | 56 tablet P £54.60 DT = £54.60
Other drugs used for Opioid dependence Buprenorphine,
p. 447 . Naltrexone hydrochloride, p. 497
▶ BY MOUTH, OR BY SUBCUTANEOUS INJECTION, OR BY
▶ Adult: 5–10 mg every 6–8 hours, adjusted according to
response, on prolonged use not to be given more
frequently than every 12 hours
Adjunct in treatment of opioid dependence
▶ BY MOUTH USING ORAL SOLUTION
▶ Adult: Initially 10–30 mg daily, increased in steps of
5–10 mg daily if required until no signs of withdrawal
nor evidence of intoxication, dose to be increased in
the first week, then increased every few days as
necessary up to usual dose, maximum weekly dose
increase of 30 mg; usual dose 60–120 mg daily
Adjunct in treatment of opioid dependence if tolerance
▶ BY MOUTH USING ORAL SOLUTION
▶ Adult: Initially 10–20 mg daily, increased in steps of
5–10 mg daily if required until no signs of withdrawal
nor evidence of intoxication, dose to be increased in
the first week, then increased every few days as
necessary up to usual dose, maximum weekly dose
increase of 30 mg; usual dose 60–120 mg daily
Adjunct in treatment of opioid dependence if tolerance
high (under expert supervision)
▶ BY MOUTH USING ORAL SOLUTION
▶ Adult: Initially up to 40 mg daily, increased in steps of
5–10 mg daily if required until no signs of withdrawal
nor evidence of intoxication, dose to be increased in
the first week, then increased every few days as
necessary up to usual dose, maximum weekly dose
increase of 30 mg; usual dose 60–120 mg daily
▶ INITIALLY BY MOUTH USING LINCTUS
▶ Adult: 1–2 mg every 4–6 hours, (by mouth) reduced to
1–2 mg twice daily, use twice daily frequency if
DOSE EQUIVALENCE AND CONVERSION
▶ See buprenorphine p. 447 for dose adjustments in
opioid substitution therapy, for patients taking
methadone who want to switch to buprenorphine.
l UNLICENSED USE Methadone hydrochloride doses for
opioid dependence in the BNF may differ from those in the
Methadone oral solution 1 mg/mL is 2½ times the
strength of Methadone Linctus (2 mg/5mL). Many
preparations of Methadone oral solution are licensed for
opioid drug addiction only but some are also licensed for
l CONTRA-INDICATIONS Phaeochromocytoma
l CAUTIONS Family history of sudden death (ECG
monitoring recommended). history of cardiac conduction
▶ QT-interval prolongation Patients with the following risk
factors for QT-interval prolongation should be carefully
monitored while taking methadone: heart or liver disease,
electrolyte abnormalities, or concomitant treatment with
drugs that can prolong QT interval; patients requiring
more than 100 mg daily should also be monitored.
l INTERACTIONS → Appendix 1: opioids
502 Substance dependence BNF 78
Asthma exacerbated . dry eye . dysuria . hyperprolactinaemia . hypothermia . menstrual cycle
irregularities . mood altered . nasal dryness . QT interval
▶ With oral use Galactorrhoea . intracranial pressure
spasm . withdrawal syndrome neonatal
SIDE-EFFECTS, FURTHER INFORMATION Methadone is a
long-acting opioid therefore effects may be cumulative.
Methadone, even in low doses is a special hazard for
children; non-dependent adults are also at risk of toxicity;
dependent adults are at risk if tolerance is incorrectly
Overdose Methadone has a very long duration of action;
patients may need to be monitored for long periods
be as low as possible and infant monitored to avoid
sedation (high doses of methadone carry an increased risk
of sedation and respiratory depression in the neonate).
l HEPATIC IMPAIRMENT Manufacturer advises caution;
consider avoiding in severe impairment (risk of increased
Dose adjustments Manufacturer advises consider dose
l RENAL IMPAIRMENT Avoid use or reduce dose; opioid
effects increased and prolonged and increased cerebral
l TREATMENT CESSATION Avoid abrupt withdrawal.
l DIRECTIONS FOR ADMINISTRATION Syrup preserved with
hydroxybenzoate (parabens) esters may be incompatible
l PRESCRIBING AND DISPENSING INFORMATION Flavours of
oral liquid formulations may include tolu.
Palliative care For further information on the use of
methadone in palliative care, see www.medicinescomplete.
com/#/content/palliative/methadone
METHADOSE ® The final strength of the methadone
mixture to be dispensed to the patient must be specified
Important—care is required in prescribing and
dispensing the correct strength since any confusion could
lead to an overdose; this preparation should be dispensed
only after dilution as appropriate with Methadose ®
Diluent (life of diluted solution 3 months) and is for drug
l NATIONAL FUNDING/ACCESS DECISIONS
▶ Methadone and buprenorphine for the management of opioid
dependence (January 2007) NICE TA114
Oral methadone and buprenorphine are recommended for
maintenance therapy in the management of opioid
dependence. Patients should be committed to a supportive
care programme including a flexible dosing regimen
administered under supervision for at least 3 months, until
compliance is assured. Selection of methadone or
buprenorphine should be made on a case-by-case basis,
but methadone should be prescribed if both drugs are
l LESS SUITABLE FOR PRESCRIBING Methadone linctus is
less suitable for prescribing for cough in terminal disease
(has a tendency to accumulate).
l MEDICINAL FORMS There can be variation in the licensing of
different medicines containing the same drug. Forms available
from special-order manufacturers include: tablet, capsule, oral
suspension, oral solution, solution for injection
CAUTIONARY AND ADVISORY LABELS 2
▶ Physeptone (Martindale Pharmaceuticals Ltd)
Methadone hydrochloride 5 mg Physeptone 5mg tablets | 50 tablet P £2.84 DT = £2.84b
▶ Methadone hydrochloride (Non-proprietary)
Methadone hydrochloride 50 mg per 1 ml Methadone 50mg/1ml
solution for injection ampoules | 10 ampoule P s DT =
£17.72b ▶ Physeptone (Martindale Pharmaceuticals Ltd)
Methadone hydrochloride 10 mg per 1 ml Physeptone 50mg/5ml
solution for injection ampoules | 10 ampoule P £16.33 DT =
Physeptone 20mg/2ml solution for injection ampoules | 10 ampoule P £13.15 DT = £13.15b
Methadone hydrochloride 25 mg per 1 ml Physeptone 50mg/2ml
solution for injection ampoules | 10 ampoule P £17.72 DT =
Methadone hydrochloride 50 mg per 1 ml Physeptone 50mg/1ml
solution for injection ampoules | 10 ampoule P £17.72 DT =
CAUTIONARY AND ADVISORY LABELS 2
▶ Methadone hydrochloride (Non-proprietary)
Methadone hydrochloride 1 mg per 1 ml Methadone 1mg/ml oral
Methadone hydrochloride 10 mg per 1 ml Methadose 10mg/ml oral
solution concentrate sugar-free | 150 ml P £12.01 DT =
£12.01bsugar-free | 500 ml P £30.75b
Methadone hydrochloride 20 mg per 1 ml Methadose 20mg/ml
oral solution concentrate sugar-free | 150 ml P £24.02 DT =
£24.02b ▶ Metharose (Rosemont Pharmaceuticals Ltd)
Methadone hydrochloride 1 mg per 1 ml Metharose 1mg/ml oral
Methadone hydrochloride 1 mg per 1 ml Physeptone 1mg/ml oral
solution sugar free sugar-free | 100 ml P £1.27 DT = £0.89b
sugar-free | 500 ml P £6.42 DT = £4.45bsugar-free | 2500 ml P £32.10b
Buprenorphine with naloxone 27-Apr-2019
The properties listed below are those particular to the
combination only. For the properties of the components
please consider, buprenorphine p. 447, naloxone
Adjunct in the treatment of opioid dependence (dose
▶ BY SUBLINGUAL ADMINISTRATION
▶ Adult: Initially 2–4 mg once daily, an additional dose of
2–4 mg may be administered on day 1 depending on
the individual patient’s requirement, increased in steps
of 2–8 mg, adjusted according to response, total weekly
dose may be divided and given on alternate days or
3 times weekly; maximum 24 mg per day
l INTERACTIONS → Appendix 1: opioids
l NATIONAL FUNDING/ACCESS DECISIONS
Scottish Medicines Consortium (SMC) decisions
The Scottish Medicines Consortium has advised (March
2007) that buprenorphine/naloxone (Suboxone ®) is
accepted for restricted use within NHS Scotland for
substitution treatment for opioid drug dependance, within
a framework of medical, social and psychological
treatment in whom methadone is not suitable.
l MEDICINAL FORMS There can be variation in the licensing of
different medicines containing the same drug.
CAUTIONARY AND ADVISORY LABELS 2, 26
▶ Buprenorphine with naloxone (Non-proprietary)
Naloxone (as Naloxone hydrochloride dihydrate) 500 microgram,
Buprenorphine (as Buprenorphine hydrochloride)
2 mg Buprenorphine 2mg / Naloxone 500microgram sublingual
tablets sugar free sugar-free | 28 tablet P £20.32–£25.60 DT =
Naloxone (as Naloxone hydrochloride dihydrate) 2 mg,
Buprenorphine (as Buprenorphine hydrochloride)
8 mg Buprenorphine 8mg / Naloxone 2mg sublingual tablets sugar
free sugar-free | 28 tablet P £60.95–£76.77 DT = £76.77c ▶ Suboxone (Indivior UK Ltd)
Naloxone (as Naloxone hydrochloride dihydrate) 500 microgram,
Buprenorphine (as Buprenorphine hydrochloride) 2 mg Suboxone
2mg/500microgram sublingual tablets sugar-free | 28 tablet P £25.40 DT = £25.60c
Naloxone (as Naloxone hydrochloride dihydrate) 2 mg,
Buprenorphine (as Buprenorphine hydrochloride)
8 mg Suboxone 8mg/2mg sublingual tablets sugar-free | 28 tablet P £76.19 DT = £76.77c
Naloxone (as Naloxone hydrochloride dihydrate) 4 mg,
Buprenorphine (as Buprenorphine hydrochloride)
16 mg Suboxone 16mg/4mg sublingual tablets sugar-free | 28 tablet P £152.38 DT = £152.38c
SYMPATHOMIMETICS › ALPHA2-ADRENOCEPTOR
l DRUG ACTION Lofexidine is an alpha2-adrenergic agonist.
Management of symptoms of opioid withdrawal
▶ Adult: Initially 800 micrograms daily in divided doses,
increased in steps of 400–800 micrograms daily (max.
per dose 800 micrograms) as required recommended
duration of treatment 7–10 days if no opioid use (but
longer may be required); maximum 2.4 mg per day
(monitor pulse rate and blood pressure). metabolic
disturbances .recent myocardial infarction . severe
l INTERACTIONS → Appendix 1: lofexidine
▶ Common or very common Bradycardia . dizziness . drowsiness . hypotension . mucosal dryness
▶ Frequency not known QT interval prolongation
l PREGNANCY Use only if benefit outweighs risk—no
l BREAST FEEDING Use only if benefit outweighs risk—no
l RENAL IMPAIRMENT Caution in chronic impairment.
l MONITORING REQUIREMENTS Monitoring of blood
pressure and pulse rate is recommended on initiation, for
at least 72 hours or until a stable dose is achieved, and on
l TREATMENT CESSATION Treatment should be withdrawn
gradually over 2–4 days (or longer) to reduce the risk of
rebound hypertension and associated symptoms.
l PRESCRIBING AND DISPENSING INFORMATION Lofexidine
has been used in children over 12 years in the
management of symptoms of opioid withdrawal.
Available from specialist importing companies.
l PATIENT AND CARER ADVICE The patient should take part
of the dose at bedtime to offset insomnia associated with
l MEDICINAL FORMS No licensed medicines listed.
504 Substance dependence BNF 78
2.4 Methicillin-resistant staphylococcus aureus 578
2.6 Urinary tract infections 589
3.1 Pneumocystis pneumonia 601
6.3 Herpesvirus infections 632
6.3a Cytomegalovirus infections 637
6.6 Respiratory syncytial virus 664
Other drugs used for Amoebic infection Metronidazole,
▶ Adult: 100 mg every 8 hours for 5–7 days
l UNLICENSED USE Not licensed for use in giardiasis.
l CAUTIONS Avoid in psoriasis . elderly . history of psychosis
l INTERACTIONS → Appendix 1: mepacrine
l SIDE-EFFECTS Aplastic anaemia (long term use). central
nervous system stimulation (with high doses). corneal
use). nail discolouration . nausea (with high doses). oral
discolouration . skin discolouration (long term use).toxic
psychosis (transient; with high doses). urine
discolouration (long term use). visual impairment. vomiting (with high doses)
l HEPATIC IMPAIRMENT Use with caution.
l MEDICINAL FORMS Forms available from special-order
Antibacterials, principles of therapy
Before selecting an antibacterial the clinician must first
consider three factors— the patient, the known or likely
causative organism, and the risk of bacterial resistance with
Factors related to the patient which must be considered
include history of allergy, renal and hepatic function,
susceptibility to infection (i.e. whether
immunocompromised), ability to tolerate drugs by mouth,
severity of illness, risk of complications, ethnic origin, age,
whether taking other medication and, if female, whether
pregnant, breast-feeding or taking an oral contraceptive.
The known or likely organism and its antibacterial
sensitivity, in association with the factors above, will provide
one or more antibacterial option.g In patients receiving
antibacterial prophylaxis, an antibacterial from a different
An example of a rational approach to the selection of an
antibacterial is treatment of a urinary-tract infection in a
as being resistant to ampicillin p. 550 but sensitive to
nitrofurantoin p. 590 (can cause nausea), gentamicin p. 519
(can be given only by injection and best avoided in
pregnancy), tetracycline p. 567 (causes dental discoloration)
and trimethoprim p. 574 (folate antagonist therefore
theoretical teratogenic risk), and cefalexin p. 524. The safest
antibiotics in pregnancy are the penicillins and
cephalosporins; therefore, cefalexin would be indicated for
Some patients may be at higher risk of treatment failure.
They include those who have had repeated antibacterial
courses, a previous or current culture with resistant bacteria,
or those at higher risk of developing complications.
BNF 78 Bacterial infection 505
Local policies often limit the antibacterials that may be used
to achieve reasonable economy consistent with adequate
cover, and to reduce the development of resistant organisms.
A policy may indicate a range of drugs for general use, and
permit other drugs only on the advice of the microbiologist
or physician responsible for the control of infectious
Antibacterials, considerations before starting
The following precepts should be considered before starting:
. Viral infections should not be treated with antibacterials.
However, antibacterials may be used to treat secondary
bacterial infection (e.g. bacterial pneumonia secondary to
. Samples should be taken for culture and sensitivity
testing; ‘ blind’ antibacterial prescribing for unexplained
pyrexia usually leads to further difficulty in establishing
. Knowledge of prevalent organisms and their current
sensitivity is of great help in choosing an antibacterial
before bacteriological confirmation is available. Generally,
indication (e.g. life-threatening sepsis);
. The dose of an antibacterial varies according to a number
of factors including age, weight, hepatic function, renal
function, and severity of infection. The prescribing of the
so-called ‘standard’ dose in serious infections may result
in failure of treatment or even death of the patient;
therefore it is important to prescribe a dose appropriate to
the condition. An inadequate dose may also increase the
likelihood of antibacterial resistance. On the other hand,
for an antibacterial with a narrow margin between the
toxic and therapeutic dose (e.g. an aminoglycoside) it is
also important to avoid an excessive dose and the
concentration of the drug in the plasma may need to be
. The route of administration of an antibacterial often
depends on the severity of the infection. Life-threatening
infections require intravenous therapy. Antibacterials that
are well absorbed may be given by mouth even for some
serious infections. Parenteral administration is also
appropriate when the oral route cannot be used (e.g.
because of vomiting) or if absorption is inadequate.
Whenever possible, painful intramuscular injections
should be avoided in children;
. Duration of therapy depends on the nature of the
infection and the response to treatment. Courses should
not be unduly prolonged because they encourage
resistance, they may lead to side-effects and they are
costly. However, in certain infections such as tuberculosis
or osteomyelitis it may be necessary to treat for prolonged
periods. Conversely a single dose of an antibacterial may
cure uncomplicated urinary-tract infections. The
prescription for an antibacterial should specify the
duration of treatment or the date when treatment is to be
Advice to be given to patients
If an antibacterial is given, advise patients about:
. g Possible adverse effects e.g. diarrhoea;
. Seeking medical help if symptoms worsen rapidly or
significantly at any time, symptoms do not start to
improve within an agreed time, or if the patient becomes
If an antibacterial is not given, advise patients about:
. g An antibacterial not being needed currently;
. Seeking medical help if symptoms worsen rapidly or
significantly at any time, if symptoms do not start to
improve within an agreed time, or if the patient becomes
Antibacterials, considerations during therapy
g Review choice of antibacterial if susceptibility results
indicate bacterial resistance and symptoms are not
improving—consult local microbiologist as needed. hIf no
bacterium is cultured, the antibacterial can be continued or
g Review intravenous antibacterials within 48 hours
and consider stepping down to oral antibacterials where
In general, broad-spectrum antibacterial drugs such as the
cephalosporins are more likely to be associated with adverse
reactions related to the selection of resistant organisms e.g.
fungal infections or antibiotic-associated colitis
(pseudomembranous colitis); other problems associated with
superinfection include vaginitis and pruritus ani.
Doctors must notify the Proper Officer of the local authority
(usually the consultant in communicable disease control) or
local health protection unit when attending a patient
suspected of suffering from any of the diseases listed below;
a form is available from the Proper Officer.
Streptococcal disease (Group A,
Note It is good practice for doctors to also inform the
consultant in communicable disease control of instances of
other infections (e.g. psittacosis) where there could be a
g Patients identified as being at high risk of severe illness
without delay (ideally within one hour). Microbiological
samples and blood cultures must be taken prior to
administration of antibiotics; the prescription should be
adjusted subsequently according to susceptibility results.
A thorough clinical examination should be carried out to
identify sources of infection. If the source of infection is
identified, treat in line with local antibacterial guidance or
Patients who require empirical intravenous treatment for a
suspected infection, but who have no confirmed diagnosis,
should be treated with an intravenous antibiotic from the
local formulary and in line with national guidelines.
The need for intravenous fluids, inotropes, vasopressors
and oxygen should also be assessed without delay, taking
into consideration the patient’s lactate concentration,
systolic blood pressure, and their risk of severe illness or
506 Bacterial infection BNF 78
death. Patients at high risk should be monitored
continuously if possible, and no less than every 30 minutes.
Patients with suspected sepsis who are not immediately
deemed to be at high risk of severe illness or death, should
be re-assessed regularly for the need for empirical treatment,
taking into consideration all risk factors including lactate
concentration and evidence of acute kidney injury. h
Antibacterials, use for prophylaxis
Rheumatic fever: prevention of recurrence
. Phenoxymethylpenicillin p. 548 or sulfadiazine p. 563.
Invasive group A streptococcal infection: prevention
Patients who are penicillin allergic, either erythromycin
p. 539 or azithromycin p. 536 [unlicensed indication].
For details of those who should receive chemoprophylaxis
contact a consultant in communicable disease control (or a
consultant in infectious diseases or the local Public Health
Meningococcal meningitis: prevention of secondary
. Ciprofloxacin p. 558 or rifampicin p. 582 or i/m ceftriaxone
p. 528 [unlicensed indication].
For details of those who should receive chemoprophylaxis
contact a consultant in communicable disease control (or a
consultant in infectious diseases or the local Public Health
England laboratory). Unless there has been direct exposure
of the mouth or nose to infectious droplets from a patient
with meningococcal disease who has received less than
24 hours of antibacterial treatment, healthcare workers do
not generally require chemoprophylaxis.
Haemophilus influenzae type b disease: prevention
. Rifampicin or (if rifampicin cannot be used) i/m or i/v
ceftriaxone [unlicensed indication].
For details of those who should receive chemoprophylaxis
contact a consultant in communicable disease control (or a
consultant in infectious diseases or the local Public Health
England laboratory). Unless there has been direct exposure
of the mouth or nose to infectious droplets from a patient
with meningococcal disease who has received less than
24 hours of antibacterial treatment, healthcare workers do
not generally require chemoprophylaxis.
Within 4 weeks of illness onset in an index case with
confirmed or suspected invasive Haemophilus influenzae type
b disease, give antibacterial prophylaxis to all household
contacts if there is a vulnerable individual in the household.
Also, give antibacterial prophylaxis to the index case if they
are in contact with vulnerable household contacts or if they
are under 10 years of age. Vulnerable individuals include the
immunocompromised, those with asplenia, or children
under 10 years of age. If there are 2 or more cases of invasive
Haemophilus influenzae type b disease within 120 days in a
pre-school or primary school, antibacterial prophylaxis
should also be given to all room contacts (including staff).
Also see immunisation against Haemophilus influenzae type b
Diphtheria in non-immune patients: prevention of
. Erythromycin (or another macrolide e.g. azithromycin or
Treat for further 10 days if nasopharyngeal swabs positive
after first 7 days’ treatment.
Pertussis, antibacterial prophylaxis
. Clarithromycin (or azithromycin or erythromycin).
Within 3 weeks of onset of cough in the index case, give
antibacterial prophylaxis to all close contacts if amongst
them there is at least one unimmunised or partially
immunised child under 1 year of age, or if there is at least
one individual who has not received a pertussis-containing
vaccine more than 1 week and less than 5 years ago (so long
as that individual lives or works with children under
4 months of age, is pregnant at over 32 weeks gestation, or is
a healthcare worker who works with children under 1 year of
Pneumococcal infection in asplenia or in patients
with sickle-cell disease, antibacterial prophylaxis
If penicillin-allergic, erythromycin.
Antibacterial prophylaxis is not fully reliable. Antibacterial
prophylaxis may be discontinued in children over 5 years of
age with sickle-cell disease who have received pneumococcal
immunisation and who do not have a history of severe
Tuberculosis antibacterial prophylaxis in
susceptible close contacts or those who have
. See Close contacts and Chemoprophylaxis for latent
tuberculosis under Tuberculosis p. 578.
Animal and human bites, antibacterial prophylaxis
. Co-amoxiclav p. 551 alone (or doxycycline p. 564 +
metronidazole p. 542 if penicillin-allergic).
Cleanse wound thoroughly. For tetanus-prone wound, give
history and risk of infection).
Consider rabies prophylaxis for bites from animals in
endemic countries. Assess risk of blood-borne viruses
(including HIV, hepatitis B and C) and give appropriate
prophylaxis to prevent viral spread.
Antibacterial prophylaxis recommended for wounds less
than 48–72 hours old when the risk of infection is high (e.g.
bites from humans or cats; bites to the hand, foot, face, or
genital area; bites involving oedema, crush or puncture
injury, or other moderate to severe injury; wounds that
cannot be debrided adequately; patients with diabetes
mellitus, cirrhosis, asplenia, prosthetic joints or valves, or
those who are immunocompromised). Give antibacterial
Early-onset neonatal infection, antibacterial
. i/v benzylpenicillin sodium p. 547 (or i/v clindamycin
p. 535 if history of allergy to penicillins).
Give intrapartum prophylaxis to women with group B
streptococcal colonisation, bacteriuria, or infection in the
current pregnancy, or to women who had a previous baby
with an invasive group B streptococcal infection. Consider
prophylaxis for women in preterm labour if there is
prelabour rupture of membranes or if intrapartum rupture of
membranes lasting more than 18 hours is suspected.
BNF 78 Bacterial infection 507
Gastro-intestinal procedures, antibacterial
Operations on stomach or oesophagus
. Single dose of i/v gentamicin p. 519 or i/v cefuroxime
p. 526 or i/v co-amoxiclav (additional intra-operative or
postoperative doses may be given for prolonged
procedures or if there is major blood loss).
Intravenous antibacterial prophylaxis should be given up to
30 minutes before the procedure.
Add i/v teicoplanin p. 532 (or vancomycin p. 534) if high
risk of meticillin-resistant Staphylococcus aureus.
. Single dose of i/v cefuroxime + i/v metronidazole or i/v
gentamicin + i/v metronidazole or i/v co-amoxiclav alone
(additional intra-operative or postoperative doses may be
given for prolonged procedures or if there is major blood
Intravenous antibacterial prophylaxis should be given up to
30 minutes before the procedure.
Where i/v metronidazole is suggested, it may alternatively
be given by suppository but to allow adequate absorption, it
should be given 2 hours before surgery.
Add i/v teicoplanin (or vancomycin) if high risk of
meticillin-resistant Staphylococcus aureus.
Resections of colon and rectum for carcinoma, and resections
in inflammatory bowel disease, and appendicectomy
. Single dose of i/v gentamicin + i/v metronidazole or i/v
cefuroxime + i/v metronidazole or i/v co-amoxiclav alone
(additional intra-operative or postoperative doses may be
given for prolonged procedures or if there is major blood
Intravenous antibacterial prophylaxis should be given up to
30 minutes before the procedure.
Where i/v metronidazole is suggested, it may alternatively
be given by suppository but to allow adequate absorption, it
should be given 2 hours before surgery.
Add i/v teicoplanin (or vancomycin) if high risk of
meticillin-resistant Staphylococcus aureus.
Endoscopic retrograde cholangiopancreatography
. Single dose of i/v gentamicin p. 519 or oral or i/v
Intravenous antibacterial prophylaxis should be given up to
30 minutes before the procedure.
Prophylaxis recommended if pancreatic pseudocyst,
immunocompromised, history of liver transplantation, or
risk of incomplete biliary drainage. For biliary complications
following liver transplantation, add i/v amoxicillin p. 548 or
i/v teicoplanin p. 532 (or vancomycin p. 534).
Percutaneous endoscopic gastrostomy or jejunostomy
. Single dose of i/v co-amoxiclav p. 551 or i/v cefuroxime
Intravenous antibacterial prophylaxis should be given up to
30 minutes before the procedure.
Use single dose of i/v teicoplanin (or vancomycin) if history
of allergy to penicillins or cephalosporins, or if high risk of
meticillin-resistant Staphylococcus aureus.
Orthopaedic surgery, antibacterial prophylaxis
Joint replacement including hip and knee
. Single dose of i/v cefuroxime alone or i/v flucloxacillin
p. 554 + i/v gentamicin (additional intra-operative or
postoperative doses may be given for prolonged
procedures or if there is major blood loss).
Intravenous antibacterial prophylaxis should be given up to
30 minutes before the procedure.
If history of allergy to penicillins or to cephalosporins or if
high risk of meticillin-resistant Staphylococcus aureus, use
single dose of i/v teicoplanin (or vancomycin) + i/v
gentamicin (additional intra-operative or postoperative
doses may be given for prolonged procedures or if there is
. Single dose of i/v cefuroxime or i/v flucloxacillin
(additional intra-operative or postoperative doses may be
given for prolonged procedures or if there is major blood
Intravenous antibacterial prophylaxis should be given up to
30 minutes before the procedure.
If history of allergy to penicillins or to cephalosporins or if
high risk of meticillin-resistant Staphylococcus aureus, use
single dose of i/v teicoplanin (or vancomycin) (additional
intra-operative or postoperative doses may be given for
prolonged procedures or if there is major blood loss).
. Use i/v co-amoxiclav alone or i/v cefuroxime + i/v
metronidazole p. 542 (or i/v clindamycin p. 535 alone if
history of allergy to penicillins or to cephalosporins).
3 hours of injury and continue until soft tissue closure (max.
At first debridement also use a single dose of i/v
gentamicin if history of allergy to penicillins or to
At time of skeletal stabilisation and definitive soft tissue
closure use a single dose of i/v gentamicin + i/v teicoplanin
(or vancomycin) (intravenous antibacterial prophylaxis
should be given up to 30 minutes before the procedure).
. Use i/v co-amoxiclav alone or i/v cefuroxime + i/v
Intravenous antibacterial prophylaxis should be given up to
30 minutes before the procedure.
Continue antibacterial prophylaxis for at least 2 doses
after procedure (max. duration of prophylaxis 5 days). If
history of allergy to penicillin or to cephalosporins, or if high
risk of meticillin-resistant Staphylococcus aureus, use i/v
teicoplanin (or vancomycin) + i/v gentamicin + i/v
Where i/v metronidazole is suggested, it may alternatively
be given by suppository but to allow adequate absorption, it
should be given 2 hours before surgery.
Urological procedures, antibacterial prophylaxis
. Single dose of oral ciprofloxacin + oral metronidazole or i/v
gentamicin + i/v metronidazole (additional intra-operative
or postoperative doses may be given for prolonged
procedures or if there is major blood loss).
Intravenous antibacterial prophylaxis should be given up to
30 minutes before the procedure.
Use single dose of i/v gentamicin + i/v metronidazole if
high risk of meticillin-resistant Staphylococcus aureus
(additional intra-operative or postoperative doses of
antibacterial may be given for prolonged procedures or if
Where i/v metronidazole is suggested, it may alternatively
be given by suppository but to allow adequate absorption, it
should be given 2 hours before surgery.
Transurethral resection of prostate
. Single dose of oral ciprofloxacin or i/v gentamicin or i/v
cefuroxime (additional intra-operative or postoperative
doses may be given for prolonged procedures or if there is
508 Bacterial infection BNF 78
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