Drugs used in substance dependence 279

4.10 Drugs used in substance dependence 279

C entral

nervous

syst em

4.11 Drugs for dementia BNF 57 longer may be required); CHILD under 18 years not

Cautions liver function tests needed before and during recommended

treatment; test for opioid dependence with naloxone BritLofex before treatment; avoid concomitant use of opioids c

(Britannia) A but increased dose of opioid analgesic may be Tablets , peach, f/c, lofexidine hydrochloride 200 micrograms, net price 60-tab pack = £61.79.

required for pain (monitor for opioid intoxication); Label: 2

hepatic impairment (Appendix 2); renal impairment (Appendix 3); pregnancy (Appendix 4); breast-feeding (Appendix 5)

Note METHADONE HYDROCHLORIDE Patients should be warned that an attempt to overcome

the blockade of opioid receptors by overdosing could result Indications adjunct in treatment of opioid depend-

in acute opioid intoxication

ence, see notes above; analgesia (section 4.7.2); cough Contra-indications patients currently dependent on in terminal disease (section 3.9.1)

opioids

Cautions section 4.7.2 Side-effects nausea, vomiting, abdominal pain, diarr- Contra-indications

hoea, constipation, reduced appetite, increased thirst; section 4.7.2

chest pain; anxiety, sleep disorders, headache, Side-effects section 4.7.2; overdosage: see Emer-

reduced energy, increased energy, irritability, emo- gency Treatment of Poisoning, p. 31

tional lability, dizziness; chills; urinary retention; Important Methadone, even in low doses is a special hazard for children; non-dependent adults are also at risk

delayed ejaculation, decreased potency; arthralgia, tem myalgia; increased lacrimation; rash, and increased of toxicity; dependent adults are at risk if tolerance is

incorrectly assessed during induction sweating; rarely hepatic dysfunction, suicidal ideation,

sys

Incompatibility Syrup preserved with hydroxybenzoate and speech disorders; very rarely hallucinations, tre- (parabens) esters may be incompatible with methadone

mor, and idiopathic thrombocytopenia hydrochloride.

Dose

. ADULT nervous over 18 years (initiate in specialist clinics only), . l Initially 10–40 mg daily, increased by up to 10 mg

Dose

25 mg initially then 50 mg daily; total weekly dose daily (max. weekly increase 30 mg) until no signs of

(350 mg) may be divided and given on 3 days of the withdrawal or intoxication; usual dose range 60–

entra week for improved compliance (e.g. 100 mg on Mon-

C 120 mg daily; CHILD not recommended (see also day and Wednesday, and 150 mg on Friday)

4 important note above)

Note Methadone hydrochloride doses in the BNF may differ Nalorex c (Bristol-Myers Squibb) A from those in the product literature

Tablets , yellow, f/c, scored, naltrexone hydrochloride (Non-proprietary)

Methadone 50 mg, net price 28-tab pack = £23.72 C Oral solution 1 mg/mL , methadone hydrochloride

Opizone c (Britannia) A

1 mg/mL, net price 20 mL = 29p, 30 mL = 60p, 40 mL Tablets , beige, f/c, scored, naltrexone hydrochloride = 58p, 50 mL = £1.03, 60 mL = 87p, 100 mL = £1.45,

50 mg, net price 28-tab pack = £23.00 500 mL = £9.60. Label: 2

Brands include Eptadone , Metharose

(sugar-free), Physeptone

(sugar-free) Important Methadone oral solution 1 mg/mL is 2½ times the strength of Methadone Linctus (section 3.9.1). Many preparations of Methadone oral solution are licensed for opioid drug addiction

4.11 Drugs for dementia

only but some are also licensed for analgesia in severe pain Oral solution 5 mg/mL , methadone hydrochloride

Acetylcholinesterase inhibiting drugs are used in the

5 mg/mL, net price 20 mL = £1.47, 1 litre = £73.33. treatment of Alzheimer’s disease, specifically for mild Label: 2

to moderate disease. Rivastigmine is also licensed for Brands include Eptadone

mild to moderate dementia associated with Parkinson’s Note Care is required in prescribing and dispensing the correct

disease. The evidence to support the use of these drugs strength since any confusion could lead to an overdose

relates to their cognitive enhancement. Injection , methadone hydrochloride 25 mg/mL, net price 2-mL amp = £2.05; 50 mg/mL, 1-mL amp =

Treatment with drugs for dementia should be initiated £2.05

and supervised only by a specialist experienced in the Brands include Synastone

management of dementia.

c Methadose Benefit is assessed by repeating the cognitive assess- (Rosemont) C ment at around 3 months. Such assessment cannot Oral concentrate , methadone hydrochloride 10 mg/

demonstrate how the disease may have progressed in mL (blue), net price 150 mL = £12.01; 20 mg/mL

the absence of treatment but it can give a good guide to (brown), 150 mL = £24.02. Label: 2

response. Up to half the patients given these drugs will Note The final strength of the methadone mixture to be dispensed to the patient must be specified on the prescription

show a slower rate of cognitive decline. Drugs for Important Care is required in prescribing and dispensing the

dementia should be discontinued in those thought not correct strength since any confusion could lead to an overdose;

to be responding. Many specialists repeat the cognitive this preparation should be dispensed only after dilution as

assessment 4 to 6 weeks after discontinuation to assess appropriate with Methadose

Diluent (life of diluted solution 3 deterioration; if significant deterioration occurs during months) and is for drug dependent persons (see also p. 7)

this short period, consideration should be given to restarting therapy.

NALTREXONE HYDROCHLORIDE

Donepezil is a reversible inhibitor of acetylcholinester- ase. Galantamine is a reversible inhibitor of acetylcho-

Indications adjunct to prevent relapse in detoxified linesterase and it also has nicotinic receptor agonist formerly opioid-dependent patients (who have

properties. Rivastigmine is a reversible non-competi- remained opioid-free for at least 7–10 days)

tive inhibitor of acetylcholinesterases; it is also licensed

BNF 57

4.11 Drugs for dementia 281

for treating mild to moderate dementia in Parkinson’s haemorrhage, bradycardia, seizures; rarely sino-atrial disease.

block, AV block, hepatitis, extrapyramidal symptoms; Acetylcholinesterase inhibitors can cause unwanted

potential for bladder outflow obstruction dose-related cholinergic effects and should be started

Dose

at a low dose and the dose increased according to . Initially 5 mg once daily at bedtime, increased if response and tolerability.

necessary after one month to max. 10 mg daily Memantine is a NMDA-receptor antagonist that affects

Aricept c glutamate transmission; it is licensed for treating mod- (Pfizer, Eisai) A erate to severe Alzheimer’s disease.

Tablets , f/c, donepezil hydrochloride 5 mg (white), net price 28-tab pack = £63.54; 10 mg (yellow), 28-tab pack = £89.06.

NICE guidance Donepezil, galantamine, rivastigmine, and

Aricept Evess c (Pfizer, Eisai) A memantine for Alzheimer’s disease

Orodispersible tablets , donepezil hydrochloride (September 2007)

5 mg (white), net price 28-tab pack = £63.54; 10 mg Donepezil, galantamine, and rivastigmine are

(yellow), 28-tab pack = £89.06. Counselling, admin- recommended for the adjunctive treatment of mod-

istration

erate Alzheimer’s disease in those whose mini men- Counselling Aricept Evess should be placed on the tongue, tal-state examination (MMSE) score is 10–20 points allowed to disperse, and swallowed

under the following conditions: .

Alzheimer’s disease must be diagnosed in a specialist clinic; the clinic should also assess

GALANTAMINE

cognitive, global, and behavioural functioning, activities of daily living, and the likelihood of Indications mild to moderate dementia in Alzheimer’s compliance with treatment;

disease

. Cautions treatment should be initiated by specialists but cardiac disease (including sick sinus can be continued by general practitioners under

syndrome or other supraventricular conduction

a shared-care protocol; abnormalities, unstable angina, congestive heart fail- .

the carers’ views of the condition should be ure); electrolyte disturbances; susceptibility to peptic sought before and during drug treatment;

ulcers; asthma, chronic obstructive pulmonary dis- .

the patient should be assessed every 6 months ease, pulmonary infection; avoid in urinary retention

and drug treatment should normally continue and gastro-intestinal obstruction; hepatic impairment only if the MMSE score remains at or above 10

(Appendix 2—avoid if severe); pregnancy (Appendix 4); interactions: Appendix 1 (parasympathomimetics)

entral C

points and if treatment is considered to have a worthwhile effect on the global, functional, and

Contra-indications renal impairment (avoid if creat- behavioural condition.

inine clearance less than 9 mL/minute; Appendix 3);

nervous

. Patients receiving acetylcholinesterase inhi- breast-feeding (Appendix 5) bitors for mild Alzheimer’s disease can continue

Side-effects nausea, vomiting, diarrhoea, abdominal treatment until they, their carers, or their spe-

pain, dyspepsia; syncope; rhinitis; sleep disturbances, cialist consider it appropriate to stop.

dizziness, confusion, depression, headache, fatigue,

syst

Healthcare professionals should not rely solely on anorexia, tremor; fever; weight loss; less commonly arrythmias, palpitation, myocardial infarction, cere-

em

the MMSE score to assess the severity of Alzhei- mer’s disease when the patient has learning or other

brovascular disease, paraesthesia, tinnitus, and leg disabilities, or other communication difficulties.

cramps; rarely bradycardia, seizures, hallucinations, NICE does not recommend memantine for moder-

agitation, aggression, dehydration, hypokalaemia, and ately severe to severe Alzheimer’s disease except as

rash; very rarely gastrointestinal bleeding, dysphagia, part of well designed clinical studies; patients

hypotension, exacerbation of Parkinson’s disease, and already receiving memantine can continue treat-

sweating

ment until they, their carers, or their specialist con-

Dose

sider it appropriate to stop. . Initially 4 mg twice daily for 4 weeks increased to

8 mg twice daily for 4 weeks; maintenance 8–12 mg twice daily

Reminyl c (Shire) A Tablets , all f/c, galantamine (as hydrobromide) 8 mg Indications mild to moderate dementia in Alzheimer’s

DONEPEZIL HYDROCHLORIDE

(pink), net price 56-tab pack = £68.32; 12 mg (orange- disease

brown), 56-tab pack = £84.00 Label: 3, 21 Cautions sick sinus syndrome or other supraventricu-

Oral solution , galantamine (as hydrobromide) 4 mg/ lar conduction abnormalities; susceptibility to peptic

mL, net price 100 mL with pipette = £120.00. Label: 3, ulcers; asthma, chronic obstructive pulmonary dis-

ease; hepatic impairment (Appendix 2); pregnancy (Appendix 4); interactions: Appendix 1 (para- sympathomimetics)

Modified release

Reminyl Contra-indications c breast-feeding XL (Shire) A Side-effects nausea, vomiting, anorexia, diarrhoea;

Capsules , m/r, galantamine (as hydrobromide) 8 mg (white), net price 28-cap pack = £54.60; 16 mg (pink),

fatigue, insomnia, headache, dizziness, syncope, hal- 28-cap pack = £68.32; 24 mg (beige), 28-cap pack = lucinations, agitation, aggression; muscle cramps;

£84.00. Label: 3, 21, 25 urinary incontinence; rash, pruritus; less commonly

Dose initially 8 mg once daily for 4 weeks increased to 16 mg gastric and duodenal ulcers, gastro-intestinal

once daily for 4 weeks; maintenance 16–24 mg daily

4.11 Drugs for dementia BNF 57

Oral solution , rivastigmine (as hydrogen tartrate) Indications

MEMANTINE HYDROCHLORIDE

2 mg/mL, net price 120 mL (with oral syringe) = moderate to severe dementia in Alzhei-

£116.64. Label: 21 mer’s disease

Dose initially 1.5 mg twice daily, increased in steps of 1.5 mg Cautions history of convulsions; renal impairment

twice daily at intervals of at least 2 weeks according to response (avoid if creatinine clearance less than 5 mL/minute;

and tolerance; usual range 3–6 mg twice daily; max. 6 mg twice Appendix 3); pregnancy (Appendix 4); interactions:

daily

Appendix 1 (memantine) Patches , self-adhesive, beige, rivastigmine 4.6 mg/24 Contra-indications breast-feeding

hours, net price 30 = £83.84; 9.5 mg/24 hours, 30 = Side-effects constipation; hypertension; headache,

dizziness, drowsiness; less commonly vomiting, Dose initially apply 4.6 mg/24 hours patch to clean, dry, non- thrombosis, confusion, fatigue, hallucinations, and

hairy, non-irritated skin on back, upper arm, or chest, removing abnormal gait; very rarely seizures; pancreatitis, psy-

after 24 hours and siting a replacement patch on a different area chosis, depression, and suicidal ideation also reported (avoid using the same area for 14 days); if well tolerated increase to 9.5 mg/24 hours patch daily after no less than 4 weeks; if patch Dose

not applied for more than several days, treatment should be . Initially 5 mg once daily, increased in steps of 5 mg at

restarted with 4.6 mg/24 hours patch weekly intervals; max. 20 mg daily Note When switching a patient from oral to transdermal therapy, patients taking 3-6 mg daily should be prescribed the 4.6 mg/24 Ebixa hours patch; patients taking 9 mg daily who do not tolerate the c (Lundbeck) A dose well should be prescribed the 4.6 mg/24 hours patch, while

tem

Tablets , f/c, scored, memantine hydrochloride 10 mg, those taking 9 mg daily who tolerate the dose well should be net price 28-tab pack = £34.50, 56-tab pack = £69.01,

prescribed the 9.5 mg/24 hours patch; patients taking 12 mg daily

sys

112-tab pack = £138.01; 20 mg, 28-tab pack = £69.01; should be prescribed the 9.5 mg/24 hours patch. The first patch should be applied on the day following the last oral dose Note The Scottish Medicines Consortium has advised (October 2007) that Exelon

patches should be restricted for use in Oral drops , memantine hydrochloride 10 mg/g, net

l nervous

patients with moderately severe Alzheimer’s disease under the

price 50 g = £61.61, 100 g = £123.23 conditions of the NICE guidance (September 2007) and when a transdermal patch is an appropriate choice of formulation

Note 5 mg : 10 drops of memantine hydrochloride oral drops

entra Note The Scottish Medicines Consortium has advised (January 2004) C that Ebixa is not recommended for the treatment of Alzheimer’s

4 disease RIVASTIGMINE

Indications mild to moderate dementia in Alzheimer’s disease or in Parkinson’s disease

Cautions gastric or duodenal ulcers (or susceptibility to ulcers); monitor body-weight; sick sinus syndrome,

conduction abnormalities; history of asthma or chronic obstructive pulmonary disease; history of seizures; bladder outflow obstruction; hepatic impairment (avoid if severe—Appendix 2); renal impairment (Appendix 3); pregnancy (Appendix 4); interactions: Appendix 1 (parasympathomimetics) Note If treatment interrupted for more than several days, re- introduce with initial dose and increase gradually (see Dose)

Contra-indications breast-feeding (Appendix 5) Side-effects nausea, vomiting, diarrhoea, dyspepsia,

anorexia, abdominal pain; dizziness, headache, drowsiness, tremor, asthenia, malaise, agitation, con- fusion; sweating; weight loss; less commonly gastric or duodenal ulceration, bradycardia, syncope, depres- sion, insomnia; rarely angina pectoris, seizures; very rarely gastro-intestinal haemorrhage, pancreatitis, cardiac arrhythmias, hypertension, hallucinations, extrapyramidal symptoms (including worsening of Parkinson’s disease), and rash; with patches applica- tion-site reactions Note Gastro-intestinal side-effects more common in women

Dose . See under preparations below

Exelon c (Novartis) TA Capsules , rivastigmine (as hydrogen tartrate) 1.5 mg (yellow), net price 28-cap pack = £39.12, 56-cap pack = £78.25; 3 mg (orange), 28-cap pack = £39.12, 56-cap pack = £78.25; 4.5 mg (red), 28-cap pack = £39.12, 56- cap pack = £78.25; 6 mg (red/orange), 28-cap pack = £39.12, 56-cap pack = £78.25. Label: 21, 25

BNF 57