Download Acamprosate - NHS Trafford CCG

GREATER MANCHESTER INTERFACE
PRESCRIBING GROUP
On behalf of the
GREATER MANCHESTER MEDICINES MANAGEMENT
GROUP
SHARED CARE GUIDELINE FOR ACAMPROSATE
(CAMPRAL EC)
Scope: As above
Reference Number
ACAM 06 fnl
Classification
SHARED CARE GUIDELINE
Issue date:
December 2006
Author(s)/Originator(s)
Pennine Care NHS Trust
To be read in conjunction with the
following documents
British National Formulary (BNF) and BNF for
Children
Summary of Product Characteristics (SPC)
Pharmaceutical company’s Patient Information
Leaflet (PIL)
Drugs & Therapeutics
Date: Oct 20
Committee
2006
20 October 2008
Authorised by
Review Date: to be confirmed
1. Introduction
Acamprosate (calcium acetylhomotaurinate) is marketed in the U.K. by Merck
Pharmaceuticals under the brand name campral EC®.
Acamprosate has a chemical structure similar to that of amino acid
neuromediators, such as taurine or gamma-amino-butyric acid (GABA),
Acamprosate is indicated for the maintenance of abstinence in alcohol
dependent patients. Acamprosate has been shown to increase abstinence
rates in people receiving treatment for alcohol dependence (i.e. from 10% to
20% or at best up to 40%). (Slattery J. et al, 2003).
Although its mechanism of action is not clearly defined, acamprosate appears
to block excitatory activity in the brain (NMDA Glutamate) – which is thought
to underlie some aspects of CNS vulnerability to relapse. It also enhances the
inhibitory system (GABA) by stimulating GABAergic inhibitory
neurotransmission. Whilst it has been known as an “anti-craving” drug, the
evidence from trials is less conclusive about this as a major effect.
Acamprosate has also been shown to reduce the number of drinks and
number of days drinking in somebody who lapses into heavy drinking.
Patients have reported that they do not feel the need to drink as much alcohol
as they would normally (Chick J. et al, 2003).
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In addition, Acamprosate use in animal models appears to have a neuroprotective effect in that the number of brain cells that die during alcohol
detoxification can be reduced with Acamprosate. (Koob et al, 2002).
Acamprosate does not constitute treatment for the symptoms of alcohol
withdrawal.
Acamprosate does not prevent the harmful effects of continuous alcohol
abuse.
Acamprosate should not impair the patient's ability to drive or operate
machinery.
There are no NICE recommendations available for the prescribing of
acamprosate.
The British Association for Psychopharmacology recommends the use of
acamprosate in the treatment of alcohol dependency (Lingford-Hughes, A.R.,
et al 2004).
The Scottish Intercollegiate Guidelines Network has also advised on the use
of acamprosate – though has emphasized the need for the medication to be
prescribed alongside psycho-social interventions such as counselling. (The
Scottish Intercollegiate Guidelines Network, 2003).
2. Scope
This protocol covers prescribing by Pennine Care NHS Trust; Pennine Acute
Hospitals NHS Trust and General Practitioners working both within and
outside of the National Enhanced Services for alcohol and drugs.
3. Clinical condition being treated
Acamprosate is licensed for the treatment of the alcohol dependency
syndrome (Edwards and Gross, 1976). This syndrome consists of the
following seven features:

physiological withdrawal symptoms, such as tremor, sweating and
hallucinations;

relief-drinking – i.e. the use of alcohol to attenuate the above
withdrawal symptoms (often in the morning when blood alcohol
levels have fallen during the night);

raised tolerance to alcohol – i.e. an ability to consume greater
amounts of alcohol without developing the usual effects of
intoxication (such as slurred speech and impaired balance);

salience of drinking behaviour – i.e. neglect of other areas of life
(such as marital relationships and employment) as drinking
assumes a primary aspect of the individual’s life;
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
rapid reinstatement of syndrome – this refers to the recurrence of
withdrawal symptoms when drinking is resumed following a period
of abstinence;

loss of control over alcohol use (i.e. an inability to drink in social or
moderate manner);

subjective awareness of a compulsion to use alcohol (i.e. identified
craving for alcohol).
Acamprosate is principally used to reduce the risk of relapse into heavy
drinking (for example, following detoxification) – though it may also attenuate
the level of alcohol use if a relapse occurs.
Acamprosate appears to be particularly effective in the following situations
(Lesch, O.M. and Walter, H. 1996):

moderate or severe dependence;

recent physiological withdrawal symptoms;

current abstinence;

recent withdrawal (i.e. within the past 2 weeks);

patient aiming for complete abstinence;

concurrent involvement in psychosocial therapy;

craving for alcohol.
Other indications (though with lesser evidence) include the following:

tendency to mild anxiety or tension in the post-withdrawal phase (not
marked anxiety disorder or panic disorder)

reported craving.
Acamprosate appears to be less effective in the following situations:

those with repeated self-harm;

antisocial personality disorder;

evidence of childhood conduct disorder;

minimal brain damage;

marked social problems (and lack of support);

those with primary psychiatric disorders (NB. acamprosate has been
successfully used with antidepressants and drugs for anxiety
disorders).
Prescribing should be reviewed on a periodic basis e.g. at 6 weeks; 12 weeks;
6 months; 9 months and 12 months. Reviews should determine whether or
not the patient is continuing to take the medication as prescribed; their level of
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alcohol consumption (if any); any relevant health problems (such as liver
disease); their continuing use of support services; and the patient’s views on
the effectiveness of the medication. The medication will usually be
discontinued if contra-indications develop (such as renal insufficiency) and / or
the medication appears to be ineffective (e.g. if the patient continues to drink
heavily). Prescribing is normally discontinued after a maximum of one year.
4. Product information and treatment regimen to be used
Acamprosate calcium is prepared in 333mg enteric-coated tablets (campral
EC®).
The tablets are packaged in aluminium / PVC sheets of blisters presented in
cartons of 168 tablets.
The following doses are recommended:
Adults > 60kg: 2 tablets three times a day with meals.
Adults < 60kg: 2 tablets in the morning, 1 tablet at noon and 1 tablet at
night with meals.
The maximum daily dose that can be prescribed is 1998 mg.
Acamprosate taken with food has lower bioavailability than in the fasting state.
Some patients, however, are more comfortable taking the tablets with food.
Steady state levels of acamprosate are achieved by the seventh day of
dosing.
It is recommended that acamprosate is commenced as soon as possible after
detoxification is completed – especially if the patient reports intense/pervasive
craving for alcohol. In some cases, however, it may be beneficial to
commence prescribing during detoxification (e.g. if the patient has previously
experienced severe craving for alcohol). Acamprosate may also be useful in
the absence of a formal detoxification programme – e.g. when the patient has
significantly reduced his/her level of alcohol consumption.
If a relapse occurs acamprosate does not interact with alcohol and so
treatment should be continued.
Acamprosate does not interact with benzodiazepines, so assisted withdrawal
can be instigated if needed.
Acamprosate should be discontinued after 6 weeks, or earlier, if more than
one relapse has occurred which is not significantly attenuated by comparison
to the patient’s previous history of relapse.
Acamprosate is classified as an “Amber” drug under the Greater Manchester
Red/Amber/ Green model. This means that when it is prescribed by nonspecialist GPs it should be in accordance with an approved shared care
protocol and in the context of an ongoing package of support and
assessment.
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Acamprosate will usually be initiated by a GPWSI; an accredited General
Practitioner working within the National Enhanced Service (NES) for alcohol;
or a Consultant Psychiatrist working within a either a Specialist Alcohol
Treatment Service or in General Psychiatry. It can also, however, be
prescribed by a GP operating outside of the NES framework. In addition, it is
also possible that acamprosate may be prescribed by a nurse prescriber
within a supplementary prescribing / clinical management prescribing
framework (providing that this is within their scope of competence). In
addition, acamprosate may be prescribed by Hospital Physicians who are
providing treatment for alcohol-dependant patients (providing that they can
offer or arrange for the ongoing package of care that its use demands).
Continued heavy alcohol use negates the therapeutic benefits of acamprosate
and therefore it is usually only initiated following detoxification (i.e. once the
patient is abstinent from alcohol).
Acamprosate should be combined with counselling or other forms of
therapeutic intervention (Soyka M, 1994).
The recommended treatment period is a maximum of one year.
Acamprosate has a shelf-life of three years.
Acamprosate currently costs £28.92 for a 168-tablet pack (- which provides 28
days treatment at a dose of 2 tablets three times a day, or 42 days treatment
at a dose of 2 tablets twice a day). The cost per patient year based on this
dose is therefore approximately £251 for patients weighing less than 60 kg
and £377 for patients over 60 kg.
5. Regimen Management
The Substance Misuse Service (SMS) can provide advice and guidance on
the use of acamprosate. This may be offered on an on-going basis for
patients who remain under the care of the SMS – or on an ad hoc basis for
other patients. The National Enhanced Service (alcohol) clinics can also be
used to provide assessment and guidance regarding clinical management.
The prescribing clinician, however, will hold continuing responsibility for the
overall regimen management.
If the medication is being prescribed by a doctor within the National Enhanced
Service and the patient is registered with a different practice it is essential that
there is effective communication between the two services. Prior to
commencing prescribing relevant health information should be obtained –
especially regarding the presence of any possible contra-indications. The
patient’s GP should be informed (in writing) when prescribing is initiated. The
GP should also be advised of any relevant clinical issues – such as the
presence of troublesome side-effects. In addition, the patient’s GP should be
requested to provide information regarding all relevant clinical developments –
such as a deterioration in the patient’s health, prescribing of additional
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medication, etc. Finally, the patient’s GP should be advised when prescribing
is discontinued.
Acamprosate is seen as being most effective when used in conjunction with
other forms of therapeutic intervention, such as counselling and AA
attendance (Soyka M, 1994). It is important, therefore that agreement is
reached with the patient regarding continued use of therapeutic resources
whilst acamprosate is being prescribed.
6. Summary of cautions, contra indications, side-effects
Adverse events associated with acamprosate tend to be mild and transient in
nature.
The following have been reported:

diarrhoea;

nausea;

vomiting;

abdominal pain;

pruritus;

maculopapular rash;

bullous skin reactions (rarely);

fluctuation in libido;

psychiatric disorders (mainly depression).
Contra-indications include the following:

hypersensitivity to the drug;

renal insufficiency (serum creatinine >120 micromol/l);

severe hepatic failure (Childs-Pugh classification C);

pregnancy;

lactation.
No interactions have been shown between acamprosate and diazepam,
disulfiram or imipramine.
There is no information available on the concomitant administration of
acamprosate with diuretics.
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There are no specific monitoring requirements for patients on acamprosate.
Five cases of overdose associated with acamprosate therapy have been
reported, including one patient who ingested 43g of acamprosate. After
gastric lavage all patients had an uneventful recovery. Diarrhoea was
observed in two cases. No case of hypercalcaemia was reported in the course
of these overdoses. However, should this occur, the patients should be
treated for acute hypercalcaemia.
Acamprosate should not be administered to children and the elderly (i.e. over
65 years).
Patients should be advised to report the development of side-effects to the
prescribing doctor (or other clinician). In most cases these will be mild and
transient. If troublesome side-effects persist, however, consideration should
be given to discontinuation of the medication. The responsibility for adjusting
or discontinuing treatment will rest with the prescribing clinician (see above).
In addition, patients should also be encouraged to advise their prescriber if
they become pregnant (or plan to become pregnant) during treatment and / or
if they commence breast-feeding.
7. Special considerations
There are no known reported sensitivity reactions regarding the handling or
preparation of acamprosate.
8. Back-up care available to GP from Hospital, including emergency
contact procedures and help line numbers
Information on acamprosate can be provided by the Substance Misuse
Service (available 9.00 a.m. – 4.45 p.m., Monday to Friday).
Further information can be obtained from the manufacturer as follows:
Merck Pharmaceuticals, Harrier House, High St., West Drayton, Middx. UB7
7QG Tel: (01895) 452 307 Fax: (01895) 452 296 Email:
[email protected]
9. Statement of agreement
It is anticipated that the most acamprosate prescribing will be initiated in
primary care by either the patient’s own GP or a GP working within the NES
framework. If prescribing is initiated by a consultant psychiatrist, however, a
request may be made to the relevant GP to continue prescribing in
accordance with the suggested care pathway. If agreement cannot be
obtained the GP should advise the consultant within 14 days of the request
and should state any relevant concerns.
10. Written information provided to the patient
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Patients will be provided with the manufacturer’s product information sheet.
Addition information is available as follows:
What is Acamprosate ?
Acamprosate is a drug used in the treatment of people who have been
dependant on alcohol and who are aiming to abstain. It is often known by the
trade name “campral”. It appears to reduce the urge or “craving” for alcohol. It
is believed that this craving may be caused by a change in the chemicals in
the brain - and that acamprosate works by helping to reverse these changes.
Acamprosate appears to be particularly helpful for those who have recently
stopped drinking - such as those undergoing detoxification programmes.
Acamprosate should always be used alongside other types of help, such as
counselling. The medication is provided in 330 mg. tablets and up to 6 are
taken daily. The medication should then be taken on a regular basis for up to
one year.
The Benefits / Advantages of Acamprosate Prescribing
Acamprosate can be very effective in reducing craving for alcohol. This will
often greatly help reduce the risk of a relapse into heavy drinking.
Acamprosate is not a sedating drug and therefore should not cause
drowsiness or tiredness. Acamprosate appears to compatible with most other
drugs, including anti-depressants and tranquillisers. Acamprosate is not an
addictive drug and can be stopped without the risk of withdrawal symptoms.
Whilst side effects can occur (see below) these are relatively rare and are
usually short - lived. Problems do not occur if an occasional dose is
accidentally missed.
Possible Disadvantages / Risks of Acamprosate Prescribing
Acamprosate does not usually provide many benefits during the first few days
it is taken - and it may take a week or two to produce it’s full effect. Possible
side effects associated with acamprosate include skin reactions and
gastrointestinal disturbances such as diarrhoea, nausea, vomiting and
abdominal discomfort. Some people also experience a loss of their sex drive.
Acamprosate does not seem to work well for people who start to take it when
they are drinking heavily. Some people mistakenly believe that acamprosate
is a “miracle cure” for all their problems - and they then fail to use other types
of help such as attending A.A. Fellowship meetings. Acamprosate is not
recommended for people with very severe liver or kidney problems. It is also
not usually used during pregnancy or breast - feeding.
11. Supporting References
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Chick J, Lehert P, Landron F (2003) Does acamprosate improve reduction of
drinking as well as aiding abstinence? J Psychopharmacol 17: 397–402.
Koob G, Mason B, De Witte P, Littlejohn J, Siggins G (2002) Potential
neuroprotective effects of acamprosate. Alcohol Clin Exp Res 26: 586–592.
Lesch O M, Walter H (1996) Subtypes of alcoholism and their role in therapy.
Alcohol 31 (Suppl 1): 63–67.
Lingford-Hughes, A.R., et al (2004) Journal of Psychopharmacology 18(3)
(2004) 293–335. Evidence-based guidelines for the pharmacological
management of substance misuse, addiction and comorbidity:
recommendations from the British Association for Psychopharmacology.
Scottish Intercollegiate Guidelines Network (2003) The management of
harmful drinking and alcohol dependence in primary care.
Slattery J, Chick J, Cochrane M, Godfrey C, Kohli H, Macpherson K, Parott S,
Quinn S, Single A, Tochel C, Watson H (2003) Prevention of relapse in
alcohol dependence. Health Technology Assessment Report 3. Health
Technology Board for Scotland, Glasgow.
Soyka M, Sass H (1994) Acamprosate: a new pharmacotherapeutic approach
to relapse prevention in alcoholism – preliminary data. Alcohol Alcohol 2:
531–536.
The Child’s Pugh Classification
12.
Score
1
2
3
bilirubin (micromol/l)
<34
34-50
>50
albumin (g/l)
>35
28-35
<28
PT (s prolonged)
<4
4-6
>6
encephalopathy
none
mild
marked
ascites
none
mild
marked
If there is primary biliary cirrhosis or sclerosing cholangitis then bilirubin is
classified as <68=1; 68-170=2; >170=3.
The individual scores are summed and then grouped as:

<7 = A

7-9 = B

>9 = C
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