Portfolio
Medicines Management
Document name:
Carbamazepine Communication
Document type:
Pharmacy
Communication
Staff group to whom it
applies:
Prescribers
All qualified nursing staff
All pharmacy staff
Distribution:
Trustwide
How to access:
Intranet
PA to Chief Pharmacist
Issue date:
March 2006
Reviewed:
December 2009
January 2012
January 2014
Next review:
Approved by:
Drug and Therapeutics Trust Action
Group
Developed by:
Director leads:
Kate Dewhirst, Deputy Chief
Pharmacist
Katie Crowe, Senior Clinical
Pharmacist
Dr Booya, Medical Director
Contact for advice:
Med.information@swyt.nhs.uk
Focus on Carbamazepine in Mental Health
Introduction
Carbamazepine is licensed for the prophylaxis of bipolar disorder in patients
unresponsive to lithium therapy. Evidence of efficacy is uncertain. It may be
beneficial in rapid cycling bipolar disorder. Additionally it is licensed for
generalised tonic-clonic and partial seizures and the paroxysmal pain of trigeminal
neuralgia.
It is also used for aggression in schizophrenia, attention-deficit hyperactivity
disorder, and self-injurious behaviour, use for these indications will require
completion on an unlicensed use form as outlined in Section 17 of the Medicines
Code.
.
Dosage and administration
The modified release form of Carbamazepine is recommended. This is prescribed
orally, with the total daily dose given as either a single dose at night or as two
divided doses. It can be given, before, after or during meals. Liquid and chewable
tablets are available if there are swallowing difficulties.
For the prophylaxis of bipolar disorder in patients (unresponsive to lithium) the
recommended starting dose of carbamazepine is 400mg daily in divided doses,
increasing gradually until symptoms are controlled or a dose of 1600mg is
reached.
Monotherapy is desirable in view of the high potential for both pharmacokinetic and
pharmacodynamic interactions.
Plasma level monitoring is established in the treatment of epilepsy, the therapeutic
range being stated as 4- 12 mg/l. The evidence of a therapeutic range is less
strong for affective illness. A serum level of at least 7mg/l has been suggested.
This should be interpreted in conjunction with symptom assessments.
For the purposes of consent to treatment carbamazepine can be authorised as:
 4.2.3 Antimanic medication
 4.8.1 Antiepileptic medications
 Carbamazepine
The BNF maximum dose is 1600mg/day, so dosing must be within this where the
BNF maximum is stated as part of the consent to treatment form.
Contra indications
Carbamazepine is contra-indicated in atrio-ventricular block, a history of bone
marrow suppression or a history of acute porphyria. Due to its structural
relationship to tricyclic anti-depressants, carbamazepine is not recommended in
combination with monoamine oxidase inhibitors (MAOIs).Carbamazepine should
never be co-prescribed with clozapine due to the potential to cause leucopenia.
Adverse events and special precautions
1. Agranulocytosis and aplastic anaemia occur with a very low incidence.
A decreased white cell count and platelet count is reported occasionally to
frequently.
Action - withdraw immediately if leucopenia is severe, is becoming progressively
worse or there are clinical symptoms (sore throat, fever, bruising, mouth ulcers
malaise, non-specific illness)
Closer monitoring is required if there are low levels of abnormal results.
2. Severe hepatic reactions to carbamazepine occur very rarely. Abnormal
results of liver function tests (LFTs) are not necessarily an indication of liver
impairment. Levels of gamma-glutamyltransferase (GGT) and alkaline
phosphatase (AP) may be raised due to enhanced hepatic metabolising capacity
i.e. enzyme induction.
Action - withdraw immediately in cases of aggravated liver dysfunction or acute
liver disease, if LFTs are severely abnormal, are becoming progressively worse or
there are clinical symptoms (jaundice, bruising, oedema, ascites hypoglycaemia,
infection)
Closer monitoring is required if there are low levels of abnormal results.
3. Severe skin reactions may occur e.g. Stevens-Johnson syndrome and Lyell’s
syndrome (toxic epidermal necrolysis)
Action - withdraw immediately is signs and symptoms suggest severe reaction.
Mild skin reactions are mostly transient and disappear within a few days or weeks.
Close surveillance is required for a worsening rash or accompanying symptoms
(systemic illness, fever, arthralgia or myalgia, vesicles are present in the mucosa of
the mouth, GI tract or conjunctivae.
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Rarely a delayed multi-organ hypersensitivity disorder may occur which can
affect the skin, liver and other organs as above, alone or in combination.
Treatment should be withdrawn immediately.
Other very rare but potentially serious adverse events include renal failure,
interstitial nephritis, neuroleptic malignant syndrome, hyponatraemia and
serotonin syndrome.
The most common problems associated with carbamazepine are dizziness,
drowsiness, ataxia and nausea. These can be minimised by starting with a
low dose and increasing gradually, or by using the slow-release formulation.
Pregnancy
Carbamazepine is estimated to increase the risk of neural tube defects from 6 in
10,000 to around 20 to 50 in 10,000 and carries a risk of other major fetal
malformations including gastrointestinal tract problems and cardiac abnormalities.
If a woman who is taking carbamazepine for mental health conditions is planning a
pregnancy healthcare professional should advise her to stop taking the medication
and if appropriate an alternative medication may be considered.
If a woman is taking carbamazepine at the time of conception and/or in the first
trimester of pregnancy health professionals should offer screening and counselling
about the continuation of the pregnancy, the need for additional monitoring and the
risks to the fetus if the woman continues to take the medication. The newborn will
require a full paediatric assessment and subsequent monitoring.
Clinically relevant interactions
Antipsychotics
Clozapine and carbamazepine must not be used together due
to the additional risks of agranulocytosis. With all
antipsychotics, CNS side effects may be additive e.g.
drowsiness, ataxia. Risperidone may increase
carbamazepine levels and carbamazepine may reduce
risperidone levels.
MAOIs
Need two week washout period
Lithium
Neurotoxicity and increased risk of side effects of both drugs
without raised serum levels
Anticonvulsants
Complex interactions with phenytoin, lamotrigine, sodium
valproate and others. Monitoring of both medications will be
required. Consult BNF, pharmacist or neurologist.
Erythromycin
Can rapidly increase carbamazepine levels by 100-200%.
Use alternative or monitor carbamazepine levels.
Grapefruit juice
A single serving can increase carbamazepine levels.
Oral contraceptives
Leads to a reduced contraceptive effect. Use at least 50
micrograms of ethinylestradiol a day or Depo Provera every
10 weeks or other methods of contraception.
Warfarin
Metabolism of warfarin is accelerated and efficacy may be
reduced. Doses may need to be increased by 100% to
achieve target INR. Care required when carbamazepine is
withdrawn, as INR will be increased with risk of bleed.
Calcium channel blockers
Diltiazem and verapamil may increase the risk of
carbamazepine toxicity.
Tricyclic antidepressants
Plasma levels of the antidepressant are reduced
Caution and increased frequency of monitoring is required when carbamazepine is
used concomitantly with other medication that may cause similar adverse events.
Recommendations
 Baseline and ongoing monitoring is required.
Full blood count
Baseline then 2 weekly for 2
months then
3-6 monthly
Hepatic function
Baseline and 3-6 monthly
As most hepatic adverse event
occur in the first month,
consider earlier monitoring if
signs and symptoms of hepatic
dysfunction are present
Serum carbamazepine
To ensure therapeutic level is
reached 2-4 weeks after dose
changes then 3-6 monthly
Renal function and
Baseline and 6 monthly
electrolytes
(Complete urinalysis and BUN
are recommended by the SPC)
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Carbamazepine should only be prescribed after a benefit–risk appraisal and
under close monitoring in patients with a history of cardiac, hepatic or renal
damage, or adverse haematological reactions to other medication.
Carbamazepine is not recommended for acute mania in part due to the time
taken to reach therapeutic levels.
Ensure service user and or carer is aware of potential serious adverse
events and the signs and symptoms to be mindful of.
Provide verbal and written information.
Continually review efficacy and symptom control, particularly in unlicensed
indications to ensure on-going benefit outweighs the risks. Document this
review
All results, including normal results and any actions required should be
recorded in the medical notes
LFT results should be considered as a combination rather than single
results. Generally, alanine aminotransferase (ALT) may be considered a
specific marker for acute hepatocellular damage and albumin, bilirubin and
prothrombin time indicate how well the liver is functioning. A mildly elevated
ALT value (less than 1.5 times normal) could be normal for gender ethnicity
or body mass index. LFTs can be normal in those with chronic hepatitis and
cirrhosis.
Due to the difficulty in interpreting results, clinical monitoring is of
primary importance throughout treatment
References
 Summary of Product Characteristics; Tegretol; Novartis Pharmaceutical UK
Ltd Wyeth; February 2011
 The Maudsley Prescribing Guidelines 10th Edition 2009. South London and
Maudsley NHS Trust, Oxleas NHS Trust
 Psychotropic Drug Directory, 2010; Bazire
 BNF www.bnf.org.uk
 Mason P. Blood tests used to investigate liver, thyroid or kidney function
and disease. PharmJ 2004; 272; 446-448
 Johnston DE. Special considerations in Interpreting Liver Function Tests.
American Family Physician 1999; 59;
 Nickless G. An overview of hepatitis. Pharm J 2008:280:411-414
 NICE CG 137: The epilepsies: the diagnosis and management of the
epilepsies in adults and children in primary and secondary care. Jan 2011.