Section 4: Central Nervous System

Section Description

BNF 4.1.1

Hypnotics

BNF 4.1.2

Anxiolytics

BNF 4.2

Drugs used in psychoses and related disorders

BNF 4.2.1

Antipsychotic drugs

BNF 4.2.2

Antipsychotic depot injections

BNF 4.2.3

Drugs used for mania and hypomania

BNF 4.3

Antidepressant drugs

BNF 4.3.1

Tricyclic and related antidepressant drugs

BNF 4.3.3

Selective serotonin re-uptake inhibitors

BNF 4.3.4

Other antidepressant drugs

BNF 4.4

CNS stimulants and drugs used for attention deficit hyperactivity disorder

BNF 4.5.1

Anti-obesity drugs acting on the GI tract

BNF 4.5.2

Centrally acting appetite suppressants

BNF 4.6

Drugs used in nausea and vertigo

BNF 4.7

Analgesics

BNF 4.7.1

Non-opioid analgesics and compound analgesic preparations

BNF 4.7.2

Opioid analgesics

BNF 4.7.3

Neuropathic pain

BNF 4.7.4.1

Treatment of the acute migraine

BNF 4.7.4.2

Prophylaxis of migraine

BNF 4.7.4.3

Cluster headache and the trigeminal autonomic cephalalgias

BNF 4.8.1

Control of the epilepsies

BNF 4.8.2

Drugs used in status epilepticus

BNF 4.9.1

Dopaminergic drugs used in parkinsonism

BNF 4.9.2

Antimuscarinic drugs used in parkinsonism

BNF 4.9.3

Drugs used in essential tremor, chorea, tics and related disorders.

BNF 4.10

Drugs used in substance dependence

BNF 4.11

Drugs for dementia

BNF 4.1.1 Hypnotics

The routine prescribing of hypnotics is undesirable. Tolerance to their effects develops within 3 to 14 days of continuous use and long-term efficacy cannot be assured. Where prolonged administration is unavoidable, hypnotics should be discontinued as soon as feasible. Benzodiazepines should not be used long-term and should only be initiated by a consultant psychiatrist or another appropriate specialist consultant. Patients prescribed hypnotics to aid sleep as a hospital in-patient should not be prescribed hypnotics on discharge (TTO).The MeReC Bulletin states ‘There is no compelling evidence of a clinically useful difference between the newer hypnotics (z-drugs) and shorter-acting benzodiazepine hypnotics’.

NICE TA77 recommends that clinicians should consider using non-medicine treatments, and then, if they think that a hypnotic medicine is the appropriate way to treat severe insomnia that is interfering with normal daily life, they should prescribe one for only short periods of time and strictly according to the licence for the drug. Because there is no firm evidence of differences in the effects of zaleplon, zolpidem, zopiclone and the shorter-acting benzodiazepines, NICE recommends that clinicians should prescribe the cheapest drug, taking into account the daily dose required and the cost for each dose. Treatment should only be changed from one of these hypnotics to another if side effects occur that are directly related to the medicine.

An audit pack is available from the Prescribing Support Team (01902 575184) to assist GP practices with the review of hypnotic prescribing.

RWHT & PCT

Temazepam

Temazepam acts for a short time, with little or no hangover effect. Withdrawal phenomena are however more common with shorter-acting benzodiazepines.
Controlled Drug: Schedule 3 of the Misuse of Drugs Regulations 2001.

PCT (Secondary Care)

RWHT &
PCT (Primary Care)

Zolpidem

Zopiclone

Zolpidem and zopiclone act on the same receptors, or receptor sub-types, as benzodiazepines, therefore may lead to dependence. Both have a short duration of action (6-8 hours) with little or no hangover effect. Zopiclone is associated with a bitter after taste.

RWHT

Chloral and derivatives

Prescribing initiated and reviewed by Paediatric Consultants. Also used prior to procedures.

Melatonin

Clinical experience suggests melatonin may be of value in treating sleep disorders in children with conditions such as visual impairment, cerebral palsy, attention deficit hyperactivity disorder and autism. The dose of melatonin has not been established but an initial dose of 2-3mg given 30-60 minutes before bedtime has been used. If there is no improvement after 1-2 weeks, the dose may be increased to 4-5mg at night. The maximum dose is generally accepted to be 10mg but higher doses have been used (BNF for Children).

The only UK licensed melatonin preparation, Circadin®, is licensed solely for the short-term relief of insomnia in patients aged 55 years or more.

Clinicians are faced with a dilemma when prescribing melatonin for patients aged less than 55 years; our advice is to prescribe the product most suitable for the patient following the lowest risk approach as recommended in the MHRA Guidance note 14; The supply of unlicensed medicinal products ("specials")

The hierarchy is provided for guidance only and each case should be considered on its individual merit.

1. Melatonin modified-release tablets 2mg (Circadin®)

2. Off label use of Melatonin modified-release tablets 2mg (Circadin®)

Although MHRA does not recommend "off label" (outside of the licensed indications) use of products, if the UK licensed product can meet the clinical need, even "off-label", it should be used instead of an unlicensed product.
It should be understood that the prescriber’s responsibility and potential liability are increased when prescribing off-label.

3. Melatonin 3mg tablet (Bio-Melatonin®) (Licensed product in Hungary)
If a UK product cannot meet the special need, then another (imported) medicinal product should be prescribed, which is licensed in the country of origin.

4. Melatonin product made as a UK manufactured "special", which is made in GMP inspected facilities.

 e.g. Penn Pharmaceutical Services products manufactured under its UK Specials license – Melatonin capsules 1mg, 2mg,  2.5mg, 3mg, 5mg & 10mg

Where a liquid is required, a Drug Tariff special strength and pack size should be prescribed – melatonin 2mg/5ml oral solution (packs of 100ml), melatonin 3mg/5ml oral solution (packs of 100ml), and melatonin 5mg/5ml oral solution (packs of 200ml).

5. Import of melatonin products unlicensed in the country of origin, and which are not classed as medicines in the country of origin.

For example where they are classed as health supplements.

 

 

BNF 4.1.2 Anxiolytics

Benzodiazepine withdrawal
Please see section 4.1 of the British National Formulary

 

Short-term treatment of anxiety
(2-4 weeks) if severe, disabling, or subjecting the individual to unacceptable distress

Diazepam

Elimination half-life ranges from 24 to 48 hours, although the main active metabolite has a half-life of 2-5 days

Acute anxiety
(Secondary Care Use Only)

Lorazepam

 

 

Licensed for short-term use in anxiety. Elimination half-life ranges from 10 to 20 hours. Greater risk of withdrawal symptoms than with other benzodiazepines.
Injection is for use under the supervision of a Psychiatrist

 

Promethazine hydrochloride

Rapid tranquilisation and anxiety (Mental Health Team)

Treatment of alcoholic withdrawal

Chlordiazepoxide

Elimination half-life ranges from 5-30 hours, although the main active metabolite has a half-life of several days.

BNF 4.2 Drugs used in psychoses and related disorders

Advice of Royal College of Psychiatrists on doses above BNF upper limit.
Unless otherwise stated, doses in the BNF are licensed doses—any higher dose is therefore unlicensed

BNF 4.2.1 Antipsychotic drugs

NICE Guidance on the use of newer (atypical) antipsychotic drugs for the treatment of schizophrenia recommends atypical antipsychotics should be chosen:

Changing to an atypical antipsychotic is not necessary if a conventional antipsychotic controls symptoms adequately and the individual does not suffer unacceptable side effects.


Atypical and conventional antipsychotics should not be prescribed concurrently.

Antipsychotic use in elderly patients with dementia - MHRA advice

CONVENTIONAL (TYPICAL) ANTIPSYCHOTICS

Chlorpromazine

 

Flupenthixol  Initiation by the Mental Health Team

Haloperidol

 

All patients require ECG before starting treatment (SPC)

Levomepromazine

Initiation by the Palliative Care Team.
Rapid tranquilisation.

Promazine

Initiation by the Mental Health Team.

Sulpiride

Initiation by the Mental HealthTeam.

Trifluoperazine  Initiation by Mental Health Team

Zuclopenthixol (oral)

Initiation by Mental Health Team

Zuclopenthixol acetate injection (Clopixol Acuphase)

Clopixol Acuphase® is for initiation and use by Mental Health Team only 

ATYPICAL ANTIPSYCHOTICS
First-line:

NICE Guidance suggests these drugs are suitable for GP initiation. http://www.nice.org.uk/cat.asp?c=32878)

Amisulpride

 

Aripiprazole

 

Aripiprazole for schizophrenia in people aged 15 to 17 years NICE TA213

Aripiprazole for treating moderate to severe manic episodes in adolescents with bipolar I disorder NICE TA292

Lurasidone Wolverhampton patients only. Specialist service initiation for 3 months then suitable for GP prescribing under a shared care agreement.

Olanzapine

 

Quetiapine

Brand prescribing in primary care for m/r preparations; 1st choice Zaluron XL®, 2nd choice Biquelle XL®

Risperidone

 

Specialist use only:

 

Clozapine

 

Clozapine will be prescribed and dispensed within the hospital service; it is considered unsuitable for prescribing and monitoring by GPs in Wolverhampton. Patient, prescriber & supplying pharmacist must be registered with the Patient Monitoring Service. Treatment is only continued if there are acceptable leucocyte and differential blood counts.
Clozapine should be introduced if schizophrenia is inadequately controlled despite sequential use of two or more antipsychotics (one of which should be an atypical) each for at least 6-8 weeks.

BNF 4.2.2 Antipsychotic depot injections

CONVENTIONAL (TYPICAL) ANTIPSYCHOTIC

Flupentixol decanoate

Depixol® is for initiation by Mental Health Team only

Fluphenazine decanoate

Modecate® is for initiation by Mental Health Team only

Haloperidol

Haldol® is for initiation by Mental Health Team only
All patients require ECG before starting treatment (SPC)

Pipotiazine

Piportil Depot® is for initiation by Mental Health Team only

Zuclopenthixol decanoate

For initiation by Mental Health Team only.

ATYPICAL ANTIPSYCHOTIC

 

Risperidone

Risperdal Consta® is for initiation by Mental Health Team only

Olanzapine embonate  For initiation by Mental Health Team only

Paliperidone

 

For initiation by Mental Health Team only. Patients to be transferred to paliperidone (Xeplion®) after stabilisation on Risperdal Consta®

Further information treatment and management of schizophrenia in primary and secondary care

BNF 4.2.3 Antimanic drugs

Lithium

  • Lithium salts should be prescribed by brand name. Wolverhampton's preferred brand is Priadel® but other brands may be prescribed.
  • Lithium salts have a narrow therapeutic/toxic ratio, requiring regular serum-lithium level monitoring (every 3 months on stabilised treatment).
  • Blood sample should be taken 12 hours after dose of lithium and at least 7 days after any changes in lithium dosage.
  • Toxicity is made worse by sodium depletion. Concurrent use of diuretics (particularly thiazides) is hazardous and should be avoided. Test renal function before initiating and if evidence of toxicity.
  • Check thyroid function every 6-12 months on stabilised regimens and advise patient to seek attention if symptoms of hypothyroidism develop.
  • See BNF for full details for toxicity, monitoring and drug interactions.

Carbamazepine

Used for prophylaxis of bipolar disorder in patients unresponsive to lithium.
NICE CG185

Lamotrigine Monotherapy or adjunctive therapy of bipolar disorder (with or without enzyme inducing drugs) NICE CG185

Valproic acid

Treatment of acute mania managed by consultant psychiatrist. The continuation of treatment after manic episode could be considered in patients who have responded to treatment for acute mania. GPs may be asked to prescribe. NICE CG185.

Valproate medicines (Epilim▼, Depakote▼): contraindicated in women and girls of childbearing potential unless conditions of Pregnancy Prevention Programme are met (MHRA 2018) 


Sodium valproate

UNLICENSED USE - For treatment of acute mania managed by consultant psychiatrist. NICE CG185. Sodium valproate should not normally be prescribed for women of child-bearing potential.

BNF 4.3 Antidepressant drugs

Hyponatraemia (usually in the elderly and possibly due to inappropriate secretion of antidiuretic hormone) has been associated with all types of antidepressants and should be considered in all patients who develop drowsiness, confusion or convulsions while taking antidepressants. [CSM advice] NICE GG90

BNF 4.3.1 Tricyclic and related antidepressant drugs

SEDATIVE

 

 

Amitriptyline

Potent anticholinergic, sedative and weight gain properties. Particularly dangerous in overdose - not recommended for treatment of derpression. Used for neuropathic pain (BNF 4.7.3) and nocturnal enuresis in children (BNF 7.4.2)

Clomipramine

More expensive than amitriptyline or dosulepin, but useful if obsessional component.

Dosulepin (dothiepin)

Hospital/ specialist prescribing only. May impair concentration and memory. Pro-convulsive & cardiac arrhythmic effects. Not recommended for the treatment of depression - should only be prescribed by a specialist.

Trazodone

Treatment of depression in dementia with anxiety

LESS SEDATIVE

 

Imipramine

 

Lofepramine

 

BNF 4.3.2 Monoamine-oxidase inhibitors

Moclobemide

Initiated by hospital consultant

BNF 4.3.3 Selective serotonin re-uptake inhibitors

The choice of SSRI is dependent on individual patient factors

Citalopram

MHRA QT interval prolongation - new maximum 40mg daily dose restrictions

Fluoxetine

 

Paroxetine

 

Sertraline

 

BNF 4.3.4 Other antidepressant drugs

Mirtazapine

For use in terminal care for pain control & depression.

Venlafaxine

Depression: Second-line after SSRI. Licensed for treatment of anxiety.
Prescribe generically for standard release and modified release tablets
Prescribe by brand (Vencarm XL®) where modified relase capsule is indicated

Duloxetine

Depression: Third-line
MTRAC advises restricted prescribing in primary care

Vortioxetine

Vortioxetine for treating major depressive episodes NICE TA367

BNF 4.4 CNS stimulants and other drugs used for attention deficit hyperactivity disorder

ATTENTION-DEFICIT HYPERACTIVITY DISORDER (ADHD)

Attention deficit hyperactivity disorder: diagnosis and management NICE NG87 

Atomoxetine

Paediatrics - shared care agreement
Dexamfetamine sulfate  Paediatrics - shared care agreement 
Lisdexamfetamine Paediatrics - shared care agreement 

Methylphenidate (Ritalin®, Equasym®)

 

15mg per day standard tablets considered equivalent to 18mg daily of m/r tablets.
Controlled Drug: Schedule 2 of the Misuse of Drugs Regulations 2001.
Paediatrics - shared care agreement

Methylphenidate m/r once a day (Concerta XL®)

NARCOLEPSY

 

 

Modafinil

For initiation by Respiratory and Neurology Consultants

SLEEP APNOEA

 

Modafinil

Product licence withdrawn August 2010

 

BNF 4.5.1 Anti-obesity drugs acting on the GI tract

Obesity: identification, assessment and management NICE CG189

Orlistat see BNF for dosage details

BNF 4.6 Drugs used in nausea and vertigo

Meniere’s disease

Betahistine  

Cinnarizine

 

Motion sickness

Cinnarizine

 

Hyoscine hydrobromide On sale to the public as Kwells® and Joy-rides®

Nausea and vomiting associated with chemotherapy

Granisetron

 
Granisetron patches (Sancuso®) For the prevention of acute nausea and vomiting in adults receiving moderately or highly emetogenic (ME or HE) chemotherapy for 3-5 days, who find swallowing difficult.
Aprepitant  
Fosaprepitant  For those patients who cannot take aprepitant

Post-operative nausea & vomiting (treatment & prevention)

Granisetron

 

Ondansetron  

Symptomatic relief of nausea from underlying disease

Domperidone

Less likely to cause sedation and dystonic reactions since does not cross blood-brain barrier. Unlikely to be effective in motion sickness or vestibular disorders. UKMI guidance on the use of Domperidone.

Metoclopramide

May induce acute dystonic reactions with facial and muscle spasms and oculogyric crises. More common in the young (especially females) and the very old. Effects occur within few hours of starting and cease within 24 hours of stopping drug. Restricted use in patients under 20 years: for details please see metoclopramide entry in the British National Formulary.

Prochlorperazine

 

Terminal care

Cyclizine

 

Hyoscine hydrobromide Available as Patches

Vertigo

Betahistine

 

Cinnarizine  
Prochlorperazine  

Vomiting of pregnancy

Cyclizine

CKS Nausea / Vomiting in Pregnancy

Promethazine  Please contact Medicines Information Service (RWHT extension 5136 or 01902 695136) for other antiemetics considered safe in pregnancy

BNF 4.7 Analgesics 

Treatment pathway for non-cancer pain in adults

BNF 4.7.1 Non-opioid analgesics

Modified-release (m/r) and enteric coated (ec) products are high cost and relatively low value – they are not recommended for routine use in primary care.

Simple analgesics

Compound analgesics

BNF 4.7.2 Opioid analgesics

PAIN RELIEF IN PALLIATIVE CARE
Please refer to West Midlands Palliative Care Physicians “Palliative Care: Guidelines for the use of drugs in symptom control”

Controlled drugs: safe use and management NICE NG46  

NICE NG46 guidance for prescribing controlled drugs advises that quantities issued should not exceed 30 day’s supply. The following information may therefore assist prescribers:

Drug name

Prescribed as

Patches per pack

One pack will last

Buprenorphine

BuTec® or Sevodyne®

4

28 days

Transtec®

4

16 days

Fentanyl

Matrifen®
Mezolar®

5

15 days

Modified-release (m/r) and enteric coated (ec) products are high cost and relatively low value – they are not recommended for routine use in primary care.

Patient Opioid Awareness Leaflet

WEAK OPIOIDS  
Codeine phosphate  
Dihydrocodeine Dihydrocodeine maybe an option for certain patients if codeine has failed to achieve expected pain relief. Note dihydrocodeine has a high addictive potential.
Tramadol Tramadol - caution in epilepsy. Hallucinations and confusion have been reported. The CSM has issued several safety warnings about this drug.
STRONG OPIOIDS  
Buprenorphine sublingual Controlled Drug
Buprenorphine patches Controlled Drug. Buprenorphine Transdermal Patches (preferred brands BuTec® & Sevodyne®). Palliative care teams may recommend use of Transtec® in a small number of patients.Transtec® is licensed for moderate to severe chronic cancer pain and severe pain unresponsive to non-opioid analgesics.
Diamorphine Controlled Drug
Fentanyl patches Controlled Drug. Fentanyl should be prescribed by brand (formulary choice patch is Matrifen® or Mezolar®). It can be used in dysphagia, intractable nausea/vomiting, or persistent adverse effects from morphine / oxycodone / diamorphine (e.g. severe constipation, nausea, drowsiness).   Fentanyl patches must not be prescribed for patients with unstable opioid requirements. The BNF suggests that the following 24-hour doses of oral morphine are approximately equivalent to fentanyl patches: morphine salt 45mg daily = fentanyl “12” patch, morphine salt 90mg daily = fentanyl “25” patch, morphine salt 180mg daily = fentanyl “50” patch, morphine salt 270mg daily = fentanyl “75” patch and morphine salt 360mg daily = fentanyl “100” patch. 
Hydromorphone Controlled Drug
Methadone Controlled Drug
Morphine Controlled Drug
Oxycodone

Controlled Drug.Oxycodone has a similar analgesic effect profile to morphine and should ONLY to be used for genuine persistent morphine-intolerance (this will apply to a very SMALL proportion of patients). To convert from morphine to oxycodone divide total daily dose of morphine by 2, then divide by 6 to give 4hrly dose (e.g. 240mg morphine daily = 120mg oxycodone daily = 20mg oxycodone 4hourly). Start with Oxycodone Normal Release (preferred brand is Shortec®) and once pain stabilised (usually after 1 – 2 weeks) convert to Slow Release Oxycodone (preferred brand in primary care is Longtec®) plus Oxycodone Normal Release for breakthrough pain. 

Oxycodone/naloxone prolonged release

Controlled Drug. Initiated by Chronic Pain Team under the direction of a consultant. Hospital/specialist prescribing only. Only for patients who have failed on morphine and a laxative, only to its maximum licensed dose without additional oxycodone.

Pethidine Controlled Drug
Tapentadol prolonged release

Controlled Drug. For recommendation by Chronic Pain Team.

BNF 4.7.3 Neuropathic and functional pain

All neuropathic pain (except trigeminal neuralgia)

Offer one of the following. If the initial treatment is not effective or is not tolerated, offer one of the other drugs; consider switching again if the second and third drugs are also not effective or not tolerated. NICE CG173

Amitriptyline

Unlicensed indication

Duloxetine

 

Gabapentin

 

Nortriptyline

Unlicensed indication

Pregabalin

 

Consider capsaicin 0.075% cream or capsaicin 8% patch (BNF 10.3.2) for people with localised neuropathic pain who wish to avoid or who cannot tolerate oral treatments. 

Trigeminal neuralgia

Offer carbamazepine as initial therapy; if it is not effective, not tolerated or contra-indicated, consider seeking expert advice from a specialist.  

BNF 4.7.4.1 Treatment of the acute migraine attack

ADULTS: Acute treatment of migraine  

Combination therapy

oral triptan and an NSAID, or an oral triptan and paracetamol  

Sumatriptan oral is suitable for most people.

Zolmitriptan oral, naratriptan oral and rizatriptan oral are alternatives.

If vomiting restricts oral treatment, consider a non-oral formulation (such as zolmitriptan nasal spray or subcutaneous sumatriptan). ‘Melt' preparations which dissolve on the tongue are absorbed after swallowing and are not classified as non-oral preparations

Monotherapy  

If monotherapy is preferred: Oral triptan, or oral NSAID, or aspirin (900 mg every 4–6 hours when necessary up to a maximum of 4 g daily), or paracetamol

Analgesic with anti-emetic  

Consider adding an anti-emetic (such as metoclopramide, domperidone, or prochlorperazine) even in the absence of nausea and vomiting.

Combination analgesics with anti-emetics are available, taken as an oral solution, such as MigraMax®(lysine acetylsalicylate and metoclopramide) and Paramax®(paracetamol and metoclopramide). If vomiting restricts oral treatment, consider a non-oral anti-emetic preparation such as domperidone suppositories, or a buccal preparation such as Buccastem®.

Metoclopramide — treatment is not recommended for longer than 5 days.

Domperidone — treatment is not recommended for longer than one week (maximum of 10 mg three times a day).  

Young people: symptomatic relief of acute attacks

Prescribe simple analgesia (paracetamol or ibuprofen) for most children with migraine.

For young people aged 12–17 years, offer combination therapy with nasal sumatriptan and a non-steroidal anti-inflammatory drug (NSAID), or nasal sumatriptan and paracetamol.

Oral triptans are not licensed for use in people under the age of 18 years.

Non-oral preparations of prochlorperazine and metoclopramide are licensed in children older than 12 years of age.  

Breastfeeding

What is the preferred triptan for the treatment of migraine in breastfeeding mothers? https://www.sps.nhs.uk/articles/what-is-the-preferred-triptan-for-the-treatment-of-migraine-in-breastfeeding-mothers/  

For further information see Clinical Knowledge Summaries Migraine 

BNF 4.7.4.2 Prophylaxis of migraine

Pizotifen

 

Propranolol or metoprolol

LINK to section 2.4 for preparations

Botulinum toxin type A  NICE guidance (Migraine chronic - botulinum toxin type A) NICE TA260

BNF 4.7.4.3 Cluster headache

The following recommendation is based on Clinical Knowledge Summaries Headache - Cluster

Management of cluster headache

For acute treatment of confirmed cluster headache. For people aged over 18 years of age, options include:

Arrange provision of home and ambulatory oxygen therapy.

GPs should not order oxygen for cluster headache. A patient that requires home oxygen must be referred to the HOSAR (Home Oxygen Service Assessment and Review) for oxygen assessment and arrangements for supply. The HOSAR will only accept a Cluster Headache referral if the patient has been seen by a Consultant Neurologist and oxygen requested by them.

Do NOT offer paracetamol, aspirin, nonsteroidal anti-inflammatory drugs (NSAIDs), ergot, or oral triptans for the acute treatment of cluster headache.


BNF 4.8.1 Control of epilepsy

NICE CG137

NICE CG137: The epilepsies: pharmacological treatment by epilepsy syndrome

CONTRACEPTION: The Faculty of Family Planning and Reproductive Health Centre (FFPRHC) Clinical Effectiveness Unit holds evidence-based guidance on the risk of interactions with oral contraceptives

The MHRA issued advice in November 2013 regarding the equivalence of antiepileptic medication products, and which drugs should be prescribed by brand name. This information is included by drug name within this section. [Drug Safety Update Volume 7 Issue 4 November 2013]

BRIVARACETAM

Brivaracetam oral: For initiation by neurologist and continuation in primary care with RICaD

Brivaracetam RICaD

CARBAMAZEPINE

Ensure patient is maintained on specific manufacturer's product (MHRA 2013)

Offer controlled release carbamazepine products (NICE Clinical Guideline 137, 2012)

Carbamazepine is an inducer of hepatic enzymes and may reduce the activity of the hormones contained in the combined oral contraceptive pill. Patients requiring an oral contraceptive should be prescribed a preparation containing not less than 50mcg oestrogen (FFPRHC 2012).  

Carbamazepine Safety Monitoring Parameter
Action required if abnormal results Additional notes
Baseline At initiation Maintenance
FBC, U+Es, LFTs
Patients of Han Chinese, Hong Kong Chinese, or Thai origin should be screened for HLA-B*1502 before prescription of carbamazepine
FBC, U&Es, LFTs periodically  FBC, U+Es, LFTs
NICE suggest that in epilepsy FBC, U&Es, liver enzymes, Vitamin D levels, and other tests of bone metabolism every 2-5 years for adults taking enzyme-inducing drugs  
Treatment should be discontinued if leucopenia develops that is severe, progressive or accompanied by clinical manifestations (e.g. fever or sore throat), or if any evidence of significant bone marrow depression.
Patients who test positive for HLA-B*1502 should not start carbamazepine unless the benefits clearly outweigh the risk of Stevens-Johnson syndrome.
Patients/carers should be told how to recognise signs of blood, liver, or skin disorders and advised to seek immediate medical attention if symptoms such as fever, sore throat, rash, mouth ulcers, bruising or bleeding develop.
Withdraw treatment immediately in cases of aggravated liver dysfunction or acute liver disease.  
Patients should be warned to monitor for clinical symptoms of neutropenia to immediately report any rash that is accompanied by fever/malaise.
Target plasma level in epilepsy 4-12mg/L.
Monitoring levels in patients with epilepsy should NOT be routinely performed unless to assess adherence or suspected toxicity.  

References:
SPC Tegretol tablets Jun 2014
NICE Clinical Guideline CG137 (The epilepsies: diagnosis and management of the epilepsies in adults in primary and secondary care) (2012)

CLOBAZAM

The need for continued supply of a particular manufacturer's product should be based on clinical judgement and consultation with the patient and/or carer, taking into account factors such as seizure frequency and treatment history (MHRA 2013).
Prescriptions for clobazam should be endorsed “SLS”.
No specific monitoring recommended.  

CLONAZEPAM

The need for continued supply of a particular manufacturer's product should be based on clinical judgement and consultation with the patient and/or carer, taking into account factors such as seizure frequency and treatment history (MHRA 2013).
No specific monitoring recommended.
Clonazepam is a benzodiazepine derivative; withdrawal may be associated with physiological and psychological symptoms.

ESLICARBAZEPINE

For initiation by specialist with continuation in primary care with RICaD. Use in patients <6 years of age is unlicensed.

Eslicarbazepine RICaD

The need for continued supply of a particular manufacturer's product should be based on clinical judgement and consultation with the patient and/or carer, taking into account factors such as seizure frequency and treatment history (MHRA 2013).

In accordance with Epilepsies: diagnosis and management NICE CG137  

ETHOSUXIMIDE

It is usually unnecessary to ensure that patients are maintained on a specific manufacturer's product unless there are specific reasons such as patient anxiety and risk of confusion or dosing errors (MHRA 2013).  

Ethosuximide Safety Monitoring Parameter
Action required if abnormal results Additional notes
Baseline At initiation Maintenance
FBC, U+Es, LFTs
FBC, U&Es, LFTs periodically  U+Es, LFTs periodically
WCC if symptoms or signs of infection 
Stop treatment if leucopenia severe, progressive or accompanied by clinical manifestations e.g. fevers or sore throat  Effective plasma levels normally between 40-100 mcg/ml; clinical response should be the criteria for regulation of dosage 

References:
SPC Emeside® syrup February 2014
SPC Zarontin® syrup August 2014

GABAPENTIN

It is usually unnecessary to ensure that patients are maintained on a specific manufacturer's product unless there are specific reasons such as patient anxiety and risk of confusion or dosing errors (MHRA 2013).
No specific monitoring recommended.
Avoid abrupt withdrawal; withdrawn gradually over a minimum of 1 week (SPC Neurontin® 2014)  

LACOSAMIDE

It is usually unnecessary to ensure that patients are maintained on a specific manufacturer's product unless there are specific reasons such as patient anxiety and risk of confusion or dosing errors (MHRA 2013).
No specific monitoring recommended.
Suitable for primary care prescribing following specialist advice  

LAMOTRIGINE

The need for continued supply of a particular manufacturer's product should be based on clinical judgement and consultation with the patient and/or carer, taking into account factors such as seizure frequency and treatment history (MHRA 2013).
No specific monitoring recommended. CSM has advised prescribers to be alert for signs and symptoms suggestive of bone marrow failure e.g. anaemia, bruising and infection
Warn patients to see their doctor immediately if rash or signs or symptoms of hypersensitivity syndrome develop
Unless safety concerns (for example rash) require abrupt withdrawal, the dose should be gradually decreased over a minimum of two weeks.

LEVETIRACETAM

It is usually unnecessary to ensure that patients are maintained on a specific manufacturer's product unless there are specific reasons such as patient anxiety and risk of confusion or dosing errors (MHRA 2013).  

Levetiracetam Safety Monitoring Parameter
Action required if abnormal results Additional notes
Baseline At initiation Maintenance
U&Es and LFTs as dosage adjustment may be necessary if renal or hepatic impairment
U&Es and LFTs U&Es and LFTs regularly, frequency based on co-morbidities and other medicines prescribed.   Dosage adjustment/ withdraw medication.   Avoid abrupt withdrawal. 

References:
SPC Keppra® January 2014
BNF October 2014

OXCARBAZEPINE

Reserved for use by the neurologists and paediatricians only.
The need for continued supply of a particular manufacturer's product should be based on clinical judgement and consultation with the patient and/or carer, taking into account factors such as seizure frequency and treatment history (MHRA 2013).
Oxcarbazepine is an inducer of hepatic enzymes and may reduce the activity of the hormones contained in the combined oral contraceptive pill. Additional non-hormonal forms of contraception are recommended when taking oxcarbazepine (FFPRHC 2012).  

Oxcarbazepine Safety Monitoring Parameter
Action required if abnormal results Additional notes
Baseline At initiation Maintenance
Serum sodium level
Serum sodium level after 2 weeks  Serum sodium levels at monthly intervals for the first three months, or according to clinical need.  If hyponatraemia is observed, water restriction is an important counter-measurement.
If abnormal liver function, evaluate and consider stopping oxcarbazepine.
Leucopenia – severe, progressive or accompanied by clinical manifestations e.g. fever or sore throat; consider stopping oxcarbazepine  
All patients with cardiac insufficiency and secondary heart failure should have regular weight measurements - if fluid retention or worsening of the cardiac condition, serum sodium should be checked.
Oxcarbazepine may, very rarely, lead to impairment of cardiac conduction, patients with pre-existing conduction disturbances (e.g. atrioventricular-block, arrhythmia) should be followed carefully.
Patients who develop a skin reaction should be promptly evaluated and oxcarbazepine withdrawn immediately unless the rash is clearly not drug related. The median time to onset of rash in trials was 19 days.  

References:
SPC Trileptal® August 2013

PERAMPANEL

Specialist initiaion with continuation in primary care with RICaD Perampanel RICaD
The need for continued supply of a particular manufacturer's product should be based on clinical judgement and consultation with the patient and/or carer, taking into account factors such as seizure frequency and treatment history (MHRA 2013).  

PHENOBARBITAL

Ensure patient is maintained on specific manufacturer's product (MHRA 2013).
No monitoring of drug levels required to optimise or to monitor treatment.
Prescriptions for phenobarbital (phenobarbitone) must comply with the following legal requirements:

PHENYTOIN

Ensure patient is maintained on specific manufacturer's product (MHRA 2013).
Changes in dosage should not be carried out at intervals shorter than 7 to 10 days.  

Phenytoin Safety Monitoring Parameter
Action required if abnormal results Additional notes
Baseline At initiation Maintenance
LFTs and FBC
Frequent FBC throughout treatment but BNF states that evidence of practical value is unsatisfactory   Frequent FBC throughout treatment but BNF states that practical value is unsatisfactory.
NICE suggest FBC, U&Es, liver enzymes, vitamin D levels, and other tests of bone metabolism every 2-5 years for adults taking enzyme-inducing drugs.
SIGN suggest that liver function and full blood count should not be monitored routinely.
Serum folate at least 6 monthly.
Leucopenia, which is severe, progressive, or associated with clinical symptoms requires withdrawal (if necessary under cover of suitable alternative).
Folic acid supplements to be initiated where necessary.  
Therapeutic serum level 10-20μg/ml although some cases of tonic clonic seizures may be controlled with lower serum levels.
Drug monitoring in patients with epilepsy should NOT be routinely performed unless to assess adherence or suspected toxicity or after adjustment of phenytoin dose. However where monitoring is felt to be necessary, dosage should be adjusted according to serum levels where assay facilities exist.
Phenytoin is highly protein bound and where protein binding is reduced, as in uraemia, total phenytoin levels will be reduced accordingly. Under these circumstances therapeutic control may be achieved with total phenytoin levels below the normal range. Patients with impaired liver function, elderly patients or those who are gravely ill may show early signs of toxicity.
Phenytoin may cause slight decrease in serum levels of total and free thyroxine, but levels of circulating TSH are not affected, therefore the latter can be used for diagnosis of hypothyroidism in a patient on phenytoin.
Phenytoin may affect blood sugar metabolism tests (no additional data provided).
Patients/carers should be told how to recognise signs of blood or skin disorders.  

References:
Epanutin capsules SPC (revised March 2012)
NICE Clinical Guideline CG137 (The epilepsies: diagnosis and management of the epilepsies in adults in primary and secondary care) (2012)
BNF Issue 65
SIGN Guideline No 70- Diagnosis and management of epilepsy in adults (April 2003 update 2005)

 

PREGABALIN

It is usually unnecessary to ensure that patients are maintained on a specific manufacturer's product unless there are specific reasons such as patient anxiety and risk of confusion or dosing errors (MHRA 2013).
Suitable for primary care prescribing following initiation by neurologists or paediatricians only.
No specific monitoring recommended. Dosage reduction, discontinuation, or substitution of alternative medication, should be done gradually over a minimum of one week.  

PRIMIDONE

Ensure patient is maintained on specific manufacturer's product (MHRA 2013).
No monitoring of drug levels required to optimise or to monitor treatment.  

RUFINAMIDE

The need for continued supply of a particular manufacturer's product should be based on clinical judgement and consultation with the patient and/or carer, taking into account factors such as seizure frequency and treatment history (MHRA 2013).
Baseline measurement of liver function is recommended because caution and careful dose titration are advisable when treating patients with mild to moderate hepatic impairment (MTRAC 2009)  

SODIUM VALPROATE

Valproate medicines (Epilim▼, Depakote▼): contraindicated in women and girls of childbearing potential unless conditions of Pregnancy Prevention Programme are met (MHRA 2018) 

The need for continued supply of a particular manufacturer's product should be based on clinical judgement and consultation with the patient and/or carer, taking into account factors such as seizure frequency and treatment history (MHRA 2013). 

Sodium valproate Safety Monitoring Parameter
Action required if abnormal results Additional notes
Baseline At initiation Maintenance
LFTs
Blood tests (blood cell count, including platelet count, bleeding time and coagulation tests) are recommended.
Should not be started in women of childbearing potential without specialist neurological advice.   LFTs and PT periodically within first 6 months of treatment.
Blood cell count, including platelet count, bleeding time and coagulation tests are recommended before surgery, and in cases of spontaneous bruising or bleeding. 
If abnormal liver function or blood dyscrasia is detected the drug should be stopped immediately.   Spontaneous bruising or bleeding is an indication for the withdrawal of medication pending investigation.
Avoid sudden withdrawal to minimise potential for increased seizure frequency.
Therapeutic drug monitoring is of little value unless toxicity is suspected.  

References:
SPC Epilim® February 2014
NICE Clinical Guideline 137: The epilepsies: diagnosis and management of the epilepsies in adults in primary and secondary care (January 2012; last modified: December 2013)

TIAGABINE

It is usually unnecessary to ensure that patients are maintained on a specific manufacturer's product unless there are specific reasons such as patient anxiety and risk of confusion or dosing errors (MHRA 2013).  

Tiagabine Safety Monitoring Parameter
Action required if abnormal results Additional notes
Baseline At initiation Maintenance
LFTs
  If bruising is observed full blood count, including platelet count is to be performed.  Reduce dosage/ dose frequency in hepatic impairment.  Recommended to taper off treatment over a period of 2-3 weeks.
If visual symptoms develop, the patient should be referred to an ophthalmologist for further evaluation including perimetry.  

References:
SPC Gabitril® June 2014

TOPIRAMATE

The need for continued supply of a particular manufacturer's product should be based on clinical judgement and consultation with the patient and/or carer, taking into account factors such as seizure frequency and treatment history (MHRA 2013).
Topiramate is an inducer of hepatic enzymes and may reduce the activity of the hormones contained in the combined oral contraceptive pill. Patients requiring an oral contraceptive should be prescribed a preparation containing not less than 50mcg oestrogen (FFPRHC 2012).  

Topiramate Safety Monitoring Parameter
Action required if abnormal results Additional notes
Baseline At initiation Maintenance
U+Es, LFTs
Should not be started in women of childbearing potential without specialist neurological advice.  U+Es, LFTs  Reduce dosage in hepatic and/or renal impairment.  Adequate hydration is recommended, decreasing risk of renal stone formation.
Acute onset of decreased visual acuity and/or ocular pain, consider topiramate-induced acute myopia associated with secondary angle closure glaucoma.
No monitoring of drug levels required to optimise or to monitor treatment.
Withdraw drug gradually to minimise potential for increased seizure frequency.  

References:
SPC Topamax® September 2013

VIGABATRIN

It is usually unnecessary to ensure that patients are maintained on a specific manufacturer's product unless there are specific reasons such as patient anxiety and risk of confusion or dosing errors (MHRA).
Suitable for prescribing in primary care only following specialist initiation (SPC Sabril® July 2014).
Sedation, fatigue and weight gain are common.  

Vigabatrin Safety Monitoring Parameter
Action required if abnormal results Additional notes
Baseline/ initiation Maintenance
Specialist initiation only by a neurologist.
Ophthalmological consultation with visual field examination required before initiation.  
Visual field testing (perimetry) by use of standardised static perimetry (Humphrey or Octopus) or kinetic perimetry (Goldmann) to be performed at 6mth intervals throughout treatment.
Electroretinography may be useful in adults unable to co-operate with perimetry.
Serum creatinine periodically.  
Refer all patients to a specialist if visual symptoms develop.
Since vigabatrin is eliminated via the kidney, caution should be exercised in patients with a creatinine clearance of less than 60ml/min and in elderly patients. These patients should be monitored closely for undesirable effects such as sedation and confusion.  
Vigabatrin is associated with visual field defects. The onset of symptoms varies from 1 month to several years after starting. In most cases, visual field defects have persisted despite discontinuation, and further deterioration after discontinuation cannot be excluded. Patients should be warned to report any new visual symptoms that develop and those with symptoms should be referred for an urgent ophthalmological opinion.
Patients should be closely observed for adverse effects on neurological function.
Withdraw drug gradually to minimise potential for increased seizure frequency.  

References:
SPC Sabril® July 2014 plus BNF November 2014 on-line

ZONISAMIDE

The need for continued supply of a particular manufacturer's product should be based on clinical judgement and consultation with the patient and/or carer, taking into account factors such as seizure frequency and treatment history (MHRA 2013). 

Initiated and stabilised by a specialist for three to six months, then suitable for GP prescribing for maintenance therapy. Continued follow-up in secondary care is required. MTRAC review of Zonisamide as monotherapy for partial seizures in epilepsy

Zonisamide Safety Monitoring Parameter
Action required if abnormal results Additional notes
Baseline Initiation/maintenance
U+Es & LFTs, a slower dose titration may be necessary if renal or hepatic function is impaired.
Women of childbearing potential must use adequate contraception during treatment and for one month after discontinuation.  Discuss with specialist Withdraw drug gradually to minimise potential for increased seizure frequency.
Adequate hydration is recommended, decreasing risk of renal stone formation.  

References:
SPC Zonegran® October 2013

 

BNF 4.8.2 Drugs used in status epilepticus

Diazepam rectal

 

Lorazepam injection

Prescribed by specialists only

Midazolam buccal

Please prescribe licensed product Buccolam®

Phenytoin injection

Prescribed by specialists only

BNF 4.9.1 Dopaminergic drugs used in parkinsonism

 
Apomorphine Link to Shared Care Agreement
Bromocriptine  
Cabergoline

When prescribing cabergoline:

  • monitor patients for signs of cardiac fibrosis during treatment
  • echocardiography should be done within 3–6 months of starting treatment and subsequently at 6–12-month intervals
  • Stop treatment if echocardiography shows new or worsened valvular regurgitation, valvular restriction, or valve leaflet thickening
  • Maximum daily dose of cabergoline is now restricted to 3mg/day in the treatment of Parkinson’s disease
  • Pregnancy should be excluded before administration of cabergoline
  • Women who are planning pregnancy should stop taking cabergoline 1 month before they try to conceive
Full revised safety advice is available

Carbidopa with entacapone and levodopa  Preferred brand for prescribing in primary care, Stanek®
Co-beneldopa

How do you convert from co-beneldopa (Madopar®) prolonged-release capsules to dispersible tablets?

Co-careldopa

Sinemet
Entacapone Specialist initiation only, suitable for continuation in primary care

Pergolide

Usually initiated by a Specialist.  
Pramipexole oral (immediate release) for the treatment of restless legs syndrome The recommended starting dose is 88 microgram of base (125 microgram of salt) taken once daily 2-3 hours before bedtime. For patients requiring additional symptomatic relief, the dose may be increased every 4-7 days to a maximum of 540 microgram of base (750 microgram of salt) per day (as shown in the table below). 
Dose Schedule for titration Steps 2 to 4 only if needed  
Titration Step 
Once Daily Evening Dose (microgram of base)  
Once Daily Evening Dose (microgram of salt)  
1
88 mcg
125 mcg
2
180 mcg
250 mcg
3
350 mcg
500 mcg
4
540 mcg
750 mcg

Ropinirole

 
Rotigotine transdermal patch

For Initiation by secondary care – can be continued in primary care after specialist initiation and stabilisation of the dose, if clinically appropriate.

For Parkinson’s patients who cannot receive their regular oral medication due to swallowing difficulties or ‘nil by mouth’  

Selegiline  

BNF 4.9.2 Antimuscarinic drugs used in parkinsonism 

First-line

Orphenadrine
Procyclidine

Second-line

Trihexyphenidyl (benzhexol)

BNF 4.9.3 Drugs used in essential tremor, chorea, tics and related disorders.

Haloperidol

 

Riluzole

Suitable for GP prescribing after initiation by specialist.

NICE Guidance (Motor neurone disease - riluzole) NICE TA20

Tetrabenazine

 

Torsion dystonia and other involuntary movements

Botulinum A toxin

It may also be prescribed by GPs who have acquired specialist skills in the management of focal dystonias.

BNF 4.10 Drugs used in substance dependence

Alcohol Dependence

Acamprosate

Acamprosate prescribing guidelines

Nalmefene

Community alcohol service prescribing for the first 3 months then transfer to GP prescribing for a further 9 months with the provision of on-going psychosocial support NICE TA32 . See the Nalmefene Pathway for more information.

Chlordiazepoxide

Reducing regimen

Wolverhampton Alcohol Liaison Team (Aquarius)

Contact: 07590 441 781 Email: nathan.lowe@nhs.net

Alcohol and Drug Addiction

Horizon House, Pitt Street, Wolverhampton 01902 444030

CIGARETTE SMOKING

FIRST LINE

Nicotine replacement therapy (NRT)

  • Must be prescribed in conjunction with advice and support on smoking cessation. Signpost to Wolverhampton Smoke free website.
  • See current BNF or Mims for full product range.
  • Patients may not tolerate the first preparation prescribed. Limiting the initial prescription quantity may avoid unnecessary wastage.
SECOND LINE
Bupropion

Must be prescribed in combination with motivational support as per SPC

Varenicline

Must be prescribed in line with SPC

Advice and motivational support on smoking cessation is available on Wolverhampton Smokefree website

OPIOID DEPENDENCE

Lofexidine

MTRAC Verdict (Jun96): not appropriate for prescription in general practice other than for use by experienced practitioners, and where close working relationships with the substance abuse team are established.

Methadone

NICE TA114. Initiated by Specialist.

Buprenorphine

Subutex® NICE TA114. Initiated by Specialist.

Naltrexone

NICE TA115

MTRAC Verdict (Jun01): initiated by a specialist experienced in the management of opioid dependence. Once a patient stabilised, it is appropriate for GPs with a special interest in drug misuse to prescribe over the longer term, within a framework of support provided by the community drug team.

 

Alcohol and Drug Addiction

Horizon House, Pitt Street, Wolverhampton 01902 444030

BNF 4.11 Drugs for dementia

Donepezil

 

Galantamine M/R

prescribed by brand, Gatalin XL®

Memantine

 

Rivastigmine

including patches

In Wolverhampton, patients should be referred to a psychiatrist for older age at the memory clinic, Penn Hospital, for assessment and initiation of drugs for dementia. Once the dosage is stable the patient’s General Practitioner (GP) can continue prescribing according to the Shared Care Agreement for anticholinesterase inhibitors

Prescribing should be in accordance with NICE technology appraisal guidance 217 (March 2011) ‘Donepezil, galantamine, rivastigmine and memantine for the treatment of Alzheimer’s disease (review)’. NICE TA217

The three acetylcholinesterase (AChE) inhibitors donepezil, galantamine and rivastigmine are recommended as options for managing mild to moderate Alzheimer’s disease. Memantine is recommended as an option for managing Alzheimer’s disease for people with moderate Alzheimer’s disease who are intolerant of or have a contraindication to AChE inhibitors or severe Alzheimer’s disease.