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4: Central nervous system Please select a topic: 4.1 Hypnotics and anxiolytics 4.3 Antidepressant drugs 4.5 Drugs used in obesity 4.6 Drugs used in nausea and vertigo 4.2 Drugs used in psychoses and related disorders 4.4 Central nervous system stimulants 4.7 Analgesics 4.9 Drugs used in parkinsonism and related 4.8 Antiepileptics disorders 4.10 Drugs used in substance dependence 4.11 Drugs for dementia Red = Hospital use only Green = GP & Hospital use. Drugs not classified as Red, Amber or Amber 2 are classified as Green by default Amber 1 = Drugs with shared care agreement Amber 2 = Initiated by Hospital specialist only Gateshead Health NHS Foundation Trust Drug Formulary Page 1 of 41 Date: 17.4.2013 4. Antidepressants - swapping and stopping General Guidelines All antidepressants have the potential to cause withdrawal phenomena. When taken continuously for six weeks or longer, antidepressants should not be stopped abruptly unless a serious adverse event has occurred (e.g. cardiac arrhythmia with a tricyclic). When swapping from one antidepressant to another, abrupt withdrawal should usually be avoided. Cross-tapering is preferred, where the dose of the ineffective or poorly tolerated drug is slowly reduced while the new drug is slowly introduced. The speed of cross-tapering is best judged by monitoring patient tolerability. No clear guidelines are available, so caution is required. Note that the co-administration of some antidepressants is absolutely contra-indicated, and even cross-tapering of small doses can be dangerous. In other cases, theoretical risks or lack of experience preclude recommending cross-tapering. In some cases cross-tapering may not be considered necessary. An example is when switching from one SSRI to another: their effects are so similar that administration of the second drug is likely to ameliorate withdrawal effects of the first. However, there is little firm evidence of this occurring. Potential dangers of simultaneously administering two antidepressants include pharmacodynamic interactions (serotonin syndrome, hypotension, drowsiness) and pharmacokinetic interactions (e.g. elevation of tricyclic plasma levels by some SSRIs). The serotonin syndrome may include restlessness, diaphoresis, tremor, shivering, myoclonus, confusion, convulsions and death. The advice given in the following table should be treated with caution and patients should be very carefully monitored when switching. ANTIDEPRESSANTS – SWAPPING AND STOPPING To From MAOIshydrazines Fluoxetine Paroxetine Withdraw and wait for two weeks Citalopram / Escitalopram Withdraw and wait for two weeks Withdraw and wait for two weeks Withdraw and wait for two weeks Withdraw and wait for two weeks Withdraw and wait for two weeks Withdraw and wait for two weeks Withdraw and wait for two weeks Withdraw and wait for two weeks Cross taper cautiously Halve dose and add citalopram then slow Halve dose and add fluoxetine then slow Halve dose and add paroxetine then slow Withdraw and wait for one week Withdraw and wait for two weeks Withdraw and wait for one week Withdraw and wait for one week Fluoxetine Withdraw and wait five to six weeks Withdraw and wait five to six weeks Sertraline Withdraw and wait for one Withdraw and wait for one week Tranylcypromine Tricyclics Citalopram/ Escitalopram Paroxetine *3 MAOIshydrazines Withdraw and wait for two weeks Withdraw and wait for two weeks Withdraw and wait for two weeks Tranylcypromine Withdraw and wait for two weeks - Tricyclics 1 week *2 *2 *2 withdrawal. withdrawal. withdrawal. Cross taper cautiously - Withdraw then start fluoxetine 10mg/day Cross taper cautiously with very low dose of Withdraw and start citalopram at 10mg/day Withdraw then start fluoxetine at 10mg/day Withdraw and start paroxetine at 10mg/day - Stop fluoxetine. Wait 47days. Start tricyclic at very low dose and increase very slowly Stop fluoxetine. Wait 4-7 days. Start citalopram at 10mg/day and increase slowly - Stop fluoxetine. Wait 4-7 days, then start paroxetine 10mg/day Cross taper cautiously with very low dose of Withdraw then start citalopram at 10mg/day Withdraw then start fluoxetine at 10mg/day Withdraw then start paroxetine at 10mg/day *2 *2 tricyclic *2 tricyclic Red = Hospital use only Green = GP & Hospital use. Drugs not classified as Red, Amber or Amber 2 are classified as Green by default Amber 1 = Drugs with shared care agreement Amber 2 = Initiated by Hospital specialist only Gateshead Health NHS Foundation Trust Drug Formulary Page 2 of 41 Date: 17.4.2013 To From MAOIshydrazines Tranylcypromine Tricyclics Sertraline Trazodone Moclobemide Reboxetine Venlafaxine Mirtazapine Duloxetine Withdraw and wait for two weeks Withdraw and wait for two weeks Withdraw and wait for two Withdraw and wait for two weeks Withdraw and wait for two weeks Withdraw and wait for two weeks Withdraw and wait for two weeks Withdraw and wait for two weeks Withdraw and wait for two weeks Withdraw and wait for two weeks Withdraw and wait for two weeks Withdraw and wait for two weeks Withdraw and wait for two weeks Halve dose and add sertraline then slow Halve dose and add trazodone then slow withdrawal. Cross taper cautiously Cross taper cautiously, starting with venlafaxine 37.5mg/day Withdraw. Start venlafaxine 37.5mg/day. Increase very slowly Withdraw paroxetine. Start venlafaxine 37.5mg/day and increase very slowly Withdraw. Wait 4-7 days. Start venlafaxine at 37.5mg/day. Increase very slowly Withdraw. Start venlafaxine at 37.5mg/day. Increase V slowly Cross taper cautiously Cross taper cautiously, starting with duloxetine 30mg per day. Increasing slowly Abrupt switch possible.Start duloxetine at 60mg per day. *2 withdrawal. *1 weeks Withdraw and wait for two *1 weeks Withdraw and wait for one week Citalopram/ Escitalopram Withdraw and start sertraline at 25mg/day Withdraw before starting titration of trazodone Withdraw and wait at least one week Cross taper cautiously Paroxetine Withdraw and start sertraline at 25mg/day Withdraw before starting titration of trazodone Withdraw and wait at least two weeks Cross taper cautiously Fluoxetine Stop fluoxetine. Wait 4-7 days, then start sertraline 25mg/day Stop fluoxetine. Wait 4-7 days, then start low dose trazodone Withdraw and wait at least five weeks Cross taper cautiously Sertraline - Withdraw before starting trazodone Withdraw and wait at least one week Cross taper cautiously *3 Cross taper cautiously Cross taper cautiously Abrupt switch possible.Start duloxetine at 60mg per day. Cross taper cautiously Abrupt switch possible.Start duloxetine at 60mg per day. Cross taper cautiously Abrupt switch possible.Start duloxetine at 60mg per day. *1. Abrupt switching is possible but not recommended. *2. Do not co-administer clomipramine and SSRIs or venlafaxine. Withdraw clomipramine before starting. *3. Beware interactions with fluoxetine may still occur for five weeks after stopping fluoxetine because of long half-life. *5. Withdrawal effects seem to be more pronounced. Slow withdrawal over 1-3 months may be necessary. th Adapted from: Taylor D, Paton C, and Kapur S. The Maudsley Prescribing Guidelines, 11 ed. London: Informa Healthcare, 2012 Red = Hospital use only Green = GP & Hospital use. Drugs not classified as Red, Amber or Amber 2 are classified as Green by default Amber 1 = Drugs with shared care agreement Amber 2 = Initiated by Hospital specialist only Gateshead Health NHS Foundation Trust Drug Formulary Page 3 of 41 Date: 17.4.2013 To From Trazodone MAOIshydrazines Withdraw and wait at least one week Tranylcypromine Withdraw and wait at least one week Moclobemide Withdraw and wait 24 hours Withdraw and wait at least one week Withdraw and wait at least one week Withdraw and wait 24 hours Withdraw and wait at least one week Withdraw and wait at least one week Reboxetine Venlafaxine Tricyclics Citalopram /Escitalopram Withdraw then start citalopram at 10mg/day Fluoxetine Paroxetine Withdraw then start fluoxetine at 10mg/day Withdraw then start paroxetine at 10mg/day Withdraw and wait 24 hours Cross taper cautiously Withdraw and wait 24 hours Cross taper cautiously Withdraw and wait 24 hours Cross taper cautiously Cross taper cautiously. Start with 10mg/day Cross taper cautiously. Start with 10mg/day Cross taper cautiously. Start with 10mg/day of tricyclic Withdraw then start tricyclic Withdraw then start citalopram Withdraw then start fluoxetine Withdraw then start paroxetine Cross taper cautiously with very low dose Withdraw then start citalopram at 10mg per day Withdraw then start fluoxetine Withdraw then start paroxetine Reduce over four weeks At 20mg/day just stop. At higher doses reduce over two weeks Reduce over four weeks or longer, if Cross taper cautiously with very low dose of tricyclic Withdraw and wait 24 hours Cross taper cautiously Cross taper cautiously with very low dose *2 Mirtazapine Duloxetine Withdraw and wait for two weeks Withdraw and wait for at least 5 days Withdraw and wait for two weeks Withdraw and wait for at least 5 days *2 *4 Reduce over four weeks Stopping Reduce over four weeks of tricyclic Reduce over four weeks *5 necessary To From Trazodone Sertraline Trazodone Moclobemide Reboxetine Venlafaxine Mirtazapine Duloxetine Withdraw then start sertraline at 25mg/day - Withdraw and wait at least one week Cross taper cautiously Withdraw . Start venlafaxine at 37.5mg/day Cross taper cautiously Cross taper cautiously .Start duloxetine at 30mg per day. Moclobemide Withdraw and wait 24 hours Cross taper cautiously Withdraw and wait 24 hours Cross taper cautiously - Withdraw and wait 24 hours - Withdraw and wait 24 hours Cross taper cautiously Withdraw and wait 24 hours Cross taper cautiously Withdraw and wait 24 hours Cross taper cautiously Venlafaxine Cross taper cautiously. Start with 25mg/day Cross taper cautiously Cross taper cautiously - Withdraw before starting mirtazapine cautiously Mirtazapine Withdraw then start sertraline Withdraw then start trazodone Withdraw and wait one week Cross taper cautiously Cross taper cautiously - Duloxetine Withdraw then start sertraline at 25mg/day Reduce over four weeks Withdraw then start trazodone Withdraw and wait one week Cross taper cautiously Cross taper cautiously Reduce over four weeks Reduce over four weeks Reduce over four weeks Withdraw, then start venlafaxine Reduce over four weeks or longer, if Withdraw. Start duloxetine 30mg/day. Increase very slowly. Withdraw. Start duloxetine 30mg/day. Increase very slowly. - Reboxetine *4 Stopping Withdraw and wait at least one week Withdraw and wait at least one week Reduce over four weeks Reduce over four weeks *5 necessary Red = Hospital use only Green = GP & Hospital use. Drugs not classified as Red, Amber or Amber 2 are classified as Green by default Amber 1 = Drugs with shared care agreement Amber 2 = Initiated by Hospital specialist only Gateshead Health NHS Foundation Trust Drug Formulary Page 4 of 41 Date: 17.4.2013 4.1 Hypnotics and anxiolytics Hypnotics Chloral Hydrate 500mg/5ml solution (unlicensed) Clomethiazole/Chlormethiazole 192mg capsule Chloral betaine (Cloral betaine) 707mg tablets Nitrazepam 2.5mg/5ml suspension Nitrazepam 5mg tablets Temazepam 10mg, 20mg tablets Temazepam 10mg/5ml oral solution Zopiclone 3.75mg and 7.5mg tablets (Critical care and Mental Health Only) Dose - Chloral hydrate oral solution 500mg/5ml: see BNF. Clomethiazole capsule 192mg; usually 1-2 capsules at bedtime Cloral betaine tablets 707mg: usually 1-2 tablets at bedtime. Nitrazepam tablets 5mg; oral solution 2.5mg/5mL: usually 5-10mg at bedtime Temazepam tablets 10mg, 20mg; oral solution 10mg/5mL: usually 10-20mg at bedtime. Prescribing notes Non-drug treatments are recommended as 1st line therapy Routine prescribing for insomnia is undesirable and should be used in short courses only when insomnia is severe, disabling, or subjecting the individual to extreme distress. New patients should not be put on a repeat prescription system and existing patients receiving an hypnotic should be reviewed and offered the chance to stop or reduce (see BNF withdrawal protocol). There is no evidence that never hypnotics (zaleplon, zolpidem, zopiclone) provide any additional clinical benefit or a free from dependence. Anxiolytics Buspirone 5mg tablets (Mental health only) Chlordiazepoxide 5mg and 10mg capsules Diazepam 2mg, 5mg tablets Diazepam 2mg/5ml, 5mg/5ml syrup Diazepam 5mg/ml injection Lorazepam 1mg, 2.5mg tablets Lorazepam 4mg/ml injection Red = Hospital use only Green = GP & Hospital use. Drugs not classified as Red, Amber or Amber 2 are classified as Green by default Amber 1 = Drugs with shared care agreement Amber 2 = Initiated by Hospital specialist only Gateshead Health NHS Foundation Trust Drug Formulary Page 5 of 41 Date: 17.4.2013 Dose - Buspirone tablets 5mg: 5mg 2-3 times daily increased if necessary to max 45mg daily in divided doses. Chlordiazepoxide tablets 5mg, 10mg; capsules 10mg: For Anxiety: 10mg 3 times daily increased if necessary to 60-100mg daily in divided doses. Diazepam tablets 2mg, 5mg; oral solution 2mg/5mL: 2mg 3 times daily increased if necessary to 15-30mg daily in divided doses. Lorazepam tablets 1mg, 2.5mg; injection 4mg/ml: By mouth: 1-4mg daily in divided doses. Injection: see BNF. Prescribing notes Benzodiazepines are indicated for the short-term relief (2-4 weeks only) of anxiety that is severe, disabling or subjecting the individual to unacceptable distress. The use of benzodiazepines benzodiazepines to treat short-term "mild" anxiety is inappropriate and unsuitable. Treatment should be limited to the lowest dose possible for the shortest possible time. Diazepam has a long duration of action and rapid onset. It is the recommended daytime anxiolytic and is used as premedication before surgery and other procedures. Older Patients - Hypnotics and anxiolytics Hypnotics and anxiolytics should be avoided in older patients if possible. Older patients can become ataxic, confused and are at increased risk of falling and injuring themselves. MHRA Drug Safety Update Addiction to benzodiazepines and codeine: supporting safer use Article date: July 2011 Summary Reminder for healthcare professionals: Given the risks associated with the use of benzodiazepines, patients should be prescribed the lowest effective dose for the shortest time possible. Maximum duration of treatment should be 4 weeks, including the dose-tapering phase Over-the-counter codeine-containing medicines should be used for the short-term (3 days) treatment of acute, moderate pain which is not relieved by paracetamol, ibuprofen, or aspirin alone (see Drug Safety Update September 2009) Link: http://www.mhra.gov.uk/Safetyinformation/DrugSafetyUpdate/CON123123 Red = Hospital use only Green = GP & Hospital use. Drugs not classified as Red, Amber or Amber 2 are classified as Green by default Amber 1 = Drugs with shared care agreement Amber 2 = Initiated by Hospital specialist only Gateshead Health NHS Foundation Trust Drug Formulary Page 6 of 41 Date: 17.4.2013 4.2 Drugs used in psychoses and related disorders Antipsychotic drugs Chlorpromazine 25mg, 50mg and 100mg tablets Chlorpromazine 25mg/5ml, 100mg/5ml syrup Chlorpromazine 50mg/2ml injection Flupentixol 500 micrograms, 1mg, 3mg tablets Haloperidol 500 microgram capsule Haloperidol 1.5mg, 5mg, 10mg tablets Haloperidol 5mg/5ml oral liquid & 10mg/5ml oral liquid Haloperidol 5mg/ml injection Levomepromazine/Methotrimeprazine 25mg/ml injection - Palliative care only Levomepromazine/Methotrimeprazine 25mg tablets – Palliative care only Loxapine 25mg capsules (Unlicensed – Mental Health only) Prochlorperazine 5mg tablets & 5mg/5ml syrup Prochlorperazine 12.5mg/1ml injection Sulpiride 200mg tablets Sulpiride 200mg/5ml SF solution Trifluoperazine 1mg, 5mg tablets Trifluoperazine 1mg/5ml SF syrup Trifluperazine 5mg/5ml SF solution Zuclopenthioxol acetate 50mg/ml and 100mg/2ml injection Dose - Chlorpromazine tablets 10mg, 25mg, 50mg, 100mg; syrup 25mg/5mL, 100mg/5mL: initially 25mg 3 times daily (or 75mg at night) adjusted to response; usual maintenance dose 75-300mg daily (up to 1g daily may be required in psychoses). - Chlorpromazine injection 25mg/mL: by deep intramuscular injection (for acute symptoms), 2550mg every 6-8 hours. - Flupentixol tablets 500microgram, 1mg, 3mg: initially 3-0mg twice daily adjusted to response to max 18mg daily. - Haloperidol capsules 500micrograms; tablets 1.5mg, 5mg, 10mg, 20mg; oral liquid 1mg/mL, 2mg/mL: initially 500micrograms-3mg daily in 1-3 divided doses; in resistant schizophrenia up to 30mg daily may be needed; adjust according to response to lowest effective maintenance dose (510mg daily). - Haloperidol injection 5mg/mL, 10mg/mL: by intramuscular injection, 2-10mg 4-8 hourly according to response to total max 18mg daily; severely disturbed patients may need initial dose of up to 18mg. - Levomepromazine: for palliative care use only. - Prochlorperazine tablets 5mg:initially 12.5mg twice daily, usual maintenance dose 75-100mg daily. - Sulpiride tablets 200mg, 400mg: 0.4-2.4g daily in divided doses. Red = Hospital use only Green = GP & Hospital use. Drugs not classified as Red, Amber or Amber 2 are classified as Green by default Amber 1 = Drugs with shared care agreement Amber 2 = Initiated by Hospital specialist only Gateshead Health NHS Foundation Trust Drug Formulary Page 7 of 41 Date: 17.4.2013 - Tifluperazine tablets 1mg, 5mg; oral solution 5mg/5ml; syrup 1mg/5ml: see BNF - Zuclopenthioxol acetate injection 50mg/ml and 100mg/2ml: see BNF Atypical antipsychotics Amisulpride 50mg, 200mg tablets & 500mg/5ml oral solution Aripiprazole 5mg, 10mg, 15mg and 30mg tablets Clozapine 25mg, 100mg tablets Quetiapine 25mg, 100mg, 150mg, 200mg tablets Quetiapine MR 50mg, 200mg, 300mg, 400mg tablets – mental health only Olanzepine 2.5mg, 5mg, 7.5mg and 10mg tablets Olanzepine 5mg and 10mg VELOTABS Risperidone 0.5mg, 1mg, 2mg and 3mg tablets Risperidone 5mg/5ml liquid - Amisulpride tablets 50mg, 200mg, 400mg: acute psychotic episode, 400-800mg daily in divided doses, adjusted according to response; max 1.2g daily. Predominantly negative symptoms, 50300mg daily. Doses up to 300mg may be given once daily. - Aripiprazole tablets 5mg, 10mg, 15mg, 30mg: see BNF. - Olanzapine tablets 2.5mg, 5mg, 7.5mg, 10mg:10mg daily adjusted to usual range of 5-20mg daily. - Quetiapine tablets 25mg, 100mg, 150mg, 200mg, 300mg: (initiate with starter pack containing 6x25mg, 2x100mg and 2x150mg tablets) schizophrenia, 25mg twice daily on day 1, 50mg twice daily on day 2, 100mg twice daily on day 3, 150mg twice daily on day 4, then adjusted to response; usual range 300-450mg daily in 2 divided doses; max 750mg daily. - Risperidone tablets 500micrograms, 1mg, 2mg, 3mg, 4mg, 6mg; liquid 1mg/mL: 2mg in 1-2 divided doses on day 1 then 4mg in 1-2 divided doses on day 2 (slower titration appropriate in some patients); usual dose 4-6mg daily. Doses above 10mg/day generally have not been shown to provide additional efficacy to lower doses and may increase risk of side-effects (max 16mg/day). - Clozapine tablets 25mg, 100mg. Antipsychotic depot injections Flupentixol deconate 20mg/ml, 40mg/2ml, 50mg/0.5ml, 100mg/ml injection Fluphenazine deconate 25mg/ml, 100mg/ml injection Haloperidol deconate 50mg/ml, 100mg/ml injection Risperidone consta 25mg, 37.5mg, 50mg injection Zuclopenthixol deconate 200mg/ml, 500mg/ml injection Dose - Flupentixol decanoate oily injection 20mg/mL, 100mg/mL, 200mg/mL: test dose 20mg then after at least 7 days 20-40mg every 2-4 weeks, adjusted to response; max 400mg weekly; usual maintenance dose 50mg every 4 weeks to 300mg every 2 weeks. - Fluphenazine decanoate oily injection 25mg/mL, 100mg/mL: test dose 12.5mg (6.25mg in elderly), then, after 4-7 days, 12.5-100mg every 14-35 days, adjusted according to response. - Haloperidol decanoate oily injection 50mg/mL, 100mg/mL: initially 50mg every 4 weeks, if Red = Hospital use only Green = GP & Hospital use. Drugs not classified as Red, Amber or Amber 2 are classified as Green by default Amber 1 = Drugs with shared care agreement Amber 2 = Initiated by Hospital specialist only Gateshead Health NHS Foundation Trust Drug Formulary Page 8 of 41 Date: 17.4.2013 necessary increasing by 50mg increments to 300mg every 4 weeks; higher doses may be needed. Note: if 2-weekly administration preferred, doses should be halved. - Zuclopenthixol decanoate oily injection 200mg/mL, 500mg/mL: test dose 100mg, followed after at least 7 days by 200-500mg or more, repeated at intervals of 1-4 weeks, adjusted according to response; max 600mg weekly. - Risperidone long-acting injection 25mg, 37.5mg, 50mg (Risperdal Consta®): refer to product information. Prescribing notes Indications for antipsychotics include schizophrenia and other psychoses, mania and short-term adjunctive management of psychomotor agitation. Antipsychotics should be initiated with caution in the first episode (i.e. start with low dose), and monitored carefully due to the risk of adverse effects. Haloperidol is a high potency antipsychotic with a high incidence of extrapyramidal sideeffects; sulpiride is useful for those who cannot tolerate haloperidol. Amisulpride may increase prolactin and cause agitation and anxiety. However, it is less likely to cause hypotension, sedation, weight gain, and anticholinergic and extrapyramidal side-effects. Olanzapine can cause weight gain and sedation. Quetiapine can be sedative and can cause weight gain but is less likely to cause hyperprolactinaemia. Risperidone is associated with a dose dependent increase in extrapyramidal side-effects, especially at doses of 6mg daily and above. Risperidone orodispersible and Olanzapine orodispersible tablets should be reserved for the treatment of acute episodes of schizophrenia in patients who are uncooperative or wary of taking oral medication. They are not intended for long-term use. Clozapine should be initiated and maintained by specialists. Patients must be registered with the Clozaril Patient Monitoring Service. Clozapine can cause serious side-effects such as agranulocytosis, seizures, cardiomyopathy and myocarditis. Gastro-intestinal obstruction and paralytic ileus may also occur. Hyperglycaemia has been reported in patients treated with atypical antipsychotics. Patients with diabetes mellitus who are started on atypical antipsychotics should be monitored regularly for worsening of glucose control. Patients with risk factors for diabetes mellitus who start atypical antipsychotics should undergo fasting blood glucose testing at the beginning of, and during, treatment. Any patient receiving atypical antipsychotics should be monitored for symptoms of hyperglycaemia e.g. polydipsia, polyuria, polyphagia, weakness. Patients who develop symptoms of hyperglycaemia during treatment should undergo fasting blood glucose testing. Hyperglycaemia may resolve when the atypical antipsychotic is discontinued but some patients require continuation of anti-diabetic treatment. Patients should remain on the antipsychotic which controlled their symptoms unless symptoms return or side-effects are intolerable; the dose should be monitored and reviewed regularly with specialist advice. Specialist advice should be sought before discontinuing antipsychotics due to the risk of relapse. Red = Hospital use only Green = GP & Hospital use. Drugs not classified as Red, Amber or Amber 2 are classified as Green by default Amber 1 = Drugs with shared care agreement Amber 2 = Initiated by Hospital specialist only Gateshead Health NHS Foundation Trust Drug Formulary Page 9 of 41 Date: 17.4.2013 Depot injections should be initiated on specialist advice, for the patient's convenience or to improve compliance. They may produce more extrapyramidal reactions than oral preparations. The BNF recommends that a test dose of the depot injection should be given first since some side-effects are prolonged. Individual responses to antipsychotic depot injections are variable; treatment should be selected and titrated according to the patient's response. There is no evidence that any one depot antipsychotic is particularly suitable for a specific patient group. Risperidone is the first atypical antipsychotic to be available as a long-acting injection. The injection should only be prescribed by specialists and not by primary care. It should be considered if the following apply: the patient has experienced unacceptable sideeffects with conventional antipsychotics; the patient has responded favourably to oral risperidone but prefers a long-acting IM injection; the patient has responded favourably to an oral atypical but there are concerns about long-term compliance. Older Patients - Antipsychotics Antipsychotics are frequently prescribed in the management of behavioural disorders associated with dementia. Other forms of management should also be considered before prescribing antipsychotics. It is important to remember that such behaviour can be a temporary phenomenon and that drugs should be prescribed on a short-term basis. In the elderly, antipsychotics should be used with caution because of the side-effect profile, including extrapyramidal symptoms, sedation, anticholinergic effects, cardiovascular effects and tardive dyskinesia. MHRA Drug Safety Update Antipsychotics: initiative to reduce prescribing to older people with dementia Article date: May 2012 Summary There have been increasing concerns over recent years about the use of antipsychotics to treat the behavioural and psychological symptoms of dementia (BPSD). Antipsychotics are associated with an increased risk of cerebrovascular adverse events and greater mortality when used in this population (see Drug Safety Update, March 2009). No antipsychotic (with the exception of risperidone in some circumstances) is licensed in the UK for the treatment of BPSD; however, antipsychotics are often prescribed off-label for this purpose. Link: http://www.mhra.gov.uk/Safetyinformation/DrugSafetyUpdate/CON152729 Red = Hospital use only Green = GP & Hospital use. Drugs not classified as Red, Amber or Amber 2 are classified as Green by default Amber 1 = Drugs with shared care agreement Amber 2 = Initiated by Hospital specialist only Gateshead Health NHS Foundation Trust Drug Formulary Page 10 of 41 Date: 17.4.2013 Antimanic drugs Lithium carbonate 250mg tablets (Camcolit) - restricted Lithium carbonate 400mg m/r tablets (Camcolit) - restricted Lithium carbonate 450mg m/r tablets (Liskonum) - restricted Lithium carbonate 200mg and 400mg m/r tablets (Priadel) Lithium citrate 5.4mmol/5ml liquid (Li-Liquid and Priadel) Sodium valproate 100mg crushable tablets Sodium valproate 200mg, 500mg EC tablets Sodium valoproate 200mg, 300mg and 500mg m/r tablets Sodium valproate 200mg/5ml liquid Valporic acid 250mg and 500mg tablets (Depakote) Dose - Lithium carbonate (Priadel®) m/r tablets 200mg, 400mg; lithium citrate (Priadel®) liquid 520mg/5mL: dose is adjusted to achieve a serum lithium concentration within the therapeutic range stated for that individual patient If aiming for a different therapeutic range from the normal 0.61mmol/L, then this must be clearly communicated to the prescriber. Lithium carbonate 200mg is equivalent to lithium citrate 509mg. - Sodium valproate tablets e/c 200mg, 500mg; crushable tablets 100mg; liquid 200mg/5mL: initially, 200mg twice daily preferably after food, increasing by 200mg/day at 3-day intervals to a max of 2.5g daily in divided doses, usual maintenance 1-2g daily. - Sodium valproate tablets m/r 200mg, 300mg, 500mg: as above, total daily dose given in 1-2 divided doses - Valproic acid tablets 250mg, 500mg: initially 750mg daily in 2-3 divided doses, increased according to response, usual dose 1-2g daily. Prescribing notes Women receiving mood stabilisers must be warned to obtain pre-conceptional advice if they plan to become pregnant; the risk of relapse following withdrawal of mood stabilisers must be balanced against their established teratogenic potential which should be fully discussed with the patient. Psychiatric advice should be sought regarding the most appropriate management of individual patients. Therapy should be initiated by a specialist and only following medical examination and careful assessment of risk/benefit. Abrupt withdrawal of lithium may precipitate an episode; all mood stabilisers should be withdrawn gradually. If a patient is unlikely to be compliant, then an alternative to lithium should be considered. Different lithium preparations vary widely in lithium content and bioavailability. The brand name should therefore be specified; a change in the preparation used requires the same precautions as initiation of treatment i.e. weekly monitoring until stable. Note that nonmodified-release formulations (Camcolit 250® and lithium citrate liquid) should be given twice daily. The benefit of routine plasma drug level monitoring for sodium valproate is not firmly established but may be helpful if side-effects are a problem, or non-compliance or nonresponse are suspected. Red = Hospital use only Green = GP & Hospital use. Drugs not classified as Red, Amber or Amber 2 are classified as Green by default Amber 1 = Drugs with shared care agreement Amber 2 = Initiated by Hospital specialist only Gateshead Health NHS Foundation Trust Drug Formulary Page 11 of 41 Date: 17.4.2013 Olanzapine, carbamazepine and lamotrigine may be prescribed for the maintenance treatment of bipolar disorder. Semisodium valproate is a newer valproic acid salt licensed only for the treatment of acute mania. Red = Hospital use only Green = GP & Hospital use. Drugs not classified as Red, Amber or Amber 2 are classified as Green by default Amber 1 = Drugs with shared care agreement Amber 2 = Initiated by Hospital specialist only Gateshead Health NHS Foundation Trust Drug Formulary Page 12 of 41 Date: 17.4.2013 4.3 Antidepressant drugs Tricyclic and related antidepressant drugs Amitriptyline 10mg, 25mg, 50mg tablets Amitriptyline 25mg/5ml syrup Clomipramine 10mg, 25mg and 50mg capsules Dosulepin/Dothiepin 25mg capsules and 75mg tablets Dosulepin/Dothiepin 25mg/5ml suspension Imipramine 10mg and 25mg tablets Lofepramine 70mg tablets Lofepramine 70mg/5ml suspension Trazodone 50mg and 100mg capsules, 150mg tablets Trazodone 50mg/5ml liquid Monoamine-oxidase inhibitors Phenelzine 15mg tablets Reversible monoamine-oxidase inhibitors Moclobemide 150mg tablets Selective serotonin re-uptake inhibitors Citalopram 10mg, 20mg and 40mg tablets Citalopram 40mg/ml oral drops Fluoxetine 20mg capsules Fluoxetine 20mg/5ml liquid Paroxetine 20mg and 30mg tablets Paroxetine 10mg/5ml syrup Dose - see BNF Prescribing notes Diagnosis and treatment is often difficult and in some case specialist advice or referral will be necessary. Some patients manage without drug treatment. For many, optimal treatment will be a combination of psychological therapy and drug treatment. There is evidence that SSRIs are effective for anxiety disorders but there are different licensed indications for each SSRI. Due to risk of gastro-intestinal bleeding, SSRIs should be avoided if possible, or used with caution, in patients aged over 80 years, those with prior upper gastro-intestinal bleeding, or in those also taking aspirin or another NSAID. Red = Hospital use only Green = GP & Hospital use. Drugs not classified as Red, Amber or Amber 2 are classified as Green by default Amber 1 = Drugs with shared care agreement Amber 2 = Initiated by Hospital specialist only Gateshead Health NHS Foundation Trust Drug Formulary Page 13 of 41 Date: 17.4.2013 Antidepressants are not recommended for the initial treatment of mild depression because the risk-benefit ratio is poor. In general, clinical trials have established little or no difference in efficacy between the various antidepressants. There is some evidence that tricyclic antidepressants (TCAs) are more effective than serotonin re-uptake inhibitors (SSRIs) in severe depression. They all have a delayed onset of action of 2-4 weeks. If previous treatment with any antidepressant has been successful it should be considered again for treatment of recurrence. Treatment should normally be continued for at least 6 months after response. Patients who have had 2 or more previous episodes of depression may benefit from longterm antidepressants at therapeutic doses. Fluoxetine is an SSRI; it is better tolerated than TCAs. It is first choice because dose instructions are simpler than with other SSRIs and it is less likely to cause a withdrawal reaction. Fluoxetine is the only SSRI shown to have a favourable balance of risks and benefits for the treatment of depressive illness in under 18's. Citalopram is an SSRI which may be better tolerated and has fewer drug interactions than most other SSRIs Patients who have had a recent cardiovascular event should be prescribed sertraline, it has less negative effects on the QT interval. Traditionally a sedative TCA may have been prescribed for anxious patients and patients with significant insomnia. An alternative strategy may be to prescribe trazadone or a formulary SSRI, plus a benzodiazepine for no longer than 1-2 weeks. Amitriptyline is a sedating TCA which has a high incidence of side- effects and can be lethal in overdose. However, it is well established in general practice and may still be useful for those who have responded to it previously. Dosulepin (dothiepin) is not recommended due to its association with ischaemic heart disease, cardiac arrhythmias and fatalities following overdose. All antidepressants may be associated with a discontinuation syndrome and, if taken continuously for 6 weeks or longer, should be withdrawn gradually unless a serious adverse effect has occurred. SSRIs have successfully been used for the treatment of post traumatic stress disorder (PTSD). Improvement of OCD may not be apparent for 12 weeks. Treatment should be continued for at least 9 months. Long-term maintenance is often necessary. Clomipramine and SSRIs have shown efficacy in OCD but clomipramine is associated with more adverse effects. Benzodiazepines are effective for short-term treatment of GAD but there is a risk of dependence, sedation, accidents and withdrawal symptoms. Antidepressants are preferred. In panic disorder symptoms frequently get worse before they get better after starting paroxetine. The initial exacerbation can be avoided by starting with 10mg (half a tablet) daily, gradually increasing. The therapeutic dose is usually higher than is required for depressive illness. The addition of a benzodiazepine is often helpful for the first 2-4 weeks of Red = Hospital use only Green = GP & Hospital use. Drugs not classified as Red, Amber or Amber 2 are classified as Green by default Amber 1 = Drugs with shared care agreement Amber 2 = Initiated by Hospital specialist only Gateshead Health NHS Foundation Trust Drug Formulary Page 14 of 41 Date: 17.4.2013 treatment, then discontinued. Most patients will require paroxetine for 6-12 months before it is gradually withdrawn. Older Patients - SSRIs SSRIs should be avoided if possible, or used with caution, in patients over 80 years due to the risk of gastro-intestinal bleeding. If an SSRI is required, then paroxetine or sertraline should be prescribed. Fluoxetine is not recommended in older patients due to its long half-life and the risk of adverse effects such as agitation. MHRA Drug Safety Update Citalopram and escitalopram: QT interval prolongation—new maximum daily dose restrictions (including in elderly patients), contraindications, and warnings Article date: December 2011 Summary Citalopram and escitalopram are associated with dose-dependent QT interval prolongation and should not be used in those with: congenital long QT syndrome; known pre-existing QT interval prolongation; or in combination with other medicines that prolong the QT interval. ECG measurements should be considered for patients with cardiac disease, and electrolyte disturbances should be corrected before starting treatment. For citalopram, new restrictions on the maximum daily doses now apply: 40 mg for adults; 20 mg for patients older than 65 years; and 20 mg for those with hepatic impairment. For escitalopram, the maximum daily dose for patients older than 65 years is now reduced to 10 mg/day; other doses remain unchanged. Link: http://www.mhra.gov.uk/Safetyinformation/DrugSafetyUpdate/CON137769 Other antidepressant drugs Duloxetine 30mg and 60mg (XPR) capsules (Cymbalta®) (Mental Health Only) Mirtazepine 30mg and 45mg tablets Mirtazepine 15mg and 30mg soluble tablets Nefazodone 200mg tablets (Restricted/ unlicensed) Reboxetine 4mg tablets Tryptophan 500mg tablets (Restricted/ non-formulary, unlicensed) Venlafaxine 37.5mg, 50mg and 75mg tablets Venlafaxine 75mg and 150mg m/r capsules – (restricted) Dose - see BNF Red = Hospital use only Green = GP & Hospital use. Drugs not classified as Red, Amber or Amber 2 are classified as Green by default Amber 1 = Drugs with shared care agreement Amber 2 = Initiated by Hospital specialist only Gateshead Health NHS Foundation Trust Drug Formulary Page 15 of 41 Date: 17.4.2013 4.4 Central nervous system stimulants Atomoxetine 10mg, 18mg, 25mg, 40mg and 60mg capsules Dexamfetamine/Dexamphetamine sulphate 5mg tablets (CD2) Methylphenidate 5mg tablets (Medikinet®) (fanning) Methylphenidate 10mg tablets (Ritalin®) (fannin) (CD2) Methylphenidate MR 18mg, 27mg & 36mg tablets (Concerta XL®) Child & Adolescent Psychiatry Only Methyphenidate MR 10mg, 20mg, 30mg and 40mg capsules (Medikinet XL®) Dose - see BNF or BNF for Children Prescribing notes Methylphenidate is a useful treatment for some children with severe forms of ADHD as part of a comprehensive treatment programme when remedial measures alone prove insufficient. It is licensed for children aged 6 years and above. Patient selection is important and therefore initiation and titration of treatment should be carried out by a child/adolescent psychiatrist, or a paediatrician working in a dedicated specialist clinic. Because of its substantially greater costs, methylphenidate m/r (Concerta® XL or Medikinet XL®) should be restricted to second-line therapy and used only in exceptional circumstances where the supervising clinician has clear evidence of compliance problems with midday dosing. Use of the m/r formulation reduces flexibility of dosage which can be a disadvantage for many children and parents. A shared care protocol for Gateshead is available which provides information about prescribing in primary & secondary care. MHRA Drug Safety Update Atomoxetine: increases in blood pressure and heart rate – new contraindications, warnings and advice for monitoring Article date: January 2012 Summary Atomoxetine causes clinically important increases in blood pressure or heart rate, or both, in a small proportion of patients. Atomoxetine should not be used in patients with severe cardiovascular or cerebrovascular disorders. Thorough pretreatment screening and regular monitoring of cardiovascular status is recommended. Specialist cardiac evaluation and advice should be sought if pretreatment findings suggest cardiac disease or history, or if symptoms suggesting cardiac disease are found during treatment. Link: http://www.mhra.gov.uk/Safetyinformation/DrugSafetyUpdate/CON140666 Red = Hospital use only Green = GP & Hospital use. Drugs not classified as Red, Amber or Amber 2 are classified as Green by default Amber 1 = Drugs with shared care agreement Amber 2 = Initiated by Hospital specialist only Gateshead Health NHS Foundation Trust Drug Formulary Page 16 of 41 Date: 17.4.2013 4.5 Drugs used in the treatment of obesity Orlistat 120mg capsules Dose - Orlistat capsules 120mg: 120mg taken immediately before, during, or up to 1 hour after each main meal; max 360mg daily; max period of treatment 2 years. Omit dose if meal is missed or contains no fat. Prescribing notes Diet and lifestyle changes are the mainstay for management of obesity. Before commencing drug therapy, patients should enter a minimum 3 month structured weight management programme to confirm that they can comply with dietary restriction. Common side-effects with orlistat may be limited by dietary compliance (decreased fat intake). Red = Hospital use only Green = GP & Hospital use. Drugs not classified as Red, Amber or Amber 2 are classified as Green by default Amber 1 = Drugs with shared care agreement Amber 2 = Initiated by Hospital specialist only Gateshead Health NHS Foundation Trust Drug Formulary Page 17 of 41 Date: 17.4.2013 4.6 Drugs used in nausea and vertigo Antihistamines Cinnarizine 15mg tablets Cyclizine 50mg tablets Cyclizine 50mg/ml injection Phenothiazines and related drugs Prochlorperazine 5mg tablets Prochlorperazine 5mg/5ml syrup Prochlorperazine 12.5mg/ml injection Prochlorperazine buccal 3mg tablets Domperidone and metoclopramide Domperidone 10mg tablets Domperidone 5mg/5ml suspension Domperidone 30mg suppositories Metoclopramide 10mg tablets Metoclopramide 5mg/5ml syrup Metoclopramide 5mg/ml injection 5HT3 antagonists Ondansetron 4mg and 8mg tablets Ondansetron 8mg melt tablets Ondansetron 8mg/4ml, 4mg/2ml injection Ondansetron 16mg suppositories Hyoscine Hyoscine 300microgram tablets Hyoscine 1mg/72 hours patch Neurokinin receptor antagonist Aprepitant 80mg and 125mg capsules (Restricted – chemotherapy use only) Nabilone Nabilone 1mg capsules Dose - Arepitant capsules 80mg, 125mg: see BNF - Cinnarizine tablets 15mg: 15-30mg 3 times daily. - Prochlorperazine tablets 5mg; syrup 5mg/5mL: 5mg 3 times daily, gradually increased if required to 30mg daily in divided doses, and reduced after several weeks to 5-10mg daily. - Prochlorperazine Buccal tablets 5mg: 5mg-10mg twice a day. - Cyclizine tablets 50mg; injection 50mg/mL: orally or by intramuscular or intravenous injection, 50mg up to 3 times daily. - Domperidone tablets 10mg; suspension 5mg/5mL: nausea and vomiting (acute attack), 10-20mg Red = Hospital use only Green = GP & Hospital use. Drugs not classified as Red, Amber or Amber 2 are classified as Green by default Amber 1 = Drugs with shared care agreement Amber 2 = Initiated by Hospital specialist only Gateshead Health NHS Foundation Trust Drug Formulary Page 18 of 41 Date: 17.4.2013 4-8 hourly for up to 12 weeks. - Domperidone suppositories 30mg: 30-60mg every 4-8 hours. - Metoclopramide tablets 10mg; oral solution 5mg/5mL; injection 5mg/mL: orally, or by intramuscular or intravenous injection, 10mg 3 times daily (5mg in 15-19 year olds under 60kg). - Ondansetron tablets 4mg, 8mg; melt tablets 8mg, suppositories 16mg; injection 4mg/2ml: see BNF - Nabilone capsules 1mg: see BNF Prescribing notes Cinnarizine and Prochlorperazine are only effective for labyrinthine vertigo. Metoclopramide can cause acute dystonic reactions, usually in the young (especially girls and young women) and the very old. Benzatropine (benztropine) may be given by intramuscular or intravenous injection if acute dystonic reactions occur (dose, 1-2mg repeated if symptoms reappear). If benzatropine is not readily available, then intravenous diazepam may be prescribed. Long-term metoclopramide and prochlorperazine may cause tardive dyskinesia in the elderly. Domperidone does not cross the blood brain barrier; it is less likely than metoclopramide and prochlorperazine to cause sedation or dystonic reactions. Note that cyclizine has potential for abuse. Surgical patients receiving morphine should be prescribed prophylactic anti-emetics such as Cyclizine. Prochlorperazine buccal tablets may be a suitable alternative in the treatment of labyrinthine vertigo for patients who are vomiting. Other drugs for Menieres disease Betahistine 8mg tablets Dose - Betahistine tablets 8mg: initially 16mg 3 times daily, up to max 24-48mg daily. Prescribing notes Prochlorperazine or cinnarizine may be used short-term for the acute treatment of Ménière's disease. Betahistine and thiazide diuretics should be reserved for prophylaxis in patients with a proven diagnosis of Ménière's disease. Older Patients - Prochlorperazine Prochlorperazine should not be prescribed for "dizziness" in older patients due to the risk of druginduced parkinsonism, postural hypotension and mental confusion. Red = Hospital use only Green = GP & Hospital use. Drugs not classified as Red, Amber or Amber 2 are classified as Green by default Amber 1 = Drugs with shared care agreement Amber 2 = Initiated by Hospital specialist only Gateshead Health NHS Foundation Trust Drug Formulary Page 19 of 41 Date: 17.4.2013 4.7 Analgesics Non-opioid analgesics Paracetamol 500mg tablets Paracetamol 500mg dispersible tablets Paracetamol 120mg/5ml, 250mg/5ml suspension Paracetamol 120mg, 240mg, 500mg, 1g suppositories Paracetamol 1g injection Aspirin 75mg, 300mg dispersible tablets Aspirin 75mg, 300mg e/c tablets Aspirin 150mg suppositories Nefopam 30mg tablets Dose - Paracetamol tablets 500mg; soluble tablets 500mg; oral suspension 120mg/5mL, 250mg/5mL; suppositories 120mg, 240mg, 500mg: 0.5-1g every 4-6 hours; max 4g daily. - Aspirin tablets 75mg, 300mg: By mouth, 300-900mg every 4-6 hours when necessary; max 4 daily. - Nefopam tablets 30mg: initially 60mg (elderly 30mg) 3 times daily, adjusted up to 30-90mg 3 times daily. Prescribing notes For further information on the use of NSAIDs see Chapter 10 of Formulary Relative contra-indications to NSAIDs include heart failure, hypertension, renal impairment, peptic ulceration; absolute contra-indications include proven hypersensitivity to aspirin or any NSAID. NSAIDs may worsen asthma; they are contra-indicated if aspirin or any other NSAID has precipitated attacks of asthma. Paracetamol 1g/100mL infusion may be prescribed for the short-term treatment of moderate and severe pain following surgery when administration by the intravenous route is clinically justified and/or other routes of administration are not possible. Compound analgesics containing an opioid may produce opioid side-effects and can complicate treatment of overdosage e.g. co-codamol For greater flexibility, codeine and paracetamol may be prescribed concomitantly as separate drugs (instead of as co-codamol). Red = Hospital use only Green = GP & Hospital use. Drugs not classified as Red, Amber or Amber 2 are classified as Green by default Amber 1 = Drugs with shared care agreement Amber 2 = Initiated by Hospital specialist only Gateshead Health NHS Foundation Trust Drug Formulary Page 20 of 41 Date: 17.4.2013 Opioid analgesic preparations Morphine 10mg, 20mg tablets (Sevredol®) Morphine MST tablets 5mg Morphine 5mg, 10mg, 30mg, 60mg, 100mg, 200mg S/R capsules (Zomorph®) Morphine 10mg/5ml,100mg/5ml solution Morphine 10mg/ml, 15mg/ml, 30mg/ml, 60mg/2ml injections Morphine 50mg/50ml vials Morphine 10mg/ml (preservative free ) injection Codeine phosphate 15mg and 30mg tablets Codeine phosphate 60mg/ml injection Diamorphine 5mg, 10mg, 30mg injection Dihydrocodeine 30mg tablets Dihydrocodeine 10mg/5ml elixir Fentanyl 100 micrograms/2ml, 500 micrograms/10ml injection Hydromorphone 1.3mg, 2.6mg capsules Hydromorphone 2mg, 4mg, 8mg, 16mg and 24mg M/R capsules Hydromorphone 10mg/ml and 20mg/ml injection Methadone 5mg tablet Methadone 2mg/5ml linctus Methadone 1mg/5ml mixture Oxycodone (Oxycontin) 5mg, 10mg, 20mg, 40mg, 80mg MR tablets Oxycodone 10mg/ml injection Oxycodone 50mg/ml injection (Palliative care use in syringe drivers only) Oxycodone 5mg/5ml solution Pethidine 50mg tablets Pethidine 50mg/ml, 100mg/2ml injection Tramadol 50mg capsules Tramadol 50mg/ml injection Prescribing notes Codeine is an inefficient analgesic in approximately 10% of patients who are unable to convert it to morphine. Red = Hospital use only Green = GP & Hospital use. Drugs not classified as Red, Amber or Amber 2 are classified as Green by default Amber 1 = Drugs with shared care agreement Amber 2 = Initiated by Hospital specialist only Gateshead Health NHS Foundation Trust Drug Formulary Page 21 of 41 Date: 17.4.2013 Morphine should be given parenterally when possible for acute severe pain. The first dose of intravenous morphine should be given slowly, titrated to effect, and respiratory rate monitored. For postoperative pain refer to relevant acute pain protocols Chronic pain is not simply a physical problem. It is associated with severe and extensive psychological, social and economic factors. Non-pharmacological treatments are often worthwhile. Consider specialist referral for additional services, e.g. Pain Clinic. For chronic non-malignant pain, if an opiate is required, treatment may be initiated with low dose modified-release morphine. Treatment with regular opiates should be reviewed regularly. Laxatives should be considered. Intranasal administration of diamorphine is approved on the formulary for hospital use only in children with severe pain in A&E only. Older Patients - Opiates Older patients are particularly susceptible to respiratory depression and constipation secondary to opiates. MHRA Drug Safety Update Addiction to benzodiazepines and codeine: supporting safer use Article date: July 2011 Summary Reminder for healthcare professionals: Given the risks associated with the use of benzodiazepines, patients should be prescribed the lowest effective dose for the shortest time possible. Maximum duration of treatment should be 4 weeks, including the dose-tapering phase Over-the-counter codeine-containing medicines should be used for the short-term (3 days) treatment of acute, moderate pain which is not relieved by paracetamol, ibuprofen, or aspirin alone (see Drug Safety Update September 2009) Link: http://www.mhra.gov.uk/Safetyinformation/DrugSafetyUpdate/CON123123 Red = Hospital use only Green = GP & Hospital use. Drugs not classified as Red, Amber or Amber 2 are classified as Green by default Amber 1 = Drugs with shared care agreement Amber 2 = Initiated by Hospital specialist only Gateshead Health NHS Foundation Trust Drug Formulary Page 22 of 41 Date: 17.4.2013 Neuropathic pain Amitriptyline 10mg, 25mg and 50mg tablets Amitriptyline 25mg/5ml syrup Gabapentin 100mg, 300mg capsules Pregabalin 25mg, 50mg, 75mg, 100mg, 150mg and 300mg capsules Dose - Amitriptyline tablets 10mg, 25mg, 50mg; oral solution 25mg/5mL, 50mg/5mL: initially 10-25mg at night increased gradually to 75mg daily. - Gabapentin tablets 600mg; capsules 300mg, 600mg: see BNF - Pregabalin capsules 25mg, 50mg, 75mg, 100mg, 150mg, 200mg: see BNF Prescribing notes There is evidence that tricyclic antidepressants have analgesic efficacy in a variety of chronic pain syndromes and their use should be considered where conventional analgesics are proving of limited benefit in the chronic situation. Tricyclic antidepressants (TCAs) appear to be more effective than other classes of antidepressants. Amitriptyline has been the most studied but other TCAs such as imipramine and nortryptiline have similar benefits and may be chosen in an attempt to avoid side-effects such as sedation. Patients should be warned of likely side-effects and that, unlike conventional analgesics, the medication may have to be taken regularly for 4-6 weeks before the full analgesic effect may be appreciated. The analgesic effect of amitriptyline is attained at a lower dose than that required to treat depression. Laxatives should be considered for patients receiving regular amitriptyline. Amitriptyline should be used with caution in the elderly and patients with glaucoma or prostatic hypertrophy. Neuropathic symptoms are characterised by a description of tingling, burning or shooting pains. There may also be allodynia (pain elicited by a non-noxious stimulus e.g. light touch) and hyperalgesia (pain that is of inappropriate severity to a noxious stimulus). Consider using amitriptyline and gabapentin together if pain is severe and refractory. Patients should be warned of likely side-effects and that, unlike conventional analgesics, medication may have to be taken regularly for 4-6 weeks before the full analgesic effect is appreciated. Carbamazepine is first choice for trigeminal neuralgia. Duloxetine may be used for diabetic peripheral neuropathic pain as 2nd or 3rd line therapy. Gabapentin tablets are substantially more expensive than capsules. When prescribing use the most cost effective strength and formulation. Red = Hospital use only Green = GP & Hospital use. Drugs not classified as Red, Amber or Amber 2 are classified as Green by default Amber 1 = Drugs with shared care agreement Amber 2 = Initiated by Hospital specialist only Gateshead Health NHS Foundation Trust Drug Formulary Page 23 of 41 Date: 17.4.2013 All strengths of pregabalin cost the same, therefore ensure the correct strength of capsule is prescribed and dispensed (i.e. 300mg instead of 2 x 150mg). Older Patients - Amitriptyline In the older patient, amitriptyline is particularly likely to cause postural hypotension, urinary retention and constipation. Antimigraine drugs Sumatriptan 50mg, 100mg tablets Sumatriptan 6mg/0.5ml s/c injection Clonidine 25 microgram tablets Pizotifen 500 microgram, 1.5 mg tablets Pizotifen 250 microgram/5ml elixir Dose - Clonidine tablets 25 microgram: 50micrograms twice daily, increased after 2 weeks to 75micrograms twice daily if necessary. - Sumatriptan tablets 50mg, 100mg: 50mg-100mg as soon as possible after onset (patient not responding should not take second dose for same attack); dose may be repeated after not less than 2 hours if migraine recurs; max 300mg in 24 hours. The optimum dose is 50mg. - Pizotifen tablets 500microgram, 1.5mg; elixir 250micrograms/5ml: initially 500micrograms at night increased gradually to usual dose of 1.5mg at night or in 3 divided doses, may be further increased up to max daily dose 4.5mg, max single dose 3mg. Prescribing notes Ensure diagnosis of migraine is correct. Triptans are expensive and ineffective in most other types of headache. Over use of triptans (more than 4 doses per week) should be discouraged due to the risk of chronic migraine. Sumatriptan 50mg and 100mg are equally efficacious. Sumatriptan 50mg produces fewer side-effects and is considered the optimum dose. Parenteral opiates should be avoided in migraine. Medication should be taken as early as possible after migraine headache starts, but not during the aura phase. Headache recurrence within the first 24hours can be treated with a 2nd dose. It the first dose of a triptan fails to help, alternative (analgesic) medication should be considered. Red = Hospital use only Green = GP & Hospital use. Drugs not classified as Red, Amber or Amber 2 are classified as Green by default Amber 1 = Drugs with shared care agreement Amber 2 = Initiated by Hospital specialist only Gateshead Health NHS Foundation Trust Drug Formulary Page 24 of 41 Date: 17.4.2013 4.8 Antiepileptics Generalised seizures Carbamazepine 100mg, 200mg tablets Carbamazepine 100mg and 200mg chewable tablets Carbamazepine 200mg and 400mg M/R tablets Carbamazepine 125mg and 250mg suppository Carbamazepine 100mg/5ml liquid Clobazam 10mg tablets Clobazam 5mg/5ml suspension (unlicensed) Clonazepam 500 microgram, 2mg tablets Clonazepam 2mg/5ml solution Gabapentin 100mg, 300mg capsules Gabapentin 600mg tablets Lamotrigine 2mg chewable tablets Lamotrigine 5mg, 25mg 100mg dispersible tablets Lamotrigine 50mg tablets Levetiracetam 250mg, 500mg and 1000mg tablets Levetiracetam 100mg/ml oral solution Levetiracetam 500mg/5ml oral infusion Oxcarbazepine 150mg, 300mg tablets Phenobarbital 15mg, 30mg tablets Phenobarbital 15mg/5ml alcohol free Mixture Phenobarbital 50mg/5ml suspension Phenobarbital 30mg/ml, 60mg/ml and 200mg/ml injection Phenytoin 25mg, 50mg, 100mg, 300mg capsules Phenytoin 30mg/5ml, 90mg/5ml suspension (90mg/5ml unlicensed drug) Phenytoin 20mg/ml injection Primidone 250mg tablets Sodium valproate 100mg crushable tablets Sodium valproate 200mg, 500mg EC tablets Sodium valoproate 200mg, 300mg and 500mg m/r tablets Sodium valproate 200mg/5ml liquid Sodium valproate 400mg injection Red = Hospital use only Green = GP & Hospital use. Drugs not classified as Red, Amber or Amber 2 are classified as Green by default Amber 1 = Drugs with shared care agreement Amber 2 = Initiated by Hospital specialist only Gateshead Health NHS Foundation Trust Drug Formulary Page 25 of 41 Date: 17.4.2013 Vigabatrin 500mg tablets Vigabatrin 500mg sachets Topiramate 15mg and 25mg sprinkle capsules Topiramate 25mg, 50mg tablets Dose - Carbamazepine tablets 100mg, 200mg, 400mg; liquid 100mg/5mL: initially, 100mg twice daily increased by 100mg each week to maintenance dose 3 times daily; dose can be increased to 2g daily. - Carbamazepine m/r tablets 200mg, 400mg: dose as above in 2 divided doses; brand to be dispensed should be specified. For epilepsy, carbamazepine m/r is preferred. - Carbamazepine suppositories 125mg, 250mg: for short-term use (max 7 days) when oral therapy not possible. One 125mg suppository may be considered to be approximately equivalent in therapeutic effect to 100mg tablet. Max 1g daily in 4 divided doses. - Clobazam tablets 10mg: see BNF - Clonazepam tablets 500microgram, 2mg; oral solution 2mg/5ml: see BNF - Gabapentin capsules 100mg, 300mg; tablets 600mg: see BNF - Phenobarbital tablets 15mg, 30mg: see BNF - Phenytoin capsules 25mg, 50mg, 100mg, 300mg; oral solution 30mg/5ml, 90mg/5ml: see BNF - Phenytoin injection 20mg/ml: see BNF - Primidone tablets 250m: see BNF - Topiramate sprinkle capsules 15mg, 25mg, 50mg: see BNF - Sodium valproate tablets e/c 200mg, 500mg; oral solution 200mg/5mL: initially, 200mg twice daily increasing by 200mg/day at weekly intervals to a max of 2.5g daily in divided doses, usual maintenance 1-2g daily. - Sodium valproate injection 400mg: see BNF. - Lamotrigine tablets 25mg, 50mg, 100mg, 200mg: monotherapy, initially 25mg daily for 14 days, then 50mg daily for 14 days; then increase by max of 50-100mg every 7-14 days. Usual maintenance as monotherapy, 100-200mg daily in 1-2 divided doses; max 500mg daily. If used in combination with other antiepileptic drugs, the dose of lamotrigine must be adjusted; see BNF. - Vigabatrin tablets 500mg; sachets 500mg: see BNF Prescribing notes Different preparations may vary in bioavailability; it may be prudent to avoid changing the formulation to avoid reduced effect or excessive side-effects. The choice of agent is determined by the type of seizure, and age and sex of patient. Antiepileptic medication should be commenced after two or more clinically definite seizures or after one seizure in a patient with a clearly epileptiform EEG or causative lesion on brain imaging. Treatment may also be considered after a single attack if the risk of a second seizure is considered to be high. If a second fit occurs before the patient is seen by a specialist then start first choice agent. Phone specialist if advice required. Antiepileptic drugs which induce hepatic enzymes may impair the efficacy of oral contraceptives; see BNF for details. Lamotrigine is now regarded as a first choice agent; however it may reduce the effectiveness of oral contraceptives. In addition, the dose of lamotriginee may need to be adjusted in Red = Hospital use only Green = GP & Hospital use. Drugs not classified as Red, Amber or Amber 2 are classified as Green by default Amber 1 = Drugs with shared care agreement Amber 2 = Initiated by Hospital specialist only Gateshead Health NHS Foundation Trust Drug Formulary Page 26 of 41 Date: 17.4.2013 women who commence or stop oral contraceptives, or who become pregnant while taking lamotrigine – see SPC. All antiepileptic drugs carry a risk of teratogenicity. Increasing the number of drugs increases the risk; ideally, women planning to conceive should use adequate contraception until on monotherapy. Lamotrigine and sodium valproate should not be taken concomitantly during pregnancy. Dose-related side-effects of carbamazepine may be reduced by using the modified-release formulation. If first choice agent fails at maximum tolerated dose, gradually change over to another first choice agent. If monotherapy fails, a combination of first choice agents may be tried. Routine plasma drug level monitoring is generally unnecessary unless side-effects are a problem, non-compliance is suspected, or phenobarbital or phenytoin are administered. Monitoring is seldom of value for patients on sodium valproate. Therapy should be reviewed within the 1st month to assess seizure control, compliance, side-effects (blood tests if required). Therapy should be reviewed at 6 weeks; if seizures are not controlled and there are no unacceptable side-effects, the dose should be increased. Gradual withdrawal of antiepileptic drugs can be considered with caution after 2 years free of seizures but note implications for driving. Specialist advice should be sought. If patients are established on vigabatrin, the potential for long-term visual side-effects should be considered. Primidone is likely to be withdrawn from the market in the future. MHRA Drug Safety Update Carbamazepine, oxcarbazepine and eslicarbazepine: potential risk of serious skin reactions associated with HLA-A* 3101 allele Article date: December 2012 Summary The risk of serious skin-related adverse drug reactions, including Stevens-Johnson syndrome, occurring with carbamazepine may be increased in the presence of the HLA-A*3101 allele in patients of European descent or Japanese origin. However, there are currently insufficient data to support screening for this allele before starting carbamazepine treatment. Patients of European descent or Japanese origin who are known to be positive for this allele should only receive carbamazepine, oxcarbazepine or eslicarbazepine after careful consideration of the benefits and risks. Link: http://www.mhra.gov.uk/Safetyinformation/DrugSafetyUpdate/CON214944 Red = Hospital use only Green = GP & Hospital use. Drugs not classified as Red, Amber or Amber 2 are classified as Green by default Amber 1 = Drugs with shared care agreement Amber 2 = Initiated by Hospital specialist only Gateshead Health NHS Foundation Trust Drug Formulary Page 27 of 41 Date: 17.4.2013 MHRA Drug Safety Update Phenytoin: risk of Stevens-Johnson syndrome associated with HLA-B*1502 allele in patients of Thai or Han Chinese ethnic origin Article date: January 2010 Summary Presence of the HLA-B*1502 allele may be associated with an increased developing SJS in individuals of Thai and Han Chinese ethnic origin when with phenytoin. If these patients are known to be HLA-B*1502-positive, should be avoided when alternative therapy can be given. Use of phenytoin only be considered if the benefits are thought to outweigh the risks. Link: http://www.mhra.gov.uk/Safetyinformation/DrugSafetyUpdate/CON087742 MHRA Drug Safety Update Vigabatrin for infantile spasms: risk of movement disorders and MRI abnormalities Article date: November 2009 Summary Movement disorders have been reported in patients treated with vigabatrin for infantile spasms. If new movement disorders occur during treatment with vigabatrin, consideration should be given to dose reduction or a gradual discontinuation of treatment in consultation with specialist advice. Link: http://www.mhra.gov.uk/Safetyinformation/DrugSafetyUpdate/CON087878 MHRA Drug Safety Update Antiepileptics: adverse effects on bone Article date: April 2009 Summary The available data suggest that long-term use of carbamazepine, phenytoin, primidone, and sodium valproate is associated with decreased bone mineral density that may lead to osteopenia, osteoporosis, and increased fractures in at-risk patients. Vitamin D supplementation should be considered for at-risk patients who are taking these medicines long term. Link: http://www.mhra.gov.uk/Safetyinformation/DrugSafetyUpdate/CON087970 MHRA Drug Safety Update Antiepileptics: risk of suicidal thoughts and behaviour Article date: August 2008 Summary Antiepileptic treatment is associated with a small increased risk of suicidal thoughts and behaviour. Patients and caregivers should be alert to signs of suicidal thoughts or behaviour throughout treatment. Link: http://www.mhra.gov.uk/Safetyinformation/DrugSafetyUpdate/CON085173 Red = Hospital use only Green = GP & Hospital use. Drugs not classified as Red, Amber or Amber 2 are classified as Green by default Amber 1 = Drugs with shared care agreement Amber 2 = Initiated by Hospital specialist only Gateshead Health NHS Foundation Trust Drug Formulary Page 28 of 41 Date: 17.4.2013 MHRA Drug Safety Update Carbamazepine: genetic testing recommended in some Asian populations Article date: April 2008 Summary The risk of carbamazepine-induced Stevens-Johnson syndrome is strongly associated with presence of the HLA-B*1502 allele in individuals of Han Chinese, Hong Kong Chinese, or Thai origin. It is recommended that these individuals should be screened for HLA-B*1502 before prescription of carbamazepine. Those who test positive should not start carbamazepine unless the benefits clearly outweigh the risks of Stevens-Johnson syndrome. Link: http://www.mhra.gov.uk/Safetyinformation/DrugSafetyUpdate/CON084888 MHRA Drug Safety Update St John’s Wort: interactions with all antiepileptics Article date: November 2007 Summary Any antiepileptic medicine may interact with St John’s wort: patients with epilepsy should not take products that contain St John’s wort. Link: http://www.mhra.gov.uk/Safetyinformation/DrugSafetyUpdate/CON079328 Drugs used in status epilepticus Diazepam 2.5mg, 5mg, 10mg rectal tubes Diazepam 10mg/2ml injection Diazemuls 10mg/2ml injection Clonazepam 1mg/2ml and 1mg/ml injection Lorazepam 4mg/ml injection Paraldehyde 50% in olive oil rectal solution (restricted use/unlicensed drug) Phenytoin 250mg/5ml injection Phenobarbital 200mg/ml injection Midazolam 10mg/ml SF buccal liquid Dose - Clonazepam injection 1mg/ml: see BNF - Midazolam buccal liquid 10mg/mL (Epistatus®): drawn up via oral syringe, and administered by the buccal route in the treatment of status epilepticus (not intravenous for this indication), 10mg as a single dose (or 5mg if under 50kg) according to individual patient protocol. - Lorazepam injection 4mg/mL: by intravenous injection (into large vein), 4mg. - Diazepam injection 10mg/2ml: see BNF - Diazepam injection (emulsion) 5mg/mL (Diazemuls®): by intravenous injection, 10-20mg at a rate of 0.5mL (2.5mg) per 30 seconds, repeated if necessary after 30-60 minutes. Red = Hospital use only Green = GP & Hospital use. Drugs not classified as Red, Amber or Amber 2 are classified as Green by default Amber 1 = Drugs with shared care agreement Amber 2 = Initiated by Hospital specialist only Gateshead Health NHS Foundation Trust Drug Formulary Page 29 of 41 Date: 17.4.2013 - Diazepam rectal solution 10mg/2.5mL: usually 10mg. - Paraldehyde injection; enema 30ml with olive oil: see BNF - Phenobarbital injection 200mg/mL in propylene glycol 90% and water for injections 10%: by intravenous injection (dilute injection 1 in 10 with water for injections), 10mg/kg at a rate of not more than 100mg/minute; max 1g. - Phenytoin sodium injection 50mg/mL: by slow intravenous injection or infusion (with blood pressure and ECG monitoring), 15mg/kg at a rate not exceeding 50mg per minute, as a loading dose. Maintenance dose may be required. - Midazolam buccal liquid 10mg/ml: see BNF Prescribing notes Where possible, treatment should be initiated in the community prior to hospital. A possible underlying cause (e.g. hypoglycaemia, hypoxia etc) must be considered. The first episode of status epilepticus should be treated with rectal diazepam if available, and an ambulance should be called. Treatment should be given if convulsion lasts longer than 5 minutes. Buccal midazolam is an alternative to rectal diazepam. This drug should be given by a trained healthcare professional or carer, according to the individual agreed protocol drawn up for the patient by the specialist. Midazolam buccal liquid 10mg/mL (Epistatus®) is available on a named patient basis from Special Products Limited. Note that Epistatus® is a different strength to midazolam injection. In some cases, rectal paraldehyde may be administered in the community for prolonged seizures, according to individual patient protocol. Is still fitting after 10 minutes, and if not already in hospital, call an ambulance. If convulsion continues beyond 30 minutes (status epilepticus), patient will need hospitalisation and preferably admission to ITU. Although the BNF recommends lorazepam injection, this requires refrigeration and may therefore not be suitable for GP use. Clobazam may be prescribed to prevent status epilepticus in patients with a previous history of status or who are known to be at risk if their seizures accelerate or begin to cluster. It may also be prescribed for those whose seizures occur or accelerate at certain times e.g. during menstruation or intercurrent infections. Prescriptions should be endorsed 'SLS'. MHRA Drug Safety Update Buccal midazolam(Buccolam®): new authorised medicine for paediatric use - care needed when transferring from unlicensed formulations Article date: October 2011 Summary Buccal midazolam (Buccolam▼) is a new authorised treatment for prolonged acute convulsive seizures. It is now available on the UK market. Buccal midazolam may be considered as an alternative to rectal diazepam for the treatment of prolonged seizures. Several factors should be considered when transferring patients to the authorised Buccolam product when an unlicensed medicine other than Buccolam has been used previously. Link: http://www.mhra.gov.uk/Safetyinformation/DrugSafetyUpdate/CON131931 Red = Hospital use only Green = GP & Hospital use. Drugs not classified as Red, Amber or Amber 2 are classified as Green by default Amber 1 = Drugs with shared care agreement Amber 2 = Initiated by Hospital specialist only Gateshead Health NHS Foundation Trust Drug Formulary Page 30 of 41 Date: 17.4.2013 4.9 Drugs used in parkinsonism and related disorders General notes The optimal regimen depends on several factors such as age, cognitive state, nature and stage of disease. It is not possible to identify a universal first choice drug therapy for either early PD or for adjuvant drug therapy for later PD. When choosing drug treatment, take into account clinical and lifestyle preferences and patient preference. Specialist advice should ideally precede initiation of drug therapy. Therapy is usually initiated with levodopa or a dopamine agonist. A number of other agents are used as adjunctive therapy. Patients who have suffered excessive sedation or sudden onset of sleep with dopaminergic drugs (levodopa and dopamine agonists) should refrain from driving or operating machines until those effects have stopped recurring. In some individuals, these drugs may cause wakefulness and should be avoided in the evening. Dopamine agonists, and less commonly levodopa, may cause impulse control disorders (pathological gambling/shopping, sexual deviancy/hypersexuality). Patients and carers should be advised in advance of these potential adverse effects. Patients with PD should be encouraged to take their medication as regulary as possible, and this is particularly relevant in situations where they are not self medicating (e.g. hospital admission). PD medication regimens should only be adjusted after discussion with a specialist. PD patients commonly have complex medication regimens with different formulations being given at unusual times. Take care when prescribing these medications and ensure that the timings are correct. When a PD patient is unwell (e.g. with sepsis) their symptoms may worsen but this is not the time to increase their medication. This is better done when they are stable. Treat the illness first. Swallowing often deteriorates when PD patients are unwell. If they miss their medication they may deteriorate further. Have a low threshold for using a nasogastric tube to administer medication in these patients & seek specialist advice if needed. Look out for and treat the many complications of PD e.g. constipation, depression, nausea, poor swallowing. Older Patients - Drugs used in parkinsonism Drugs used in parkinsonism are particularly prone to give side-effects in older patients. Treatment should be initiated with low doses which should be increased with caution. Dopaminergic drugs used in parkinsonism Red = Hospital use only Green = GP & Hospital use. Drugs not classified as Red, Amber or Amber 2 are classified as Green by default Amber 1 = Drugs with shared care agreement Amber 2 = Initiated by Hospital specialist only Gateshead Health NHS Foundation Trust Drug Formulary Page 31 of 41 Date: 17.4.2013 (a) Dopamine agonists Amantadine 100mg capsules Apomorphine 10mg/ml and 20mg/2ml injection Ropinirole (Requip®) 250 microgram, 1mg and 2mg tablets Ropinirole MR (Requip XL®) 2mg, 4mg and 8mg modified release tablets Rotigotine 2mg, 4mg and 8mg patches Pramipexole 88 microgram, 180 microgram, 350 microgram and 700 microgram tablets Dose - Amantadine capsules 100mg:100mg daily increased after one week to 100mg twice daily, some patients may require up to 400mg daily. - Apomorphine (Apo-Go®) injection 10mg/1ml, 20mg/2ml: see BNF - Ropinirole tablets 250micrograms, 1mg, 2mg, 5mg: 28-day starter pack of 42x250microgram, 42x500microgram and 21x1mg tablets. 28-day follow-on pack of 42x500microgram, 42x1mg, 63x2mg tablets. Initial dose is 750micrograms daily in 3 divided doses, increased by increments of 750micrograms at weekly intervals to 3mg daily; further increased by increments of up to 3mg at weekly intervals according to response; usual range 9-16mg daily. Higher doses (max. 24mg daily) are often necessary under specialist advice. - Ropinirole tablets m/r 2mg, 4mg, 8mg: stable patients transferring from ropinirole immediate release tablets, initially once daily dose substituted for total daily dose of equivalent immediaterelease tablet. - Rotigotine patches 2mg, 6mg,4mg, 8mg: see BNF. - Pramipexole tablets 88micrograms, 180 micrograms, 350 micrograms, 700 micrograms: Initial dose 88 micrograms 3 times daily, dose doubled every 5-7 days if tolerated, to 350 micrograms 3 times daily; further increased if necessary by 180 micrograms 3 times daily at weekly intervals; max 3.3mg daily in 3 divided doses. Prescribing notes Ropinirole or pramipexole are recommended as the first choice dopamine-agonist for monotherapy or adjunctive therapy. Prolonged release ropinirole tablets are only licensed for patients with established adequate symptomatic control on immediate release (standard) ropinirole. Substitution should be supervised by an appropriate specialist in Parkinson's disease. Other oral dopamine agonists (cabergoline, pergolide) are licensed as adjunctive therapy to levodopa in established cases, but it is recommended that the introduction of such medications follows specialist advice. Ergot derivatives (bromocriptine, cabergoline and pergolide) have rarely been associated with pulmonary, retroperitoneal, pericardial and valvular fibrotic reactions and require regular clinical monitoring (see BNF). They are no longer recommended as first line treatment. Dopamine-agonists are emetogenic; patients are often pre-treated with domperidone 1020mg 3 times daily for 48 hours, continued for at least 4 weeks after which it may usually be safely withdrawn. Prochlorperazine and metoclopramide should be avoided since they may exacerbate or induce parkinsonism. Red = Hospital use only Green = GP & Hospital use. Drugs not classified as Red, Amber or Amber 2 are classified as Green by default Amber 1 = Drugs with shared care agreement Amber 2 = Initiated by Hospital specialist only Gateshead Health NHS Foundation Trust Drug Formulary Page 32 of 41 Date: 17.4.2013 When used as adjunctive therapy, dopamine agonists can exacerbate levodopa-induced adverse effects. All dopamine agonists can cause postural hypotension and neuropsychiatric adverse effects. All dopamine agonists, except cabergoline, require careful dose titration according to BNF guidelines. For driving advice, see General notes. Apomorphine is a powerful dopamine agonist that must be given subcutaneously, either by infusion or on an 'as required' basis. It is approved for use under a shared care protocol. Amantadine improves mild bradykinetic disabilities, tremor and rigidity. It may also be useful in dyskinesias in more advanced disease. MHRA Drug Safety Update Dopamine agonists: pathological gambling, increased libido, and hypersexuality Article date: August 2007 Summary Compulsive behaviour with dopamine agonists may be dose-related. Link: http://www.mhra.gov.uk/Safetyinformation/DrugSafetyUpdate/CON079100 (b)Levodopa Available Preparations Drug components Generic Brand name levodopa benserazide carbidopa entacapone name CoMadopar ® beneldopa 62.5 caps Co- 50mg 12.5mg - - Madopar ® 125 caps 100mg 25mg - - Madopar ® 250 caps 200mg 50mg - - Madopar ® dispersible tabs 50mg 12.5mg - - 100mg 25mg - - Madopar ® CR 100mg 25mg - - Co-careldopa 100mg - 10mg - comments A generic product is not available, but, generic prescribing is preferred. Prescribers should take care with what they prescribe. The total daily Red = Hospital use only Green = GP & Hospital use. Drugs not classified as Red, Amber or Amber 2 are classified as Green by default Amber 1 = Drugs with shared care agreement Amber 2 = Initiated by Hospital specialist only Gateshead Health NHS Foundation Trust Drug Formulary Page 33 of 41 Date: 17.4.2013 careldopa 10/100 tabs Co-careldopa 25/100 tabs 100mg - 25mg - Co-careldopa 25/250 tabs 250mg - 25mg - Sinemet®62.5 tabs 50mg - 12.5mg - Sinemet®110 tabs 100mg - 10mg - Sinemet®Plus tabs 100mg - 25mg - Sinemet®275 tabs 250mg - 25mg - Half Sinemet® CR tabs 100mg - 25mg - Sinemet® CR tabs 200mg - 50mg - Stalevo® 50/12.5/200 50mg - 12.5mg 200mg Stalevo® 100/25/200 100mg - 25mg 200mg Stalevo® 150mg 150/37.5/200 - 37.5mg 200mg Stalevo® 200/50/200 - 50mg 200mg 200mg dose of carbidopa should be at least 70mg. A lower dose may not achieve full inhibition of extracerebral dopadecarboxylase, with a resultant increase in adverse effects. Only 1 tablet of Stalevo® for each dose, to limit the amount of entacapone taken. Max 10 tablets daily. Red = Hospital use only Green = GP & Hospital use. Drugs not classified as Red, Amber or Amber 2 are classified as Green by default Amber 1 = Drugs with shared care agreement Amber 2 = Initiated by Hospital specialist only Gateshead Health NHS Foundation Trust Drug Formulary Page 34 of 41 Date: 17.4.2013 Dose - Dose expressed as levodopa: initially 50mg levodopa up to 3 times daily. Increase at weekly intervals if necessary according to response. Max 800mg levodopa daily in 3-4 divided doses. Higher doses may be necessary under specialist advice. Prescribing notes To reduce the risk of nausea, levodopa should be taken initially with food and the dose increased slowly. Protein may interefere with levo-dopa absorption. Levodopa should not be withdrawn abruptly. It may colour urine red. Co-beneldopa (Madopar®) and co-careldopa (Sinemet®) are used equally and there is no evidence of benefit of one over the other. Sinemet-110® (co-careldopa) is not recommended for initiation of therapy as the dose of carbidopa may be inadequate for full inhibition of dopa-decarboxylase. Sinemet-110® may have a use in patients on more than 700mg levodopa. Dispersible Madopar® may be useful for patients, who are on co-beneldopa or co-careldopa at equivalent levodopa doses, with swallowing difficulties, or where rapid absorption is desired, for example first thing in the morning. Often an inactive sediment remains in the glass. Modified-release formulations of levodopa are not recommended for initiation of therapy. They may be useful for end-of-dose deterioration or nocturnal immobility and rigidity. For driving advice, see General notes. (c) Dopamine enzyme inhibitors Entacapone 200mg tablets Rasagiline 1mg tablets Selegiline 1.25mg, 5mg tablets Selegiline 10mg/5ml oral liquid Dose - Entacapone tablets 200mg: 200mg with each dose of levodopa with dopa-decarboxylase inhibitor, max 2g daily. - Rasagiline tablets 1mg: 1mg daily. - Selegiline tablets 1.25mg, 5mg; oral liquid 10mg/5ml: 10mg in the morning or 5mg at breakfast and midday Prescribing notes Entacapone (oral) or selegiline (oral or buccal) may be used for management of motor fluctuations There is no evidence to support their use as neuroprotective therapies. For patients stabilized on co-careldopa and entacapone, Stalevo® may be suitable. Serious adverse reactions have been reported with the concomitant use of SSRIs, SNRIs, tricyclic, tetracyclic antidepressants and MAO inhibitors. Therefore, in view of the MAO Red = Hospital use only Green = GP & Hospital use. Drugs not classified as Red, Amber or Amber 2 are classified as Green by default Amber 1 = Drugs with shared care agreement Amber 2 = Initiated by Hospital specialist only Gateshead Health NHS Foundation Trust Drug Formulary Page 35 of 41 Date: 17.4.2013 inhibitory activity of rasagiline & selegiline, antidepressants should be administered with caution. The concomitant use of rasagiline and fluoxetine or fluvoxamine should be avoided. At least five weeks should elapse between discontinuation of fluoxetine and initiation of treatment with rasagiline. At least 14 days should elapse between discontinuation of rasagiline and initiation of treatment with fluoxetine or fluvoxamine. – no longer on People taking selegiline should not use selective serotonin reuptake inhibitors or tricyclic antidepressants. Trazodone or mirtazapine may be used. Antimuscarinic drugs used in parkinsonism Procyclidine 5mg tablets Procyclidine 5mg/5ml syrup Procyclidine 5mg/ml injection Prescribing notes Procyclidine may be useful for the treatment of drug-induced dystonic reactions and extrapyramidal side-effects of neuroleptic medication. Drugs used in essential tremor, chorea, tics and related disorders Haloperidol 500 microgram capsules Haloperidol 1.5mg, 5mg and 10mg tablets Tetrabenazine 25mg tablets Botulinum A toxin 100 units (Botox) Red = Hospital use only Green = GP & Hospital use. Drugs not classified as Red, Amber or Amber 2 are classified as Green by default Amber 1 = Drugs with shared care agreement Amber 2 = Initiated by Hospital specialist only Gateshead Health NHS Foundation Trust Drug Formulary Page 36 of 41 Date: 17.4.2013 4.10 Drugs used in substance dependence Alcohol dependence Acamprosate 333mg E/C tablets Disulfiram 200mg tablets Chlordiazepoxide 5mg, 10mg capsules Diazepam 2mg, 5mg, 10mg tablets and oral solution 2mg/5ml Dose - Chlordiazepoxide capsules 5mg, 10mg: 10-40mg four times daily titrated to response, gradually reducing over 5 to 7 days. - Diazepam tablets 2mg, 5mg, 10mg; oral solution 2mg/5mL: 10-40mg up to 4 times daily, titrated to response, gradually reducing over 5 to 7 days. Prescribing notes For in-patients refer to local alcohol withdrawal protocols To gain control of severe symptoms, adjunctive treatment may be necessary. Haloperidol may be considered. Benzodiazepines have dependence potential. To minimise risk of dependence, administer short-term only. Benzodiazepines should not be prescribed if the patient is likely to drink alcohol concomitantly. Choice of benzodiazepines: (a) Chlordiazepoxide is first choice oral agent for outpatients and general practice alcohol withdrawal, because it has less abuse potential and 'street value' than diazepam. (b) Diazepam or chlordiazepoxide are used for in-patients. (c) Diazepam is first choice for in-patients if the parenteral route is required. (d) In liver failure, oxazepam may be considered due to its shorter duration of action and fewer metabolites. Older Patients - Benzodiazepines Caution needs to be exercised when benzodiazepines are prescribed in older patients since accumulation may result in oversedation. Maintenance of abstinence First choices: disulfiram or acamprosate Dose - Disulfiram (Antabuse®) tablets 200mg: 800mg as single dose on first day, reducing over 5 days to 100-200mg daily. Not to be continued for longer than 6 months without review. - Acamprosate (Campral EC®) tablets e/c 333mg: 18-65 years, 60kg and above, 666mg 3 times daily; under 60kg, 666mg at breakfast, 333mg at midday and 333mg in early evening. Prescribing notes Red = Hospital use only Green = GP & Hospital use. Drugs not classified as Red, Amber or Amber 2 are classified as Green by default Amber 1 = Drugs with shared care agreement Amber 2 = Initiated by Hospital specialist only Gateshead Health NHS Foundation Trust Drug Formulary Page 37 of 41 Date: 17.4.2013 These treatments are an adjunct to counselling. Choice of treatment will be influenced by patient acceptability; disulfiram is prescribed for patients who would benefit from a deterrent, particularly if they can nominate a partner who can help them to take it regularly. Patients receiving disulfiram suffer unpleasant systemic reactions if alcohol is consumed. Disulfiram self-administration should be supervised by, for example, a partner or an appropriate nurse, or at a day hospital. Acamprosate should be initiated as soon as possible after alcohol withdrawal and maintained if the patient relapses. Repeated relapsing to heavy drinking indicates nonefficacy. Recommended treatment period is 1 year. Vitamin supplementation Prophylaxis of Wernicke-Korsakoff syndrome First choices: thiamine (vitamin B1) or parenteral vitamins B and C (Pabrinex®) Treatment of patients with Wernicke-Korsakoff syndrome (hospital in-patients) First choice: parenteral vitamins B and C (Pabrinex®) Dose - Thiamine tablets 100mg: 100mg three times daily or 300mg as a single daily dose according to local policy, for 5 to 7 days.. - Pabrinex® I/V high potency injection (ascorbic acid 500mg, anhydrous glucose 1g, nicotinamide 160mg, pyridoxine hydrochloride 50mg, riboflavin 4mg, thiamine hydrochloride 250mg/10mL): by slow intravenous injection or infusion over at least 10 minutes, treatment, 2 pairs of ampoules every 8 hours for 2 to 3 days; prophylaxis, 1 pair of ampoules daily for 3 days. Prescribing notes Refer to local alcohol withdrawal protocols Prophylactic doses of parenteral vitamins (Pabrinex®) should be given to patients at risk of Wernicke-Korsakoff syndrome e.g. those with recent diarrhoea, vomiting, poor diet, other physical illness or signs of weight loss or malnutrition. The patient may have been consuming more than 20 units of alcohol per day. Oral thiamine is indicated for less severe cases while receiving detoxification treatment for 5 to 7 days. Patients who resume drinking or continue to drink and are at risk of malnourishment should be given oral thiamine 50mg or 300mg daily, according to local protocol, on a long-term basis. Patients with any sign of Wernicke-Korsakoff syndrome must be given treatment doses of parenteral vitamins (Pabrinex®) in hospital. Signs include confusion, ataxia, ophthalmoplegia/nystagmus, memory disturbance, hypothermia and hypotension, coma/unconsciousness. Pabrinex® should usually be administered in hospitals where facilities for treating anaphylaxis are available. Red = Hospital use only Green = GP & Hospital use. Drugs not classified as Red, Amber or Amber 2 are classified as Green by default Amber 1 = Drugs with shared care agreement Amber 2 = Initiated by Hospital specialist only Gateshead Health NHS Foundation Trust Drug Formulary Page 38 of 41 Date: 17.4.2013 Opioid dependence Methadone 1mg/ml SF mixture Dose - Methadone mixture 1mg/mL: use formulation containing 1mg/mL. Do not use stronger formulation (10mg/mL) or methadone tablets. Sugar-free formulation is available and is thought to cause fewer dental problems. Mark prescription "Methadone mixture 1mg/mL S/F". Smoking cessation Nicorrette 10mg inhalator starter pack and refill pack Nicorette 2mg and 4mg gum Nicorette 10mg, 15mg, 25mg invisi patches Nicorette Microtab 2mg s/l tablets NiQuitin CQ 4mg gum NiQuitin CQ 2mg, 4mg lozenges Varenicline starter pack Varenicline 500microgram and 1mg tablets Prescribing notes General notes • Prescribing of NRT should not commence until the patient has decided on a ‘target stop date’. Initial prescriptions should be sufficient to last one month after this date. Further prescriptions should only be issued if the quit attempt is continued at review. NRT must not be added to repeat prescribing systems. • Symptom control of nicotine withdrawal in hospital in-patients, is the only exception to a ‘target stop date’ being set prior to prescribing NRT. • Stopping smoking may result in slower metabolism and a consequent rise in blood levels of drug catalysed by CYP1A2 (and possibly CYP1A1). This is because the inhalation of induction agents such as polycyclic aromatic hydrocarbons has stopped. There are a few drugs for which this is clinically significant, eg warfarin, theophylline and clozapine. • NRT may be prescribed to adolescents (12-18 years) and ideally there should be a referral to a specialist stop smoking service for young people for provision of suitable support. Nicotine Replacement Therapy (NRT) If the first cigarette of the day is taken less than 30 minutes after waking, then initiate with a patch providing nicotine over 24 hours, reducing over 8–12 weeks as per product information. If the first cigarette of the day is taken more than 30 minutes after waking, then initiate with a patch providing nicotine over 16 hours, reducing over 8–12 weeks as per product information. If patients require treatment beyond 12 weeks they should be referred to specialist stop smoking service for further support and advice. Red = Hospital use only Green = GP & Hospital use. Drugs not classified as Red, Amber or Amber 2 are classified as Green by default Amber 1 = Drugs with shared care agreement Amber 2 = Initiated by Hospital specialist only Gateshead Health NHS Foundation Trust Drug Formulary Page 39 of 41 Date: 17.4.2013 • In patients with stable cardiovascular disease, NRT is a lesser risk than continuing to smoke and is therefore recommended. • Nicotine releases catecholamines which can effect carbohydrate metabolism. Smokers with diabetes should be advised to monitor the blood sugar levels more closely than usual when attempting to quit smoking (with or without NRT) • Moderate to severe hepatic impairment and/or severe renal impairment decreases the clearance of nicotine or its metabolites and NRT should be used with caution. Varenicline • When NRT has failed, varenicline may be prescribed on the recommendation of specialist smoking cessation services. • Varenicline should only be prescribed as a component of a smoking cessation support programme. The efficacy and safety in patients with significant co-morbidity is unclear. It should be prescribed for a maximum of 12 weeks only. • Varenicline should not be used in patients under 18 years old or in those that are pregnant or breastfeeding. • Patients prescribed varenicline should be advised of the MHRA/CSM advice regarding suicidal thoughts and behaviour. Those with a history of psychiatric illness should be monitored closely. • Patients should be advised to discontinue treatment and seek prompt medical advice if they develop agitation, depression or suicidal thoughts. • Varenicline is a ‘black triangle’ drug, therefore all adverse drug reactions should be reported to the MHRA, not just serious events. Bupropion • Bupropion is a non-formulary drug. Bupropion should not be used in combination with NRT products. • Bupropion is not licensed in patients under 18 years old. • Bupropion is contra-indicated in patients with a current or previous seizure disorder, diagnosis of bulimia or anorexia nervosa, severe hepatic cirrhosis, history of bipolar disorder, pregnancy, breast feeding, and caution advised in heavy alcohol intake. • Drug interactions are a significant problem with bupropion; see BNF. • Varenicline may be an alternative to bupropion as a component of a smoking cessation support programme. Trials show it appears to have fewer drug interactions and contraindications than bupropion, but the efficacy and safety in patients with significant co-morbidity is unclear. It should be prescribed for a maximum of 12 weeks only. Red = Hospital use only Green = GP & Hospital use. Drugs not classified as Red, Amber or Amber 2 are classified as Green by default Amber 1 = Drugs with shared care agreement Amber 2 = Initiated by Hospital specialist only Gateshead Health NHS Foundation Trust Drug Formulary Page 40 of 41 Date: 17.4.2013 4.11 Drugs for dementia Donepezil 5mg, 10mg tablets Donepezil 5mg, 10mg orthodispersible tablets Memantine 10mg, 20mg tablets Memantine Treatment Initiation Pack Rivastigmine 1.5mg, 3mg, 4.5mg, 6mg capsules Rivastigmine 2mg/ml oral solution Rivastigmine 4.6mg and 9.5mg patches Galantamine XL 8mg, 16mg, 24mg capsules Galantamine 4mg/ml oral solution Dose Doses are gradually titrated upwards by a specialist consultant according to response and sideeffects. The following dosing schedules are suggested: - Donepezil tablets 5mg, 10mg; orthodispersible tablets 5mg, 10mg: initially 5mg daily increased to 10mg daily after 6-12 weeks if necessary and tolerated. - Galantamine MR capsules 8mg, 16mg, 24mg: initially 8mg once daily for 4 weeks then 16mg once daily for 8 weeks then 16-24mg once daily. - Memantine tablets; as per BNF - Rivastigmine capsules 1.5mg, 3mg, 4.5mg, 6mg; oral solution 2mg/ml: initially 1.5mg twice daily for 4 weeks, then 3mg twice daily for 6 weeks, then 4.5mg twice daily for 6-10 weeks; max dose 6mg twice daily if tolerated. - Rivastigmine patches 4.6mg, 9.5mg: initially 4.6mg/24hour patched once daily for 4 weeks, then 9.5mg/24h hour patch. Prescribing notes Referral to old age psychiatry services should be made in the usual way if any doctor considers that a patient may have Alzheimer's disease and may be suitable for treatment. Treatment should not be initiated by GPs but may be prescribed under shared-care protocol. Donepezil orodispersible tablets are available for patients who have difficulty in swallowing oral dose formulations. Rivastigmine patches may be an appropriate choice of formulation for some patients. Memantine to be used as per NICE guidance. MHRA Drug Safety Update Rivastigmine transdermal patch: risk of medication errors Article date: June 2010 Summary Medication errors and inappropriate use of the rivastigmine transdermal patch have been reported, some of which resulted in overdose. Healthcare professionals should be aware of the correct use of rivastigmine, and should advise patients and caregivers as outlined in this article. Link: http://www.mhra.gov.uk/Safetyinformation/DrugSafetyUpdate/CON085079 Red = Hospital use only Green = GP & Hospital use. Drugs not classified as Red, Amber or Amber 2 are classified as Green by default Amber 1 = Drugs with shared care agreement Amber 2 = Initiated by Hospital specialist only Gateshead Health NHS Foundation Trust Drug Formulary Page 41 of 41 Date: 17.4.2013
