MHRA Drug Safety Update (August 2020): Clozapine and other antipsychotics - monitoring blood concentrations for toxicity:

• Please see the clozapine entry below for the clozapine protocol which defines the circumstances in which monitoring of plasma clozapine levels is appropriate
• For antipsychotics other than clozapine, drug level monitoring for toxicity is not routine practice. This service is not provided by local trust laboratories. Local advice is that clinicians who have concerns about a patient receiving an antipsychotic should in the first instance contact the mental health specialist team for advice. This applies to patients with symptoms suggestive of toxicity, or when concomitant medicines may interact to increase antipsychotic drug levels, and also when non-adherence or poor response to treatment is suspected.

Antipsychotics (first-generation)

Haloperidol

• Tablets 1.5mg, 5mg, 10mg (£14.97 = 28 x 10mg)
• Oral solution sugar free 5mg/5ml (£7.51 = 100ml)
• Solution for injection ampoules 5mg/1ml (£6.26 = 1ml ampoule)

Indications

• Schizophrenia and other psychoses

Notes

1. MHRA Drug Safety Update (December 2021): Haloperidol (Haldol): reminder of risks when used in elderly patients for the acute treatment of delirium
   1. special caution is required when using haloperidol for the acute treatment of delirium in frail, elderly patients
   2. only consider haloperidol for delirium when non-pharmacological interventions are ineffective and no contraindications are present (including Parkinson's disease and dementia with Lewy bodies)
   3. before initiating treatment, a baseline electrocardiogram (ECG) and correction of any electrolyte disturbances is recommended; cardiac and electrolyte monitoring should be repeated during treatment (see safety update)
   4. prescribe the lowest possible dose for the shortest possible time, ensuring that any dose up-titration is gradual and reviewed frequently
   5. monitor for and investigate early any extrapyramidal adverse effects, such as acute dystonia, parkinsonism, tardive dyskinesia, akathisia, hypersalivation, and dysphagia

Levomepromazine

• Tablets 25mg (£22.51 = 84 tablets)
• Solution for injection ampoules 25mg/1ml (£2.01 = 1ml ampoule)

Indications

• Nausea and vomiting in palliative care

Sulpiride

• Tablets 200mg, 400mg (£21.23 = 30 x 400mg)
• Oral solution sugar free 200mg/5ml (£93.64 = 150ml)

Indications

• Schizophrenia

Antipsychotics (second-generation)

Amisulpride

• Tablets 50mg, 100mg, 200mg, 400mg (£35.44 = 400mg daily)
• Oral solution sugar free 100mg/1ml (£98.60 = 60ml)

Indications

• Schizophrenia

Aripiprazole

• Tablets 5mg, 10mg, 15mg, 30mg (£6.66 = 15mg daily)
• Orodispersible tablets 10mg, 15mg (£58.72 = 15mg daily)

Indications

• Schizophrenia

Notes

1. NICE TA213 Schizophrenia - aripiprazole (January 2011)
2. NICE TA292 Bipolar disorder (adolescents) - aripiprazole (July 2013)
3. MHRA Drug Safety Update (December 2023): Aripiprazole (Abilify and generic brands): risk of pathological gambling
   1. Yellow Card reports of gambling disorder and pathological gambling associated with aripiprazole use have increased in number. The reports occurred in patients with and without a prior history of gambling disorder and the majority were reported to resolve upon reduction of dose or stopping treatment with aripiprazole. 
   2. Advise patients and their caregivers to be alert to the development of new or increased urges to gamble and other impulse control symptoms, such as excessive eating or spending, or an abnormally high sex drive.
   3. Consider dose reduction or stopping the medication if a patient develops these symptoms.
   4. Refer to the safety update for advice for patients, parents, and carers.

Lurasidone

• Tablets 18.5mg, 37mg, 74mg (£80.00 = 28 x 74mg)

Indications

• Schizophrenia in adults:
  • who have not responded to, or not tolerated, separate trials of amisulpride and aripiprazole.
  • with QTc prolongation (at baseline or during antipsychotic treatment) where patients have previously not responded to, or not tolerated, aripiprazole.
• Schizophrenia in children and adolescents aged 13 years and above who have not responded to, or not tolerated, aripiprazole.

Notes

1. Lurasidone has a higher cost compared to other antipsychotics and no evidence of superior efficacy. However, some evidence suggests it has a lower incidence of antipsychotic associated weight gain; therefore, for the cohort of patients where treatment is routinely commissioned (see notes above), lurasidone may be beneficial for patients with cardiovascular disease and/or diabetes, or for patients who have significant risk factors for developing these conditions (e.g., high Q-RISK score, obesity, pre-diabetic).
2. The routine commissioning of lurasidone is accepted in Devon for the management of schizophrenia in adults only in line with specified criteria (see Commissioning Policy for more details).
3. The routine commissioning of lurasidone is accepted in Devon for the management of schizophrenia in children and adolescents (aged 13 years and above) only in line with specified criteria (see Commissioning Policy for more details).

Olanzapine

• Tablets 2.5mg, 5mg, 7.5mg, 10mg, 15mg, 20mg (£0.94 = 10mg daily)
• Orodispersible tablets sugar free 5mg, 10mg, 15mg, 20mg (£14.60 = 10mg daily) (see note 1)
• Powder for solution for injection vials 10mg (see note 2)

Indications

• Schizophrenia
• Mania

Notes

1. Orodispersible tablets should only be used for patients with swallowing difficulties or to support supervised administration.
2. Short-acting injection should be used only in secondary care in accordance with Trust's rapid tranquillisation policy.

Quetiapine

• Tablets 25mg, 100mg, 150mg, 200mg, 300mg (£2.50 = 400mg daily)
• Modified-release tablets 50mg, 150mg, 200mg, 300mg, 400mg (click here for preferred brand)

Indications

• Schizophrenia

Notes:

1. Quetiapine modified-release tablets should only be used when individuals cannot tolerate immediate-release or if concordance with a twice daily regimen is difficult.
2. Where a preferred brand is recommended for a particular presentation, prescribing by brand helps ensure cost-efficient use of local NHS resources (see preferred brand link above)

Risperidone

• Tablets 500micrograms, 1mg, 2mg, 3mg, 4mg (£1.67 = 2 x 3mg daily)

Indications

• Acute and chronic psychoses
• Mania
• Short term treatment (up to 6 weeks) of persistent aggression in moderate to severe Alzheimer's dementia unresponsive to non-pharmacological approaches and where there is risk of harm to the patient or others

Notes:

1. Due to their cost risperidone 6mg tablets have not been included in the formulary. Prescribing 2 x 3mg tablets costs significantly less.
2. No new patients will receive risperidone long-acting injection. There is an existing cohort of patients who will continue to receive risperidone.
3. Refer to the DPT prescribing guideline PG14: Pharmacological Management of Severe Behavioural & Psychological Symptoms of Dementia (BPSD) for dosing regimen, cautions, treatment review and discontinuation
4. Exercise caution if risperidone is prescribed together with furosemide (higher incidence of mortality observed although mechanism unclear). The risks and benefits of combining risperidone with furosemide or other potent diuretics must be considered prior to use. Refer to risperidone Summary of Product Characteristics for more information.

Clozapine

• Clozaril tablets 25mg, 100mg
• Denzapine oral suspension 50mg/ml

Indications

• Schizophrenia in patients unresponsive to, or intolerant of, conventional antipsychotic drugs

Notes

1. Prescribers, pharmacies and patients must be registered with either the Clozaril® Patient Monitoring Service (CPMS) for those taking tablets or the Denzapine® Monitoring Service (DMS) for those taking suspension. Make sure patients are registered in the correct service; they cannot be registered for both. Refer to hospital Pharmacy Department and the:
   1. DPT policy Pharmacological Treatment of Schizophrenia and Related Psychoses
   2. DPT Clinical Protocol for Clozapine CP19
2. Treatment needs to re-titrated if there has been more than 48 hours between doses. Patient needs to be urgently reviewed by their specialist.
3. MHRA Drug Safety Update (October 2017): Clozapine: reminder of potentially fatal risk of intestinal obstruction, faecal impaction, and paralytic ileus
   1. the antipsychotic drug clozapine has been associated with varying degrees of impairment of intestinal peristalsis; this effect can range from constipation, which is very common, to very rare intestinal obstruction, faecal impaction, and paralytic ileus
   2. exercise particular care in patients receiving other drugs known to cause constipation (especially those with anticholinergic properties), patients with a history of colonic disease or lower abdominal surgery, and in patients aged 60 years and older
   3. advise patients to report constipation immediately and actively treat any constipation that occurs, with an osmotic and/or stimulant laxative
   4. Additional local information and advice is available in the Medicines Optimisation Post Live article here (requires N3 connection)
4. MHRA Drug Safety Update (August 2020): Clozapine and other antipsychotics - monitoring blood concentrations for toxicity. For guidance on monitoring blood concentrations of clozapine, follow the DPT Clinical Protocol for Clozapine CP19