clozapine

Question 1

when is clozapine indicated

Answer 1

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

Question 2

important safety info with clozapine - reminder of potentially fatal risk of intestinal obstruction, faecal impaction, and paralytic ileus

Answer 2

Clozapine has been associated with varying degrees of impairment of intestinal peristalsis.
Patients and their carers should be advised to seek immediate medical advice before taking the next dose of clozapine if constipation develops.

Question 3

a patient has got constipation and they are taking clozapine. is this ok?

Answer 3

Clozapine has been associated with varying degrees of impairment of intestinal peristalsis
Seek immediate medical advice before taking the next dose of clozapine if constipation develops

Question 4

MHRA - Clozapine and other antipsychotics: monitoring blood concentrations for toxicity

Answer 4

following fatal cases involving toxicity of clozapine + other antipsychotics, MHRA recommends monitoring blood conc clozapine for toxicity in certain clinical situations e.g.
- pt stops smoking or switches to e-cigarette
- concomitant meds may interact to increase [clozapine]
- pnuemonia or other serious infection
- reduced clopazine metabolism suspected
- toxicity suspected

Question 5

a patient who is on clozapine and aripiprazole has recently quit smoking. what does this mean

Answer 5

Following fatal cases involving toxicity of clozapine and other antipsychotic medicines, the MHRA recommends monitoring blood concentration of clozapine for toxicity in certain clinical situations e.g. when a pt stops smoking or switches to e-cig

Question 6

monitoring for clozapine

Answer 6

• prolactin at astart, at 6 months, yearly
• leucocytes and differential blood counts - DBC weekly for 18 weeks, then fornightly for up to 1 year, then monthly as part of clozapine pt monitoring service
• only monotor [clozapine] in certain clincal situations
• close medical supervision during initiated - risk of collapse because of hypotension and convulsions
• blood lipids and weight base line, 3 months (frequent intervals during first 3 months), every 3 months for first year, yearly
• FBG baseline, one month, then 4-6 months

Question 7

a patient is on clozapine. what does this mean for you

Answer 7

Patient, prescriber, and supplying pharmacist must be registered with the appropriate Patient Monitoring Service—it takes several days to do this.

Question 8

clozapine planned withdrawal

Answer 8

reduce dose over 1–2 weeks to avoid risk of rebound psychosis. If abrupt withdrawal necessary observe patient carefully.

Question 9

for clozapine, in addition to normal monitoring requirements for all antipsychotics, you also need to monitor leucuocyte and differential blood counts. how often?

Answer 9

differential white blood cell monitoring weekly for 18 weeks, then fortnightly for up to one year, and then monthly as part of the clozapine patient monitoring service.

Question 10

hypersalivation with clozapine therapy can be treated with this drug (unlicensed indication) provided that the patient is not at particular risk from the additive antimuscarinic side-effects of this drug and clozapine.

Answer 10

hyoscine hydrobromide

Question 11

what blood disorders can clozapine cause, hence the monitoring requirements for luecocytes and differential blood counts

Answer 11

Neutropenia and potentially fatal agranulocytosis reported

Question 12

Myocarditis and cardiomyopathy with clozapine

Answer 12

Fatal myocarditis (most commonly in first 2 months) and cardiomyopathy reported
discontinue permanently if this occurs induced by clozapine

Persistent tachycardia especially in first 2 months should prompt observation for other indicators for myocarditis or cardiomyopathy
If myocarditis or cardiomyopathy suspected clozapine should be stopped and patient evaluated urgently by cardiologist
Discontinue permanently in clozapine-induced myocarditis or cardiomyopathy

Question 13

clozapine should be used with caution in pt recieving drugs that may cause constipation e.g. antimuscarinics or in hisotry of colonic disease of lower abdominal surgery because…

Answer 13

Impairment of intestinal peristalsis, including constipation, intestinal obstruction, faecal impaction, and paralytic ileus, (including fatal cases) reported.

Question 14

drugs that can cause constipation need to be used with caution as concurrent use might increase risk of developing intestinal obstruction

Answer 14

antimuscarinics - chlorphenamine, amitriptyline, darifenacin, solifenacin, tolterodine
opioids
antipsychotics
iron

Question 15

can you use in severe cardiac disorders

Answer 15

e.g. myocarditis
no

Question 16

do you still need to measure FBC after discontinuation

Answer 16

yes 4 weeks after discontinuation

Question 17

pt on clozapine has persistent tachycardia especially in first 2 months - this should prompt the following

Answer 17

observation for other indicators for myocarditis or cardiomyopathy

Question 18

what should pt report (hint bloods)

Answer 18

patients should report immediately symptoms of infection, especially influenza-like illness.

Question 19

Which drugs may need dose asdjustment if smoking started or stopped

Answer 19

Clozapine and olanzapine dose adjustment might be necessary if smoking started or stopped during treatment.

Question 20

Manufacturer advises avoid concomitant use of clozapine with drugs that have a substantial potential for causing agranulocytosis or a substantial potential to depress bone marrow function e.g.

Answer 20

carbamazepine
sulfonamide abx e.g. co trimoxazole, trimethoprim

Question 21

electrolyte disturbance

Answer 21

hyponatraemia

Question 22

Interaction with BZDPNs

Answer 22

Clozapine might increase the risk of respiratory depression and circulatory collapse when given with Chlordiazepoxide. Manufacturer advises caution.

Question 23

name 3 important SE

Answer 23

Neutropenia and potentially fatal agranulocytosis
Fatal myocarditis (most commonly in first 2 months) and cardiomyopathy
Impairment of intestinal peristalsis, including constipation, intestinal obstruction, faecal impaction, and paralytic ileus, (including fatal cases) reported.

Question 24

missed doses

Answer 24

If you miss 2 or more days of clozapine doses, talk to your doctor before you start taking it again. May need retitration

Question 25

monitoring hepatic

Answer 25

Manufacturer advises caution—monitor liver function (discontinue if liver enzymes are greater than 3 times the upper limit of normal or jaundice occurs); avoid in symptomatic or progressive impairment and in hepatic failure.