Clozapine

In the UK, clozapine is licensed for use in patients with ‘treatment-resistant’ schizophrenia, which is defined as a “lack of satisfactory clinical improvement despite the use of adequate doses of at least two different antipsychotic agents, including an atypical antipsychotic agent, prescribed for adequate duration”. 

Prescribed by a specialist in the majority of cases, routine monitoring is a prerequisite of clozapine use because of the risk of neutropenia and agranulocytosis. Regular blood tests are required and dispensing must not occur without a valid blood test. Prescribers and pharmacists must also be registered with the companies that manufacture Clozaril, Denzapine or Zaponex to supply clozapine. Patients must be registered with the Clozapine Patient Monitoring Service (CPMS).

Due to a high occurrence of side-effects, clozapine is slowly titrated to a treatment dose. A break in treatment of greater than 48 hours requires re-titration due to the increased risk of seizures, cardiac issues and enhanced sedation.

Clozapine levels are affected by the hydrocarbons in cigarette smoke, so stopping smoking can significantly increase plasma levels of the drug and should be monitored. The same caution should be exercised when supplying NRT.

Clozapine has been associated with varying degrees of intestinal peristalsis impairment; from constipation, which is very common, to very rare intestinal obstruction, faecal impaction and paralytic ileus. Identification and treatment of constipation should be addressed promptly.

Some antibiotics can interact with clozapine by either increasing/decreasing drug levels or by increasing neutropenia risk. Caution should be exercised as clozapine may not always be on GP prescribing systems to highlight these risks.