What Went Wrong? Clozapine Vol 40 No 3 - Mar 2015 | Mar. 24, 2015 Safety, Drug Interactions, What Went Wrong, adverse drug reaction

Dear College,

I recently spent 3 weeks on the psychiatric unit of the local hospital.  During my stay, the psychiatrist changed my antipsychotic medication to clozapine. I was initially concerned about clozapine’s side effects but the doctor and nurse spent a lot of time answering my questions. I did experience sedation but that improved with time. The most annoying part of using clozapine was the weekly blood work!

Once out of hospital I picked up a month supply of clozapine from my local pharmacy. I noticed that the pills looked slightly different from what I received in hospital but the pharmacist reassured me that it was clozapine.

Two weeks later, I met with my Case Manager Worker at the Mental Health Center. I brought in my clozapine to discuss the changes but to my surprise I was told that this was the wrong product and that I had been given far too many pills.

Now I am not sure that I should be taking clozapine at all.

-Confused about clozapine

The pharmacist involved reports:

• The client brought in a prescription for clozapine (Genpharm) 350mg HS, 1 month and 2 repeats. I usually carry the Apotex brand so I provided a one month supply as per directions. The client did comment on the different appearance so I spent time reassuring her that it was the same drug.
• Two weeks later I was contacted by the client’s Case Manager Worker concerned about the change in brand and asking about a registration form. I know that the products are considered interchangeable. I thought that registration was the responsibility of the psychiatrist.
• We do not handle a lot of clozapine prescriptions at our store.

Why does Health Canada require mandatory monitoring for clozapine?

Clients using clozapine have a small but significant risk of developing agranulocytosis.  Mandatory hematological monitoring significantly reduces the incidence of agranulocytosis.

The ability to identify patients experiencing a drop in their WBC and differential permits the physician to intervene in a timely manner. 

Is this the “wrong” product?  Is there a concern about switching to the Apotex product?

1. Health Canada mandates that all clozapine distributors maintain independent registration and monitoring systems to optimize patient safety.  All patients must be registered with either Apotex, Genpharm or Novartis.  Patient registration forms must be completed and registration confirmed prior to initiating clozapine treatment. 
2. Since the prescribing physician is ultimately responsible for verifying a patient's hematological/non-rechallengable status the physician must know which monitoring system the patient is registered in.
3. Patients cannot be switched from one brand of clozapine to another unless the pharmacist obtains a new, registry-specific patient registration form filled out by the prescribing physician.
4. Any change in the Laboratory, Case Coordinator/Manager, pharmacy or physician requires a modification of that section of the registration form.  It is not necessary to complete the entire form just the relevant sections.

Apotex clozapine is the wrong product if the patient is registered on Genpharm clozapine.  Switching brands requires registering the patient on the new brand.  The physician and pharmacist are responsible for completing/updating their section of the registration form.

Why is it unacceptable to dispense the one month supply of clozapine to a patient starting clozapine?  What about patients on clozapine residing in boarding homes?

1. By signing a manufacturer specific, patient registration form, pharmacists agree to provide clozapine on a weekly, every two weeks or monthly basis.  The quantity provided depends on the stage of the clozapine trial.
2. Lab work is required weekly for the first 28 weeks or 6 months of clozapine.  After 6 months, if there have been no abnormalities in lab work, the interval can be extended to 2 weeks.  After 52 weeks or 12 months, the interval can be extended to monthly.
3. Pharmacies are able to dispense a larger supply of clozapine if a patient is residing in a boarding home and they have the ability to retrieve the supply.  The pharmacy should continue to confirm that the appropriate lab work is completed at the appropriate intervals (i.e. weekly, every 2 weeks or monthly).

The pharmacist is permitted to dispense one week, 2 weeks and one month supply of clozapine respectively depending on the frequency of the lab work and/or their ability to retrieve the supply.

Dear College,

Although I have been taking clozapine for 4 months and doing well, I really hate the lab work.  I usually go to the lab work every Wednesdays then pick up my clozapine from my pharmacy.  On more than one occasion, my pharmacist has refused to release my supply of clozapine if they cannot see my lab work results. 

Last week my Case Manager called and reported that I had a “yellow alert” and needed to increase the frequency of my lab work to twice a week.  However, when I went to pick up my clozapine I received a limited supply.  Now I am running between the lab and the pharmacy.

-Exhausted and frustrated

Does the pharmacist need to see the lab work before they release clozapine?

1. Signing the registration form means that the pharmacist agrees to provide an appropriate supply of clozapine after confirming that lab work has been completed (eg.No blood – no drug).
2. The pharmacist does not need to see the lab work results to release clozapine, they only need to confirm that lab work has been collected.

What happens if the patient misses their lab work and they are out of medication?

1. It is important that clients on clozapine stay on medication.  Patient’s missing more than 48 hours of clozapine can rapidly deteriorate.  After 48 hours, patients cannot restart at their regular dose and clozapine has to be re-started/re-titrated to avoid serious cardiovascular adverse effects.
2. The pharmacist can dispense a small emergency supply of clozapine and refer the patient to the lab ASAP. 
3. Patient’s refusing lab work have to discontinue clozapine.

What about yellow, flashing yellow and red alerts?

1. If a patient’s lab work triggers a “yellow” or “flashing yellow” alert their monitoring frequency should increase to twice a week.  The prescribing physician and/or their delegate is responsible for informing the patient of the change in lab work.  The pharmacist can continue to deliver a minimum of a week’s supply of clozapine.
2. On receipt of a “red” alert, clozapine should be held until the lab work is repeated, preferably within 24 hours.  The physician and/or their delegate will contact the patient to provide instructions regarding lab work and to discontinue clozapine once the “red” alert is confirmed with a repeat CBC and differential.
3. The pharmacist can support these processes by contacting the physician and/or their delegate to confirm the patients status (eg. Hold or discontinue clozapine, etc).