Thread by @theABofPharmaC

Today I verified an order for clozapine for the very first time of my entire first year of being a pharmacist😳

Here are 5 clinical pearls I learned today about the use of clozapine for schizophrenia, important for new residents & interns to learn about this therapy! #pharmpearl

1⃣ Clozapine➡️second-generation, atypical antipsychotic➡️HIGHLY effective for treatment resistant schizophrenia

Unlike other antipsychotics➡️clozapine⬇️incidence of EPS or tardive dyskinesia➡️beneficial agent for pts who experience this debilitating ADE from other agents

So why if it is so effective is it reserved after failure of 2⃣adequate trials of other antipsychotics? 🤔

Clozapines use in clinical practice is limited due to its significant adverse effects and judicious monitoring required on treatment...see below...

Clozapine uniquely requires enrollment into a REMS program 2/2 risk of severe, fatal neutropenia🦠

ANC <500/uL is reported to occur in up to 1.3% of individuals➡️NOT dose dependent➡️⬆️ risk during first 18 weeks of treatment

MUST review REMS prescribing info for monitoring ANC!

Another significant ADE of clozapine is metabolic, clozapine is amongst the atypical with ⤴️ risk of weight gain & metabolic disturbances
Mechanism🔁 2/2 non-selective antagonism🚫@ histaminergic & seritonergic receptors

40% individuals➡️>7% weight gain..(continued below)

>33% of patients may expect total cholesterol elevations of >40mg/dL & 50% of patients may have an increase in triglycerides by >50mg/dL from baseline over a 42 week period 😳

Vigilant monitoring&initiation of CV therapy is critical to maintain benefit w/o developing ♥️ADE

Clozapine also has a BBW for orthostasis ♥️

Has a high affinity to the alpha-1-adrenergic receptors in the peripheral smooth muscle➡️ predisposing patients to orthostasis

Take at bedtime and keep up fluid intake! Monitor BP medications and make adjustments as needed!

Clozapine also causes tachycardia➡️combined antagonism at the alpha-1-adrenergic receptors in the periphery & direct M1 antagonism at the myocardium that leads to sympathetic hyperactivity

An⤴️in resting heart rate by 10-15 bpm occurs in around 25% of patients➡️usually benign

Lastly (although there are many more) Despite its anticholinergic effects, clozapine causes hypersalivation (~30-80% of pts)
Some case reports suggest sublingual atropine eye drops may relieve sx without exacerbating systemic anticholinergic ADE!
ncbi.nlm.nih.gov/pmc/articles/P…

Overall, clozapine is a high risk med, comes w/ MANY toxicities not included in this thread, if you have more pearls, please share. For all new pharmacy or medical residents, please be aware of the REMs for clozapine and how to monitor the unique adverse effects of this therapy!

What other clozapine pearls do you have to share? @JonathanGLeung @runthismomlife @psypharmacopeia @AJWPharm @MadelineBelk @DRxDray