NAPLEX® Review Question of the Week: Clozapine Conundrum

AF, a 62-year-old male, has been a patient at your specialty pharmacy for 10 years now. He comes into the pharmacy to pick up a refill for his clozapine, famotidine, and atorvastatin, which are medications he’s been taking for many years. AF was recently diagnosed with colorectal cancer, and he has opened up to you about the challenges he’s faced since starting chemotherapy last week.
PMH
Schizophrenia
Colorectal cancer
GERD
Hyperlipidemia
Current Medications
Clozapine 300 mg PO QD
5-fluorouracil IV 2400mg/m2 Q2wks
Leucovorin IV 2000mg/m2/cycle
Famotidine 20 mg PO QD
Atorvastatin 40 mg PO QD
As a pharmacist, what is your biggest concern for AF at this moment?
A. Counseling AF on pharyngeal dysesthesias that can occur from taking 5-fluorouracil
B. Drug-drug interaction between clozapine and famotidine
C. Increased risk of agranulocytosis
D. Facilitate new enrollment of AF in a REMS program
Answer with Rationale
Risk Mitigation Evaluation Strategy (REMS) Programs are implemented to promote the safe use of medications with serious safety concerns. As of 2007, the U.S. Food and Drug Administration (FDA) can require a REMS program for certain medications in order to ensure that the benefits of using the medication will outweigh the risks. There are currently FDA approved REMS programs for over 70 different medications, including clozapine.1 Clozapine is a second generation atypical antipsychotic that interferes with the binding of dopamine to its receptors, and due to its boxed warnings for agranulocytosis, seizures, myocarditis, as well as increased mortality in elderly patients with dementia-related psychosis, clozapine is reserved for severely ill schizophrenic patients who have already tried and failed other standard therapies. It is important to remember that clozapine should not be taken with other medications that cause myelosuppression or increase a patient’s risk for agranulocytosis.2
Answer A is incorrect. 5-fluorouracil (5-FU) is an antimetabolite and pyrimidine analog that prevents DNA synthesis through inhibition of thymidylate synthetase. It is a chemotherapeutic used for a number of cancers. While 5-FU can cause a number of adverse effects, pharyngeal dysesthesia is not a common adverse reaction one would see with 5-FU. Cold-induced pharyngeal dysesthesia is a hallmark side effect of taking oxaliplatin, so this would be an important counseling point if the patient was on this medication.
Answer B is incorrect. There is currently no known clinically significant interaction between clozapine and famotidine.
Answer C is correct. Clozapine has a black box warning for causing agranulocytosis, and for this reason, it is only available for patients through the Risk Evaluation and Mitigation Strategy (REMS) Program. Due to the patient’s recent cancer diagnosis and initiation of a chemotherapy regimen, the potential increased risk of agranulocytosis is a significant concern. The myelosuppressive effects of 5-FU can increase the risk of severe neutropenia with clozapine.
Answer D is incorrect. Clozapine is only available through adequate enrollment in the REMS program; however, the patient has been taking clozapine for years, so it is likely that the patient is already enrolled in the REMS program.
Brand/Generic: atorvastatin (Lipitor), clozapine (Clozaril, Versacloz), famotidine (Pepcid), 5-fluorouracil (Adrucil), folinic acid (Leucovorin)
NAPLEX Content Domains Covered
Domain 1 - Foundational Knowledge for Pharmacy Practice
A. Pharmaceutical science principles and concepts
1. Pharmacology
Domain 2. Medication Use Process (Prescribing, Transcribing and Documenting, Dispensing, Administering, and Monitoring)
A. Prescriptions and medication order interpretation
1. Drug names and therapeutic classes.
4. Prescription regulations (eg, boxed warnings, risk evaluation and mitigation strategies)
Domain 3. Person-Centered Assessment and Treatment Planning
A. Medication history, allergy history, and reconciliation
C. 3. Interactions (eg, drug-drug, drug-condition, drug-food, drug-allergy, drug-laboratory)
D. Therapeutic monitoring, plan development, evaluation, and modifications
2. Safety
Resources
- Approved risk evaluation and mitigation strategies (REMS). Accessed January 15, 2025. https://www.accessdata.fda.gov/scripts/cder/rems/index.cfm
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