Recently, a clinical pharmacist was verifying medication orders and came across this interesting case. What would you have done in this situation?
A 42-year old homeless male is admitted to the medical floor for alcohol withdrawal. On admission, the physician orders chlordiazepoxide 25 mg every 6 hours, lorazepam 1 mg IV every 4 hours for agitation, and IVF with vitamins, thiamine, folic acid, and magnesium. Based on his past medical history, the patient is placed on his regular antipsychotic medication, lurasidone (Latuda) 40 mg at dinner. A few hours later, the patient is started on the 4-drug regimen: rifampin, isoniazid, pyrazinamide, and ethambutol. Vitamin B6 (pyridoxine) 50 mg daily was also ordered.
As you review the medication profile, a drug-drug interaction pops up on the computer screen. It reads, “Rifampin and lurasidone, MAJOR ” The warning surprises you as you don’t recall serious interactions with this antipsychotic. What is your next step? This is the part when our clinical skills kick into high gear. We have to ask the right questions and conduct our research with due diligence.
What is the interaction?
Rifampin is a cytochrome P450 3A4 inducer and will significantly reduce the concentration of lurasidone in the body. The combination is listed as a contraindication.
Does the patient have active TB or are we waiting for the final lab results?
The physician calls back and tells you that the patient has active TB and will be on the TB regimen for at least 6 months. Therefore, we cannot use lurasidone as an antipsychotic agent.
Why was lurasidone prescribed for this patient initially?
Lurasidone is a new antipsychotic with less effect on weight gain, hyperglycemia, and QT prolongation compared to other atypical agents. However, it is not available in generic form and its efficacy is similar to other antipsychotics. The patient has not reported any allergies or intolerances to other medications and according to the patient history and physician, it is unknown why the psychiatrist selected lurasidone.
The physician wants to start an antipsychotic since the patient is very combative. What antipsychotics can we use?
There are two classes of antipsychotics available, typical and atypical. Both classes are equally effective in reducing psychotic symptoms. However, typical or older generation agents can cause sedation, extrapyramidal symptoms, tardive dyskinesia, prolactinemia, drooling, and neuroleptic malignant syndrome. Atypical or 2nd generation antipsychotics can cause the same side effects but the incidence is much lower. The newer antipsychotics are generally known to cause more metabolic side effects such as hyperglycemia, weight gain, and dyslipidemia. A few agents are notorious for causing QT prolongation and agranulocytosis. Therefore, it is imperative to consider the patient’s comorbid conditions before selecting an agent. Financial ability and medication compliance are two other variables that should be considered as well.
Experts recommend using atypical agents as first-line therapy, to avoid the bothersome side effects of typical agents. Which atypical antipsychotic medication (listed below) is most suitable for this patient?
List of Atypical Antipyschotics
Which antipsychotics interact with rifampin?
Aripiprazole, asenapine, clozapine, iloperidone, lurasidone, paliperidone, and quetiapine have moderate to major drug interactions with rifampin. They cannot be considered in this patient. The patient is left with two options, olanzapine or risperidone. Both of them can cause weight gain, hyperglycemia, and dyslipidemia. Therefore, they should be avoided in patients with glucose intolerance, obesity, or hyperlipidemia. However, the patient does not present with any other illness than alcoholism and schizophrenia. His cholesterol levels are unknown (42 year old male with no family history of CHD). Risperidone can increase the QT interval but in this case, the patient has normal electrolytes and is not on a medication that can prolong the QT interval. He is at low risk of developing QT prolongation from risperidone.
Which antipsychotic agents can we recommend to the physician?
The physician may prescribe olanzapine or risperidone. Both are oral medications and they have a generic formulation, making them affordable. If medication compliance is an issue, olanzapine and risperidone are also available as fast-acting disintegrating tablets and intramuscular injections.
After discussing the case with the physician, Zyprexa Zydis (olanzapine) 10 mg daily was ordered. The patient tolerated the medication.
Lacy CF, Armstrong LL, Goldman MP et al. Drug Information Handbook. 20th ed. Hudson, Ohio: Lexi-Comp, 2012.
About the Author
Dr. Karine Wong has a 10 year history of working in hospital management and 2 years as a hospital pharmacist and outpatient pharmacist. She recently published a children's book called Don't Sit on Her.
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