While working in an assisted-living facility, a provider wants to prescribe olanzapine for a 73-year-old patient (RS) who is having trouble with insomnia. Before placing the order, they ask you if there is anything about olanzapine they should consider for the patient.

Past medical history:

Type 2 Diabetes: Metformin 1000mg PO BID, Tresiba 16 units SQ daily

Hypertension: Amlodipine 10mg PO daily, Coreg 6.25mg PO BID

Depression: Fluoxetine 20mg PO daily

CAP: Azithromycin 250mg PO daily (day 4 of 5)

Atrial fibrillation: Eliquis 5mg PO BID  

Dementia: Donepezil 5mg PO nightly

Which of the following should be considered before prescribing olanzapine to RS? Select all that apply.

A. Increased risk of hypoglycemia

B. Increased risk of uncontrolled hypertension 

C. Increased risk of mortality 

D. Increased risk of QTc prolongation

E. Increased risk of acute kidney injury

Answer with rationale:

Antipsychotics can be tricky, because they tend to carry a large amount of potential adverse effects and drug interactions. Olanzapine in particular is typically used to treat bipolar I disorder, schizophrenia, and treatment resistant major depressive disorder. However, due to its sedating properties, it can also be used off-label for insomnia.

Olanzapine can cause significant increases in blood glucose levels, potentially leading to hyperglycemia or new-onset diabetes. It may also contribute to changes in blood pressure, specifically orthostatic hypotension, especially during initial treatment. The medication carries a boxed warning for increased mortality in elderly patients with dementia-related psychosis. While not as strongly associated with QTc prolongation as some other antipsychotics, olanzapine still has that risk, particularly when combined with other QTc-prolonging drugs. The concern with significant QTc prolongation is causing Torsades de Pointes, a potentially fatal arrhythmia. There are no initial dosing adjustments necessary with impaired renal or hepatic function, although the potential for induced liver injury does exist and should be monitored appropriately. 

Answer A is incorrect: Olanzapine has a risk of hyperglycemia, not hypoglycemia. It is important to ensure proper blood glucose monitoring while initiating olanzapine.

Answer B is incorrect: Olanzapine has a risk of causing orthostatic hypotension, and patients on blood pressure medications should be monitored for these risks, especially in an elderly population where a fall risk is more common.

Answer C is correct: Olanzapine and all other antipsychotics carry a boxed warning for increased risk of mortality in elderly patients with dementia-related psychosis. The risk of death is typically through cardiovascular events or infections.

Answer D is correct: While on its own, the risk of QTc prolongation is relatively low for olanzapine, it has an additive effect when combined with other QTc prolonging drugs, such as fluoxetine and azithromycin. The risk of drug-induced QTc prolongation and subsequent Torsades de Pointes is rare fortunately, but the more medications the higher the risk. 

Answer E is incorrect: Olanzapine is not associated with an increased risk of acute kidney injury. 

Brand/generics Covered:

Olanzapine (Zyprexa), Metformin (Glucophage), Insulin degludec (Tresiba), Amlodipine (Norvasc), Carvedilol (Coreg), Fluoxetine (Prozac), Azithromycin (Zithromax, Z-Pak),  Apixaban (Eliquis), Donepezil (Aricept)

Naplex Content Domains Covered

2.A.4,5 - Prescription regulations (boxed warnings) and safety measures

3.C.2,3,5 - Appropriateness of therapy, interactions, and adverse drug reactions

3.D.2 - Safety evaluation, plan development