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Olanzapine interactions to avoid

The most serious olanzapine interactions occur when it is used along with drugs that prolong QTc
Marissa Walsh headshot
By | Feb. 8, 2024
Rx prescription pad and Rx pills: Olanzapine interactions

Key takeaways

  • The most dangerous olanzapine interactions include concomitant administration with QTc-prolonging medications.

  • Concomitant use of olanzapine and medications known to cause long QT syndrome can result in cardiac conduction abnormalities, including life-threatening heart rhythm patterns like Torsades de Pointes. 

  • Olanzapine consumed with other medications that impact the central nervous system (CNS) as CNS depressants or with activity on serotonin may have additive effects, which can result in side effects related to the toxicity of olanzapine.

  • Any extreme changes in mental status, like extreme drowsiness, delirium, or impaired cognitive function, warrant immediate medical help.

  • Less serious interactions may occur with antidiabetic agents and blood pressure-lowering medications, resulting in additive effects of those drug classes.

  • In the event of an assumed olanzapine interaction, contact a healthcare provider immediately.

In this article:

Olanzapine, the generic drug of Zyprexa, is a second-generation antipsychotic medication. While it can be used to manage many mental health conditions, including bipolar disorder and schizophrenia, it also plays a role in the prevention and treatment of chemotherapy-induced nausea and vomiting. 

Olanzapine interacts with medications that impact the central nervous system, like antidepressants, other medications that lower the seizure threshold, and medications with anticholinergic effects. Olanzapine can prolong the QTc interval, and combining it with similar medications can have additive effects that can result in serious medical conditions. 

When olanzapine is added to a medication regimen, consulting a healthcare professional such as a pharmacist to review for possible drug-drug interactions is critical. It is important to be aware of olanzapine’s interactions with other drugs and foods that can increase the risk of or worsen side effects, and always to take olanzapine per the doctor’s instructions.  

Olanzapine drug interactions

Olanzapine interacts with medications that cause similar side effects, which can range from additive QTc prolongation and potentially deadly risks to the possibility of anticholinergic delirium and serotonin syndrome. Some of these effects can result from concomitant prescription medications, but some interacting medications can also be obtained over-the-counter (OTC). Whenever initiating olanzapine, it’s critical to give your healthcare provider a complete list of your medications so that a thorough medication reconciliation can be performed to identify any possible interactions. 

QT-prolonging, CYP3A4 inhibiting medications

Olanzapine treatment may enhance the QTc-prolonging effect of other QTc-prolonging medications with a single dose. The QT interval is the part of an electrocardiogram (EKG) report that represents the time it takes the heart to contract and recover. Long QT syndromes can be inherited. This occurs as the result of an issue with the heart’s electrical conduction such that it takes longer than normal to recharge between heartbeats, which is due to an issue with ion channels or the flow of ions (sodium, calcium, potassium, and chloride) in and out of heart muscle cells to produce electrical activity, resulting in an irregular heartbeat. Medications can also cause long QT syndrome. When the QT interval is prolonged, the risk for irregular heartbeats like ventricular tachycardias is increased, which can result in cardiac arrest and sudden death due to the heart’s inability to pump blood throughout the body effectively. The risk of QT prolongation is increased with additional risk factors, including older adults, female gender, low levels of potassium or magnesium, and a medical history of heart problems. 

Here are the most concerning QTc-prolonging medications that may interact with olanzapine:

Fluoroquinolone antibiotics, including:

  • Ciprofloxacin
  • Delafloxacin
  • Levofloxacin
  • Moxifloxacin

Macrolide antibiotics, including:

  • Azithromycin
  • Clarithromycin
  • Erythromycin

Azole antifungals, including:

  • Fluconazole
  • Ketoconazole
  • Isavuconazole
  • Posaconazole
  • Itraconazole
  • Voriconazole

Anticholinergics

Olanzapine may enhance the anticholinergic effects of other medications with the same known effects. Anticholinergic medications block the activity of the neurotransmitter acetylcholine in both the central and peripheral nervous systems. In turn, anticholinergics inhibit the actions of the parasympathetic nervous system, which controls involuntary actions of muscle in the gastrointestinal tract, lungs, and urinary tract, among others. Many medications possess anticholinergic activity, with specific drugs with activity deemed therapeutic to be problematic in combination with olanzapine. Some medications depend on their anticholinergic effects for their therapeutic effects, while others—like olanzapine and other antipsychotics—possess these properties but are not responsible for their intended effects. 

Common side effects of anticholinergic medications include constipation, reduced gut motility, and dry mucous membranes. Effects on the central nervous system include headache, impaired memory, and reduced cognitive dysfunction. Higher doses of anticholinergic medications and additive effects from multiple medications with anticholinergic properties can result in anticholinergic delirium, presenting as agitation, delirium, and potentially seizures. The effects of anticholinergic medications require caution with their use, especially when used in combination with other medications with similar effects, particularly in susceptible elderly patient populations. Healthcare providers prescribing medications with anticholinergic properties or pharmacists counseling patients on over-the-counter medications added to their prescription medications need to be aware of the potential additive side effects to prevent adverse events. 

The following group of medications possess strong anticholinergic effects:

Central Nervous System (CNS) depressants

Olanzapine CNS depression may enhance the CNS depressant effects of other medications, like opioids and benzodiazepines. The presumed mechanism of CNS depression caused by olanzapine is through histamine-1 receptor antagonism. Combinations of medications with these effects should be avoided when possible and only combined when alternative options are inadequate. If deemed necessary to combine, the dosages and durations of the contributing medications should be reduced and kept to a minimum. Side effects to monitor include slowed or difficult breathing—either of which warrants immediate attention by a healthcare professional. 

Seizure threshold-lowering medications

Olanzapine and other antipsychotics are known to reduce the seizure threshold, which can provoke epileptic seizures. Many other medications can also lower the seizure threshold, including certain antidepressants. Seizures triggered by these medications have a dose-dependent effect but are also dependent on the seizure-inducing potential of the medication and the individual’s seizure history. Suppose medications with seizure threshold lowering potential are co-administered. In that case, it is important to start with low doses and titrate them up slowly, as well as maintain the minimal effective dose. Development of any seizure-like activity while on olanzapine requires emergent medical attention.

Serotonergic agents

Olanzapine’s therapeutic effect is in part due to its serotonergic activity, which sets second-generation antipsychotics apart from typical antipsychotics. This allows for decreased extrapyramidal symptoms, including tardive dyskinesia—which is a movement disorder where individuals can’t control certain movements. However, combination with additional serotonergic agents, like selective serotonin reuptake inhibitors (SSRIs) or serotonin-norepinephrine reuptake inhibitors (SNRIs) may increase the risk of adverse and toxic effects, including the development of serotonin syndrome. Additional serotonergic agents may increase dopamine blockage, which increases the risk for the development of neuroleptic malignant syndrome. Both of these conditions are considered medical emergencies requiring immediate medical attention, with symptoms ranging from agitation and confusion, heavy sweating, high blood pressure, and muscle rigidity to seizures and unconsciousness. Combinations of known serotonergic medications with olanzapine should only occur under the oversight of a medical professional with close monitoring and education concerning adverse effects.

Blood pressure-lowering medications

Concomitant use of blood pressure medications for the management of hypertension with second-generation (atypical) antipsychotic medications like olanzapine may enhance its hypotensive effects. Caution should be exercised when taking these medications in combination with increased monitoring for low blood pressure. The mechanism of this interaction is due to the alpha-1 adrenergic blocking activity of atypical antipsychotics, causing excessive hypotensive effects. The prescribing information of olanzapine states that orthostatic hypotension and associated syncope may occur with its use, so increased monitoring for these effects should be advised for patients taking this combination. 

The following class of drugs are some blood pressure-lowering medications which may contribute to this interaction.

Olanzapine food interactions

Olanzapine, and other second-generation antipsychotic drugs, can cause weight gain and alterations in blood sugar levels. These effects can in turn result in high cholesterol, which can cause heart disease. It is important to consume a balanced healthy diet without increasing portion sizes, with individualized intervention provided by a dietitian an important consideration for an individual on olanzapine. One food that directly interacts with olanzapine is broccoli. Broccoli may decrease the serum concentration of olanzapine due to its ability to induce the metabolism of olanzapine.

Olanzapine and grapefruit

Grapefruit juice may increase the amount of a drug available in the body by decreasing the way the body breaks down or metabolizes the medication. Grapefruit interacts with many prescription drugs, and when consumed with olanzapine can further increase the risk of drug interactions. Grapefruit juice is known to inhibit CYP3A4, so when taken concomitantly with olanzapine the inhibition may be additive. If olanzapine and grapefruit juice are consumed with another medication that requires metabolism to an inactive form via CYP3A4, its blood levels and potential side effects could increase. Without definitive research to show that grapefruit juice is safe, it may be best to limit or avoid grapefruit juice when taking olanzapine minimally to ensure a consistent intake, especially if also receiving other medications metabolized by CYP3A4. 

Other olanzapine interactions

Olanzapine can interact with recreational products and have serious effects on special patient populations. 

Olanzapine and alcohol 

Alcohol interacts with many prescription drugs. Alcohol is considered a CNS depressant, so when taken in conjunction with other CNS depressants an individual can experience additive CNS depression. There is no contraindication to consuming alcoholic drinks while taking olanzapine, but given the alteration of effects on the individual, it should be done cautiously and in moderation. If serious side effects result, it is best to avoid the combination altogether. 

Olanzapine and cigarettes

Cigarette smoking of tobacco or use of other tobacco products increases the activity of CYP1A2, which is partially responsible for the metabolism of olanzapine. The role of the smoking-induced cytochrome P1A2 results in decreased steady-state concentration of olanzapine, which could have serious implications on the potential benefit of this medication on symptoms of schizophrenia or other conditions for which it’s being used. The dose of olanzapine may need to be increased by 30-50% in individuals who use tobacco products. 

Olanzapine and special patient populations

Older adults with dementia-related psychosis treated with antipsychotics like olanzapine are at an increased risk of death when compared to placebo. Causes of death in clinical data vary, but most of the deaths were cardiovascular in nature (e.g., heart failure, sudden death) or due to infection (e.g., pneumonia). In a placebo-controlled olanzapine retrospective analysis in older adult patients with dementia-related psychosis, an increased incidence of cerebrovascular effects, including fatalities, was reported with olanzapine. For these reasons, olanzapine is not approved for the treatment of dementia-related psychosis. Olanzapine can also cause low levels of white blood cells, so caution should be used in immunocompromised individuals to avoid further exacerbating their lack of an immune system.

Olanzapine and cannabis 

Cannabis may decrease the serum concentration of CYP1A2 substrates like olanzapine, resulting in reduced blood levels through induction of this hepatic isoenzyme. Patients may, therefore, not experience the desired effects of olanzapine if used in conjunction with cannabis. To date, this interaction has only been described with smoked cannabis. 

How to minimize olanzapine interactions

Always carry a complete list of medications, including non-prescription, on your person. Any time you’re receiving medical advice with new therapy recommendations, provide this list so that a thorough review and drug information assessment can be performed to minimize the risk of drug interactions. Whenever initiating a new medication and new signs or symptoms arise, it’s best to review them with your healthcare professional for any potential risks with the use of this medicine. 

When to talk to a healthcare provider about olanzapine interactions

This article is not a complete list of olanzapine interactions nor a complete list of possible side effects. Be mindful of the risk of side effects and direct drug interactions which may occur when olanzapine is used in combination with prescription and over-the-counter medications or supplements. Communicate directly with a healthcare professional anytime you require olanzapine, even a single dose so that a comprehensive review of interactions—of both medications, diet, and conditions—can occur to ensure a proper monitoring plan is put in place. 

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