Olanzapine with Betel Nut Interaction Details
Brand Names Associated with Olanzapine
- Olanzapine
- Symbyax® (as a combination product containing Fluoxetine, Olanzapine )
- Zyprexa®
- Zyprexa® Zydis
Medical Content Editor Dr. Brian Staiger, PharmD
Last updated
Dec 03, 2023
Interaction Effect
Increased extrapyramidal side effects of olanzapine (difficulty with movement or abnormal movement of muscles)
Interaction Summary
Case reports have described increased extrapyramidal side effects when betel nut was chewed by patients taking fluphenazine and fluphenthixol for schizophrenia. The extrapyramidal effects were not improved with anticholinergic therapy with procyclidine, and resolved with betel nut discontinuation . A similar effect may occur if betel nut is chewed with concomitant olanzapine therapy. The cholinergic activity of betel nut has been attributed to the arecoline content. When given with peripheral anticholinergics, arecoline increased the heart rate due to central muscarinic agonist activity . Case reports suggest the onset of betel nut activity to be within 3 weeks with resolution within 4 to 7 days after discontinuation .
Severity
Moderate
Onset
Delayed
Evidence
Probable
How To Manage Interaction
It is unclear to what extent the cholinergic effect of betel nut may increase the incidence of extrapyramidal side effects of olanzapine, especially if patients are treated with anticholinergic agents to control these side effects. Deterioration in symptoms of patients with Parkinson's disease or other extrapyramidal movement disorders may be expected. Persons who have been chewing betel nut have a characteristic red stain on the teeth which may help the clinician discover betel nut use.
Mechanism Of Interaction
Cholinergic effect of betel nut
Literature Reports
A) Within 3 weeks of initiating betel nut chewing, a 51-year-old Indian man experienced marked rigidity, bradykinesia, and jaw tremor. This patient had been stabilized for the previous 2 years on fluphenazine decanoate depot 50 milligrams (mg) every 3 weeks for schizophrenia and procyclidine 5 mg twice daily for a mild Parkinsonian tremor. Within one week of discontinuation of betel nut chewing, the patient's condition returned to baseline. This report appears to demonstrate decreased anticholinergic effects of procyclidine when coadministered with betel nut .
B) Following betel nut ingestion, a 45-year-old Indian man developed akathisia, tremor and stiffness which was not affected by dosage escalations of up to 20 mg daily of procyclidine. This patient had been previously stabilized on fluphenthixol 60 mg depot every two weeks for the previous year for schizoaffective disorder without extrapyramidal side effects. His symptoms resolved over 4 days after discontinuing betel nut. It appears that the anticholinergic effects of procyclidine were diminished when betel nut was chewed concomitantly .
C) High doses (5 mg, 10 mg, and 20 mg) of subcutaneous (SC) arecoline given one hour after SC administration of 0.5 mg of the peripheral anticholinergic agent methscopolamine increased the heart rate and blood pressure of six patients with Huntington's disease. Significant increases in blood pressure occurred at doses of 5 mg, 10 mg (p less than 0.01) and 20 mg (p less than 0.05). Heart rate increased at doses of 5 mg and 20 mg (p less than 0.01), and 10 mg (p less than 0.05). Subjective effects in some patients included tremor, flushing or pallor at the time of peak drug effect and nausea, weakness, and mental changes at the higher doses. No peripheral cholinergic effects were noted. The results indicated a central muscarinic effect for arecoline .
D) A low dose (0.5 mg) of arecoline given intravenously 3 minutes after the peripheral anticholinergic agent glycopyrrolate 0.15 mg to 8 patients with major depressive disorder increased their heart rates. The peak heart rate increase in a non-REM portion of the sleep cycle during the 10 minute post-infusion period was 6.75 +/- 12.9 beats per minute for placebo and 25 +/- 10.3 beats per minute for arecoline. The peak heart rates all began 1 to 8 minutes after the arecoline infusion, and the mean heart rate was significantly elevated over placebo from 2 to 10 minutes after arecoline infusion (p less than 0.05) .
E) Though chewing betel nut alone does not significantly increase catecholamine levels, a popular betel nut preparation does. Six to eight minutes after chewing betel nut, 4 subjects had only a moderate increase in plasma noradrenaline from 266.2 +/- 105.7 picograms/milliliter (pg/mL) to 313.7 +/- 92.9 pg/mL (p equal to 0.0607). Combining betel nut with lime, catechu and Piper betel flower as is commonly done caused significant elevation of norepinephrine in nine subjects from 292.2 +/- 59.5 pg/mL to 375.1 +/- 130.0 pg/mL (p equal to 0.0244) and epinephrine from 62.5 +/- 23.9 pg/mL to 102.2 +/- 45.0 pg/mL (p equal to 0.0226). In this group dopamine was also elevated in 8 of 9 subjects, but the mean was not significant .
Olanzapine Overview
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Olanzapine is used to treat the symptoms of schizophrenia (a mental illness that causes disturbed or unusual thinking, loss of interest in life, and strong or inappropriate emotions) in adults and teenagers 13 years of age and older. It is also used to treat bipolar disorder (manic depressive disorder; a disease that causes episodes of depression, episodes of mania, and other abnormal moods) in adults and teenagers 13 years of age and older. Olanzapine is in a class of medications called atypical antipsychotics. It works by changing the activity of certain natural substances in the brain.
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Definitions
Severity Categories
Contraindicated
These drugs, generally, should not be used together simultaneously due to the high risk of severe adverse effects. Combining these medications can lead to dangerous health outcomes and should be strictly avoided unless otherwise instructed by your provider.
Major
This interaction could result in very serious and potentially life-threatening consequences. If you are taking this drug combination, it is very important to be under close medical supervision to minimize severe side effects and ensure your safety. It may be necessary to change a medication or dosage to prevent harm.
Moderate
This interaction has the potential to worsen your medical condition or alter the effectiveness of your treatment. It's important that you are monitored closely and you potentially may need to make adjustments in your treatment plan or drug dosage to maintain optimal health.
Minor
While this interaction is unlikely to cause significant problems, it could intensify side effects or reduce the effectiveness of one or both medications. Monitoring for changes in symptoms and your condition is recommended, and adjustments may be made if needed to manage any increased or more pronounced side effects.
Onset
Rapid: Onset of drug interaction typically occurs within 24 hours of co-administration.
Delayed: Onset of drug interaction typically occurs more than 24 hours after co-administration.
Evidence
Level of documentation of the interaction.
Established: The interaction is documented and substantiated in peer-reviewed medical literature.
Theoretical: This interaction is not fully supported by current medical evidence or well-documented sources, but it is based on known drug mechanisms, drug effects, and other relevant information.
How To Manage The Interaction
Provides a detailed discussion on how patients and clinicians can approach the identified drug interaction as well as offers guidance on what to expect and strategies to potentially mitigate the effects of the interaction. This may include recommendations on adjusting medication dosages, altering the timing of drug administration, or closely monitoring for specific symptoms.
It's important to note that all medical situations are unique, and management approaches should be tailored to individual circumstances. Patients should always consult their healthcare provider for personalized advice and guidance on managing drug interactions effectively.
Mechanism Of Interaction
The theorized or clinically determined reason (i.e., mechanism) why the drug-drug interaction occurs.
Disclaimer: The information provided on this page is for informational purposes only and should not be considered medical advice. Always consult with a qualified healthcare professional regarding your specific circumstances and medical conditions.
Where Does Our Information Come From?
Information for our drug interactions is compiled from several drug compendia, including:
The prescribing information for each drug, as published on DailyMED, is also used.
Individual drug-drug interaction detail pages contain references specific to that interaction. You can click on the reference number within brackets '[]' to see what reference was utilized.
The information posted is fact-checked by HelloPharmacist clinicians and reviewed quarterly.