What Can You Not Take with Ziprasidone?

October 10, 2025 •

3 min read

Ziprasidone (brand name Geodon), like many potent medications, carries a significant risk of adverse drug interactions, with official drug inserts often highlighting a black box warning for potentially fatal heart rhythm problems. Understanding what you can not take with ziprasidone is crucial for patient safety, as combining it with certain substances can lead to severe side effects ranging from excessive sedation to life-threatening cardiac complications. It is imperative to always consult with a healthcare provider to review your full medication list before starting or stopping any drugs while on ziprasidone.

Quick Summary

This article details the critical and potentially dangerous interactions associated with ziprasidone, including substances that can affect heart rhythm, increase sedation, or alter medication levels. It outlines the specific drug classes and individual medications that should be avoided, such as QT-prolonging agents, MAOIs, and central nervous system depressants. Dietary and lifestyle interactions, like alcohol and grapefruit, are also discussed. The summary emphasizes the importance of informing your doctor about all current medications, over-the-counter drugs, and herbal supplements to ensure safe treatment.

Key Points

Avoid QT-Prolonging Drugs: Ziprasidone should not be combined with other medications that prolong the QT interval, such as certain antiarrhythmics and antibiotics, due to the risk of fatal heart arrhythmias.
Never Mix with MAOIs: The combination of ziprasidone and Monoamine Oxidase Inhibitors is contraindicated and can cause life-threatening serotonin syndrome.
Be Cautious with CNS Depressants: Combining ziprasidone with alcohol, benzodiazepines, opioids, or muscle relaxers can lead to excessive drowsiness, impaired coordination, and slowed breathing.
Heed Warnings for Hypotension: Ziprasidone has blood pressure-lowering effects, and combining it with other antihypertensive medications can cause dangerously low blood pressure.
Mind Dietary and Herbal Interactions: Substances like grapefruit juice and St. John's wort can alter ziprasidone's effectiveness and increase side effects by affecting its metabolism.
Discuss All Medications with Your Doctor: Always inform your healthcare provider of all prescription, OTC drugs, and supplements to avoid dangerous interactions.

Critical Contraindications for Ziprasidone

Ziprasidone carries a serious risk of prolonging the QT interval, a measure of the heart's electrical activity. This can increase the likelihood of a dangerous heart rhythm called torsades de pointes, and the risk is higher with larger doses. Therefore, ziprasidone is not recommended for individuals with a history of QT prolongation, recent heart attack, or uncompensated heart failure. Combining ziprasidone with certain other medications also increases this risk and is contraindicated.

QT-Prolonging Drugs

Several medications can lengthen the QT interval, and taking them with ziprasidone significantly increases the risk of heart rhythm problems. These include certain antiarrhythmics (like quinidine and sotalol), some antipsychotics (such as thioridazine), specific antibiotics (including moxifloxacin), and other drugs like halofantrine and pentamidine.

Monoamine Oxidase Inhibitors (MAOIs)

Combining ziprasidone with MAOIs is highly dangerous and can lead to serotonin syndrome, a severe condition resulting from too much serotonin in the brain. Ziprasidone should not be taken by anyone currently on an MAOI or who has stopped one within the past two weeks. Examples of MAOIs include phenelzine and selegiline; the antibiotic linezolid and intravenous methylene blue also have similar effects and should be avoided.

Drug Classes to Use with Caution or Avoid

Besides absolute contraindications, other drug classes and substances should be used cautiously or avoided due to potential negative reactions.

Central Nervous System (CNS) Depressants

Combining ziprasidone with CNS depressants can lead to excessive drowsiness, dizziness, difficulty thinking, and slowed breathing. This includes avoiding alcohol, which worsens ziprasidone's sedative effects. Benzodiazepines like alprazolam and opioids such as oxycodone can increase sedation. Methadone also poses a risk of QT prolongation. Sleep medications and muscle relaxers can have similar compounded sedative effects.

Other Interacting Medications

Ziprasidone can lower blood pressure, so taking it with other blood pressure medications might cause dangerously low blood pressure (hypotension). Some drugs affect how ziprasidone is processed by the body. Medications and substances like ketoconazole and grapefruit juice can increase ziprasidone levels, potentially leading to more side effects. Conversely, drugs like carbamazepine and St. John's wort can decrease ziprasidone levels, making it less effective. Ziprasidone may also interfere with medications for Parkinson's disease, such as levodopa, because it acts on dopamine receptors.

Comparison of Ziprasidone Interactions with Common Drug Classes


Drug Class	Example Medications	Type of Interaction with Ziprasidone	Potential Consequences	Action Required
QT-prolonging Drugs	Amiodarone, Quinidine, Moxifloxacin	Additive QT prolongation	Potentially fatal heart arrhythmias (torsades de pointes)	Contraindicated (Do NOT take)
MAOIs	Phenelzine, Selegiline, Linezolid	Increased serotonin levels	Life-threatening serotonin syndrome (agitation, muscle stiffness, fever)	Contraindicated (Do NOT take)
CNS Depressants	Alcohol, Alprazolam, Opioids	Additive CNS depression	Excessive drowsiness, impaired coordination, slowed breathing	Avoid/Monitor Closely
Antihypertensives	Amlodipine, Lisinopril	Additive blood pressure lowering	Excessive hypotension (dangerously low blood pressure)	Monitor Closely
CYP3A4 Inhibitors	Ketoconazole, Grapefruit juice	Increased ziprasidone plasma levels	Increased risk of ziprasidone-related side effects	Avoid/Monitor Closely
CYP3A4 Inducers	Carbamazepine, St. John's wort	Decreased ziprasidone plasma levels	Reduced effectiveness of ziprasidone	Monitor Closely/Adjust Dose

Patient Considerations and Safe Practices

To manage ziprasidone therapy safely, patients must understand potential interactions. Always consult a healthcare provider before starting any new medication, supplement, or even consuming grapefruit. Keeping a current list of all drugs and substances is essential. Complete avoidance of alcohol while on ziprasidone is also necessary. Doctors may perform baseline heart (ECG) and electrolyte tests to check for existing risks.

Conclusion

Ziprasidone is effective for schizophrenia and bipolar disorder but has crucial interactions that must be managed. The most serious risks are QT prolongation, leading to potentially fatal heart arrhythmias, and serotonin syndrome, a risk with MAOIs. Other concerns include increased sedation with CNS depressants and changes in drug levels caused by certain medications or substances like grapefruit. Open communication with healthcare providers, following instructions, and proactive screening are key to safe ziprasidone use.

Frequently Asked Questions

No, you should avoid drinking alcohol while taking ziprasidone. The combination can significantly increase the sedative effects of the medication, causing excessive dizziness, drowsiness, and impaired judgment, which increases the risk of accidents.

It depends on the specific antidepressant. Ziprasidone is contraindicated with MAOIs (e.g., phenelzine) due to the risk of serotonin syndrome. Other antidepressants, such as SSRIs like citalopram, can also prolong the QT interval and should be used with caution. Always consult your doctor before combining these medications.

Combining ziprasidone with other QT-prolonging drugs (such as certain antiarrhythmics, antibiotics, or antipsychotics) is dangerous. This can lead to a significant lengthening of the QT interval, which increases the risk of a fatal heart arrhythmia called torsades de pointes.

It is best to avoid grapefruit and grapefruit juice. Grapefruit can inhibit the enzyme (CYP3A4) that metabolizes ziprasidone, which can lead to increased drug levels in your blood and a higher risk of side effects.

Yes, some OTC products should be avoided. These include sedating antihistamines (like diphenhydramine) and herbal supplements such as St. John's wort, which can cause additive drowsiness or affect ziprasidone's metabolism. Always check with your doctor or pharmacist before taking any new OTC medication or supplement.

For oral ziprasidone, taking it with food is not an interaction to avoid, but a requirement for proper absorption. Taking it with a meal of at least 500 calories ensures adequate and predictable absorption, which is crucial for its effectiveness.

Using illegal or recreational drugs while on ziprasidone is strongly discouraged. Combining substances like cannabis with ziprasidone can significantly increase CNS depression, drowsiness, and other adverse effects.

Yes, you should inform your doctor if you have a history of heart disease, irregular heartbeat, low electrolytes (potassium or magnesium), or have recently had a heart attack. Ziprasidone is contraindicated in these conditions due to its effect on the QT interval.