Who cannot take linezolid? A Guide to Contraindications and Risks

October 7, 2025 •

3 min read

According to the FDA, administering linezolid with certain serotonergic psychiatric medications can cause severe central nervous system reactions, including serotonin syndrome. This highlights the critical importance of understanding who cannot take linezolid due to its significant interaction profile and inherent risks.

Quick Summary

Linezolid is contraindicated in patients taking MAOIs, those with uncontrolled hypertension, or pheochromocytoma. It carries risks of serotonin syndrome, myelosuppression, and other adverse effects, requiring careful patient selection and monitoring.

Key Points

Avoid MAOIs: Linezolid should not be used in patients taking monoamine oxidase inhibitors (MAOIs) or within two weeks of stopping them, due to the high risk of serotonin syndrome.
Watch for Serotonin Syndrome: Concomitant use with other serotonergic medications, such as SSRIs, SNRIs, and certain opioids, increases the risk of this potentially fatal condition.
Manage Hypertensive Risk: Patients with uncontrolled high blood pressure, pheochromocytoma, or thyrotoxicosis are contraindicated unless closely monitored, especially if taking adrenergic drugs.
Monitor Blood Counts: Prolonged use (over 28 days) can cause myelosuppression, including thrombocytopenia, requiring weekly monitoring of blood counts.
Heed Diet Restrictions: Patients must limit intake of tyramine-rich foods like aged cheeses and fermented products to prevent a hypertensive crisis.
Assess for Neuropathy: Extended therapy can lead to peripheral and optic neuropathy, requiring regular vision checks and observation for nerve-related symptoms.
Use Caution with Organ Impairment: Patients with severe renal or moderate-to-severe hepatic impairment may be at increased risk of adverse effects due to metabolite accumulation.

Absolute Contraindications

Monoamine Oxidase Inhibitors (MAOIs)

Linezolid is a reversible, non-selective MAO inhibitor, affecting neurotransmitter levels. It is strictly contraindicated in patients currently on or who have recently taken (within two weeks) any MAO-A or MAO-B inhibitor. Combining linezolid with MAOIs can cause fatal serotonin syndrome. Examples of MAOIs include phenelzine, isocarboxazid, and selegiline.

Hypersensitivity

Patients with known allergy to linezolid or its components should avoid it due to risks of reactions from skin rashes to severe conditions like toxic epidermal necrolysis.

Serious Drug Interactions and Precautions

Serotonergic Agents

Linezolid's MAOI properties increase the risk of serotonin syndrome when combined with other serotonergic drugs like SSRIs, SNRIs, and certain opioids. The FDA has warned about this interaction. Generally, these combinations should be avoided. If linezolid is life-saving, the serotonergic drug must be stopped, and the patient monitored closely.

Adrenergic Agents and Hypertension

Linezolid can increase the effects of adrenergic drugs, potentially causing hypertensive crisis. It should not be used in patients with uncontrolled hypertension, pheochromocytoma, or thyrotoxicosis unless blood pressure is strictly controlled. Caution is needed with sympathomimetics (e.g., pseudoephedrine), vasopressors (e.g., epinephrine), and dopaminergic agents (e.g., dopamine).

Tyramine-Rich Foods

Due to MAOI activity, linezolid can prevent tyramine breakdown, leading to hypertensive crisis. Patients should limit aged cheeses, fermented products, smoked meats, and tap beer/red wine.

Conditions that Increase Risk or Require Monitoring

Myelosuppression

Myelosuppression, including low platelet counts, anemia, and leukopenia, can occur with linezolid, especially with prolonged use. Patients with pre-existing myelosuppression, severe renal/hepatic issues, or those on other myelosuppressive drugs are at higher risk. Weekly complete blood counts are recommended, and linezolid may be stopped if myelosuppression worsens.

Neuropathies

Peripheral and optic neuropathy, potentially causing vision loss or tingling, have been reported with extended linezolid therapy (over 28 days). Patients with visual changes should see an ophthalmologist.

Renal and Hepatic Impairment

Linezolid metabolites can build up in renal impairment, increasing myelosuppression risk. Caution and monitoring are needed in moderate-to-severe hepatic impairment.

Diabetes

Hypoglycemia has occurred in diabetic patients on insulin or oral agents while taking linezolid. Blood glucose monitoring is advised.

Comparison of Linezolid and Alternatives for Resistant Infections


Feature	Linezolid (Zyvox)	Daptomycin (Cubicin)	Vancomycin
Class	Oxazolidinone	Lipopeptide	Glycopeptide
MAOI Activity	Yes (weak, reversible)	No	No
Serotonin Syndrome Risk	High, when combined with serotonergic drugs	Low/None	Low/None
Myelosuppression Risk	Yes, especially with prolonged use (>28 days)	Less common; check prescribing information	Rare, but monitor for neutropenia
Neuropathy Risk	Peripheral and optic, especially with prolonged use	No	No
Tyramine Interaction	Yes, potential for hypertensive reactions	No	No
Drug Interactions	High risk with MAOIs, serotonergics, and adrenergics	Fewer interactions than linezolid	Fewer interactions than linezolid
Renal Impairment	Metabolites accumulate; use with caution	Requires dose adjustment	Requires dose adjustment; potentially nephrotoxic
Monitoring Needs	Weekly CBCs, blood pressure, blood glucose, vision checks	Creatine kinase (for muscle toxicity)	Trough levels, renal function

Conclusion

Linezolid is vital for severe drug-resistant gram-positive infections but requires careful assessment of risks and contraindications. Patients on MAOIs or with uncontrolled hypertension should not take it without strict monitoring. Combining linezolid with other serotonergic drugs risks serotonin syndrome. Myelosuppression, neuropathy, and hypertensive reactions are potential concerns, necessitating monitoring, especially during prolonged treatment. Patients must inform their doctor of all medications and conditions to determine if linezolid is suitable. The official FDA Drug Safety Communication provides further information.

Frequently Asked Questions

You should generally not take linezolid if you are on an antidepressant, particularly SSRIs or SNRIs, due to the risk of a serious drug interaction called serotonin syndrome. In emergency situations, your doctor may decide the benefit outweighs the risk and will stop the antidepressant and monitor you closely.

Taking linezolid with a monoamine oxidase inhibitor (MAOI) can lead to a severe and potentially fatal reaction known as serotonin syndrome, caused by a dangerous increase in serotonin levels. You should not take linezolid if you have taken an MAOI in the last two weeks.

Linezolid should not be used in patients with uncontrolled hypertension, pheochromocytoma, or thyrotoxicosis unless their blood pressure is closely and continuously monitored. It can increase blood pressure, especially when taken with certain medications.

You must avoid large quantities of tyramine-rich foods and beverages while on linezolid. This is because linezolid inhibits the enzyme that breaks down tyramine, which can lead to dangerously high blood pressure levels.

Linezolid can cause myelosuppression, which is a suppression of bone marrow activity, leading to low blood cell counts. The most common hematologic side effect is thrombocytopenia (low platelets), especially with prolonged treatment. Patients with pre-existing low blood counts are at higher risk.

Patients who receive linezolid for extended periods (typically longer than 28 days) are at risk of developing peripheral and optic neuropathy, which can cause vision changes or nerve-related symptoms. Your doctor may recommend regular eye exams during prolonged therapy.

Yes, if you are on linezolid for an extended period, particularly over two weeks, your doctor should monitor your complete blood counts weekly. This is to check for signs of myelosuppression, such as low platelets, white blood cells, or red blood cells.

Linezolid passes into breast milk and its effects on a nursing infant are not well studied. It is generally advised to discuss the risks and benefits with your doctor before using this medication while breastfeeding.