What drugs cause low neutrophils? Understanding Drug-Induced Neutropenia

October 12, 2025 •

3 min read

Drug-induced neutropenia, a significant cause of severe neutropenia and agranulocytosis, is often attributed to medications and their adverse idiosyncratic reactions. This phenomenon raises the crucial question: what drugs cause low neutrophils, and how can they be managed effectively?

Quick Summary

Many medications, including cytotoxic chemotherapy, antibiotics, and antipsychotics like clozapine, can lead to drug-induced neutropenia through bone marrow suppression or immune-mediated destruction. Management typically involves discontinuing the offending medication and, in severe cases, treatment with G-CSF.

Key Points

Chemotherapy is a major cause of predictable, dose-related neutropenia, suppressing bone marrow production of neutrophils.
Many antibiotics can trigger idiosyncratic, immune-mediated neutropenia, including vancomycin, ceftriaxone, and trimethoprim-sulfamethoxazole.
The antipsychotic clozapine carries a significant risk of severe neutropenia, requiring mandatory and frequent blood count monitoring.
Immunosuppressants and certain cardiovascular drugs also have the potential to cause neutropenia, sometimes with a delayed onset, as seen with rituximab.
The primary management for drug-induced neutropenia is discontinuation of the causative medication, followed by supportive care and, in severe cases, treatment with G-CSF.
Symptoms of neutropenia-related infection include fever, chills, and mouth sores, but the condition may be asymptomatic until an infection occurs.

A significant number of medications across various therapeutic classes have been linked to causing a decrease in the body's neutrophil count, a condition known as neutropenia. While this side effect can be a predictable, dose-dependent reaction with some drugs, such as chemotherapy, it is often an unpredictable idiosyncratic reaction with others. Understanding which drugs pose a risk, their underlying mechanisms, and how to manage the condition is critical for patient safety.

Drugs Known to Cause Low Neutrophils

Chemotherapy Agents

Chemotherapy-induced neutropenia (CIN) is a common and often unavoidable side effect of cancer treatment. The mechanism is predictable and dose-related, as these drugs are designed to kill rapidly dividing cells, including the hematopoietic stem cells in the bone marrow that produce neutrophils. The lowest point of the neutrophil count, known as the nadir, typically occurs 10 to 14 days after chemotherapy administration. Examples include alkylating agents (cyclophosphamide), anthracyclines (doxorubicin), antimetabolites (methotrexate), and taxanes (paclitaxel).

Antibiotics and Antimicrobials

Antibiotic-induced neutropenia is typically an idiosyncratic, immune-mediated reaction rather than a dose-dependent one. It often occurs after about one to three weeks of therapy and can be seen with prolonged or high-dose courses. This can include beta-lactam antibiotics like penicillin G and cephalosporins, glycopeptides such as vancomycin, and sulfonamides like trimethoprim-sulfamethoxazole.

Psychiatric Medications

Several psychotropic drugs have been associated with a risk of neutropenia, with some requiring mandatory blood monitoring. The atypical antipsychotic clozapine has a significant risk of severe neutropenia (agranulocytosis), while olanzapine and paliperidone have also been reported. Mood stabilizers and anticonvulsants like carbamazepine and valproic acid can also induce neutropenia.

Immunosuppressants

Patients on immunosuppressive therapy are at risk for neutropenia. Examples include mycophenolate mofetil (MMF), rituximab which can cause delayed-onset neutropenia, and azathioprine.

Other Drug Classes

Other medications linked to neutropenia include antithyroid drugs (methimazole, propylthiouracil), some cardiovascular drugs like antiarrhythmics and antiplatelet agents (procainamide, clopidogrel), and rarely, NSAIDs such as ibuprofen and naproxen.

Mechanisms of Drug-Induced Neutropenia

Drug-induced neutropenia can occur through predictable bone marrow suppression or unpredictable immune-mediated destruction. Direct myelosuppression, common with chemotherapy, targets hematopoietic progenitor cells. Immune-mediated destruction is an idiosyncratic reaction where the drug triggers anti-neutrophil antibodies. Some drugs, like clozapine, can also accelerate neutrophil apoptosis.

Comparison of Neutropenia Types


Feature	Chemotherapy-Induced Neutropenia (Myelosuppression)	Idiosyncratic Drug-Induced Neutropenia (Immune-Mediated)
Predictability	Predictable and dose-dependent.	Unpredictable, not related to dose.
Onset	Occurs at a consistent nadir (e.g., 10-14 days) after treatment.	Variable onset, often within weeks to months of starting the drug.
Mechanism	Direct toxicity to bone marrow progenitor cells.	Immune response (antibodies or T-cells) against neutrophils.
Severity	Often severe and sustained, proportional to drug dosage.	Can range from mild to severe (agranulocytosis).
Associated Drugs	Alkylating agents, antimetabolites, taxanes.	Antibiotics (vancomycin, cephalosporins), antipsychotics (clozapine), antithyroid drugs.
Recovery	Often resolves within 3-4 weeks after treatment cycle ends.	Rapid recovery (days to weeks) upon drug discontinuation.

Symptoms and Diagnosis

Low neutrophil counts increase the risk of bacterial and fungal infections, leading to symptoms like fever (febrile neutropenia), chills, sore throat, and mouth sores. Diagnosis involves a complete blood count (CBC) to measure the absolute neutrophil count (ANC) and assessing the temporal relationship with medication use.

Management and Treatment

Discontinuing the offending medication is the primary management strategy. For febrile neutropenia, immediate broad-spectrum antibiotics are necessary. In severe cases, granulocyte colony-stimulating factors (G-CSF) can be used to stimulate neutrophil production. Regular monitoring is essential for high-risk drugs like clozapine.

Conclusion

Many medications can cause low neutrophils through various mechanisms. Recognizing the risk, monitoring patients, and promptly discontinuing the drug are crucial for management. Supportive care, including G-CSF, has improved outcomes. Further information on neutropenia is available from resources like the National Institutes of Health.

Frequently Asked Questions

Chemotherapy agents are the most common cause of neutropenia, as they predictably suppress bone marrow function in a dose-dependent manner.

Yes, many antibiotics can cause neutropenia, usually through an unpredictable immune-mediated reaction. Common culprits include vancomycin, ceftriaxone, and piperacillin/tazobactam.

Clozapine is the psychiatric medication most notably associated with a high risk of severe neutropenia (agranulocytosis), which requires mandatory blood count monitoring.

The most critical step is to stop the medication suspected of causing the neutropenia. In severe cases or with fever, treatment may include broad-spectrum antibiotics and G-CSF to boost neutrophil production.

Signs of low neutrophils often appear when an infection develops and can include fever, chills, sore throat, mouth sores, or pain and swelling at an infection site. Fatigue can also be a symptom.

While uncommon and idiosyncratic, NSAIDs like ibuprofen and naproxen have been reported in rare cases to cause neutropenia. The risk is considered low.

Recovery time can vary, but in many cases of idiosyncratic drug-induced neutropenia, neutrophil counts return to normal within days to a few weeks after discontinuing the offending medication.