What Medications Cause Low WBC and Neutrophils? A Comprehensive Guide

October 13, 2025 •

4 min read

Up to two-thirds of severe neutropenia cases are suspected to be caused by adverse drug-induced reactions. This phenomenon, known as leukopenia or neutropenia, can be a serious side effect of various medications. This article explores what medications cause low WBC and neutrophils, detailing the different classes of drugs implicated and the mechanisms involved.

Quick Summary

This guide covers various medications that can suppress white blood cell and neutrophil counts. It explains the mechanisms behind drug-induced leukopenia and outlines key drug classes, including chemotherapy, antibiotics, and antipsychotics. Essential monitoring and management strategies are also discussed.

Key Points

Chemotherapy and bone marrow suppression: Cytotoxic chemotherapy agents cause low WBC counts by damaging the fast-growing cells in the bone marrow.
Clozapine's high risk: The antipsychotic medication clozapine is well-known for its potential to cause severe neutropenia, necessitating mandatory and frequent blood monitoring.
Antibiotic-induced neutropenia: Specific antibiotics, including beta-lactams and sulfa drugs, can trigger idiosyncratic immune reactions that destroy neutrophils.
Anticonvulsants and immunosuppressants: Medications used for seizures (e.g., carbamazepine) and autoimmune diseases (e.g., methotrexate) are also implicated in lowering WBC counts.
Monitoring is vital: Regular blood count monitoring, especially for high-risk drugs, is critical for early detection and management of drug-induced leukopenia and neutropenia.
Immune-mediated vs. toxic effects: Drug-induced neutropenia can result from either direct toxicity to bone marrow cells or an immune-mediated response where the body's own antibodies attack blood cells.

A decrease in the body's white blood cell (WBC) count is known as leukopenia, while a specific reduction in neutrophil levels is called neutropenia. These conditions can leave the body vulnerable to infection. While various medical conditions and infections can be causes, medications are a significant and often overlooked contributor. Drug-induced neutropenia can occur predictably with certain therapies, such as chemotherapy, or as a rare, idiosyncratic reaction to other drugs. Understanding the types of drugs and mechanisms involved is crucial for prevention and proper management.

How Medications Can Lower White Blood Cell Counts

Medications can induce leukopenia and neutropenia through two primary mechanisms: direct bone marrow suppression or an immune-mediated response.

Direct Bone Marrow Toxicity

This occurs when a drug directly damages the hematopoietic stem cells in the bone marrow, the 'factory' where all blood cells are produced. Chemotherapy is the most well-known example of this mechanism, intentionally targeting rapidly dividing cells, including healthy bone marrow cells, alongside cancer cells. Other immunosuppressants, like azathioprine or methotrexate, also operate by suppressing bone marrow function.

Immune-Mediated Destruction

Some medications can trigger an immune response where the body mistakenly produces antibodies that attack and destroy neutrophils or their precursors. This is often an idiosyncratic reaction, meaning it is not dose-dependent and only occurs in susceptible individuals. A classic example is the antipsychotic clozapine, which carries a black box warning due to its risk of severe neutropenia via this mechanism. Other drugs, including certain antibiotics, can also cause immune-mediated destruction of white blood cells.

Key Drug Classes Causing Leukopenia and Neutropenia

Chemotherapy and Immunosuppressants

Chemotherapy Drugs: Most cytotoxic chemotherapeutic agents cause myelosuppression, leading to predictable drops in WBC and neutrophil counts. The severity and duration depend on the specific drug, dosage, and frequency.
Immunosuppressants: Used for autoimmune diseases and organ transplants, these medications suppress the immune system, affecting WBC production. Examples include mycophenolate mofetil, azathioprine, and methotrexate.

Antibiotics

Beta-Lactams: High-dose or prolonged use of penicillins (e.g., penicillin G, nafcillin) and cephalosporins can cause neutropenia.
Sulfonamides: Drugs like sulfamethoxazole-trimethoprim are associated with neutropenia, often due to folate deficiency interference or immune reactions.
Other Antibiotics: Vancomycin is another notable antibiotic that can cause neutropenia, frequently through an immune-mediated mechanism. Metronidazole and nitrofurantoin have also been implicated.

Antipsychotics and Anticonvulsants

Clozapine: This is a high-risk medication for severe neutropenia and agranulocytosis (a near-absence of neutrophils), necessitating mandatory blood count monitoring.
Other Antipsychotics: While less common than with clozapine, other antipsychotics like quetiapine, olanzapine, and chlorpromazine can also cause leukopenia.
Anticonvulsants: Carbamazepine, valproic acid, and phenytoin are anti-seizure medications that can suppress bone marrow function.

Other Drug Classes

Antithyroid Drugs: Methimazole and propylthiouracil, used to treat hyperthyroidism, are known to cause idiosyncratic neutropenia.
Anti-inflammatories: Non-steroidal anti-inflammatory drugs (NSAIDs) like ibuprofen can cause neutropenia, although rarely.
Cardiovascular Drugs: Some medications for heart conditions, including the antiarrhythmics quinidine and procainamide, and the anticoagulant ticlopidine, are associated with this side effect.
Antivirals: Certain antiviral drugs, such as ganciclovir and valganciclovir, can cause neutropenia by suppressing bone marrow.

Comparison of Medications Causing Neutropenia


Drug Class	Mechanism	Risk Level	Monitoring Requirements
Chemotherapy	Direct bone marrow suppression	High and predictable	Frequent, routine monitoring of complete blood counts (CBC).
Clozapine	Immune-mediated destruction, bone marrow suppression	Moderate to high, idiosyncratic	Mandatory, regular monitoring of WBC counts due to high agranulocytosis risk.
Antithyroid Drugs	Idiosyncratic immune reaction	Low to moderate, idiosyncratic	Close monitoring during initial treatment; patient education on symptoms.
Antibiotics (e.g., Vancomycin)	Immune-mediated destruction	Low, idiosyncratic	Monitoring for prolonged courses or in susceptible patients; patient education.
Anticonvulsants	Bone marrow suppression, idiosyncratic	Low to moderate	Monitoring may be required during the first few months of therapy.

Management and Monitoring

For patients on medications with a known risk of causing leukopenia or neutropenia, regular blood count monitoring is essential. This is particularly critical for high-risk drugs like clozapine, where monitoring is mandated. If a drop in WBC and neutrophil counts is detected, the offending medication is typically discontinued. For chemotherapy-induced neutropenia, the use of granulocyte colony-stimulating factors (G-CSFs) can help stimulate the bone marrow to produce more white blood cells. Patients should also be educated on the signs and symptoms of infection, such as fever, and when to seek immediate medical attention. Early intervention can significantly reduce morbidity and mortality associated with drug-induced neutropenia.

Conclusion

Many different drug classes have the potential to cause low WBC and neutrophil counts, ranging from predictable effects with chemotherapy to rare idiosyncratic reactions with antibiotics and antipsychotics. The underlying mechanisms vary, but the result is often an increased risk of infection. Vigilant monitoring and a strong collaboration between patient and healthcare provider are key to identifying and managing this potentially serious side effect. Anyone concerned about a medication's impact on their blood counts should consult their doctor for evaluation and proper guidance.

For more information on neutropenia and its causes, you can visit MedlinePlus, a service of the National Library of Medicine: Low white blood cell count and cancer.

Frequently Asked Questions

Leukopenia refers to a general decrease in the total number of white blood cells (WBCs). Neutropenia is a more specific term, referring to a decrease in the specific type of WBCs called neutrophils.

A low WBC count is typically detected through a routine complete blood count (CBC) test ordered by a doctor. Many drug-induced cases are initially asymptomatic and discovered during routine monitoring. Symptoms may only appear if the count is severely low, increasing the risk of infection.

Clozapine is the antipsychotic most strongly associated with severe neutropenia and agranulocytosis. Other atypical antipsychotics like quetiapine and olanzapine carry a lower risk but can still cause a drop in WBC counts.

The initial decline in WBC counts may not cause any noticeable symptoms. When severe, low WBC counts can increase the risk of infection, with the first signs often being fever, chills, sore throat, or mouth sores.

Yes, some over-the-counter medications, including non-steroidal anti-inflammatory drugs (NSAIDs) like ibuprofen, have been reported to cause neutropenia, though it is considered a rare side effect.

The standard treatment is to discontinue the offending drug. In cases of chemotherapy-induced neutropenia, granulocyte colony-stimulating factors (G-CSFs) may be administered to boost white blood cell production. Any infections that develop must be treated promptly with antibiotics.

Recovery time can vary depending on the drug and the individual. For chemotherapy, counts usually begin to recover a couple of weeks after a treatment cycle. For other drugs, discontinuing the medication often leads to recovery within a few days to weeks.