What Drugs Cause Bone Marrow Aplasia? A Comprehensive Guide

October 12, 2025 •

4 min read

The incidence of aplastic anemia is estimated to be around 1.6 to 2.35 cases per million people per year [1.2.2, 1.2.6]. While often idiopathic, a significant portion of cases can be triggered by medications. Understanding what drugs cause bone marrow aplasia is crucial for risk assessment and patient safety.

Quick Summary

A detailed overview of medications linked to bone marrow aplasia (aplastic anemia). It covers specific drug classes, the mechanisms of toxicity, and risk factors associated with this serious condition.

Key Points

Two Mechanisms: Drug-induced aplasia is caused by either predictable, dose-dependent direct toxicity or rare, unpredictable idiosyncratic reactions [1.5.1].
Chemotherapy is a Major Cause: Cytotoxic chemotherapy agents are a common cause of dose-dependent, reversible bone marrow suppression [1.3.4].
Chloramphenicol is High-Risk: The antibiotic chloramphenicol is famously linked to both reversible suppression and rare, fatal idiosyncratic aplastic anemia [1.7.3, 1.7.4].
Multiple Drug Classes Involved: Besides antibiotics and chemotherapy, anticonvulsants (e.g., carbamazepine), NSAIDs (e.g., indomethacin), and antithyroid drugs (e.g., methimazole) are also implicated [1.3.1, 1.3.2, 1.8.3].
Withdrawal is Key: The first and most critical step in management is to discontinue the suspected causative drug [1.6.2].
Idiosyncratic Reactions are Severe: Dose-independent, idiosyncratic aplasia is often immune-mediated, may be irreversible, and has a high mortality rate [1.5.1].
Treatment Varies: Management ranges from stopping the drug and supportive care (transfusions, antibiotics) to immunosuppressive therapy or bone marrow transplant for severe cases [1.6.5].

Understanding Drug-Induced Bone Marrow Aplasia

Bone marrow aplasia, also known as aplastic anemia, is a serious and potentially life-threatening condition where the bone marrow fails to produce enough new blood cells, leading to pancytopenia—a deficiency of red cells, white cells, and platelets [1.6.1]. While causes can be congenital, viral, or idiopathic, exposure to certain drugs is a well-established trigger [1.4.6]. Drug-induced aplasia can occur through two primary mechanisms: a predictable, dose-related toxic effect on the bone marrow, or an unpredictable, idiosyncratic reaction that is not dependent on the dose [1.5.1, 1.5.3]. The latter is often immune-mediated, where the drug triggers the body's immune system to attack its own hematopoietic stem cells [1.5.1, 1.5.2].

Mechanisms of Drug-Induced Aplasia

Direct Toxicity (Dose-Dependent): This form of bone marrow suppression is a known and predictable side effect of certain drugs, most notably cytotoxic chemotherapy agents used in cancer treatment [1.3.4]. Drugs like 5-fluorouracil and cisplatin directly damage the rapidly dividing cells in the bone marrow [1.3.4]. The effect is generally reversible upon discontinuation of the offending drug [1.5.1]. Chloramphenicol can also cause a dose-related, reversible suppression, particularly when plasma concentrations are high [1.3.4].
Idiosyncratic Reaction (Dose-Independent): This is a rare, unpredictable, and often more severe reaction that can occur at any dose and at any time during or after treatment [1.5.1, 1.5.3]. The mechanism is thought to be immune-mediated, where a drug or its metabolite prompts lymphocytes to destroy myeloid progenitor cells [1.5.1]. This type of aplasia is generally irreversible and carries a high mortality rate [1.5.1, 1.5.3]. Chloramphenicol is famously associated with this type of reaction, with an estimated risk of 1 in 30,000 users, though some estimates vary [1.3.4, 1.2.4].

Key Drug Classes Implicated in Bone Marrow Aplasia

A wide range of medications has been associated with bone marrow aplasia. While the risk for many is very low, awareness is key for early detection.

Antibiotics

Chloramphenicol: This is the most notorious drug linked to aplastic anemia. It can cause both dose-dependent suppression and rare, fatal idiosyncratic aplasia [1.7.2, 1.7.3]. Due to this risk, its use is highly restricted [1.7.2].
Sulfonamides: Drugs like trimethoprim/sulfamethoxazole are known to be associated with aplastic anemia [1.4.1, 1.4.7].
Beta-Lactams and Macrolides: Though rare, antibiotics such as penicillins, cephalosporins (including ceftriaxone), and macrolides have been implicated [1.3.2, 1.3.7].

Antineoplastic (Chemotherapy) Agents

As discussed, these drugs are designed to kill rapidly dividing cells, making bone marrow suppression a common and expected side effect [1.3.4]. Nearly all traditional cytotoxic agents can cause some degree of aplasia.

Anticonvulsants

Carbamazepine, Phenytoin, Felbamate: These anti-seizure medications have been associated with an increased risk of aplastic anemia [1.3.5, 1.4.1]. The association is significant enough that they are often cited as important causes [1.2.3].

Anti-inflammatory Drugs (NSAIDs)

Phenylbutazone, Indomethacin, Diclofenac: Several NSAIDs have been linked to aplastic anemia [1.8.1, 1.8.3]. Studies have shown that indomethacin and diclofenac are significantly associated with the condition [1.8.3]. Even naproxen has been reported to cause reversible bone marrow aplasia [1.8.5].

Antithyroid Drugs

Methimazole (Tapazole) and Propylthiouracil (PTU): These drugs, used to treat hyperthyroidism, are known causes of aplastic anemia, though it is a rare complication [1.3.2, 1.4.7]. The reaction tends to occur within the first six months of therapy, especially with higher doses of methimazole [1.3.2].

Other Notable Drugs

Gold Compounds: Previously used for rheumatoid arthritis, gold salts are associated with aplastic anemia [1.4.7].
Penicillamine: Another drug for rheumatoid arthritis, also linked to aplasia [1.2.3].
Clozapine: An antipsychotic medication known to cause agranulocytosis, but also implicated in aplastic anemia [1.4.4].

Comparison of Common Drugs Causing Aplasia


Drug Class	Common Examples	Mechanism Type	Relative Risk
Antibiotics	Chloramphenicol, Sulfonamides	Idiosyncratic & Dose-Dependent	Chloramphenicol (High); Others (Low) [1.3.4, 1.4.1]
Anticonvulsants	Carbamazepine, Phenytoin	Idiosyncratic	Moderate [1.2.3, 1.3.5]
NSAIDs	Indomethacin, Phenylbutazone, Diclofenac	Idiosyncratic	Low to Moderate [1.8.3]
Antithyroid	Methimazole, Propylthiouracil	Idiosyncratic	Low, higher with large doses [1.3.2]
Chemotherapy	Alkylating agents, Topoisomerase inhibitors	Direct Toxicity (Dose-Dependent)	High (Expected Side Effect) [1.3.4]

Diagnosis and Management

Diagnosis of drug-induced aplastic anemia begins with a complete blood count (CBC) showing pancytopenia, followed by a bone marrow biopsy to confirm hypocellularity [1.6.1]. The most critical first step in management is to identify and withdraw the suspected offending drug [1.6.2]. In some cases, especially dose-dependent toxicity, this may be enough for the bone marrow to recover [1.6.3].

Supportive care is essential and includes blood and platelet transfusions and antibiotics to prevent or treat infections due to low white blood cell counts [1.6.2, 1.6.5]. For severe cases, especially idiosyncratic aplasia, definitive treatment may involve immunosuppressive therapy with agents like antithymocyte globulin (ATG) and cyclosporine, or a hematopoietic stem cell (bone marrow) transplant [1.6.5].

Conclusion

Drug-induced bone marrow aplasia is a serious adverse event linked to a variety of medications across different therapeutic classes. While chemotherapy agents cause predictable, dose-dependent myelosuppression, many other drugs can trigger rare and unpredictable idiosyncratic reactions. The antibiotic chloramphenicol remains the classic example, but clinicians must remain vigilant about the potential hematologic toxicity of anticonvulsants, NSAIDs, antithyroid drugs, and others. Prompt identification and withdrawal of the causative agent, coupled with aggressive supportive care and potentially immunosuppressive therapy or transplantation, are paramount for managing this life-threatening condition.

For more in-depth information on aplastic anemia, an authoritative resource is the Aplastic Anemia & MDS International Foundation.

Frequently Asked Questions

Yes, in some cases. If the aplasia is a dose-dependent toxic effect (like from chemotherapy), it often reverses after the drug is stopped. Idiosyncratic aplasia is less likely to be reversible and often requires more aggressive treatment [1.5.1, 1.6.3].

Historically and in many reports, the antibiotic chloramphenicol is the single drug most famously associated with causing idiosyncratic aplastic anemia [1.3.5, 1.7.2]. However, many other drugs are also known to cause it [1.4.1].

Diagnosis involves a complete blood count (CBC) to identify low levels of red cells, white cells, and platelets (pancytopenia), and is confirmed with a bone marrow biopsy showing a hypocellular marrow [1.6.1].

Yes, several nonsteroidal anti-inflammatory drugs (NSAIDs) have been associated with aplastic anemia, including indomethacin, phenylbutazone, and diclofenac [1.8.1, 1.8.3]. While the risk is low, it is a recognized potential side effect.

The onset can vary. For antithyroid drugs, it often occurs within the first 6 months of treatment [1.3.2]. For idiosyncratic reactions like those from chloramphenicol, it can occur weeks or months after the drug has been stopped [1.7.6].

Bone marrow aplasia (aplastic anemia) involves a failure to produce all three major blood cell lines: red cells, white cells, and platelets. Agranulocytosis is a more specific condition characterized by a severe deficiency of a type of white blood cell called neutrophils, which dramatically increases the risk of infection [1.3.2].

After stopping the causative drug, the standard treatment for severe cases is immunosuppressive therapy, typically with antithymocyte globulin (ATG) and cyclosporine. For younger patients with a suitable donor, a bone marrow (stem cell) transplant may be the preferred option [1.6.5].