Drug-induced splenomegaly refers to enlargement of the spleen, often to over 400-500 g or 11 cm in widest diameter, attributed to the initiation of a new medication or drug. Patients with splenomegaly are typically asymptomatic, and this diagnosis is frequently detected on examination with a palpable spleen or incidentally on imaging. In some instances, patients can have vague left-sided abdominal pain, early satiety, or can present with signs of anemia (ie, pallor, fatigue) if the splenomegaly is due to hemolysis.
Drug-induced splenomegaly can occur due to a direct hypertrophic effect on splenic cells or due to an effect on other organ systems (ie, hemolysis, portal hypertension) leading to splenic enlargement. Chemotherapeutic drugs (eg, oxaliplatin, fluorouracil, bevacizumab, etc) are often implicated in drug-induced splenomegaly. RhoGAM is also known to cause splenomegaly in some patients.
For a more exhaustive list of medications associated with splenomegaly, see Drug Reaction Data below.
Drug-induced splenomegaly
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Synopsis

Codes
ICD10CM:
R16.1 – Splenomegaly, not elsewhere classified
SNOMEDCT:
16294009 – Splenomegaly
R16.1 – Splenomegaly, not elsewhere classified
SNOMEDCT:
16294009 – Splenomegaly
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Diagnostic Pearls
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Differential Diagnosis & Pitfalls
- Hemolytic anemia – such as in hereditary spherocytosis and alpha and beta thalassemia, cardiac valvular disease, or hemolysis as medication side effect
- Trauma – can lead to intracapsular hematoma
- Portal vein hypertension
- Sickle cell disease
- Gaucher disease – abnormal lipid deposition
- Niemann-Pick disease
- Infection – infectious mononucleosis, malaria, typhoid, tuberculosis, human immunodeficiency virus, and visceral leishmaniasis
- Lymphoma
- Myeloproliferative disease (eg, polycythemia vera, essential thrombocytosis, myelofibrosis, chronic myelogenous leukemia)
- Splenic angiosarcoma – vascular neoplasm
- Congestive heart failure
- Splenic vein obstruction
- Sarcoidosis
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Therapy
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Drug Reaction Data
Below is a list of drugs with literature evidence indicating an adverse association with this diagnosis. The list is continually updated through ongoing research and new medication approvals. Click on Citations to sort by number of citations or click on Medication to sort the medications alphabetically.
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References
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Last Reviewed:01/10/2018
Last Updated:07/11/2023
Last Updated:07/11/2023