Drug-induced agranulocytosis is a life-threatening, severe neutropenia, with an absolute neutrophil count of less than 100 neutrophils per microlitre of blood, caused by a medication. The danger lies in the development of infectious complications, such as severe sepsis, which is strongly associated. Agranulocytosis is very rare, with less than 5 cases per million population per year. It is seen more frequently in women, especially older women. The incidence rate increases overall with patient age, possibly due to increased drug use.

Although other etiologies of agranulocytosis include autoimmune diseases, infectious diseases, and inherited genetic diseases, the majority are drug induced. Up to 70% of cases are medication related. The reaction generally occurs weeks to months after drug initiation but can occur within days or after years.

Over 200 individual drugs have been reported as causes of agranulocytosis in the medical literature. A thorough list of individual drug names, classes, and implicating citations are provided in the Drug Reaction Data section on this page. Causative drugs classes include but are not limited to:

• Antibiotics (sulfonamides, cephalosporins, macrolides, penicillins, leprostatics, glycopeptides, beta-lactam)
• Psychiatric agents (typical antipsychotics, atypical antipsychotics, tricyclic antidepressants, tetracyclic antidepressants, SNRIs, SSRIs, benzodiazepines)
• Chelating agents
• Anticonvulsants
• Anti-inflammatory and analgesics (NSAIDs, salicylics, opioids)
• Antiparasitics (antimalarials, anthelmintics)
• Antithyroids
• Diuretics (thiazides, carbonic anhydrase inhibitors)
• Chemotherapy (monoclonal antibodies, antimetabolites)
• Cardiovascular agents (antiarrhythmics, ACE inhibitors, beta blockers, calcium channel blockers, cocaine)
• Antifungals
• Antihistamines (histamine H1 antangonists, histamine H2 antagonists)
• Sulfonylureas
• Gastrointestinal agents (5-aminosalicylic acid derivatives, proton pump inhibitors, antiemetics)
• Retinoids

Presentation is varied, with some patients appearing ill or toxic and others presenting asymptomatically and discovered through routine / screening laboratory tests, such as a CBC with differential. Diagnosis requires a high degree of suspicion.

Suspect drug-induced agranulocytosis in patients with recent new medication, or who currently use any listed causative medications, and who have other symptoms such as:

• High fever
• Tachycardia
• Tachypnea
• Hypotension
• Infected oral ulcers
• Sore throat
• Skin abscesses

More favorable prognosis is associated with patient age younger than 65 years, higher neutrophil count, and a lack of symptoms at diagnosis. With treatment, the mortality rate is about 5%.

Best practice is to stop the suspected medication once detected. Absolute neutrophil count should recover between 7 days and 3 weeks after cessation of the culprit drug. Granulocyte-colony stimulating factor (G-CSF) can be utilized to improve neutrophil production.

Advise the patient to avoid infections by practicing social distancing, wearing a face mask, and maintaining strong oral and hand hygiene. Any skin breaks should be covered promptly.

A high suspicion for bacterial infection should be maintained and a broad-spectrum antibiotic initiated if signs or symptoms of infection are present. See bacterial sepsis for more information.