Nonchemotherapy Drug-Induced Neutropenia and Agranulocytosis

Pick, Amy M.; Nystrom, Kelly K.

doi:10.1177/0897190014546115

Cited by 48 publications

(57 citation statements)

References 27 publications

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“…It has been documented that the offending medications associated with severe neutropenia are methimazole, ticlopidine, clozapine, sulfasalazine, trimethoprim-sulfamethoxazole and dipyrone in descending order of likelihood [17–19]. The hematologic complication of hypersensitivity to penicillin is rare, with an overall acute neutropenia of 2.4 to 15.4 cases per million populations over the last 20 years [14].…”

Section: Discussionmentioning

confidence: 99%

Neutropenia induced by high-dose intravenous benzylpenicillin in treating neurosyphilis: Does it really matter?

Peng

Zhao

et al. 2017

PLoS Negl Trop Dis

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BackgroundPrompt therapy with high-dose intravenous benzylpenicillin for a prolonged period is critical for neurosyphilis patients to avoid irreversible sequelae. However, life-threatening neutropenia has been reported as a complication of prolonged therapy with high doses of benzylpenicillin when treating other diseases. This study aimed to investigate the incidence, presentation, management and prognosis of benzylpenicillin-induced neutropenia in treating neurosyphilis based on a large sample of syphilis patients in Shanghai.Methodology/Principal findingsBetween 1st January 2013 and 31st December 2015, 1367 patients with neurosyphilis were treated with benzylpenicillin, 578 of whom were eligible for recruitment to this study. Among patients without medical co-morbidities, the total incidence of benzylpenicillin-induced neutropenia and severe neutropenia was 2.42% (95% CI: 1.38–4.13%) and 0.35% (95% CI: 0.06–1.39%), respectively. The treatment duration before onset of neutropenia ranged from 10 to 14 days, with a total cumulative dose of between 240 and 324 megaunits of benzylpenicillin. Neutropenia was accompanied by symptoms of chills and fever (5 patients), fatigue (2 patients), cough (1 patient), sore throat (1 patient), diarrhea (1 patient) and erythematous rash (1 patient). The severity of neutropenia was not associated with age, gender or type of neurosyphilis (p>0.05). Neutropenia, even when severe, was often tolerated and normalized within one week. A more serious neutropenia did not occur when reinstituting benzylpenicillin in patients with mild or moderate neutropenia nor when ceftriaxone was used three months after patients had previously experienced severe neutropenia.Conclusions/SignificanceBenzylpenicillin-induced neutropenia was uncommon in our cohort of patients. Continuation of therapy was possible with intensive surveillance for those with mild or moderate neutropenia. For severe neutropenia, it is not essential to aggressively use hematopoietic growth factors or broad-spectrum antibiotics for patients in good physical condition after withdrawing anti-neurosyphilis regimen. We did not see an exacerbation of neutropenia in patients with the readministration of benzylpenicillin.

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Section: Discussionmentioning

confidence: 99%

Neutropenia induced by high-dose intravenous benzylpenicillin in treating neurosyphilis: Does it really matter?

Peng

Zhao

et al. 2017

PLoS Negl Trop Dis

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“…Most cases of agranulocytosis are drug-induced, and its incidence appears to increase with age, particularly in elderly patients who receive, on average, more drugs than the younger patients [28]. The clinical manifestations of drug-induced agranulocytosis (DIA) include fever, septic shock, pneumonia, sore throat, cutaneous infection, and other infections [29]. The mechanism of DIA has not been fully elucidated; however, two main hypotheses have been proposed [30].…”

Section: Discussionmentioning

confidence: 99%

Iatrogenic AKI and Agranulocytosis: a Cautious Tale of Medication Use in Elderly Patients

Qin¹,

Cang²,

Liu³

et al. 2017

J Clin Exp Nephrol

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A 83-year-old female patient suffered from acute kidney injury a month after percutaneous coronary intervention. Two weeks before hospitalization, she experienced nausea and intermittent watery diarrhea. Laboratory test showed high levels of serum creatine kinase and lactate dehydrogenase, which were remarkably decreased after ceasing rosuvastatin and valsartan treatment. Despite the recovery of renal function, unfortunately one week later, she was diagnosed with agranulocytosis because of antibiotic therapy. When we stopped meropenem and switched to granulocyto-colony stimulating factor treatment, her white blood cell count returned to a normal range. In our case, both rhabdomyolysis and agranulocytosis were induced by drugs. We provided a literature review of the causes of acute kidney injury and the pathogenesis of rhabdomyolysis and agranulocytosis. We discussed how drugs might lead to these complications. This case highlights the need to be aware of the potential side effects of drugs, especially those given to elderly patients who are likely to be receiving several medications concurrently for managing chronic diseases.

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“…Episodes of drug‐induced neutropenia and agranulocytosis are considered rare; an analysis in 2014 determined the incidence to be 5 cases per 1 million inhabitants per year . However, given that the estimated mortality rate of drug‐induced agranulocytosis is 5%, it is essential to identify medications that can increase the risk for neutropenia . Although neutropenia is commonly associated with patients receiving chemotherapeutic agents, nonchemotherapeutic agents, such as analgesics and anticonvulsants, have also been associated with drug‐induced neutropenia .…”

Section: Selected Medications With At Least One Definite Report Of Nementioning

confidence: 99%

Octreotide-Associated Neutropenia

Tse

Kish

2017

Pharmacotherapy

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Drug-induced neutropenia and agranulocytosis are rare adverse events but can be fatal. Neutropenia can be induced by a myriad of drugs from almost every pharmacologic class. Octreotide is a somatostatin analog that has been used to treat variceal bleeding, acromegaly, and severe diarrhea associated with metastatic tumors, and to reduce symptoms in the setting of malignant bowel obstruction and pseudoobstruction. The most common adverse effects associated with octreotide include pain at the injection site and gastrointestinal effects such as loose stools, cramping, and nausea; neutropenia is not currently listed as an adverse effect of the drug. We describe the case of an 87-year-old man who developed neutropenia immediately after administration of three doses of subcutaneous octreotide. He presented to the hospital with a history of constipation and straining for 3 days. He was admitted, and laxatives, suppositories, and enemas were administered over the next 3 days to induce a bowel movement; however, they were ineffective. Bowel obstruction secondary to a mass was confirmed by computed tomography; the mass was eventually diagnosed as colon cancer. Octreotide 100 µg subcutaneously every 8 hours was started for the obstruction on the evening of hospital day 4. After the patient had received 3 doses of octreotide, his white blood cell count (WBC) had decreased from 4.1 × 10 /mm (neutrophils 75.4%, absolute neutrophil count [ANC] 3.1 × 10 /mm ) on admission to 1.6 × 10 /mm (neutrophils 62%, ANC 0.99 × 10 /mm ) on day 5. Given the temporal relationship of octreotide and neutropenia as well as the lack of a reasonable alternative cause, it was suspected that octreotide was the most likely culprit of the patient's neutropenia. Octreotide was subsequently discontinued, and his WBC increased to 4.9 × 10 /mm (neutrophils 66.3%, ANC 3.2 × 10 /mm ) the next day. The remainder of the patient's hospitalization was not significant for any further hematologic abnormalities. His WBC and ANC (WBC 6.7 × 10 /mm , neutrophils 83.2%, ANC 5.6 × 10 /mm ) remained stable 30 days after the incident. Use of the Naranjo Adverse Drug Reaction Probability Scale indicated a probable relationship (score of 5) between the patient's development of neutropenia and octreotide therapy. To our knowledge, this report highlights the first case of octreotide-associated neutropenia. Although the frequency of drug-induced neutropenia remains rare outside of cytotoxic chemotherapy, the importance of recognizing this adverse effect cannot be understated given the mortality risks for neutropenic patients.

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Nonchemotherapy Drug-Induced Neutropenia and Agranulocytosis

Cited by 48 publications

References 27 publications

Neutropenia induced by high-dose intravenous benzylpenicillin in treating neurosyphilis: Does it really matter?

Neutropenia induced by high-dose intravenous benzylpenicillin in treating neurosyphilis: Does it really matter?

Iatrogenic AKI and Agranulocytosis: a Cautious Tale of Medication Use in Elderly Patients

Octreotide-Associated Neutropenia

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