Agranulocytosis and Citrobacter Infection Associated with Jamu, a Herbal Remedy Containing Phenylbutazone

Paul, John; Duncan, J.R.; Sharp, P.; Norris, Andrew J.; Siddiq, Mirza A.; Bacon, Clare; Weighill, J. S.

doi:10.1086/430447

Cited by 4 publications

(5 citation statements)

References 1 publication

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“…Kampo medicine has been frequently reported to be associated with agranulocytosis, but the mechanisms by which it induces agranulocytosis remain unclear. [6][7][8][9][10][11][12] However, in our case, the timing between the onset of agranulocytosis and the initiation of Hange-koboku-toh suggests an allergic mechanism.…”

Section: Discussioncontrasting

confidence: 57%

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Identifying causative medications for agranulocytosis: A case report of an older adult with cerebral infarction

Kurokawa,

Watanabe,

Kashiwabara

et al. 2024

Clinical Case Reports

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Key Clinical MessageMost drugs that cause adverse events are difficult to identify in critically ill patients undergoing polypharmacy. We share our experience in identifying the causative drug among four suspect drugs administered during emergency treatment.AbstractWe present the case of a 93‐year‐old man who was admitted for the treatment of cerebrovascular events. The patient was initially prescribed dual antiplatelet therapy with aspirin and clopidogrel along with lansoprazole, Hange‐koboku‐toh, and elobixibat. On day 36 after admission, the patient was found to have developed agranulocytosis. To improve his cerebrovascular prognosis, we first discontinued medications other than the anticoagulant medicines and initiated filgrastim. We discontinued clopidogrel 9 days after the discontinuation of the other medicines considering his low white blood cell count. One day after the discontinuation of clopidogrel, the agranulocytosis was alleviated. Considering the time course, clopidogrel, lansoprazole, Hange‐koboku‐toh, and elobixibat were suspected as the culprit medicines. This case highlights the considerable challenges encountered in clinical practice when attempting to identify the drugs responsible for agranulocytosis, particularly in patients on intensive medication therapy.

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Section: Discussioncontrasting

confidence: 57%

“…Kampo medicine has been frequently reported to be associated with agranulocytosis, but the mechanisms by which it induces agranulocytosis remain unclear. 6 , 7 , 8 , 9 , 10 , 11 , 12 …”

Section: Discussionmentioning

confidence: 99%

Identifying causative medications for agranulocytosis: A case report of an older adult with cerebral infarction

Kurokawa,

Watanabe,

Kashiwabara

et al. 2024

Clinical Case Reports

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“…Total yield 15.5 g (34%) based on the original 50 g of diethyl malonate (8% [41]). IR spectrum, , cm -1 : 3300, 3040 (NH 2 …”

Section: Methodsmentioning

confidence: 99%

Synthesis and crystal structure of some 3,5-pyrazolidinediones

Metwally

Moneim

Elossely

et al. 2010

Chem Heterocycl Comp

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Syntheses of various derivatives of 3,5-pyrazolidenedione are reported. This includes 4-arylidene (alkylidene or aralkylidene)-3,5-pyrazolidinediones, which on epoxidation gave unreported oxiranes. The syntheses of these derivatives were based on either the Knoevenagel reaction of carbonyl derivatives with 3,4-pyrazolidinedione or cyclization of arylidene (alkylidene) malonic acid hydrazide with glacial acetic acid. 4-Arylazo-3,5-pyrazolidinedione derivatives were also prepared by coupling of aryldiazonium salts with 3,5-pyrazolidinedione or cyclization of arylazomalonic acid hydrazide. Reduction of 4-benzylidene derivatives gave the corresponding benzyl derivatives. The structure of the new products was confirmed by elemental and spectral analyses and X-ray crystallography.

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“…Associated hazards Adulteration with phenylbutazone EFSA/EMA (2013) and Lees and Toutain (2013) Blood dyscrasias Sperling (1969) and Faich (1987) Nausea, vomiting, skin rash, oedema, stomatitis and peptic ulcer, haematological disturbances such as agranulocytosis, leukopoenia, anaemia, and thrombocytopenia Giam et al (1986) Erythroderma with hepatitis, and Steven Johnson syndrome Paul et al (2005) Agranulocytosis Doshi et al (2009) Neutropenia and necrotising fasciitis Adulteration with paracetamol/acetaminophen James et al (2003) and Ye et al (2018) Drug-induced liver injury (DILI) Agrawal and Khazaeni (2020) Skin reactions like Stevens-Johnson syndrome, toxic epidermal necrolysis, and acute generalised exanthematous pustulosis are the side effects of paracetamol which are extremely painful and can lead to blindness and death Adulteration with piroxicam Aronson (2016) Gastrointestinal upset and a more serious side effect is the onset of peptic ulcers Lipscomb et al (1998) and Aronson (2016) Headache, dizziness, drowsiness, fatigue, and sweating Murray and Brater (1993) Blurred vision, burning eyes, permanent sensorineural hearing loss, tinnitus, thrombocytopenia, leukopoenia, agranulocytosis, renal, and liver toxicity Adulteration with methampyrone Levy et al (1995) Vomiting and excreting red urine Andrade et al (1998) Gastrointestinal disorders, such as somnolence, gastric discomfort and nausea, agranulocytosis, aplastic anaemia, anaphylaxis, and serious upper gastrointestinal complications EMA (2018a)…”

Section: Referencesmentioning

confidence: 99%

“…Although there are also some reported cases on potential microbiological and metal/metalloid contamination in jamu (Limyati and Juniar 1998;Ali et al 2005;Paul et al 2005;Noveriza 2015;Wasita and Hendrayana 2016;Asra et al 2019;Latifa et al 2020), the present review presents an overview of the current state-of-the art related to the hazards and risks of APIs as well as of constituents that are genotoxic and carcinogenic reported to be present in jamu. This overview informs risk managers aiming at enabling prioritising of regulatory actions to support the safety in use of jamu.…”

Section: Introductionmentioning

confidence: 95%

Risk characterisation of constituents present in jamu to promote its safe use

Suparmi

Wahidin²,

Rietjens

2021

Critical Reviews in Toxicology

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Safety in use of jamu consumption, as part of traditional medicine from Indonesia, is dependent on the complete and adequate assessment of potential hazards and risks of the botanicals and botanical constituents included. This includes especially hazards and risks related to the presence in jamu of active pharmaceutical ingredients (APIs) as well as of constituents that are genotoxic and carcinogenic. The present review presents an overview of the current state-of-the art on these hazards and risks based on case reports on adulteration, and the actual detection of genotoxic and carcinogenic ingredients of concern in jamu. Based on the overview thus obtained, it appears that drug-adulteration presents important hazards responsible for potential adverse effects, due to overdosing. The potential hazards of exposure to APIs mainly relate to the presence of constituents that may cause liver damage, renal impairment, kidney failure, steroid dependence or genotoxicity and carcinogenicity. For these APIs, a risk characterisation was performed based on comparison of health-based guidance values (HBGVs) and exposure, while for the genotoxic carcinogens the margin of exposure (MOE) approach was used. Results of this risk characterisation should be used by risk managers to impose specification for constituents of health concern to protect consumers. It is concluded that to manage the risks identified and further improve the safety in use of jamu, a collaboration between farmers, manufacturer/producers, academia, government, health professionals, and consumers is indicated.

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Agranulocytosis and Citrobacter Infection Associated with Jamu, a Herbal Remedy Containing Phenylbutazone

Cited by 4 publications

References 1 publication

Identifying causative medications for agranulocytosis: A case report of an older adult with cerebral infarction

Identifying causative medications for agranulocytosis: A case report of an older adult with cerebral infarction

Synthesis and crystal structure of some 3,5-pyrazolidinediones

Risk characterisation of constituents present in jamu to promote its safe use

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