Agranulocytosis Associated with Initiation of Famotidine Therapy

Marcus, Esther‐Lee; Clarfield, A. Mark; Kleinman, Yosef; Bits, Helena; Darmon, David; Da’as, Nael

doi:10.1345/aph.1a045

Cited by 5 publications

(4 citation statements)

References 21 publications

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“…Therefore, we presume that the possibility of drug-induced hepatitis or HCC-related increase in LFTs is much lower than that of HBV reactivation, although famotidine-induced hepatitis remains much less likely. Famotidine is also known to induce agranulocytosis 5) and can cause immunosuppression. However, the lowest white blood cell count and absolute neutrophil count in our patient were 2900/ml and 2240/ml, respectively, so the possibility of famotidine-induced agranulocytosis leading to HBV reactivation was thought to be quite low.…”

Section: Discussionmentioning

confidence: 99%

Reactivation of Hepatitis B Virus After Glioblastoma Treatment With Temozolomide -Case Report-

Ohno

Narita

Miyakita

et al. 2011

Neurol. Med. Chir.(Tokyo)

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A 61-year-old man with glioblastoma and positive for hepatitis B surface antigen (HBsAg) developed acute hepatitis due to hepatitis B virus (HBV) reactivation after concomitant postoperative treatment with temozolomide (75 mg/m 2 /day) and radiation therapy (60 Gy in 30 fractions). Corticosteroids were not used during chemo-radiation therapy, and grade 4 lymphocytopenia was observed. The levels of liver function tests (LFTs), including levels of aspartate aminotransferase and alanine aminotransferase, increased 5 weeks after the completion of chemo-radiation therapy, and reached the maximum levels of 1,549 IU/l (normal 13 to 33 IU/l) and 1,653 IU/l (normal 8 to 42 IU/l), respectively, after 2 weeks. At this point, serum HBV-deoxyribonucleic acid (DNA) level had increased to 630-fold over the baseline, and therapy with the antivirus agent entecavir (0.5 mg daily) was started. Over the next 2 weeks, the levels of LFTs and HBV-DNA improved. The present and previous cases suggest that grade 3/4 lymphocytopenia or grade 2 lymphocytopenia with corticosteroid use might have a significant effect on HBV reactivation. To avoid this complication, HBsAg-positive patients with glioblastoma should consult a hepatologist for initiating antivirus therapy before temozolomide treatment.

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Section: Discussionmentioning

confidence: 99%

Reactivation of Hepatitis B Virus After Glioblastoma Treatment With Temozolomide -Case Report-

Ohno

Narita

Miyakita

et al. 2011

Neurol. Med. Chir.(Tokyo)

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“…However, other drugs examined in this study, for example amitriptyline, can also induce agranulocytosis (Flanagan and Dunk 2008b), and the pK i and pK B values of this drug for H 2 R are within the therapeutic reference range (Table 1). Moreover, rare cases of agranulocytosis following therapy with the high-affinity H 2 R antagonist famotidine have been reported (Marcu et al 2002). Collectively, H 2 R antagonism as a cause of agranulocytosis/neutropenia during therapy with various drugs may be more relevant than was previously appreciated.…”

Section: Structure-activity Relationships For Antidepressants and Antmentioning

confidence: 98%

Interactions of recombinant human histamine H1, H2, H3, and H4 receptors with 34 antidepressants and antipsychotics

Appl

Holzammer

Dove

et al. 2011

Naunyn-Schmiedeberg's Arch Pharmacol

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Antidepressants and antipsychotics affect multiple molecular targets. Consequently, these drugs exhibit not only unique profiles of therapeutic effects but also several undesired effects. Histamine receptors (H₁R, H₂R, H₃R, and H₄R) belong to the large family of G protein-coupled receptors and are very important drug targets. All four H(x)R subtypes are expressed in the CNS. Interactions of lipophilic, blood-brain barrier-penetrating drugs with H(x)Rs could contribute to therapeutic and unwanted effects. Therefore, we investigated potencies H(x)R as well as potencies and (inverse) agonistic efficacies of 34 antidepressants and antipsychotics at HxRs in functional assays. We expressed human H(x)Rs in Sf9 insect cells and conducted radioligand competition binding experiments and functional steady-state GTPase assays. Ligand affinities and potencies were compared with literature data and related to therapeutic reference ranges. Almost all antidepressants and antipsychotics displayed high binding affinities to H₁R and behaved as antagonists. The atypical antidepressant trimipramine behaved as a high-affinity/high-potency H₂R antagonist (pK(i), 7.39; pK(B), 7.36; pA₂, 7.55). Docking to an H₂R model suggested a probable binding mode. The affinity of antidepressants and antipsychotics for H₃R was low. The atypical antipsychotic clozapine, known to induce agranulocytosis, exhibited partial H₄R agonism for which docking experiments provided a molecular basis. Clozapine also exhibited H₂R antagonism. We observed dissociations between pK(i) and pK (B) values as well as between pK(i) and pIC₅₀ values for H(x)Rs. Antidepressants and antipsychotics interact differentially with H(x)Rs. The concept of functional selectivity (also referred to as ligand-specific receptor conformations or biased signaling) explains dissociations between pK(i) and pK(B) values as well as differences between pK(i) and pIC₅₀ values. The H₁R antagonism of numerous antidepressants and antipsychotics is very pronounced. The H₂R antagonism of trimipramine and partial H₄R agonism of clozapine may be clinically relevant. We also discuss the possible role of the H₂R antagonism of clozapine for neutropenia/agranulocytosis induced by this compound. Finally, we discuss the methodological, conceptual, and clinical limitations of our study.

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“…[2][3][4]9,10 Researchers discussing the nature of the reaction concluded that omeprazole produced a hypersensitivity reaction via a toxic mechanism, with no conclusively determined cause. 6,9,10 While there have been postmarketing reports of agranulocytosis in association with lansoprazole, this has not yet been reported in the literature. 11 To our knowledge, our study is the first to examine the relationship between coprescribed medications and the occurrence of hematological adverse effects in a sample of patients being treated with clozapine.…”

Section: Literature Reviewmentioning

confidence: 99%

“…5 A second proposed mechanism for neutropenia is based on the formation of drug-dependent antibodies. 6 Olaison et al reviewed all beta-lactam orders with a duration of therapy greater than 10 days. 7 Of 215 orders, 70 (33%) were associated with an adverse reaction, 18 of which (8%) involved neutropenia.…”

Section: Literature Reviewmentioning

confidence: 99%

Exploring the Potential Effect of Polypharmacy on the Hematologic Profiles of Clozapine Patients

Shuman

Trigoboff

Demler³

et al. 2014

Journal of Psychiatric Practice

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Agranulocytosis Associated with Initiation of Famotidine Therapy

Abstract: Although agranulocytosis is a rare adverse effect of famotidine, the pharmacist and physician should be aware of this potentially fatal event. If any patient treated with famotidine develops fever, the clinician should consider, among other things, performing a white blood cell count.

Cited by 5 publications

References 21 publications

Reactivation of Hepatitis B Virus After Glioblastoma Treatment With Temozolomide -Case Report-

Reactivation of Hepatitis B Virus After Glioblastoma Treatment With Temozolomide -Case Report-

Interactions of recombinant human histamine H1, H2, H3, and H4 receptors with 34 antidepressants and antipsychotics

Exploring the Potential Effect of Polypharmacy on the Hematologic Profiles of Clozapine Patients

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