Fatal Drug Reaction Associated with Prochlorperazine (Compazine): Report of a Case Characterized by Jaundice, Thrombocytopenia, and Agranulocytosis

McFarland, Robert B.

doi:10.1093/ajcp/40.3.284

Cited by 21 publications

(4 citation statements)

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“…Phenothiazines also displayed notable toxicity against primary human granulocytes and to a lesser extent, lymphocytes. TDZ exhibited greater toxicity than PCZ, but this was not surprising given that agranulocytosis is a noted adverse effect of TDZ. − For this reason, TDZ is perhaps unsuitable for clinical use as a dynII-inhibiting adjuvant therapy in cancer patients undergoing combination chemotherapy with drugs that cause leukopenia. The white cell toxicity exhibited in the present study may, however, be a consequence of the low in vitro concentration (5%) of FCS used.…”

Section: Discussionmentioning

confidence: 99%

Dose-Dependent Effect of Phenothiazines as Dynamin II Inhibitors on the Uptake of PEGylated Liposomes by Endocytic Cells and In Vivo Pharmacokinetics of PEGylated Liposomal Doxorubicin in Rats

et al. 2023

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Dynamin II (dynII) plays a significant role in the internalization pathways of endocytic cells, by allowing membrane invaginations to "bud off". An important class of dynII inhibitors that are used clinically are phenothiazines, such as prochlorperazine (PCZ). PCZ is an antipsychotic drug but is also currently in clinical trials at higher concentrations as an adjuvant in cancer patients that increases the efficacy of monoclonal antibodies at high intravenous doses. It is unknown, however, whether high-dose dynII inhibitors have the potential to alter the pharmacokinetics of co-administered chemotherapeutic nanomedicines that are largely cleared via the mononuclear phagocyte system. This work therefore sought to investigate the impact of clinically relevant concentrations of phenothiazines, PCZ and thioridazine, on in vitro liposome endocytosis and in vivo liposome pharmacokinetics after PCZ infusion in rats. The uptake of fluorescently labeled PEGylated liposomes into differentiated and undifferentiated THP-1 and RAW246.7 cells, and primary human peripheral white blood cells, was investigated via flow cytometry after co-incubation with dynII inhibitors. The IV pharmacokinetics of PEGylated liposomes were also investigated in rats after a 20 min infusion with PCZ. Phenothiazines and dyngo4a reduced the uptake of PEGylated liposomes by THP-1 and RAW264.7 cells in a concentrationdependent manner in vitro. However, dynII inhibitors did not alter the mean uptake of liposomes by human peripheral white blood cells, but endocytic white cells from some donors exhibited sensitivity to phenothiazine exposure. When a clinically relevant dose of PCZ was co-administered with PEGylated liposomal doxorubicin (Caelyx/Doxil) in rats, the pharmacokinetics and biodistribution of liposomes were unaltered. These data suggest that while clinically relevant doses of dynII inhibitors can inhibit the uptake of liposomes by endocytic cells in vitro, they are unlikely to significantly affect the pharmacokinetics of long-circulating, coadministered liposomes.

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Section: Discussionmentioning

confidence: 99%

Dose-Dependent Effect of Phenothiazines as Dynamin II Inhibitors on the Uptake of PEGylated Liposomes by Endocytic Cells and In Vivo Pharmacokinetics of PEGylated Liposomal Doxorubicin in Rats

et al. 2023

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“…Occasional cases of jaundice, including one case of jaundice with cholestasis, have been reported (9,18,19,56,83,90). At least four cases of blood dyscrasia (agranulocytosis, aplastic anzmia and thrombocytopenia) have been documented (5,27,43,56).…”

Section: Side Effectsmentioning

confidence: 99%

Prochlorperazine — A Review of the Literature since 1956^*

Lapierre

Amin

Hattangadi

1969

Canadian Psychiatric Association Journal

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“…Two fatal cases of coexistent leukopenia and thrombocytopenia were reported in the past; one was a 28-year-old female patient receiving chlorpromazine (2) and the other secondary to jaundice, agranulocytosis, and thrombocytopenia associated with pro-chlorperazine administration in 1963 (3). Isolated NL-induced thrombocytopenia is a more rare occurrence, but it has been reported three times during the last decade and a half (4)(5)(6).…”

Section: Introductionmentioning

confidence: 99%

Neuroleptic Malignant Syndrome and Severe Thrombocytopenia: Case Report and Literature Review

Ghani¹,

Ahmed²,

Marco³

2000

Ann. of Clinical Psychiatry

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We report an unusual case of thrombocytopenia associated with neuroleptic malignant syndrome (NMS). A 31-year-old Black male with a history of hypertension, partial seizures, and schizophrenia developed acute rigidity closely followed by severe hyperpyrexia (temperature 102ЊF), tachypnea, and tachycardia. His home medications at the time of presentation included propanolol 10 mg tid, haloperidol 10 mg bid, sodium valproate 500 mg bid, benztropine 1 mg bid, and haloperidol decanoate 100 mg i.m. every 3 weeks, from another psychiatric facility. Despite vigorous therapy for the hyperthermia, he rapidly developed significant hypoxia requiring mechanical ventilation. A diagnosis of neuroleptic malignant syndrome was made and the patient continued to receive aggressive supportive care. On hospital day 2 his platelet count dropped to 47,000/Ȑl and bottomed out at 36,000/Ȑl by day 3 with other blood cell counts remaining within normal limits. Over the next few days he showed rapid clinical improvement with normalization of his blood chemistries and he was discharged home after 5 days of hospitalization in good condition.

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Fatal Drug Reaction Associated with Prochlorperazine (Compazine): Report of a Case Characterized by Jaundice, Thrombocytopenia, and Agranulocytosis

Cited by 21 publications

References 0 publications

Dose-Dependent Effect of Phenothiazines as Dynamin II Inhibitors on the Uptake of PEGylated Liposomes by Endocytic Cells and In Vivo Pharmacokinetics of PEGylated Liposomal Doxorubicin in Rats

Dose-Dependent Effect of Phenothiazines as Dynamin II Inhibitors on the Uptake of PEGylated Liposomes by Endocytic Cells and In Vivo Pharmacokinetics of PEGylated Liposomal Doxorubicin in Rats

Prochlorperazine — A Review of the Literature since 1956^*

Neuroleptic Malignant Syndrome and Severe Thrombocytopenia: Case Report and Literature Review

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Fatal Drug Reaction Associated with Prochlorperazine (Compazine): Report of a Case Characterized by Jaundice, Thrombocytopenia, and Agranulocytosis

Cited by 21 publications

References 0 publications

Dose-Dependent Effect of Phenothiazines as Dynamin II Inhibitors on the Uptake of PEGylated Liposomes by Endocytic Cells and In Vivo Pharmacokinetics of PEGylated Liposomal Doxorubicin in Rats

Dose-Dependent Effect of Phenothiazines as Dynamin II Inhibitors on the Uptake of PEGylated Liposomes by Endocytic Cells and In Vivo Pharmacokinetics of PEGylated Liposomal Doxorubicin in Rats

Prochlorperazine — A Review of the Literature since 1956*

Neuroleptic Malignant Syndrome and Severe Thrombocytopenia: Case Report and Literature Review

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Product

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Prochlorperazine — A Review of the Literature since 1956^*