INVEGA - Adverse Event - Hematological Disorders

Summary

• Leukopenia, neutropenia, and agranulocytosis have been reported with antipsychotics, including INVEGA. Patients with a history of a clinically significant low white blood cell count (WBC) or a drug-induced leukopenia/neutropenia should have their complete blood count (CBC) monitored frequently during the first few months of therapy and discontinuation of INVEGA should be considered at the first sign of a clinically significant decline in WBC in the absence of other causative factors.¹

Clinical Data

Trials

Si et al (2015)² conducted an 8-week, open-label, single-arm, multicenter study, in patients with first-episode psychosis having a Positive and Negative Syndrome Scale (PANSS) total score of 70 and treated with flexible-dose paliperidone ER (3-12 mg/day). The safety analysis included 308 Chinese patients. Leukopenia was reported as one treatment emergent adverse event (TEAE) leading to permanent discontinuation of the study drug. No additional information was provided.

Luthringer et al (2007)³ conducted a double-blind, randomized, placebo-controlled study assessing the effect of paliperidone ER on sleep architecture and sleep continuity. One treatment emergent adverse event of thrombocytopenia was reported. No additional information was provided.

Case Studies

Wakuda et al (2019)⁴ detailed a case report of a 46-year-old male with a 5-year schizophrenia history. He was previously treated with blonanserin 24 mg/day plus risperidone 4 mg/day. No significant abnormalities in WBC or other blood cell counts were noted at the time. The patient exhibited worsening suspiciousness and irritability leading to a decrease in risperidone to 2 mg/day plus addition of paliperidone 6 mg/day.

• Thirteen days following the initiation of paliperidone, the patient was brought to the emergency room due to his inability to walk. The patient was hospitalized due to suspected paliperidone-induced agranulocytosis (WBC: 0.3×10⁹/L) as well as a bilateral pulmonary infection.
• All psychotropics were discontinued and the patient was administered granulocyte-colony stimulating factor (G-CSF) 75 μg/day for 3 consecutive days plus doripenem 3 mg/day.
• Two days later, the patient’s WBC count was elevated (4.95×10⁹/L).
• Ten days later, the bilateral pulmonary infection resolved, and the patient was discharged.
• Following discharge, the paliperidone/risperidone regimen was replaced with aripiprazole without further hematological complications.

Matsuura et al (2016)⁵ reported a case of a 50-year-old female with schizoaffective disorder hospitalized after developing auditory hallucinations and aggressive behavior while on quetiapine 200 mg/day, olanzapine 10 mg/day and valproic acid 200 mg/day. Following admission to the hospital, olanzapine was increased to 20 mg/day and valproic acid to 1000 mg/day. After 28 days of hospitalization, the patient continued to experience refractory auditory hallucinations (WBC: 4.03×10⁹/L; neutrophil count: 2.26×10⁹/L).

• Paliperidone was added and the dose was increased to 12 mg/day over the next 2 weeks.
• On day 55 there was a sudden drop in WBC (2.83×10⁹/L) and neutrophil count (0.79×10⁹/L) with normal renal and liver function.
• Paliperidone was discontinued immediately, valproic acid was reduced to 600 mg/day and lithium carbonate 200 mg/day was added to her regimen.
• Four days following initiation of lithium carbonate, her WBC and neutrophil counts returned to normal, 4.34×10⁹/L and 2.29×10⁹/L, respectively. After 28 days, WBC and neutrophils increased to 6.86×10⁹/L and 4.74×10⁹/L, respectively.
• Lithium carbonate was gradually discontinued. There were no further reports of leukopenia or neutropenia over the next 6 months.

Kim et al (2011)⁶ presented a case report of a 33-year-old female who was admitted to the hospital with a 1-year history of auditory and visual hallucinations, persecutory delusions, aggressive behavior, and unstable mood. Upon admission, she had a WBC count of 6.17×10⁹/L and a neutrophil count of 3.97×10⁹/L, with her other cell counts within normal limits.

• She was initially treated with paliperidone ER 6 mg/day and was increased to paliperidone 9 mg/day on day 9.
• On day 14, her WBC count decreased to 2.96×109/L, neutrophil count decreased to 1.18x10⁹/L, and her red blood cell (RBC) count, hemoglobin, and hematocrit decreased slightly to 3.23×10⁶/µL, 10.7 g/dL, and 31.5%, respectively.
• On day 22, after no change in her cell counts, paliperidone was discontinued.
• Three days following discontinuation, her leukopenia and neutropenia improved (WBC count: 3.42×10⁹/L; neutrophil count: 1.57×10⁹/L) and returned to normal by day 36 (WBC count: 4.70×10⁹/L; neutrophil count: 2.77×10⁹/L).

LITERATURE SEARCH

A literature search of MEDLINE^®, Embase^®, BIOSIS Previews^®, and Derwent Drug File (and/or other resources, including internal/external databases) pertaining to this topic was conducted on 04 November 2024. Additional case studies have been referenced.^7,8