Busulfan (Page 3 of 6)

6.2 Postmarketing Experience

Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure. The following adverse reactions have been identified during post-approval use of busulfan injection:

Blood and Lymphatic System Disorders: febrile neutropenia

Gastrointestinal Disorders: tooth hypoplasia

Metabolism and Nutrition Disorders: tumor lysis syndrome

Vascular Disorders: thrombotic microangiopathy (TMA)

Infections and Infestations: severe bacterial, viral (e.g., cytomegalovirus viremia) and fungal infections; and sepsis.

6.3 Oral Busulfan Literature Review

A literature review identified four randomized, controlled trials that evaluated a high-dose oral busulfan-containing conditioning regimen for allogeneic bone marrow transplantation in the setting of CML [see Clinical Studies (14)]. The safety outcomes reported in those trials are summarized in Table 2 below for a mixed population of hematological malignancies (AML, CML, and ALL).

Table 2: Summary of Safety Analyses from the Randomized, Controlled Trials Utilizing a High Dose Oral Busulfan-Containing Conditioning Regimen That Were Identified in a Literature Review
*
TRM = Transplantation Related Mortality
VOD = Veno-Occlusive Disease of the liver
GVHD = Graft-versus-Host Disease

Clift

CML Chronic Phase

TRM *

VOD

GVHD

Pulmonary

Hemorrhagic Cystitis

Seizure

Death ≤ 100d = 4.1% (3/73)

No report

Acute ≥ Grade 2 = 35%

Chronic = 41% (30/73)

1 death from Idiopathic Interstitial Pneumonitis and 1 death from Pulmonary Fibrosis

No Report

No Report

Devergie

CML Chronic Phase

TRM

VOD

GVHD

Pulmonary

Hemorrhagic Cystitis

Seizure

38%

7.7% (5/65) Deaths = 4.6% (3/65)

Acute ≥ Grade 2 = 41% (24/59 at risk)

Interstitial Pneumonitis = 16.9% (11/65)

10.8% (7/65)

No Report

Ringden

CML, AML, ALL

TRM

VOD

GVHD

Pulmonary

Hemorrhagic Cystitis

Seizure

28%

12%

Acute ≥ Grade 2 GVHD = 26%

Chronic GVHD = 45%

Interstitial Pneumonitis = 14%

24%

6%

Blume

CML, AML, ALL

TRM

VOD

GVHD

Pulmonary

Hemorrhagic Cystitis

Seizure

No Report

Deaths = 4.9%

Acute ≥ Grade 2 GVHD = 22% (13/58 at risk)

Chronic GVHD = 31% (14/45 at risk)

No Report

No Report

No Report

All MedLibrary.org resources are included in as near-original form as possible, meaning that the information from the original provider has been rendered here with only typographical or stylistic modifications and not with any substantive alterations of content, meaning or intent.

This site is provided for educational and informational purposes only, in accordance with our Terms of Use, and is not intended as a substitute for the advice of a medical doctor, nurse, nurse practitioner or other qualified health professional.

Privacy Policy | Copyright © 2022. All Rights Reserved.