Busulfex

Last updated on RxList: 3/17/2021
Busulfex Side Effects Center

What Is Busulfex?

Busulfex (busulfan) is a cancer (antineoplastic) medication used to treat the symptoms of chronic myelogenous leukemia (a type of blood cancer). Busulfex is not a cure for leukemia.

What Are Side Effects of Busulfex?

Common side effects of Busulfex include:

  • nausea,
  • vomiting,
  • diarrhea,
  • constipation,
  • loss of appetite,
  • weight loss,
  • mouth sores,
  • upset stomach,
  • abdominal pain,
  • dizziness,
  • weakness,
  • swelling of the ankles/feet/hand,
  • flushing (warmth,
  • redness, or tingly feeling),
  • headache,
  • trouble sleeping,
  • swelling or irritation around the IV needle,
  • missed menstrual periods,
  • hair loss,
  • darkened skin color, and
  • fatigue.

Tell your doctor if you have serious side effects of Busulfex including:

  • pale skin,
  • lightheadedness,
  • shortness of breath,
  • trouble concentrating,
  • easy bruising,
  • unusual bleeding,
  • purple or red pinpoint spots under your skin,
  • signs of infection (such as fever, chills, sore throat, flu symptoms, loss of appetite, weight loss, unusual weakness, mouth and throat ulcers, rapid and shallow breathing),
  • weight gain,
  • stomach swelling or tenderness,
  • yellowing of the skin or eyes (jaundice),
  • coughing up blood,
  • stomach pain,
  • sharp chest pain,
  • trouble breathing,
  • lower back pain,
  • blood in your urine,
  • urinating less than usual or not at all,
  • confusion,
  • jerking muscle movements,
  • muscle tightness or contraction,
  • overactive reflexes,
  • muscle weakness or limp feeling,
  • leg discomfort,
  • numbness or tingly feeling around your mouth,
  • fast/slow/uneven heart rate,
  • weak pulse,
  • confusion,
  • fainting,
  • seizures (convulsions),
  • persistent cough,
  • congestion, or
  • low fever

Dosage for Busulfex

The usual adult dose of Busulfex is 0.8 mg/kg of ideal body weight or actual body weight, whichever is lower, administered every six hours for four days (a total of 16 doses).

What Drugs, Substances, or Supplements Interact with Busulfex?

Busulfex may interact with acetaminophen, itraconazole, or phenytoin. Tell your doctor all medications and supplements you use.

Busulfex During Pregnancy and Breastfeeding

Busulfex is not recommended for use during pregnancy. It may harm a fetus. Discuss birth control with your doctor. If you become pregnant or think you may be pregnant, tell your doctor. It is unknown if this drug passes into breast milk. Because of the possible risk to the infant, breastfeeding while using this drug is not recommended.

Additional Information

Our Busulfex (busulfan) Side Effects Drug Center provides a comprehensive view of available drug information on the potential side effects when taking this medication.

This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

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Busulfex Consumer Information

Get emergency medical help if you have signs of an allergic reaction (hives, difficult breathing, swelling in your face or throat) or a severe skin reaction (fever, sore throat, burning eyes, skin pain, red or purple skin rash with blistering and peeling).

Call your doctor at once if you have:

  • easy bruising, unusual bleeding, purple or red spots under your skin;
  • fever, chills, tiredness, sore throat;
  • cough, trouble breathing, chest pain, wheezing;
  • coughing with bloody mucus;
  • pale skin, cold hands and feet;
  • vision problems;
  • persistent cough, congestion, or breathing problems that occur several months or years after using busulfan;
  • a seizure;
  • adrenal gland problems--nausea, vomiting, loss of appetite, weight loss and severe weakness or tired feeling;
  • signs of a heart problem--stomach pain, vomiting, sharp chest pain, trouble breathing;
  • signs of liver problems--weight gain, stomach swelling or tenderness, jaundice (yellowing of the skin or eyes); o
  • signs of an electrolyte imbalance--muscle contractions, muscle weakness, leg cramps, irregular heartbeats, fluttering in your chest, increased thirst or urination, numbness or tingling.

Common side effects may include:

  • fever, chills, headache, weakness;
  • pain;
  • nausea, vomiting, stomach pain, diarrhea;
  • fast heartbeats;
  • changes in your menstrual periods;
  • blisters or ulcers in your mouth, red or swollen gums, trouble swallowing;
  • dry mouth, nose, or throat;
  • dry or thinning skin, darkened skin color;
  • breast swelling;
  • sleep problems (insomnia); or
  • anxiety.

This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

Read the entire detailed patient monograph for Busulfex (Busulfan)

QUESTION

What is leukemia? See Answer
Busulfex Professional Information

SIDE EFFECTS

The following adverse reactions are discussed in more detail in other sections of the labeling:

  • Myelosuppression [see WARNINGS AND PRECAUTIONS]
  • Seizures [see WARNINGS AND PRECAUTIONS]
  • Hepatic Veno-Occlusive Disease (HVOD) [see WARNINGS AND PRECAUTIONS]
  • Embryo-fetal Toxicity [see WARNINGS AND PRECAUTIONS]
  • Cardiac Tamponade [see WARNINGS AND PRECAUTIONS]
  • Bronchopulmonary Dysplasia [see WARNINGS AND PRECAUTIONS]
  • Cellular Dysplasia [see WARNINGS AND PRECAUTIONS]

Clinical Trials Experience

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.

Adverse reaction information is primarily derived from the clinical study (N=61) of BUSULFEX and the data obtained for high-dose oral busulfan conditioning in the setting of randomized, controlled trials identified through a literature review.

In the BUSULFEX (busulfan) Injection allogeneic stem cell transplantation clinical trial, all patients were treated with BUSULFEX 0.8 mg per kg as a two-hour infusion every six hours for 16 doses over four days, combined with cyclophosphamide 60 mg per kg ×2 days. Ninetythree percent (93%) of evaluable patients receiving this dose of BUSULFEX maintained an AUC less than 1,500 μM•min for dose 9, which has generally been considered the level that minimizes the risk of HVOD.

Table 1 lists the non-hematologic adverse reactions events through Bone Marrow Transplantation (BMT) Day +28 at a rate greater than or equal to 20% in patients treated with BUSULFEX prior to allogeneic hematopoietic cell transplantation.

Table 1: Summary of the Incidence (greater than or equal to 20%) of Non-Hematologic Adverse Reactions through BMT Day +28 in Patients who Received BUSULFEX Prior to Allogeneic Hematopoietic Progenitor Cell Transplantation

Non-Hematological Adverse Reactions* Percent Incidence
BODY AS A WHOLE
  Fever 80
  Headache 69
  Asthenia 51
  Chills 46
  Pain 44
  Edema General 28
  Allergic Reaction 26
  Chest Pain 26
  Inflammation at Injection Site 25
  Back Pain 23
CARDIOVASCULAR SYSTEM
  Tachycardia 44
  Hypertension 36
  Thrombosis 33
  Vasodilation 25
DIGESTIVE SYSTEM
  Nausea 98
  Stomatitis (Mucositis) 97
  Vomiting 95
  Anorexia 85
  Diarrhea 84
  Abdominal Pain 72
  Dyspepsia 44
  Constipation 38
  Dry Mouth 26
  Rectal Disorder 25
  Abdominal Enlargement 23
METABOLIC AND NUTRITIONAL SYSTEM
  Hypomagnesemia 77
  Hyperglycemia 66
  Hypokalemia 64
  Hypocalcemia 49
  Hyperbilirubinemia 49
  Edema 36
  SGPT Elevation 31
  Creatinine Increased 21
NERVOUS SYSTEM
  Insomnia 84
  Anxiety 72
  Dizziness 30
  Depression 23
RESPIRATORY SYSTEM
  Rhinitis 44
  Lung Disorder 34
  Cough 28
  Epistaxis 25
  Dyspnea 25
SKIN AND APPENDAGES
  Rash 57
  Pruritus 28
* Includes all reported adverse reactions regardless of severity (toxicity grades 1-4)

Additional Adverse Reactions By Body System

Hematologic: Prolonged prothrombin time

Gastrointestinal: Esophagitis, ileus, hematemesis, pancreatitis, rectal discomfort

Hepatic: Alkaline phosphatase increases, jaundice, hepatomegaly

Graft-versus-host disease: Graft-versus-host disease. There were 3 deaths (5%) attributed to GVHD.

Edema: Hypervolemia, or documented weight increase

Infection: Infection, pneumonia (fatal in one patient and life-threatening in 3% of patients)

Cardiovascular: Arrhythmia, atrial fibrillation, ventricular extrasystoles, third degree heart block, thrombosis (all episodes were associated with the central venous catheter), hypotension, flushing and hot flashes, cardiomegaly, ECG abnormality, left-sided heart failure, and pericardial effusion

Pulmonary: Hyperventilation, alveolar hemorrhage (fatal in 3%), pharyngitis, hiccup, asthma, atelectasis, pleural effusion, hypoxia, hemoptysis, sinusitis, and interstitial fibrosis (fatal in a single case)

Neurologic: Cerebral hemorrhage, coma, delirium, agitation, encephalopathy, confusion, hallucinations, lethargy, somnolence

Renal: BUN increased, dysuria, oliguria, hematuria, hemorrhagic cystitis

Skin: Alopecia, vesicular rash, maculopapular rash, vesiculo-bullous rash, exfoliative dermatitis, erythema nodosum, acne, skin discoloration

Metabolic: Hypophosphatemia, hyponatremia

Other Events: Injection site pain, myalgia, arthralgia, ear disorder

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 BUSULFEX (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.

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] . 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.

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
* TRM = Transplantation Related Mortality
VOD = Veno-Occlusive Disease of the liver
GVHD = Graft versus Host Disease

DRUG INTERACTIONS

Drugs That Decrease BUSULFEX Clearance

Itraconazole decreases busulfan clearance by up to 25%. Metronidazole decreases the clearance of busulfan to a greater extent than does itraconazole; metronidazole coadministration has been associated with increased busulfan toxicity. Fluconazole (200 mg) has been used with BUSULFEX.

Decreased clearance of busulfan was observed with concomitant use with deferasirox. The mechanism of this interaction is not fully elucidated. Discontinue iron chelating agents well in advance of administration of BUSULFEX to avoid increased exposure to busulfan.

Because busulfan is eliminated from the body via conjugation with glutathione, use of acetaminophen prior to (less than 72 hours) or concurrent with BUSULFEX may result in reduced busulfan clearance based upon the known property of acetaminophen to decrease glutathione levels in the blood and tissues.

Drugs That Increase BUSULFEX Clearance

Phenytoin increases the clearance of busulfan by 15% or more, possibly due to the induction of glutathione-S-transferase. Since the pharmacokinetics of BUSULFEX were studied in patients treated with phenytoin, the clearance of BUSULFEX at the recommended dose may be lower and exposure (AUC) higher in patients not treated with phenytoin.

Read the entire FDA prescribing information for Busulfex (Busulfan)

© Busulfex Patient Information is supplied by Cerner Multum, Inc. and Busulfex Consumer information is supplied by First Databank, Inc., used under license and subject to their respective copyrights.

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