Busulfex Side Effects

Generic Name: busulfan

Please note - some side effects for Busulfex may not be reported. Always consult your doctor or healthcare specialist for medical advice. You may also report side effects to the FDA at http://www.fda.gov/medwatch/ or 1-800-FDA-1088 (1-800-332-1088).

Side Effects of Busulfex - for the Consumer

Busulfex

All medicines may cause side effects, but many people have no, or minor, side effects. Check with your doctor if any of these most COMMON side effects persist or become bothersome when using Busulfex:

Anxiety; asthma; back pain; blood clots; change in menstrual cycle; chest pain; confusion; constipation; cough; diarrhea; dizziness; dry mouth; fast heart beat; flushing; headache; hiccup; high blood pressure; increased blood sugar levels; indigestion; inflammation at the injection site; itching; joint pain; loss of appetite; lung disorder; muscle pain; nausea; nosebleed; pain; rash; rectal disorder; runny nose; sinus inflammation; sleeplessness; swelling; tiredness; weakness.

Severe allergic reactions (rash; hives; itching; difficulty breathing; tightness in the chest; swelling of the mouth, face, lips, or tongue); blurred vision or vision changes; congestion; decreased ability to fight infection; depression; fever, chills, or sore throat; hallucinations; irregular heartbeat; loss of consciousness; missed menstrual period; pain and distention of the abdomen; pain, redness, or swelling at the injection site; pale skin; persistent cough; rapid weight gain; rash; seizures; shortness of breath; stomach pain; sudden onset of sweating; unusual bruising or bleeding; unusual tiredness or fatigue; vomiting; yellowing of the skin or eyes.

Side Effects by Body System

Hematologic

Hematologic side effects including myelosuppression resulting in leukopenia, thrombocytopenia and anemia, comprise the most frequent toxic effects that have been reported with the use of busulfan. Dose limiting myelosuppression is the main side effect with usual doses.

Myelosuppression can develop suddenly and may be prolonged, but is usually reversible. Myelosuppression is most frequently the result of a failure to discontinue further drug administration in the face of an undetected decrease in leukocyte or platelet counts. During high dose therapy, neutrophils start to increase on approximately the 19th day and platelets on approximately the 30th day. In one study, four out of 243 patients treated with busulfan developed leukemia.

Respiratory

Corticosteroids have been reported to have been beneficial in arresting or reversing the fibrosis in some cases.

Respiratory side effects including lung damage have frequently been reported (approximately 33% of patients with the higher doses used for bone marrow transplant). While reported only rarely, interstitial pulmonary fibrosis (busulfan lung) warrants the immediate discontinuation of busulfan administration. Presentation of symptoms is delayed by several years in many patients. There is a slow onset of cough, dyspnea and low grade fever. (However, the clinician needs to rule out infection or leukemia in the lungs.) Next, patients may present with pulmonary insufficiency, tachypnea and cyanosis which may eventually be fatal. A single case of pulmonary alveolar proteinosis has also been reported.

Cardiovascular

Cardiovascular side effects including mild or moderate tachycardia have been reported in 44% of patients. In 7 patients (11%) it was first reported during busulfan administration. Other rhythm abnormalities, which were all mild or moderate, included arrhythmia (5%), atrial fibrillation (2%), ventricular extrasystoles (2%), and third degree heart block (2%).

Mild or moderate thrombosis occurred in 33% of patients. (All episodes were associated with the central venous catheter.)

Hypertension (36%), mild vasodilation (flushing and hot flashes) (25%), and hypotension (11%) have also been reported.

Other cardiovascular events included cardiomegaly (5%), mild ECG abnormality (2%), Grade 3/4 left-sided heart failure in one patient (2%), and moderate pericardial effusion (2%). (These events were reported primarily in the post-cyclophosphamide phase.)

One case of endocardial fibrosis has been reported.

The case of endocardial fibrosis was reported in a 79-year-old woman who received a total dose of 7,200 mg over a period of 9 years for the management of chronic myelogenous leukemia. At autopsy, she was found to have endocardial fibrosis of the left ventricle in addition to interstitial pulmonary fibrosis.

Ocular

The drug has also been reported to induced cataracts in rats.

Ocular side effects including cataracts and vision changes have been reported rarely after prolonged administration.

Dermatologic

Dermatologic side effects including hyperpigmentation (usually seen in skin folds near nails and hands) have been reported (5% to 10%). Urticaria, erythema multiforme, erythema nodosum, alopecia, porphyria cutanea tarda, and excessive dryness and fragility of the skin with anhidrosis have also been reported.

In one study, 31 out of 65 patients that received busulfan prior to bone marrow transplantation had some degree of alopecia. In 19 of these patients, the alopecia was extensive. While all patients received the same dosage per kg, patients that had higher blood concentrations developed more extensive alopecia.

Hyperpigmentation has most frequently been reported in patients with a dark complexion.

Some cases of alopecia have been permanent.

Metabolic

The symptoms of the syndrome (which resembles adrenal insufficiency) have sometimes been reversible after the drug has been withdrawn. Adrenal responsiveness to exogenously administered ACTH has usually been normal. However, pituitary function testing with metyrapone revealed a blunted 17-hydroxycorticosteroid excretion in two patients. Following the discontinuation of the drug (which was associated with clinical improvement), rechallenge with metyrapone revealed normal pituitary-adrenal function.

Adverse effects due to the increased urate pool can be minimized by increased hydration, urine alkalinization and the prophylactic administration of a xanthine oxidase inhibitor (e.g., allopurinol).

Metabolic side effects including several cases of a clinical syndrome closely resembling adrenal insufficiency, characterized by weakness, severe fatigue, anorexia, weight loss, melanoderma, nausea, and vomiting, have been reported after prolonged therapy.

While hyperuricemia and/or hyperuricosuria are not uncommon in patients with chronic myelogenous leukemia, additional rapid destruction of granulocytes may accompany the initiation of chemotherapy and increase the urate pool.

Hepatic

Hepatic side effects including hepatic veno-occlusive disease have been reported. Esophageal varices have been reported in patients receiving busulfan in combination with thioguanine. Jaundice and hepatitis have also been reported.

Based on clinical examination and laboratory findings, hepatic veno-occlusive disease was diagnosed in 8% (5/61) of patients treated with busulfan in the setting of allogeneic transplantation, was fatal in 2/5 cases (40%), and yielded an overall mortality from hepatic veno-occlusive disease in the entire study population of 2/61 (3%).

Nervous system

Nervous system side effects including seizures have generally been reported after the third or fourth day in patients receiving high dose therapy.

In one study of 28 bone marrow transplant recipients that had received busulfan, 3 cases of convulsions have been reported. Two of the 3 patients that experienced the convulsions had been pretreated with anticonvulsants. Another study reported 2 patients out of 130 experienced seizures. There have been 16 cases of busulfan-related seizures reported in the literature. Prophylactic anticonvulsant therapy (phenytoin) should be considered in patients receiving high dose busulfan.

Oncologic

Oncologic side effects including cytologic and histologic changes in the urinary and respiratory tracts as well as the uterine cervix and liver have been reported. The International Agency for Research on Cancer (IARC) has classified the activity of busulfan as sufficient to indicate potential carcinogenicity (in short-term tests). Two cases of endometrial cancer have been reported (each case followed two years of treatment).

Other

Other side effects in patients receiving allogenic transplant were some form of edema (79%), hypervolemia, or documented weight increase (8%). All events were reported as mild or moderate.

Genitourinary

Genitourinary side effects including hemorrhagic cystitis, gynecomastia, amenorrhea, ovarian and testicular atrophy (resulting in sterility) have been reported.

Gastrointestinal

Gastrointestinal side effects including dryness of the oral mucous membranes and cheilosis have been reported.

Musculoskeletal

Musculoskeletal side effects including myasthenia gravis have been reported.

Disclaimer: Every effort has been made to ensure that the information provided is accurate, up-to-date, and complete, but no guarantee is made to that effect. In addition, the drug information contained herein may be time sensitive and should not be utilized as a reference resource beyond the date hereof. This information does not endorse drugs, diagnose patients, or recommend therapy. This drug information is a reference resource designed as supplement to, and not a substitute for, the expertise, skill , knowledge, and judgement of healthcare practitioners in patient care. The absence of a warning for a given drug or drug combination in no way should be construed to indicate that the drug of drug combination is safe, effective, or appropriate for any given patient. Drugs.com does not assume any responsibility for any aspect of healthcare administered with the aid of information provided. The information contained herein is not intended to cover all possible uses, directions, precautions, warnings, drug interactions, allergic reactions, or adverse effects. If you have questions about the drugs you are taking, check with your doctor, nurse, or pharmacist.