Article Contents ::

Details About Generic Salt ::  Busulfan

Main Medicine Class::    

(byoo-FULL-fan)
Myleran
Tablets
2 mg
Solution for injection
6 mg/mL
Class: Alkylating agents
Alkyl sulfonates

 Indications Palliative treatment of chronic myelogenous leukemia (oral); allogeneic bone marrow transplantation for chronic myelogenous leukemia (IV).

Pediatric

Palliative treatment of chronic myelogenous leukemia (oral).

Severe thrombocytosis, polycythemia vera, myelofibrosis; bone marrow transplantation (oral).

 Contraindications

Tablets

Do not use unless a diagnosis of chronic myelogenous leukemia has been adequately established. Patients whose disease has demonstrated prior resistance to the drug without a diagnosis of CML. Busulfan is of no value in chronic lymphocytic leukemia, acute leukemia, or in the “blastic crisis” of CML.

Injection

Hypersensitivity to any of its components.

 Route/Dosage

Remission Induction of Chronic Myelogenous Leukemia

ADULTS: PO 4 to 8 mg/day (60 mcg/kg or 1.8 mg/m2/day). When the total leukocyte count is < 15,000/mm3, withhold drug. During remission, treatment is resumed when a monthly WBC reaches 50,000/mm.3

PEDIATRIC: PO 60 to 120 mcg/kg or 1.8 to 4.6 mg/m2 once daily. When total leukocyte count is < 15,000/mm,3 withhold drug. During remission, treatment is resumed when a monthly WBC reaches 50,000/mm.3

Bone Marrow Ablation

ADULTS: PO 1 mg/kg q 6 hr for 16 doses (for a total dose of 16 mg/kg over 4 days) in combination with other agents. An alternate regimen is busulfan 0.4375 to 0.5 mg/kg q 6 hr for 16 doses (total dose of 7 to 8 mg/kg, respectively, over 4 days) alone or in combination with other chemotherapy agents.

ADULTS: IV 0.8 mg/kg q 6 hr for 16 doses (for a total dose of 12.8 mg/kg over 4 days). Base dose on ideal body weight or actual body weight, whichever is lower. For obese patients, dosage should be based on adjusted body weight.

Dosage Adjustment

PEDIATRIC: PO Reduce dose 50% for WBC between 30,000 to 40,000/mm.3 Discontinue therapy if WBC count falls to £ 20,000/mm3.

Interactions

Acetaminophen

May decrease busulfan clearance.

Itraconazole

Decreases busulfan clearance 25%, increasing serum levels and effects.

Phenytoin

Increases busulfan clearance ³ 15%, reducing serum levels and effects.

Thioguanine

Long term, concomitant use has resulted in hepatotoxicity and esophageal varices.

Lab Test Interferences None well documented.

 Adverse Reactions

CARDIOVASCULAR: Tachycardia, thrombotic events, hypertension, generalized edema, chest pain, vasodilatation (IV). CNS: Confusion; seizures; insomnia, anxiety, headache, asthenia, dizziness, depression (IV). DERMATOLOGIC: Hyperpigmentation, urticaria, alopecia; rash, pruritus (IV). ENDOCRINE: Clinical syndrome similar to adrenal insufficiency. GI: Nausea; vomiting; diarrhea; transient LFT elevations; hepatic veno-occlusive disease after bone marrow transplantation; stomatitis, anorexia, abdominal pain, hyperbilirubinemia, dyspepsia, constipation, dry mouth, jaundice (IV). GU: Amenorrhea; ovarian failure;, sterility; azoospermia; testicular atrophy. HEMATOLOGIC: Pancytopenia; delayed bone marrow suppression. METABOLIC: Hypomagnesemia, hypokalemia, hyperglycemia, hypocalcemia (IV). RENAL: Uric acid nephropathy; renal stones; acute renal failure. RESPIRATORY: Interstitial pulmonary fibrosis; rhinitis, cough, epistaxis, dyspnea (IV). SPECIALSENSES: Cataracts. OTHER: Acute leukemia and malignant tumors; cellular dysplasia; fever, chills (IV).

 Precautions

Pregnancy: Category D. Lactation: Undetermined. Children: Safety and efficacy not established. Adrenal insufficiency: A clinical syndrome closely resembling adrenal insufficiency and characterized by weakness, severe fatigue, anorexia, weight loss, nausea, vomiting, and melanoderma has developed after prolonged therapy. Carcinogenesis: Malignant tumors have occurred in patients on busulfan therapy; this drug may be a human carcinogen. Cardiovascular: Cardiac tamponade, which was often fatal, has been reported in a small number of pediatric patients with thalassemia (2% in 1 series) who received high doses of busulfan and cyclophosphamide as the preparatory regimen for bone marrow transplantation and hematopoietic progenitor cell transplantation. Abdominal pain and vomiting preceded the tamponade in most patients. Cellular dysplasia: Busulfan may cause cellular dysplasia in many organs in addition to the lung. Giant hyperchromatic nuclei have been reported in the lymph nodes, pancreas, thryroid, adrenal glands, bone marrow, and liver. Fertility impairment: Ovarian suppression and amenorrhea with menopausal symptoms commonly occur during busulfan therapy in premenopausal patients. Hematopoietic toxicity: Most frequent and serious side effect is bone marrow failure, resulting in severe pancytopenia. Recovery from busulfan-induced pancytopenia may take from 1 mo to 2 yr. The most consistent dose-related toxicity is bone marrow suppression. This may be manifested by neutropenia, anemia, leukopenia, thrombocytopenia, or any combination of these. Busulfan-induced bone marrow suppression may be prolonged. The WBC may continue to drop for 2 to 3 wk after therapy is discontinued and may take up to 2 mo to recover. Hepatic function impairment: High doses may be associated with an increased risk of developing hepatic VOD. Hyperuricemia and hyperuricosuria: May occur in patients with chronic myelogenous leukemia. Minimize adverse effects by increased hydration, urine alkalization, and the prophylactic administration of allopurinol. Pulmonary effects: A rare but important complication of busulfan therapy is the development of bronchopulmonary dysplasia with pulmonary fibrosis. Symptoms have occurred within 8 mo to 10 yr after initiation of therapy. Clinically, patients report the insidious onset of cough, dyspnea, and low-grade fever. Pulmonary function studies reveal diminished diffusion capacity and decreased pulmonary compliance. Seizures: Seizures have been reported in patients receiving high oral doses of busulfan. Risk of seizures may be reduced by prophylactic administration of phenytoin. Some clinicians administer a loading dose of phenytoin 15 to 18 mg/kg orally prior to starting busulfan followed by a maintenance dose of phenytoin 300 mg/day orally until 24 hr after administering the final busulfan dose. Maintenance doses ranging from 4 to 8 mg/kg/day orally have also been given, titrated to achieve therapeutic phenytoin serum levels (10 to 20 mcg/mL).

PATIENT CARE CONSIDERATIONS


 Administration/Storage

  • Store oral tablets at room temperature.
  • Refrigerate solution for injection in unopened ampules.
  • Withdraw dose from the ampule, using the provided 5 micron filter needle. Remove the filter needle and use a new needle to add busulfan to the diluent.
  • Dilute solution for injection with 5% Dextrose or 0.9% Sodium Chloride, for a final busulfan concentration of » 0.5 mg/mL. Add the busulfan to the diluent; do not add the diluent to busulfan.
  • To determine the approximate volume of diluent required, multiply the volume of busulfan injection by 10.
  • Diluted busulfan solutions are stable for up to 8 hr at room temperature and for up to 12 hr under refrigeration.
  • Administer by oral, IV infusion
  • Follow safe handling procedures and disposal of chemotherapy drugs. Wear gloves and avoid skin contact and inhalation of fumes.

IV

  • Infuse over 2 hr. Vigorous hydration reduces the risk of renal toxicity

 Assessment/Interventions

  • Monitor patients for signs of local or systemic infection or bleeding. Frequently evaluate their hematologic status.
  • Periodic measurement of serum transaminases, alkaline phosphatase, and bilirubin is indicated for early detection of hepatotoxicity.
  • It is recommended that evaluation of the hemoglobin or hematocrit, total WBC, complete blood count, including differential count and quantitative platelet count, be obtained weekly (daily for injection) while the patient is on busulfan therapy, and until engraftment has been demonstrated.
  • Evaluate serum transaminase, alkaline phosphatase, and bilirubin daily through transplant day 28 to detect hepatotoxicity, which may herald the onset of hepatic VOD.
  • Risk of seizures may be reduced by prophylactic administration of phenytoin. Some clinicians administer a loading dose of phenytoin 15 to 18 mg/kg orally prior to starting busulfan followed by a maintenance dose of phenytoin 300 mg/day orally until 24 hr after administering the final busulfan dose. Maintenance doses ranging from 4 to 8 mg/kg/day orally have also been given, titrated to achieve therapeutic phenytoin serum levels (10 to 20 mcg/mL).

PO

  • Some clinicians place patients on a clear-liquid diet to decrease the risk of vomiting. In addition, they may prescribe additional doses of busulfan if tablets are visible in emesis. A full replacement dose may be given if vomiting occurs within 30 min of a dose and pill fragments are visible in the vomitus. If vomiting occurs > 30 min after a dose, the replacement dose may be estimated based on the number of visible pill fragments; patients typically receive 50% of the usual dose.
OVERDOSAGE: SIGNS & SYMPTOMS
  Tablets: Bone marrow hypoplasia/aplasia, pancytopenia

 Patient/Family Education

  • Inform patients beginning therapy with busulfan of the importance of having periodic blood counts.
  • Notify health care provider if unusual bleeding or bruising; fever; persistent cough; congestion; shortness of breath; flank, stomach or joint pain; abrupt weakness; unusual fatigue; anorexia; or weight loss occurs.
  • Tell patients that diffuse pulmonary fibrosis is an infrequent but serious and potentially life-threatening complication of long-term busulfan therapy.
  • Inform patients that some toxicities to busulfan include infertility, amenorrhea, skin hyperpigmentation, drug hypersensitivity, dryness of the mucous membranes.
  • Medication may cause darkening of skin, diarrhea, dizziness, fatigue, appetite loss, mental confusion, nausea, vomiting, and melanoderma that could be associated with a syndrome resembling adrenal insufficiency; notify health care provider if these become pronounced.
  • Take medication at the same time each day.
  • Extra fluid intake may be recommended.
  • Contraceptive measures are recommended during therapy.
  • If nausea or vomiting occurs, take the drug on an empty stomach.
  • Explain the increased risk of a second malignancy to the patient.
  • Instruct patients to promptly report the development of fever, sore throat, signs of local infection, bleeding from any site or symptoms suggestive of anemia.

Medicscientist Drug Facts

 

Drugs Class ::

(byoo-FULL-fan)
Myleran
Tablets
2 mg
Solution for injection
6 mg/mL
Class: Alkylating agents
Alkyl sulfonates

Indications for Drugs ::

 Indications Palliative treatment of chronic myelogenous leukemia (oral); allogeneic bone marrow transplantation for chronic myelogenous leukemia (IV).

Pediatric

Palliative treatment of chronic myelogenous leukemia (oral).

Severe thrombocytosis, polycythemia vera, myelofibrosis; bone marrow transplantation (oral).

Drug Dose ::

 Route/Dosage

Remission Induction of Chronic Myelogenous Leukemia

ADULTS: PO 4 to 8 mg/day (60 mcg/kg or 1.8 mg/m2/day). When the total leukocyte count is < 15,000/mm3, withhold drug. During remission, treatment is resumed when a monthly WBC reaches 50,000/mm.3

PEDIATRIC: PO 60 to 120 mcg/kg or 1.8 to 4.6 mg/m2 once daily. When total leukocyte count is < 15,000/mm,3 withhold drug. During remission, treatment is resumed when a monthly WBC reaches 50,000/mm.3

Bone Marrow Ablation

ADULTS: PO 1 mg/kg q 6 hr for 16 doses (for a total dose of 16 mg/kg over 4 days) in combination with other agents. An alternate regimen is busulfan 0.4375 to 0.5 mg/kg q 6 hr for 16 doses (total dose of 7 to 8 mg/kg, respectively, over 4 days) alone or in combination with other chemotherapy agents.

ADULTS: IV 0.8 mg/kg q 6 hr for 16 doses (for a total dose of 12.8 mg/kg over 4 days). Base dose on ideal body weight or actual body weight, whichever is lower. For obese patients, dosage should be based on adjusted body weight.

Dosage Adjustment

PEDIATRIC: PO Reduce dose 50% for WBC between 30,000 to 40,000/mm.3 Discontinue therapy if WBC count falls to £ 20,000/mm3.

Contraindication ::

 Contraindications

Tablets

Do not use unless a diagnosis of chronic myelogenous leukemia has been adequately established. Patients whose disease has demonstrated prior resistance to the drug without a diagnosis of CML. Busulfan is of no value in chronic lymphocytic leukemia, acute leukemia, or in the “blastic crisis” of CML.

Injection

Hypersensitivity to any of its components.

Drug Precautions ::

 Precautions

Pregnancy: Category D. Lactation: Undetermined. Children: Safety and efficacy not established. Adrenal insufficiency: A clinical syndrome closely resembling adrenal insufficiency and characterized by weakness, severe fatigue, anorexia, weight loss, nausea, vomiting, and melanoderma has developed after prolonged therapy. Carcinogenesis: Malignant tumors have occurred in patients on busulfan therapy; this drug may be a human carcinogen. Cardiovascular: Cardiac tamponade, which was often fatal, has been reported in a small number of pediatric patients with thalassemia (2% in 1 series) who received high doses of busulfan and cyclophosphamide as the preparatory regimen for bone marrow transplantation and hematopoietic progenitor cell transplantation. Abdominal pain and vomiting preceded the tamponade in most patients. Cellular dysplasia: Busulfan may cause cellular dysplasia in many organs in addition to the lung. Giant hyperchromatic nuclei have been reported in the lymph nodes, pancreas, thryroid, adrenal glands, bone marrow, and liver. Fertility impairment: Ovarian suppression and amenorrhea with menopausal symptoms commonly occur during busulfan therapy in premenopausal patients. Hematopoietic toxicity: Most frequent and serious side effect is bone marrow failure, resulting in severe pancytopenia. Recovery from busulfan-induced pancytopenia may take from 1 mo to 2 yr. The most consistent dose-related toxicity is bone marrow suppression. This may be manifested by neutropenia, anemia, leukopenia, thrombocytopenia, or any combination of these. Busulfan-induced bone marrow suppression may be prolonged. The WBC may continue to drop for 2 to 3 wk after therapy is discontinued and may take up to 2 mo to recover. Hepatic function impairment: High doses may be associated with an increased risk of developing hepatic VOD. Hyperuricemia and hyperuricosuria: May occur in patients with chronic myelogenous leukemia. Minimize adverse effects by increased hydration, urine alkalization, and the prophylactic administration of allopurinol. Pulmonary effects: A rare but important complication of busulfan therapy is the development of bronchopulmonary dysplasia with pulmonary fibrosis. Symptoms have occurred within 8 mo to 10 yr after initiation of therapy. Clinically, patients report the insidious onset of cough, dyspnea, and low-grade fever. Pulmonary function studies reveal diminished diffusion capacity and decreased pulmonary compliance. Seizures: Seizures have been reported in patients receiving high oral doses of busulfan. Risk of seizures may be reduced by prophylactic administration of phenytoin. Some clinicians administer a loading dose of phenytoin 15 to 18 mg/kg orally prior to starting busulfan followed by a maintenance dose of phenytoin 300 mg/day orally until 24 hr after administering the final busulfan dose. Maintenance doses ranging from 4 to 8 mg/kg/day orally have also been given, titrated to achieve therapeutic phenytoin serum levels (10 to 20 mcg/mL).

PATIENT CARE CONSIDERATIONS


Drug Side Effects ::

 Adverse Reactions

CARDIOVASCULAR: Tachycardia, thrombotic events, hypertension, generalized edema, chest pain, vasodilatation (IV). CNS: Confusion; seizures; insomnia, anxiety, headache, asthenia, dizziness, depression (IV). DERMATOLOGIC: Hyperpigmentation, urticaria, alopecia; rash, pruritus (IV). ENDOCRINE: Clinical syndrome similar to adrenal insufficiency. GI: Nausea; vomiting; diarrhea; transient LFT elevations; hepatic veno-occlusive disease after bone marrow transplantation; stomatitis, anorexia, abdominal pain, hyperbilirubinemia, dyspepsia, constipation, dry mouth, jaundice (IV). GU: Amenorrhea; ovarian failure;, sterility; azoospermia; testicular atrophy. HEMATOLOGIC: Pancytopenia; delayed bone marrow suppression. METABOLIC: Hypomagnesemia, hypokalemia, hyperglycemia, hypocalcemia (IV). RENAL: Uric acid nephropathy; renal stones; acute renal failure. RESPIRATORY: Interstitial pulmonary fibrosis; rhinitis, cough, epistaxis, dyspnea (IV). SPECIALSENSES: Cataracts. OTHER: Acute leukemia and malignant tumors; cellular dysplasia; fever, chills (IV).

Drug Mode of Action ::  

(byoo-FULL-fan)
Myleran
Tablets
2 mg
Solution for injection
6 mg/mL
Class: Alkylating agents
Alkyl sulfonates

Drug Interactions ::

Interactions

Acetaminophen

May decrease busulfan clearance.

Itraconazole

Decreases busulfan clearance 25%, increasing serum levels and effects.

Phenytoin

Increases busulfan clearance ³ 15%, reducing serum levels and effects.

Thioguanine

Long term, concomitant use has resulted in hepatotoxicity and esophageal varices.

Drug Assesment ::

 Assessment/Interventions

  • Monitor patients for signs of local or systemic infection or bleeding. Frequently evaluate their hematologic status.
  • Periodic measurement of serum transaminases, alkaline phosphatase, and bilirubin is indicated for early detection of hepatotoxicity.
  • It is recommended that evaluation of the hemoglobin or hematocrit, total WBC, complete blood count, including differential count and quantitative platelet count, be obtained weekly (daily for injection) while the patient is on busulfan therapy, and until engraftment has been demonstrated.
  • Evaluate serum transaminase, alkaline phosphatase, and bilirubin daily through transplant day 28 to detect hepatotoxicity, which may herald the onset of hepatic VOD.
  • Risk of seizures may be reduced by prophylactic administration of phenytoin. Some clinicians administer a loading dose of phenytoin 15 to 18 mg/kg orally prior to starting busulfan followed by a maintenance dose of phenytoin 300 mg/day orally until 24 hr after administering the final busulfan dose. Maintenance doses ranging from 4 to 8 mg/kg/day orally have also been given, titrated to achieve therapeutic phenytoin serum levels (10 to 20 mcg/mL).

PO

  • Some clinicians place patients on a clear-liquid diet to decrease the risk of vomiting. In addition, they may prescribe additional doses of busulfan if tablets are visible in emesis. A full replacement dose may be given if vomiting occurs within 30 min of a dose and pill fragments are visible in the vomitus. If vomiting occurs > 30 min after a dose, the replacement dose may be estimated based on the number of visible pill fragments; patients typically receive 50% of the usual dose.
OVERDOSAGE: SIGNS & SYMPTOMS
  Tablets: Bone marrow hypoplasia/aplasia, pancytopenia

Drug Storage/Management ::

 Administration/Storage

  • Store oral tablets at room temperature.
  • Refrigerate solution for injection in unopened ampules.
  • Withdraw dose from the ampule, using the provided 5 micron filter needle. Remove the filter needle and use a new needle to add busulfan to the diluent.
  • Dilute solution for injection with 5% Dextrose or 0.9% Sodium Chloride, for a final busulfan concentration of » 0.5 mg/mL. Add the busulfan to the diluent; do not add the diluent to busulfan.
  • To determine the approximate volume of diluent required, multiply the volume of busulfan injection by 10.
  • Diluted busulfan solutions are stable for up to 8 hr at room temperature and for up to 12 hr under refrigeration.
  • Administer by oral, IV infusion
  • Follow safe handling procedures and disposal of chemotherapy drugs. Wear gloves and avoid skin contact and inhalation of fumes.

IV

  • Infuse over 2 hr. Vigorous hydration reduces the risk of renal toxicity

Drug Notes ::

 Patient/Family Education

  • Inform patients beginning therapy with busulfan of the importance of having periodic blood counts.
  • Notify health care provider if unusual bleeding or bruising; fever; persistent cough; congestion; shortness of breath; flank, stomach or joint pain; abrupt weakness; unusual fatigue; anorexia; or weight loss occurs.
  • Tell patients that diffuse pulmonary fibrosis is an infrequent but serious and potentially life-threatening complication of long-term busulfan therapy.
  • Inform patients that some toxicities to busulfan include infertility, amenorrhea, skin hyperpigmentation, drug hypersensitivity, dryness of the mucous membranes.
  • Medication may cause darkening of skin, diarrhea, dizziness, fatigue, appetite loss, mental confusion, nausea, vomiting, and melanoderma that could be associated with a syndrome resembling adrenal insufficiency; notify health care provider if these become pronounced.
  • Take medication at the same time each day.
  • Extra fluid intake may be recommended.
  • Contraceptive measures are recommended during therapy.
  • If nausea or vomiting occurs, take the drug on an empty stomach.
  • Explain the increased risk of a second malignancy to the patient.
  • Instruct patients to promptly report the development of fever, sore throat, signs of local infection, bleeding from any site or symptoms suggestive of anemia.

Medicscientist Drug Facts

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