Usual Adult Dose for Brain/Intracranial Tumor

IV:

• As a single agent in previously untreated patients: 150 to 200 mg/m2 IV every 6 weeks administered as a single dose or divided into daily injections (75 to 100 mg/m2 IV on two successive days)
• In combination with other myelosuppressive drugs or in patients in whom bone marrow reserve is depleted, doses should be adjusted accordingly.

• Nadir after prior dose: Leukocytes greater than 4000/mm3 and platelets greater than 100,000/m3: Give 100% of the prior dose.
• Nadir after prior dose: Leukocytes 3000 to 3999/mm3 and platelets 75,000 to 99,999/m3: Give 100% of the prior dose.
• Nadir after prior dose: Leukocytes 2000 to 2999/mm3 and platelets 25,000 to 74,999/m3: Give 70% of the prior dose.
• Nadir after prior dose: Leukocytes less than 2000/mm3 and platelets less than 25,000/m3: Give 50% of the prior dose.

• NOTE: The dosing presented here is manufacturer suggested. Consult the literature and local protocol for more information.
• Administer reconstituted solution only as a slow IV infusion over at least 2 hours.
• Premedicate each dose with antiemetics.
• The usual interval between courses is 6 weeks.

• Brain tumors glioblastoma, brainstem glioma, medulloblastoma, astrocytoma, ependymoma, and metastatic brain tumors
• Multiple myeloma in combination with prednisone
• Relapsed or refractory Hodgkin's lymphoma in combination with other approved drugs
• Relapsed or refractory Non-Hodgkin's lymphomas in combination with other approved drugs

Usual Adult Dose for non-Hodgkin's Lymphoma

IV:

• As a single agent in previously untreated patients: 150 to 200 mg/m2 IV every 6 weeks administered as a single dose or divided into daily injections (75 to 100 mg/m2 IV on two successive days)
• In combination with other myelosuppressive drugs or in patients in whom bone marrow reserve is depleted, doses should be adjusted accordingly.

• Nadir after prior dose: Leukocytes greater than 4000/mm3 and platelets greater than 100,000/m3: Give 100% of the prior dose.
• Nadir after prior dose: Leukocytes 3000 to 3999/mm3 and platelets 75,000 to 99,999/m3: Give 100% of the prior dose.
• Nadir after prior dose: Leukocytes 2000 to 2999/mm3 and platelets 25,000 to 74,999/m3: Give 70% of the prior dose.
• Nadir after prior dose: Leukocytes less than 2000/mm3 and platelets less than 25,000/m3: Give 50% of the prior dose.

• NOTE: The dosing presented here is manufacturer suggested. Consult the literature and local protocol for more information.
• Administer reconstituted solution only as a slow IV infusion over at least 2 hours.
• Premedicate each dose with antiemetics.
• The usual interval between courses is 6 weeks.

• Brain tumors glioblastoma, brainstem glioma, medulloblastoma, astrocytoma, ependymoma, and metastatic brain tumors
• Multiple myeloma in combination with prednisone
• Relapsed or refractory Hodgkin's lymphoma in combination with other approved drugs
• Relapsed or refractory Non-Hodgkin's lymphomas in combination with other approved drugs

Usual Adult Dose for Hodgkin's Disease

IV:

• As a single agent in previously untreated patients: 150 to 200 mg/m2 IV every 6 weeks administered as a single dose or divided into daily injections (75 to 100 mg/m2 IV on two successive days)
• In combination with other myelosuppressive drugs or in patients in whom bone marrow reserve is depleted, doses should be adjusted accordingly.

• Nadir after prior dose: Leukocytes greater than 4000/mm3 and platelets greater than 100,000/m3: Give 100% of the prior dose.
• Nadir after prior dose: Leukocytes 3000 to 3999/mm3 and platelets 75,000 to 99,999/m3: Give 100% of the prior dose.
• Nadir after prior dose: Leukocytes 2000 to 2999/mm3 and platelets 25,000 to 74,999/m3: Give 70% of the prior dose.
• Nadir after prior dose: Leukocytes less than 2000/mm3 and platelets less than 25,000/m3: Give 50% of the prior dose.

• NOTE: The dosing presented here is manufacturer suggested. Consult the literature and local protocol for more information.
• Administer reconstituted solution only as a slow IV infusion over at least 2 hours.
• Premedicate each dose with antiemetics.
• The usual interval between courses is 6 weeks.

• Brain tumors glioblastoma, brainstem glioma, medulloblastoma, astrocytoma, ependymoma, and metastatic brain tumors
• Multiple myeloma in combination with prednisone
• Relapsed or refractory Hodgkin's lymphoma in combination with other approved drugs
• Relapsed or refractory Non-Hodgkin's lymphomas in combination with other approved drugs

Usual Adult Dose for Multiple Myeloma

IV:

• As a single agent in previously untreated patients: 150 to 200 mg/m2 IV every 6 weeks administered as a single dose or divided into daily injections (75 to 100 mg/m2 IV on two successive days)
• In combination with other myelosuppressive drugs or in patients in whom bone marrow reserve is depleted, doses should be adjusted accordingly.

• Nadir after prior dose: Leukocytes greater than 4000/mm3 and platelets greater than 100,000/m3: Give 100% of the prior dose.
• Nadir after prior dose: Leukocytes 3000 to 3999/mm3 and platelets 75,000 to 99,999/m3: Give 100% of the prior dose.
• Nadir after prior dose: Leukocytes 2000 to 2999/mm3 and platelets 25,000 to 74,999/m3: Give 70% of the prior dose.
• Nadir after prior dose: Leukocytes less than 2000/mm3 and platelets less than 25,000/m3: Give 50% of the prior dose.

• NOTE: The dosing presented here is manufacturer suggested. Consult the literature and local protocol for more information.
• Administer reconstituted solution only as a slow IV infusion over at least 2 hours.
• Premedicate each dose with antiemetics.
• The usual interval between courses is 6 weeks.

• Brain tumors glioblastoma, brainstem glioma, medulloblastoma, astrocytoma, ependymoma, and metastatic brain tumors
• Multiple myeloma in combination with prednisone
• Relapsed or refractory Hodgkin's lymphoma in combination with other approved drugs
• Relapsed or refractory Non-Hodgkin's lymphomas in combination with other approved drugs

Usual Adult Dose for Glioblastoma Multiforme

WAFER:

• Eight 7.7 mg wafers (61.6 mg total dose) implanted intracranially

• NOTE: The dosing presented here is manufacturer suggested. Consult the literature and local protocol for more information.

• Newly-diagnosed high-grade glioma as an adjunct to surgery and radiation
• Recurrent glioblastoma as an adjunct to surgery

Usual Adult Dose for Malignant Glioma

WAFER:

• Eight 7.7 mg wafers (61.6 mg total dose) implanted intracranially

• NOTE: The dosing presented here is manufacturer suggested. Consult the literature and local protocol for more information.

• Newly-diagnosed high-grade glioma as an adjunct to surgery and radiation
• Recurrent glioblastoma as an adjunct to surgery

Renal Dose Adjustments

IV Formulation: If CrCl less than 10 mL/min: Do not administer this drug.
Wafer Formulation: Data not available

Liver Dose Adjustments

Data not available

Precautions

US BOXED WARNINGS:
IV FORMULATION:
Myelosuppression and Pulmonary Toxicity:

• MYELOSUPPRESSION: This drug, when given IV, causes suppression of marrow function (including thrombocytopenia and leukopenia), which may result in bleeding and infections.

• Monitor blood counts weekly for at least 6 weeks after each dose.
• Adjust doge based on nadir blood counts from the prior dose.
• Do not administer a repeat course of therapy until blood counts recover.
• PULMONARY TOXICITY: This drug, when given IV, causes dose-related pulmonary toxicity. Patients receiving greater than 1400 mg/m2 cumulative dose are at significantly higher risk than those receiving less. Delayed pulmonary toxicity can occur years after discontinuing therapy and can result in death, particularly in patients treated in childhood.

• IV formulation: Hypersensitivity to the active component or any of the ingredients
• Wafer formulation: None

Dialysis

Data not available

Other Comments

Administration advice:
IV FORMULATION:

• The manufacturer product information should be consulted.

• The safety and effectiveness of repeat wafer administration have not been studied.
• It is recommended that 8 wafers be placed in the resection cavity if the size and shape of it allows. Should the size and shape not accommodate 8 wafers, the maximum number of wafers as allowed should be placed. Slight overlapping of the wafers is acceptable. Since there is no clinical experience, no more than 8 wafers should be used per surgical procedure. Wafers broken in half may be used, but discard wafers broken in more than 2 pieces.
• Oxidized regenerated cellulose may be placed over the wafers to secure them against the cavity surface.
• After placement of the wafers, irrigate the resection cavity and close the dura in a water-tight fashion.
• Wafers are biodegradable when implanted into the human brain. Wafer remnants were visible on CT scans obtained 49 days after implantation. More than 70% of the copolymer degrades within 3 weeks. Wafer remnants have been present at re-operation and autopsy up to 7.8 months after implantation and consisted mostly of water and monomeric components with minimal detectable drug present.

• Store unopened product and diluent in the refrigerator 2C to 8C (36F to 46F).

• Store unopened wafer at or below -20C (-4F).
• Do not keep unopened foil pouches at ambient room temperature for more than 6 hours at a time for up to 3 cycles within a 30-day period.

• The manufacturer product information should be consulted.

• The IV solution is unstable in polyvinyl chloride (PVC) container. Administer the solution from the glass bottles or polypropylene container only. Ensure the polypropylene containers used are PVC free and DEHP free.

• This drug is a cytotoxic drug and special handling and disposal procedures should be considered.
• The IV formulation has a low melting point (30.5C to 32C or 86.9F to 89.6F). Exposure of the drug to this temperature or above will cause it to liquefy and appear as an oil film on the vials. This is a sign of decomposition and vials should be discarded.
• If there is a question of adequate refrigeration upon receipt of this product, immediately inspect the vial in each individual carton. Hold the vial to a bright light. It should appear as a very small number of dry flakes or dry congealed mass. If this is evident, the vial 1 is suitable for use and should be refrigerated immediately.

• Renal function
• Hepatic function
• Cardiac function