Temozolomide

TEMOZOLOMIDE — temozolomide capsule
Sun Pharmaceutical Industries, Inc.

1 INDICATIONS AND USAGE

1.1 Newly Diagnosed Glioblastoma

Temozolomide capsules are indicated for the treatment of adult patients with newly diagnosed glioblastoma concomitantly with radiotherapy and then as maintenance treatment.

1.2 Refractory Anaplastic Astrocytoma

Temozolomide capsules are indicated for the treatment of adult patients with refractory anaplastic astrocytoma who have experienced disease progression on a drug regimen containing nitrosourea and procarbazine.

2 DOSAGE AND ADMINISTRATION

2.1 Recommended Dosage and Dosage Modifications for Newly Diagnosed Glioblastoma

Administer temozolomide capsules once daily for 42 consecutive days during the concomitant phase with focal radiotherapy and then once daily on Days 1 to 5 of each 28-day cycle for 6 cycles during the maintenance phase.

Provide Pneumocystis pneumonia (PCP) prophylaxis during the concomitant phase and continue in patients who develop lymphocytopenia until resolution to grade 1 or less [see Warnings and Precautions (5.3)].

Concomitant Phase

The recommended dosage of temozolomide capsules is 75 mg/m2 once daily for 42 days (up to 49 days) concomitant with focal radiotherapy (60 Gy administered in 30 fractions). Focal radiotherapy includes the tumor bed or resection site with a 2- to 3-cm margin.

Obtain a complete blood count weekly. No dose reductions are recommended during the concomitant phase. The recommended dosage modifications during the concomitant phase are provided in Table 1.

TABLE 1: Temozolomide Dosage Modifications During Concomitant Phase

Adverse Reaction Interruption Discontinuation
Absolute Neutrophil Count Withhold temozolomide capsules if ANC is greater than or equal to 0.5 x 109 /L and less than 1.5 x 109 /L.Resume temozolomide capsules when ANC is greater than or equal to 1.5 x 109 /L. Discontinue temozolomide capsules if platelet count is less than 0.5 × 109 /L
Platelet Count Withhold temozolomide capsules if platelet count is greater than or equal to 10 x 109 /L and less than 100 x 109 /L. Resume temozolomide capsules when platelet count is greater than or equal to 100 x 109 /L. Discontinue temozolomide capsules if platelet count is less than 10 × 109 /L
Non-hematological Adverse Reaction (except for alopecia, nausea, vomiting) Withhold temozolomide capsules if Grade 2 adverse reaction occurs.Resume temozolomide capsules when resolution to Grade 1 or less. Discontinue temozolomide capsules if Grade 3 or 4 adverse reaction occurs.

Maintenance Phase

Beginning 4 weeks after Concomitant Phase completion, administer temozolomide capsules once daily on Days 1 to 5 of each 28-day cycle for 6 cycles. The recommended dosage of temozolomide capsules are as follows:

  • Cycle 1: 150 mg/m2 per day
  • Cycles 2 to 6: May increase to 200 mg/m2 per day if the following conditions are met before starting cycle 2. If the dose was not escalated at the onset of Cycle 2, do not increase the dose for Cycles 3 to 6.
    • Nonhematologic toxicity is grade 2 or less (except for alopecia, nausea, and vomiting)
    • ANC is greater than or equal to 1.5 x 109 /L and
    • Platelet count is greater than or equal to 100 x 109 /L.

Obtain a complete blood count on Day 22 and then weekly until the ANC is above 1.5 x 109 /L and the platelet count is above 100 x 109 /L. Do not start the next cycle until the ANC and platelet count exceed these levels.

The recommended dosage modifications during the maintenance phase are provided in Table 2. If temozolomide capsules are withheld, reduce the dose for the next cycle by 50 mg/m2 per day. Permanently discontinue temozolomide capsules in patients who are unable to tolerate a dose of 100 mg/m2 per day.

TABLE 2: Temozolomide Dosage Modifications During Maintenance Treatment

Adverse Reaction Interruption and Dose Reduction Discontinuation
Absolute Neutrophil Count Withhold temozolomide capsules if ANC less than 1 x 109 /L. When ANC is above 1.5 x 109 /L, resume temozolomide capsules at reduced dose for the next cycle. Unable to tolerate a dose of 100 mg/m2 per day.
Platelet Count Withhold temozolomide capsules if platelet less than 50 x 109 /L.When platelet count is above 100 x 109 /L, resume temozolomide capsules at reduced dose for the next cycle. Unable to tolerate a dose of 100 mg/m2 per day.
Non-hematological Adverse Reaction (except for alopecia, nausea, vomiting) Withhold temozolomide capsules if Grade 3 adverse reaction.When resolved to grade 1 or less, resume temozolomide capsules at reduced dose for the next cycle. Recurrent Grade 3 after dose reduction.Grade 4Unable to tolerate a dose of 100 mg/m2 per day.

2.2 Recommended Dosage and Dosage Modifications for Refractory Anaplastic Astrocytoma

The recommended initial dosage of temozolomide capsules are 150 mg/m2 once daily on Days 1 to 5 of each 28-day cycle. Increase the temozolomide dose to 200 mg/m2 per day if the following conditions are met at the nadir and on Day 1 of the next cycle:

  • ANC is greater than or equal to 1.5 x 109/L and
  • Platelet count is greater than or equal to 100 x 109/L

Continue temozolomide capsules until disease progression or unacceptable toxicity. In the clinical trial, treatment could be continued for a maximum of 2 years, but the optimum duration of therapy is not known.
Obtain a complete blood count on Day 22 and then weekly until the ANC is above 1.5 x 109 /L and the platelet count is above 100 x 109 /L. Do not start the next cycle until the ANC and platelet count exceed these levels.
If the ANC is less than 1 x 109 /L or the platelet count is less than 50 x 109 /L during any cycle, reduce the temozolomide dose for the next cycle by 50 mg/m2 per day. Permanently discontinue temozolomide capsules in patients who are unable to tolerate a dose of 100 mg/m2 per day.

2.3 Preparation and Administration

Temozolomide is a cytotoxic drug. Follow applicable special handling and disposal procedures.1

Temozolomide capsules

Administer temozolomide capsules consistently with respect to food (fasting vs. nonfasting) [see Clinical Pharmacology (12.3)]. To reduce nausea and vomiting, take temozolomide capsules on an empty stomach or at bedtime and consider antiemetic therapy prior to and/or following temozolomide capsule administration.

Swallow temozolomide capsules whole. Do not open or chew capsules. If capsules are accidentally opened or damaged, take precautions to avoid inhalation or contact with the skin or mucous membranes. In case of powder contact, the hands should be washed.

3 DOSAGE FORMS AND STRENGTHS

  • 5 mg hard gelatin capsules have white opaque caps and bodies, imprinted with band and the dosage strength “5 mg” on body and “890” on cap in green ink, containing white to light tan/light pink powder.
  • 20 mg hard gelatin capsules have white opaque caps and bodies, imprinted with band and the dosage strength “20 mg” on body and “891” on cap in golden ink, containing white to light tan/light pink powder.
  • 100 mg hard gelatin capsules have white opaque caps and bodies, imprinted with band and the dosage strength “100 mg” on body and “892” on cap in pink ink, containing white to light tan/light pink powder.
  • 140 mg hard gelatin capsules have white opaque caps and bodies, imprinted with band and the dosage strength “140 mg” on body and “929” on cap in blue ink, containing white to light tan/light pink powder.
  • 180 mg hard gelatin capsules have white opaque caps and bodies, imprinted with band and the dosage strength “180 mg” on body and “930” on cap in brown ink, containing white to light tan/light pink powder.
  • 250 mg hard gelatin capsules have white opaque caps and bodies, imprinted with band and the dosage strength “250 mg” on body and “893” on cap in black ink, containing white to light tan/light pink powder.

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