Temodar Dosage

​2.1 Monitoring to Inform Dosage and Administration

​Prior to dosing, withhold TEMODAR until patients have an absolute neutrophil count (ANC) of 1.5 x 109/L or greater and a platelet count of 100 x 109/L or greater.

​For concomitant radiotherapy, obtain a complete blood count prior to initiation of treatment and weekly during treatment.

​For the 28-day treatment cycles, obtain a complete blood count prior to treatment on Day 1 and on Day 22 of each cycle. Perform complete blood counts weekly until recovery if the ANC falls below 1.5 x 109/L and the platelet count falls below 100 x 109/L.

​For concomitant use with focal radiotherapy, obtain a complete blood count weekly and as clinically indicated.

Recommended Dosage and Dosage Modifications for Newly Diagnosed Glioblastoma

​Administer TEMODAR either orally or intravenously once daily for 42 to 49 consecutive days during the concomitant use phase with focal radiotherapy, and then once daily on Days 1 to 5 of each 28-day cycle for 6 cycles during the maintenance use phase.

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

​Concomitant Use Phase:

​The recommended dosage of TEMODAR is 75 mg/m2 either orally or intravenously once daily for 42 to 49 days in combination with focal radiotherapy. Focal radiotherapy includes the tumor bed or resection site with a 2 to 3 cm margin.

​Other administration schedules have been used.

​Obtain a complete blood count weekly. The recommended dosage modifications due to adverse reactions during concomitant use phase are provided in Table 1.

​Single Agent Maintenance Use Phase:

​Beginning 4 weeks after concomitant use phase completion, administer TEMODAR either orally or intravenously once daily on Days 1 to 5 of each 28-day cycle for 6 cycles. The recommended dosage of TEMODAR in the maintenance use phase is:

• ​Cycle 1: 150 mg/m2 per day on days 1 to 5.
• ​Cycles 2 to 6: May increase to 200 mg/m2 per day on days 1 to 5 before starting Cycle 2 if no dosage interruptions or discontinuations are required (Table 1). If the dose is not escalated at the onset of Cycle 2, do not increase the dose for Cycles 3 to 6.

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

​The recommended dosage modifications due to adverse reactions during the maintenance use phase are provided in Table 2.

If TEMODAR is withheld, reduce the dose for the next cycle by 50 mg/m2 per day. Permanently discontinue TEMODAR in patients who are unable to tolerate a dose of 100 mg/m2 per day.

​2.3 Recommended Dosage and Dosage Modifications for Anaplastic Astrocytoma

​Adjuvant Treatment of Newly Diagnosed Anaplastic Astrocytoma

​Beginning 4 weeks after the end of radiotherapy, administer TEMODAR orally in a single dose on days 1 to 5 of a 28-day cycle for 12 cycles. The recommended dosage of TEMODAR is:

• ​Cycle 1: 150 mg/m2 per day on days 1 to 5.
• ​Cycles 2 to 12: 200 mg/m2 per day on days 1 to 5 if patient experienced no or minimal toxicity in Cycle 1. If the dose was not escalated at the onset of Cycle 2, do not increase the dose during Cycles 3 to 6.

​The recommended complete blood count testing and dosage modifications due to adverse reactions during adjuvant treatment are provided above and in Table 2 [see Dosage and Administration (2.2)].

​Refractory Anaplastic Astrocytoma

The recommended initial dosage of TEMODAR is 150 mg/m2 once daily on Days 1 to 5 of each 28-day cycle. Increase the TEMODAR 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 × 109/L, and
• Platelet count is greater than or equal to 100 × 109/L.

​Continue TEMODAR until disease progression or unacceptable toxicity.

​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 × 109/L or the platelet count is less than 50 × 109/L during any cycle, reduce the TEMODAR dose for the next cycle by 50 mg/m2 per day. Permanently discontinue TEMODAR in patients who are unable to tolerate a dose of 100 mg/m2 per day.

Preparation and Administration

​TEMODAR is a hazardous drug. Follow applicable special handling and disposal procedures.1

TEMODAR capsules

Take TEMODAR at the same time each day. Administer TEMODAR consistently with respect to food (fasting vs. nonfasting) [see Clinical Pharmacology (12.3)]. To reduce nausea and vomiting, take TEMODAR on an empty stomach or at bedtime and consider antiemetic therapy prior to and following TEMODAR administration.

​Swallow TEMODAR capsules whole with water. Advise patients not to open, chew, or dissolve the contents of the capsules [see Warnings and Precautions (5.6)].

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, wash the affected area with water immediately.

TEMODAR for injection

Bring the vial to room temperature prior to reconstitution with Sterile Water for Injection.

Reconstitute the vial with 41 mL of Sterile Water for Injection to yield a TEMODAR solution with a concentration of 2.5 mg/mL temozolomide. Reconstituted TEMODAR is a clear solution and essentially free of visible particles.

Gently swirl vial. Do not shake.

​Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit. Discard if particulate matter or discoloration is observed.

Do not further dilute the reconstituted solution.

Store reconstituted solution at room temperature (25°C [77°F]). Discard reconstituted solution if not used within 14 hours, including infusion time.

Withdraw up to 40 mL from each vial to make up the total dose and discard any unused portion. Transfer reconstituted solution from each vial into an empty 250 mL infusion bag.

Administer reconstituted solution using a pump over a period of 90 minutes. Administer TEMODAR by intravenous infusion only. Infusion over a shorter or longer period of time may result in suboptimal dosing. Flush the lines before and after each infusion. TEMODAR for injection may be administered in the same intravenous line with 0.9% Sodium Chloride injection only.

Because no data are available on the compatibility of TEMODAR for injection with other intravenous substances or additives, do not infuse other medications simultaneously through the same intravenous line.