Temodar (temozolomide)

Temodar can cause serious side effects.

• Decreased blood cells.Temodar affects cells that grow rapidly, including bone marrow cells. This can cause you to have a decrease in blood cells. Your doctor can monitor your blood for these effects.
  • White blood cells are needed to fight infections. Neutrophils are a type of white blood cell that help preventbacterial infections. Decreased neutrophils can lead to serious infections that can lead to death. Other white blood cells called lymphocytes may also be decreased.
  • Platelets are blood cells needed for normal blood clotting. Low platelet counts can lead to bleeding. Tell your doctor about any unusualbruisingor bleeding.

Your doctor will check your blood regularly while you are taking Temodar to see if these side effects are happening. Your doctor may need to change the dose of Temodar or when you get it depending on your blood cell counts. People who are age 70 or older and women may be more likely to have their blood cells affected.

• Pneumocystispneumonia(PCP).PCP is an infection that people can get when their immune system is weak. Temodar decreases white blood cells, which makes your immune system weaker and can increase your risk of getting PCP.All patientstaking Temodar will be watched carefully by their doctor for this infection, especially patients who take steroids. Tell your doctor if you have any of the following signs and symptoms of PCP infection:shortness of breathand/orfever,chills, drycough.
• Secondarycancers.Blood problems such as myelodysplastic syndrome and secondary cancers, such as a certain kind ofleukemia,可以发生在人Temodar. Your doctor will watch you for this.
• Convulsions.Convulsions may be severe or life-threatening in people who take Temodar.
• Liverside effectshave been reported, which very rarely included death.

Common side effects with Temodar include:

• nauseaandvomiting. Your doctor can prescribe medicines that may help reduce these symptoms.
• headache
• feeling tired
• loss of appetite
• hair loss
• constipation
• bruising
• rash
• paralysison one side of the body
• diarrhea
• weakness
• fever
• dizziness
• coordination problems
• viral infection
• sleep problems
• memory loss
• pain, irritation,itching, warmth, swelling or redness at the site of infusion
• bruising or small red or purple spots under the skin

Tell your doctor about any side effect that bothers you or that does not go away.

These are not all the possible side effects with Temodar. For more information, ask your doctor or pharmacist.

Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

Recommended Dosage And Dosage Modifications For Newly Diagnosed Glioblastoma

• Administer Temodar either orally or intravenously 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.
• ProvidePneumocystispneumonia(PCP) prophylaxis during the concomitant phase and continue in patients who developlymphocytopeniauntil resolution to Grade 1 or less.

Concomitant Phase

• The recommended dosage of Temodar is 75 mg/m² either orally or intravenously once daily for 42 days (up to 49 days) concomitant with focal radiotherapy (60 Gy administered in 30 fractions). Focal radiotherapy includes thetumorbed or resection site with a 2- to 3-cm margin.
• Obtain acomplete blood countweekly. 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 Temodar if ANC is greater than or equal to 0.5 109/L and less than 1.5 109/L. Resume Temodar when ANC is greater than or equal to 1.5 109/L.	Discontinue Temodar if platelet count is less than 0.5 109/L.
Platelet Count	Withhold Temodar if platelet count is greater than or equal to 10 109/L and less than 100 109/L. Resume Temodar when platelet count is greater than or equal to 100 109/L.	Discontinue Temodar if platelet count is less than 10 109/L.
Non-hematological Adverse Reaction (except for alopecia, nausea, vomiting)	Withhold Temodar if Grade 2 adverse reaction occurs. Resume Temodar when resolution to Grade 1 or less.	Discontinue Temodar if Grade 3 or 4 adverse reaction occurs.

Maintenance Phase

Beginning 4 weeks after Concomitant 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 is 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 foralopecia,nausea, andvomiting)
  • 非国大大于或等于1.5 x 10⁹/L, and
  • Platelet countis 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 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.

TABLE 2: Temozolomide Dosage Modifications During Maintenance Treatment

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

Recommended Dosage And Dosage Modifications For 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:

• 非国大大于或等于1.5 x 10⁹/L, and
• Platelet count is greater than or equal to 100 x 10⁹/L.

Continue Temodar 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 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 cytotoxic drug. Follow applicable special handling and disposal procedures.

Temodar Capsules

• Administer Temodar consistently with respect to food (fasting vs. nonfasting). To reduce nausea and vomiting, take Temodar on an empty stomach or at bedtime and consider antiemetic therapy prior to and/or following Temodar administration.
• Swallow Temodar capsules whole. Do not open or chew capsules.
• If capsules are accidentally opened or damaged, take precautions to avoidinhalationor contact with the skin or mucous membranes. In case of powder contact, the hands should be washed.

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.
• Visually inspect reconstituted solution for particulate matter and discoloration. 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.Flushthe 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.

No information provided

• Based on its mechanism of action and findings from animal studies, Temodar can cause fetal harm when administered to apregnantwoman.
• Available postmarketing reports describe cases of spontaneous abortions andcongenital malformations, including polymalformations with central nervous system, facial, cardiac, skeletal, and genitourinary system anomalies with exposure to Temodar duringpregnancy.
• There are no data on the presence of Temodar or its metabolites inhuman milk, the effects on abreastfedchild, or the effects on milk production.
• Because of the potential for serious adverse reactions, including myelosuppression from temozolomide in the breastfed children, advise women not to breastfeed during treatment with Temodar and for at least 1 week after the final dose.