Temodar

Temozolomide interferes with the development of cancer cells, slowing their growth and spread in the body.

Temozolomide is used together with radiation therapy to treat certain types of brain tumor in adults.

Temozolomide is usually given after other cancer medicines have been tried without success.

Temozolomide may also be used for purposes not listed in this medication guide.

Follow all directions on your medicine label and package. Tell each of your healthcare providers about all your medical conditions, allergies, and all medicines you use.

You should not take this medicine if you are allergic to temozolomide or to another cancer medication called dacarbazine (DTIC).

To make sure temozolomide is safe for you, tell your doctor if you have:

• liver disease; or
• kidney disease.

Using temozolomide may increase your risk of developing certain types of bone marrow cancer. Ask your doctor about your specific risk.

Do not use temozolomide if you are pregnant. It could harm the unborn baby. Use effective birth control, and tell your doctor if you become pregnant during treatment.

Use birth control to prevent pregnancy while you are receiving temozolomide, whether you are a man or a woman. Temozolomide use by either parent may cause birth defects.

It is not known whether temozolomide passes into breast milk or if it could harm a nursing baby. You should not breast-feed while using this medicine.

Newly Diagnosed Glioblastoma Multiforme

TEMODAR® (temozolomide) is indicated for the treatment of adult patients with newly diagnosed glioblastoma multiforme concomitantly with radiotherapy and then as maintenance treatment.

Refractory Anaplastic Astrocytoma

TEMODAR is indicated for the treatment of adult patients with refractory anaplastic astrocytoma, i.e., patients who have experienced disease progression on a drug regimen containing nitrosourea and procarbazine.

Included as part of the PRECAUTIONS section.

Medicines can interact with certain foods. In some cases, this may be harmful and your doctor may advise you to avoid certain foods. In the case of Temodar there are no specific foods that you must exclude from your diet when receiving Temodar.

It is not known if Temodar crosses into human milk. Because many medications can cross into human milk and because of the possibility for serious adverse reactions in nursing infants with use of this medication, a choice should be made whether to stop nursing or stop the use of this medication. Your doctor and you will decide if the benefits outweigh the risk of using Temodar.

• Temodar may be taken by mouth as a capsule at home, or you may receive Temodar by injection into a vein (intravenous). Your doctor will decide the best way for you to take Temodar.

There are two common dosing schedules for taking Temodar.

• Some people take Temodar for 42 days in a row (possibly 49 days depending on side effects) with radiation treatment. This is one cycle of treatment. After this, you may have "maintenance" treatment. Your doctor may prescribe 6 more cycles of Temodar. For each of these cycles, you take Temodar one time each day for 5 days in a row and then you stop taking it for the next 23 days. This is a 28-day maintenance treatment cycle.
• Another way to take Temodar is to take it one time each day for 5 days in a row only, and then you stop taking it for the next 23 days. This is one cycle of treatment (28 days). Your doctor will watch your progress on Temodar and decide how long you should take it. You might take Temodar until your tumor gets worse or for possibly up to 2 years.
• Your dose is based on your height and weight, and the number of treatment cycles will depend on how you respond to and tolerate this treatment.
• Your doctor may modify your schedule based on how you tolerate the treatment.
• If your doctor prescribes a treatment regimen that is different from the information provided here, make sure you follow the specific instructions given to you by your doctor.

Oral:

• Take Temodar capsules exactly as prescribed.
• Temodar capsules come in different strengths. Each strength has a different color cap. Your doctor may prescribe more than one strength of Temodar capsules for you, so it is important that you understand how to take your medicine the right way. Be sure that you understand exactly how many capsules you need to take on each day of your treatment, and what strengths to take. This may be different whenever you start a new cycle.
• Talk to your doctor before you take your dose if you are not sure how much to take. This will help to prevent taking too much Temodar and decrease your chances of getting serious side effects.
• Take each day's dose of Temodar capsules at one time, with a full glass of water.
• Swallow Temodar capsules whole. Do not chew, open, or split the capsules.
• If Temodar capsules are accidentally opened or damaged, be careful not to breathe in (inhale) the powder from the capsules or get the powder on your skin or mucous membranes (for example, in your nose or mouth). If contact with any of these areas happens, flush the area with water.
• If you vomit Temodar capsules, do not take any more capsules. Wait and take your next planned dose.
• The medicine is used best by your body if you take it at the same time every day in relation to a meal.
• To lessen nausea, try to take Temodar on an empty stomach or at bedtime. Your doctor may prescribe medicine to prevent or treat nausea, or other medicines to lessen side effects with Temodar.
• See your doctor regularly to check your progress. Your doctor will check you for side effects that you might not notice.
• If you miss a dose of Temodar, talk with your doctor for instructions about when to take your next dose of Temodar.
• Call your doctor right away if you take more than the prescribed amount of Temodar. It is important that you do not take more than the amount of Temodar prescribed for you.

Injectable

• You will receive Temodar as an infusion directly into your vein. Your treatment will take about 90 minutes.
• Your doctor may prescribe medicine to prevent or treat nausea, or other medicines to relieve side effects with Temodar.

Temozolomide interferes with the development of cancer cells, slowing their growth and spread in the body.

Temozolomide is used together with radiation therapy to treat certain types of brain tumor in adults.

Temozolomide is usually given after other cancer medicines have been tried without success.

Temozolomide may also be used for purposes not listed in this medication guide.

Follow all directions on your medicine label and package. Tell each of your healthcare providers about all your medical conditions, allergies, and all medicines you use.

Avoid being near people who are sick or have infections. Tell your doctor at once if you develop signs of infection.

Avoid activities that may increase your risk of bleeding or injury. Use extra care to prevent bleeding while shaving or brushing your teeth.

This medicine can pass into body fluids (urine, feces, vomit). Caregivers should wear rubber gloves while cleaning up a patient's body fluids, handling contaminated trash or laundry or changing diapers. Wash hands before and after removing gloves. Wash soiled clothing and linens separately from other laundry.

Tell your doctor about all medicines you use, and those you start or stop using during your treatment with temozolomide, especially:

• steroid medicine (dexamethasone, prednisone, and others); or

• valproic acid (Depakene, Stavzor).

This list is not complete. Other drugs may interact with temozolomide, including prescription and over-the-counter medicines, vitamins, and herbal products. Not all possible interactions are listed in this medication guide.

Brain Tumors

Adjunct to radiation therapy for treatment of newly diagnosed glioblastoma multiforme; also used as maintenance therapy.1

Treatment of refractory anaplastic astrocytoma in adults whose disease has progressed after therapy with a nitrosourea and procarbazine.1

Recommended Dosing and Dose Modification Guidelines

The recommended dose for Temodar as an intravenous infusion over 90 minutes is the same as the dose for the oral capsule formulation. Bioequivalence has been established only when Temodar for Injection was given over 90 minutes [see Clinical Pharmacology (12.3)]. Dosage of Temodar must be adjusted according to nadir neutrophil and platelet counts in the previous cycle and the neutrophil and platelet counts at the time of initiating the next cycle. For Temodar dosage calculations based on body surface area (BSA) see Table 5. For suggested capsule combinations on a daily dose see Table 6.

Patients with Newly Diagnosed High Grade Glioma:

Concomitant Phase:

Temodar is administered at 75 mg/m2 daily for 42 days concomitant with focal radiotherapy (60 Gy administered in 30 fractions) followed by maintenance Temodar for 6 cycles. Focal RT includes the tumor bed or resection site with a 2- to 3-cm margin. No dose reductions are recommended during the concomitant phase; however, dose interruptions or discontinuation may occur based on toxicity. The Temodar dose should be continued throughout the 42-day concomitant period up to 49 days if all of the following conditions are met: absolute neutrophil count greater than or equal to 1.5 × 109/L, platelet count greater than or equal to 100 × 109/L, common toxicity criteria (CTC) nonhematological toxicity less than or equal to Grade 1 (except for alopecia, nausea, and vomiting). During treatment a complete blood count should be obtained weekly. Temozolomide dosing should be interrupted or discontinued during concomitant phase according to the hematological and nonhematological toxicity criteria as noted in Table 1. Pneumocystis pneumonia (PCP) prophylaxis is required during the concomitant administration of Temodar and radiotherapy, and should be continued in patients who develop lymphocytopenia until recovery from lymphocytopenia (CTC Grade less than or equal to 1).

Maintenance Phase:

Cycle 1:

Four weeks after completing the Temodar+RT phase, Temodar is administered for an additional 6 cycles of maintenance treatment. Dosage in Cycle 1 (maintenance) is 150 mg/m2 once daily for 5 days followed by 23 days without treatment.

Cycles 2–6:

At the start of Cycle 2, the dose can be escalated to 200 mg/m2, if the CTC nonhematologic toxicity for Cycle 1 is Grade less than or equal to 2 (except for alopecia, nausea, and vomiting), absolute neutrophil count (ANC) is greater than or equal to 1.5 × 109/L, and the platelet count is greater than or equal to 100 × 109/L. The dose remains at 200 mg/m2 per day for the first 5 days of each subsequent cycle except if toxicity occurs. If the dose was not escalated at Cycle 2, escalation should not be done in subsequent cycles.

Dose Reduction or Discontinuation During Maintenance:

Dose reductions during the maintenance phase should be applied according to Tables 2 and 3.

During treatment, a complete blood count should be obtained on Day 22 (21 days after the first dose of Temodar) or within 48 hours of that day, and weekly until the ANC is above 1.5 × 109/L (1500/µL) and the platelet count exceeds 100 × 109/L (100,000/µL). The next cycle of Temodar should not be started until the ANC and platelet count exceed these levels. Dose reductions during the next cycle should be based on the lowest blood counts and worst nonhematologic toxicity during the previous cycle. Dose reductions or discontinuations during the maintenance phase should be applied according to Tables 2 and 3.

Patients with Refractory Anaplastic Astrocytoma:

For adults the initial dose is 150 mg/m2 once daily for 5 consecutive days per 28-day treatment cycle. For adult patients, if both the nadir and day of dosing (Day 29, Day 1 of next cycle) ANC are greater than or equal to 1.5 × 109/L (1500/µL) and both the nadir and Day 29, Day 1 of next cycle platelet counts are greater than or equal to 100 × 109/L (100,000/µL), the Temodar dose may be increased to 200 mg/m2/day for 5 consecutive days per 28-day treatment cycle. During treatment, a complete blood count should be obtained on Day 22 (21 days after the first dose) or within 48 hours of that day, and weekly until the ANC is above 1.5 × 109/L (1500/µL) and the platelet count exceeds 100 × 109/L (100,000/µL). The next cycle of Temodar should not be started until the ANC and platelet count exceed these levels. If the ANC falls to less than 1.0 × 109/L (1000/µL) or the platelet count is less than 50 × 109/L (50,000/µL) during any cycle, the next cycle should be reduced by 50 mg/m2, but not below 100 mg/m2, the lowest recommended dose (see Table 4). Temodar therapy can be continued until disease progression. In the clinical trial, treatment could be continued for a maximum of 2 years, but the optimum duration of therapy is not known.

Preparation and Administration

Temodar Capsules:

In clinical trials, Temodar was administered under both fasting and nonfasting conditions; however, absorption is affected by food [see Clinical Pharmacology (12.3)], and consistency of administration with respect to food is recommended. There are no dietary restrictions with Temodar. To reduce nausea and vomiting, Temodar should be taken on an empty stomach. Bedtime administration may be advised. Antiemetic therapy may be administered prior to and/or following administration of Temodar.

Temodar (temozolomide) Capsules should not be opened or chewed. They should be swallowed whole with a glass of water.

If capsules are accidentally opened or damaged, precautions should be taken to avoid inhalation or contact with the skin or mucous membranes [see How Supplied/Storage and Handling (16.1)].

Temodar for Injection:

Each vial of Temodar for Injection contains sterile and pyrogen-free temozolomide lyophilized powder. When reconstituted with 41 mL Sterile Water for Injection, the resulting solution will contain 2.5 mg/mL temozolomide. Bring the vial to room temperature prior to reconstitution with Sterile Water for Injection. The vials should be gently swirled and not shaken. Vials should be inspected, and any vial containing visible particulate matter should not be used. Do not further dilute the reconstituted solution. After reconstitution, store at room temperature (25°C [77°F]). Reconstituted product must be used within 14 hours, including infusion time.

Using aseptic technique, withdraw up to 40 mL from each vial to make up the total dose based on Table 5 above and transfer into an empty 250 mL infusion bag {2}. Temodar for Injection should be infused intravenously using a pump over a period of 90 minutes. Temodar for Injection should be administered only by intravenous infusion. Flush the lines before and after each Temodar 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, other medications should not be infused simultaneously through the same intravenous line.

• Temodar (temozolomide) Capsules for oral administration – 5-mg capsules have opaque white bodies with green caps. The capsule body is imprinted with two stripes, the dosage strength, and the Schering-Plough logo. The cap is imprinted with "Temodar." – 20-mg capsules have opaque white bodies with yellow caps. The capsule body is imprinted with two stripes, the dosage strength, and the Schering-Plough logo. The cap is imprinted with "Temodar." – 100-mg capsules have opaque white bodies with pink caps. The capsule body is imprinted with two stripes, the dosage strength, and the Schering-Plough logo. The cap is imprinted with "Temodar." – 140-mg capsules have opaque white bodies with blue caps. The capsule body is imprinted with two stripes, the dosage strength, and the Schering-Plough logo. The cap is imprinted with "Temodar." – 180-mg capsules have opaque white bodies with orange caps. The capsule body is imprinted with two stripes, the dosage strength, and the Schering-Plough logo. The cap is imprinted with "Temodar." – 250-mg capsules have opaque white bodies with white caps. The capsule body is imprinted with two stripes, the dosage strength, and the Schering-Plough logo. The cap is imprinted with "Temodar."
• Temodar (temozolomide) is available as 100-mg/vial powder for injection. The lyophilized powder is white to light tan/light pink.

Hypersensitivity

Temodar (temozolomide) is contraindicated in patients who have a history of hypersensitivity reaction (such as urticaria, allergic reaction including anaphylaxis, toxic epidermal necrolysis, and Stevens-Johnson syndrome) to any of its components. Temodar is also contraindicated in patients who have a history of hypersensitivity to dacarbazine (DTIC), since both drugs are metabolized to 5-(3-methyltriazen-1-yl)-imidazole-4-carboxamide (MTIC).

Temodar contains temozolomide, an imidazotetrazine derivative. The chemical name of temozolomide is 3,4-dihydro-3-methyl-4-oxoimidazo[5,1-d]-as-tetrazine-8-carboxamide. The structural formula is:

The material is a white to light tan/light pink powder with a molecular formula of C6H6N6O2 and a molecular weight of 194.15. The molecule is stable at acidic pH (<5) and labile at pH >7; hence Temodar can be administered orally and intravenously. The prodrug, temozolomide, is rapidly hydrolyzed to the active 5-(3-methyltriazen-1-yl) imidazole-4-carboxamide (MTIC) at neutral and alkaline pH values, with hydrolysis taking place even faster at alkaline pH.

Temodar Capsules:

Each capsule for oral use contains either 5 mg, 20 mg, 100 mg, 140 mg, 180 mg, or 250 mg of temozolomide.

The inactive ingredients for Temodar Capsules are as follows:

The body of the capsules is made of gelatin, and is opaque white. The cap is also made of gelatin, and the colors vary based on the dosage strength. The capsule body and cap are imprinted with pharmaceutical branding ink, which contains shellac, dehydrated alcohol, isopropyl alcohol, butyl alcohol, propylene glycol, purified water, strong ammonia solution, potassium hydroxide, and ferric oxide.

Temodar for Injection:

Each vial contains 100 mg of sterile and pyrogen-free temozolomide lyophilized powder for intravenous injection. The inactive ingredients are: mannitol (600 mg), L-threonine (160 mg), polysorbate 80 (120 mg), sodium citrate dihydrate (235 mg), and hydrochloric acid (160 mg).

Carcinogenesis, Mutagenesis, Impairment of Fertility

Temozolomide is carcinogenic in rats at doses less than the maximum recommended human dose. Temozolomide induced mammary carcinomas in both males and females at doses 0.13 to 0.63 times the maximum human dose (25–125 mg/m2) when administered orally on 5 consecutive days every 28 days for 6 cycles. Temozolomide also induced fibrosarcomas of the heart, eye, seminal vesicles, salivary glands, abdominal cavity, uterus, and prostate, carcinomas of the seminal vesicles, schwannomas of the heart, optic nerve, and harderian gland, and adenomas of the skin, lung, pituitary, and thyroid at doses 0.5 times the maximum daily dose. Mammary tumors were also induced following 3 cycles of temozolomide at the maximum recommended daily dose.

Temozolomide is a mutagen and a clastogen. In a reverse bacterial mutagenesis assay (Ames assay), temozolomide increased revertant frequency in the absence and presence of metabolic activation. Temozolomide was clastogenic in human lymphocytes in the presence and absence of metabolic activation.

Temozolomide impairs male fertility. Temozolomide caused syncytial cells/immature sperm formation at 0.25 and 0.63 times the maximum recommended human dose (50 and 125 mg/m2) in rats and dogs, respectively, and testicular atrophy in dogs at 0.63 times the maximum recommended human dose (125 mg/m2).

Animal Toxicology and/or Pharmacology

Toxicology studies in rats and dogs identified a low incidence of hemorrhage, degeneration, and necrosis of the retina at temozolomide doses equal to or greater than 0.63 times the maximum recommended human dose (125 mg/m2). These changes were most commonly seen at doses where mortality was observed.

Newly Diagnosed Glioblastoma Multiforme

Five hundred and seventy-three patients were randomized to receive either Temodar (TMZ)+Radiotherapy (RT) (n=287) or RT alone (n=286). Patients in the Temodar+RT arm received concomitant Temodar (75 mg/m2) once daily, starting the first day of RT until the last day of RT, for 42 days (with a maximum of 49 days). This was followed by 6 cycles of Temodar alone (150 or 200 mg/m2) on Days 1 to 5 of every 28-day cycle, starting 4 weeks after the end of RT. Patients in the control arm received RT only. In both arms, focal radiation therapy was delivered as 60 Gy/30 fractions. Focal RT includes the tumor bed or resection site with a 2- to 3-cm margin. Pneumocystis pneumonia (PCP) prophylaxis was required during the TMZ+RT, regardless of lymphocyte count, and was to continue until recovery of lymphocyte count to less than or equal to Grade 1.

At the time of disease progression, Temodar was administered as salvage therapy in 161 patients of the 282 (57%) in the RT alone arm, and 62 patients of the 277 (22%) in the Temodar+RT arm.

The addition of concomitant and maintenance Temodar to radiotherapy in the treatment of patients with newly diagnosed GBM showed a statistically significant improvement in overall survival compared to radiotherapy alone (Figure 1). The hazard ratio (HR) for overall survival was 0.63 (95% CI for HR=0.52-0.75) with a log-rank P<0.0001 in favor of the Temodar arm. The median survival was increased by 2.5 months in the Temodar arm.
 

FIGURE 1: Kaplan-Meier Curves for Overall Survival (ITT Population)

Refractory Anaplastic Astrocytoma

A single-arm, multicenter study was conducted in 162 patients who had anaplastic astrocytoma at first relapse and who had a baseline Karnofsky performance status of 70 or greater. Patients had previously received radiation therapy and may also have previously received a nitrosourea with or without other chemotherapy. Fifty-four patients had disease progression on prior therapy with both a nitrosourea and procarbazine, and their malignancy was considered refractory to chemotherapy (refractory anaplastic astrocytoma population). Median age of this subgroup of 54 patients was 42 years (19–76). Sixty-five percent were male. Seventy-two percent of patients had a KPS of >80. Sixty-three percent of patients had surgery other than a biopsy at the time of initial diagnosis. Of those patients undergoing resection, 73% underwent a subtotal resection and 27% underwent a gross total resection. Eighteen percent of patients had surgery at the time of first relapse. The median time from initial diagnosis to first relapse was 13.8 months (4.2–75.4).

Temodar Capsules were given for the first 5 consecutive days of a 28-day cycle at a starting dose of 150 mg/m2/day. If the nadir and day of dosing (Day 29, Day 1 of next cycle) absolute neutrophil count was greater than or equal to 1.5 × 109/L (1500/µL) and the nadir and Day 29, Day 1 of next cycle platelet count was greater than or equal to 100 × 109/L (100,000/µL), the Temodar dose was increased to 200 mg/m2/day for the first 5 consecutive days of a 28-day cycle.

In the refractory anaplastic astrocytoma population, the overall tumor response rate (CR+PR) was 22% (12/54 patients) and the complete response rate was 9% (5/54 patients). The median duration of all responses was 50 weeks (range: 16–114 weeks) and the median duration of complete responses was 64 weeks (range: 52–114 weeks). In this population, progression-free survival at 6 months was 45% (95% CI: 31%–58%) and progression-free survival at 12 months was 29% (95% CI: 16%–42%). Median progression-free survival was 4.4 months. Overall survival at 6 months was 74% (95% CI: 62%–86%) and 12-month overall survival was 65% (95% CI: 52%–78%). Median overall survival was 15.9 months.

Safe Handling and Disposal

Care should be exercised in the handling and preparation of Temodar. Vials and capsules should not be opened. If vials or capsules are accidentally opened or damaged, rigorous precautions should be taken with the contents to avoid inhalation or contact with the skin or mucous membranes. The use of gloves and safety glasses is recommended to avoid exposure in case of breakage of the vial or capsules. Procedures for proper handling and disposal of anticancer drugs should be considered {1–4}. Several guidelines on this subject have been published.

How Supplied

Temodar Capsules:

Temodar (temozolomide) Capsules are supplied in child-resistant sachets containing the following capsule strengths:

Temodar Capsules 5 mg: have opaque white bodies with green caps. The capsule body is imprinted with two stripes, the dosage strength, and the Schering-Plough logo. The cap is imprinted with "Temodar".
They are supplied as follows:

Temodar Capsules 20 mg: have opaque white bodies with yellow caps. The capsule body is imprinted with two stripes, the dosage strength, and the Schering-Plough logo. The cap is imprinted with "Temodar".
They are supplied as follows:

Temodar Capsules 100 mg: have opaque white bodies with pink caps. The capsule body is imprinted with two stripes, the dosage strength, and the Schering-Plough logo. The cap is imprinted with "Temodar".
They are supplied as follows:

Temodar Capsules 140 mg: have opaque white bodies with blue caps. The capsule body is imprinted with two stripes, the dosage strength, and the Schering-Plough logo. The cap is imprinted with "Temodar".
They are supplied as follows:

Temodar Capsules 180 mg: have opaque white bodies with orange caps. The capsule body is imprinted with two stripes, the dosage strength, and the Schering-Plough logo. The cap is imprinted with "Temodar".
They are supplied as follows:

Temodar Capsules 250 mg: have opaque white bodies with white caps. The capsule body is imprinted with two stripes, the dosage strength, and the Schering-Plough logo. The cap is imprinted with "Temodar".
They are supplied as follows:

Temodar for Injection:

Temodar (temozolomide) for Injection is supplied in single-use glass vials containing 100 mg temozolomide. The lyophilized powder is white to light tan/light pink.

Temodar for Injection 100 mg:
  NDC 0085-1381-01

Storage

Store Temodar Capsules at 25°C (77°F); excursions permitted to 15–30°C (59–86°F) [see USP Controlled Room Temperature].

Store Temodar for Injection refrigerated at 2–8°C (36–46°F). After reconstitution, store reconstituted product at room temperature (25°C [77°F]). Reconstituted product must be used within 14 hours, including infusion time.

NDC 0085-1381-01

Temodar®
[temozolomide]
for Injection

100 mg/VIAL

For Intravenous Use Only

Single-Use Vial.
Discard after use.

Rx only

Temodar (temozolomide) interferes with the development of cancer cells, slowing their growth and spread in the body.

Temodar is used together with radiation therapy to treat certain types of brain tumor in adults.

Temodar is usually given after other cancer medicines have been tried without success.

Tell your doctor about all medicines you use, and those you start or stop using during your treatment with Temodar, especially:

• steroid medicine (dexamethasone, prednisone, and others); or

• valproic acid (Depakene, Stavzor).

This list is not complete. Other drugs may interact with temozolomide, including prescription and over-the-counter medicines, vitamins, and herbal products. Not all possible interactions are listed in this medication guide.

Applies to temozolomide: oral capsule

Other dosage forms:

• intravenous powder for solution

Along with its needed effects, temozolomide (the active ingredient contained in Temodar) may cause some unwanted effects. Although not all of these side effects may occur, if they do occur they may need medical attention.

Check with your doctor immediately if any of the following side effects occur while taking temozolomide:

• Amnesia
• black, tarry stools
• blood in the urine or stools
• convulsions
• cough or hoarseness
• fever or chills
• lower back or side pain
• muscle weakness or paralysis on one or both sides of the body
• painful or difficult urination
• pinpoint red spots on the skin
• swelling of the feet or lower legs
• unusual bleeding or bruising

• Abdominal or stomach pain or tenderness
• blistering, peeling, or loosening of the skin
• chest pain
• clay colored stools
• cough
• decreased appetite
• diarrhea
• difficulty swallowing
• dizziness
• fast heartbeat
• headache
• hives, itching, or skin rash
• joint or muscle pain
• nausea or vomiting
• puffiness or swelling of the eyelids or around the eyes, face, lips, or tongue
• red skin lesions, often with a purple center
• red, irritated eyes
• sneezing
• sore throat
• sores, ulcers, or white spots in the mouth or on the lips
• tightness in the chest
• troubled breathing
• unusual tiredness or weakness
• yellow skin or eyes

Some side effects of temozolomide may occur that usually do not need medical attention. These side effects may go away during treatment as your body adjusts to the medicine. Also, your health care professional may be able to tell you about ways to prevent or reduce some of these side effects. Check with your health care professional if any of the following side effects continue or are bothersome or if you have any questions about them:

• Constipation

• Anxiety
• blurred or double vision
• breast pain (in females)
• burning or prickling feeling on the skin
• confusion
• diarrhea
• difficulty with speaking
• drowsiness
• increased urge to urinate
• loss of appetite
• loss of muscle coordination
• mental depression
• runny or stuffy nose
• trouble sleeping
• unusual weight gain