Temodar Side Effects

Generic Name: temozolomide

Please note - some side effects for Temodar may not be reported. Always consult your doctor or healthcare specialist for medical advice. You may also report side effects to the FDA.

Side Effects of Temodar - for the Consumer

Temodar

All medicines may cause side effects, but many people have no, or minor, side effects. Check with your doctor if any of these most COMMON side effects persist or become bothersome when using Temodar:

Anxiety; back pain; breast pain; constipation; cough; diarrhea; dizziness; drowsiness; dry skin; hair loss; headache; joint pain; loss of appetite; mild stomach pain; mouth or tongue sores; muscle aches; nausea; taste changes; tiredness; trouble sleeping; vomiting; weakness; weight gain.

Seek medical attention right away if any of these SEVERE side effects occur when using Temodar:

Severe allergic reactions (rash; hives; itching; difficulty breathing; tightness in the chest; swelling of the mouth, face, lips, or tongue); chest pain; confusion; coughing up blood; depression; difficulty swallowing; increased, difficult, or painful urination; fever, chills, or sore throat; loss of bladder control; loss of coordination; memory loss; muscle pain or weakness; numbness, burning, or tingling; pain, irritation, itching, warmth, swelling, or redness at the injection site; paralysis on one side of the body; persistent cough; red, swollen, peeling, or blistered skin; seizures; severe or persistent headache, nausea, or vomiting; severe or persistent tiredness or weakness; shortness of breath; small red or purple spots under the skin; speech changes; sudden or unusual weight gain; swelling of the ankles, feet, or hands; symptoms of liver problems (eg, dark urine, pale stools, persistent loss of appetite, severe stomach pain, yellowing of the skin or eyes); unusual bruising or bleeding; trouble walking; vision changes (eg, blurred vision, double vision).

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Temodar Side Effects - for the Professional

Temodar

Clinical Trials Experience

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.

Newly Diagnosed Glioblastoma Multiforme:

During the concomitant phase (Temodar+radiotherapy), adverse reactions including thrombocytopenia, nausea, vomiting, anorexia, and constipation were more frequent in the Temodar+RT arm. The incidence of other adverse reactions was comparable in the two arms. The most common adverse reactions across the cumulative Temodar experience were alopecia, nausea, vomiting, anorexia, headache, and constipation. Forty-nine percent (49%) of patients treated with Temodar reported one or more severe or life-threatening reactions, most commonly fatigue (13%), convulsions (6%), headache (5%), and thrombocytopenia (5%). Overall, the pattern of reactions during the maintenance phase was consistent with the known safety profile of Temodar.

TABLE 7: Number (%) of Patients with Adverse Reactions: All and Severe/Life Threatening (Incidence of 5% or Greater)

	Concomitant Phase RT Alone (n=285)				Concomitant Phase RT+TMZ (n=288)*				Maintenance Phase TMZ (n=224)
	All		Grade ≥3		All		Grade ≥3		All		Grade ≥3
RT+TMZ=radiotherapy plus temozolomide; NOS=not otherwise specified.
Note: Grade 5 (fatal) adverse reactions are included in the Grade ≥3 column.
* One patient who was randomized to RT only arm received RT+temozolomide.
Subjects Reporting any Adverse Reaction	258	(91)	74	(26)	266	(92)	80	(28)	206	(92)	82	(37)
Body as a Whole - General Disorders
Anorexia	25	(9)	1	(<1)	56	(19)	2	(1)	61	(27)	3	(1)
Dizziness	10	(4)	0		12	(4)	2	(1)	12	(5)	0
Fatigue	139	(49)	15	(5)	156	(54)	19	(7)	137	(61)	20	(9)
Headache	49	(17)	11	(4)	56	(19)	5	(2)	51	(23)	9	(4)
Weakness	9	(3)	3	(1)	10	(3)	5	(2)	16	(7)	4	(2)
Central and Peripheral Nervous System Disorders
Confusion	12	(4)	6	(2)	11	(4)	4	(1)	12	(5)	4	(2)
Convulsions	20	(7)	9	(3)	17	(6)	10	(3)	25	(11)	7	(3)
Memory Impairment	12	(4)	1	(<1)	8	(3)	1	(<1)	16	(7)	2	(1)
Disorders of the Eye
Vision Blurred	25	(9)	4	(1)	26	(9)	2	(1)	17	(8)	0
Disorders of the Immune System
Allergic Reaction	7	(2)	1	(<1)	13	(5)	0		6	(3)	0
Gastrointestinal System Disorders
Abdominal Pain	2	(1)	0		7	(2)	1	(<1)	11	(5)	1	(<1)
Constipation	18	(6)	0		53	(18)	3	(1)	49	(22)	0
Diarrhea	9	(3)	0		18	(6)	0		23	(10)	2	(1)
Nausea	45	(16)	1	(<1)	105	(36)	2	(1)	110	(49)	3	(1)
Stomatitis	14	(5)	1	(<1)	19	(7)	0		20	(9)	3	(1)
Vomiting	16	(6)	1	(<1)	57	(20)	1	(<1)	66	(29)	4	(2)
Injury and Poisoning
Radiation Injury NOS	11	(4)	1	(<1)	20	(7)	0		5	(2)	0
Musculoskeletal System Disorders
Arthralgia	2	(1)	0		7	(2)	1	(<1)	14	(6)	0
Platelet, Bleeding and Clotting Disorders
Thrombocytopenia	3	(1)	0		11	(4)	8	(3)	19	(8)	8	(4)
Psychiatric Disorders
Insomnia	9	(3)	1	(<1)	14	(5)	0		9	(4)	0
Respiratory System Disorders
Coughing	3	(1)	0		15	(5)	2	(1)	19	(8)	1	(<1)
Dyspnea	9	(3)	4	(1)	11	(4)	5	(2)	12	(5)	1	(<1)
Skin and Subcutaneous Tissue Disorders
Alopecia	179	(63)	0		199	(69)	0		124	(55)	0
Dry Skin	6	(2)	0		7	(2)	0		11	(5)	1	(<1)
Erythema	15	(5)	0		14	(5)	0		2	(1)	0
Pruritus	4	(1)	0		11	(4)	0		11	(5)	0
Rash	42	(15)	0		56	(19)	3	(1)	29	(13)	3	(1)
Special Senses Other, Disorders
Taste Perversion	6	(2)	0		18	(6)	0		11	(5)	0

Myelosuppression (neutropenia and thrombocytopenia), which is a known dose-limiting toxicity for most cytotoxic agents, including Temodar, was observed. When laboratory abnormalities and adverse reactions were combined, Grade 3 or Grade 4 neutrophil abnormalities including neutropenic reactions were observed in 8% of the patients, and Grade 3 or Grade 4 platelet abnormalities, including thrombocytopenic reactions, were observed in 14% of the patients treated with Temodar.

Refractory Anaplastic Astrocytoma:

Tables 8 and 9 show the incidence of adverse reactions in the 158 patients in the anaplastic astrocytoma study for whom data are available. In the absence of a control group, it is not clear in many cases whether these reactions should be attributed to temozolomide or the patients' underlying conditions, but nausea, vomiting, fatigue, and hematologic effects appear to be clearly drug-related. The most frequently occurring adverse reactions were nausea, vomiting, headache, and fatigue. The adverse reactions were usually NCI Common Toxicity Criteria (CTC) Grade 1 or 2 (mild to moderate in severity) and were self-limiting, with nausea and vomiting readily controlled with antiemetics. The incidence of severe nausea and vomiting (CTC Grade 3 or 4) was 10% and 6%, respectively. Myelosuppression (thrombocytopenia and neutropenia) was the dose-limiting adverse reaction. It usually occurred within the first few cycles of therapy and was not cumulative.

Myelosuppression occurred late in the treatment cycle and returned to normal, on average, within 14 days of nadir counts. The median nadirs occurred at 26 days for platelets (range: 21–40 days) and 28 days for neutrophils (range: 1–44 days). Only 14% (22/158) of patients had a neutrophil nadir and 20% (32/158) of patients had a platelet nadir, which may have delayed the start of the next cycle. Less than 10% of patients required hospitalization, blood transfusion, or discontinuation of therapy due to myelosuppression.

In clinical trial experience with 110 to 111 women and 169 to 174 men (depending on measurements), there were higher rates of Grade 4 neutropenia (ANC<500 cells/µL) and thrombocytopenia (<20,000 cells/µL) in women than men in the first cycle of therapy (12% vs. 5% and 9% vs. 3%, respectively).

In the entire safety database for which hematologic data exist (N=932), 7% (4/61) and 9.5% (6/63) of patients over age 70 experienced Grade 4 neutropenia or thrombocytopenia in the first cycle, respectively. For patients less than or equal to age 70, 7% (62/871) and 5.5% (48/879) experienced Grade 4 neutropenia or thrombocytopenia in the first cycle, respectively. Pancytopenia, leukopenia, and anemia have also been reported.

TABLE 8: Adverse Reactions in the Anaplastic Astrocytoma Trial in Adults (≥5%)

	No. (%) of Temodar Patients (N=158)
	All Reactions	Grade 3/4
Any Adverse Reaction	153 (97)	79 (50)
* Blurred vision; visual deficit; vision changes; vision troubles
Body as a Whole
Headache	65 (41)	10 (6)
Fatigue	54 (34)	7 (4)
Asthenia	20 (13)	9 (6)
Fever	21 (13)	3 (2)
Back pain	12 (8)	4 (3)
Cardiovascular
Edema peripheral	17 (11)	1 (1)
Central and Peripheral Nervous System
Convulsions	36 (23)	8 (5)
Hemiparesis	29 (18)	10 (6)
Dizziness	19 (12)	1 (1)
Coordination abnormal	17 (11)	2 (1)
Amnesia	16 (10)	6 (4)
Insomnia	16 (10)	0
Paresthesia	15 (9)	1 (1)
Somnolence	15 (9)	5 (3)
Paresis	13 (8)	4 (3)
Urinary incontinence	13 (8)	3 (2)
Ataxia	12 (8)	3 (2)
Dysphasia	11 (7)	1 (1)
Convulsions local	9 (6)	0
Gait abnormal	9 (6)	1 (1)
Confusion	8 (5)	0
Endocrine
Adrenal hypercorticism	13 (8)	0
Gastrointestinal System
Nausea	84 (53)	16 (10)
Vomiting	66 (42)	10 (6)
Constipation	52 (33)	1 (1)
Diarrhea	25 (16)	3 (2)
Abdominal pain	14 (9)	2 (1)
Anorexia	14 (9)	1 (1)
Metabolic
Weight increase	8 (5)	0
Musculoskeletal System
Myalgia	8 (5)
Psychiatric Disorders
Anxiety	11 (7)	1 (1)
Depression	10 (6)	0
Reproductive Disorders
Breast pain, female	4 (6)
Resistance Mechanism Disorders
Infection viral	17 (11)	0
Respiratory System
Upper respiratory tract infection	13 (8)	0
Pharyngitis	12 (8)	0
Sinusitis	10 (6)	0
Coughing	8 (5)	0
Skin and Appendages
Rash	13 (8)	0
Pruritus	12 (8)	2 (1)
Urinary System
Urinary tract infection	12 (8)	0
Micturition increased frequency	9 (6)	0
Vision
Diplopia	8 (5)	0
Vision abnormal*	8 (5)

TABLE 9: Adverse Hematologic Effects (Grade 3 to 4) in the Anaplastic Astrocytoma Trial in Adults

	Temodar*
* Change from Grade 0 to 2 at baseline to Grade 3 or 4 during treatment.
Hemoglobin	7/158 (4%)
Lymphopenia	83/152 (55%)
Neutrophils	20/142 (14%)
Platelets	29/156 (19%)
WBC	18/158 (11%)

Temodar for injection delivers equivalent temozolomide dose and exposure to both temozolomide and 5-(3-methyltriazen-1-yl)-imidazole-4-carboxamide (MTIC) as the corresponding Temodar capsules. Adverse reactions probably related to treatment that were reported from the 2 studies with the intravenous formulation (n=35) that were not reported in studies using the Temodar capsules were: pain, irritation, pruritus, warmth, swelling, and erythema at infusion site as well as the following adverse reactions: petechiae and hematoma.

Postmarketing Experience

The following adverse reactions have been identified during postapproval use of Temodar. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to the drug exposure.

Temodar Capsules: allergic reactions, including anaphylaxis, have been reported. Erythema multiforme has been reported, which resolved after discontinuation of Temodar and, in some cases, recurred upon rechallenge. Cases of toxic epidermal necrolysis and Stevens-Johnson syndrome have been reported.

There have been reported cases of hepatotoxicity, including elevations of liver enzymes, hyperbilirubinemia, cholestasis, and hepatitis.

Opportunistic infections including Pneumocystis carinii pneumonia (PCP) have also been reported. Cases of interstitial pneumonitis/pneumonitis, alveolitis, and pulmonary fibrosis have been reported. Prolonged pancytopenia, which may result in aplastic anemia, has been reported, and in some cases has resulted in a fatal outcome.

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Side Effects by Body System - for Healthcare Professionals

Gastrointestinal

Gastrointestinal effects including nausea (53%), vomiting (42%), constipation (33%), diarrhea (16%), abdominal pain (9%), and anorexia (9%) have been reported.

General

General effects including headache (41%), fatigue (34%), asthenia (13%), fever (13%), and back pain (8%) have been reported.

Nervous system

Nervous system effects including convulsions (23%), hemiparesis (18%), dizziness (12%), abnormal coordination (11%) amnesia (10%), insomnia (10%), paresthesia (9%), somnolence (9%), paresis (8%), urinary incontinence (8%), ataxia (8%), dysphasia (7%), local convulsions (6%), abnormal gait (6%), and confusion (5%) have been reported.

Cardiovascular

Cardiovascular effects including peripheral edema (11%) have been reported.

Other

Other effects including viral infection (11%) have been reported.

Endocrine

Endocrine effects including adrenal hypercorticism (8%) have been reported.

Genitourinary

Genitourinary effects including urinary tract infection (8%), increased frequency of micturition (6%) and female breast pain (6%) have been reported.

Respiratory

Respiratory effects including upper respiratory tract infection (8%), pharyngitis (8%), sinusitis (6%), and coughing (5%) have been reported. Cases of interstitial pneumonitis/pneumonitis, alveolitis, and pulmonary fibrosis have been reported.

Dermatologic

Dermatologic effects including rash (8%) and pruritus (8%) have been reported.

A case of diffuse erythematous skin rash that progressed to an extensive full body desquamative skin rash has been reported. Even though temozolomide was permanently discontinued, the patient continued to experience the rash on a long-term basis with periodic exacerbations.

Psychiatric

Psychiatric effects including anxiety (7%) and depression (6%) have been reported.

Metabolic

Metabolic effects including weight gain (5%) have been reported.

Musculoskeletal

Musculoskeletal effects including myalgia (5%) have been reported.

Ocular

Ocular effects including diplopia (5%) and abnormal vision (5%) have been reported.

Immunologic

Immunologic side effects including rare cases of opportunistic infections such as Pneumocystis carinii pneumonia have been reported.

Oncologic

Oncologic side effects such as very rare cases of myelodysplastic syndrome and secondary malignancies, including leukemia and newly diagnosed glioblastoma multiforme have been reported.

Hematologic

Hematologic side effects have been reported very rarely including prolonged pancytopenia (which may result in aplastic anemia).

Hepatic

Postmarketing hepatic side effects have included elevated liver enzymes, hyperbillirubinemia, cholestasis, and hepatitis.

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