temozolomide

Contraindicated in:

Hypersensitivity to temozolomide or dacarbazine;
OB: Pregnancy;
Lactation: Lactation;

Use Cautiously in:

Severe hepatic impairment;
Severe renal impairment;
Women (↑ risk of myelosuppression);
Active infection;
↓bone marrow reserve;
Other chronic debilitating illness;
Rep: Women of reproductive potential, men with female partners of reproductive potential, or men with pregnant partners;
Pedi: Safety and effectiveness not established in children;
Geri: ↑risk of myelosuppression in older adults.

Adv. Reactions/Side Effects ⬆ ⬇

CV: peripheral edema

Derm: pruritus, rash

EENT: abnormal vision, diplopia

Endo: adrenal hypercorticism

GI: nausea, vomiting, abdominal pain, anorexia, constipation, diarrhea, dysphagia, HEPATOTOXICITY

GU: breast pain (women)

Hemat: neutropenia, thrombocytopenia, anemia

Local: injection site reactions, pain at injection site

Metab: ↑weight

MS: back pain, myalgia

Neuro: fatigue, headache, abnormal coordination, abnormal gait, anxiety, depression, dizziness, drowsiness, hemiparesis, mental status changes, SEIZURES, weakness

Resp: cough

Misc: fever, SECONDARY MALIGNANCY

Interactions ⬆ ⬇

Drug-drug:

↑bone marrow depression may occur with other antineoplastics or radiation therapy.
May ↓ the antibody response to live-virus vaccines and ↑ risk of adverse reactions.

Availability ⬆ ⬇

(Generic available)

Capsules: 5 mg; 20 mg; 100 mg; 140 mg; 180 mg; 250 mg
Powder for injection: 100 mg/vial

Route/Dosage ⬆ ⬇

Newly Diagnosed Anaplastic Astrocytoma

PO (Adults ): Starting 4 wk after the end of radiotherapy, administer 150 mg/m² once daily for 5 consecutive days of one 28-day treatment cycle (Cycle 1); then 200 mg/m² once daily for 5 consecutive days of each 28-day treatment cycle for Cycles 2–12.

Refractory Anaplastic Astrocytoma

PO (Adults ): 150 mg/m² once daily for 5 consecutive days of each 28-day treatment cycle; ↑ dose to 200 mg/m² once daily if the following conditions are met at the nadir and on Day 1 of the next cycle: ANC ≥1.5 × 10⁹/L, and platelet count ≥100 × 10⁹ /L. Continue until disease progression or unacceptable toxicity.

Glioblastoma Multiforme

PO IV (Adults ): 75 mg/m² once daily for 42–49 consecutive days concurrently with radiation initially; then starting 4 wk after last dose, maintenance dose of 150 mg/m² once daily for 5 consecutive days of one 28-day treatment cycle (Cycle 1); then 200 mg/m² once daily for 5 consecutive days of each 28-day treatment cycle for 5 cycles (Cycles 2–6).

US Brand Names ⬆ ⬇

Action ⬆ ⬇

Temozolomide is not active until converted at physiologic pH to MTIC, which alkylates DNA, disrupting its synthesis.

Therapeutic effects:

Death of rapidly replicating cells, especially malignant ones, resulting in regression or slowed tumor growth.

Classifications ⬆ ⬇

Therapeutic Classification: antineoplastics

Pharmacologic Classification: alkylating agents

Pharmacokinetics ⬆ ⬇

Absorption: Rapidly converted to MTIC, the active metabolite.

Distribution: Unknown.

Metabolism/Excretion: Further metabolism results in the formation of methylhydrazine, which is responsible for most activity.

Half-Life: 1.8 hr.

Canadian Brand Names ⬆ ⬇

Time/Action Profile ⬆ ⬇

(effect on blood counts)

ROUTE	ONSET	PEAK	DURATION
PO/IV (WBC)	unknown	28 days (range 1–44 days)	14 days
PO/IV (platelets)	unknown	26 days (range 21–40 days)	14 days

Patient/Family Teaching ⬆ ⬇

Explain purpose and side effects of temozolomide to patient. Instruct patient to take medication as directed, at the same time each day. Capsules should be packaged in five separate packets or vials labeled "Day 1," "Day 2," "Day 3," "Day 4," and "Day 5." Capsules may be different sizes or colors in each packet. Contact pharmacist or prescriber if there are questions about the packaging. Keep out of children's reach. Advise patient to read Patient Information before starting and with each Rx refill in case of changes.
Emphasize the importance of follow-up examination to monitor progress and side effects; may include hair loss, fatigue, nausea, vomiting, headache, constipation, ↓ appetite, and seizures.
Inform patient that antiemetic medication may be taken if nausea and vomiting occur. To ↓ nausea and vomiting, temozolomide should be taken on an empty stomach or at bedtime.
Instruct patient to notify health care professional if dyspnea, sore throat, mouth pain or sores, fever, chills, unusual bleeding or bruising, or fatigue occur. Caution patient to avoid crowds and persons with known infections. Instruct patient to use a soft toothbrush and electric razor and to be especially careful to avoid falls. Caution patients not to drink alcohol or take medication containing aspirin or NSAIDs; may precipitate gastric bleeding.
Advise the patient to immediately report symptoms of hepatotoxicity (fatigue, abdominal pain, nausea, vomiting, jaundice, poor appetite, fever, dark urine, clay-colored stools).
Counsel patient of the ↑ risk of myelodysplastic syndrome and secondary malignancies.
Caution patient not to receive any vaccinations without advice of health care professional.
Advise patient to notify health care professional of all Rx or OTC medications, vitamins, or herbal products being taken and to consult health care professional before taking other medications.
Rep: May cause fetal harm. Females of reproductive potential should use effective contraception during therapy and for 6 mo after the final dose. Male patients with female partners of reproductive potential should use condoms during treatment and for 3 mo after the last dose. Male patients should be advised not to donate semen during treatment and for 3 mo after last dose. Advise women not to breastfeed during therapy and for 1 wk after the last dose.

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Indications ⬇

Contraind./Precautions ⬆ ⬇