temozolomide

REMS

Refractory anaplastic astrocytoma progressing despite treatment with a nitrosurea and procarbazine.
Newly diagnosed glioblastoma multiforme (with radiation and then alone as maintenance therapy).

Contraind./Precautions ⬆ ⬇

Contraindicated in:

Hypersensitivity to temozolomide or dacarbazine (DTIC);
OB: Pregnancy or lactation.

Use Cautiously in:

Severe hepatic or renal impairment;
Geri: Geriatric patients and women (↑ risk of myelosuppression);
Active infection;
↓bone marrow reserve;
Other chronic debilitating illness;
OB: Patients with childbearing potential;
Pedi: Safety not established.

Adv. Reactions/Side Effects ⬆ ⬇

CNS: SEIZURES, fatigue, headache, abnormal coordination, anxiety, depression, dizziness, drowsiness, mental status changes, weakness

EENT: abnormal vision, diplopia

Resp: cough

CV: peripheral edema

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

Derm: pruritus, rash

Endo: adrenal hypercorticism

Hemat: leukopenia, thrombocytopenia, anemia

Metab: ↑weight

MS: abnormal gait, back pain

Neuro: hemiparesis, myalgia

Misc: breast pain (women), fever, injection site reactions, pain at injection site, secondary malignancies (rare)

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 ⬆ ⬇

PO IV (Adults ): Anaplastic astrocytoma—150 mg/m²/day for 5 consecutive days of each 28-day treatment cycle; doses adjusted on the basis of blood counts; Glioblastoma multiforme—75 mg/m²/day for 42 consecutive days concurrently with radiation initially, then starting 4 wk after last dose, maintenance dose of 150 mg/m²/day for 5 consecutive days of one 28-day treatment cycle then 200 mg/m² for 5 consecutive days of each 28-day treatment cycle for 5 cycles; doses adjusted on the basis of blood counts. Concurrent prophylaxis against Pneumocystis jiroveci pneumonia is required during first 42 days of regimen.

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 ⬆ ⬇

Instruct patient to take medication as directed, at the same time each day. Capsules should be packaged in 5 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.
Inform patient that antiemetic medication may be taken if nausea and vomiting occur.
Instruct patient to notify health care professional if dyspnea, sore throat, fever, chills, unusual bleeding or bruising, or fatigue occurs. 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.
Caution patient not to receive any vaccinations without advice of health care professional.
Advise patient to use a nonhormonal method of contraception throughout therapy.
Emphasize the importance of follow-up examination to monitor progress and side effects.

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Indications ⬇