temozolomide

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.

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

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.

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.

Availability ⬆ ⬇

(Generic available)

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

Assessment ⬆ ⬇

Monitor patient for seizures. Institute seizure precautions as needed.

Lab Test Considerations:

Monitor CBC with differential and platelet count. Glioblastoma multiformeDuring Concomitant Phase, patient must have an absolute neutrophil count (ANC) ≥1.5 x 10⁹/L, a platelet count of ≥100 x 10⁹/L and common toxicity criteria (CTC) non-hematological toxicity ≤Grade 1 (except for alopecia, nausea and vomiting). Obtain CBC weekly. If ANC is ≥0.5 and <1.5 x 10⁹/L or platelet count is ≥10 and <100 x 10⁹/L or CTC is Grade 2 during any cycle, interrupt therapy until ANC and platelet count have returned to above parameters. If ANC <0.5 x 10 ⁹/L or platelet count is <10 x 10 ⁹/L or CTC is Grade 3 or 4, discontinue therapy. For the Maintenance Phase, see manufacturer's recommended dosing guidelines. Anaplastic astrocytomaObtain CBC on Day 22 (21 days after first dose) or within 48 hr of that day, and weekly until ANC is above 1.5 x 10⁹/L and platelet count exceeds 100 x 10⁹/L. If the ANC falls to <1.0 x 10⁹/L or the platelet count is <50 x 10⁹/L during any cycle, the next cycle should be reduced by 50 mg/m², but not below 100 mg/m², the lowest recommended dose. See manufacturer's recommendations for specific guidelines. Women and geriatric patients are at greater risk for developing myelosuppression. Nadir for thrombocytopenia usually occurs at 26 days and for neutropenia usually occurs at 28 days. Recovery usually occurs within 14 days of the nadir.
- Obtain liver function tests at baseline, midway through 1st cycle, prior to each subsequent cycle, and approximately 2–4 wks after last dose; hepatotoxicity may be fatal.

Implementation ⬆ ⬇

Prophylactically treat patients with glioblastoma who are receiving concurrent temazolamide and radiotherapy for
Pneumocystis jirovecii
pneumonia. Continue treatment in patients who develop lymphocytopenia ANC ≥1.5 x 10⁹/L and platelet count exceeds 100 x 10⁹/L.
PO: Administer capsules one at a time with a full glass of water at the same time each day. Take on an empty stomach or at bedtime to reduce nausea and vomiting. Swallow capsules whole; do not chew or open. If capsules are accidently opened or damaged, avoid inhaling powder or getting on mucous membranes in nose or mouth. May administer antiemetics before of following administration.

IV Administration:

Intermittent Infusion: Bring vial to room temperature before reconstitution. Diluent: Reconstitute with 41 mL or Sterile Water for Injection. Swirl gently; do not shake. Do not dilute further or administer solutions containing particulate matter. Concentration: 2.5 mg/mL. Withdraw 40 mL from each vial to make desired dose and transfer into empty 250 mL PVC infusion bag. Solution is stable for 14 hr at room temperature, including infusion time.
Rate: Infuse over 90 min. Flush line before and after infusion.

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.

section name header

Pronunciation ⬇

Classifications ⬆ ⬇

Indications ⬆ ⬇

Action ⬆ ⬇

Pharmacokinetics ⬆ ⬇

Time/Action Profile ⬆ ⬇

Contraind./Precautions ⬆ ⬇

Adv. Reactions/Side Effects ⬆ ⬇

Interactions ⬆ ⬇

Route/Dosage ⬆ ⬇

Availability ⬆ ⬇

Assessment ⬆ ⬇

Implementation ⬆ ⬇

Patient/Family Teaching ⬆ ⬇

Evaluation/Desired Outcomes ⬆ ⬇

US Brand Names ⬆ ⬇

Canadian Brand Names ⬆ ⬇

Pot. Nursing Diagnoses ⬆