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.

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).

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.
Monitor for signs and symptoms of hepatotoxicity (fatigue, abdominal pain, nausea, vomiting, jaundice, anorexia, fever, dark urine, clay-colored stools); if signs and symptoms occur, notify provider and provide supportive care; therapy interruption or dose adjustment may be required.
Monitor for signs and symptoms of myelodysplastic syndrome and secondary malignancies, including myeloid leukemia (fatigue, dyspnea, easy bruising and bleeding, pale skin and sclera, frequent infections, mouth pain or nonhealing sore on the lips or in the mouth).
Monitor for signs and symptoms of Pneumocystis jirovecii pneumonia (cough, fever, chills, dyspnea, tachypnea, night sweats, weight loss); ↑ risk in patients receiving corticosteroids or longer dosing regimens; prophylaxis is recommended in patients with newly diagnosed glioblastoma.

Lab Test Considerations:

Verify negative pregnancy test before starting therapy.
Myelosuppression, including pancytopenia, leukopenia, and anemia, can occur; ↑ risk in older adults and females. Lymphopenia risk highest in patients also receiving corticosteroids.
Glioblastoma multiforme: During Concomitant Phase, patient must have an ANC≥1.5 × 10⁹/L, a platelet count ≥100 × 10⁹/L, and nonhematological toxicity ≤Grade 1 (except for alopecia, nausea, and vomiting). Obtain CBC with differential weekly. If ANC ≥0.5 and <1.5 × 10⁹/L or platelet count ≥10 and <100 × 10⁹/L or Grade 2 nonhematological toxicity during any cycle, interrupt therapy until ANC and platelet count have returned to above parameters. If ANC <0.5 × 10 ⁹/L or platelet count <10 × 10 ⁹/L or Grade 3 or 4 nonhematological toxicity, discontinue temozolomide. For the Maintenance Phase, see manufacturer's recommended dosing guidelines. Anaplastic astrocytoma: Obtain CBC with differential on Day 22 (21 days after first dose) or within 48 hr of that day, and weekly until ANC >1.5 × 10⁹/L and platelet count >100 × 10⁹/L. If the ANC <1.0 × 10⁹/L or the platelet count <50 × 10⁹/L during any cycle, the dose in next cycle should be ↓ by 50 mg/m², but not below 100 mg/m², the lowest recommended dose. See manufacturer's recommendations for specific guidelines. 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 wk after last dose.

Implementation ⬆ ⬇

Prophylactically treat patients with glioblastoma who are receiving concurrent temozolomide and radiotherapy for Pneumocystis jirovecii pneumonia. Continue prophylaxis in patients who develop lymphopenia, ANC ≥1.5 × 10⁹/L, and platelet count >100 × 10⁹/L.
PO: Administer capsules one at a time with a full glass of water at the same time each day. Consistency of administration with respect to food is recommended as absorption is affected, but there are no dietary restrictions with temozolomide. Take on an empty stomach or at bedtime to ↓ nausea and vomiting. DNC: Swallow capsules whole; do not open, chew, or dissolve the contents of the capsules. May administer antiemetics before or following administration.
- Handle intact capsules with single gloves; use single gloves, respiratory protection, and a protective gown in the handling of capsules. In case of powder contact, wash the affected area with water immediately. If capsules are accidently opened or damaged, avoid inhaling powder or getting on mucous membranes in nose or mouth.

IV Administration:

Intermittent Infusion: Bring vial to room temperature before reconstitution. Reconstitution: 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.
- Use double gloves, eye and respiratory protection, and a protective gown in the administration of infusions. During administration, if there is a potential that the substance could splash or if the patient may resist, use eye and face protection. Administer certain dosage forms via a closed system drug transfer device.
Y-Site Incompatibility: Do not infuse with other drugs simultaneously through the same IV line.

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.

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

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Pronunciation ⬇

Classifications ⬆ ⬇

Indications ⬆ ⬇

Action ⬆ ⬇

Pharmacokinetics ⬆ ⬇

Time/Action Profile ⬆ ⬇

Contraind./Precautions ⬆ ⬇