temozolomide

Action

Rapidly converts to monomethyl triazeno imidazole carboxamide, an active compound that prevents DNA transcription

Availability

Capsules: 5 mg, 20 mg, 100 mg, 140 mg, 180 mg, 250 mg

Injection (powder for solution, lyophilized): 100 mg

Indications and dosages

➣ Refractory anaplastic astrocytoma

Adults: 150 mg/m² P.O. or by 90-minute I.V. infusion daily for 5 consecutive days of each 28-day treatment cycle. Adjust dosage as appropriate based on absolute neutrophil count.

➣ Newly diagnosed glioblastoma multiforme with radiotherapy

Adults: 75 mg/m² P.O. or by 90-minute I.V. infusion for 42 days with focal radiotherapy (RT), followed by initial maintenance dose of 150 mg/m² P.O. or by 90-minute I.V. infusion daily for days 1 to 5 of a 28-day cycle for six cycles. Four weeks after completing the drug plus RT phase, administer drug for an additional six cycles of maintenance treatment. Dosage in maintenance cycle 1 is 150 mg/m² P.O. or by 90-minute I.V. infusion daily for 5 days, followed by 23 days without treatment. At start of maintenance cycle 2, dosage may be escalated to 200 mg/m² based on absolute neutrophil and platelet counts. Continue dosage at 200 mg/m² daily for first 5 days of each subsequent cycle except if toxicity occurs. If dosage wasn't escalated at maintenance cycle 2, escalation shouldn't be done in subsequent cycles.

Dosage adjustment

• Neutropenia, thrombocytopenia

Contraindications

• Hypersensitivity to drug, its components, or dacarbazine

Precautions

Use cautiously in:

• severe hepatic or renal impairment, active infection, decreased bone marrow reserve, other chronic debilitating illness

• elderly patients

• pregnant or breastfeeding patients

• children (safety not established).

Administration

• Follow facility policy for handling and disposing of chemotherapeutic drugs.

• Give capsules whole daily with a full glass of water, consistently either with or without food.

• Bring powder for injection to room temperature before reconstituting with 41 ml sterile water for injection that results in a 2.5-mg/ml solution. Gently swirl but don't shake vials. Don't further dilute reconstituted solution. Use reconstituted solution within 14 hours, including infusion time. Withdraw prescribed dose and transfer into empty 250-ml infusion bag. Give reconstituted solution only by I.V. infusion using infusion pump over 90 minutes. Flush lines before and after each infusion.

• Know that drug may be given in same I.V. line with normal saline solution for injection only.

• Be aware that dosages in 28-day cycle depend on nadir neutrophil and platelet counts.

Adverse reactions

CNS: fatigue, headache, dysphasia, poor coordination, ataxia, anxiety, depression, dizziness, drowsiness, confusion, amnesia, insomnia, mental status changes, weakness, paresis, hemiparesis, paresthesias, seizures

CV: peripheral edema

EENT: abnormal vision, diplopia, pharyngitis, sinusitis

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

GU: urinary incontinence or frequency, urinary tract infection, breast pain (in women)

Hematologic: anemia, leukopenia, thrombocytopenia

Metabolic: adrenal hypercorticism

Musculoskeletal: abnormal gait, back pain, myalgia

Respiratory: cough, upper respiratory infection

Skin: pruritus, rash

Other: fever, viral infection, weight gain

Interactions

Drug-drug. Antineoplastics: additive bone marrow depression

Live-virus vaccines: decreased antibody response to vaccine, greater risk of adverse reactions

Valproic acid: decreased oral clearance of temozolomide

Drug-diagnostic tests. Neutrophils, platelets: decreased counts

Drug-food. Any food: reduced rate and extent of temozolomide absorption

Patient monitoring

Monitor CBC with white cell differential. Stay alert for evidence of bone marrow depression.

• Assess neurologic status carefully.

• Monitor fluid intake and output, and weigh patient regularly.

• Be aware that Pneumocystis jiroveci pneumonia prophylaxis is required during concomitant administration of RT and should be continued in patients who develop lymphocytopenia until recovery from lymphocytopenia (circulating tumor cells Grade 1 or less).

Patient teaching

• Tell patient to take capsules consistently with or without food, and with a full glass of water.

• Instruct patient to swallow capsules whole without opening or chewing them and if capsules are accidentally opened or damaged, to avoid inhalation or contact with the skin or mucous membranes.

• If drug causes nausea or vomiting, advise patient to take it 1 hour before or 2 hours after a meal.

• Inform patient that drug may cause abnormal gait and dizziness.

Instruct patient to immediately report unusual bleeding or bruising.

• Advise patient to avoid live-virus vaccines.

• Caution patient to avoid driving and other hazardous activities until he knows how drug affects concentration, alertness, and vision.

• Instruct patient to report suspected pregnancy. Caution her not to breastfeed.

• As appropriate, review all other significant and life-threatening adverse reactions and interactions, especially those related to the drugs and tests mentioned above.