warnings and cautions
5 WARNINGS AND PRECAUTIONS • Myelosuppression: Monitor absolute neutrophil count (ANC) and platelet count prior to each cycle and during treatment. Geriatric patients and women have a higher risk of developing myelosuppression. ( 5.1 ) • Myelodysplastic Syndrome and Secondary Malignancies , including myeloid leukemia, have been observed. ( 5.2 ) • Pneumocystis pneumonia (PCP): Closely monitor all patients, particularly those receiving steroids, for the development of lymphopenia and PCP. ( 5.3 ) • Hepatotoxicity: Fatal and severe hepatotoxicity have been reported. Perform liver tests at baseline, midway through the first cycle, prior to each subsequent cycle, and approximately two to four weeks after the last dose of temozolomide capsules. ( 5.4 ) • Embryo-Fetal Toxicity: Can cause fetal harm. Advise females of reproductive potential of the potential risk to a fetus and to use effective contraception. Advise male patients with pregnant partners or female partners of reproductive potential to use condoms. ( 5.5 , 8.1 , 8.3 ) 5.1 Myelosuppression Myelosuppression, including pancytopenia, leukopenia and anemia, some with fatal outcomes, have occurred with temozolomide capsules [see Adverse Reactions ( 6.1 , 6.2 )] . Geriatric patients and women have been shown in clinical trials to have a higher risk of developing myelosuppression. Prior to dosing, patients must have an ANC of 1.5 x 10 9 /L or greater and a platelet count of 100 x 10 9 /L or greater. For the concomitant phase with radiotherapy, obtain a complete blood count prior to initiation of treatment and weekly during treatment [see Dosage and Administration ( 2.1 )] . For the 28-day treatment cycles, obtain a complete blood count prior to treatment on Day 1 and on Day 22 of each cycle. Perform complete blood counts weekly until recovery if the ANC falls below 1.5 x 10 9 /L and the platelet count falls below 100 x 10 9 /L [see Dosage and Administration ( 2.1 , 2.2 )] . 5.2 Myelodysplastic Syndrome and Secondary Malignancies Cases of myelodysplastic syndrome and secondary malignancies, including myeloid leukemia, have been observed following temozolomide capsule administration. 5.3 Pneumocystis Pneumonia Pneumocystis pneumonia (PCP) can occur in patients receiving temozolomide capsules. The risk of PCP is increased in patients receiving steroids or with longer treatment regimens. For patients with newly diagnosed glioblastoma, provide PCP prophylaxis for all patients during the concomitant phase. Continue in patients who experience lymphopenia until resolution to grade 1 or less [see Dosage and Administration ( 2.1 )] . Monitor all patients receiving temozolomide capsules for the development of lymphopenia and PCP. 5.4 Hepatotoxicity Fatal and severe hepatotoxicity have been reported in patients receiving temozolomide. Perform liver tests at baseline, midway through the first cycle, prior to each subsequent cycle, and approximately two to four weeks after the last dose of temozolomide. 5.5 Embryo-Fetal Toxicity Based on findings from animal studies and its mechanism of action, temozolomide capsules can cause fetal harm when administered to a pregnant woman. Adverse developmental outcomes have been reported in both pregnant patients and pregnant partners of male patients. Oral administration of temozolomide to rats and rabbits during the period of organogenesis resulted in embryolethality and polymalformations at doses less than the maximum human dose based on body surface area. Advise pregnant women of the potential risk to the fetus. Advise females of reproductive potential to use effective contraception during treatment with temozolomide capsules and for at least 6 months after the final dose. Because of potential risk of genotoxic effects on sperm, advise male patients with female partners of reproductive potential to use condoms during treatment with temozolomide capsules and for at least 3 months after the final dose. Advise male patients not to donate semen during treatment with temozolomide capsules and for at least 3 months after the final dose [see Use in Specific Populations ( 8.1 , 8.3 )] .