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 , 8.5 ) 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 2 to 4 weeks after the last dose of TEMOZOLOMIDE ( 5.2 ) Pneumocystis Pneumonia (PCP): Closely monitor all patients, particularly those receiving steroids, for the development of lymphopenia and PCP.( 5.3 ) Secondary Malignancies : Myelodysplastic syndrome and secondary malignancies, including myeloid leukemia, have been observed. ( 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 ) Exposure to Opened Capsules : TEMOZOLOMIDE capsules should not be opened, chewed, or dissolved but should be swallowed whole with a glass of water. ( 5.6 ) 5.1 Myelosuppression Myelosuppression, including pancytopenia, leukopenia and anemia, some with fatal outcomes, have occurred with TEMOZOLOMIDE [see Adverse Reactions ( 6.1 , 6.2 )] . In MK-7365-006, myelosuppression usually occurred during the first few cycles of therapy and was generally not cumulative. The median nadirs occurred at 26 days for platelets (range: 21 to 40 days) and 28 days for neutrophils (range: 1 to 44 days). Approximately 10% of patients required hospitalization, blood transfusion, or discontinuation of therapy due to myelosuppression. Geriatric patients and women have been shown in clinical trials to have a higher risk of developing myelosuppression. Obtain a complete blood count and monitor ANC and platelet counts before initiation of treatment and as clinically indicated during treatment. When TEMOZOLOMIDE is used in combination with radiotherapy, obtain a complete blood count prior to initiation of treatment, weekly during treatment, and as clinically indicated [see Dosage and Administration ( 2.1 , 2.2 , 2.3 )] . For severe myelosuppression, withhold TEMOZOLOMIDE and then resume at same or reduced dose, or permanently discontinue, based on occurrence [see Dosage and Administration ( 2.1 , 2.2 , 2.3 )]. 5.2 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. 5.3 Pneumocystis Pneumonia Pneumocystis pneumonia (PCP) can occur in patients receiving TEMOZOLOMIDE. The risk of PCP is increased in patients receiving steroids or with longer treatment regimens of TEMOZOLOMIDE. 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 for the development of lymphopenia and PCP. 5.4 Secondary Malignancies The incidence of secondary malignancies is increased in patients treated with TEMOZOLOMIDE containing regimens. Cases of myelodysplastic syndrome and secondary malignancies, including myeloid leukemia, have been observed following TEMOZOLOMIDE administration. 5.5 Embryo-Fetal Toxicity Based on findings from animal studies and its mechanism of action, TEMOZOLOMIDE 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 and females of reproductive potential of the potential risk to a fetus. Advise females of reproductive potential to use effective contraception during treatment with TEMOZOLOMIDE and for 6 months after the last 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 and for 3 months after the last dose. Advise male patients not to donate semen during treatment with TEMOZOLOMIDE and for 3 months after the last dose [see Use in Specific Populations ( 8.1 , 8.3 )]. 5.6 Exposure to Opened Capsules Advise patients not to open, chew or dissolve the contents of the TEMOZOLOMIDE capsules. Swallow capsules whole with a glass of water. If a capsule becomes damaged, avoid contact of the powder contents with skin or mucous membranes. In case of powder contact, wash affected area with water immediately [see Dosage and Administration ( 2.4 )] . If TEMOZOLOMIDE capsules must be opened or the contents must be dissolved, this should be done by a professional trained in safe handling of hazardous drugs using appropriate equipment and safety procedures.