Drug information of Temozolomide

Mechanism of effect

Temozolomide is a prodrug and has little, if any, pharmacologic activity until hydrolyzed in vivo to MTIC MTIC is further hydrolyzed to active metabolites that may alkylate DNA at the O6 and N7positions of guanine

Pharmacodynamic

Temozolomide is an imidazotetrazine deritave and an antineoplastic agent. It is a prodrug that has little to no pharmacological activity until it is hydrolyzed in vivo to 5-(3-methyltriazen-1-yl)imidazole-4-carboxamide (MTIC). After administration, temozolomide undergoes rapid, nonenzymatic hydrolysis at physiological pH to MTIC, which is the active form of the drug. MTIC is generated through the effect of water at the highly electropositive C4 position of temozolomide, causing the ring of temozolomide to open, release carbon dioxide, and generate MTIC.

Pharmacokinetics

Rapidly and completely absorbed after oral administration, with nearly 100% bioavailability. Food decreases rate and extent of absorption after oral administration. Plasma Protein Binding:Approximately 15%. Temozolomide is a prodrug. undergoes rapid, nonenzymatic hydrolysis at physiologic pH to MTIC. MTIC is further hydrolyzed to 5-amino-imidazole-4-carboxamide (AIC) and to methylhydrazineCYP isoenzymes play only a minor role in metabolism of temozolomide and MTIC. About 38% of administered dose is recovered over 7 days, principally in urine with <1% in feces. Half-life:Approximately 1.8 hours

Drug indications

Glioblastoma Multiforme , Anaplastic Astrocytoma

Dosage

Usual Adult Dose for Anaplastic Astrocytoma Oral: Initial Dose: 150 mg/m2 orally once a day Maintenance Dose: 200 mg/m2 orally once a day Duration of Therapy: 5 consecutive days per 28-day treatment cycle IV: Initial Dose: 150 mg/m2 IV over 90 minutes once a day Maintenance Dose: 200 mg/m2 IV over 90 minutes once a day Duration of Therapy: 5 consecutive days per 28-day treatment cycle

Drug contraindications

hypersensitivity to drug or its components. , hypersensitivity to dacarbazine

Side effects

nausea , Headache , insomnia , constipation , abdominal pain , dizziness , vomiting , fatigue , Blurred vision , Hepatic dysfunction , allergic reaction , rash , Depression , Diarrhea , Dyspnea , asthenia , pruritus , thrombocytopenia , neutropenia , lymphopenia , leukopenia , Erythema , palpitations , paresthesia , neuropathy , dyspepsia , Urinary tract infection , Peripheral edema , Cough , sinusitis , impotence , Flu-like symptoms , anxiety , Stevens-Johnson syndrome , Alopecia , Infections , anorexia , somnolence , Otitis media , gastritis , Arthralgia , back pain , Upper respiratory tract infection , Tremor , stomatitis , taste perversion , dysphagia , hemorrhoids , eye pain , dry eyes

Interactions

Trastuzumab , Phenobarbital , Phenytoin , Natalizumab , Adenovirus types 4 and 7 live, oral , Remdesivir , Meningococcal conjugate vaccine

Alerts

1-Hematologic Effects:Prolonged pancytopenia reported; may result in potentially fatal aplastic anemia, Myelosuppression (dose-limiting thrombocytopenia and neutropenia,), Hospitalization, blood transfusion, or drug discontinuance may be required. Monitor CBC periodically and adjust dosage and schedule as appropriate 2- Secondary Malignancies:Myelodysplastic syndrome and secondary malignancies, including myeloid leukemia, reported 3- Hepatic Effects:Fatal reactivation of hepatitis B reported 4- Avoid pregnancy during therapy 5- Serious hypersensitivity reactions, including anaphylaxis, erythema multiforme, toxic epidermal necrolysis, and Stevens-Johnson syndrome reported

Points of recommendation

• Importance of adhering to dosage and laboratory appointment schedules. • Importance of PCP prophylaxis for patients with glioblastoma multiforme . Importance of patients informing clinicians of signs and symptoms of PCP infection (e.g., shortness of breath, fever, chills, dry cough). • Importance of women informing clinicians immediately if they are or plan to become pregnant or plan to breast-feed.Advise women and men to avoid pregnancy during therapy. Advise pregnant women of risk to the fetus. • Importance of patients informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs, as well as concomitant illnesses. • Importance of taking temozolomide in a consistent manner relative to food. • Importance of swallowing capsules whole without chewing. • Importance of avoiding exposure to capsule contents and of correct, safe storage and disposal away from children and pets. • Risk of nausea and vomiting. Premedication with antiemetics and bedtime administration recommended.

Pregnancy level

D

Related drugs

Thalidomide , Lomustine , Melphalan , Treosulfan , thiotepa , Bendamustine