Temozolomide

BRAND NAMES

Temodar, Temodal

The typical dosage is 150 mg/m² taken orally once daily.

MECHANISM OF ACTION

Temozolomide works by converting into its active form, MTIC, in the body. MTIC methylates DNA, primarily targeting the guanine bases, which results in DNA damage. This damage disrupts the cell cycle and ultimately triggers apoptosis, or programmed cell death. However, the drug’s effectiveness can be reduced by cellular DNA repair mechanisms—particularly the enzyme O6-methylguanine-DNA methyltransferase (MGMT), which can repair the methylated DNA and diminish temozolomide’s cytotoxic impact.

PHARMACOKINETICS

Absorption

Temozolomide is a prodrug that is quickly and effectively absorbed when taken orally, with a bioavailability close to 100%. After reaching systemic circulation, it rapidly crosses the blood-brain barrier. 

Distribution

Temozolomide has an average apparent volume of distribution of 0.4L/kg.

Metabolism

Temozolomide (TMZ) is a prodrug that is converted into its active form through spontaneous, non-enzymatic hydrolysis at a physiological pH of 7.4. Unlike many other chemotherapy drugs, its metabolism does not require activation by liver enzymes from the cytochrome P450 system.

Excretion 

Temozolomide is primarily excreted through the kidneys, with about 38% of the dose eliminated in the urine within seven days. By comparison, only roughly 0.8% is eliminated via the feces.

PHARMACODYNAMICS

Temozolomide is an oral alkylating agent and prodrug that exerts its cytotoxic effects by modifying DNA, primarily through methylation. This damage triggers cell cycle arrest and apoptosis (programmed cell death) in rapidly dividing cancer cells, including those in brain tumors like glioblastoma multiforme.

ADMINISTRATION

Take this medication at the same time every day, with or without food. Nausea and vomiting are common side effects of temozolomide, but it is important to keep taking the medication even if you begin to feel sick. Taking it on an empty stomach or at bedtime may help reduce nausea.

DOSAGE AND STRENGTH

Temozolomide is available in two primary dosage forms: oral capsules and an intravenous (IV) injection.

Available strengths are: 

5 mg 

20 mg 

100 mg 

140 mg

 180 mg and 250 mg.

DRUG INTERACTIONS

Temozolomide has several key drug interactions, notably increasing the risk of myelosuppression and infection when combined with other immunosuppressants, chemotherapy, and radiation. The antiseizure drug valproic acid can decrease temozolomide's clearance from the body, potentially increasing its effects and toxicity. Live vaccines, such as those for influenza, measles, and yellow fever, should be avoided, as temozolomide can weaken the immune response and increase the risk of infection. Additionally, interactions with other medications like deferiprone, which also carries a risk of low white blood cell counts, are considered serious.

FOOD INTERACTIONS

Taking it on an empty stomach is generally advised to reduce nausea, a common side effect. A high-fat meal can decrease the drug's absorption. To minimize an upset stomach, some people take the dose at bedtime. For children who cannot swallow the capsule, mixing the contents with a small amount of an acidic food like apple juice is sometimes done under medical supervision, however, this may result in incorrect dosing or cause the drug to break down.

CONTRAINDICATIONS

Temozolomide is contraindicated in patients with a history of serious hypersensitivity reactions to the drug, its components, or the related chemotherapy drug dacarbazine. It is also contraindicated in patients with severe myelosuppression. 

SIDE EFFECTS

Temozolomide is an anticancer medication that can cause both common and serious side effects, primarily due to its impact on bone marrow and the immune system.

• Gastrointestinal issues.

• Hair loss.

• Fatigue.

• Headache.

• Neurological symptoms.

• Skin reactions.

• Mouth sores.

• Blood disorders.

• Liver damage.

• New or secondary cancers.

• Seizures.

OVERDOSE

• Unusual bleeding or bruising.

• Signs of infection, such as fever, persistent sore throat, or congestion.

• Unusual fatigue or weakness.

• Nausea and vomiting.

• Diarrhea.

• Hepatotoxicity.

• Multi-organ failure, in severe cases.

• abdominal pain, or dark urine.

TOXICITY

Temozolomide is an oral alkylating chemotherapy agent for treating brain tumors that is associated with both common and serious toxicities. The most significant risk is myelosuppression, which can be severe and life-threatening. Other toxicities include gastrointestinal issues, liver damage, fatigue, and a risk of opportunistic infections.