Temozolomide 20mg Capsules

Temozolomide is an imidazotetrazine derivative that functions as a prodrug. It undergoes rapid non-enzymatic chemical conversion at physiological pH to the active compound 3-methyl-(triazen-1-yl)imidazole-4-carboxamide (MTIC). MTIC then spontaneously hydrolyzes to the active methylating agent, methyldiazonium ion. This ion methylates DNA at various sites, primarily at the O6 and N7 positions of guanine. The O6-methylguanine adduct is the most cytotoxic lesion, leading to DNA mismatch repair pathway activation, subsequent double-strand breaks, and ultimately apoptosis (programmed cell death) in rapidly dividing cancer cells.

Urgent Side Effects: Seek Medical Help Right Away

Although rare, some people may experience severe and potentially life-threatening side effects while taking this medication. If you notice any of the following symptoms, contact your doctor or seek immediate medical attention:

Signs of an allergic reaction, such as:
+ Rash
+ Hives
+ Itching
+ Red, swollen, blistered, or peeling skin with or without fever
+ Wheezing
+ Tightness in the chest or throat
+ Trouble breathing, swallowing, or talking
+ Unusual hoarseness
+ Swelling of the mouth, face, lips, tongue, or throat
Signs of infection, including:
+ Fever
+ Chills
+ Severe sore throat
+ Ear or sinus pain
+ Cough
+ Increased or changed sputum production
+ Pain while urinating
+ Mouth sores
+ Wounds that won't heal
Unexplained bruising or bleeding
Shortness of breath, significant weight gain, or swelling in the arms or legs
Weakness on one side of the body, trouble speaking or thinking, balance changes, drooping on one side of the face, or blurred vision
Confusion
Mood changes
Difficulty swallowing
Loss of bladder control
Memory problems or loss
Abnormal burning, numbness, or tingling sensations
Seizures
Changes in vision
Pinpoint red spots on the skin
Breast pain
Signs of severe and potentially life-threatening liver problems, including:
+ Dark urine
+ Fatigue
+ Decreased appetite
+ Upset stomach or stomach pain
+ Light-colored stools
+ Vomiting
+ Yellow skin or eyes

Other Possible Side Effects

Like all medications, this drug can cause side effects. Many people may not experience any side effects or only minor ones. If you notice any of the following side effects or any other unusual symptoms, contact your doctor or seek medical help if they bother you or persist:

Hair loss
Headache
Dizziness, drowsiness, tiredness, or weakness
Constipation, diarrhea, stomach pain, upset stomach, vomiting, or decreased appetite
Trouble sleeping
Back, muscle, or joint pain
Dry skin
Changes in taste
Weight gain
Signs of a common cold
* Mouth irritation or mouth sores

Reporting Side Effects

This list is not exhaustive, and you may experience other side effects. If you have questions or concerns about side effects, contact your doctor. You can also report side effects to the FDA at 1-800-332-1088 or online at https://www.fda.gov/medwatch.

Before Taking This Medication: Important Information to Share with Your Doctor

It is essential to inform your doctor about the following:

Any allergies you have, including allergies to this medication, its components, or other substances. Be sure to describe the allergic reaction and its symptoms.
A known allergy to dacarbazine.
If you have a low white blood cell count (leukopenia) or a low platelet count (thrombocytopenia).
If you are breastfeeding. Note that you should not breastfeed while taking this medication and for 1 week after your last dose.

To ensure safe treatment, it is crucial to discuss the following with your doctor and pharmacist:

All medications you are currently taking, including prescription and over-the-counter (OTC) drugs, natural products, and vitamins.
Any existing health problems.
* Potential interactions between this medication and other substances or health conditions.

Do not start, stop, or change the dose of any medication without first consulting your doctor to confirm it is safe to do so.

It is essential to inform all your healthcare providers, including doctors, nurses, pharmacists, and dentists, that you are taking this medication. Regular blood tests will be necessary, as directed by your doctor, to monitor your condition. Be sure to discuss your test results with your doctor.

Before receiving any vaccinations, consult with your doctor, as certain vaccines may not be effective or may increase the risk of infection when taken with this medication.

If you experience stomach upset, vomiting, diarrhea, or a decrease in appetite, talk to your doctor, as there may be ways to minimize these side effects.

This medication can cause low blood cell counts, which may lead to bleeding problems, infections, or anemia. In severe cases, low blood cell counts can be life-threatening and may require hospitalization or blood transfusions. If you have any concerns, discuss them with your doctor.

You may be more susceptible to infections due to this medication. To reduce the risk of infection, practice good hygiene by washing your hands frequently and avoid close contact with people who have infections, colds, or flu.

Be cautious, as this medication can increase the risk of bleeding. To minimize this risk, use a soft toothbrush and an electric razor, and avoid injuries.

Rare but serious side effects of this medication include bone marrow problems and the development of secondary cancers. Discuss these risks with your doctor.

If you are 70 years or older, use this medication with caution, as you may be more prone to side effects.

This medication may affect fertility in men. Discuss this potential side effect with your doctor.

The medication is present in semen, so do not donate semen while taking this medication or for 3 months after your last dose.

This medication can harm an unborn baby. A pregnancy test will be performed before starting the medication to confirm that you are not pregnant. If you or your partner may become pregnant, use effective birth control during treatment and for a specified period after the last dose, as advised by your doctor. If you or your partner becomes pregnant, notify your doctor immediately.

• Valproic acid (may decrease temozolomide clearance, requiring dose reduction of temozolomide)
• Myelosuppressive agents (additive myelosuppression)

• Phenytoin (may decrease temozolomide levels, monitor for decreased efficacy)
• Dexamethasone (commonly co-administered, monitor for additive side effects like hyperglycemia, immunosuppression)

• Signs of myelosuppression (fever, chills, sore throat, unusual bruising, bleeding, petechiae)
• Gastrointestinal toxicity (nausea, vomiting, constipation, diarrhea, abdominal pain)
• Fatigue
• Headache
• Neurological changes (seizures, confusion, memory problems)
• Skin rash
• Hair loss (alopecia)
• Signs of opportunistic infections (e.g., Pneumocystis jirovecii pneumonia - PCP, requiring prophylaxis)

Category D. Temozolomide can cause fetal harm when administered to a pregnant woman. Advise pregnant women of the potential risk to the fetus. Women of reproductive potential should be advised to use effective contraception during treatment and for at least 6 months after the last dose.

Contraindicated. It is not known whether temozolomide is excreted in human milk. Because of the potential for serious adverse reactions in breastfed infants, women should be advised not to breastfeed during treatment with temozolomide and for at least one week after the last dose.

Safety and efficacy have not been established in children under 3 years of age. For children 3 years and older, temozolomide is approved for certain indications (e.g., newly diagnosed GBM, refractory anaplastic astrocytoma). Dosing is BSA-based and requires careful monitoring for myelosuppression and other adverse effects.

No overall differences in safety or effectiveness were observed between elderly patients and younger patients in clinical trials. However, elderly patients (≥70 years) may be at increased risk of myelosuppression, particularly lymphopenia. Close monitoring of blood counts is recommended.

• Temozolomide capsules should be swallowed whole with a glass of water. Do not open, chew, or crush them. If a capsule is accidentally opened or damaged, avoid contact with the powder and wash any exposed skin thoroughly.
• Administer on an empty stomach or at bedtime to minimize nausea and vomiting, which are common side effects.
• Prophylaxis for *Pneumocystis jirovecii* pneumonia (PCP) is strongly recommended for all patients receiving temozolomide with concomitant radiotherapy, and for patients who develop lymphopenia during adjuvant therapy, due to increased risk of opportunistic infections.
• Myelosuppression, particularly thrombocytopenia and neutropenia, is the dose-limiting toxicity. Blood counts must be monitored frequently, and dose adjustments are often necessary.
• Fatigue is a very common side effect; advise patients to plan for rest periods.
• Patients should be educated on signs of infection and bleeding and instructed to report them immediately.

• Surgery (resection of tumor)
• Radiation therapy
• Other chemotherapeutic agents (e.g., PCV regimen: Procarbazine, Lomustine, Vincristine)
• Tumor Treating Fields (TTFields, e.g., Optune)
• Targeted therapies (e.g., BRAF inhibitors for specific mutations)
• Immunotherapy (e.g., checkpoint inhibitors, though less established for primary brain tumors)

If your symptoms or health issues persist or worsen, it is essential to contact your doctor promptly. To ensure safe and effective treatment, never share your medication with others or take someone else's medication. Some medications may come with an additional patient information leaflet, so it's a good idea to check with your pharmacist for more information. If you have any questions or concerns about your medication, don't hesitate to reach out to your doctor, nurse, pharmacist, or other healthcare provider. In the event of a suspected overdose, immediately call your local poison control center or seek emergency medical attention. When seeking help, be prepared to provide details about the medication taken, the amount, and the time it happened.