Temodar 20mg Capsules
It is used to treat brain cancer.It may be given to you for other reasons. Talk with the doctor.
Drug Class
Antineoplastic agent
Pharmacologic Class
Alkylating agent; DNA methylating agent
Pregnancy Category
Category D
FDA Approved
Aug 1999
DEA Schedule
Not Controlled
Overview
What is this medicine?
Temozolomide is a chemotherapy medicine used to treat certain types of brain tumors. It works by damaging the DNA of cancer cells, which helps to slow or stop their growth. It's often taken as capsules by mouth.
How to Use This Medicine
Taking Your Medication Correctly
To get the most benefit from your medication, follow your doctor's instructions carefully. Read all the information provided to you and follow the instructions closely.
Take your medication at the same time every day.
You can take your medication with or without food, but be consistent in how you take it each time. If you choose to take it with food, always take it with food. If you choose to take it on an empty stomach, always take it on an empty stomach. Taking it on an empty stomach may help prevent stomach upset.
Consider taking your medication at bedtime, as this may also help minimize stomach upset. However, consult with your doctor before making any changes to your dosage schedule.
Your doctor may prescribe other medications to be taken with this drug to help reduce side effects.
Take your medication with a full glass of water.
Swallow the capsule whole; do not chew, break, crush, or dissolve it.
Continuing Your Medication
Continue taking your medication as directed by your doctor or healthcare provider, even if you start feeling well. Your prescribed dose may consist of two or more different strengths and colors of capsules.
Handling and Disposal
If you vomit after taking your medication, do not take an additional dose. Handle your medication with care, and consult your doctor or pharmacist for specific guidance.
Wear gloves when handling the capsules.
If a capsule is opened or broken, avoid touching the contents. Do not inhale the contents of the capsule. If you accidentally touch the contents or get them in your eyes, wash your hands or eyes immediately.
Storage and Disposal
Store your medication at room temperature in a dry place, avoiding storage in a bathroom.
Missing a Dose
If you miss a dose, contact your doctor to determine the best course of action.
To get the most benefit from your medication, follow your doctor's instructions carefully. Read all the information provided to you and follow the instructions closely.
Take your medication at the same time every day.
You can take your medication with or without food, but be consistent in how you take it each time. If you choose to take it with food, always take it with food. If you choose to take it on an empty stomach, always take it on an empty stomach. Taking it on an empty stomach may help prevent stomach upset.
Consider taking your medication at bedtime, as this may also help minimize stomach upset. However, consult with your doctor before making any changes to your dosage schedule.
Your doctor may prescribe other medications to be taken with this drug to help reduce side effects.
Take your medication with a full glass of water.
Swallow the capsule whole; do not chew, break, crush, or dissolve it.
Continuing Your Medication
Continue taking your medication as directed by your doctor or healthcare provider, even if you start feeling well. Your prescribed dose may consist of two or more different strengths and colors of capsules.
Handling and Disposal
If you vomit after taking your medication, do not take an additional dose. Handle your medication with care, and consult your doctor or pharmacist for specific guidance.
Wear gloves when handling the capsules.
If a capsule is opened or broken, avoid touching the contents. Do not inhale the contents of the capsule. If you accidentally touch the contents or get them in your eyes, wash your hands or eyes immediately.
Storage and Disposal
Store your medication at room temperature in a dry place, avoiding storage in a bathroom.
Missing a Dose
If you miss a dose, contact your doctor to determine the best course of action.
Lifestyle & Tips
- Take on an empty stomach (at least 1 hour before or 2 hours after a meal) to reduce nausea and vomiting.
- Take at the same time each day, preferably at bedtime, to minimize nausea.
- Swallow capsules whole with a glass of water; do not open, chew, or crush them.
- If a capsule is accidentally opened or damaged, avoid contact with skin or mucous membranes. Wear gloves to clean up any spilled powder.
- Stay well-hydrated unless otherwise instructed by your doctor.
- Avoid live vaccines during treatment.
- Use effective contraception during treatment and for at least 6 months after for women, and 3 months after for men.
- Report any signs of infection (fever, chills, sore throat) or unusual bleeding/bruising immediately.
Available Forms & Alternatives
Available Strengths:
Generic Alternatives:
Dosing & Administration
Adult Dosing
Standard Dose:
Varies significantly by indication and concomitant therapy. For newly diagnosed glioblastoma multiforme (GBM) with concomitant radiotherapy: 75 mg/m² orally once daily for 42 days, followed by adjuvant phase. For adjuvant phase: 150-200 mg/m² orally once daily for 5 days every 28 days for 6 cycles. For refractory anaplastic astrocytoma: 150 mg/m² orally once daily for 5 days every 28 days, increasing to 200 mg/m² if tolerated.
Dose Range:
75 - 200 mg
Condition-Specific Dosing:
Newly Diagnosed Glioblastoma Multiforme (GBM) with Concomitant Radiotherapy:
75 mg/m² orally once daily for 42 days (concomitant phase).
Adjuvant Phase for Newly Diagnosed GBM:
150 mg/m² orally once daily for 5 days, then increased to 200 mg/m² orally once daily for 5 days if tolerated, every 28 days for 6 cycles.
Refractory Anaplastic Astrocytoma:
Initial: 150 mg/m² orally once daily for 5 days every 28 days. If tolerated, increase to 200 mg/m² orally once daily for 5 days every 28 days.
Pediatric Dosing
Neonatal:
Not established
Infant:
Not established
Child:
Dosing for pediatric patients (≥3 years) with refractory anaplastic astrocytoma or newly diagnosed GBM is generally based on BSA, similar to adult dosing, but specific guidelines should be consulted. Safety and efficacy in pediatric patients <3 years have not been established.
Adolescent:
Dosing based on BSA, similar to adult dosing.
Dose Adjustments
Renal Impairment:
Mild:
No specific dose adjustment recommended.
Moderate:
No specific dose adjustment recommended.
Severe:
Use with caution; no specific dose recommendations due to limited data.
Dialysis:
Not available; use with caution due to limited data.
Hepatic Impairment:
Mild:
No specific dose adjustment recommended.
Moderate:
No specific dose adjustment recommended.
Severe:
Use with caution; no specific dose recommendations due to limited data.
Pharmacology
Mechanism of Action
Temozolomide is an imidazotetrazine derivative that undergoes rapid chemical conversion at physiological pH to the active compound monomethyl triazenoimidazole carboxamide (MTIC). MTIC is an alkylating agent that primarily methylates DNA at the O6 and N7 positions of guanine. This methylation leads to DNA damage, triggering cell cycle arrest (G2/M phase) and ultimately apoptosis, particularly in rapidly dividing tumor cells.
Pharmacokinetics
Absorption:
Bioavailability:
Approximately 100%
Tmax:
0.5-1.5 hours (oral)
FoodEffect:
Food decreases the rate and extent of absorption (Cmax decreased by 33%, AUC by 9%). Should be taken on an empty stomach.
Distribution:
Vd:
0.4 L/kg (similar to total body water)
ProteinBinding:
10-15%
CnssPenetration:
Yes (readily crosses the blood-brain barrier)
Elimination:
HalfLife:
1.8 hours (plasma)
Clearance:
Not available (primarily non-enzymatic degradation)
ExcretionRoute:
Mainly renal (approximately 38% of dose excreted in urine over 7 days, with 5-10% as unchanged drug).
Unchanged:
5-10% (in urine)
Pharmacodynamics
OnsetOfAction:
Not directly applicable (prodrug with rapid conversion)
PeakEffect:
Not directly applicable (cytotoxic effect is cumulative)
DurationOfAction:
Not directly applicable (cytotoxic effects persist due to DNA damage)
Safety & Warnings
BLACK BOX WARNING
Myelosuppression: Temozolomide causes myelosuppression (thrombocytopenia and neutropenia), which may be severe and result in hospitalization and/or death. Obtain a complete blood count (CBC) on Day 22 (or Day 29) of each cycle and weekly during the concomitant phase. Do not administer Temodar if ANC is <1.5 x 10^9/L or platelet count is <100 x 10^9/L. Dose reductions or interruptions may be required.
Side Effects
Urgent Side Effects: Seek Medical Help Right Away
Although rare, this medication can cause severe and potentially life-threatening side effects. If you experience any of the following symptoms, contact your doctor immediately or seek emergency medical attention:
Signs of an allergic reaction, such as:
+ Rash or hives
+ Itching or red, swollen, blistered, or peeling skin (with or without fever)
+ Wheezing or 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 or chills
+ Severe sore throat, ear or sinus pain, or cough
+ Increased or changed sputum production
+ Painful urination
+ Mouth sores or a wound that won't heal
Unexplained bruising or bleeding
Shortness of breath, sudden weight gain, or swelling in the arms or legs
Weakness on one side of the body, difficulty speaking or thinking, balance problems, drooping on one side of the face, or blurred vision
Confusion or 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
+ Nausea or stomach pain
+ Light-colored stools
+ Vomiting
+ Yellowing of the skin or eyes
Other Possible Side Effects
Like all medications, this drug can cause side effects. While many people may not experience any side effects or only minor ones, it's essential to discuss any concerns with your doctor. If you experience any of the following side effects, contact your doctor if they bother you or don't go away:
Hair loss
Headache
Dizziness, drowsiness, fatigue, or weakness
Constipation, diarrhea, stomach pain, nausea, vomiting, or decreased appetite
Sleep disturbances
Back, muscle, or joint pain
Dry skin
Changes in taste
Weight gain
Common cold symptoms
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, 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.
Although rare, this medication can cause severe and potentially life-threatening side effects. If you experience any of the following symptoms, contact your doctor immediately or seek emergency medical attention:
Signs of an allergic reaction, such as:
+ Rash or hives
+ Itching or red, swollen, blistered, or peeling skin (with or without fever)
+ Wheezing or 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 or chills
+ Severe sore throat, ear or sinus pain, or cough
+ Increased or changed sputum production
+ Painful urination
+ Mouth sores or a wound that won't heal
Unexplained bruising or bleeding
Shortness of breath, sudden weight gain, or swelling in the arms or legs
Weakness on one side of the body, difficulty speaking or thinking, balance problems, drooping on one side of the face, or blurred vision
Confusion or 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
+ Nausea or stomach pain
+ Light-colored stools
+ Vomiting
+ Yellowing of the skin or eyes
Other Possible Side Effects
Like all medications, this drug can cause side effects. While many people may not experience any side effects or only minor ones, it's essential to discuss any concerns with your doctor. If you experience any of the following side effects, contact your doctor if they bother you or don't go away:
Hair loss
Headache
Dizziness, drowsiness, fatigue, or weakness
Constipation, diarrhea, stomach pain, nausea, vomiting, or decreased appetite
Sleep disturbances
Back, muscle, or joint pain
Dry skin
Changes in taste
Weight gain
Common cold symptoms
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, 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.
Seek Immediate Medical Attention If You Experience:
- Fever (especially 100.4°F or higher)
- Chills
- Sore throat or other signs of infection
- Unusual bleeding or bruising (e.g., nosebleeds, bleeding gums, petechiae)
- Severe nausea or vomiting that prevents eating or drinking
- Severe fatigue or weakness
- Yellowing of the skin or eyes (jaundice)
- Dark urine or pale stools
- Severe headache
- New or worsening seizures
- Shortness of breath or cough
- Severe skin rash or blistering
Before Using This Medicine
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, such as foods or drugs. Be sure to describe the allergic reaction you experienced.
A specific 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.
Remember, 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 your doctor about the following:
Any allergies you have, including allergies to this medication, its components, or other substances, such as foods or drugs. Be sure to describe the allergic reaction you experienced.
A specific 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.
Remember, do not start, stop, or change the dose of any medication without first consulting your doctor to confirm it is safe to do so.
Precautions & Cautions
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 some 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, wash 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. Use a soft toothbrush and an electric razor to minimize the risk of injury.
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 conducted 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 period after the last dose, as advised by your doctor. If you or your partner becomes pregnant, notify your doctor immediately.
Before receiving any vaccinations, consult with your doctor, as some 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, wash 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. Use a soft toothbrush and an electric razor to minimize the risk of injury.
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 conducted 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 period after the last dose, as advised by your doctor. If you or your partner becomes pregnant, notify your doctor immediately.
Overdose Information
Overdose Symptoms:
- Severe myelosuppression (e.g., profound neutropenia, thrombocytopenia)
- Severe nausea and vomiting
- Fatigue
What to Do:
There is no known antidote for temozolomide overdose. Management is supportive, including frequent monitoring of blood counts and appropriate medical interventions for myelosuppression (e.g., transfusions, growth factors) and other symptoms. Call 1-800-222-1222 (Poison Control) or seek emergency medical attention immediately.
Drug Interactions
Major Interactions
- Valproic acid (decreases temozolomide clearance, potentially increasing myelosuppression)
- Other myelosuppressive agents (additive myelosuppression)
Moderate Interactions
- Cimetidine (may slightly increase temozolomide exposure, clinical significance uncertain)
Monitoring
Baseline Monitoring
Complete Blood Count (CBC) with differential and platelets
Rationale: To establish baseline hematologic parameters before initiating therapy, as myelosuppression is a dose-limiting toxicity.
Timing: Prior to initiation of therapy
Liver function tests (LFTs)
Rationale: To assess baseline hepatic function, although temozolomide is primarily metabolized non-enzymatically.
Timing: Prior to initiation of therapy
Renal function tests (e.g., serum creatinine, BUN)
Rationale: To assess baseline renal function, as a portion of the drug is renally excreted.
Timing: Prior to initiation of therapy
Pneumocystis jirovecii pneumonia (PCP) prophylaxis assessment
Rationale: Patients receiving temozolomide with concomitant radiation are at risk for PCP; prophylaxis is recommended.
Timing: Prior to initiation of therapy
Routine Monitoring
Complete Blood Count (CBC) with differential and platelets
Frequency: Weekly during concomitant phase; prior to each cycle (Day 1) and on Day 22 (or Day 29) of each cycle during adjuvant phase.
Target: Absolute Neutrophil Count (ANC) ≥1.5 x 10^9/L, Platelets ≥100 x 10^9/L for dose initiation/continuation.
Action Threshold: ANC <1.5 x 10^9/L or Platelets <100 x 10^9/L requires dose delay or reduction. ANC <0.5 x 10^9/L or Platelets <10 x 10^9/L requires significant dose modification or discontinuation.
Liver function tests (LFTs)
Frequency: Periodically, especially if signs of hepatic dysfunction develop.
Target: Within normal limits or acceptable for patient's condition.
Action Threshold: Significant elevations may warrant dose modification or discontinuation.
Renal function tests
Frequency: Periodically, as clinically indicated.
Target: Within normal limits or acceptable for patient's condition.
Action Threshold: Significant impairment may warrant caution.
Symptom Monitoring
- Signs of infection (fever, chills, sore throat)
- Unusual bleeding or bruising
- Severe nausea or vomiting
- Severe fatigue or weakness
- Headache
- Seizures
- Allergic reactions (rash, itching, swelling)
- Signs of liver dysfunction (yellowing of skin/eyes, dark urine, abdominal pain)
- Signs of lung toxicity (shortness of breath, cough)
Special Patient Groups
Pregnancy
Temozolomide is classified as Pregnancy Category D. It can cause fetal harm when administered to a pregnant woman. Advise pregnant women of the potential risk to a fetus. Advise females of reproductive potential to use effective contraception during treatment and for at least 6 months after the last dose. Advise males with female partners of reproductive potential to use effective contraception during treatment and for at least 3 months after the last dose.
Trimester-Specific Risks:
First Trimester:
High risk of major birth defects and fetal loss due to its cytotoxic and genotoxic effects.
Second Trimester:
Potential for fetal harm, including growth restriction and organ toxicity.
Third Trimester:
Potential for fetal harm, including myelosuppression in the neonate.
Lactation
It is not known whether temozolomide or its metabolites are excreted in human milk. Because of the potential for serious adverse reactions in breastfed infants, advise women not to breastfeed during treatment with temozolomide and for at least 1 week after the last dose.
Infant Risk:
High risk (L5 - Contraindicated)
Pediatric Use
Safety and effectiveness in pediatric patients <3 years of age have not been established. In pediatric patients ≥3 years of age, dosing is typically based on body surface area, similar to adults. Myelosuppression is a significant concern. Long-term effects on growth and development are not fully characterized.
Geriatric Use
No overall differences in safety or effectiveness were observed between elderly patients (≥65 years) and younger patients, but greater sensitivity of some older individuals cannot be ruled out. Dose adjustments are generally not required based on age alone, but careful monitoring for myelosuppression is crucial.
Clinical Information
Clinical Pearls
- Temozolomide is a prodrug that undergoes spontaneous hydrolysis to its active form, MTIC, at physiological pH. This means its activation is not dependent on liver enzymes.
- Administer on an empty stomach to reduce nausea and vomiting, and to optimize absorption.
- Pneumocystis jirovecii pneumonia (PCP) prophylaxis is strongly recommended for all patients receiving temozolomide with concomitant radiotherapy, and should be considered for all patients during the adjuvant phase, especially those with lymphopenia.
- Capsules should be swallowed whole. If a capsule is opened or damaged, there is a risk of exposure to the active drug, which is an irritant. Handle with gloves.
- Myelosuppression, particularly thrombocytopenia and neutropenia, is the dose-limiting toxicity. Close monitoring of CBC is essential, and dose adjustments are frequently required.
- Patients should be educated on signs of infection and bleeding and instructed to report them immediately.
- Temozolomide is highly lipophilic and readily crosses the blood-brain barrier, which is crucial for its efficacy in brain tumors.
Alternative Therapies
- Carmustine (BCNU)
- Lomustine (CCNU)
- Bevacizumab (for recurrent glioblastoma)
- Optune (tumor treating fields, often used with temozolomide for GBM)
- Other chemotherapy agents depending on tumor type and patient history (e.g., procarbazine, vincristine for anaplastic astrocytoma in PCV regimen)
Cost & Coverage
Average Cost:
Varies widely, typically several thousand dollars per 30 capsules (e.g., 100mg strength)
Generic Available:
Yes
Insurance Coverage:
Specialty Tier (requires prior authorization, often subject to high co-pays or co-insurance)
General Drug Facts
If your symptoms or health issues persist or worsen, it is essential to contact your doctor promptly. To ensure your safety, 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. If you have any questions or concerns about this medication, don't hesitate to discuss them with your doctor, nurse, pharmacist, or other healthcare provider. In the event of a suspected overdose, immediately call your local poison control center or seek medical attention. When seeking help, be prepared to provide information about what was taken, the amount, and the time it happened.