Temozolomide 5 mg Capsule, 5-count
Other active recalls for Temozolomide (different manufacturers) — 1 · tap to view
🆔 Identity & classification
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🏷️ RxNorm drug class
This medicine belongs to the Alkylating Drug class.
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🏭 Manufacturer & labeler
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🩺 Clinical
Temozolomide is used to treat certain types of brain tumors. Temozolomide is in a class of medications called alkylating agents. It works by slowing or stopping the growth of cancer cells in your body.
Read the full MedlinePlus article ↗- Temozolomide is a chemotherapy drug used to treat aggressive brain tumors in adults. It's most commonly used for glioblastoma — one of the most serious types of brain cancer — give...
- Food does affect how temozolomide is absorbed — a high-fat meal can reduce how much reaches your bloodstream and slow its absorption. That said, your prescriber will give you speci...
- Should I take this with food or on an empty stomach?
- The most common things people notice are nausea, vomiting, fatigue, hair loss, headache, constipation, and reduced appetite — these are expected and your team can help manage them....
Patient education
Supplement & herbal interactions
Some supplements/herbs that may interact with Temozolomide — tap one for details:
Temozolomide may be associated with lower levels of 1 nutrient — worth a chat with your pharmacist, not a cause for alarm.
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Ask a licensed pharmacist directly — free, answered by our team.
💊 What it looks like
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🧪 Inactive Ingredients / Excipients
Inactive ingredients, also called excipients, are components of the drug product other than the active ingredient. They may include fillers, dyes, coatings, preservatives, flavors, or other formulation ingredients.
💡 Tap an ingredient (hover on desktop) to see what it is and why it’s used.
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UNII 3K9958V90M
A liquid solvent derived from fermentation or chemical synthesis. In medicines, alcohol dissolves active ingredients, helps preserve the product, and improves how the body absorbs certain drugs.
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UNII 5138Q19F1X
Ammonia is a colorless gas made from nitrogen and hydrogen. It's used in medicines as a pH buffer to maintain the correct acidity level and help keep the product stable.
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UNII 3SY5LH9PMK
Anhydrous lactose is a milk sugar with no water content. It acts as a filler and binder in tablets and capsules, adding bulk and helping ingredients stick together.
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UNII 8PJ61P6TS3
Butyl alcohol is a clear liquid organic solvent derived from petroleum or natural sources. In medicines, it helps dissolve active ingredients and serves as a solvent in liquid formulations and some topical products.
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UNII H3R47K3TBD
FD&C Blue No. 1 is a synthetic blue dye approved for use in foods and medicines. It serves as a colorant to give the medication its distinctive appearance and help with product identification.
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UNII EX438O2MRT
Ferric oxide yellow is a naturally occurring iron compound used as a colorant in medications. It gives tablets, capsules, and other forms a yellow or golden hue for identification and appearance.
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UNII 2G86QN327L
Gelatin is a protein derived from animal collagen, commonly used in medicines as a gelling agent and capsule material. It helps create soft or hard capsule shells that hold and release medication, and can also thicken liquid formulations.
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UNII 6DC9Q167V3
Propylene glycol is a clear liquid derived from petroleum or vegetable sources. It acts as a solvent, humectant, and preservative in medicines, helping dissolve active ingredients and maintain product stability.
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UNII 46N107B71O
Shellac is a natural resin secreted by the lac beetle. It's used as a coating on tablets and capsules to control how quickly the medicine dissolves and to improve appearance and stability.
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UNII 368GB5141J
A detergent and foaming agent derived from coconut or palm oil. In medications, it helps break down and mix oil and water-based ingredients, aids in tablet disintegration, and improves how the drug dissolves and spreads in the mouth or digestive system.
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UNII AG9B65PV6B
A starch derivative made from corn that helps tablets and capsules break apart quickly when swallowed. It acts as a disintegrant, allowing the medicine to dissolve and be absorbed in your stomach and intestines.
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UNII 4ELV7Z65AP
Stearic acid is a fatty acid derived from plant or animal sources. It acts as a binder and lubricant in tablets and capsules, helping them hold together and flow smoothly during manufacturing.
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UNII W4888I119H
Tartaric acid is a natural organic acid found in grapes and tamarinds. In medicines, it works as a buffer to control acidity, an antioxidant to prevent spoilage, and sometimes a flavoring or binding agent.
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UNII 15FIX9V2JP
Titanium dioxide is a bright white mineral powder commonly used as a colorant and opacifying agent. It makes pills and tablets white or lighter in color and helps make coatings non-transparent.
14 inactive ingredients listed in the exact product block matched to this NDC.
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ingredient classCode="IACT" elements from the exact product block matched by this NDC. Label-section narrative from DailyMed / the openFDA label index is shown separately when available.Inactive ingredient FAQ
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💲 Pricing
A drug doesn't have one price. Each row is a different public payment system, and none is what you'd pay at the counter — that depends on your insurance. The ⓘ on each row explains what it measures.
| Price system | Per each | Per package |
|---|---|---|
| Retail pharmacies payNADAC · weekly | Not in the retail survey — common for institutional, discontinued, or low-volume packs. | |
| Medicaid paysCMS SDUD · 12 mo | No recent Medicaid claims on file for this NDC — rare and low-volume NDCs are suppressed in the public data. | |
| Medicare drug plans payPart D · quarterly | No Part D plan price is available for this NDC in our data. | |
| Medicare Part B allowsASP · NONE | No ASP payment limit on file for NONE this quarter. | |
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🧾 Billing & reimbursement
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🔁 Therapeutic equivalents
| Product | Labeler | Pack | NADAC/unit | TE | Status | Price vs. this |
|---|---|---|---|---|---|---|
| Temozolomide 5 mg 16729-0048-53 | Accord | 5 capsules | $1.931 | AB | Availability likely | — |
| Temozolomide 5 mg 31722-0411-14 | Camber | 14 capsules | $1.931 | AB | Availability likely | — |
| Temozolomide 5 mg 65162-0801-14 | Amneal | 14 capsules | $1.931 | AB | Availability likely | — |
| Temozolomide 5 mg 67877-0537-07 | Ascend | 5 capsules | $1.931 | AB | Availability likely | — |
| Temozolomide 5 mg 73043-0011-05 | Devatis, | 5 capsules | $1.931 | AB | Availability likely | — |
| Temodar 5 mg 00085-3004-03 | Merck | 5 capsules | — | — | FDA listed | — |
| Temozolomide 5 mg 16571-0816-02 | Rising | 20 capsules | — | AB | FDA listed | — |
| Temozolomide 5 mgthis 47335-0890-80 | Sun | 5 capsules | — | AB | FDA listed | — |
| Temozolomide 5 mg 72162-2659-02 | Bryant | 5 capsules | — | AB | FDA listed | — |
| temozolomide 5 mg 75834-0132-05 | Nivagen | 5 capsules | — | — | FDA listed | — |
| Temozolomide 5 mg 82249-0404-05 | CivicaScript | 5 capsules | — | AB | FDA listed | — |
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⏳ Availability & generic status
This product is an FDA-approved generic. Other versions of the same drug are listed under Therapeutic equivalents, least expensive first.
Where does this data come from?
📊 Medicare Part D spend CMS · PART D · 2025 (Q1-Q4)
🔬 Reported adverse events (FAERS)
Top reported reactions
Reporter sex
Serious outcomes
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📦 Packaging — all sizes for this product
| Package NDC | Description | Per unit | Per pack | Marketing start | Status |
|---|---|---|---|---|---|
| 47335-0890-21 | 1 BOTTLE in 1 CARTON (47335-890-21) / 14 CAPSULE in 1 BOTTLE | — | — | 2014-02-13 | Active |
| 47335-0890-72 | 15 BLISTER PACK in 1 CARTON (47335-890-72) / 1 CAPSULE in 1 BLISTER PACK | $1.93 / ea | $28.97 | 2014-02-13 | Active |
| 47335-0890-74 | 5 BLISTER PACK in 1 CARTON (47335-890-74) / 1 CAPSULE in 1 BLISTER PACK | $1.93 / ea | $9.66 | 2014-02-13 | Active |
| 47335-0890-75 | 20 BLISTER PACK in 1 CARTON (47335-890-75) / 1 CAPSULE in 1 BLISTER PACK | — | — | 2014-02-13 | Active |
| 47335-0890-80 You're viewing this | 1 BOTTLE in 1 CARTON (47335-890-80) / 5 CAPSULE in 1 BOTTLE | — | — | 2014-02-13 | Active |
| 47335-0890-87 | 1 BOTTLE in 1 CARTON (47335-890-87) / 20 CAPSULE in 1 BOTTLE | — | — | 2014-02-13 | Active |
Pack size FAQ
What quantity is in NDC 47335-0890-80?
What is the difference between NDC 47335-0890-80 and NDC 47335-0890-74?
What NDC number is used to bill for this package of Temozolomide 5 mg Capsule?
Prices are the latest CMS NADAC pharmacy acquisition cost per NDC; per-pack figures are per-unit × pack quantity, shown only when the pack is denominated in the same measure NADAC prices.
🧭 About this NDC listing & data coverage
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| NDC identity (package / product / labeler codes) | ✓ Available |
| Labeler | ✓ Available |
| Product & package description | ✓ Available |
| Marketing category & status | ✓ Available |
| Active ingredient / dosage form / route | ✓ Available |
| FDA label (SPL via DailyMed) | ✓ Available |
| Package photos | ✓ Available |
| Inactive ingredients (structured) | ✓ Available |
| NADAC pharmacy acquisition price (CMS) | — Not published for this NDC CMS publishes NADAC only for NDCs reported in its retail-pharmacy survey. |
| Orange Book / therapeutic-equivalence data | ✓ Available |
| HCPCS J-code billing crosswalk | ✓ Available |
| Medicaid utilization (CMS SDUD) | — Not published for this NDC CMS reports utilization only for NDCs with Medicaid claims above its privacy threshold. |
Questions about this listing
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📄 Full prescribing information FDA SPL
🎯 Indications and Usage ▾
1 INDICATIONS AND USAGE Temozolomide is an alkylating drug indicated for the treatment of adults with: • Newly diagnosed glioblastoma concomitantly with radiotherapy and then as maintenance treatment. (1.1) • Anaplastic astrocytoma. (1.2) o Adjuvant treatment of adults with newly diagnosed anaplastic astrocytoma. (1.2) o Treatment of adults with refractory anaplastic astrocytoma. (1.2)
1.1Newly Diagnosed Glioblastoma Temozolomide capsules are indicated for the treatment of adults with newly diagnosed glioblastoma, concomitantly with radiotherapy and then as maintenance treatment.
1.2Anaplastic Astrocytoma Temozolomide capsules are indicated for the: • adjuvant treatment of adults with newly diagnosed anaplastic astrocytoma; • treatment of adults with refractory anaplastic astrocytoma.
⏱️ Dosage and Administration ▾
2 DOSAGE AND ADMINISTRATION Administer orally. (2.4) Newly Diagnosed Glioblastoma: o 75 mg/m2 once daily for 42 to 49 days concomitant with focal radiotherapy followed by initial maintenance dose of 150 mg/m2 once daily for Days 1 to 5 of each 28-day cycle for 6 cycles. May increase maintenance dose to 200 mg/m2 for Cycles 2 to 6 based on toxicity.
(2.1) o Provide Pneumocystis pneumonia (PCP) prophylaxis during concomitant phase and continue in patients who develop lymphopenia until resolution to Grade 1 or less. (2.1) Adjuvant Treatment of Newly Diagnosed Anaplastic Astrocytoma: Beginning 4 weeks after the end of radiotherapy, administer temozolomide orally in a single dose on days 1 to 5 of a 28-day cycle for 12 cycles. The recommended dosage for Cycle 1 is 150 mg/m2 per day and for Cycles 2 to 12 is 200 mg/m2 if patient experienced no or minimal toxicity in Cycle 1.
(2.2) Refractory Anaplastic Astrocytoma: Initial dose of 150 mg/m2 once daily on Days 1 to 5 of each 28-day cycle. (2.2)
2.1Monitoring to Inform Dosage and Administration Prior to dosing, withhold temozolomide capsules until patients have an absolute neutrophil count (ANC) of 1.5 x 10 9 /L or greater and a platelet count of 100 x 10 9 /L or greater. For concomitant radiotherapy, obtain a complete blood count prior to initiation of treatment and weekly during treatment. For the 28-day treatment cycles, obtain a complete blood count prior to treatment on Day 1 and on Day 22 of each cycle.
Perform complete blood counts weekly until recovery if the ANC falls below 1.5 x 10 9 /L and the platelet count falls below 100 x 10 9 /L. For concomitant use with focal radiotherapy, obtain a complete blood count weekly and as clinically indicated.
2.2Recommended Dosage and Dosage Modifications for Newly Diagnosed Glioblastoma Administer temozolomide capsules once daily for 42 to 49 consecutive days during the concomitant use phase with focal radiotherapy, and then once daily on Days 1 to 5 of each 28-day cycle for 6 cycles during the maintenance use phase. Provide Pneumocystis pneumonia (PCP) prophylaxis during the concomitant use phase and continue in patients who develop lymphopenia until resolution to Grade 1 or less [see Warnings and Precautions (5.3)]. Concomitant Use Phase: The recommended dosage of temozolomide capsules is 75 mg/m2 once daily for 42 to 49 days in combination with focal radiotherapy.
Focal radiotherapy includes the tumor bed or resection site with a 2 to 3 cm margin. Other administration schedules have been used. Obtain a complete blood count weekly.
The recommended dosage modifications due to adverse reactions during concomitant use phase are provided in Table 1. TABLE 1: Dosage Modifications Due to Adverse Reactions During Concomitant Use Phase Adverse Reaction Interruption Discontinuation Absolute Neutrophil Count Withhold temozolomide capsules if ANC is greater than or equal to 0.5 x 10 9 /L and less than 1.5 x 10 9 /L. Resume temozolomide capsules at the same dose when ANC is greater than or equal to 1.5 x 109/L.
Discontinue temozolomide capsules if ANC is less than 0.5 × 10 9 /L Platelet Count Withhold temozolomide capsules if platelet count is greater than or equal to 10 x 10 9 /L and less than 100 x 10 9 /L. Resume temozolomide capsules at the same dose when platelet count is greater than or equal to 100 x 109/L. Discontinue temozolomide capsules if platelet count is less than 10 × 10 9 /L Non-hematological Adverse Reaction (except for alopecia, nausea, vomiting) Withhold temozolomide capsules if Grade 2 adverse reaction occurs.
Resume temozolomide capsules at the same dose when resolution to Grade 1 or less. Discontinue temozolomide capsules if Grade 3 or 4 adverse reaction occurs. Single Agent Maintenance Use Phase: Beginning 4 weeks after concomitant use phase completion, administer temozolomide capsules once daily on Days 1 to 5 of each 28-day cycle for 6 cycles.
The recommended dosage of temozolomide capsules in the maintenance use phase is…
💊 Dosage Forms and Strengths ▾
3 DOSAGE FORMS AND STRENGTHS 5 mg hard gelatin capsules have white opaque caps and bodies, imprinted with band and the dosage strength “5 mg” on body and “890” on cap in green ink, containing white to light tan/light pink powder. 20 mg hard gelatin capsules have white opaque caps and bodies, imprinted with band and the dosage strength “20 mg” on body and “891” on cap in yellow ink, containing white to light tan/light pink powder. 100 mg hard gelatin capsules have white opaque caps and bodies, imprinted with band and the dosage strength “100 mg” on body and “892” on cap in pink ink, containing white to light tan/light pink powder.
140 mg hard gelatin capsules have white opaque caps and bodies, imprinted with band and the dosage strength “140 mg” on body and “929” on cap in blue ink, containing white to light tan/light pink powder. 180 mg hard gelatin capsules have white opaque caps and bodies, imprinted with band and the dosage strength “180 mg” on body and “930” on cap in reddish brown ink, containing white to light tan/light pink powder. 250 mg hard gelatin capsules have white opaque caps and bodies, imprinted with band and the dosage strength “250 mg” on body and “893” on cap in black ink, containing white to light tan/light pink powder.
Capsules: 5 mg, 20 mg, 100 mg, 140 mg, 180 mg, and 250 mg. (3)
⛔ Contraindications ▾
4 CONTRAINDICATIONS Temozolomide is contraindicated in patients with a history of serious hypersensitivity reactions to: temozolomide or any other ingredients in temozolomide capsules; and dacarbazine, since both temozolomide and dacarbazine are metabolized to the same active metabolite 5-(3-methyltriazen-1-yl)-imidazole-4-carboxamide. Reactions to temozolomide have included anaphylaxis [see Adverse Reactions (6.2)]. History of serious hypersensitivity to temozolomide or any other ingredients in temozolomide capsules and dacarbazine.
(4)
⚠️ 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)
5.1Myelosuppression 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)].
5.2Hepatotoxicity 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.
5.3Pneumocystis Pneumonia Pneumocystis pneumonia (PCP) has been reported 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 PCP prophylaxis 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.
5.4Secondary 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.
5.5Embryo-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…
🤒 Adverse Reactions ▾
6 ADVERSE REACTIONS The following clinically significant adverse reactions are described elsewhere in the labeling: Myelosuppression [see Warnings and Precautions (5.1)] Hepatotoxicity [see Warnings and Precautions (5.2)] Pneumocystis Pneumonia [see Warnings and Precautions (5.3)] Secondary Malignancies [see Warnings and Precautions (5.4)] The most common adverse reactions (≥20%) are: alopecia, fatigue, nausea, vomiting, headache, constipation, anorexia, and convulsions. (6.1) The most common Grade 3 to 4 hematologic laboratory abnormalities (≥10%) in patients with anaplastic astrocytoma are: decreased lymphocytes, decreased platelets, decreased neutrophils, and decreased leukocytes.
(6.1) To report SUSPECTED ADVERSE REACTIONS, contact Sun Pharmaceutical Industries, Inc. at 1-800-818-4555 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.
6.1Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. Newly Diagnosed Glioblastoma The safety of temozolomide was evaluated in study MK-7365-051 [see Clinical Studies (14.1)]. Severe or life-threatening adverse reactions occurred in 49% of patients treated with temozolomide; the most common were fatigue (13%), convulsions (6%), headache (5%), and thrombocytopenia (5%).
The most common adverse reactions (≥20%) in patients treated with temozolomide were alopecia, fatigue, nausea, anorexia, headache, constipation and vomiting. Table 3 summarizes the adverse reactions in MK-7365-051. TABLE 3: Adverse Reactions (≥10%) in Patients with Newly Diagnosed Glioblastoma Adverse Reactions Concomitant Use Phase Maintenance Use Phase Radiation Therapy and temozolomide N=288* Radiation Therapy Alone N=285 Temozolomide N=224 All Grades (%) Grade ≥3 (%) All Grades (%) Grade ≥3 (%) All Grades (%) Grade ≥3 (%) Skin and Subcutaneous Tissue Alopecia 69 0 63 0 55 0 Rash 19 1 15 0 13 1 General Fatigue 54 7 49 5 61 9 Anorexia 19 1 9 <1 27 1 Headache 19 2 17 4 23 4 Gastrointestinal System Nausea 36 1 16 <1 49 1 Vomiting 20 <1 6 <1 29 2 Constipation 18 1 6 0 22 0 Diarrhea 6 0 3 0 10 1 Central and Peripheral Nervous System Convulsions 6 3 7 3 11 3 * One patient who was randomized to radiation therapy-only arm received radiation therapy and temozolomide.
NOS = not otherwise specified. Note: Grade 5 (fatal) adverse reactions are included in the Grade ≥3 column. Clinically relevant adverse reactions in <10% of patients are presented below: Central & Peripheral Nervous System: memory impairment, confusion Eye: vision blurred Gastrointestinal System: stomatitis, abdominal pain General: weakness, dizziness Immune System: allergic reaction Injury: radiation injury not otherwise specified Musculoskeletal System: arthralgia Platelet, Bleeding, & Clotting: thrombocytopenia Psychiatric: insomnia Respiratory System: coughing, dyspnea Special Senses Other: taste perversion Skin & Subcutaneous Tissue: dry skin, pruritus, erythema When laboratory abnormalities and adverse reactions were combined, Grade 3 or Grade 4 neutrophil abnormalities including neutropenic reactions were observed in 8% of patients, and Grade 3 or Grade 4 platelet abnormalities including thrombocytopenic reactions were observed in 14% of patients.
Newly Diagnosed Anaplastic Astrocytoma The safety of temozolomide for the adjuvant treatment of adults with newly diagnosed anaplastic astrocytoma was derived from published literature [see Clinical Studies (14.2)]. The safety of temozolomide for the adjuvant treatment of patients with newly diagnosed anaplastic astrocytoma was consistent with the known safety profile of temozolomide. Refractory Anaplastic Astrocytoma The safety of temozolomide was evaluated in study MK-7365-006 [see Clinical Studies (14.2)].
The most common adverse reactions (≥20%) were nausea, vomiting, headache, fat…
👥 Use in Specific Populations ▾
8 USE IN SPECIFIC POPULATIONS Lactation: Advise not to breastfeed. (8.2)
8.1Pregnancy Risk Summary Based on findings from animal studies and its mechanism of action [see Clinical Pharmacology (12.1)], temozolomide can cause fetal harm when administered to a pregnant woman. Available postmarketing reports describe cases of spontaneous abortions and congenital malformations, including polymalformations with central nervous system, facial, cardiac, skeletal, and genitourinary system anomalies with exposure to temozolomide during pregnancy. These cases report similar adverse developmental outcomes to those observed in animal studies.
Administration of temozolomide to rats and rabbits during the period of organogenesis caused numerous external, internal, and skeletal malformations at doses less than the maximum human dose based on body surface area (see Data) . Advise pregnant women of the potential risk to a fetus. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively.
Data Animal Data Five consecutive days of oral administration of temozolomide at doses of 75 and 150 mg/m 2 (0.38 and 0.75 times the human dose of 200 mg/m 2 ) in rats and rabbits, respectively, during the period of organogenesis (Gestation Days 8 to 12) caused numerous malformations of the external and internal organs and skeleton in both species. In rabbits, temozolomide at the 150 mg/m 2 dose (0.75 times the human dose of 200 mg/m 2 ) caused embryolethality as indicated by increased resorptions.
8.2Lactation There are no data on the presence of temozolomide or its metabolites in human milk, the effects on a breastfed child, or the effects on milk production. Because of the potential for serious adverse reactions, including myelosuppression from temozolomide in the breastfed children, advise women not to breastfeed during treatment with temozolomide and for 1 week after the last dose.
8.3Females and Males of Reproductive Potential Temozolomide can cause fetal harm when administered to a pregnant woman [see Use in Specific Populations (8.1)]. Pregnancy Testing Verify pregnancy status in females of reproductive potential prior to initiating temozolomide [see Use in Specific Populations (8.1)] . Contraception Females Advise females of reproductive potential to use effective contraception during treatment with temozolomide and for 6 months after the last dose.
Males Because of the potential for embryofetal toxicity and genotoxic effects on sperm cells, advise male patients with pregnant partners or female partners of reproductive potential to use condoms during treatment with temozolomide and for 3 months after the last dose [see Use in Specific Populations (8.1), Nonclinical Toxicology (13.1)]. Advise male patients not to donate semen during treatment with temozolomide and for 3 months after the last dose. Infertility Temozolomide may impair male fertility [see Nonclinical Toxicology (13.1 ) ] .
Limited data from male patients show changes in sperm parameters during treatment with temozolomide; however, no information is available on the duration or reversibility of these changes.
8.4Pediatric Use Safety and effectiveness of temozolomide have not been established in pediatric patients. Safety and effectiveness of temozolomide capsules were assessed, but not established, in 2 open-label studies in pediatric patients aged 3 to 18 years. In one study, 29 patients with recurrent brain stem glioma and 34 patients with recurrent high-grade astrocytoma were enrolled.
In a second study conducted by the Children’s Oncology Group (COG), 122 patients were enrolled, including patients with medulloblastoma/PNET (29), high grade astrocytoma (23), low grade astrocytoma (22), brain stem glioma (16), ependymoma (14), other CNS tumors (9), and non-CNS tumors (9). The adverse reaction profile in pediatric patients was similar to adults.
8.5 Geriatric Use In M…
🤰 Pregnancy ▾
8.1Pregnancy Risk Summary Based on findings from animal studies and its mechanism of action [see Clinical Pharmacology (12.1)], temozolomide can cause fetal harm when administered to a pregnant woman. Available postmarketing reports describe cases of spontaneous abortions and congenital malformations, including polymalformations with central nervous system, facial, cardiac, skeletal, and genitourinary system anomalies with exposure to temozolomide during pregnancy. These cases report similar adverse developmental outcomes to those observed in animal studies.
Administration of temozolomide to rats and rabbits during the period of organogenesis caused numerous external, internal, and skeletal malformations at doses less than the maximum human dose based on body surface area (see Data) . Advise pregnant women of the potential risk to a fetus. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively.
Data Animal Data Five consecutive days of oral administration of temozolomide at doses of 75 and 150 mg/m 2 (0.38 and 0.75 times the human dose of 200 mg/m 2 ) in rats and rabbits, respectively, during the period of organogenesis (Gestation Days 8 to 12) caused numerous malformations of the external and internal organs and skeleton in both species. In rabbits, temozolomide at the 150 mg/m 2 dose (0.75 times the human dose of 200 mg/m 2 ) caused embryolethality as indicated by increased resorptions.
🧒 Pediatric Use ▾
8.4Pediatric Use Safety and effectiveness of temozolomide have not been established in pediatric patients. Safety and effectiveness of temozolomide capsules were assessed, but not established, in 2 open-label studies in pediatric patients aged 3 to 18 years. In one study, 29 patients with recurrent brain stem glioma and 34 patients with recurrent high-grade astrocytoma were enrolled.
In a second study conducted by the Children’s Oncology Group (COG), 122 patients were enrolled, including patients with medulloblastoma/PNET (29), high grade astrocytoma (23), low grade astrocytoma (22), brain stem glioma (16), ependymoma (14), other CNS tumors (9), and non-CNS tumors (9). The adverse reaction profile in pediatric patients was similar to adults.
🧓 Geriatric Use ▾
8.5Geriatric Use In MK-7365-051, 15% of patients with newly diagnosed glioblastoma were 65 years and older. This study did not include sufficient numbers of patients aged 65 years and older to determine differences in effectiveness from younger patients. No overall differences in safety were observed between patients ≥65 years and younger patients.
The CATNON trial did not include sufficient numbers of patients aged 65 years and older to determine differences in safety or effectiveness when compared to younger patients. In MK-7365-006, 4% of patients with refractory anaplastic astrocytoma were 70 years and older. This study did not include sufficient numbers of patients aged 70 years and older to determine differences in effectiveness from younger patients.
Patients 70 years and older had a higher incidence of Grade 4 neutropenia (25%) and Grade 4 thrombocytopenia (20%) in the first cycle of therapy than patients less than 70 years of age [see Warnings and Precautions (5.1), Adverse Reactions (6.1)]. In the entire safety database for which hematologic data exist (N=932), 7% (4/61) and 10% (6/63) of patients >70 years experienced Grade 4 neutropenia or thrombocytopenia in the first cycle, respectively. For patients ≤70 years, 7% (62/871) and 6% (48/879) experienced Grade 4 neutropenia or thrombocytopenia in the first cycle, respectively.
Pancytopenia, leukopenia, and anemia also occurred.
🆘 Overdosage ▾
10 OVERDOSAGE Dose-limiting toxicity was myelosuppression and was reported with any dose but is expected to be more severe at higher doses. An overdose of 2000 mg per day for 5 days was taken by one patient and the adverse reactions reported were pancytopenia, pyrexia, multi-organ failure, and death. There are reports of patients who have taken more than 5 days of treatment (up to 64 days), with adverse reactions reported including myelosuppression, which in some cases was severe and prolonged, and infections and resulted in death.
In the event of an overdose, monitor complete blood count and provide supportive measures as necessary.
🧬 Clinical Pharmacology ▾
12 CLINICAL PHARMACOLOGY
12.1Mechanism of Action Temozolomide is not directly active but undergoes rapid nonenzymatic conversion at physiologic pH to the reactive compound 5-(3-methyltriazen-1-yl)-imidazole-4-carboxamide (MTIC). The cytotoxicity of MTIC is thought to be primarily due to DNA alkylation, mainly at the O6 and N7 positions of guanine, which causes DNA double strand breaks and results in programmed cell death.
12.2Pharmacodynamics Temozolomide exposure-response relationships and the time course of pharmacodynamic response are unknown.
12.3Pharmacokinetics Following a single oral dose of 150 mg/m 2 , the mean C max is 7.5 mcg/mL for temozolomide and 282 ng/mL for MTIC. The mean AUC is 23.4 mcg·hr/mL for temozolomide and 864 ng·hr/mL for MTIC. Following a single 90-minute intravenous infusion of 150 mg/m 2 , the mean C max is 7.3 mcg/mL for temozolomide and 276 ng/mL for MTIC.
The mean AUC is 24.6 mcg·hr/mL for temozolomide and 891 ng·hr/mL for MTIC. Temozolomide exhibits linear kinetics over the therapeutic dosing range of 75 mg/m 2 /day to 250 mg/m 2 /day. Absorption The median T max is 1 hour.
Effect of Food The mean temozolomide C max and AUC decreased by 32% and 9%, respectively, and median T max increased by 2-fold (from 1 to 2.25 hours) when temozolomide capsules were administered after a modified high-fat breakfast (587 calories comprised of 1 fried egg, 2 strips of bacon, 2 slices of toast, 2 pats of butter, and 8 oz whole milk). Distribution Temozolomide has a mean (CV%) apparent volume of distribution of
0.4L/kg (13%). The mean percent bound of drug-related total radioactivity is 15%. Elimination Clearance of temozolomide is approximately
5.5L/hr/m 2 and the mean elimination half-life is 1.8 hours. Metabolism Temozolomide is spontaneously hydrolyzed at physiologic pH to the active species, MTIC and to temozolomide acid metabolite. MTIC is further hydrolyzed to 5-amino-imidazole-4-carboxamide (AIC), which is known to be an intermediate in purine and nucleic acid biosynthesis, and to methylhydrazine, which is believed to be the active alkylating species.
Cytochrome P450 enzymes play a minor role in the metabolism of temozolomide and MTIC. Relative to the AUC of temozolomide, the exposure to MTIC and AIC is 2.4% and 23%, respectively. Excretion Approximately 38% of the administered temozolomide total radioactive dose is recovered over 7 days: 38% in urine and 0.8% in feces.
The majority of the recovered radioactivity in urine is unchanged temozolomide (6%), AIC (12%), temozolomide acid metabolite (2.3%), and unidentified polar metabolite(s) (17%). Specific Populations No clinically significant differences in the pharmacokinetics of temozolomide were observed based on age (range: 19 to 78 years), gender, smoking status (smoker vs. non-smoker), creatinine clearance (CLcr) of 36 to 130 mL/min/m 2 , or mild to moderate hepatic impairment (Child Pugh class A and B). The pharmacokinetics of temozolomide has not been studied in patients with CLcr <36 mL/min/m 2 , end-stage renal disease on dialysis, or severe hepatic impairment (Child-Pugh class C).
Drug Interaction Studies Clinical Studies and Model-Informed Approaches No clinically significant differences in the pharmacokinetics of temozolomide or MTIC were observed when coadministered with ranitidine. No clinically significant differences in the clearance of temozolomide or MTIC were predicted when coadministered with the following drugs: valproic acid, dexamethasone, prochlorperazine, phenytoin, carbamazepine, ondansetron, histamine-2-receptor antagonists, or phenobarbital.
🧬 Mechanism of Action ▾
12.1Mechanism of Action Temozolomide is not directly active but undergoes rapid nonenzymatic conversion at physiologic pH to the reactive compound 5-(3-methyltriazen-1-yl)-imidazole-4-carboxamide (MTIC). The cytotoxicity of MTIC is thought to be primarily due to DNA alkylation, mainly at the O6 and N7 positions of guanine, which causes DNA double strand breaks and results in programmed cell death.
📦 How Supplied / Storage and Handling ▾
16 HOW SUPPLIED/STORAGE AND HANDLING Temozolomide is a hazardous drug. Follow applicable special handling and disposal procedures.1 Temozolomide capsules, USP are supplied in amber glass bottles with child-resistant caps or child-resistant blister packs containing the following capsule strengths: 5 mg hard gelatin capsules have white opaque caps and bodies, imprinted with band and the dosage strength “5 mg” on body and “890” on cap in green ink, containing white to light tan/light pink powder and are supplied as: Bottles of 5 with Child Resistant Cap…….………..NDC 47335-890-80 Bottles of 14 with Child Resistant Cap………….....NDC 47335-890-21 Bottles of 20 with Child Resistant Cap…………….NDC 47335-890-87 Unit-dose blister pack of 5 (1 × 5).............................NDC 47335-890-74 Unit-dose blister pack of 15 (3 x 5)...........................NDC 47335-890-72 Unit-dose blister pack of 20 (4 × 5)...........................NDC 47335-890-75 20 mg hard gelatin capsules have white opaque caps and bodies, imprinted with band and the dosage strength “20 mg” on body and “891” on cap in yellow ink, containing white to light tan/light pink powder and are supplied as: Bottles of 5 with Child Resistant Cap…….………..NDC 47335-891-80 Bottles of 14 with Child Resistant Cap………….....NDC 47335-891-21 Bottles of 20 with Child Resistant Cap…………….NDC 47335-891-87 Unit-dose blister pack of 5 (1 × 5) ...........................NDC 47335-891-74 Unit-dose blister pack of 15 (3 x 5)..........................NDC 47335-891-72 Unit-dose blister pack of 20 (4 × 5) .........................NDC 47335-891-75 100 mg hard gelatin capsules have white opaque caps and bodies, imprinted with band and the dosage strength “100 mg” on body and “892” on cap in pink ink, containing white to light tan/light pink powder and are supplied as: Bottles of 5 with Child Resistant Cap…….………..NDC 47335-892-80 Bottles of 14 with Child Resistant Cap………….....NDC 47335-892-21 Bottles of 20 with Child Resistant Cap…………….NDC 47335-892-87 Unit-dose blister pack of 5 (1 × 5) ...........................NDC 47335-892-74 Unit-dose blister pack of 15 (3 x 5)..........................NDC 47335-892-72 Unit-dose blister pack of 20 (4 × 5)..........................NDC 47335-892-75 140 mg hard gelatin capsules have white opaque caps and bodies, imprinted with band and the dosage strength “140 mg” on body and “929” on cap in blue ink, containing white to light tan/light pink powder and are supplied as: Bottles of 5 with Child Resistant Cap…….………..NDC 47335-929-80 Bottles of 14 with Child Resistant Cap………….....NDC 47335-929-21 Bottles of 20 with Child Resistant Cap…………….NDC 47335-929-87 Unit-dose blister pack of 5 (1 × 5) ...........................NDC 47335-929-74 Unit-dose blister pack of 15 (3 x 5)..........................NDC 47335-929-72 Unit-dose blister pack of 20 (4 × 5)..........................NDC 47335-929-75 180 mg hard gelatin capsules have white opaque caps and bodies, imprinted with band and the dosage strength “180 mg” on body and “930” on cap in reddish brown ink, containing white to light tan/light pink powder and are supplied as: Bottles of 5 with Child Resistant Cap…….………..NDC 47335-930-80 Bottles of 14 with Child Resistant Cap…………....
NDC 47335-930-21 Bottles of 20 with Child Resistant Cap…………….NDC 47335-930-87 Unit-dose blister pack of 5 (1 × 5) ...........................NDC 47335-930-74 Unit-dose blister pack of 15 (3 x 5)..........................NDC 47335-930-72 Unit-dose blister pack of 20 (4 × 5) .........................NDC 47335-930-75 250 mg hard gelatin capsules have white opaque caps and bodies, imprinted with band and the dosage strength “250 mg” on body and “893” on cap in black ink, containing white to light tan/light pink powder and are supplied as: Bottles of 5 with Child Resistant Cap……................NDC 47335-893-80 Bottles of 14 with Child Resistant Cap…………......NDC 47335-893-21 Bottles of 20 with Child Resistant Cap……………..NDC 47335-893-87 Unit-dose blister pack o…
📋 Description ▾
11 DESCRIPTION Temozolomide is an alkylating drug. The chemical name of temozolomide is 3,4-dihydro-3-methyl-4-oxoimidazo[5,1-d]- as -tetrazine-8-carboxamide. The structural formula of temozolomide is: The material is a white to light tan or light pink powder with a molecular formula of C 6 H 6 N 6 O 2 and a molecular weight of 194.15.
The molecule is stable at acidic pH (<5) and labile at pH >7; hence temozolomide capsules, USP can be administered orally. The prodrug, temozolomide, is rapidly hydrolyzed to the active 5-(3-methyltriazen-1-yl) imidazole-4-carboxamide (MTIC) at neutral and alkaline pH values, with hydrolysis taking place even faster at alkaline pH. Each capsule for oral use contains either 5 mg, 20 mg, 100 mg, 140 mg, 180 mg, or 250 mg of temozolomide, USP.
The inactive ingredients for temozolomide capsules, USP are: lactose anhydrous, sodium starch glycolate, tartaric acid, and stearic acid. The capsule shell contains gelatin, titanium dioxide, and sodium lauryl sulfate. The imprinting ink contains shellac, dehydrated alcohol, butyl alcohol, propylene glycol, strong ammonia solution, FD&C Blue # 1 Aluminum Lake (5 mg, 140 mg), yellow iron oxide (5 mg, 20 mg, 100 mg), red iron oxide (100 mg, 180 mg), titanium dioxide (100 mg, 140 mg), potassium hydroxide (100 mg, 250 mg) and black iron oxide (250 mg). spl-temozolomide-structure
💬 Information for Patients ▾
17 PATIENT COUNSELING INFORMATION Advise the patient to read the FDA-approved patient labeling (Patient Information). Myelosuppression Inform patients that temozolomide capsules can cause low blood cell counts and the need for frequent monitoring of blood cell counts. Advise patients to contact their healthcare provider immediately for bleeding, fever, or other signs of infection [see Warnings and Precautions (5.1)].
Hepatotoxicity Advise patients of the increased risk of hepatotoxicity and to contact their healthcare provider immediately for signs or symptoms of hepatotoxicity. Inform patients that they will have periodic liver enzyme tests during treatment and following the last dose of temozolomide capsules [see Warnings and Precautions (5.2)]. Pneumocystis Pneumonia Advise patients of the increased risk of Pneumocystis pneumonia and to contact their healthcare provider immediately for new or worsening pulmonary symptoms.
Inform patients that prophylaxis for Pneumocystis pneumonia may be needed [see Dosage and Administration (2.1), Warnings and Precautions (5.3)] . Secondary Malignancies Advise patients of the increased risk of myelodysplastic syndrome and secondary malignancies [see Warnings and Precautions (5.4)]. Exposure to Opened Capsules Advise patient to not open, chew, or dissolve the capsules.
If capsules are accidentally opened or damaged, advise patients to take rigorous precautions with capsule contents to avoid inhalation or contact with the skin or mucous membranes [see Warnings and Precautions (5.6)] . In case of powder contact, wash the affected area with water immediately [see Dosage and Administration (2.4)]. Embryo-Fetal Toxicity Advise pregnant women and females of reproductive potential of the potential risk to a fetus.
Advise females to inform their healthcare provider of a known or suspected pregnancy [see Warnings and Precautions (5.5), Use in Specific Populations (8.1)] . Advise females of reproductive potential to use effective contraception during treatment with temozolomide and for 6 months after the last dose [see Use in Specific Populations (8.3)]. Advise male patients with pregnant partners or female partners of reproductive potential to use condoms during treatment with temozolomide and for 3 months after the last dose [see Use in Specific Populations (8.3), Nonclinical Toxicology (13.1)].
Advise male patients not to donate semen during treatment with temozolomide and for 3 months after the last dose [see Use in Specific Populations (8.3), Nonclinical Toxicology (13.1)]. Lactation Advise women not to breastfeed during treatment with temozolomide and for 1 week after the last dose [see Use in Specific Populations (8.2)]. Infertility Advise males of reproductive potential that temozolomide may impair fertility [see Use in Specific Populations (8.3), Nonclinical Toxicology (13.1)].
Patient Information Temozolomide (TEM-oh-ZOE-loe-mide) Capsules, USP What are temozolomide capsules? Temozolomide capsules are a prescription medicine used to treat adults with certain brain cancer tumors. It is not known if temozolomide capsules are safe and effective in children.
Do not take temozolomide capsules if you: • have had an allergic reaction to temozolomide or any of the other ingredients in temozolomide capsules. See the end of this leaflet for a list of ingredients in temozolomide capsules. Symptoms of an allergic reaction with temozolomide capsules may include: a red itchy rash, or a severe allergic reaction, such as trouble breathing, swelling of the face, throat, or tongue, or severe skin reaction.
If you are not sure, ask your healthcare provider. • have had an allergic reaction to dacarbazine (DTIC), another cancer medicine. Before taking or receiving temozolomide capsules, tell your healthcare provider about all of your medical conditions, including if you: • have kidney problems • have liver problems • are pregnant or plan to become pregnant. Temozolomide capsule can harm your unborn baby and cau…