Thiotepa 100mg Inj, 1 Vial

Thiotepa is an alkylating agent. It forms highly reactive ethylenimine groups that cross-link DNA strands, leading to inhibition of DNA synthesis and function. This action is not cell-cycle specific, but rapidly proliferating cells are more sensitive. It also has some activity against RNA and proteins. The cytotoxic effects result in cell death.

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 medical attention immediately:

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
+ Difficulty 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 sputum production or a change in sputum color
+ Painful urination or mouth sores
+ A wound that won't heal
Signs of bleeding, such as:
+ Vomiting or coughing up blood
+ Coffee ground-like vomit
+ Blood in the urine
+ Black, red, or tarry stools
+ Bleeding gums or abnormal vaginal bleeding
+ Unexplained bruises or bruises that enlarge
+ Uncontrollable bleeding
Signs of liver problems, including:
+ Dark urine
+ Fatigue or decreased appetite
+ Nausea or stomach pain
+ Light-colored stools
+ Vomiting or yellow skin and eyes
Weakness on one side of the body, difficulty speaking or thinking, balance changes, or drooping on one side of the face
Blurred vision
Absence of menstrual period
Mouth irritation or mouth sores
Difficulty urinating
Blood in the urine
Changes in vision, eye pain, or severe eye irritation
Severe brain problems, which can be life-threatening, especially at high doses. Seek medical help immediately if you experience:
+ Extreme sleepiness or confusion
+ Changes in behavior or hallucinations (seeing or hearing things that aren't there)
+ Memory problems or seizures
+ Difficulty moving or severe headaches

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 for guidance:

Hair loss
Dizziness, fatigue, or weakness
Headache
Stomach pain
Irritation at the injection site
Diarrhea, vomiting, nausea, or decreased appetite (common side effects that can be managed with your doctor's guidance)

If any of these side effects bother you, don't improve, or are severe, contact your doctor for advice.

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.

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.
All medications you are currently taking, including prescription and over-the-counter (OTC) drugs, natural products, and vitamins. This medication can interact with various drugs, such as those used to treat HIV, infections, or seizures.
If you are breastfeeding or plan to breastfeed. You should not breastfeed while taking this medication, and you may need to avoid breastfeeding for a certain period after your last dose. Consult your doctor to determine the necessary timeframe.

Please note that this is not an exhaustive list of all potential interactions or health concerns related to this medication. To ensure your safety, it is crucial to:

Inform your doctor and pharmacist about all your medications (prescription and OTC), natural products, vitamins, and health issues.
Verify that it is safe to take this medication with your existing medications and health conditions.
Never start, stop, or modify the dosage of any medication without first consulting your doctor.

It is essential to inform all your healthcare providers, including doctors, nurses, pharmacists, and dentists, that you are taking this medication. Regular blood work and laboratory tests, as directed by your doctor, are crucial to monitor your health.

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.

Due to the increased risk of bleeding, exercise caution to avoid injury. Use a soft-bristled toothbrush and an electric razor to minimize the risk of bleeding.

You may be more susceptible to infections, so it is crucial to practice good hygiene by washing your hands frequently and avoiding close contact with individuals who have infections, colds, or flu.

This medication may cause skin reactions, such as changes in skin color, itching, blisters, or peeling, particularly in areas like the groin, armpits, skin folds, neck, and under bandages or dressings. Follow your doctor's instructions for showering, bathing, changing dressings, and cleaning the affected skin. Additionally, change your bed sheets daily while taking this medication.

This medication may affect menstrual cycles and sperm production. If you have concerns, discuss them with your doctor.

Fertility may be impacted, potentially leading to difficulty conceiving or fathering a child. If you plan to become pregnant or father a child, consult with your doctor before initiating this medication.

This medication may harm an unborn baby. A pregnancy test will be conducted before starting the medication to confirm that you are not pregnant. If you may become pregnant, use effective birth control during treatment and for six months after the final dose. If you become pregnant, notify your doctor immediately.

If your partner may become pregnant, use birth control during your treatment and for one year after the final dose. If your partner becomes pregnant, inform the doctor promptly.

• Live vaccines (risk of severe infection due to immunosuppression)
• Other myelosuppressive agents (additive myelosuppression)
• CYP3A4 inhibitors (e.g., ketoconazole, ritonavir, clarithromycin, grapefruit juice) - may increase thiotepa exposure and toxicity.
• CYP3A4 inducers (e.g., rifampin, carbamazepine, phenytoin, St. John's Wort) - may decrease thiotepa exposure and efficacy.
• Warfarin (increased risk of bleeding due to myelosuppression and potential effect on coagulation factors)
• Succinylcholine (prolonged neuromuscular blockade due to inhibition of pseudocholinesterase by TEPA)

• Phenytoin (potential for decreased phenytoin levels)
• Cimetidine (may inhibit thiotepa metabolism)
• Allopurinol (may increase myelosuppression, especially with high doses of thiotepa)
• Radiation therapy (additive myelosuppression and mucositis)
• Other nephrotoxic or hepatotoxic agents (additive organ toxicity)

• Not specifically identified as minor, most interactions are significant due to the drug's toxicity profile.

• Fever, chills, signs of infection (due to neutropenia)
• Unusual bleeding or bruising (due to thrombocytopenia)
• Fatigue, pallor, shortness of breath (due to anemia)
• Nausea, vomiting, diarrhea, mucositis (oral, GI)
• Skin rash, erythema, desquamation (especially with high-dose IV)
• Pain or irritation at injection site
• Signs of neurotoxicity (e.g., headache, confusion, seizures - particularly with intrathecal administration)
• Signs of allergic reaction

Thiotepa is classified as Pregnancy Category D. It can cause fetal harm when administered to a pregnant woman. It is teratogenic and embryotoxic in animals. Women of reproductive potential should be advised to avoid becoming pregnant during treatment and for at least 6 months after the last dose. Men should use effective contraception during treatment and for at least 1 year after the last dose.

Lactation Risk Category L5 (Contraindicated). It is unknown if thiotepa or its metabolites are excreted in human milk. Due to the potential for serious adverse reactions in the breastfed infant, including myelosuppression and carcinogenicity, breastfeeding is contraindicated during thiotepa treatment and for at least 1 week after the last dose.

Safety and efficacy have not been fully established in pediatric patients for all indications. However, thiotepa is used in pediatric oncology, particularly in high-dose regimens for stem cell transplant conditioning and certain solid tumors/lymphomas. Dosing is typically based on body surface area. Close monitoring for myelosuppression and other toxicities is crucial.

No specific dose adjustments are generally recommended based solely on age. However, elderly patients may have decreased organ function (renal, hepatic) and reduced bone marrow reserve, which may increase susceptibility to myelosuppression and other toxicities. Close monitoring of hematologic parameters and organ function is essential. Start with lower doses and titrate carefully based on tolerance and response.

• Thiotepa is a vesicant; ensure proper IV access and monitor for extravasation. For intravesical administration, ensure complete emptying of the bladder before instillation and instruct the patient to retain the solution for 2 hours.
• High-dose thiotepa can cause severe skin toxicity (e.g., diffuse erythema, desquamation, blistering), especially in areas of skin folds or pressure points. Prophylactic skin care (e.g., frequent bathing, moisturizing, avoiding friction) is crucial.
• Myelosuppression is the dose-limiting toxicity. Nadir typically occurs 10-14 days after administration. Close monitoring of CBC is essential.
• Thiotepa is metabolized to TEPA, which also has cytotoxic activity and a longer half-life. Both contribute to toxicity.
• When administered intrathecally, thiotepa can cause neurotoxicity, including seizures, encephalopathy, and chemical arachnoiditis. Strict adherence to intrathecal dosing guidelines is critical.
• Patients receiving high-dose thiotepa should be managed in a specialized oncology setting with access to supportive care, including blood product transfusions and G-CSF.
• Due to its alkylating nature, thiotepa carries a risk of secondary malignancies (e.g., acute myeloid leukemia, myelodysplastic syndrome) and infertility.

• Cyclophosphamide (another alkylating agent)
• Ifosfamide (another alkylating agent)
• Melphalan (another alkylating agent, often used in high-dose settings)
• Busulfan (another alkylating agent, often used in high-dose settings)
• Cisplatin (for bladder/ovarian cancer)
• Doxorubicin (for breast/ovarian cancer)

If your symptoms or health problems do not improve or worsen over time, it is essential to contact your doctor for further evaluation and guidance. To ensure safe use, do not share your medication with others, and never take someone else's medication. Store all medications in a secure location, out of reach of children and pets, to prevent accidental ingestion. Properly dispose of unused or expired medications by checking with your pharmacist for guidance on the best disposal method. Unless instructed to do so, avoid flushing medications down the toilet or pouring them down the drain, as this can harm the environment. Many communities offer drug take-back programs, which can be a safe and convenient way to dispose of unwanted medications. Some medications may come with an additional patient information leaflet, so be sure to check with your pharmacist for more information. If you have any questions or concerns about your medication, consult 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 emergency medical attention. Be prepared to provide information about the medication taken, the amount, and the time it was taken, as this will help healthcare providers deliver appropriate care.