Tiotepa Vivanta 15 mg
Alkylating agent for high-dose chemotherapy and stem cell transplant conditioning
Tiotepa Vivanta contains the active substance thiotepa, a polyfunctional alkylating cytotoxic agent used in high-dose chemotherapy regimens before autologous or allogeneic hematopoietic stem cell transplantation (HSCT). Supplied as a 15 mg powder for reconstitution and intravenous infusion, it is administered only in specialist hospital centers by physicians experienced in cytotoxic therapy. Thiotepa is approved for use in adults and children with hematological malignancies, solid tumors — including germ cell tumors, breast cancer, and pediatric central nervous system tumors — and selected non-malignant diseases such as thalassemia major.
Quick Facts
Key Takeaways
- Tiotepa Vivanta (thiotepa 15 mg) is an alkylating cytotoxic drug used for high-dose conditioning before autologous or allogeneic stem cell transplantation in adults and children.
- It is administered only in specialist hospital units as an intravenous infusion, always in combination with other chemotherapy agents such as busulfan, fludarabine, cyclophosphamide, carboplatin, or melphalan.
- Thiotepa penetrates the blood-brain barrier, making it particularly useful for central nervous system (CNS) tumors and malignancies with a risk of CNS involvement.
- Profound, dose-limiting myelosuppression is the expected effect; additional serious risks include hepatic veno-occlusive disease (VOD/SOS), seizures, severe mucositis, and skin toxicity from drug excretion through sweat.
- Thiotepa is teratogenic, mutagenic, and frequently causes permanent infertility; pregnancy is strictly contraindicated and fertility preservation should be discussed before treatment.
What Is Tiotepa Vivanta and What Is It Used For?
Tiotepa Vivanta contains the active substance thiotepa (chemical name: N,N',N''-triethylenethiophosphoramide), which belongs to the ethyleneimine subclass of alkylating cytotoxic drugs. It is classified under the World Health Organization Anatomical Therapeutic Chemical (ATC) system with code L01AC01, reflecting its role as a systemic antineoplastic agent. First synthesized in the 1950s, thiotepa has remained a cornerstone of high-dose chemotherapy for more than six decades because of its reliable myeloablative effect and its ability to cross the blood-brain barrier.
Thiotepa works by chemically modifying DNA within rapidly dividing cells. Once infused, the compound is metabolized in the liver by the cytochrome P450 enzymes CYP2B6 and CYP3A4 into its principal active metabolite TEPA (triethylenephosphoramide). Both the parent compound and TEPA release reactive ethyleneimine groups that form covalent bonds at the N-7 position of guanine bases in DNA, producing inter- and intrastrand cross-links. These cross-links prevent DNA replication and RNA transcription, triggering programmed cell death (apoptosis) in bone marrow stem cells and tumor cells.
The primary clinical purpose of Tiotepa Vivanta is to provide myeloablative or immunoablative conditioning before a stem cell transplant. By destroying the patient's existing bone marrow (in autologous transplantation) or both the diseased marrow and the host immune system (in allogeneic transplantation), thiotepa creates physical and immunological space for the new stem cells to engraft. Without adequate conditioning, transplanted cells may fail to engraft or the underlying malignancy may relapse.
Tiotepa Vivanta is licensed as a conditioning agent in two broad populations. In adults, it is used in combination with other cytotoxic drugs as conditioning treatment prior to both autologous and allogeneic HSCT for hematological diseases such as Hodgkin and non-Hodgkin lymphoma, multiple myeloma, acute myeloid leukemia (AML), acute lymphoblastic leukemia (ALL), and chronic lymphocytic leukemia, as well as for certain solid tumors, notably germ cell tumors and breast cancer. In the pediatric population (from neonates to adolescents), thiotepa is used before allogeneic HSCT for hematological diseases including thalassemia major, sickle cell disease, aplastic anemia, and primary immunodeficiency disorders, and before autologous HSCT for high-risk solid tumors such as neuroblastoma, medulloblastoma, and other primitive neuroectodermal tumors (PNET) of the central nervous system.
Historically, thiotepa has also been used at lower doses as intravesical instillation treatment for superficial bladder cancer and as palliative therapy for advanced ovarian or breast cancer. However, the modern high-dose formulation supplied as Tiotepa Vivanta is specifically positioned as a transplant-conditioning agent rather than a stand-alone anticancer therapy.
Tiotepa Vivanta is administered only in specialist transplant or oncology centers under the direct supervision of physicians experienced in high-dose cytotoxic therapy and stem cell transplantation. It is never dispensed to patients for self-administration and is never used outside of a carefully planned conditioning protocol.
What Should You Know Before Taking Tiotepa Vivanta?
Contraindications
There are strict situations in which Tiotepa Vivanta must not be used. Understanding and respecting these contraindications is essential for patient safety:
- Hypersensitivity: Do not use Tiotepa Vivanta if you have a known allergy to thiotepa or to any of the other ingredients of the medicine.
- Pregnancy and breastfeeding: Thiotepa is strictly contraindicated in pregnant and breastfeeding women. It is a confirmed teratogen and mutagen that causes fetal harm in animal studies.
- Concurrent yellow fever vaccination: Thiotepa must not be given together with the yellow fever vaccine, since severe and often fatal generalized vaccinal disease can result in immunosuppressed patients.
- Other live attenuated vaccines: Concurrent administration of live vaccines including measles, mumps, rubella, oral polio (OPV), and BCG is contraindicated during and for several months after thiotepa treatment.
Warnings and Precautions
Tiotepa Vivanta is a powerful cytotoxic medicine that produces profound and intended reductions in all blood cell counts when given at conditioning doses. This dose-limiting myelosuppression is essential for successful transplantation but carries significant associated risks of bleeding, infection, and prolonged transfusion dependence. Close monitoring of complete blood counts with differential, liver and kidney function tests, and clinical status is therefore mandatory throughout treatment and the early post-transplant period.
Before starting therapy, your transplant team will carefully review your overall fitness (often using scoring systems such as the Hematopoietic Cell Transplant Comorbidity Index, HCT-CI) to ensure that the anticipated benefits of transplantation outweigh the risks of high-dose chemotherapy. This pre-treatment evaluation typically includes cardiac function (echocardiogram or MUGA scan), pulmonary function tests, liver and kidney biochemistry, viral serologies (HIV, hepatitis B and C, CMV, EBV), and imaging to assess disease status. You should inform your medical team of any of the following conditions before receiving thiotepa:
- Liver disease: Thiotepa is extensively metabolized by the liver. Pre-existing hepatic dysfunction, iron overload, chronic hepatitis, or prior exposure to hepatotoxic drugs increases the risk of serious complications, particularly hepatic veno-occlusive disease (VOD), also known as sinusoidal obstruction syndrome (SOS).
- Kidney disease: Although thiotepa and its metabolites are only partly excreted in urine, impaired renal clearance may increase overall toxicity. Fluid balance and electrolytes are monitored closely.
- Heart disease: High-dose thiotepa can cause cardiotoxicity, including arrhythmias, pericarditis, and heart failure, particularly when combined with other cardiotoxic agents (e.g. cyclophosphamide). Baseline cardiac assessment is required.
- Lung disease: Interstitial pneumonitis and pulmonary fibrosis have been reported. Patients with pre-existing pulmonary disease, heavy smoking history, or prior thoracic radiotherapy are at increased risk.
- History of seizures: Thiotepa lowers the seizure threshold. Patients with a history of epilepsy or recent CNS disease need prophylactic anticonvulsant therapy before and during treatment.
- Active or recent infection: Because profound immunosuppression will follow, any active infection should be treated and controlled before conditioning begins.
Because thiotepa is partly excreted through the skin in sweat, severe cutaneous reactions including erythema, blistering, desquamation, and hyperpigmentation are common. These occur most often in skin folds (groin, axillae, neck), under occlusive dressings, and at sites of pressure. Frequent showering with plain water (typically twice daily), daily change of bedding and nightwear, and avoidance of occlusive dressings help reduce skin toxicity. Some centers use cooling devices or scalp cooling to limit local skin exposure in pediatric patients.
The use of thiotepa may also increase the risk of secondary malignancies later in life. This long-term risk, which is shared by all alkylating agents, is accepted as part of the risk-benefit balance when transplantation is being performed for a life-threatening primary disease. Long-term surveillance for secondary cancers is recommended throughout survivorship.
Blood clots and endothelial damage in small hepatic venules and sinusoids can occur after high-dose thiotepa-containing conditioning, especially when combined with busulfan, cyclophosphamide, or melphalan. Clinical features include rapid weight gain, painful hepatomegaly, fluid retention (ascites), and jaundice. Severe VOD/SOS may progress to multi-organ failure. Report any of these symptoms to your medical team immediately; prophylactic strategies (e.g. defibrotide, ursodeoxycholic acid) may be considered in high-risk patients.
Pregnancy, Breastfeeding, and Fertility
If you are pregnant, breastfeeding, think you may be pregnant, or are planning to start a family, you must discuss this with your doctor before receiving Tiotepa Vivanta. The implications for reproductive health are significant and require thorough counseling well in advance of treatment.
Pregnancy: Thiotepa is strictly contraindicated during pregnancy. It is a known teratogen that can cause major congenital malformations, embryonic death, and fetal growth restriction. Women of childbearing potential must have a documented negative pregnancy test before therapy begins. Effective contraception must be used during treatment and for at least 6 months after the final dose. If pregnancy occurs despite precautions, urgent specialist counseling is required.
Breastfeeding: It is not known whether thiotepa or its metabolites pass into breast milk, but given their cytotoxic nature, breastfeeding must be stopped before therapy begins and must not be resumed while the patient is on treatment.
Fertility: High-dose thiotepa almost universally causes severe, often permanent, damage to fertility in both men and women. In women it causes premature ovarian insufficiency with early menopause and permanent loss of fertility, and in men it causes azoospermia. In prepubertal children, it may impair or prevent normal pubertal development. Fertility preservation options — sperm banking for post-pubertal males, and oocyte or embryo cryopreservation (or, for children, experimental ovarian or testicular tissue cryopreservation) — should be discussed, and where possible arranged, before treatment begins. Men are advised not to father a child for at least 1 year after thiotepa treatment, and both partners should use effective contraception during this period.
Vaccines and Immunizations
Patients receiving Tiotepa Vivanta will become severely immunocompromised. Live attenuated vaccines (including yellow fever, measles, mumps, rubella, varicella, oral polio, BCG, oral typhoid, and intranasal influenza) should not be given during or in the months following treatment, owing to risk of disseminated vaccine-strain infection. Inactivated vaccines may be less effective during severe immunosuppression; a structured re-immunization schedule is usually started 6 to 12 months after HSCT according to national and international transplant guidelines.
How Does Tiotepa Vivanta Interact with Other Drugs?
Because thiotepa has a narrow therapeutic window and is converted to its active metabolite TEPA by hepatic CYP450 enzymes, interactions that affect these enzymes or that add to its hematological and organ toxicity are clinically important. Tell your doctor or hospital pharmacist about every medicine you are taking, including prescription and over-the-counter drugs, herbal remedies, dietary supplements, and vitamins, before conditioning begins. Even apparently innocuous products such as St John's wort can significantly alter the balance between efficacy and toxicity.
Major Interactions
| Drug / Class | Type | Effect | Recommendation |
|---|---|---|---|
| Phenytoin, carbamazepine, phenobarbital | CYP3A4 inducers / anticonvulsants | Induce hepatic metabolism of thiotepa, potentially altering TEPA exposure and reducing conditioning efficacy | Review anticonvulsant choice before therapy; benzodiazepines (e.g. clonazepam) are often preferred for seizure prophylaxis |
| Rifampicin, rifabutin | Antimycobacterial / enzyme inducer | Strong induction of CYP3A4 may reduce thiotepa / TEPA plasma levels | Avoid during conditioning if possible; substitute with non-inducing agent |
| Ketoconazole, itraconazole, voriconazole | Azole antifungals / CYP3A4 inhibitors | Inhibit CYP-mediated thiotepa metabolism, potentially increasing toxicity | Use with caution; consider echinocandins or posaconazole-based prophylaxis per local protocol |
| Ritonavir, clarithromycin | Strong CYP3A4 inhibitors | May significantly increase thiotepa exposure and organ toxicity | Avoid concurrent use; substitute with non-inhibiting alternatives |
| Ciclosporin, tacrolimus | Calcineurin inhibitors (for GVHD prophylaxis) | Additive immunosuppression and myelotoxicity; possible nephrotoxicity | Used as part of planned transplant regimen; monitor trough levels and organ function |
| Clozapine | Atypical antipsychotic | Increased risk of agranulocytosis when combined with myelosuppressive chemotherapy | Avoid during treatment; collaborate with psychiatry to transition to an alternative |
| Live attenuated vaccines | Yellow fever, MMR, BCG, oral polio, varicella | Risk of severe, disseminated vaccine-strain infection | Contraindicated during treatment and for several months after HSCT |
| Warfarin and other coumarin anticoagulants | Vitamin K antagonists | Anticoagulant effect may be altered; bleeding risk is compounded by thrombocytopenia | Replace with low molecular weight heparin during thrombocytopenic period where anticoagulation is needed |
| St John's wort (Hypericum perforatum) | Herbal supplement | Potent CYP3A4 induction, may reduce efficacy | Stop at least 2 weeks before conditioning |
Other Important Interactions
Other cytotoxic drugs: Thiotepa is routinely combined with agents such as busulfan, cyclophosphamide, fludarabine, carboplatin, etoposide, and melphalan. Although these combinations are the basis of many effective conditioning regimens, they can produce overlapping toxicity — especially hepatic (VOD/SOS), mucosal, renal, and neurological. Combined regimens should only be prescribed according to established, guideline-based protocols.
Nephrotoxic drugs: Aminoglycoside antibiotics, amphotericin B, and high-dose NSAIDs should be used with caution alongside thiotepa-containing conditioning to avoid additive renal injury, particularly in the setting of concomitant ciclosporin or tacrolimus therapy.
Digoxin tablets: Laboratory studies suggest that thiotepa may reduce the dissolution of digoxin tablets in the gut, potentially reducing digoxin absorption. This is rarely relevant in the acute transplant setting but should be considered in long-term cardiac patients.
Ciprofloxacin and other fluoroquinolones: May be used as prophylaxis against gram-negative infection during neutropenia. There is no direct pharmacokinetic interaction with thiotepa, but combined antimicrobial and cytotoxic pressure increases the risk of QT prolongation and of Clostridioides difficile infection.
What Is the Correct Dosage of Tiotepa Vivanta?
Dosing of Tiotepa Vivanta is always calculated individually by the prescribing transplant physician, based on the patient's body surface area (BSA) in mg/m² or, in infants and small children, body weight (mg/kg). Because thiotepa is given as part of carefully designed multi-drug conditioning regimens, the exact dose, duration, and infusion schedule vary between regimens and between centers. The doses shown below are typical ranges based on the European Medicines Agency Summary of Product Characteristics and published international consensus protocols; they are not a substitute for individualized prescribing.
Adults – Autologous HSCT
Hematological Diseases (autologous HSCT)
- Dose range: 125–300 mg/m² per day
- Infusion duration: 2–4 hours per infusion
- Frequency: Once or twice daily
- Duration: 1 to 5 consecutive days before stem cell infusion
- Maximum cumulative dose: 900 mg/m² over the entire conditioning course
- Typical combinations: Thiotepa plus busulfan, carmustine, etoposide, carboplatin, or cyclophosphamide
Solid Tumors (autologous HSCT)
- Dose range: 120–250 mg/m² per day
- Infusion duration: 2–4 hours
- Frequency: Once or twice daily
- Duration: 1 to 5 consecutive days
- Maximum cumulative dose: 800 mg/m² for solid tumor indications
- Typical combinations: Thiotepa with carboplatin, etoposide, or cyclophosphamide (e.g. for germ cell tumors, breast cancer)
Adults – Allogeneic HSCT
Hematological Diseases (allogeneic HSCT)
- Dose range: 185–481 mg/m² per total course
- Infusion duration: 2–4 hours per infusion
- Frequency: Once or twice daily
- Duration: 1 to 3 consecutive days before stem cell infusion
- Typical combinations: Thiotepa-Busulfan-Fludarabine (TBF), Thiotepa-Treosulfan-Fludarabine, or thiotepa plus cyclophosphamide
- Adjustment: Dose reductions of 20–30% are common in reduced-intensity conditioning for older or comorbid patients
Children and Adolescents (0–17 Years)
In children, dosing is carefully adjusted for age, weight, body surface area, underlying disease, and transplant type. Because pharmacokinetic variability is large in the pediatric population, many centers use therapeutic drug monitoring and target exposure (AUC) when possible. Typical regimens are shown below.
| Indication | Transplant Type | Daily Dose | Duration |
|---|---|---|---|
| Hematological diseases | Autologous HSCT | 125–250 mg/m²/day | 1–3 days (max 900 mg/m² total) |
| Solid tumors (incl. CNS tumors) | Autologous HSCT | 150–350 mg/m²/day | 1–3 days (max 1050 mg/m² total) |
| Hematological diseases | Allogeneic HSCT | 125–250 mg/m²/day | 1–3 days |
| Thalassemia major | Allogeneic HSCT | 10 mg/kg (single dose) | 1 day |
| Neonates / infants (< 12 months) | Weight-based dosing | 5–8 mg/kg/day | Per protocol (dose reduced by 25–50%) |
Older Adults
Although no formal upper age limit exists, high-dose thiotepa is used with particular caution in patients over 65 years, given the higher risk of regimen-related mortality, veno-occlusive disease, and cardiac toxicity. In this group, reduced-intensity regimens (for example Thiotepa-Treosulfan-Fludarabine or low-dose Thiotepa-Busulfan-Fludarabine) are often preferred. Dose adjustments are guided by performance status, frailty scores, organ function, and HCT-CI score rather than by chronological age alone.
Patients with Renal or Hepatic Impairment
Formal pharmacokinetic studies of thiotepa in patients with renal or hepatic impairment are limited. In severe renal impairment, dose reduction and careful monitoring of blood levels (where available) are recommended. In significant hepatic impairment, elevated baseline bilirubin or transaminases, or a history of VOD/SOS, transplantation may be postponed or an alternative conditioning regimen chosen.
How Tiotepa Vivanta Is Prepared and Administered
Preparation and administration of Tiotepa Vivanta is carried out by trained hospital pharmacy and nursing staff using cytotoxic-handling precautions. Each 15 mg vial is reconstituted with 1.5 mL of sterile water for injections to yield a 10 mg/mL solution, which is then further diluted in 500 mL of 0.9% sodium chloride (or a smaller volume for fluid-restricted pediatric patients, typically at least 10 times the reconstituted volume). The final diluted solution is infused through a central venous catheter over 2 to 4 hours at room temperature.
Before, during, and after each infusion, patients receive antiemetic prophylaxis (typically a 5-HT₃ antagonist such as ondansetron together with dexamethasone and, in high-emetic-risk regimens, aprepitant) and supportive care including mouth care, skin washing, bladder protection, and, in children, seizure prophylaxis. Patients are encouraged to shower at least twice daily to minimize skin toxicity from drug excreted in sweat.
Missed or Delayed Dose
Because Tiotepa Vivanta is administered exclusively in hospital as part of a carefully timed conditioning schedule, missed doses do not occur in the way they do with oral medicines. If, for clinical reasons (for example uncontrolled infection, severe organ dysfunction, or logistical problems), a scheduled infusion cannot be given, the transplant team will decide whether to delay the infusion, reduce the dose, or modify the overall regimen. Never attempt to adjust the schedule yourself.
Overdose
There is no specific antidote for thiotepa overdose. Overdose produces profound and prolonged pancytopenia with severe infection risk, as well as intensified mucositis, skin and organ toxicity. Management is entirely supportive and may include broad-spectrum antimicrobials, red cell and platelet transfusion, hematopoietic growth factors (G-CSF), intensive care, and occasionally backup stem cell rescue. Hemodialysis is not effective at removing thiotepa or TEPA from the body because of their rapid tissue distribution and extensive intracellular binding.
What Are the Side Effects of Tiotepa Vivanta?
Like all medicines, Tiotepa Vivanta can cause side effects, although not all patients experience the same pattern. Many of the effects listed below are intended or expected consequences of high-dose conditioning chemotherapy and the transplantation process itself, rather than unexpected adverse reactions. Your transplant team will monitor you closely, provide intensive supportive care, and treat any complications promptly. The frequency categories follow the European Medicines Agency MedDRA convention.
The most serious adverse effects include dose-limiting myelosuppression, infections (bacterial, fungal, viral, and parasitic), hepatic veno-occlusive disease/sinusoidal obstruction syndrome (VOD/SOS), mucositis (painful inflammation of the entire gastrointestinal mucosa), pulmonary toxicity, neurotoxicity (including seizures, encephalopathy, and leukoencephalopathy), and secondary malignancies that may develop years after treatment. Careful pre-treatment evaluation and modern supportive care have substantially reduced early mortality from these complications, but they remain the principal determinants of transplant-related outcome.
Very Common
May affect more than 1 in 10 patients
- Blood: Anemia, leukopenia, neutropenia, thrombocytopenia, pancytopenia (the intended myeloablative effect)
- Infections: Bacteremia, pneumonia, urinary tract infections, viral reactivation (CMV, EBV, HSV, HHV-6), invasive fungal infections
- Immune: Acute and chronic graft-versus-host disease (GVHD) in allogeneic HSCT
- Nervous system: Headache, dizziness, insomnia, confusion, memory impairment
- Metabolism: Anorexia, hyperglycemia, electrolyte disturbances (low potassium, magnesium, calcium, sodium, phosphate)
- Heart and circulation: Tachycardia, arrhythmias, hypertension or hypotension
- Lungs: Dyspnea, cough, epistaxis, pharyngitis
- Gastrointestinal: Nausea, vomiting, mucositis/stomatitis, abdominal pain, diarrhea, constipation, anorexia
- Liver: Elevated transaminases, bilirubin, and alkaline phosphatase; hepatic VOD/SOS
- Skin: Rash, pruritus, hyperpigmentation (especially flexural), alopecia
- Kidney / urinary: Hematuria, raised creatinine, hemorrhagic cystitis (particularly with cyclophosphamide co-administration)
- General: Fever, chills, weakness, mucosal hemorrhage, edema, pain at infusion site
- Investigations: Weight gain, elevated liver enzymes, abnormal coagulation
Common
May affect 1 in 10 to 1 in 100 patients
- Nervous system: Encephalopathy, convulsions, paresthesia, extrapyramidal symptoms
- Psychiatric: Anxiety, depression, agitation
- Heart: Cardiomyopathy, pericarditis, pericardial effusion, reduced left ventricular function
- Lungs: Pneumonitis, pulmonary edema, alveolar hemorrhage, pleural effusion, adult respiratory distress syndrome
- Gastrointestinal: Esophagitis, pancreatitis, gastrointestinal bleeding, intestinal perforation
- Liver: Severe VOD/SOS, acute hepatic failure
- Skin: Bullous dermatitis, severe desquamation (typical chemical “burn-like” appearance in skin folds), erythema multiforme
- Kidney: Acute renal failure, bladder hemorrhage
- Reproductive: Amenorrhea, menopausal symptoms, azoospermia
Uncommon
May affect 1 in 100 to 1 in 1,000 patients
- Nervous system: Leukoencephalopathy, cerebral hemorrhage, cerebrovascular accident, reversible posterior leukoencephalopathy syndrome (PRES)
- Heart / vasculature: Capillary leak syndrome, deep vein thrombosis, pulmonary embolism
- Hypersensitivity: Anaphylactic reactions, angioedema
- Respiratory: Hypoxia, pulmonary fibrosis
- Gastrointestinal: Colitis, ileus, severe vomiting with hematemesis
- Endocrine: Thyroid dysfunction (hypothyroidism or hyperthyroidism)
Rare / Frequency Not Known
Less than 1 in 1,000 patients or cannot be estimated from available data
- Secondary malignancies: Therapy-related myelodysplastic syndrome (MDS), acute leukemia, solid tumors appearing years after treatment
- Eye: Conjunctivitis, cataracts, keratoconjunctivitis, visual disturbances
- Endocrine / growth: Growth retardation in children, gonadal failure, permanent infertility
- Reproductive: Premature ovarian failure, impaired pubertal development
- Musculoskeletal: Muscle weakness, rhabdomyolysis (very rare)
- Dental: Incomplete tooth development and enamel defects in treated children
- Neurological long-term: Neurocognitive impairment, especially in young children treated for CNS tumors
During and after Tiotepa Vivanta treatment, contact your transplant team urgently if you experience any of the following: sudden weight gain or painful abdominal swelling, yellowing of the skin or eyes (jaundice), difficulty breathing, chest pain, persistent fever ≥ 38 °C, unusual bleeding or bruising, seizures, severe confusion or drowsiness, severe skin blistering, or a sudden decrease in urine output. These may indicate serious complications requiring urgent treatment.
If you experience any side effect, whether or not listed in this article, report it to your treating physician or your national medicines safety authority. Spontaneous reporting helps improve the safety monitoring of chemotherapy worldwide. In the European Union, patients can report suspected adverse drug reactions through their national pharmacovigilance program.
How Should Tiotepa Vivanta Be Stored?
Proper storage of Tiotepa Vivanta is essential to maintain the chemical stability and sterility of the product. Because this medication is handled exclusively within hospital pharmacies and specialist transplant or oncology units, storage is managed by trained pharmacy and nursing staff in compliance with cytotoxic-handling standards. Patients and families do not store Tiotepa Vivanta at home.
Unopened vials: Store in a refrigerator at 2 °C to 8 °C (36 °F to 46 °F). Keep the vials in the outer carton to protect them from light. Do not freeze. Do not use after the expiry date printed on the label and carton (EXP).
Reconstituted concentrate: After reconstitution of the 15 mg vial with 1.5 mL of sterile water for injections, chemical and physical in-use stability has been demonstrated for up to 8 hours at 2–8 °C. From a microbiological point of view, the product should be used immediately; if not used immediately, in-use storage times and conditions before use are the responsibility of the user.
Final infusion solution (after further dilution): Chemical and physical stability has been demonstrated for:
- At room temperature (around 25 °C), normal lighting: up to 4 hours including infusion time
- Refrigerated at 2–8 °C: up to 24 hours including infusion time
The reconstituted or diluted solution must not be frozen. Only clear, colorless to slightly yellow solutions without visible particles should be used. Any unused medicine or waste material must be disposed of as cytotoxic waste in accordance with local regulations. Keep this medicine out of the sight and reach of children at all times. Medicines must not be disposed of via wastewater or household waste.
Tiotepa is a genotoxic, mutagenic substance. Preparation and administration must be performed in a designated cytotoxic handling area using closed-system transfer devices or Class II biological safety cabinets where available. Personnel must wear appropriate personal protective equipment (double nitrile gloves, gown, eye protection, and respiratory protection where aerosolization may occur). Pregnant or breastfeeding staff should not handle thiotepa. Accidental spillage must be cleaned using approved cytotoxic spill kits, and accidental skin or eye contact should be irrigated with copious water immediately.
What Does Tiotepa Vivanta Contain?
Understanding the precise composition of Tiotepa Vivanta is important for healthcare professionals preparing and administering the product, and for patients who wish to understand the source of possible hypersensitivity reactions. The formulation has been designed to provide a pure, reliable presentation of the active substance for subsequent reconstitution and dilution.
Active substance: Each vial of Tiotepa Vivanta contains 15 mg of thiotepa (N,N',N''-triethylenethiophosphoramide). After reconstitution with 1.5 mL of sterile water for injections, the concentrate contains 10 mg/mL of thiotepa. Following further dilution for infusion, the final concentration is typically around 0.03–0.5 mg/mL depending on the volume of diluent used.
Other ingredients (excipients): The powder presentation contains no other excipients. The diluent used for reconstitution is sterile water for injections. The diluent for infusion is sodium chloride 9 mg/mL (0.9%) solution for injection.
Appearance and packaging: Tiotepa Vivanta is a white crystalline powder supplied in a clear Type I glass vial with a chlorobutyl rubber stopper and an aluminium crimp seal with a flip-off cap. A standard pack contains 1 vial of 15 mg. After reconstitution and dilution, the solution should appear clear, colorless to slightly yellow, and free from visible particles.
Chemical identity: Thiotepa is an organophosphorus ethyleneimine derivative with molecular formula C₆H₁₂N₃PS and molecular weight 189.22 g/mol. It is freely soluble in ethanol and chloroform, sparingly soluble in water, and hydrolyzed to inactive products in acidic aqueous solution. Its activity depends on the intact aziridine rings.
Tiotepa Vivanta is manufactured and distributed by Vivanta as a generic equivalent of the originator thiotepa product (TEPADINA). Alternative brands of thiotepa with equivalent pharmaceutical quality include TEPADINA, Tiotepa Accord, and Tepylute. All thiotepa products are approved by national and regional regulators (EMA, FDA, TGA, Health Canada) and supplied exclusively to specialist hospital centers.
Frequently Asked Questions About Tiotepa Vivanta
Tiotepa Vivanta is used as part of high-dose conditioning chemotherapy before autologous or allogeneic hematopoietic stem cell transplantation (HSCT) in adults and children. Typical indications include hematological diseases such as Hodgkin and non-Hodgkin lymphoma, multiple myeloma, acute leukemia and thalassemia, and solid tumors such as germ cell tumors, breast cancer, and pediatric central nervous system tumors. It is always combined with other chemotherapy agents according to protocol.
The most common side effects (affecting more than 1 in 10 patients) include severe bone marrow suppression (the intended effect), infections, nausea, vomiting, diarrhea, mucositis (mouth and gastrointestinal inflammation), hair loss, fever, fatigue, elevated liver enzymes, skin reactions such as redness and hyperpigmentation, electrolyte disturbances, and neurological effects such as headache and confusion. Severe complications such as hepatic veno-occlusive disease and seizures can occur and require urgent management.
Tiotepa Vivanta is supplied as a 15 mg powder that is reconstituted with sterile water for injections, further diluted in sodium chloride 0.9%, and then administered as an intravenous infusion through a central venous catheter in a specialist transplant or oncology unit. Each infusion typically lasts 2 to 4 hours. Dosing is individualized based on body surface area or body weight and on the specific conditioning regimen. Patients are closely monitored before, during, and after each infusion with supportive antiemetic, anticonvulsant and skin care measures.
Thiotepa is metabolized by hepatic CYP2B6 and CYP3A4 enzymes, so CYP-modulating drugs can alter its effects. Strong CYP3A4 inhibitors such as ketoconazole, itraconazole, voriconazole, clarithromycin, and ritonavir may increase thiotepa toxicity. Inducers including phenytoin, carbamazepine, rifampicin, and St John's wort may reduce its efficacy. Ciclosporin and tacrolimus compound myelotoxicity, clozapine raises the risk of agranulocytosis, warfarin carries increased bleeding risk during thrombocytopenia, and live attenuated vaccines such as yellow fever are strictly contraindicated.
No. Thiotepa is strictly contraindicated during pregnancy and breastfeeding. It is teratogenic, mutagenic, and embryotoxic in animal studies, and case reports describe congenital anomalies in exposed pregnancies. Women of childbearing potential must have a negative pregnancy test before therapy, use effective contraception during treatment and for at least 6 months afterward. Men are advised to use contraception and not to father a child for at least 1 year after treatment. Thiotepa frequently causes permanent infertility, so sperm banking, egg or embryo cryopreservation, or ovarian/testicular tissue cryopreservation should be discussed before treatment begins.
Thiotepa is partly excreted in sweat, so the drug accumulates on the skin, particularly in skin folds and under dressings or bedding. This can cause painful redness, blistering, desquamation, and permanent dark discoloration (hyperpigmentation). To minimize these reactions, patients are normally asked to shower or bathe with plain water at least twice daily during the infusion period and for 48 hours after the final dose, to change bedding and clothing daily, to avoid occlusive dressings where possible, and to keep skin folds clean and dry. Dedicated scalp and body cooling may also be used in some pediatric regimens.
Unopened vials of Tiotepa Vivanta 15 mg powder must be stored refrigerated at 2 to 8 °C in the outer carton to protect from light, and must not be frozen. After reconstitution with sterile water for injections, the concentrate can be stored at 2–8 °C for up to 8 hours. The final diluted infusion solution is stable for up to 24 hours refrigerated or 4 hours at room temperature and must not be frozen. Only clear, colorless to slightly yellow solutions free of particles should be used; all unused material is disposed of as cytotoxic waste.
References
- European Medicines Agency (EMA). TEPADINA (thiotepa) – Summary of Product Characteristics (SmPC). www.ema.europa.eu. Accessed January 2026.
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Medical Editorial Team
This article has been written and reviewed by the iMedic Medical Editorial Team, which consists of licensed specialist physicians in hematology, oncology, and stem cell transplantation medicine. Our editorial process follows international medical guidelines from the WHO, EMA, EBMT, and FDA. All medical claims are supported by peer-reviewed evidence, product Summary of Product Characteristics (SmPC), and international transplant consensus documents, following the GRADE evidence framework.
All content is reviewed by board-certified hematologists, oncologists, and transplant physicians with substantial clinical experience in high-dose chemotherapy and stem cell transplantation. Our review process ensures accuracy, currency, and clinical relevance of all information presented.
We follow Evidence Level 1A standards, basing our content on systematic reviews, meta-analyses, randomized controlled trials, and regulatory-grade sources. Sources include EMA and FDA SmPC documentation, EBMT Handbook guidelines, and high-impact peer-reviewed journals.
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