Data from FDA - Curated by EPG Health - Last updated 25 January 2018

Indication(s)

1 INDICATIONS AND USAGE TEPADINA (thiotepa) is an alkylating drug indicated: To reduce the risk of graft rejection when used in conjunction with high-dose busulfan and cyclophosphamide as a preparative regimen for allogeneic hematopoietic progenitor (stem) cell transplantation (HSCT) for pediatric patients with class 3 beta-thalassemia. (1.1, 14) For treatment of adenocarcinoma of the breast or ovary. (1.2) For controlling intracavitary effusions secondary to diffuse or localized neoplastic diseases of various serosal cavities. (1.3) For treatment of superficial papillary carcinoma of the urinary bladder. (1.4) 1.1 Class 3 Beta-Thalassemia TEPADINA is indicated to reduce the risk of graft rejection when used in conjunction with high-dose busulfan and cyclophosphamide as a preparative regimen for allogeneic hematopoietic progenitor (stem) cell transplantation (HSCT) for pediatric patients with class 3 beta-thalassemia [see Clinical Studies (14)]. 1.2 Adenocarcinoma of the Breast or Ovary TEPADINA is indicated for treatment of adenocarcinoma of the breast or ovary. 1.3 Malignant Effusions TEPADINA is indicated for controlling intracavitary effusions secondary to diffuse or localized neoplastic diseases of various serosal cavities. 1.4 Superficial Papillary Carcinoma of the Urinary Bladder TEPADINA is indicated for treatment of superficial papillary carcinoma of the urinary bladder.

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Advisory information

contraindications
4 CONTRAINDICATIONS TEPADINA is contraindicated in: Patients with severe hypersensitivity to thiotepa [ see Warnings and Precautions (5.2)] Concomitant use with live or attenuated vaccines [ see Warnings and Precautions (5.4)]. Hypersensitivity to the active substance (4). Concomitant use with live or attenuated vaccines (4).
Adverse reactions
6 ADVERSE REACTIONS The following clinically significant adverse reactions are described elsewhere in the labeling: Myelosuppression [ see Warnings and Precautions ( 5.1)] Infection [ see Warnings and Precautions ( 5.1)] Hypersensitivity [ see Warnings and Precautions ( 5.2 )]. Cutaneous Toxicity [ see Warnings and Precautions ( 5.3 )] Hepatic Veno-Occlusive Disease [ see Warnings and Precautions ( 5.5 )] Central Nervous System Toxicity [ see Warnings and Precautions (5.6)] Carcinogenicity [ see Warnings and Precautions (5.7)] The most common adverse reactions (incidence greater than 10%) were neutropenia, anemia, thrombocytopenia, elevated alanine aminotransferase, elevated aspartate aminotransferase, elevated bilirubin, mucositis, cytomegalovirus infection, hemorrhage, diarrhea, hematuria and rash. (6.1) To report SUSPECTED ADVERSE REACTIONS, contact ADIENNE at 844-668-3940 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. 6.1 Clinical 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. Adverse Reactions With the Preparative Regimen for Class 3 Beta-Thalassemia​ The safety of TEPADINA was evaluated by retrospective analysis of 76 pediatric patients with class 3 beta-thalassemia who underwent allogeneic hematopoietic progenitor (stem) cell transplantation (HSCT) using busulfan and cyclophosphamide with TEPADINA (n=25) or without TEPADINA (n=51) [ ]. Adverse reactions were abstracted retrospectively from the medical records. Serious adverse events that occurred in the TEPADINA-treated and control cohort were, respectively: gastrointestinal hemorrhage (4% vs 2%), pneumonia (4% vs 0), seizure (4% vs 2%), subarachnoid hemorrhage (4% vs 0) and veno-occlusive disease (4% vs 2%). By 90 days after HSCT, grades 2 to 4 acute graft-versus-host disease was observed in 7 (28%) patients in the TEPADINA cohort and in 13 (26%) patients in the control cohort. By 1-year after transplantation, chronic graft-versus-host disease was observed in 8 (35%) of 23 evaluable patients in the TEPADINA cohort, and 7 (14%) of 49 evaluable patients in the control cohort. Adverse reactions occurring in at least 5% of patients treated with TEPADINA from start of the preparative regimen through 30 days after transplantation are shown in Table 3. Table 3: Common Adverse Reactions (>5%) Occurring Through 30 Days After Transplantation In Patients With Class 3 Beta-Thalassemia Using Busulfan And Cyclophosphamide With Or Without TEPADINA in the Preparative Regimen Preparative Regimen of Busulfan and Cyclophosphamide With TEPADINA N=25 patients (%) Without TEPADINA N=51 patients (%) Adverse Reaction Any Grade Grade 3-5 1 Any Grade Grade 3-5 1 Mucositis 2 16 (64%)16 (64%) 4 (16%)4 (16%) 22 (43%)22 (43%) 1 (2%)1 (2%) Cytomegalovirus InfectionCytomegalovirus Infection 12 (48%)12 (48%) 00 15 (29%)15 (29%) 0 Hemorrhage 3 7 (28%)7 (28%) 2 (8%)2 (8%) 12 (24%)12 (24%) 3 (6%)3 (6%) Diarrhea 6 (24%)6 (24%) 0 7 (14%)7 (14%) 2 (4%)2 (4%) Hematuria 4 5 (20%)5 (20%) 0 10 (20%)10 (20%) 3 (6%)3 (6%) Rash 5 3 (12%)3 (12%) 0 11 (22%)11 (22%) 0 Intracranial Hemorrhage 6 2 (8%)2 (8%) 1 (4%)1 (4%) 0 0 Pseudomonas Infection 2 (8%)2 (8%) 0 0 0 1Severe, life-threatening or fatal 2Mucositis includes mouth hemorrhage, mucosal inflammation and stomatitis 3Hemorrhage includes all hemorrhage terms 4Hematuria includes cystitis hemorrhagic and hematuria 5Rash includes dermatitis exfoliative, palmar erythema, rash, rash maculo-papular, rash pruritic and skin toxicity 6Hemorrhage Intracranial includes hemorrhage intracranial and subarachnoid hemorrhage All patients in the TEPADINA-treated and control cohorts developed profound cytopenias, including neutropenia, anemia, thrombocytopenia. Table 4 shows the selected chemistry abnormalities that occurred from start of the preparative regimen through 30 days after transplantation. Preparative Regimen of Busulfan and Cyclophosphamide With TEPADINA N=25 patients (%) Without TEPADINA N=51 patients (%) Adverse Reaction Any Grade Grade 3-4 Any Grade Grade 3-4 Elevated alanine aminotransferase 22 (88%)22 (88%) 6 (24%)6 (24%) 49 (96%)49 (96%) 14 (27%)14 (27%) Elevated aspartate aminotransferase 20 (80%)20 (80%) 4 (16%)4 (16%) 45 (88%)45 (88%) 9 (18%)9 (18%) Elevated total bilirubin 20 (80%)20 (80%) 4 (16%)4 (16%) 39 (77%)39 (77%) 2 (4%)2 (4%) Adverse Reactions with Treatment of adenocarcinoma of the breast, adenocarcinoma of the ovary, malignant effusions and superficial papillary carcinoma of the urinary bladder​ Gastrointestinal: Nausea, vomiting, abdominal pain, anorexia. General: Fatigue, weakness. Febrile reaction and discharge from a subcutaneous lesion may occur as the result of breakdown of tumor tissue. Hypersensitivity Reactions: Allergic reactions - rash, urticaria, laryngeal edema, asthma, anaphylactic shock, wheezing. Local Reactions: Contact dermatitis, pain at the injection site. Neurologic: Dizziness, headache, blurred vision. Renal: Dysuria, urinary retention, chemical cystitis or hemorrhagic cystitis. Reproductive: Amenorrhea, interference with spermatogenesis. Respiratory: Prolonged apnea has been reported when succinylcholine was administered prior to surgery, following combined use of thiotepa and other anticancer agents. It was theorized that this was caused by decrease of pseudocholinesterase activity caused by the anticancer drugs. Skin: Dermatitis, alopecia. Skin depigmentation has been reported following topical use. Special Senses​: Conjunctivitis. 6.2 Postmarketing Experience Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure. The following adverse reactions have been identified during post approval use of TEPADINA in preparative regimens prior to allogeneic or autologous hematopoietic progenitor (stem) cell transplantation (HSCT) in adult and pediatric patients. Blood and lymphatic system disorders: Febrile bone marrow aplasia. Cardiac disorder: Bradycardia, cardiac failure congestive, cardio-respiratory arrest, pericardial effusion, pericarditis, right ventricular hypertrophy. Congenital, familial and genetic disorders: Aplasia. Ear and labyrinth disorders: Deafness. Eye disorders: Blindness, eyelid ptosis, papilledema, strabismus. Gastrointestinal disorders: Ascites, dysphagia, enterocolitis, gastritis, palatal disorder. General disorders and administration site conditions: Device related infection, gait disturbance, malaise, multi-organ failure, pain. Hepatobiliary disorders: Hepatomegaly. Immune system disorders: Bone marrow transplant rejection, immunosuppression. Infection and infestation: Acute sinusitis, bronchopulmonary aspergillosis, candida sepsis, enterococcal infection, Epstein-Barr virus infection, Escherichia sepsis, Fusarium infection, gastroenteritis, infection, lower respiratory tract infection fungal, lower respiratory tract infection viral, parainfluenza virus infection, Pneumonia legionella, relapsing fever, respiratory tract infection, sepsis, septic shock, Staphylococcal bacteremia, Staphylococcal infection, systemic candida, urinary tract infection. Injury, poisoning and procedural complications: Refractoriness to platelet transfusion, subdural hematoma. Investigations: Coagulation test abnormal, hemoglobin decreased, Klebsiella test positive, nuclear magnetic resonance imaging brain abnormal, transaminases increased, weight increased. Metabolism and nutrition disorders: Hyponatremia. Neoplasms benign, malignant and unspecified (incl. cysts and polyps): Breast cancer metastatic, central nervous system lymphoma, leukemia recurrent, lymphoma, malignant neoplasm progression, metastatic neoplasm, post transplant lymphoproliferative disorder. Nervous system disorders: Aphasia, brain injury, bulbar palsy, central nervous system lesion, cerebral microangiopathy, cerebral ventricle dilatation, cerebrovascular accident, cognitive disorder, convulsion, coordination abnormal, encephalitis, encephalopathy, hemiplegia, hypotonia, leukoencephalopathy, memory impairment, motor dysfunction, neurotoxicity, quadriparesis, speech disorder, tremor, VIIth nerve paralysis, white matter lesion. Psychiatric disorders: Delirium, depression, disorientation, suicidal ideation. Renal and urinary disorders: Renal failure, nephropathy toxic. Respiratory, thoracic and mediastinal disorders: Acute respiratory distress, aspiration, dyspnea exertional, interstitial lung disease, lung disorder, pneumonitis, pulmonary arteriopathy, pulmonary sepsis, pulmonary veno-occlusive disease, respiratory distress, respiratory failure, pulmonary hypertension. Skin and subcutaneous tissue disorders: Stevens-Johnson syndrome and toxic epidermal necrolysis. Vascular disorders: Capillary leak syndrome.

Usage information

Dosing and administration
2 DOSAGE AND ADMINISTRATION The recommended dose of TEPADINA for class 3 beta-thalassemia is two administrations of 5 mg/kg given intravenously approximately 12 hours apart on Day -6 before allogeneic HSCT in conjunction with high-dose busulfan and cyclophosphamide. (2.1) The recommended dose of TEPADINA for treatment of adenocarcinoma of the breast or ovary is 0.3 to 0.4 mg/kg intravenously. (2.1) The recommended dose of TEPADINA for treatment of malignant effusions is 0.6 to 0.8 mg/kg intracavitary. (2.1) The recommended dose of TEPADINA for treatment of superficial papillary carcinoma of the urinary bladder is 60 mg in 30 to 60 mL of Sodium Chloride Injection into the bladder by catheter. (2.1) 2.1 Recommended Dosage The recommended dose of TEPADINA in pediatric patients is two administrations of 5 mg/kg given intravenously approximately 12 hours apart on Day -6 before allogeneic HSCT in conjunction with high-dose busulfan and cyclophosphamide as outlined in Table 1. See Prescribing Information for cyclophosphamide and busulfan for information on these drugs. Table 1: Dosage Regimen For Allogeneic HSCT In Pediatric Patients With Class 3 Beta-Thalassemia Day prior to transplantation Treatment Day -10 Day -9 Day -8 Day -7 Day -6 Day -5 Day -4 Day -3 Day -2 Day -1 Day -0 Busulfan IV weight-based dose *Busulfan IV weight-based dose * ▲ ▲ ▲ ▲ TEPADINA IV 5 mg/kg twiceTEPADINA IV 5 mg/kg twice ▲ Cyclophosphamide IV 40 mg/kg/day ▲ ▲ ▲ ▲ Stem cell InfusionStem cell Infusion ▲ *Busulfan IV weight-based dose: 1.0 mg/kg every 6 hours for patients less than 9 kg; 1.2 mg/kg every 6 hours for patients 9 to 16 kg; 1.1 mg/kg every 6 hours for patients 16.1 to 23 kg; 0.95 mg/kg every 6 hours for patients 23.1 to 34 kg; 0.8 mg/kg every 6 hours for patients more than 34 kg. Infuse TEPADINA via a central venous catheter over 3 hours using an infusion set equipped with a 0.2 micron in-line filter. Prior to and following each infusion, flush the catheter with approximately 5 ml sodium chloride 0.9% solution for injection. TEPADINA is excreted through the skin of patients receiving high-dose therapy. Take precautions to prevent skin toxicity [ see Warnings and Precautions ( 5.3)]. Adenocarcinoma of the Breast or Ovary​ The recommended dose of TEPADINA for treatment of adenocarcinoma of the breast or ovary is 0.3 to 0.4 mg/kg intravenously. Doses should be given at 1 to 4 week intervals. Initially the higher dose in the given range is commonly administered. The maintenance dose should be adjusted weekly on the basis of pretreatment control blood counts and subsequent blood counts. Maintenance doses should not be administered more frequently than weekly. Malignant Effusions The recommended dose of TEPADINA for treatment of malignant effusions is 0.6 to 0.8 mg/kg intracavitary. Administration is usually effected through the same tubing which is used to remove the fluid from the cavity involved. Doses should be given at 1 to 4 week intervals. Initially the higher dose in the given range is commonly administered. The maintenance dose should be adjusted weekly on the basis of pretreatment control blood counts and subsequent blood counts. Maintenance doses should not be administered more frequently than weekly. Superficial Papillary Carcinoma of the Urinary Bladder​ The recommended dose of TEPADINA for treatment of superficial papillary carcinoma of the urinary bladder is 60 mg in 30 to 60 mL of Sodium Chloride Injection into the bladder by catheter. The solution should be retained for 2 hours. If the patient finds it impossible to retain 60 mL for 2 hours, the dose may be given in a volume of 30 mL. The patient may be repositioned every 15 minutes for maximum area contact. The usual course of treatment is once a week for 4 weeks. The course may be repeated if necessary, but second and third courses must be given with caution since bone-marrow depression may be increased. 2.2 Preparation Instructions TEPADINA is a cytotoxic drug. Follow applicable special handling and disposal procedures1. Reconstitution Reconstitute TEPADINA 15 mg with 1.5 ml of sterile water for injection. Using a syringe fitted with a needle, aseptically withdraw 1.5 ml of sterile water for injection. Inject the content of the syringe into the vial through the rubber stopper. Remove the syringe and needle, and mix manually by repeated inversions. Reconstitute TEPADINA 100 mg with 10 ml of sterile water for injection. Using a syringe fitted with a needle, aseptically withdraw 10 ml of sterile water for injection. Inject the content of the syringe into the vial through the rubber stopper. Remove the syringe and needle, and mix manually by repeated inversions. The reconstituted solution is hypotonic and must be diluted in saline prior to administration. Reconstituted solutions, free of visible particulate matter, may occasionally show opalescence; such solutions can still be used for further dilution. If not used immediately after reconstitution, the product is stable for 8 hours when stored at 2°C to 8°C (36° to 46°F). Dilution in the infusion bag Prior to administration, dilute the reconstituted solution further with an appropriate volume of sodium chloride 0.9% solution for injection to obtain a final TEPADINA concentration between 0.5 and 1 mg/mL. Dilute TEPADINA as recommended in Table 2. Table 2: Dilution of TEPADINA in the infusion bag Calculated TEPADINA Dose Dilution Volume (Sodium Chloride 0.9% solution for injection) Less than 250 mg Appropriate volume to obtain a final concentration of 0.5 to 1 mg/mL 250 mg to 500 mg 500 mL or appropriate volume to obtain a final concentration of 0.5 to 1 mg/mL Greater than 500 mg 1000 mL or appropriate volume to obtain a final concentration of 0.5 to 1 mg/mL After dilution the product is stable for 24 hours when stored at 2°C to 8°C (36° to 46°F) and for 4 hours when stored at 25°C (77°F). From a microbiological point of view, the product should be used immediately. Inspect the diluted solution visually for particulate matter and discoloration prior to administration. Use TEPADINA diluted solutions only if free of visible particulate matter. Filter using a 0.2 micron filter prior to administration. Filtering does not alter solution potency
Use in special populations
8 USE IN SPECIFIC POPULATIONS Lactation: Breastfeeding is not recommended. (8.2) Moderate or severe renal impairment: Monitor patients more frequently for toxicity. (8.6, 12.2) Moderate or severe hepatic impairment: Monitor patients more frequently for toxicity. (8.7, 12.2) See 17 for PATIENT COUNSELING INFORMATION 8.1 Pregnancy Risk Summary TEPADINA can cause fetal harm when administered to a pregnant woman based on findings from animals and the drug’s mechanism of action [ see Clinical Pharmacology ( 12.1 )]. Limited available data with TEPADINA use in pregnant women are insufficient to inform a drug-associated risk of major birth defects and miscarriage. In animal reproduction studies, administration of thiotepa to pregnant rats and rabbits during organogenesis produced teratogenic effects (alterations in embryo development, anomalies of the skeletal system of the fetus) at doses approximately 0.125 and 1 times, respectively, the maximum recommended human daily dose on a mg/m 2 basis. Thiotepa was lethal to rabbit fetuses at approximately 2 times the maximum recommended human therapeutic dose based on body-surface area [ see Data]. Consider the benefits and risks of TEPADINA for the mother and possible risks to the fetus when prescribing TEPADINA to a pregnant woman. The estimated background risk of major birth defects and miscarriage for the indicated population is unknown. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2-4% and 15-20%, respectively. Data Animal Data Thiotepa given by the IP route in mice at doses ≥ 1 mg/kg (3.2 mg/m 2), approximately 8-fold less than the maximum recommended human therapeutic dose based on body-surface area, and in rats at doses ≥ 3 mg/kg (21 mg/m 2), approximately equal to the maximum recommended human therapeutic dose based on body-surface area, resulted in various malformations including neural tube defects, omphalocele, renal agenesis, atresia ani, limb and digit defects, cleft palate, micrognathia, other skeletal anomalies in the skull, vertebrae and ribs, and reduced skeletal ossification. Thiotepa was lethal to rabbit fetuses at a dose of 3 mg/kg (41 mg/m 2), approximately 2 times the maximum recommended human therapeutic dose based on bodysurface area. 8.2 Lactation Risk Summary There is no information regarding the presence of thiotepa in human milk, the effects on the breastfed infant, or the effects on milk production. Because of the potential for serious adverse reactions, including the potential for tumorigenicity shown for thiotepa in animal studies, advise patients not to breastfeed during TEPADINA treatment. 8.3 Females and Males of Reproductive Potential Pregnancy testing TEPADINA can cause fetal harm when administered to a pregnant female. Verify the pregnancy status of females of reproductive potential prior to initiating TEPADINA therapy. Contraception Females Advise females of reproductive potential to avoid pregnancy during TEPADINA treatment and for at least 6 months after the final dose of TEPADINA. Advise females to immediately report pregnancy [ see Use in Specific Populations (8.1)] . Males TEPADINA may damage spermatozoa and testicular tissue, resulting in possible genetic abnormalities. Males with female sexual partners of reproductive potential should use effective contraception during TEPADINA treatment and for at least 1 year after the final dose of TEPADINA [ see Nonclinical Toxicology ( 13.1 )]. Infertility Based on nonclinical findings, male and female fertility may be compromised by treatment with TEPADINA. Inform male patients about the possibility of sperm conservation before the start of therapy [ see Nonclinical Toxicology (13.1)]. 8.4 Pediatric Use The safety and effectiveness of TEPADINA for prevention of graft rejection in pediatric patients undergoing allogeneic HSCT for class 3 beta-thalassemia was established in one prospective study and one retrospective study [ see Clinical Studies (14)] that included 1 infant (1 month to 1 year), 23 children (2 to 11 years) and 13 adolescents (12 to 16 years) who received TEPADINA as part of their preparative regimen. Safety and effectiveness of TEPADINA in neonates have not been established. Safety and effectiveness of TEPADINA for treatment of adenocarcinoma of the breast, adenocarcinoma of the ovary, malignant effusions and superficial papillary carcinoma of the urinary bladder in pediatric patients have not been established. 8.5 Geriatric Use The safety and effectiveness of TEPADINA as a preparative regimen prior to allogeneic hematopoietic progenitor (stem) cell transplantation (HSCT) for patients with class 3 beta-thalassemia have not been established in geriatric patients. Clinical studies of TEPADINA for this indication did not include subjects aged 65 and over. Clinical studies of TEPADINA for treatment of adenocarcinoma of the breast, adenocarcinoma of the ovary, malignant effusions and superficial papillary carcinoma of the urinary bladder did not include sufficient numbers of subjects aged 65 and over to determine whether elderly subjects respond differently from younger subjects, and other reported clinical experience has not identified differences in responses between the elderly and younger patients. In general, dose selection for an elderly patient should be cautious, usually starting at the low end of the dosing range, reflecting the greater frequency of decreasing hepatic, renal or cardiac function, and of concomitant disease or other drug therapy. 8.6 Renal Impairment In patients with moderate (creatinine clearance (CLcr) of 30 mL/min to 59 mL/min) renal impairment, decreased renal excretion may result in increased plasma levels of thiotepa and TEPA [see Clinical Pharmacology ( 12.2 )]. This may result in increased toxicity. Monitor patients with moderate to severe (CLcr < 30 mL/min) renal impairment for signs and symptoms of toxicity following treatment with TEPADINA for an extended period of time. 8.7 Hepatic Impairment Thiotepa is extensively metabolized in the liver. Patients with moderate (bilirubin levels greater than 1.5 times to 3 times the upper limit of normal and any AST) hepatic impairment may have increased plasma levels of thiotepa [ see Clinical Pharmacology ( 12.2 )] . This may result in toxicity. Monitor patients with moderate to severe (bilirubin levels greater than 3 times upper limit of normal and any AST) hepatic impairment for signs and symptoms of toxicity following treatment with TEPADINA for an extended period of time.

Interactions

7 DRUG INTERACTIONS 7.1 Effect of Cytochrome CYP3A Inhibitors and Inducers In vitro studies suggest that thiotepa is metabolized by CYP3A4 and CYP2B6 to its active metabolite TEPA. Avoid coadministration of strong CYP3A4 inhibitors (e.g., itraconazole, clarithromycin, ritonavir) and strong CYP3A4 inducers (e.g., rifampin, phenytoin) with TEPADINA due to the potential effects on efficacy and toxicity [see Clinical Pharmacology ( 12.2 )]. Consider alternative medications with no or minimal potential to inhibit or induce CYP3A4. If concomitant use of strong CYP3A4 modulators cannot be avoided, closely monitor for adverse drug reactions. 7.2 Effect of TEPADINA on Cytochrome CYP2B6 Substrates In vitro studies suggest that thiotepa inhibits CYP2B6. TEPADINA may increase the exposure of drugs that are substrates of CYP2B6 in patients; however, the clinical relevance of this in vitro interaction is unknown [see Clinical Pharmacology ( 12.2 )]. The administration of thiotepa with cyclophosphamide in patients reduces the conversion of cyclophosphamide to the active metabolite, 4-hydroxycyclophosphamide; the effect appears sequence dependent with a greater reduction in the conversion to 4-hydroxycyclophosphamide when thiotepa is administered 1.5 hours prior to the intravenous administration of cyclophosphamide compared to administration of thiotepa after intravenous cyclophosphamide [see Clinical Pharmacology ( 12.2 )]. The reduction in 4-hydroxycyclophosphamide levels may potentially reduce efficacy of cyclophosphamide treatment.

More information

Category Value
Authorisation number NDA208264
Agency product number 905Z5W3GKH
Orphan designation No
Product NDC 53964-001,53964-002
Date Last Revised 12-05-2017
Type HUMAN PRESCRIPTION DRUG
RXCUI 1919209
Marketing authorisation holder ADIENNE SA
Warnings WARNING: SEVERE MYELOSUPPRESSION, CARCINOGENICITY TEPADINA may cause severe marrow suppression, and high doses may cause marrow ablation with resulting infection or bleeding. Monitor hematologic laboratory parameters. Hematopoietic progenitor (stem) cell transplantation (HSCT) is required to prevent potentially fatal complications of the prolonged myelosuppression after high doses of TEPADINA [see Warnings and Precautions (5.1)] TEPADINA should be considered potentially carcinogenic in humans [see Warnings and Precautions (5.7)] WARNING: SEVERE MYELOSUPPRESSION, CARCINOGENICITY TEPADINA may cause severe marrow suppression, and high doses may cause marrow ablation with resulting infection or bleeding. Monitor hematologic laboratory parameters. Hematopoietic progenitor (stem) cell transplantation (HSCT) is required to prevent potentially fatal complications of the prolonged myelosuppression after high doses of TEPADINA [see Warnings and Precautions (5.1)] TEPADINA should be considered potentially carcinogenic in humans [see Warnings and Precautions (5.7)]