Tepadina Injection

Name: Tepadina Injection

Indications and Usage for Tepadina Injection

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)].

Adenocarcinoma of the Breast or Ovary

TEPADINA is indicated for treatment of adenocarcinoma of the breast or ovary.

Malignant Effusions

TEPADINA is indicated for controlling intracavitary effusions secondary to diffuse or localized neoplastic diseases of various serosal cavities.

Superficial Papillary Carcinoma of the Urinary Bladder

TEPADINA is indicated for treatment of superficial papillary carcinoma of the urinary bladder.

Warnings and Precautions

Myelosuppression

The consequence of treatment with high doses of TEPADINA together with other chemotherapy at the recommended dose and schedule in the preparative regimen for class 3 beta- thalassemia is profound myelosuppression occurring in all patients. Do not begin the preparative regimen if a stem cell donor is not available. Monitor complete blood counts, and provide supportive care for infections, anemia and thrombocytopenia until there is adequate hematopoietic recovery.

For patients receiving TEPADINA for treatment of adenocarcinoma of the breast, adenocarcinoma of the ovary, malignant effusions and superficial papillary carcinoma of the urinary bladder, if the bone marrow has been compromised by prior irradiation or chemotherapy, or is recovering from chemotherapy, the risk of severe myelosuppression with TEPADINA may be increased. Perform periodic complete blood counts during the course of treatment with TEPADINA. Provide supportive care for infections, bleeding, and symptomatic anemia [see Adverse Reactions (6.1)].

Hypersensitivity

Clinically significant hypersensitivity reactions, including anaphylaxis, have occurred following administration of TEPADINA. If anaphylactic or other clinically significant allergic reaction occurs, discontinue treatment with TEPADINA, initiate appropriate therapy, and monitor until signs and symptoms resolve [see Contraindications (4), Adverse Reactions (6.1)].

Cutaneous Toxicity

TEPADINA and/or its active metabolites may be excreted in part via skin patients receiving high-dose therapy. Treatment with TEPADINA may cause skin discoloration, pruritus, blistering, desquamation, and peeling that may be more severe in the groin, axillae, skin folds, in the neck area, and under dressings. Instruct patients to shower or bathe with water at least twice daily through 48 hours after administration of TEPADINA. Change occlusive dressing and clean the covered skin at least twice daily through 48 hours after administration of TEPADINA. Change bed sheets daily during treatment.

Skin reactions associated with accidental exposure to TEPADINA may also occur. Wash the skin thoroughly with soap and water in case TEPADINA solution contacts the skin. Flush mucous membranes in case of TEPADINA contact with mucous membranes.

Concomitant Use of Live and Attenuated Vaccines

Do not administer live or attenuated viral or bacterial vaccines to a patient treated with TEPADINA until the immunosuppressive effects have resolved.

Hepatic Veno-Occlusive Disease

Hepatic veno-occlusive disease may occur in patients who have received high-dose TEPADINA in conjunction with busulfan and cyclophosphamide [see Adverse Reactions (6.1)]. Monitor by physical examination, serum transaminases and bilirubin daily through BMT Day +28, and provide supportive care to patients who develop hepatic veno-occlusive disease.

Central Nervous System Toxicity

Fatal encephalopathy has occurred in patients treated with high doses of thiotepa. Other central nervous system toxicities, such as headache, apathy, psychomotor retardation, disorientation, confusion, amnesia, hallucinations, drowsiness, somnolence, seizures, coma, inappropriate behaviour and forgetfulness have been reported to occur in a dose-dependent manner during or shortly after administration of high-dose thiotepa. In pediatric patients treated with TEPADINA at the recommended dose in combination with busulfan and cyclophosphamide, 8% developed central nervous system toxicity (seizures and intracranial hemorrhage). Do not exceed the recommended dose of TEPADINA. If severe or life-threatening central nervous system toxicity occurs, discontinue administration of TEPADINA and provide supportive care.

Carcinogenicity

Like many alkylating agents, thiotepa has been reported to be carcinogenic when administered to laboratory animals [see Nonclinical Toxicity (13.1)]. Carcinogenicity is shown most clearly in studies using mice, but there is some evidence of carcinogenicity in man. There is an increased risk of a secondary malignancy with use of TEPADINA.

Embryo-Fetal Toxicity

Based on the mechanism of action and findings in animals, TEPADINA can cause fetal harm when administered to a pregnant woman. There are no adequate and well-controlled studies of TEPADINA in pregnant women. Thiotepa given by the intraperitoneal (IP) route was teratogenic in mice at doses ≥ 1 mg/kg (3.2 mg/m 2), approximately 8-fold less than the maximum recommended human therapeutic dose (0.8 mg/kg, 27 mg/m 2), based on body-surface area. Thiotepa given by the IP route was teratogenic 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. Thiotepa was lethal to rabbit fetuses at a dose of 3 mg/kg (41 mg/m 2), approximately two times the maximum recommended human therapeutic dose based on body-surface area.

Advise pregnant women of the potential risk to the fetus [ see Use in Specific Populations (8.1, 8.3)]. Advise females of reproductive potential to use highly effective contraception during and after treatment with TEPADINA for at least 6 months after therapy. Advise males of reproductive potential to use effective contraception during and after treatment with TEPADINA for at least 1 year after therapy [ see Use in Specific Populations (8.1, 8.3)].

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)]

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.

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.

Use in specific populations

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.

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.

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 [seeUse 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)].

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.

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.

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.

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.

Clinical Studies

TEPADINA was evaluated in a retrospective study of pediatric patients with class 3 beta-thalassemia who underwent allogeneic hematopoietic progenitor (stem) cell transplantation (HSCT) from a human leukocyte antigen (HLA)-identical sibling donor. Twenty-five patients (10 male and 15 female) of median age 10 years (range, 5-16 years) were treated with intravenous busulfan at weight-based dosing from Day -10 to Day -7 pretransplant [ see Table 1]), intravenous TEPADINA 5 mg/kg twice on Day -6, intravenous cyclophosphamide 40 mg/kg/day on Day -5 to Day -2, and marrow infusion on Day 0. All patients had also received precytoreduction with hydroxyurea, azathioprine and fludarabine prior to start of the preparative regimen.

Efficacy was based on the incidence of graft rejection (primary or late rejection). The incidence of graft rejection in these 25 patients using TEPADINA was 0% (95% CI: [0, 0.12]). Of the 51 patients who received the same preparative regimen, historically, without TEPADINA, the incidence of graft rejection reported was 25.5% (95% CI: [0.13, 0.37]).

Uses

Thiotepa is used to treat cancer. It works by slowing or stopping the growth of cancer cells. Thiotepa is often given into the bladder to treat bladder cancer.

Thiotepa is also used with other medications to prevent rejection of a stem cell transplant.

How to use Tepadina Vial

This medication is given by injection into a vein by a health care professional. Sometimes, thiotepa is injected directly into the tumor. Tell your doctor or nurse right away if you experience pain, burning, or redness at the injection site.

For treatment of bladder cancer, thiotepa is usually given into the bladder through a tube (catheter). Your doctor may direct you to limit fluids for 8 to 12 hours before the medication is given. The solution is usually left in place for 2 hours and then drained out through the bladder tube. Your doctor may direct you to change positions every 15 minutes while the solution is in your bladder to make sure the solution treats all parts of your bladder.

If you are using this medication to prevent rejection of a stem cell transplant, you should receive 2 doses of this medication 12 hours apart. During treatment, skin problems may occur. To reduce the risk of skin problems, shower or bathe with water and change any bandages or dressings at least twice a day until 48 hours after stopping treatment. Also, change your bed sheets daily while receiving treatment. See also Side Effects section.

The dosage and how often the medication is given is based on your medical condition and response to treatment. Your doctor will do blood tests (complete blood count) to find the right dose for you. Your next dose may need to be rescheduled if your white blood cell count or platelets are too low.

Learn how to handle, use, and discard chemotherapy and medical supplies safely. Consult your pharmacist. Wear gloves and wash your hands carefully after handling this drug. Avoid getting this medication in your eyes or on your skin. If the medication gets in your eye, wash the affected eye(s) well with water and contact your doctor. If the medication gets on your skin, wash the area well with soap and water.

Side Effects

See also Warning section.

Pain/redness at the injection site, dizziness, headache, blurred vision, fever, nausea, vomiting, stomach/abdominal pain, or loss of appetite may occur. Changes in diet such as eating several small meals or limiting activity may help lessen some of these effects. In some cases, drug treatment may be necessary to prevent or relieve nausea and vomiting. If any of these effects persist or worsen, tell your doctor or pharmacist promptly.

Temporary hair loss is another common side effect. Normal hair growth should return after treatment has ended.

People using this medication may have serious side effects. However, your doctor has prescribed this drug because he or she has judged that the benefit to you is greater than the risk ofside effects. Careful monitoring by your doctor may decrease your risk.

Painful sores on the lips, mouth, and throat may occur. To decrease the risk, limit hot foods and drinks, brush your teeth carefully, avoid using mouthwash that contains alcohol, and rinse your mouth frequently with cool water.

This medication may also cause very serious bleeding. Tell your doctor right away if any signs of serious bleeding occur, including: bloody/black/tarry stools, coughing up blood, nosebleeds that are frequent or hard to stop, dizziness/fainting, fast/irregular heartbeat, pale/gray/bluish skin, vomit that is bloody or looks like coffee grounds.

Tell your doctor right away if you have any serious side effects, including: severe stomach/abdominal pain, lower back/side pain, painful/difficult urination, pink/dark urine.

If you are using this medication to prevent rejection, tell your doctor right away if you have any serious side effects, including: signs of skin problems (such as changes in skin color, skin peeling/blisters), signs of liver problems (such as nausea/vomiting that doesn't stop, loss of appetite, stomach/abdominal pain, yellowing of eyes/skin), mental/mood changes (such as confusion, hallucinations, changes in behavior).

This medication can affect sperm production, an effect that may lower male fertility. Consult your doctor for more details.

A very serious allergic reaction to this drug is rare. However, get medical help right away if you notice any symptoms of a serious allergic reaction, including: rash, itching/swelling (especially of the face/tongue/throat), severe dizziness, trouble breathing.

This is not a complete list of possible side effects. If you notice other effects not listed above, contact your doctor or pharmacist.

In the US -

Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088 or at www.fda.gov/medwatch.

In Canada - Call your doctor for medical advice about side effects. You may report side effects to Health Canada at 1-866-234-2345.

List Tepadina Vial side effects by likelihood and severity.

Precautions

Before using thiotepa, tell your doctor or pharmacist if you are allergic to it; or if you have any other allergies. This product may contain inactive ingredients, which can cause allergic reactions or other problems. Talk to your pharmacist for more details.

Before using this medication, tell your doctor or pharmacist your medical history, especially: bone marrow problems (e.g., low white blood cell count/platelets from previous chemotherapy/radiation treatment), kidney disease, liver disease.

Thiotepa can make you more likely to get infections or may worsen any current infections. Avoid contact with people who have infections that may spread to others (such as chickenpox, measles, flu). Consult your doctor if you have been exposed to an infection or for more details.

Do not have immunizations/vaccinations without the consent of your doctor. Avoid contact with people who have recently received live vaccines (such as flu vaccine inhaled through the nose).

To lower your risk of getting cut, bruised, or injured, use caution with sharp objects like razors and nail cutters, and avoid activities such as contact sports.

Before having surgery, tell your doctor or dentist about all the products you use (including prescription drugs, nonprescription drugs, and herbal products).

Tell your doctor if you are pregnant or plan to become pregnant. You should not become pregnant while using thiotepa. Thiotepa may harm an unborn baby. Women should ask about reliable forms of birth control while using this medication and for 6 months after stopping treatment. Women should also take a pregnancy test before starting treatment. Men should ask about reliable forms of birth control while using this medication and for 1 year after stopping treatment. If you or your partner becomes pregnant, talk to your doctor right away about the risks and benefits of this medication.

It is unknown if this medication passes into breast milk. Because of the possible risk to the infant, breast-feeding while using this drug is not recommended. Consult your doctor before breast-feeding.

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