The recommended dose is 370 mg/m2/day (10 mg/kg/day) divided in two daily infusions, administered before allogeneic HPCT, without exceeding the total maximum cumulative dose of 370 mg/m2 (10 mg/ kg), during the time of the entire conditioning treatment.
The recommended dose is 370 mg/m2/day (10 mg/kg/day) divided in two daily infusions, administered before allogeneic HPCT, without exceeding the total maximum cumulative dose of 370 mg/m2 (10 mg/ kg), during the time of the entire conditioning treatment.
|offLabelAdultGuideSupport=There is limited information regarding <i>Off-Label Guideline-Supported Use</i> of Thiotepa in adult patients.
|offLabelAdultNoGuideSupport=There is limited information regarding <i>Off-Label Non–Guideline-Supported Use</i> of Thiotepa in adult patients.
|fdaLIADPed=AUTOLOGOUS HPCT
|fdaLIADPed=AUTOLOGOUS HPCT
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Prior to and following each infusion, the indwelling catheter line should be flushed with approximately 5 ml sodium chloride 9 mg/ml (0.9 %) solution for injection.
Prior to and following each infusion, the indwelling catheter line should be flushed with approximately 5 ml sodium chloride 9 mg/ml (0.9 %) solution for injection.
|offLabelPedGuideSupport=There is limited information regarding <i>Off-Label Guideline-Supported Use</i> of Thiotepa in pediatric patients.
|offLabelPedNoGuideSupport=There is limited information regarding <i>Off-Label Non–Guideline-Supported Use</i> of Thiotepa in pediatric patients.
|contraindications=* existing hepatic, renal or bone marrow damage (may use low dosage and frequent monitoring if need outweighs risk)
|contraindications=* existing hepatic, renal or bone marrow damage (may use low dosage and frequent monitoring if need outweighs risk)
* hypersensitivity to thiotepa
* hypersensitivity to thiotepa
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|useInOthers=(Description)
|useInOthers=(Description)
|administration=* Oral
|administration=* Oral
|monitoring=* Blood counts and liver enzymes
|monitoring=* Blood counts and liver enzymes
|drugBox={{Drugbox2
|drugBox={{Drugbox2
| verifiedrevid =
| verifiedrevid =
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Each carton contains 1 vial.
Each carton contains 1 vial.
: [[File:{{PAGENAME}}01.png|thumb|none|600px|This image is provided by the National Library of Medicine.]]
: [[File:{{PAGENAME}}01.png|thumb|none|600px|This image is provided by the National Library of Medicine.]]
|alcohol=Alcohol-Thiotepa interaction has not been established. Talk to your doctor about the effects of taking alcohol with this medication.
|alcohol=Alcohol-Thiotepa interaction has not been established. Talk to your doctor about the effects of taking alcohol with this medication.
|brandNames=* ®<ref>{{Cite web | title = | url = }}</ref>
|brandNames=* ®<ref>{{Cite web | title = | url = }}</ref>
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The recommended dose in haematological diseases ranges from 125 mg/m2/day (3.38 mg/kg/day) to 300 mg/m2/day (8.10 mg/kg/day) as a single daily infusion, administered from 2 up to 4 consecutive days before autologous HPCT depending on the combination with other chemotherapeutic medicinal products, without exceeding the total maximum cumulative dose of 900 mg/m2 (24.32 mg/kg), during the time of the entire conditioning treatment.
LYMPHOMA
The recommended dose ranges from 125 mg/m2/day (3.38 mg/kg/day) to 300 mg/m2/day (8.10 mg/ kg/day) as a single daily infusion, administered from 2 up to 4 consecutive days before autologous HPCT depending on the combination with other chemotherapeutic medicinal products, without exceeding the total maximum cumulative dose of 900 mg/m2 (24.32 mg/kg), during the time of the entire conditioning treatment.
CNS LYMPHOMA
The recommended dose is 185 mg/m2/day (5 mg/kg/day) as a single daily infusion, administered for 2 consecutive days before autologous HPCT, without exceeding the total maximum cumulative dose of 370 mg/m2 (10 mg/kg), during the time of the entire conditioning treatment.
MULTIPLE MYELOMA
The recommended dose ranges from 150 mg/m2/day (4.05 mg/kg/day) to 250 mg/m2/day (6.76 mg/ kg/day) as a single daily infusion, administered for 3 consecutive days before autologous HPCT depending on the combination with other chemotherapeutic medicinal products, without exceeding the total maximum cumulative dose of 750 mg/m2 (20.27 mg/kg), during the time of the entire conditioning treatment.
Solid tumours
The recommended dose in solid tumours ranges from 120 mg/m2/day (3.24 mg/kg/day) to 250 mg/ m2/day (6.76 mg/kg/day) divided in one or two daily infusions, administered from 2 up to 5 consecutive days before autologous HPCT depending on the combination with other chemotherapeutic medicinal products, without exceeding the total maximum cumulative dose of 800 mg/m2 (21.62 mg/kg), during the time of the entire conditioning treatment.
BREAST CANCER
The recommended dose ranges from 120 mg/m2/day (3.24 mg/kg/day) to 250 mg/m2/day (6.76 mg/ kg/day) as a single daily infusion, administered from 3 up to 5 consecutive days before autologous HPCT depending on the combination with other chemotherapeutic medicinal products, without exceeding the total maximum cumulative dose of 800 mg/m2 (21.62 mg/kg), during the time of the entire conditioning treatment.
CNS TUMOURS
The recommended dose ranges from 125 mg/m2/day (3.38 mg/kg/day) to 250 mg/m2/day (6.76 mg/ kg/day) divided in one or two daily infusions, administered from 3 up to 4 consecutive days before autologous HPCT depending on the combination with other chemotherapeutic medicinal products, without exceeding the total maximum cumulative dose of 750 mg/m2 (20.27 mg/kg), during the time of the entire conditioning treatment.
OVARIAN CANCER
The recommended dose is 250 mg/m2/day (6.76 mg/kg/day) as a single daily infusion, administered in 2 consecutive days before autologous HPCT, without exceeding the total maximum cumulative dose of 500 mg/m2 (13.51 mg/kg), during the time of the entire conditioning treatment.
GERM CELL TUMOURS
The recommended dose ranges from 150 mg/m2/day (4.05 mg/kg/day) to 250 mg/m2/day (6.76 mg/ kg/day) as a single daily infusion, administered for 3 consecutive days before autologous HPCT depending on the combination with other chemotherapeutic medicinal products, without exceeding the total maximum cumulative dose of 750 mg/m2 (20.27 mg/kg), during the time of the entire conditioning treatment.
ALLOGENEIC HPCT
Haematological diseases
The recommended dose in haematological diseases ranges from 185 mg/m2/day (5 mg/kg/day) to 481 mg/m2/day (13 mg/kg/day) divided in one or two daily infusions, administered from 1 up to 3 consecutive days before allogeneic HPCT depending on the combination with other chemotherapeutic medicinal products, without exceeding the total maximum cumulative dose of 555 mg/m2 (15 mg/kg), during the time of the entire conditioning treatment.
LYMPHOMA
The recommended dose in lymphoma is 370 mg/m2/day (10 mg/kg/day) divided in two daily infusions before allogeneic HPCT, without exceeding the total maximum cumulative dose of 370 mg/m2 (10 mg/ kg), during the time of the entire conditioning treatment.
MULTIPLE MYELOMA
The recommended dose is 185 mg/m2/day (5 mg/kg/day) as a single daily infusion before allogeneic HPCT, without exceeding the total maximum cumulative dose of 185 mg/m2 (5 mg/kg), during the time of the entire conditioning treatment.
LEUKEMIA
The recommended dose ranges from 185 mg/m2/day (5 mg/kg/day) to 481 mg/m2/day (13 mg/kg/day) divided in one or two daily infusions, administered from 1 up to 2 consecutive days before allogeneic HPCT depending on the combination with other chemotherapeutic medicinal products, without exceeding the total maximum cumulative dose of 555 mg/m2 (15 mg/kg), during the time of the entire conditioning treatment.
THALASSEMIA
The recommended dose is 370 mg/m2/day (10 mg/kg/day) divided in two daily infusions, administered before allogeneic HPCT, without exceeding the total maximum cumulative dose of 370 mg/m2 (10 mg/ kg), during the time of the entire conditioning treatment.
Off-Label Use and Dosage (Adult)
Guideline-Supported Use
There is limited information regarding Off-Label Guideline-Supported Use of Thiotepa in adult patients.
Non–Guideline-Supported Use
There is limited information regarding Off-Label Non–Guideline-Supported Use of Thiotepa in adult patients.
Pediatric Indications and Dosage
FDA-Labeled Indications and Dosage (Pediatric)
AUTOLOGOUS HPCT
Solid tumours
The recommended dose in solid tumours ranges from 150 mg/m2/day (6 mg/kg/day) to 350 mg/ m2/day (14 mg/kg/day) as a single daily infusion, administered from 2 up to 3 consecutive days before autologous HPCT depending on the combination with other chemotherapeutic medicinal products, without exceeding the total maximum cumulative dose of 1050 mg/m2 (42 mg/kg), during the time of the entire conditioning treatment.
CNS TUMOURS
The recommended dose ranges from 250 mg/m2/day (10 mg/kg/day) to 350 mg/m2/day (14 mg/kg/ day) as a single daily infusion, administered for 3 consecutive days before autologous HPCT depending on the combination with other chemotherapeutic medicinal products, without exceeding the total maximum cumulative dose of 1050 mg/m2 (42 mg/kg), during the time of the entire conditioning treatment.
ALLOGENEIC HPCT
Haematological diseases
The recommended dose in haematological diseases ranges from 125 mg/m2/day (5 mg/kg/day) to 250 mg/ m2/day (10 mg/kg/day) divided in one or two daily infusions, administered from 1 up to 3 consecutive days before allogeneic HPCT depending on the combination with other chemotherapeutic medicinal products, without exceeding the total maximum cumulative dose of 375 mg/m2 (15 mg/kg), during the time of the entire conditioning treatment.
LEUKEMIA
The recommended dose is 250 mg/m2/day (10 mg/kg/day) divided in two daily infusions, administered before allogeneic HPCT, without exceeding the total maximum cumulative dose of 250 mg/m2 (10 mg/ kg), during the time of the entire conditioning treatment.
THALASSEMIA
The recommended dose ranges from 200 mg/m2/day (8 mg/kg/day) to 250 mg/m2/day (10 mg/kg/ day) divided in two daily infusions, administered before allogeneic HPCT without exceeding the total maximum cumulative dose of 250 mg/m2 (10 mg/kg), during the time of the entire conditioning treatment.
REFRACTORY CYTOPENIA
The recommended dose is 125 mg/m2/day (5 mg/kg/day) as a single daily infusion, administered for 3 consecutive days before allogeneic HPCT, without exceeding the total maximum cumulative dose of 375 mg/m2 (15 mg/kg), during the time of the entire conditioning treatment.
GENETIC DISEASES
The recommended dose is 125 mg/m2/day (5 mg/kg/day) as a single daily infusion, administered for 2 consecutive days before allogeneic HPCT, without exceeding the total maximum cumulative dose of 250 mg/m2 (10 mg/kg), during the time of the entire conditioning treatment.
SICKLE CELL ANAEMIA
The recommended dose is 250 mg/m2/day (10 mg/kg/day) divided in two daily infusions, administered before allogeneic HPCT, without exceeding the total maximum cumulative dose of 250 mg/m2 (10 mg/ kg), during the time of the entire conditioning treatment.
Reconstitution
TEPADINA® must be reconstituted with 1.5 ml of sterile water for injections.
Using a syringe fitted with a needle, aseptically withdraw 1.5 ml of sterile water for injections.
Inject the content of the syringe into the vial through the rubber stopper.
Remove the syringe and the needle and mix manually by repeated inversions.
Only clear colourless solutions, without any particulate matter, must be used.
Further dilution in the infusion bag
The reconstituted solution is hypotonic and must be further diluted prior to administration with 500 ml sodium chloride 9 mg/ml (0.9 %) solution for injection (1000 ml if the dose is higher than 500 mg) or with an appropriate volume of sodium chloride 9 mg/ml (0.9 %) in order to obtain a final TEPADINA®concentration between 0.5 and 1 mg/ml.
Administration
TEPADINA® infusion solution should be inspected visually for particulate matter and opalescence prior to administration. Solutions containing a precipitate should be discarded.
It is recommended that the infusion solution be administered to patients using an infusion set equipped with a 0.2 µm in-line filter.
TEPADINA® should be aseptically administered as a 2 - 4 hours infusion under room temperature and normal light conditions.
Prior to and following each infusion, the indwelling catheter line should be flushed with approximately 5 ml sodium chloride 9 mg/ml (0.9 %) solution for injection.
Off-Label Use and Dosage (Pediatric)
Guideline-Supported Use
There is limited information regarding Off-Label Guideline-Supported Use of Thiotepa in pediatric patients.
Non–Guideline-Supported Use
There is limited information regarding Off-Label Non–Guideline-Supported Use of Thiotepa in pediatric patients.
Contraindications
existing hepatic, renal or bone marrow damage (may use low dosage and frequent monitoring if need outweighs risk)
hypersensitivity to thiotepa
Warnings
There is limited information regarding Thiotepa Warnings' in the drug label.
Adverse Reactions
Clinical Trials Experience
There is limited information regarding Thiotepa Clinical Trials Experience in the drug label.
Postmarketing Experience
decrease in circulating blood cell counts (intended effect of the medicine to prepare you for your transplant infusion)
infection
liver disorders including blocking of a liver vein
the graft attacks your body (graft versus host disease)
respiratory complications.
increased susceptibility to infection
whole-body inflammatory state (sepsis)
decreased counts of white blood cells, platelets and red blood cells (anaemia)
the transplanted cells attack your body (graft versus host disease)
dizziness, headache, blurred vision
uncontrolled shaking of the body (convulsion)
sensation of tingling, pricking or numbness (paraesthesia)
partial loss of movement
cardiac arrest
nausea, vomiting, diarrhoea
inflammation of the mucosa of the mouth (mucositis)
irritated stomach, gullet, intestine
inflammation of the colon
anorexia, decreased appetite
high glucose in the blood
skin rash, itching, shedding
skin colour disorder (do not confuse with jaundice - see below)
redness of the skin (erythema)
hair loss
back and abdominal pain, pain
muscle and joint pain
abnormal electrical activity in the heart (arrhythmia)
inflammation of lung tissue
enlarged liver
altered organ function
blocking of a liver vein (VOD)
yellowing of the skin and eyes (jaundice)
hearing impaired
lymphatic obstruction
high blood pressure
increased liver, renal and digestive enzymes
abnormal blood electrolytes
weight gain
fever, general weakness, chills
bleeding (haemorrhage)
nasal bleeding
general swelling due to fluid retention (oedema)
pain or inflammation at the injection site
eye infection (conjunctivitis)
decreased sperm cell count
vaginal bleeding
absence of menstrual periods (amenorrhea)
memory loss
delaying in weight and height increase
bladder disfunction
underproduction of testosterone
insufficient production of thyroid hormone
deficient activity of the pituitary gland
confusional state
Drug Interactions
There is limited information regarding Thiotepa Drug Interactions in the drug label.
Use in Specific Populations
Pregnancy
Pregnancy Category (FDA):
You must tell your doctor if you are or think you may be pregnant before you receive TEPADINA® . You must not use TEPADINA® during pregnancy.
Both women and men using TEPADINA® must use effective contraceptive methods during treatment.
It is not known whether this medicinal product is excreted in breast milk. As a precautionary measure, women must not breast-feed during treatment with TEPADINA® .
TEPADINA® can impair male and female fertility. Male patients should seek for sperm preservation before therapy is started and should not father while treated and during the year after cessation of treatment.
Pregnancy Category (AUS):
(Description)
Labor and Delivery
(Description)
Nursing Mothers
(Description)
Pediatric Use
(Description)
Geriatic Use
(Description)
Gender
(Description)
Race
(Description)
Renal Impairment
(Description)
Hepatic Impairment
(Description)
Females of Reproductive Potential and Males
(Description)
Immunocompromised Patients
(Description)
Others
(Description)
Administration and Monitoring
Administration
Oral
Monitoring
Blood counts and liver enzymes
IV Compatibility
There is limited information regarding the compatibility of Thiotepa and IV administrations.
Overdosage
There is limited information regarding Thiotepa overdosage. If you suspect drug poisoning or overdose, please contact the National Poison Help hotline (1-800-222-1222) immediately.
TEPADINA® 15 mg
powder for concentrate for solution for infusion
Thiotepa
Read all of this leaflet carefully before you start using this medicine.
Keep this leaflet. You may need to read it again.
If you have any further questions, ask your doctor.
If any of the side effects get serious, or if you notice any side effects not listed in this leaflet, please tell your doctor.
In this leaflet:
What TEPADINA® is and what it is used for
Before you use TEPADINA®
How to use TEPADINA®
Possible side effects
How to store TEPADINA®
Further information
1. WHAT TEPADINA® IS AND WHAT IT IS USED FOR
TEPADINA® contains the active substance thiotepa, which belongs to a group of medicines called alkylating agents.
TEPADINA® is used to prepare patients for bone marrow transplantation. It works by destroying bone marrow cells. This enables the transplantation of new bone marrow cells (haematopoietic progenitor cells), which in turn enable the body to produce healthy blood cells. TEPADINA® can be used in adults and children.
2. BEFORE YOU USE TEPADINA®
Do not use TEPADINA®
if you are allergic (hypersensitive) to thiotepa,
if you are pregnant or think you may be pregnant (see below),
if you are breast-feeding,
if you are receiving yellow fever vaccination, live virus and bacterial vaccines.
Take special care with TEPADINA®
You should tell your doctor if you have:
liver or kidney problems,
heart or lung problems,
seizures/fits (epilepsy) or have had them in the past (if treated with phenytoin or fosphenytoin).
You will have to take regular blood tests during treatment to check your blood cell counts.
You will have to use anti-infectives to prevent and manage infections.
TEPADINA® may cause another type of cancer in the future. Your doctor will discuss this risk with you.
Pregnancy and breast-feeding
You must tell your doctor if you are or think you may be pregnant before you receive TEPADINA® . You must not use TEPADINA® during pregnancy.
Both women and men using TEPADINA® must use effective contraceptive methods during treatment.
It is not known whether this medicinal product is excreted in breast milk. As a precautionary measure, women must not breast-feed during treatment with TEPADINA® .
TEPADINA® can impair male and female fertility. Male patients should seek for sperm preservation before therapy is started and should not father while treated and during the year after cessation of treatment.
Using other medicines
Please tell your doctor if you are taking or have recently taken any other medicines, including medicines obtained without a prescription.
3. HOW TO USE TEPADINA®
Your doctor will calculate the dose according to your body surface or weight and your disease.
How TEPADINA® is given
TEPADINA® is administered by a qualified healthcare professional as an intravenous infusion (drip in a vein) after dilution of the individual vial. Each infusion will last 2 - 4 hours.
Frequency of administration
You will receive your infusions every 12 or 24 hours. The duration of treatment can last up to 3 days. Frequency of administration and duration of treatment depend on your disease.
4. POSSIBLE SIDE EFFECTS
Like all medicines, TEPADINA® can cause side effects, although not everybody gets them.
The most serious side effects of TEPADINA® therapy or the transplant procedure may include
decrease in circulating blood cell counts (intended effect of the medicine to prepare you for your transplant infusion)
infection
liver disorders including blocking of a liver vein
the graft attacks your body (graft versus host disease)
respiratory complications
Your doctor will monitor your blood counts and liver enzymes regularly to detect and manage these events.
Side effects of TEPADINA® may occur with certain frequencies, which are defined as follows:
very common: affects more than 1 user in 10
common: affects 1 to 10 users in 100
uncommon: affects 1 to 10 users in 1,000
rare: affects 1 to 10 users in 10,000
very rare: affects less than 1 user in 10,000
not known: frequency cannot be estimated from the available data.
Very common side effects
increased susceptibility to infection
whole-body inflammatory state (sepsis)
decreased counts of white blood cells, platelets and red blood cells (anaemia)
the transplanted cells attack your body (graft versus host disease)
dizziness, headache, blurred vision
uncontrolled shaking of the body (convulsion)
sensation of tingling, pricking or numbness (paraesthesia)
partial loss of movement
cardiac arrest
nausea, vomiting, diarrhoea
inflammation of the mucosa of the mouth (mucositis)
irritated stomach, gullet, intestine
inflammation of the colon
anorexia, decreased appetite
high glucose in the blood
skin rash, itching, shedding
skin colour disorder (do not confuse with jaundice - see below)
redness of the skin (erythema)
hair loss
back and abdominal pain, pain
muscle and joint pain
abnormal electrical activity in the heart (arrhythmia)
inflammation of lung tissue
enlarged liver
altered organ function
blocking of a liver vein (VOD)
yellowing of the skin and eyes (jaundice)
hearing impaired
lymphatic obstruction
high blood pressure
increased liver, renal and digestive enzymes
abnormal blood electrolytes
weight gain
fever, general weakness, chills
bleeding (haemorrhage)
nasal bleeding
general swelling due to fluid retention (oedema)
pain or inflammation at the injection site
eye infection (conjunctivitis)
decreased sperm cell count
vaginal bleeding
absence of menstrual periods (amenorrhea)
memory loss
delaying in weight and height increase
bladder disfunction
underproduction of testosterone
insufficient production of thyroid hormone
deficient activity of the pituitary gland
confusional state
Common side effects
anxiety, confusion
abnormal bulging outward of one of the arteries in the brain (intracranial aneurysm)
creatinine elevated
allergic reactions
occlusion of a blood vessel (embolism)
heart rhythm disorder
heart inability
cardiovascular inability
oxygen deficiency
fluid accumulation in the lungs (pulmonary oedema)
pulmonary bleeding
respiratory arrest
blood in the urine (haematuria) and moderate renal insufficiency
inflammation of the urinary bladder
discomfort in urination and decrease in urine output (disuria and oliguria)
increase in the amount of nitrogen components in the blood stream (BUN increase)
cataract
inability of the liver
cerebral haemorrhage
cough
constipation and upset stomach
obstruction of the bowel
perforation of stomach
changes in muscle tone
gross lack of coordination of muscle movements
bruises due to a low platelet count
menopausal symptoms
cancer (second primary malignancies)
abnormal brain function
Uncommon side effects
inflammation and exfoliation of the skin (erythrodermic psoriasis)
delirium, nervousness, hallucination, agitation
gastrointestinal ulcer
inflammation of the muscular tissue of the heart (myocarditis)
abnormal heart condition (cardiomyopathy)
male and female infertility
If any of the side effects gets serious, or if you notice any side effects not mentioned in this leaflet, please tell your doctor or nurse.
5. HOW TO STORE TEPADINA®
Keep out of the reach and sight of children.
Do not use TEPADINA® after the expiry date which is stated on the carton and vial label, after EXP. The expiry date refers to the last day of that month.
Store and transport refrigerated (2 °C - 8 °C).
Do not freeze.
After reconstitution the product is stable for 8 hours when stored at 2 °C - 8 °C.
After dilution the product is stable for 24 hours when stored at 2 °C - 8 °C and for 4 hours when stored at 25 °C. From a microbiological point of view, the product should be used immediately.
Any unused product or waste material should be disposed of in accordance with local requirements.
6. FURTHER INFORMATION
What TEPADINA® contains
The active substance is thiotepa. One vial contains 15 mg thiotepa. After reconstitution, each ml contains 10 mg thiotepa (10 mg/ml).
TEPADINA ® does not contain any other ingredients.
What TEPADINA® looks like and contents of the pack
TEPADINA® is a white crystalline powder supplied in a glass vial containing 15 mg thiotepa.
Each carton contains 1 vial.
File:Thiotepa01.pngThis image is provided by the National Library of Medicine.
Precautions with Alcohol
Alcohol-Thiotepa interaction has not been established. Talk to your doctor about the effects of taking alcohol with this medication.
