Tepadina

Tepadina is a prescription medication used to treat certain types of ovarian cancer (cancer that begins in the female reproductive organs where eggs are formed). It may also be used to treat breast and bladder cancer. It is also used to treat malignant effusions (a condition when fluid collects in the lungs or around the heart) that are caused by cancerous tumors.

This medication may be prescribed for other uses. Ask your doctor or pharmacist for more information.

• Adienne Sa

The most serious side effects of Tepadina therapy 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.

Tepadina may interfere with the normal menstrual cycle (period) in women, may stop sperm production in men, and may cause infertility (difficulty becoming pregnant).

Before taking Tepadina, tell your doctor about all of your medical conditions. Especially tell your doctor if you:

• are allergic to Tepadina or to any of its ingredients
• liver, kidney, or bone-marrow damage. However, if the need outweighs the risks, Tepadina may be used in low dosage, and accompanied by monitoring tests.

Tell your doctor if you are pregnant or plan to become pregnant.

The FDA categorizes medications based on safety for use during pregnancy. Five categories - A, B, C, D, and X, are used to classify the possible risks to an unborn baby when a medication is taken during pregnancy.

This medication falls into category D. In animal studies, pregnant animals were given this medication and had some babies born with problems. No well-controlled studies have been done in humans.

Tell your doctor if you are breastfeeding or plan to breastfeed.

It is not known if Tepadina crosses into human milk. Because many medications can cross into human milk and because of the possibility for serious adverse reactions in nursing infants with use of this medication, a choice should be made whether to stop nursing or stop the use of this medication. Your doctor and you will decide if the benefits outweigh the risk of using Tepadina.

Thiotepa injection is used to lower risk of graft rejection when used with other medicines (eg, high-dose busulfan, cyclophosphamide) as a preparative regimen for stem cell transplantation in children with class 3 beta-thalassemia. It is also used to treat cancer of the breast, ovary, and urinary bladder. This medicine is also used to treat malignant effusions (accumulation of fluid in the body cavity) caused by cancer.

Thiotepa belongs to the group of medicines called alkylating agents. It interferes with the growth of cancer cells, which are eventually destroyed. Since the growth of normal body cells may also be affected by thiotepa, other effects will also occur. Some of these may be serious and must be reported to your doctor. Other effects, like hair loss, may not be serious but may cause concern. Some effects do not occur for months or years after the medicine is used.

This medicine is to be given only by or under the immediate supervision of your doctor.

• Tell all of your health care providers that you take this medicine. This includes your doctors, nurses, pharmacists, and dentists.
• Have blood work checked as you have been told by the doctor. Talk with the doctor.
• Talk with your doctor before getting any vaccines. Use with Tepadina may either raise the chance of an infection or make the vaccine not work as well.
• If you have upset stomach, throwing up, loose stools (diarrhea), or are not hungry, talk with your doctor. There may be ways to lower these side effects.
• You may bleed more easily. Be careful and avoid injury. Use a soft toothbrush and an electric razor.
• You may have more chance of getting an infection. Wash hands often. Stay away from people with infections, colds, or flu.
• This medicine may cause change in skin color, itching, blisters, and peeling. These effects may be worse in the groin, armpit, skin folds, neck area, and under coverings (bandages, dressings). Shower or bathe, change coverings, and clean the covered skin as you have been told by your doctor. Change bed sheets every day while getting this medicine.
• This medicine may stop menstrual periods in females and affect sperm in males. Talk with the doctor.
• This medicine may affect fertility. Fertility problems may lead to not being able to get pregnant or father a child. Talk with the doctor.
• If you are a man and have sex with a female who could get pregnant, protect her from pregnancy during care and for 12 months after care ends. Use birth control that you can trust.
• If you are a man and your sex partner gets pregnant while you take Tepadina or within 12 months after your last dose, call your doctor right away.
• This medicine may cause harm to the unborn baby if you take it while you are pregnant.
• If you are able to get pregnant, a pregnancy test will be done to show that you are NOT pregnant before starting this medicine. Talk with your doctor.
• Use birth control that you can trust to prevent pregnancy while taking Tepadina and for 6 months after stopping this medicine.
• If you get pregnant while taking Tepadina or within 6 months after your last dose, call your doctor right away.

• If you need to store Tepadina at home, talk with your doctor, nurse, or pharmacist about how to store it.

Applies to thiotepa: injection powder for solution

Along with its needed effects, thiotepa (the active ingredient contained in Tepadina) may cause some unwanted effects. Although not all of these side effects may occur, if they do occur they may need medical attention.

Check with your doctor or nurse immediately if any of the following side effects occur while taking thiotepa:

• Bleeding gums
• blood in the urine
• blurred or double vision
• confusion
• coughing up blood
• cracked lips
• diarrhea
• difficulty with breathing or swallowing
• difficulty with walking
• dizziness
• drooping eyelids
• headache, sudden, severe
• increased menstrual flow or vaginal bleeding
• jaw pain
• nausea and vomiting
• nosebleeds
• numbness or tingling in the fingers and toes
• pain in the fingers and toes
• paralysis
• prolonged bleeding from cuts
• red or black, tarry stools
• red or dark brown urine
• sores, ulcers, or white spots on the lips, tongue, or inside the mouth
• weakness

• Absent, missed, or irregular menstrual periods
• blistering, peeling, or loosening of the skin
• bloated abdomen
• cough or hoarseness
• fast heartbeat
• fever or chills
• hives or welts, itching, or skin rash
• joint or muscle pain
• lower back or side pain
• pain and fullness in the right upper abdomen or stomach
• painful or difficult urination
• pale skin
• puffiness or swelling of the eyelids or around the eyes, face, lips, or tongue
• red skin lesions, often with a purple center
• red, irritated eyes
• redness of the skin
• stopping of menstrual bleeding
• tightness in the chest
• troubled breathing with exertion
• unusual bleeding or bruising
• unusual tiredness or weakness
• weight gain
• yellow eyes and skin

Some side effects of thiotepa may occur that usually do not need medical attention. These side effects may go away during treatment as your body adjusts to the medicine. Also, your health care professional may be able to tell you about ways to prevent or reduce some of these side effects. Check with your health care professional if any of the following side effects continue or are bothersome or if you have any questions about them:

• Abdominal or stomach pain
• blistering, burning, crusting, dryness, or flaking of the skin
• hair loss or thinning of the hair
• itching, scaling, severe redness, soreness, or swelling of the skin
• loss of appetite
• pain at the injection site
• stopping of menstrual bleeding
• weight loss

Applies to thiotepa: injectable powder for injection, intravenous powder for injection

Hematologic

Hematologic side effects have included bone-marrow depression, which is the most serious complication of excessive thiotepa (the active ingredient contained in Tepadina) therapy, or sensitivity to the effects of thiotepa. If proper precautions are not observed, leukopenia, thrombocytopenia and/or anemia may develop. The nadir in the leukocyte and platelet counts generally occur in 7 to 10 days and 21 days respectively.

Death has occurred after intravesical administration, caused by bone-marrow depression from systemically absorbed drug. However, if the drug is administered by intracavitary or intravesical injection, myelosuppression is not predictable. Death from septicemia and hemorrhage has occurred as a direct result of hematopoietic depression. Thiotepa is highly toxic to the hematopoietic system.

Pancytopenia has been reported. One case report was of early onset life-threatening pancytopenia following a total dosage of 120 mg.[Ref]

In one study of 670 bladder installations in 72 patients, the white blood cell or platelet count decreased to below normal in 18% of the patients (3.9% of the installations). None of these decreased counts lead to any problems other than delays in therapy.

New York Hospital reviewed its records of patients who received at least one intravesicular installation of thiotepa for localized bladder cancer. Ten of 25 consecutive patients had at least one episode of acute myelosuppression. Thrombocytopenia occurred in 9 patients, leukopenia in 5, and anemia in 2.[Ref]

Oncologic

Oncologic side effects have included cases of myelodysplastic syndromes and acute nonlymphocytic leukemia. Carcinogenicity has been reported in animal studies.[Ref]

In mice, repeated IP administration produced a significant increase in the combined incidence of squamous-cell carcinomas of the skin, preputial gland, and ear canal, and combined incidence of lymphoma and lymphocytic leukemia. In other studies in mice, repeated IP administration resulted in an increased incidence of lung tumors. In rats, repeated IP administration produced significant increases in the incidence of squamous-cell carcinomas of the skin or ear canal, combined hematopoietic neoplasms, and uterine adenocarcinomas. Thiotepa given intravenously to rats produced an increased incidence of malignant tumors (abdominal cavity sarcoma, lymphosarcoma, myelosis, seminoma, fibrosarcoma, salivary gland hemangioendothelioma, mammary sarcoma, pheochromocytoma) and benign tumors. The lowest reported carcinogenic dosages in mice and rats are approximately 7-fold and 6-fold less than the maximum recommended human therapeutic dose based on body-surface area.[Ref]

General

General side effects including fatigue and weakness have been reported. Febrile reaction and discharge from a subcutaneous lesion may occur as the result of breakdown of tumor tissue.[Ref]

Hypersensitivity

Allergic reactions including rash, urticaria, laryngeal edema, asthma, hives, anaphylactic shock, and wheezing have been reported.[Ref]

Local

Local reactions including contact dermatitis and pain at the injection site have been reported.[Ref]

Gastrointestinal

Gastrointestinal side effects including nausea, vomiting, and anorexia have been reported. Abdominal pain has been reported, particularly after intravesical administration.[Ref]

Renal

Renal side effects including dysuria and urinary retention have been reported. There have been rare reports of chemical or hemorrhagic cystitis following intravesical administration.[Ref]

A case of renal failure due to a reaction causing urethral obstruction (following a bladder installation) has been reported.[Ref]

Respiratory

Respiratory side effects including prolonged apnea has been reported when succinylcholine was administered prior to surgery, followed by the combined use of thiotepa (the active ingredient contained in Tepadina) and other anticancer agents.[Ref]

Nervous system

Neurologic side effects including dizziness, headache, blurred vision, lower extremity weakness, pain, and paresthesia have been reported. Spinal cord demyelination may occur after intrathecal administration.[Ref]

Dermatologic

Dermatologic side effects including alopecia and dermatitis have been reported. Skin depigmentation has been reported following topical use.[Ref]

Genitourinary

Genitourinary side effects including amenorrhea, interference with spermatogenesis and sterility have been reported.[Ref]

Ocular

Ocular side effects including conjunctivitis have been reported. Following ocular administration, periorbital depigmentation has been reported.[Ref]

Other

An in vitro study has shown that the drug causes chromosomal aberrations of the chromatid type and that the frequency of induced aberrations increases with the age of the subject.[Ref]

Other side effects include a mutagenic effect in vitro assays including those on human lymphocytes.[Ref]

Some side effects of Tepadina may not be reported. Always consult your doctor or healthcare specialist for medical advice. You may also report side effects to the FDA.