Thioplex

Thioplex is part of the drug class:

• Ethylene imines

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

It is not known if thiopeta 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 thiopeta.

Take thiopeta exactly as prescribed by your doctor. Follow the directions on your prescription label carefully.

• Into the vein (IV) dosing: Thioplex may be given by rapid intravenous administration in doses of 0.3 to 0.4 mg/kg. Doses should be given at 1 to 4 week intervals.
• Intracavitary (within a body cavity) dosing: The dosage recommended is 0.6 to 0.8 mg/kg.
• Intravesical (into the urinary bladder) dosing: 60 mg of Thioplex injected into the bladder. 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 due to serious side effects.

• Keep out of the reach and sight of children.
• Do not use Thioplex after the expiration date which is stated on the carton and vial label. The expiration 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.
• Any unused product or waste material should be disposed of in accordance with local requirements.

Get emergency medical help if you have signs of an allergic reaction: hives; wheezing, difficult breathing; swelling of your face, lips, tongue, or throat.

Call your doctor at once if you have:

• skin lesions;

• pain or burning when you urinate, blood in your urine;

• little or no urinating;

• easy bruising, unusual bleeding (nose, mouth, vagina, or rectum), purple or red pinpoint spots under your skin;

• signs of infection--fever, flu symptoms, mouth and throat ulcers, rapid heart rate, rapid and shallow breathing, fainting;

• low red blood cells (anemia)--pale skin, feeling light-headed or short of breath, rapid heart rate, trouble concentrating; or

• liver problems--nausea, upper stomach pain, itching, tired feeling, loss of appetite, dark urine, clay-colored stools, jaundice (yellowing of the skin or eyes).

Common side effects may include:

• dizziness, headache, blurred vision;

• nausea, vomiting, stomach pain, loss of appetite;

• feeling weak or tired;

• eye redness;

• pain or irritation where the injection was given;

• hair loss; or

• missed menstrual periods.

This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

Applies to thiotepa: injection powder for solution

Along with its needed effects, thiotepa (the active ingredient contained in Thioplex) 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 Thioplex) 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 Thioplex) 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 Thioplex may not be reported. Always consult your doctor or healthcare specialist for medical advice. You may also report side effects to the FDA.

0.3 to 0.4 mg/kg by rapid IV administration once.
or
0.6 to 0.8 mg/kg by intracavitary injection once.
or
0.6 to 0.8 mg/kg by intratumor injection once.
or
30 to 60 mg by intravesical instillation once.
or
10 to 15 mg by intrathecal injection once.
or
500 to 1000 mg IV once.

The manufacturer states that therapy is probably contraindicated in cases of existing bone marrow damage. However, if the need outweighs the risk, thiotepa may be used in low dosage, accompanied by appropriate testing.

Dosages are calculate by actual body weight.

Dosages must be carefully individualized. Dosages of thiotepa may depend upon the specific indication for its use, and whether other cytotoxic agents are coadministered. Reference to specific protocols is recommended.

Intratumor injections can be mixed with 2% procaine or 0.1% epinephrine injection in order to decrease pain.

A slow response to thiotepa does not necessarily indicate a lack of effect. Therefore, increasing the frequency of dosing may only increase toxicity. After maximum benefit is obtained by initial therapy, it is necessary to continue the patient on maintenance therapy, generally at approximately 1 to 4 week intervals. The maintenance dose should be adjusted on the basis of pretreatment control blood count and subsequent blood counts. In order to continue optimal effect, maintenance doses should not be administered more frequently than once weekly, in order to preserve correlation between dose and blood counts.