"Sabahaddin Akman, owner of the Istanbul, Turkey, firm Ozay Pharmaceuticals, has pleaded guilty to charges of smuggling misbranded and adulterated cancer treatment drugs into the United States.
Akman pleaded guilty in the U.S. District Court"...
Before using MUSTARGEN, an accurate histologic diagnosis of the disease, a knowledge of its natural course, and an adequate clinical history are important. The hematologic status of the patient must first be determined. It is essential to understand the hazards and therapeutic effects to be expected. Careful clinical judgment must be exercised in selecting patients. If the indication for its use is not clear, the drug should not be used.
As nitrogen mustard therapy may contribute to extensive and rapid development of amyloidosis, it should be used only if foci of acute and chronic suppurative inflammation are absent.
Usage in Pregnancy
Mechlorethamine hydrochloride can cause fetal harm when administered to a pregnant woman. MUSTARGEN has been shown to produce fetal malformations in the rat and ferret when given as single subcutaneous injections of 1 mg/kg (2-3 times the maximum recommended human dose). There are no adequate and well-controlled studies in pregnant women. If this drug is used during pregnancy, or if the patient becomes pregnant while taking this drug, the patient should be apprised of the potential hazard to the fetus. Women of childbearing potential should be advised to avoid becoming pregnant.
This drug is HIGHLY TOXIC and both powder and solution must be handled and administered with care. (See BOXED WARNING and DOSAGE AND ADMINISTRATION, Special Handling.) Since MUSTARGEN is a powerful vesicant, it is intended primarily for intravenous use, and in most cases is given by this route. Inhalation of dust or vapors and contact with skin or mucous membranes, especially those of the eyes, must be avoided. Appropriate protective equipment should be worn when handling MUSTARGEN. Should accidental eye contact occur, copious irrigation for at least 15 minutes with water, normal saline or a balanced salt ophthalmic irrigating solution should be instituted immediately, followed by prompt ophthalmologic consultation. Should accidental skin contact occur, the affected part must be irrigated immediately with copious amounts of water, for at least 15 minutes while removing contaminated clothing and shoes, followed by 2% sodium thiosulfate solution. Medical attention should be sought immediately. Contaminated clothing should be destroyed. (See DOSAGE AND ADMINISTRATION, Special Handling.)
Because of the toxicity of MUSTARGEN, and the unpleasant side effects following its use, the potential risk and discomfort from the use of this drug in patients with inoperable neoplasms or in the terminal stage of the disease must be balanced against the limited gain obtainable. These gains will vary with the nature and the status of the disease under treatment. The routine use of MUSTARGEN in all cases of widely disseminated neoplasms is to be discouraged.
The use of MUSTARGEN in patients with leukopenia, thrombocytopenia, and anemia, due to invasion of the bone marrow by tumor carries a greater risk. In such patients a good response to treatment with disappearance of the tumor from the bone marrow may be associated with improvement of bone marrow function. However, in the absence of a good response or in patients who have been previously treated with chemotherapeutic agents, hematopoiesis may be further compromised, and leukopenia, thrombocytopenia and anemia may become more severe and lead to the demise of the patient.
Tumors of bone and nervous tissue have responded poorly to therapy. Results are unpredictable in disseminated and malignant tumors of different types.
Precautions must be observed with the use of MUSTARGEN and x-ray therapy or other chemotherapy in alternating courses. Hematopoietic function is characteristically depressed by either form of therapy, and neither MUSTARGEN following x-ray therapy nor x-ray therapy subsequent to the drug should be given until bone marrow function has recovered. In particular, irradiation of such areas as sternum, ribs, and vertebrae shortly after a course of nitrogen mustard may lead to hematologic complications.
Hyperuricemia may develop during therapy with MUSTARGEN. The problem of urate precipitation should be anticipated, particularly in the treatment of the lymphomas, and adequate methods for control of hyperuricemia should be instituted and careful attention directed toward adequate fluid intake before treatment.
Since drug toxicity, especially sensitivity to bone marrow failure, seems to be more common in chronic lymphatic leukemia than in other conditions, the drug should be given in this condition with great caution, if at all.
Extreme caution must be used in exceeding the average recommended dose. (See OVERDOSAGE.)
Many abnormalities of renal, hepatic, and bone marrow function have been reported in patients with neoplastic disease and receiving mechlorethamine. It is advisable to check renal, hepatic, and bone marrow functions frequently.
Carcinogenesis, Mutagenesis, Impairment of Fertility
Therapy with alkylating agents such as MUSTARGEN may be associated with an increased incidence of a second malignant tumor, especially when such therapy is combined with other antineoplastic agents or radiation therapy.
The International Agency for Research on Cancer has judged that mechlorethamine is a probable carcinogen in humans. This is supported by limited evidence of carcinogenicity in humans and sufficient evidence of carcinogenicity in animals. Young-adult female RF mice were injected intravenously with four doses of 2.4 mg/kg of mechlorethamine (0.1% solution) at 2-week intervals with observations for up to 2 years. An increased incidence of thymic lymphomas and pulmonary adenomas was observed. Painting mechlorethamine on the skin of mice for periods up to 33 weeks resulted in squamous cell tumors in 9 of 33 mice.
Mechlorethamine induced mutations in the Ames test, in E. coli, and Neurospora crassa. Mechlorethamine caused chromosome aberrations in a variety of plant and mammalian cells. Dominant lethal mutations were produced in ICR/Ha Swiss mice.
Mechlorethamine impaired fertility in the rat at a daily dose of 500 mg/kg intravenously for two weeks.
Pregnancy Category D. See WARNINGS.
It is not known whether this drug is excreted in human milk. Because many drugs are excreted in human milk and because of the potential for serious adverse reactions in nursing infants from MUSTARGEN, a decision should be made whether to discontinue nursing or to discontinue the drug, taking into account the importance of the drug to the mother.
Safety and effectiveness in pediatric patients have not been established by well-controlled studies. Use of MUSTARGEN in pediatric patients has been quite limited. MUSTARGEN has been used in Hodgkin's disease, stages III and IV, in combination with other oncolytic agents (MOPP schedule). The MOPP chemotherapy combination includes mechlorethamine, vincristine, procarbazine, and prednisone or prednisolone.2,3
Clinical studies of MUSTARGEN did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects. 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 decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy.
2. Kolygin, B.A.: Combination chemotherapy of Hodgkin's disease in children, CancerPhiladelphia 38:1494-1497, Oct. 1976. Page 11 of 12
3. Young, R.C.; DeVita, V.T.; Johnson, R.E.: Hodgkin's disease in childhood, Blood 42: 163-174, Aug. 1973.
Last reviewed on RxList: 9/18/2013
This monograph has been modified to include the generic and brand name in many instances.
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