"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"...
Methotrexate is used alone or in combination with other anticancer agents in the treatment of breast cancer, epidermoid cancers of the head and neck, advanced mycosis fungoides, (cutaneous T cell lymphoma), and lung cancer, particularly squamous cell and small cell types. Methotrexate is also used in combination with other chemotherapeutic agents in the treatment of advanced stage non-Hodgkin's lymphomas.
Trexall™ (methotrexate tablets) are indicated in the symptomatic control of severe, recalcitrant, disabling psoriasis that is not adequately responsive to other forms of therapy, but only when the diagnosis has been established, as by biopsy and/or after dermatologic consultation. It is important to ensure that a psoriasis "flare" is not due to an undiagnosed concomitant disease affecting immune responses.
Rheumatoid Arthritis including Polyarticular-Course Juvenile Rheumatoid Arthritis:
Trexall™ (methotrexate tablets) are indicated in the management of selected adults with severe, active, rheumatoid arthritis (ARC criteria), or children with active polyarticular-course juvenile rheumatoid arthritis, who have had an insufficient therapeutic response to, or are intolerant of, an adequate trial of first-line therapy including full dose non-steroidal anti-inflammatory agents (NSAIDs).
Aspirin, NSAIDs, and/or low dose steroids may be continued, although the possibility of increased toxicity with concomitant use of NSAIDs including salicylates has not been fully explored (see PRECAUTIONS: DRUG INTERACTIONS.). Steroids may be reduced gradually in patients who respond to methotrexate. Combined use of methotrexate with gold, penicillamine, hydroxychloroquine, sulfasalazine, or cytotoxic agents, has not been studied and may increase the incidence of adverse effects. Rest and physiotherapy as indicated should be continued.
DOSAGE AND ADMINISTRATION
Oral administration in tablet form is often preferred when low doses are being administered since absorption is rapid and effective serum levels are obtained.
Choriocarcinoma and similar trophoblastic diseases: Methotrexate is administered orally or intramuscularly in doses of 15 to 30 mg daily for a five-day course. Such courses are usually repeated for 3 to 5 times as required, with rest periods of one or more weeks interposed between courses, until any manifesting toxic symptoms subside. The effectiveness of therapy is ordinarily evaluated by 24-hour quantitative analysis of urinary chorionic gonadatropin (hCG), which should return to normal or less than 50 lU/24 hr usually after the third or fourth course and usually be followed by a complete resolution of measurable lesions in 4 to 6 weeks. One to two courses of methotrexate after normalization of hCG is usually recommended. Before each course of the drug careful clinical assessment is essential. Cyclic combination therapy of methotrexate with other antitumor drugs has been reported as being useful.
Chorioadenoma destruens is considered to be an invasive form of hydatidiform mole. Methotrexate is administered in these disease states in doses similar to those recommended for choriocarcinoma.
Leukemia: Acute Iymphoblastic leukemia in pediatric patients and young adolescents is the most responsive to present day chemotherapy. In young adults and older patients, clinical remission is more difficult to obtain and early relapse is more common.
Methotrexate alone or in combination with steroids was used initially for induction of remission in acute Iymphoblastic leukemias. More recently corticosteroid therapy, in combination with other antileukemic drugs or in cyclic combinations with methotrexate included, has appeared to produce rapid and effective remissions. When used for induction, methotrexate in doses of 3.3 mg/m2 in combination with 60 mg/m2 of prednisone, given daily, produced remissions in 50% of patients treated, usually within a period of 4 to 6 weeks. Methotrexate in combination with other agents appears to be the drug of choice for securing maintenance of drug-induced remissions. When remission is achieved and supportive care has produced general clinical improvement, maintenance therapy is initiated, as follows: Methotrexate is administered 2 times weekly either by mouth or intramuscularly in total weekly doses of 30 mg/m2. It has also been given in doses of 2.5 mg/kg intravenously every 14 days. If and when relapse does occur, reinduction of remission can again usually be obtained by repeating the initial induction regimen.
A variety of combination chemotherapy regimens have been used for both induction and maintenance therapy in acute Iymphoblastic leukemia. The physician should be familiar with the new advances in antileukemic therapy.
Lymphomas: In Burkitt's tumor, Stages I-II, methotrexate has produced prolonged remissions in some cases. Recommended dosage is 10 to 25 mg/day orally for 4 to 8 days. In Stage III, methotrexate is commonly given concomitantly with other antitumor agents. Treatment in all stages usually consists of several courses of the drug interposed with 7 to 10 day rest periods. Lymphosarcomas in Stage llI may respond to combined drug therapy with methotrexate given in doses of 0.625 to 2.5 mg/kg daily.
Mycosis fungoides (cutaneous T cell lymphoma): Therapy with methotrexate as a single agent appears to produce clinical responses in up to 50% of patients treated. Dosage in early stages is usually 5 to 50 mg once weekly. Dose reduction or cessation is guided by patient response and hematologic monitoring. Methotrexate has also been administered twice weekly in doses ranging from 15 to 37.5 mg in patients who have responded poorly to weekly therapy. Combination chemotherapy regimens that include intravenous methotrexate administered at higher doses with leucovorin rescue have been utilized in advanced stages of the disease.
Psoriasis, Rheumatoid Arthritis and Juvenile Rheumatoid Arthritis:
Adult Rheumatoid Arthritis: Recommended Starting Dosage Schedules
- Single oral doses of 7.5 mg once weekly.
- Divided oral dosages of 2.5 mg at 12 hour intervals for 3 doses given as a course once weekly.
Polyarticular-Course Juvenile Rheumatoid Arthritis: The recommended starting dose is 10 mg/m2 given once weekly.
For either adult RA or polyarticular-course JRA dosages may be adjusted gradually to achieve an optimal response. Limited experience shows a significant increase in the incidence and severity of serious toxic reactions, especially bone marrow suppression, at doses greater than 20 mg/wk in adults. Although there is experience with doses up to 30 mg/m2/wk (0.65 to 1.0 mg/kg/wk) may have better absorption and fewer gastrointestinal side effects if methotrexate is administered either intramuscularly or subcutaneously. Therapeutic response usually begins within 3 to 6 weeks and the patient may continue to improve for another 12 weeks or more.
The optimal duration of therapy is unknown. Limited data available from long-term studies in adults indicate that the initial clinical improvement is maintained for at least two years with continued therapy. When methotrexate is discontinued, the arthritis usually worsens within 3 to 6 weeks. The patient should be fully informed of the risks involved and should be under constant supervision of the physician. (see Information for Patients under PRECAUTIONS). Assessment of hematologic, hepatic, renal and pulmonary function should be made by history, physical examination, and laboratory tests before beginning, periodically during, and before reinstituting methotrexate therapy. (see PRECAUTIONS). Appropriate steps should be taken to avoid conception during methotrexate therapy. (see PRECAUTIONS and CONTRAINDICATIONS).
Weekly therapy may be instituted to provide doses over a range of 5 mg to 15 mg administered as a single weekly dose. All schedules should be continually tailored to the individual patient. An initial test dose may be given prior to the regular dosing schedule to detect any extreme sensitivity to adverse effects (see ADVERSE REACTIONS). Maximal myelosuppression usually occurs in seven to ten days.
Psoriasis: Recommended Starting Dose Schedules
- Weekly single oral, IM or IV dose schedule: 10 to 25 mg per week until adequate response is achieved.
- Divided oral dose schedule: 2.5 mg at 12-hour intervals for three doses.
Dosages in each schedule may be gradually adjusted to achieve optimal clinical response; 30 mg/week should not ordinarily be exceeded.
Once optimal clinical response has been achieved, each dosage schedule should be reduced to the lowest possible amount of drug and to the longest possible rest period. The use of methotrexate may permit the return to conventional topical therapy, which should be encouraged.
HANDLING AND DISPOSAL:
Procedures for proper handling and disposal of anticancer drugs should be considered. Several guidelines on this subject have been published.1-8 There is no general agreement that all of the procedures recommended in the guidelines are necessary or appropriate.
Trexall™ (methotrexate tablets, USP) are available as:
5 mg: Green, oval-shaped, film-coated, scored, biconvex tablet. Debossed with b on one side and 927/5 on the other side. Each 5 mg tablet contains an amount of methotrexate sodium equivalent to 5 mg of methotrexate. Available in bottles of: 30 NDC 51285-366-01
7.5 mg: Blue, oval-shaped, film-coated, scored, biconvex tablet. Debossed with b on one side and 928/7½ on the other side. Each 7.5 mg tablet contains an amount of methotrexate sodium equivalent to 7.5 mg of methotrexate. Available in bottles of: 30 NDC 51285-367-01
10 mg: Pink, oval-shaped, film-coated, scored, biconvex tablet. Debossed with b on one side and 929/10 on the other side. Each 10 mg tablet contains an amount of methotrexate sodium equiv- alent to 10 mg of methotrexate. Available in bottles of: 30 NDC 51285-368-01
15 mg: Purple, oval-shaped, film-coated, scored, biconvex tablet. Debossed with b on one side and 945/15 on the other side. Each 15 mg tablet contains an amount of methotrexate sodium equiv- alent to 15 mg of methotrexate. Available in bottles of: 30 NDC 51285-369-01
Dispense with a child-resistant closure in a well-closed container.
Store at 20° to 25°C (68° to 77°F) [See USP Controlled Room Temperature].
Protect from light.
1. Controlling occupational exposure to hazardous drugs (OSHA Work-Practice Guidelines). Am J Health Syst Pharm 1996; 53:1669-1685.
2. Recommendations for the Safe Handling of Parenteral Antineoplastic Drugs. NIH Publication No. 83-2621. For sale by the Superintendent of Documents, US Government Printing Office, Washington DC 20402.
3. AMA Council Report. Guidelines for Handling Parenteral Antineoplastics. JAMA, 1985; 253(11):1590-1592.
4. National Study Commission on Cytotoxic Exposure - Recommendations for Handling Cytotoxic Agents. Available from Louis P. Jeffrey, Sc D, Chairman, National Study Commisssion on Cytotoxic Exposure, Massachusetts College of Pharmacy and Allied Health Sciences, 179 Longwood Avenue, Boston Massachusetts 02115.
5. Clinical Oncological Society of Australia: Guidelines and recommendations for safe handling of anti- neoplastic agents. Med J Australia 1983; 1:426-428.
6. Jones RB, et al. Safe handling of chemotherapeutic agents: A report from the Mount Sinai Medical Center. Ca - A Cancer Journal for Clinicians Sept/Oct 1983; 258-263.
7. American Society of Hospital Pharmacists technical assistance bulletin on handling cytotoxic and hazardous drugs. Am J Hosp Pharm 1990; 47:1033-1049.
8. OSHA Work-Practice Guidelines for Personnel Dealing with Cytotoxic (Antineoplastic) Drugs. Am J Hosp Pharm, 1986; 43:1193-1204.
DURAMED PHARMACEUTICALS, INC. Subsidiary of Barr Pharmaceuticals, Inc. Pomona, New York 10970. Revised OCTOBER 2005. FDA rev date: 7/9/2002
Last reviewed on RxList: 11/20/2007
This monograph has been modified to include the generic and brand name in many instances.
Additional Trexall Information
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