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Rheumatrex

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Rheumatrex

Indications
Dosage
How Supplied

INDICATIONS

Neoplastic Diseases

Methotrexate is indicated in the treatment of gestational choriocarcinoma, chorioadenoma destruens and hydatidiform mole.

Methotrexate is used in maintenance therapy in combination with other chemotherapeutic agents.

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.

Psoriasis

Methotrexate is 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

Methotrexate is indicated in the management of selected adults with severe, active, rheumatoid arthritis (ACR 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 antiinflammatory 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

Neoplastic Diseases

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 gonadotropin (hCG), which should return to normal or less than 50 IU/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.

Since hydatidiform mole may precede choriocarcinoma, prophylactic chemotherapy with methotrexate has been recommended.

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 lymphoblastic 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 lymphoblastic 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 lymphoblastic 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 III 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 usuallly 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.

Psoriasis, Rheumatoid Arthritis, and Juvenile Rheumatoid Arthritis

Adult Rheumatoid Arthritis

Recommended Starting Dosage Schedules

  1. Single oral doses of 7.5 mg once weekly.
  2. 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 in children, there are too few published data to assess how doses over 20 mg/m²/wk might affect the risk of serious toxicity in children. Experience does suggest, however, that children receiving 20 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 PATIENT INFORMATION.) 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 with the RHEUMATREX® Methotrexate Tablets, USP, 2.5 mg Dose Packs which are designed to provide doses over a range of 5 mg to 20 mg administered as a single weekly dose. The dose packs are not recommended for administration of methotrexate in weekly doses greater than 20 mg. 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

  1. Weekly single oral, IM or IV dose schedule: 10 to 25 mg per week until adequate response is achieved.
  2. 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.1-5 There is no general agreement that all of the procedures recommended in the guidelines are necessary or appropriate.

HOW SUPPLIED

Oral

Description

Methotrexate Tablets, USP contain an amount of methotrexate sodium equivalent to 2.5 mg of methotrexate and are round, convex, yellow tablets, scored in half on one side, engraved with M above the score, and 1 below.

RHEUMATREX® Methotrexate Tablets, USP, 2.5 mg Dose Packs - (each tablet equivalent to 2.5 mg of methotrexate)

NDC 67253-580-42 - RHEUMATREX® Methotrexate Tablets, USP Dose Pack – 4 cards each containing two 2.5 mg tablets, i.e., 5 mg per week.

NDC 67253-580-43 - RHEUMATREX® Methotrexate Tablets, USP Dose Pack – 4 cards each containing three 2.5 mg tablets, i.e., 7.5 mg per week.

NDC 67253-580-44 - RHEUMATREX® Methotrexate Tablets, USP Dose Pack – 4 cards each containing four 2.5 mg tablets, i.e., 10 mg per week.

NDC 67253-580-45 - RHEUMATREX® Methotrexate Tablets, USP Dose Pack – 4 cards each containing five 2.5 mg tablets, i.e., 12.5 mg per week.

NDC 67253-580-46 - RHEUMATREX® Methotrexate Tablets, USP Dose Pack – 4 cards each containing six 2.5 mg tablets, i.e., 15 mg per week.

NDC 67253-580-47 - RHEUMATREX® Methotrexate Tablets, USP Dose Pack – 4 cards each containing seven 2.5 mg tablets, i.e., 17.5 mg per week.

NDC 67253-580-48 - RHEUMATREX® Methotrexate Tablets, USP Dose Pack – 4 cards each containing eight 2.5 mg tablets, i.e., 20 mg per week.

Store at 20°-25°C (68°-77°F) [See USP Controlled Room Temperature]. Protect from light.

REFERENCES

1. Controlling occupational exposure to hazardous drugs (OSHA Work-Practice Guidelines). Am J Health Syst Pharm 1996: 53: 1669-1685.

2. National Study Commission on Cytotoxic Exposure - Recommendations for Handling Cytotoxic Agents. Available from Louis P. Jeffrey, Sc D, Chairman, National Study Commission on Cytotoxic Exposure, Massachusetts College of Pharmacy and Allied Health Sciences, 179 Longwood Avenue, Boston, Massachusetts 02115.

3. Clinical Oncological Society of Australia: Guidelines and recommendations for safe handling of antineoplastic agents. Med J Australia 1983; 1:426-428.

4. 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.

5. American Society of Hospital Pharmacists technical assistance bulletin on handling cytotoxic and hazardous drugs. Am J Hosp Pharm 1990; 47:1033-1049.

Manufactured for: DAVA Pharmaceuticals, Inc., Fort Lee, NJ 07024 USA. By: EXCELLA GmbH, Feucht, Germany. Rev. 09/10

Last reviewed on RxList: 8/29/2013
This monograph has been modified to include the generic and brand name in many instances.

Indications
Dosage
How Supplied
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