A1,
A2,
B,
C1,
C2,
D,
E,
F,
G-H,
I-K,
L,
M,
N,
O,
P1,
P2,
Q-R,
S,
T,
U-V,
W-Z
Trexall Indications, Dosage, Storage, Stability - Methotrexate
Trexall Indications, Dosage, Storage, Stability - Methotrexate
INDICATIONS
Neoplastic Diseases
Methotrexate is indicated in the treatment
of gestational choriocarcinoma, chorioadenoma destruens and hydatidiform
mole.
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, 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, classical or definite rheumatoid
arthritis (ARA criteria)
who have had an insufficient therapeutic
response to, or are
intolerant of, an adequate trial of first-line therapy
including full dose NSAIDs
and usually a trial of at least one or more disease-modifying antirheumatic
drugs.
Aspirin, nonsteroidal anti-inflammatory
agents, 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. Methotrexate sodium
injection and for
injection may be given
by the intramuscular,
intravenous, intra-arterial
or intrathecal route.
However, the preserved formulation contains Benzyl Alcohol and must
not be used for intrathecal
or high dose therapy. Parenteral
drug products should be
inspected visually for particulate
matter and discoloration
prior to administration, whenever solution
and container permit.
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 children 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 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.
HOW SUPPLIED:
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 0555-0927-01
60 NDC 0555-0927-09
100 NDC
0555-0927-02 |
| 7.5 mg: |
Blue, oval-shaped, film-coated, scored,
biconvex tablet. Debossed with b on one side and
928/71/2 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 0555-0928-01
60 NDC 0555-0928-09
100 NDC
0555-0928-02 |
| 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 equivalent to 10 mg of methotrexate.
Available in bottles of:
30 NDC 0555-0929-01
60 NDC
0555-0929-09
100 NDC 0555-0929-02 |
| 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 equivalent to 15 mg of methotrexate.
Available in bottles
of:
30 NDC 0555-0945-01
60 NDC 0555-0945-09
100 NDC
0555-0945-02 |
Dispense with a child-resistant closure in a
well-closed container as defined in the USP. Store at
controlled room temperature 15°-30°C (59°-86°F) [see USP].
Protect from light.
REFERENCES:
- Controlling occupational exposure to hazardous
drugs (OSHA Work-Practice
Guidelines). Am J
Health Syst Pharm 1996; 53:1669-1685.
- 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.
- AMA Council Report. Guidelines for Handling Parenteral
Antineoplastics. JAMA,
1985;
253(11):1590-1592.
- 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.
- Clinical Oncological
Society of Australia: Guidelines and recommendations for safe
handling
of antineoplastic agents. Med J Australia 1983; 1:426-428.
- 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.
- American Society of Hospital Pharmacists
technical assistance bulletin on handling
cytotoxic and hazardous drugs. Am J Hosp Pharm 1990;
47:1033-1049.
- OSHA Work-Practice
Guidelines for Personnel Dealing with Cytotoxic (Antineoplastic)
Drugs. Am J Hosp
Pharm, 1986; 43:1193-1204.
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