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meth-oh-TREK-sate)
Folex, Folex PFS, Rheumatrex Dose Pack, Rheumatrex Tablets
Class: Antineoplastic/antimetabolite; antipsoriatic; antiarthritic
Action Competitively inhibits dihydrofolic acid reductase and thereby
day rest period (maximum 6.25 mg qd). This schedule may pose increased risk of
liver toxicity.
Interactions
Charcoal, folic acid: May reduce methotrexate efficacy. Digoxin: May reduce
serum digoxin levels and actions. Hydantoins: May reduce plasma levels.
Etretinate, NSAIDs, penicillins, probenecid, salicylates, sulfonamides: May
increase methotrexate blood levels and toxicity.
Lab Test Interferences None well documented.
Adverse Reactions
reactions may occur if live vaccines are administered. Intrathecal therapy: Large
doses may cause convulsions and systemic toxicity. Dosage regimens based on
age may be more effective and associated with fewer neurotoxic side effects. Do
not use formulations or diluents containing preservatives. Renal impairment: Use
drug with extreme caution. Determine renal status before and during therapy.
Severe effects: Use of high-dose methotrexate regimens (ie, to treat osteosarcoma)
require meticulous care. Deaths have occurred after use of methotrexate for any
condition. Potential toxicities include bone marrow depression; hepatotoxicity;
lung disease (suggested by symptoms of dry, nonproductive cough);
nephrotoxicity and GI toxicity.
PATIENT CARE
CONSIDERATIONS
Administration/Storage
Ensure that leucovorin is available from pharmacy before beginning highdose administration of methotrexate. Leucovorin diminishes methotrexate
toxicity.
Obtain patient history, including drug history and any known allergies.
Inspect patient's mouth daily. Report any patchy necrotic areas, bleeding
and discomfort or black/furry tongue.
Advise patient and parents that immunization with live virus vaccines is
generally not recommended during methotrexate therapy.
Inform patient of possibility of hair loss and reassure patient that hair will
regrow following discontinuation of therapy.
DEWASA: PO 10-25 mg / hari selama 4-8 hari. Memberikan 7-10hari masa istirahat antara kursus.
Tahap 3 Lymphosarcoma sebagai Bagian dari Terapi Kombinasi
DEWASA: PO 0,625-2,5 mg / kg / hari.
mikosis fungoides
DEWASA: PO 2,5-10 mg / hari selama minggu ke bulan
(berdasarkan respon klinis atau fungsi hematologi). IM 25 mg
dua kali seminggu atau 50 mg mingguan.
osteosarcoma
Kompleks dosis tinggi dengan penyelamatan leucovorin dan
agen kemoterapi lainnya. Mulai dosis untuk metotreksat dosis
tinggi adalah 12 gm / m2.
Radang sendi
DEWASA: AWAL TERAPI: PO 7,5 mg / minggu di dosis tunggal
atau 2,5 mg tiap 12 jam selama 3 dosis setiap minggu. Secara
bertahap menyesuaikan dosis untuk respon maksimal; tidak
melebihi 20 mg / minggu.
Psorias
Individualize dosis. Mengelola 5-10 mg tes parenteral dosis 1
minggu sebelum terapi. DEWASA: IM / IV 10-25 mg / minggu
(maksimal 50 mg / minggu). DEWASA: PO 2,5 mg tiap 12 jam
selama 3 dosis atau 8 interval jam untuk 4 dosis q wk
(maksimum 30 mg / minggu). ALTERNATIF JADWAL: PO 2,5 mg
qd selama 5 hari diikuti oleh 2-hari masa istirahat (maksimum
6,25 mg qd). Jadwal ini dapat menimbulkan peningkatan risiko
toksisitas hati. interaksi
Arang, asam folat: Dapat mengurangi efikasi metotreksat.
Digoxin: Dapat mengurangi tingkat digoxin serum dan tindakan.
Hydantoins: Dapat mengurangi kadar plasma. Etretinate, NSAID,
penisilin, probenesid, salisilat, sulfonamid: Dapat meningkatkan
kadar metotreksat dan toksisitas. Lab Uji Gangguan Tidak
didokumentasikan dengan baik. Reaksi yang merugikan
SSP: Pusing; kelelahan; sakit kepala; aphasia; hemiparesis;
paresis; kejang; eukoencephalopathy (IV setelah iradiasi
craniospinal); arachnoiditis kimia; paresis ransient;
neurotoksisitas. Derm: ruam eritematosa; pruritus; urtikaria;
fotosensitifitas; Perubahan igmentary; alopecia; ecchymosis;
telangiectasia; jerawat; furunculosis; ggravation psoriasis oleh
sinar ultraviolet. EENT: Penglihatan kabur; ulseratif stomatitis;
radang gusi; faringitis. GI: Mual; distress abdominal (umum);
anoreksia; muntah; diare; hematemesis; elena; ulserasi GI dan
perdarahan; radang usus. GU: Gagal ginjal; azotemia; sistitis;
hematuria; nefropati parah; gangguan reproduksi; infertilitas;
abortus; cacat janin. HEMA: Leukopenia; sumsum depresi tulang;
trombositopenia; anemia; ypogammaglobulinemia; pendarahan;
keracunan darah. HEPA: Hepatotoksisitas; sirosis hati dan
fibrosis. RESP: Kematian akibat pneumonitis interstitial; penyakit
paru kronik interstitial obstruktif. LAIN: Malaise; panas dingin;
demam; resistensi rendah terhadap infeksi; arthralgia; yalgia;
diabetes; osteoporosis; Reaksi anafilaktoid; kematian mendadak.
kewaspadaan
Kehamilan: Kategori X (untuk rheumatoid arthritis dan psoriasis);
Kategori D (kegunaan lain). Laktasi: Kontraindikasi pada ibu
menyusui. Anak-anak: Keamanan dan kemanjuran tidak didirikan
selain untuk pengobatan kanker. pasien usia lanjut: Erat
memantau tanda-tanda awal keracunan. Mungkin memerlukan
pengurangan dosis. Infeksi: Reaksi parah dapat terjadi jika
vaksin hidup yang diberikan. Terapi intratekal: dosis besar dapat
menyebabkan kejang-kejang dan toksisitas sistemik. regimen
dosis berdasarkan usia mungkin lebih efektif dan dikaitkan
dengan lebih sedikit efek samping neurotoksik. Jangan
menggunakan formulasi atau pengencer yang mengandung
pengawet. gangguan ginjal: Gunakan obat dengan hati-hati.
Menentukan status ginjal sebelum dan selama terapi. Efek yang
parah: Penggunaan rejimen metotreksat dosis tinggi (yaitu,
untuk mengobati osteosarkoma) memerlukan perawatan teliti.
Kematian terjadi setelah penggunaan methotrexate untuk
kondisi apapun. Potensi toksisitas termasuk depresi sumsum
tulang; hepatotoksisitas; Penyakit paru-paru (disarankan oleh
gejala kering, batuk tidak produktif); nefrotoksisitas dan
toksisitas GI.
PASIEN PERAWATAN PERTIMBANGAN
________________________________________ Administrasi / Storage
Pastikan bahwa leucovorin tersedia dari apotek sebelum
memulai pemberian dosis tinggi metotreksat. Leucovorin
mengurangi toksisitas methotrexate.
Oral sering disukai. Berikan obat 1-2 jam sebelum makan.
methotrexate Pengawet bebas dapat diberikan IM, IV, intraarterially atau intratekal.
Untuk penggunaan intratekal, menyusun kembali segera
sebelum digunakan dengan media bebas pengawet seperti 0,9%
Natrium Klorida untuk Injeksi.
prosedur Ikuti untuk penanganan dan pembuangan obat
antikanker. Pakailah sarung tangan dan menghindari paparan
kulit dan menghirup asap.
obat Simpan dalam tertutup rapat, kontainer cahaya-tahan.
Penilaian / Intervensi
Mendapatkan riwayat pasien, termasuk riwayat obat dan alergi
dikenal.
Sebelum memulai terapi, periksa kreatinin serum normal dan
kreatinin> 60 ml / menit.
Kaji alkoholisme, penyakit hati alkoholik atau penyakit hati
kronis lainnya.
Tentukan apakah pasien memiliki bukti sindrom
imunodefisiensi, infeksi aktif, yang sudah ada sebelumnya
diskrasia darah (misalnya, hipoplasia sumsum tulang,
leukopenia, trombositopenia atau anemia yang signifikan).
Kaji fungsi paru; perhatikan terutama Adanya efusi paru.
Membangun pengukuran fungsi paru dasar.
Pertahankan hidrasi yang memadai dan alkalinization urin
Methotrexate (Systemic)
Introductory Information
Antineoplastic agent and immunosuppressant; folic acid antagonist.a, b, c
Class: 10:00 Antineoplastic Agents; an300 (VA primary)
Brands*: Rheumatrex, Trexall
*
Most effective in patients who have had disease for only a short period prior to
initiation of chemotherapy, who have low initial gonadotropin concentrations, and
who do not have metastases.a
First-line therapy with or without leucovorin in patients with nonmetastatic or
good-prognosis metastatic gestational trophoblastic neoplasms.d, e
Component of combination chemotherapy regimen with dactinomycin and
chlorambucil in patients with good-prognosis metastatic gestational trophoblastic
neoplasms with refractory disease.e
In patients with poor-prognosis metastatic trophoblastic neoplasms, methotrexate
in combination with etoposide, dactinomycin, vincristine, and cyclophosphamide
(EMA-CO) is a standard treatment option.e A dose-intensive regimen, EMA-CE,
in which etoposide and cisplatin are substituted for vincristine and
cyclophosphamide of the EMA-CO regimen, may offer additional benefits.e
Has been used prophylactically against malignant trophoblastic disease in patients
with hydatidiform mole.a
Use of leucovorin rescue or deletion of methotrexate is advised if methotrexatecontaining regimens are being considered for the treatment of advanced or
metastatic bladder cancer in patients with renal dysfunction, edema, pleural fluid
collections, or ascites.205
Crohn's Disease
Management of chronically active Crohn's disease
Ectopic Pregnancy
Used as an alternative to surgical management of ectopic pregnancy
in
Psoriatic Arthritis
Has been used for its immunosuppressive and/or anti-inflammatory effects in
treatment of psoriatic arthritis
.109, 110
General
Consult specialized references for procedures for proper handling and disposal of
antineoplastics.b, c
Do not prescribe or dispense on as-needed ("prn") basis.c
If toxicity previously necessitated discontinuance, reinstitute with caution; consider
further need for drug and risk of toxicity recurrence.a, b, c
High-Dose Methotrexate Therapy with Leucovorin Rescue
Use of high-dose regimens employed in adjunctive treatment of osteosarcoma
requires meticulous understanding of risks associated with therapy and leucovorin
rescue.a, b
Hydrate patients with 1 L/m2 of IV fluid over 6 hours prior to initiation of
methotrexate infusion.b Continue hydration at 125 mL/m2 per hour (3 L/m2 daily)
during methotrexate infusion and for 2 days after completion of infusion.b
Alkalinize urine with sodium bicarbonate to maintain pH >7 during methotrexate
infusion and leucovorin calcium therapy; administer sodium bicarbonate orally or
via a separate IV solution.b
Scr must be normal and Clcr >60 mL/minute before therapy initiation.b Repeat Scr
and serum methotrexate 24 hours after starting methotrexate and at least once
daily until the methotrexate concentration is <0.023 mcg/mL (0.05 mcM).b
Measure Scr prior to each subsequent course of therapy; if Scr increases by 50%
compared to prior value, measure and document that Clcr >60 mL/minute (even if
Scr is still within normal range).b
Also consult manufacturer's labeling and published protocols for specific
recommendations based on laboratory and clinical findings.a
Administration
Administer orally or by IM, IV, or intrathecal injection; may also administer intraarterially.b, c Has been administered by sub-Q injection.c, p
Do not use formulations or diluents containing preservatives (e.g., benzyl alcohol)
for intrathecal administration or high-dose therapy.b
Oral Administration
Administer orally as tablets.c
Oral administration is often preferred when low doses are used since absorption is
rapid and effective serum concentrations are achieved.b, c
Manufacturer makes no specific recommendations regarding administration with
meals; food delays absorption and reduces peak serum concentrations.214, b, c
Children receiving 20-30 mg/m2 (0.65-1 mg/kg) weekly may have better
absorption and fewer adverse GI effects if administered either IM or sub-Q.b, c
Optimum duration of therapy is unknown.b, c
>IM or Sub-Q
Children receiving 20-30 mg/m2 (0.65-1 mg/kg) weekly may have better
absorption and fewer adverse GI effects if administered either IM or sub-Q.b, c
Leukemias
>Meningeal Leukemia
Intrathecal: Regardless of method used to determine intrathecal dosage, carefully
check dose prior to administration to minimize risk of inadvertent intrathecal
overdosage.106
Clinical studies indicate that intrathecal dosage regimens based on age may be
more effective and less neurotoxic than dosage regimens based on body surface
area.107, 108, 127, b
>Recommended Intrathecal Dose Based on Age107, 108, 127
Age
Dose
<1 year
6 mg
1 year
8 mg
2 years
10 mg
3 years
12 mg
Intrathecal doses based on body surface area (i.e., 12 mg/m2, maximum 15 mg)
reported to result in low CSF methotrexate concentrations and reduced efficacy in
pediatric patients.b
Treatment: may administer at intervals of 2-5 days until CSF cell count returns to
normal, at which point 1 additional dose is advisable.b Administration at intervals
of <1 week may result in increased subacute toxicity.b
Prophylaxis: dosage is the same as for treatment; administration intervals differ
from regimen used in treatment.a, b Consult specialized references and medical
literature for specific recommendations.a, b
Adults
Breast Cancer
Various combination chemotherapy regimens have been used in the treatment of
breast cancer; consult published protocols for dosages and method and sequence
of administration.168, 169, 170, 171, 172, 173, 174, 176, 180, 181, 183, 185, 187
Dose intensity of adjuvant combination chemotherapy appears to be an important
factor influencing clinical outcome in patients with early node-positive breast
cancer, with response increasing with increasing dose intensity; avoid arbitrary
reductions in dose intensity.166, 170, 187
>IV
Renal Impairment
Dose reduction and especially careful monitoring for toxicity required.b, c
Geriatric Patients
Select dosage with caution since hepatic and renal function and folate stores may
be decreased; closely monitor for early signs of toxicity.b, c
Patients with Ascites or Pleural Effusions
Dose reduction and especially careful monitoring for toxicity required.b, c
Cautions
Contraindications
Pregnant women with psoriasis or rheumatoid arthritis; use in treatment of
neoplastic diseases only when potential benefit outweighs risk to fetus.b, c (See
Boxed Warning.)
Nursing women.127, b, c
Excessive alcohol consumption, alcoholic liver disease, or other chronic liver
disease in patients with psoriasis or rheumatoid arthritis.127, b, c
Overt or laboratory evidence of immunodeficiency syndromes in patients with
psoriasis or rheumatoid arthritis.127, b, c
Preexisting blood dyscrasias (e.g., bone marrow hypoplasia, leukopenia,
thrombocytopenia, clinically important anemia) in patients with psoriasis or
rheumatoid arthritis.127, b, c
Known hypersensitivity to methotrexate.b, c
Warnings/Precautions
Warnings
Also see Boxed Warnings.
Fetal/Neonatal Morbidity and Mortality
Fetal death and/or congenital anomalies reported.b, c Exclude pregnancy before
initiating treatment.b, c Avoid pregnancy if either partner is receiving methotrexate;
avoid pregnancy during therapy and for 3 months after therapy in male patients
and for at least one ovulatory cycle after therapy in female patients.b, c If used
during pregnancy or patient becomes pregnant, apprise of potential fetal hazard.b, c
Sensitivity Reactions
Dermatologic and Sensitivity Reactions
Severe, occasionally fatal cutaneous or sensitivity reactions (e.g., toxic epidermal
necrolysis, Stevens-Johnson syndrome, exfoliative dermatitis, skin necrosis,
erythema multiforme) reported in pediatric and adult patients within days of
receiving drug at various dosages, by various routes, and for various conditions.193,
b, c
Hepatic Effects
Possible hepatotoxicity; may be acute (increased serum aminotransferase
concentrations) or chronic (fibrosis and cirrhosis).127, 128, 131, 155, 164, b, c
Chronic hepatotoxicity, potentially fatal, generally occurs after prolonged use (2
years) and after a total dose of 1.5 g.127, 128, 131, 164, b, c
Risk of hepatotoxicity in patients with psoriasis appears to be related to
cumulative dose and may be enhanced by alcoholism, obesity, diabetes, and
advanced age.116, 127, 131, 141, 142, 150, 158, 160, b, c These risk factors also may apply to
patients with rheumatoid arthritis;127, 150 age at first use and duration of therapy
also reported as risk factors in rheumatoid arthritis patients.b, c
Use with particular caution in patients with preexisting liver damage or hepatic
impairment.b, c
Psoriasis: Perform liver function tests, including serum albumin, periodically prior
to dosing, although results may be normal despite developing fibrosis or
cirrhosis.116, 127, 131, 138, 141, 142, 147, 148, b, c Liver biopsy recommended before therapy
or shortly after therapy initiation (2-4 months), at cumulative dose of 1.5 g, and
after each additional 1-1.5 g.127, 163, b, c Usually discontinue drug if moderate
fibrosis or any cirrhosis; repeat biopsy in 6 months if mild fibrosis.b, c Continue
use with caution if milder changes (e.g., fatty changes, low-grade portal
inflammation).b, c
Rheumatoid arthritis: Prolonged, substantial abnormalities in liver function test
results may precede appearance of hepatic fibrosis or cirrhosis; 127, b, c perform
liver function tests at baseline and at 4- to 8-week intervals.b, c Pretreatment liver
biopsy recommended if history of excessive alcohol consumption, persistently
abnormal baseline liver function tests, or chronic hepatitis B or C infection.127
Perform liver biopsy during therapy if persistent liver function test abnormalities
or serum albumin concentrations fall below normal (in setting of well-controlled
rheumatoid arthritis).b, c If liver biopsy shows mild changes (Roenigk grade I, II,
or IIIa), continue therapy and monitoring; discontinue if persistently abnormal
liver function tests, if biopsy shows moderate to severe changes (Roenigk grade
IIIb or IV), or if patient refuses biopsy.b, c
Respiratory Effects
Potentially fatal119, 127, 154 pulmonary toxicity; can progress rapidly117, 118, 119, 127, 128,
129, 130
and may not be fully reversible.119, 127, 128 Adverse pulmonary effects (i.e.,
acute or chronic interstitial pneumonitis, pulmonary fibrosis) may occur at any
dosage at any time during therapy.117, 118, 119, 242, b, c
If manifestations (e.g., fever, cough [especially dry and nonproductive], dyspnea,
chest pain, hypoxemia [possibly severe], radiographic evidence of pulmonary
infiltrates [usually diffuse and/or alveolar])117, 118, 119, 127, 128, 129, 130, 159, 160, b, c occur,
discontinue and carefully evaluate, including exclusion of possible infectious
causes.119, 127, 128, 129, 130
Management is mainly supportive and may include mechanical ventilation.119, 128,
129, 130
Nephrotoxicity is due principally to precipitation of methotrexate and 7hydroxymethotrexate in the renal tubules.b, c
Careful attention to renal function, including adequate hydration, urine
alkalinization, and measurement of methotrexate and Scr concentrations is
essential.c
Perform renal function tests prior to and periodically during therapy (at 1- to 2month intervals in patients with psoriasis or rheumatoid arthritis; more frequently
in patients with neoplastic disease).a, b, c
If renal impairment develops during therapy, reduce dosage or discontinue drug
until renal function is improved or restored.a, b, c
Immunosuppressive Effects
Consider immunosuppressive effects when evaluating use in patients in whom
immune response may be important or essential.a (See Vaccines under
Interactions.)
Usually contraindicated in patients with overt or laboratory evidence of
immunodeficiency syndromes.a, b, c (See Contraindications under Cautions.)
Use with extreme caution in presence of active infection.a, b, c
Hypogammaglobulinemia reported rarely.b, c
Neurologic Effects
Leukoencephalopathy reported following IV administration in patients who had
received craniospinal irradiation; chronic leukoencephalopathy also reported in
patients receiving repeated high-dose therapy with leucovorin rescue even without
cranial irradiation.b
Severe neurotoxic effects, manifested mainly by focal or generalized seizures,
reported with increased frequency in pediatric patients with ALL who received
intermediate-dose IV therapy (1 g/m2);193, b leukoencephalopathy and/or
microangiopathic calcifications usually were observed in diagnostic imaging
procedures of symptomatic patients.193
A transient acute neurologic syndrome observed in patients receiving high-dosage
regimens; exact cause unknown.b Manifestations of this stroke-like
encephalopathy may include confusion, hemiparesis, transient blindness, seizures,
and coma.b
Intrathecal Administration
Possible acute chemical arachnoiditis manifested by headache, back pain, nuchal
rigidity, and/or fever; subacute myelopathy manifested by paraparesis/paraplegia
involving one or more spinal nerve roots; chronic leukoencephalopathy (may be
Pediatric Use
Safety and efficacy established only for cancer chemotherapy or polyarticularcourse juvenile rheumatoid arthritis.b, c
In clinical studies, safety in pediatric patients 2-16 years of age with juvenile
rheumatoid arthritis was similar to that observed in adults with rheumatoid
arthritis.b, c
Severe neurotoxic effects (e.g., focal or generalized seizures) reported in pediatric
patients with ALL who received intermediate-dose IV therapy (1 g/m2).193, b (See
Neurologic Effects under Cautions.)
Preparations containing benzyl alcohol preservative not recommended in neonates
because of toxicity.b
Geriatric Use
Insufficient experience in patients 65 years of age to determine whether geriatric
patients respond differently than younger adults; select dosage with caution due to
greater frequency of decreased hepatic and renal function and folate stores and of
concomitant disease and drug therapy (i.e., that interfere with renal function or
methotrexate or folate metabolism) observed in the elderly.b, c
Occurrence of bone marrow suppression, thrombocytopenia, and pneumonitis
may increase with age.b, c
Closely monitor geriatric patients for early signs of hepatic, bone marrow, and
renal toxicity; certain toxicities may be reduced by folate supplementation.b, c Scr
may overestimate renal function in geriatric patients; consider more accurate
methods (i.e., Clcr). Serum methotrexate concentrations may be helpful.b, c
Hepatic Impairment
Contraindicated in patients with psoriasis or rheumatoid arthritis who have
alcoholic liver disease or other chronic liver disease.b c Use with extreme caution,
if at all, in patients with malignant disease who have preexisting liver damage or
impaired hepatic function.a
Renal Impairment
Usually contraindicated.a
Debilitated Patients
Use with extreme caution.c
Common Adverse Effects
Ulcerative stomatitis, leukopenia, nausea, abdominal distress, malaise, undue
fatigue, chills, fever, dizziness, decreased resistance to infection.b, c
Interactions
Protein-bound Drugs
Possible increased methotrexate toxicity because of displacement from protein
binding sites.a (See Specific Drugs under Interactions.)
Weak Organic Acids
Potential to delay renal excretion and increase accumulation of methotrexate.a
(See Specific Drugs under Interactions.)
Hepatotoxic Agents
Increase in adverse hepatic effects expected.b, c
Nephrotoxic Drugs
Possible altered renal elimination of methotrexate. Exercise caution if high-dose
methotrexate administered in conjunction with nephrotoxic drugs in patients with
osteosarcoma.b
Specific Drugs
Drug
Adalimumab
Aminobenzoic acid
Amiodarone
Anakinra
Asparaginase
Interaction
Comments
Decreased adalimumab
Dosage adjustment not
clearance
needed
Possible increased
methotrexate toxicity because Use concomitantly with
of displacement from protein cautiona
binding sitesa, b, c
Possible inhibition of
methotrexate metabolism with
prolonged administration (2
weeks) of oral amiodarone
Administered concurrently in
clinical studies, but specific
drug interactions not
evaluated in humans
No effect on clearance or
toxicologic profile of either
drug when administered
concurrently in rats
Administration of
Decreased effectiveness of
methotrexate with or
methotrexate during period of shortly after
asparagine suppression
asparaginase not
recommended
Azathioprine
Chloramphenicol
Cisplatin
Co-trimoxazole
Cyclosporine
Possible synergistic
antineoplastic effects
Exercise caution if highdose methotrexate
administered in
conjunction with
cisplatin in patients with
osteosarcomab
Infliximab
Avoid NSAIAs in
patients receiving
125, 126, 127, 128, b, c
relatively high dosages
NSAIAs (e.g.,
NSAIAs and salicylates may of methotrexate (e.g.,
indomethacin,
inhibit renal elimination of
those used in
ketoprofen,
methotrexate;120, 121, 122, 123, 124, osteosarcoma)127, 128, 155
phenylbutazone [not
125, 126, b, c
possibly increased Use caution if low-dose
commercially available in
and prolonged serum
methotrexate and
US], salicylates)
methotrexate
NSAIAs or salicylates
127, 128, 138, 139, a
concentrations
used concomitantly127,
128, b, c
Possible increased
methotrexate toxicity because
of displacement from protein
binding sites by
phenylbutazone or
salicylatesa, c
Possible decreased
methotrexate renal
clearance127, 188, 190
Increased serum methotrexate Carefully monitor
Penicillins (e.g.,
concentrations and GI or
patients during
amoxicillin, carbenicillin) hematologic toxicity reported concomitant use127, 188,
in patients receiving low- or 189, 190
high-dose methotrexate
therapy concomitantly with
penicillins127, 188, 189, 190
Possible increased
methotrexate toxicity because Use concomitantly with
Phenytoin
of displacement from protein cautiona
binding sitesa, c
Renal tubular transport of
Probenecid
Carefully monitorc
methotrexate diminishedb, c
Possible increased risk of
Do not administer
Pyrimethamine
myelosuppressionm
concomitantlya
Retinoids
Possible increased risk of
Closely monitor for
Sulfasalazine
Sulfonamides
Tetracyclines
hepatotoxicity127, b
Possible increased risk of
hepatotoxicity127, b
Possible increased
methotrexate toxicity because
of displacement from protein
binding sitesa, c
Possible increased
methotrexate toxicity because
of displacement from protein
binding sitesa, b, c
Possible decreased intestinal
absorption of methotrexate or
interference with
enterohepatic circulationb, c
toxicity127, b
Closely monitor for
toxicity127, b
Use concomitantly with
cautiona
Theophylline
Possible decreased
theophylline clearancec
Monitor serum
theophylline
concentrationsc
Vaccines
Disseminated vaccinia
infection reported following
smallpox vaccination in
patients receiving
methotrexate127, 128, 151
Although antibody response
to killed virus vaccines is not
normal, partial or complete
protection may still be
attained; however, may be
ineffectivea, b, c
Pharmacokinetics
Absorption
Bioavailability
Oral absorption appears to be highly variable and dose dependent;127, 214, 215 oral
bioavailability may be <50%.215 Bioavailability decreases with increasing oral
doses; absorption may be substantially reduced at doses >80 mg/m2.127, 214, 215
Following oral administration, peak serum concentrations are attained in 1-2
hours.127
Appears to be completely absorbed following IM administration at doses 100
mg;127, 215 peak serum concentrations are attained within 30-60 minutes.127
Onset
Elimination
Metabolism
Undergoes hepatic and intracellular metabolism to polyglutamate metabolites;127
partially metabolized by intestinal flora after oral administration.127
Polyglutamate metabolites may be converted back to methotrexate by
hydrolysis,127 and metabolites may remain in tissues for extended periods of
time.127
Elimination Route
Excreted principally by the kidneys and to a lesser extent via feces.a
Half-life
At low-doses (<30 mg/m2), terminal half-life is about 3-10 hours.127, b, c At high
doses, elimination half-life is about 8-15 hours.127, b, c
Special Populations
Excretion is impaired and accumulation occurs more rapidly in patients with
impaired renal function, pleural effusion, or other substantial third-space
accumulations (e.g., ascites).a, b, c
Stability
Storage
Oral
Tablets
Well-closed containers at 15-30C.c Protect from light.c
Parenteral
Injection
20-25C (may be exposed to 15-30C).b Protect from light.b
Storage of solutions containing preservatives after further dilution for 24 hours at
21-25C results in a product within 90% of label potency.b Use preservative-free
solution immediately after further dilution.b
Powder for Injection
20-25C (may be exposed to 15-30C).b Protect from light.b
Use immediately after reconstitution.b
Compatibility
For information on systemic interactions resulting from concomitant use, see
Interactions.
Parenteral
Solution Compatibilityb, HID
Compatible
Amino acids 4.25%, dextrose 25%
Dextrose 5% in water
Sodium bicarbonate 0.05 M
Sodium chloride 0.9%
>Drug Compatibility
>Admixture CompatibilityHID
Compatible
Cyclophosphamide
Cyclophosphamide with fluorouracil
Cytarabine
Fluorouracil
Hydroxyzine HCl
Mercaptopurine sodium
Ondansetron HCl
Sodium bicarbonate
Vincristine sulfate
Incompatible
Bleomycin sulfate
>Y-Site CompatibilityHID
Compatible
Allopurinol sodium
Amifostine
Amphotericin B cholesteryl sulfate complex
Asparaginase
Aztreonam
Bleomycin sulfate
Cefepime HCl
Ceftriaxone sodium
Cimetidine HCl
Cisplatin
Cyclophosphamide
Cytarabine
Daunorubicin HCl
Dexchlorpheniramine maleate
Diphenhydramine HCl
Doxorubicin HCl
Doxorubicin HCl liposome injection
Etoposide
Etoposide phosphate
Famotidine
Filgrastim
Fludarabine phosphate
Fluorouracil
Furosemide
Ganciclovir sodium
Gallium nitrate
Granisetron HCl
Heparin
Heparin sodium
Hydromorphone HCl
Imipenem-cilastatin sodium
Lansoprazole
Leucovorin calcium
Linezolid
Lorazepam
Melphalan HCl
Mesna
Methylprednisolone sodium succinate
Metoclopramide HCl
Mitomycin
Morphine sulfate
Ondansetron HCl
Oxacillin sodium
Oxaliplatin
Paclitaxel
Piperacillin sodium-tazobactam sodium
Prochlorperazine edisylate
Ranitidine HCl
Sargramostim
Teniposide
Thiotepa
Vinblastine sulfate
Vincristine sulfate
Vindesine sulfate
Vinorelbine tartrate
Incompatible
Chlorpromazine HCl
Gemcitabine HCl
Idarubicin HCl
Ifosfamide
Midazolam HCl
Nalbuphine HCl
Promethazine HCl
Propofol
Variable
Advice to Patients
Necessity of informing patients of potential benefits and risks of therapy and
importance of remaining under care of clinician throughout therapy.b, c
Risk of hematologic, hepatic, pulmonary, and renal toxicities; importance of close
follow-up, including periodic laboratory tests to monitor toxicity.b, c
Importance of recognizing early manifestations of toxicity and informing clinician
promptly if such manifestations occur.b, c
Importance of emphasizing to patients that the recommended dose is taken weekly
in rheumatoid arthritis and psoriasis, and that mistaken daily use of recommended
dose has led to fatal toxicity.c Encourage patients to read patient instruction sheet
provided with mnemonic dispensing packages.c
Importance of informing clinicians of existing or contemplated concomitant
therapy, including prescription and OTC drugs, as well as any concomitant
illnesses.b
Importance of women informing clinicians if they are or plan to become pregnant
or plan to breast-feed.b Importance of informing both male and female patients of
risks to fetus if pregnancy occurs.b, c Advise patients to avoid pregnancy while
either partner is receiving methotrexate, and for a minimum of 3 months after
therapy in men and at least 1 ovulatory cycle after therapy in women.b, c
Importance of informing patients of other important precautionary information.b
(See Cautions.)
Preparations
Excipients in commercially available drug preparations may have clinically
important effects in some individuals; consult specific product labeling for
details.
Methotrexate Sodium
Dosage
Routes
Strengths
Brand Names
Manufacturer
Forms
2.5 mg (of
Rheumatrex Dose Pack
Oral
Tablets
Wyeth
methotrexate)*
(scored)
Tablets,
5 mg (of
Trexall (scored)
Barr
film-coated methotrexate)*
7.5 mg (of
Trexall (scored)
Barr
methotrexate)*
10 mg (of
Trexall (scored)
Barr
methotrexate)*
15 mg (of
Trexall (scored)
Barr
methotrexate)*
25 mg (of
Methotrexate Sodium
Abraxis,
Parenteral Injection methotrexate) per Injection Isotonic (with
Mayne
mL
benzyl alcohol 0.9%)
* available from one or more manufacturer, distributor, and/or repackager by
generic (nonproprietary) name
Methotrexate Sodium (Preservative-free)
Dosage
Routes
Strengths
Brand Names
Forms
Methotrexate
For
20 mg (of
Parenteral
Sodium for
injection methotrexate)
Injection
Methotrexate
1 g (of
Sodium for
methotrexate)
Injection
25 mg (of
Methotrexate
Injection methotrexate) per Sodium Injection
mL
Isotonic
Manufacturer
Mayne
Abraxis, Mayne
Abraxis, Bedford,
Mayne, Bedford
Comparative Pricing
This pricing information is subject to change at the sole discretion of DS
Pharmacy. This pricing information was updated 03/2011. For the most current
and up-to-date pricing information, please visit www.drugstore.com. Actual costs
kemas Peringatan
Pengalaman Pembimbing Clinician
Berikan hanya di bawah pengawasan dokter yang berkualitas
berpengalaman dalam penggunaan antimetabolit therapy.b, c
Serius Reaksi Beracun (Kadang-kadang Fatal) Kemungkinan
Kematian dilaporkan dengan penggunaan dalam pengobatan
keganasan, psoriasis, dan arthritis.b arthritis, c
hati berikutnya, c
Biopsi hati setelah digunakan berkelanjutan sering menunjukkan
histologis changes.b, c Fibrosis dan sirosis mungkin tidak didahului oleh
gejala atau gangguan fungsi hati pada pasien dengan psoriasis;
periodik biopsi hati biasanya dianjurkan pada pasien tersebut
menjalani therapy.b jangka panjang, c
kelainan persisten pada tes fungsi hati dapat mendahului penampilan
fibrosis atau sirosis pada pasien dengan arthritis.b arthritis, c
Keracunan paru
Lesi paru berpotensi berbahaya, tidak selalu reversibel, dapat terjadi
secara akut pada setiap saat selama terapi dan telah dilaporkan pada
dosis serendah 7,5 mg weekly.b, c gejala paru (terutama kering, batuk
tidak produktif) mungkin memerlukan gangguan terapi dan evaluasi
hati-hati .b, c
GI Keracunan
Diare dan stomatitis ulseratif memerlukan penghentian terapi; jika
tidak, hemoragik enteritis dan kematian dari perforasi usus dapat
occur.b, c
Limfoma ganas
limfoma maligna (misalnya, non-Hodgkin lymphoma) dapat terjadi
pada pasien yang menerima terapi oral dosis rendah; limfoma tersebut
dapat mundur berikut methotrexate penghentian dan mungkin tidak
memerlukan therapy.a sitotoksik, b, c Jika limfoma tidak mundur
penghentian berikut, lembaga therapy.b tepat, c
Tumor Syndrome Lisis
Dapat menginduksi tumor sindrom lisis pada pasien dengan tumor
berkembang pesat; farmakologis yang tepat dan pengobatan suportif
dapat mencegah atau meringankan syndrome.b, c
Reaksi dermatologi
parah, reaksi kulit kadang-kadang fatal yang dilaporkan berikut dosis
tunggal atau ganda; Reaksi terjadi dalam beberapa hari oral, IM, IV,
atau administration.b intratekal, c Pemulihan dilaporkan dengan
penghentian therapy.b, c (Lihat Dermatologic dan Sensitivitas Reaksi
bawah Perhatian.)
Infeksi oportunistik
infeksi oportunistik Berpotensi fatal, terutama jiroveci pneumonia
(sebelumnya Pneumocystis carinii) pneumonia.b, c
Radioterapi bersamaan
peningkatan risiko Kemungkinan nekrosis jaringan lunak dan
penggunaan
Kanker payudara
Pengobatan (sendiri atau, lebih umum, dalam kombinasi kemoterapi)
dari cancer.a payudara, b, c
Pertama-line kemoterapi adjuvan dalam kombinasi dengan obat lain
(yaitu, siklofosfamid dan fluorouracil, dengan atau tanpa terapi
hormonal) 0,166, 167, 168, 169, 170, 171, 172, 173, 174, 175, 178,
179, 182, 185, 186, 187, d An rejimen anthracycline mengandung lebih
disukai pada pasien dengan disease.d node-positif
Beberapa studi menunjukkan sedikit keuntungan untuk rejimen
anthracycline mengandung tingkat kambuh bebas dan kelangsungan
hidup di kedua patients.l premenopause dan menopause
Juga digunakan pada pasien dengan disease.d metastasis, l
Kanker Kepala dan Leher
perawatan paliatif (sendirian dan dalam terapi kombinasi) dari
berulang atau kepala metastasis dan leher carcinoma.182, 210, 211,
212, b, c, d
Sering digunakan dalam kombinasi rejimen dengan agen antineoplastik
lainnya (misalnya, bleomycin, fluorouracil, vincristine) 0,210
Terapi kombinasi dengan cisplatin, methotrexate, bleomycin, dan
vincristine telah digunakan untuk karsinoma sel skuamosa berulang
atau metastasis dari kepala dan neck.212
Penelitian lebih lanjut diperlukan untuk membangun keuntungan
komparatif regimens.210 methotrexate mengandung, 212
leukemia
Komponen berbagai rejimen kemoterapi dalam pengobatan paliatif
akut leukemias.a, b, c
Intrathecal untuk profilaksis dan pengobatan leukemia.a meningeal, b,
d
terapi lini pertama dalam kombinasi dengan merkaptopurin untuk
pemeliharaan remisi obat-induced leukemia limfoblastik akut (ALL) .b,
c, d
Telah digunakan dalam dosis tinggi sebagai komponen dari beberapa
rejimen kombinasi kemoterapi alternatif untuk induksi remisi pada
SEMUA, tetapi umumnya tidak dianggap sebagai obat pilihan untuk
remisi induction.d
Jarang efektif sendirian untuk pengobatan leukemia myeloblastic akut
(AML); telah digunakan sebagai komponen tambahan dalam beberapa
rejimen kemoterapi untuk induksi atau terapi pasca-induksi AML.a, d
Kanker paru-paru
Telah digunakan dalam terapi lini kedua berulang cancer.235 paru-paru
sel kecil, b, c, n
normal) .b
Juga berkonsultasi protokol pembuat label dan diterbitkan untuk
rekomendasi tertentu berdasarkan laboratorium dan findings.a klinis
Administrasi
Mengelola secara lisan atau dengan IM, IV, atau injeksi intratekal;
mungkin juga mengelola intra-arterially.b, c Telah dikelola oleh sub-Q
injection.c, p
Jangan menggunakan formulasi atau pengencer yang mengandung
pengawet (misalnya, benzyl alcohol) untuk administrasi intratekal atau
therapy.b dosis tinggi
Administrasi Oral
Mengelola secara lisan sebagai tablets.c
oral sering disukai ketika dosis rendah digunakan sejak penyerapan
konsentrasi serum yang cepat dan efektif adalah achieved.b, c
Produsen tidak membuat rekomendasi spesifik tentang administrasi
dengan makanan; penyerapan penundaan makanan dan mengurangi
puncak serum concentrations.214, b, c
Sengaja harian bukannya administrasi mingguan pada pasien dengan
psoriasis atau rheumatoid arthritis dapat menyebabkan keracunan
yang fatal; hati-hati menginstruksikan pasien mengenai rejimen dan
frekuensi administration.c (Lihat Nasihat untuk Pasien.)
dispensing paket mnemonic (misalnya, Rheumatrex Dosis Pack)
dapat digunakan untuk terapi awal dan pemeliharaan pada pasien
yang menerima dosis mingguan 5-15 mg tetapi tidak dianjurkan untuk
titrasi dosis mingguan> 15 mg.a, c
Administrasi IV
Untuk solusi dan informasi kompatibilitas obat, lihat Kompatibilitas
bawah Stabilitas.
Mengelola melalui suntikan IV atau infusion.b
rekonstitusi
Menyusun kembali bubuk lyophilized untuk injeksi langsung sebelum
digunakan dengan steril, bebas pengawet solusi (misalnya, 5%
dextrose injeksi, 0,9% natrium klorida injeksi) .b
Menyusun kembali 20 mg vial untuk konsentrasi 25 mg / mL.b
menyusun kembali 1 g vial dengan 19,4 mL solusi yang tepat untuk
menghasilkan konsentrasi dari 50 mg / mL.b
Pengenceran
Ketika dosis tinggi diberikan oleh IV infus, encer dosis total solusi
dilarutkan dalam 5% dekstrosa injection.b
Lebih lanjut dapat encer solusi yang tersedia secara komersial untuk
injeksi IV yang mengandung pengawet dengan solusi yang kompatibel
(misalnya, 0,9% natrium klorida injeksi) .b
solusi bebas pengawet dapat diencerkan segera sebelum digunakan
dengan tepat steril, bebas pengawet solusi (misalnya, 5% dextrose
injeksi, 0,9% natrium klorida injeksi) .b
Administrasi IM
Mengelola dengan injection.b IM
rekonstitusi
Menyusun kembali bubuk lyophilized untuk injeksi langsung sebelum
digunakan dengan steril, bebas pengawet solusi (misalnya, 5%
dextrose injeksi, 0,9% natrium klorida injeksi) .b
Administrasi intratekal
Bebas pengawet solusi (1 mg / mL) digunakan untuk injection.b
intratekal Jangan mengelola larutan yang mengandung pengawet
intrathecally.b
Harus mengelola intrathecal untuk pengobatan leukemia meningeal
sejak berlalunya obat dari darah ke CSF adalah minimal.a, b
Sebelum administrasi intratekal, volume CSF kurang lebih setara
dengan volume larutan harus disuntikkan (misalnya, 5-15 mL)
biasanya removed.a
Jika pungsi lumbal adalah traumatis, tidak mengelola intrathecal;
memungkinkan 2 hari untuk dilalui sebelum kembali mencoba
injection.a
Menyuntikkan intrathecal hanya jika ada aliran mudah fluid.a spinal
darah bebas
Beberapa dokter merekomendasikan bahwa seluruh volume injeksi
methotrexate disuntikkan intrathecal di 15-30 seconds.a Aspirasi tidak
harus performed.a
Muncul dalam sirkulasi sistemik setelah pemberian intratekal;
menyesuaikan, mengurangi, atau menghentikan setiap pemberian
sistemik bersamaan sebagai appropriate.a, b
administrasi sistemik kalsium leucovorin bersamaan dengan
methotrexate intratekal dapat mencegah toksisitas sistemik tanpa
menghapuskan aktivitas obat di CNS.a
rekonstitusi
Untuk injeksi intratekal, menyusun kembali bubuk lyophilized untuk
konsentrasi 1 mg / mL dengan steril bebas pengawet pengencer yang
sesuai (misalnya, 0,9% natrium klorida injeksi) .b
Pengenceran
Untuk injeksi intratekal, encer methotrexate solusi bebas pengawet
untuk injeksi untuk konsentrasi 1 mg / mL dengan tepat steril bebas
pengawet pengencer (misalnya, 0,9% natrium klorida injeksi) .b
Dosis
Tersedia sebagai methotrexate natrium; dosis dinyatakan dalam
methotrexate.b, c
Berbagai jadwal dosis telah digunakan; individualize dosis, rute
pemberian, dan durasi terapi sesuai dengan penyakit yang diobati,
terapi lain yang digunakan, dan kondisi, respon, dan toleransi patient.a
yang Consult diterbitkan protokol untuk informasi tambahan tentang
rejimen alternatif dan dosis.
Pasien Pediatric
Psorias
> Oral, IM, atau IV
Biasanya tidak melebihi 30 mg weekly.c
Radang sendi
> Oral, IM, atau IV
Biasanya tidak melebihi 20 mg weekly.c
pengalaman terbatas menunjukkan peningkatan yang substansial
dalam insiden dan keparahan dari reaksi toksik yang serius, terutama
penekanan sumsum tulang, pada dosis> 20 mg weekly.c
Populasi khusus
Gangguan ginjal
pengurangan dosis dan pemantauan ekstra hati-hati untuk toksisitas
required.b, c
Pasien geriatri
Pilih dosis dengan hati-hati karena hati dan fungsi ginjal dan folat toko
mungkin akan menurun; memonitor tanda-tanda awal dari toxicity.b, c
Pasien dengan Ascites atau pleura Efusi
pengurangan dosis dan pemantauan ekstra hati-hati untuk toksisitas
required.b, c
Perhatian
kontraindikasi
Wanita hamil dengan psoriasis atau arthritis rheumatoid; digunakan
dalam pengobatan penyakit neoplastik hanya ketika potensi
keuntungan melebihi risiko untuk fetus.b, c (Lihat kemas Peringatan.)
Perawatan women.127, b, c
Konsumsi berlebihan alkohol, penyakit hati alkoholik, atau penyakit
hati kronis lain pada pasien dengan psoriasis atau arthritis.127
arthritis, b, c
jelas baru atau laboratorium bukti immunodeficiency sindrom pada
pasien dengan psoriasis atau arthritis.127 arthritis, b, c
diskrasia darah yang sudah ada sebelumnya (misalnya, sumsum
tulang hipoplasia, leukopenia, trombositopenia, anemia klinis penting)
pada pasien dengan psoriasis atau arthritis.127 arthritis, b, c
Dikenal hipersensitivitas terhadap methotrexate.b, c
Peringatan / Kewaspadaan
peringatan
Juga lihat Peringatan kemas.
Janin / neonatus Morbidity and Mortality
kematian janin dan / atau reported.b anomali kongenital, c Kecualikan
kehamilan sebelum memulai treatment.b, c Hindari kehamilan jika
salah satu pasangan menerima metotreksat; menghindari kehamilan
selama terapi dan untuk 3 bulan setelah terapi pada pasien laki-laki
dan untuk setidaknya satu siklus ovulasi setelah terapi di patients.b
perempuan, c Jika digunakan selama kehamilan atau pasien menjadi
hamil, memberitahukan potensi hazard.b janin, c
Reaksi sensitivitas
Dermatologi dan Sensitivitas Reaksi
Efek hematologi
Efek GI
Efek hati
Efek pernapasan
Efek ginjal
Populasi tertentu
kehamilan
Laktasi
Gunakan Pediatric
Gunakan Geriatric
hati Penurunan
Gangguan ginjal
Obat tertentu
Interaksi Obat Komentar
farmakokinetik
Penyerapan
bioavailabilitas
Serangan
Lamanya
Makanan
Populasi khusus
Distribusi
Tingkat
penghapusan Route
Setengah hidup
Populasi khusus
Stabilitas
Penyimpanan
Lisan
tablet
parenteral
Injeksi
Kesesuaian
Untuk informasi tentang interaksi sistemik yang disebabkan dari
penggunaan bersamaan, melihat Interaksi.
parenteral
Cocok
Dekstrosa 5% dalam air
Natrium klorida 0,9%
Cocok
siklofosfamid
sitarabin
fluorouracil
hydroxyzine HCl
ondansetron HCl
natrium bikarbonat
vincristine sulfat
tidak kompatibel
bleomycin sulfat
Cocok
amifostine
aztreonam
bleomycin sulfat
ceftriaxone sodium
cimetidine HCl
cisplatin
siklofosfamid
sitarabin
daunorubisin HCl
diphenhydramine HCl
doxorubicin HCl
Doxorubicin HCl liposom injeksi
etoposide
famotidine
fosfat fludarabine
fluorouracil
furosemide
gansiklovir natrium
granisetron HCl
heparin
heparin natrium
hidromorfon HCl
Imipenem-cilastatin natrium
lorazepam
mesna
Methylprednisolone sodium suksinat
metoclopramide HCl
morfin sulfat
ondansetron HCl
oxaliplatin
paclitaxel
proklorperazin edisylate
ranitidin HCl
Teniposide
thiotepa
sulfat vinblastin
vincristine sulfat
vinorelbine tartrate
tidak kompatibel
klorpromazin HCl
idarubicin HCl
ifosfamida
Nalbuphine HCl
prometazin HCl
propofol
Variabel
Deksametason sodium fosfat
droperidol
vankomisin HCl
tindakan
persiapan
Eksipien dalam persiapan obat yang tersedia secara komersial
mungkin memiliki efek klinis penting pada beberapa individu;
berkonsultasi pelabelan produk tertentu untuk rincian.
Harga komparatif
informasi harga ini dapat berubah kebijaksanaan DS Farmasi subjek.
informasi harga ini diperbarui 03/2011. Untuk yang terbaru dan up-todate informasi harga, silahkan kunjungi www.drugstore.com. biaya
yang sebenarnya kepada pasien akan bervariasi tergantung pada
penggunaan lokasi ritel atau mail-order khusus dan copays asuransi
kesehatan.
DIH
Methotrexate
Lexi-Drugs Online
English
English
Sound-alike/look-alike issues:
Methotrexate may be confused with metolazone, mitoxantrone
Apo-Methotrexate; ratio-Methotrexate
Pharmacologic Category
Dosing: Elderly
12 years: 8 g/m2
Acute lymphocytic leukemia (intermediate-dose): I.V.: Loading: 100 mg/m2
bolus dose, followed by 900 mg/m2/day infusion over 23-41 hours.
Meningeal leukemia: I.T.: 10-15 mg/m2 (maximum dose: 15 mg) or an agebased dosing regimen; one possible system is:
3 months: 3 mg/dose
4-11 months: 6 mg/dose
1 year: 8 mg/dose
2 years: 10 mg/dose
3 years: 12 mg/dose
Dosing: Renal Impairment
The FDA-approved labeling does not contain dosage adjustment guidelines. The
following guidelines have been used by some clinicians (Floyd, 2006):
Bilirubin 3.1-5 mg/dL or transaminases >3 times ULN: Administer 75% of dose
Bilirubin >5 mg/dL: Avoid use
Dosing: Combination Regimens
Bladder cancer:
CMV
M-VAC (Bladder Cancer)
Breast cancer:
CMF
CMF-IV
CMFP
CMFVP (Cooper Regimen, VPCMF)
Dox-CMF (Sequential)
MF
M-VAC (Breast Cancer)
Cervical cancer: M-VAC (Cervical Cancer)
Endometrial cancer: MVAC (Endometrial Cancer)
Gastric cancer: FAMTX
Gestational trophoblastic tumor:
CHAMOCA (Modified Bagshawe Regimen)
CHAMOMA (Bagshawe Regimen)
EMA/CO
EP/EMA
Head and neck cancer:
CABO
MVAC (Head and Neck)
Leukemia, acute lymphocytic:
Hyper-CVAD + Imatinib
May be administered I.V.; I.V. administration may be as slow push, short bolus
infusion, or 24- to 42-hour continuous infusion
Specific dosing schemes vary, but high dose should be followed by leucovorin
calcium to prevent toxicity; refer to Leucovorin monograph
Administration: Other
Store tablets and intact vials at room temperature (15C to 25C). Protect from
light. Solution diluted in D5W or NS is stable for 24 hours at room temperature
(21C to 25C). Reconstituted solutions with a preservative may be stored
under refrigeration for up to 3 months, and up to 4 weeks at room temperature.
Intrathecal dilutions are stable at room temperature for 7 days, but it is generally
recommended that they be used within 4-8 hours.
Reconstitution
Methotrexate/Trimetrexate Allergy
Warnings/Precautions
Boxed Warnings:
Acute renal failure: See Concerns related to adverse effects
below.
Ascites/pleural effusion: See Disease-related concerns below.
Bone marrow suppression: See Concerns related to adverse
effects below.
Dermatologic reactions: See Concerns related to adverse effects
below.
Diarrhea/stomatitis: See Concerns related to adverse effects
below.
Experienced physician: See Other warnings/precautions below.
Hepatotoxicity: See Concerns related to adverse effects below.
Lymphomas: See Concerns related to adverse effects below.
NSAID's: See Concurrent drug therapy issues below.
Opportunistic infections: See Concerns related to adverse effects
below.
Pneumonitis: See Concerns related to adverse effects below.
Pregnancy: See Special populations below.
outweighs the possible risk to the fetus. Pregnancy should be excluded prior to
therapy in women of childbearing potential. Pregnancy should be avoided for
3 months following treatment in male patients and 1 ovulatory cycle in
female patients.
Lactation
No
Oncology: Emetic Potential
Do not take any new medication during therapy unless approved by prescriber.
Infusion/injection: Report immediately any redness, swelling, pain, or burning at
infusion/injection site. It is very important to maintain adequate hydration (2-3
L/day of fluids) unless instructed to restrict fluid intake and nutrition (small
frequent meals may help). Avoid alcohol to prevent serious side effects. You will
be more susceptible to infection (avoid crowds and exposure to infection and do
not have any vaccinations without consulting prescriber). May cause sensitivity to
sunlight (use sunscreen, wear protective clothing, and eyewear); nausea or
vomiting (small frequent meals, frequent mouth care, sucking lozenges, or
chewing gum may help; if unresolved, contact prescriber); drowsiness, dizziness,
numbness, or blurred vision (use caution when driving or engaging in tasks that
require alertness until response to drug is known); loss of hair (may be reversible);
color change of skin; permanent sterility; or mouth sores (frequent mouth care
with soft toothbrush or cotton swabs and frequent rinses may help). Report
immediately any rash, excessive or unusual fatigue, or respiratory difficulty.
Report rapid heartbeat or palpitations, black or tarry stools, fever, chills, unusual
bleeding or bruising, shortness of breath, persistent GI disturbances, diarrhea,
constipation, pain on urination or change in urinary patterns, or any other
persistent adverse effects. Pregnancy/breast-feeding precautions: Do not get
pregnant while taking this medication. This drug should not be used in the 2nd or
3rd trimester of pregnancy. Consult prescriber for appropriate contraceptive
measures if necessary or if you suspect you might be pregnant. This drug may
cause birth defects. Do not breast-feed.
Dosage Forms
Yes
Pricing: U.S. (www.drugstore.com)
Pemulihan: 21 hari
Hati: Sirosis dan fibrosis portal telah dikaitkan dengan terapi
methotrexate kronis; elevasi akut enzim hati yang umum setelah
metotreksat dosis tinggi, dan biasanya diselesaikan dalam waktu 10
hari.
Neuromuskular & skeletal: Artralgia
Okular: Penglihatan kabur
Ginjal: Disfungsi ginjal: Diwujudkan oleh kenaikan mendadak kreatinin
serum dan BUN dan penurunan output urin; lebih umum dengan
metotreksat dosis tinggi, dan mungkin karena pengendapan obat.
Pernapasan: Pneumonitis: Terkait dengan demam, batuk, dan infiltrat
paru interstitial; pengobatan adalah untuk menahan metotreksat
selama reaksi akut; pneumonitis interstitial telah dilaporkan terjadi
dengan kejadian 1% pada pasien dengan RA (dosis 7,5-15 mg /
minggu)
<1% (terbatas untuk penting atau mengancam jiwa): sindrom
neurologis akut (pada dosis tinggi - gejala termasuk kebingungan,
hemiparesis, kebutaan sementara, dan koma); anafilaksis, alveolitis,
disfungsi kognitif (telah dilaporkan pada dosis rendah), penurunan
resistensi terhadap infeksi, eritema multiforme, gagal hati,
leukoencephalopathy (terutama setelah iradiasi craniospinal atau
terapi dosis tinggi berulang), gangguan limfoproliferatif, osteonekrosis
dan nekrosis jaringan lunak (dengan radioterapi), perikarditis, erosi
plak (psoriasis), kejang (lebih sering pada pasien anak dengan ALL),
sindrom Stevens-Johnson, tromboemboli
Onkologi: yg menyebabkan bengkak
Tidak
Onkologi: Emetik Potensi
Rendah (10% sampai 30%): <250 mg / m2
Sedang (30% sampai 90%): 250 mg / m2
Methotrexate (oral): Sangat rendah (<10%)
Interaksi obat
Acitretin: Semoga meningkatkan efek hepatotoksik dari Methotrexate.
Risiko X: Hindari kombinasi
Bile Acid sequestrants: Semoga menurunkan penyerapan
Methotrexate. Risiko C: Terapi Memantau
Glikosida jantung: Agen antineoplastik dapat menurunkan penyerapan
jantung Glikosida. Hal ini hanya dapat mempengaruhi tablet digoxin.
Pengecualian: digitoksin. Risiko C: Terapi Memantau
Ciprofloxacin: Dapat meningkatkan konsentrasi serum Methotrexate.
Risiko C: Terapi Memantau
Siklosporin: Methotrexate dapat meningkatkan konsentrasi serum
siklosporin. Hal ini dapat mengakibatkan nefrotoksisitas. Siklosporin
dapat meningkatkan konsentrasi serum Methotrexate. Hal ini dapat
mengakibatkan mual, muntah, ulkus oral, hepatotoksisitas dan / atau
nefrotoksisitas. Risiko D: Pertimbangkan modifikasi terapi
mL, 40 mL)
Tablet: 2.5 mg
Trexall ": 5 mg, 7,5 mg, 10 mg, 15 mg
Tablet, natrium [pack dosis] (Rheumatrex Dosis Pack): 2,5 mg (4
kartu dengan 2, 3, 4, 5, atau 6 tablet masing-masing)
generik Tersedia
iya nih
Harga: AS (www.drugstore.com)
Solusi (Methotrexate Sodium)
25 mg / mL (2): $ 8,99
25 mg / mL (2): $ 14,99
25 mg / mL (10): $ 24,99
25 mg / mL (40): $ 58,99
Solusi (Methotrexate Sodium LPF)
25 mg / mL (2): $ 7,99
Tablet (Rheumatrex)
2,5 mg (8): $ 49,99
Tablet (Trexall)
10 mg (30): $ 426,29
Mekanisme aksi
Metotreksat adalah antimetabolit folat yang menghambat sintesis DNA.
Methotrexate ireversibel mengikat dihidrofolat reduktase, menghambat
pembentukan berkurang folat, dan timidilat sintetase, yang
mengakibatkan penghambatan purin dan timidilat sintesis asam.
Metotreksat adalah siklus sel spesifik untuk fase S dari siklus.
MOA dalam pengobatan rheumatoid arthritis tidak diketahui, tetapi
dapat mempengaruhi fungsi kekebalan tubuh. Pada psoriasis,
methotrexate diduga menargetkan cepat berkembang biak sel epitel di
kulit.
Farmakodinamik / Kinetics
melintasi plasenta;