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methotrexate
generic
Black Box Warnings .
Appropriate Use
admin. only under supervision of physician experienced w/ antimetabolite tx; use only in life-threatening neoplastic dz or for severe, recalcitrant, disabling psoriasis or RA not responsive to other tx; deaths reported w/ use in malignancy, psoriasis, and RA; closely monitor for bone marrow, liver, lung, and kidney toxicities; caution w/ high-dose osteosarcoma regimens, high-dose regimens for other neoplastic dz are investigational w/o demonstrated therapeutic advantage; inform pts of risks and monitor throughout tx
Appropriate Use for Intrathecal or High-Dose Tx
admin. only preservative-free INJ form for tx of neonates, low birth wt infants, intrathecal use, or high-dose regimens; preservative INJ form contains benzyl alcohol, which can cause severe central nervous toxicity or metabolic acidosis
Embryo-Fetal Toxicity and Death
may cause embryo-fetal toxicity and death; contraindicated in pregnant pts w/ RA, psoriasis, or JIA, weigh risk/benefit in pregnant pts w/ neoplastic dz; use effective contraception during tx and x6mo after D/C in female pts of reproductive potential and during tx and for at least 3mo after D/C in male pts
Hypersensitivity Rxn
contraindicated in pts w/ hx of severe hypersens. rxns to methotrexate, incl. anaphylaxis; D/C tx immed. and permanently if serious hypersens. rxn or anaphylaxis
Impaired Drug Elimination
drug elimination reduced in renal impairment, ascites, or pleural effusions; closely monitor for toxicity, reduce dose or in some cases D/C tx
Concomitant NSAID Use
unexpectedly severe and sometimes fatal myelosuppression, aplastic anemia, and GI toxicity reported w/ methotrexate (usually high dose) in combo w/ some NSAIDs
Hepatotoxicity
hepatotoxicity, fibrosis and cirrhosis generally only after prolonged use; acute LFT elevation common, usually transient and asymptomatic, not predictive of later hepatic dz; abnormal LFTs or sx may not precede fibrosis or cirrhosis in psoriasis pts, periodic liver biopsies recommended if chronic tx; persistent abnormal LFTs may precede fibrosis or cirrhosis in RA pts
Pulmonary Toxicity
methotrexate-induced lung dz, incl. acute or chronic interstitial pneumonitis, may occur acutely or any time during tx; has occurred at low doses; not always reversible and fatalities reported; pulmonary sx, especially nonproductive dry cough, may require interruption of tx and careful investigation
GI Toxicity
diarrhea and ulcerative stomatitis require tx interruption, otherwise intestinal perforation may lead to hemorrhagic enteritis and death
Malignant Lymphoma
may occur w/ low-dose tx and may regress when D/C tx; if lymphoma does not regress when D/C tx, start appropriate cytotoxic tx
Tumor Lysis Syndrome
tumor lysis syndrome (TLS) may occur in pts w/ rapidly growing tumors; use appropriate supportive and pharmacologic measures to prevent or alleviate TLS
Skin Rxns
severe, occasionally fatal; rxns may occur w/in days after single or multiple PO, IM, IV, or intrathecal doses; recovery may occur when tx D/C
Opportunistic Infections
potentially fatal; incl. PCP
Concomitant Radiotherapy
incr. risk of soft tissue necrosis and osteonecrosis
Adult Dosing .
Dosage forms: TAB: 2.5 mg; INJ: various
Special Note
- [uses, dosing may vary]
- Info: refer to institution protocols and pkg insert prior to prescribing for uses and dosing incl. toxicity-related dose adjustments
ALL
- [IM/IV route]
- Dose: 10-5000 mg/m^2/dose IV x1 on specific day(s) of cycle per regimen; Alt: 20-30 mg/m^2/dose IM qwk; Info: individualize dose, frequency based on dz state, pt risk, concurrent drugs, tx phase, response to tx; admin. leucovorin rescue if high-dose (500 mg/m^2/dose or greater); consider leucovorin rescue if intermediate-dose regimen (100-500 mg/m^2/dose); use preservative-free formulation for high-dose regimen; alkalinize urine to maintain pH of 7 or higher, admin. fluids to maintain adequate hydration and UO before 1st dose and throughout high-dose tx; part of multi-drug chemo regimen
- [PO route, maintenance tx]
- Dose: individualize dose PO qwk; Start: 20 mg/m^2/dose PO qwk; Info: part of multi-drug chemo regimen
meningeal leukemia
- [treatment]
- Dose: 12-15 mg intrathecally q2-5 days up to 2x/wk; Info: use only preservative-free formulation; cont. until CSF normal, then give one additional dose; admin. leucovorin rescue in pts w/ Down syndrome
- [prophylaxis]
- Dose: 12-15 mg intrathecally no more frequently than qwk; Max: 1 dose/wk Info: use only preservative-free formulation; admin. leucovorin rescue in pts w/ Down syndrome
mycosis fungoides
- [monotherapy]
- Dose: 25-75 mg PO qwk
- [combo tx]
- Dose: 10 mg/m^2/dose PO 2x/wk
non-Hodgkin lymphoma
- [induction tx]
- Dose: 1000 mg/m^2/dose IV x1 on specific day of cycle per regimen; Alt: 3000 mg/m^2/dose IV x1 on specific day of cycle per regimen; Info: admin. leucovorin rescue; use preservative-free formulation; alkalinize urine to maintain pH of 7 or higher, admin. fluids to maintain adequate hydration and UO before 1st dose and throughout tx; part of multi-drug chemo regimen
- [relapsed or refractory dz]
- Dose: 2.5 mg PO 2-4x/wk; Max 10 mg/wk; Info: part of metronomic multi-drug chemo regimen
CNS lymphoma
- [monotherapy]
- Dose: 8000 mg/m^2/dose IV x1 on specific day of cycle per regimen; Info: admin. leucovorin rescue; use preservative-free formulation; alkalinize urine to maintain pH of 7 or higher, admin. fluids to maintain adequate hydration and UO before 1st dose and throughout tx
- [combo tx]
- Dose: 3000 mg/m^2/dose IV x1 on specific day of cycle per regimen; Alt: 3500 mg/m^2/dose or 8000 mg/m^2/dose IV x1 on specific day of cycle per regimen; Info: admin. leucovorin rescue; use preservative-free formulation; alkalinize urine to maintain pH of 7 or higher, admin. fluids to maintain adequate hydration and UO before 1st dose and throughout tx
osteosarcoma
- [12 g/m^2/dose IV x1 at wk 4, 5, 6, 7, 11, 12, 15, 16, 29, 30, 44, 45]
- Start: 4wk after surgery; Max: 20 g/dose; Info: individualize dose, frequency based on peak serum MTX conc., pt comorbidities, dz, prior tx; if peak serum MTX conc. <10 mol/L at end of infusion, may incr. subsequent dose to 15 g/m^2/dose; admin. leucovorin rescue; use preservative-free formulation; alkalinize urine to maintain pH of 7 or higher, admin. fluids to maintain adequate hydration and UO before 1st dose and throughout tx; part of multi-drug chemo regimen
breast CA
- [40 mg/m^2/dose IV x1 on days 1, 8 of 28-day cycle x6 cycles]
- Info: part of multi-drug chemo regimen
squamous cell head/neck CA
- [40-60 mg/m^2/dose IV qwk]
gestational trophoblastic neoplasia
- [low-risk dz]
- Dose: 30-200 mg/m^2/dose IM/IV x1 on specific day(s) of cycle per regimen; Alt: 0.4-1 mg/kg/dose IM/IV x1 on specific day(s) of cycle per regimen; Info: part of multi-drug chemo regimen
- [high-risk dz]
- Dose: 300 mg/m^2/dose IV x1 on specific day(s) of cycle per regimen; Info: part of multi-drug chemo regimen
rheumatoid arthritis
- [7.5-20 mg PO/SC/IM qwk]
- Start: 7.5 mg PO/SC/IM qwk; Max: 25 mg/wk; Info: use lowest effective dose; give w/ folic acid 1 mg qd or leucovorin 5 mg qwk
psoriasis, severe
- [7.5-25 mg PO/SC/IM/IV qwk]
- Max: 30 mg/wk PO; 25 mg/wk SC/IM/IV; Alt: may give divided doses PO q12h x3 doses qwk; Info: use lowest effective dose; give w/ folic acid 1 mg qd or leucovorin 5 mg qwk
ectopic pregnancy (off-label)
- [50 mg/m^2/dose IM/IV x1]
- Info: repeat dose in 7 days if beta-HCG levels have not decr. at least 15% from day of first injection
Crohn dz, mod-severe (off-label)
- [15 mg SC/IM qwk]
- Start: 25 mg SC/IM qwk x16-25wk, then decr. dose to 15 mg SC/IM qwk; Info: for induction or remission maintenance tx; give w/ folic acid 1 mg qd or leucovorin 5 mg qwk
renal dosing
- [ectopic pregnancy]
- significant impairment: contraindicated
- HD/PD: contraindicated
- [all other indications]
- CrCl 10-50: decr. usual dose by 50%; CrCl <10: avoid use
- HD: decr. usual dose by 50%, on dialysis days admin. after dialysis; no supplement; PD: avoid use
hepatic dosing
- [ectopic pregnancy]
- significant impairment: contraindicated
- [all other indications]
- hepatic impairment: not defined, caution advised; chronic hepatic dz: avoid use
Peds Dosing .
- Dosage forms: TAB: 2.5 mg; INJ: various
Special Note
- [uses, dosing may vary]
- Info: refer to institution protocols and pkg insert prior to prescribing for uses and dosing incl. toxicity-related dose adjustments
ALL
- [IM/IV route]
- Dose: 10-5000 mg/m^2/dose IV x1 on specific day(s) of cycle per regimen; Alt: 20-30 mg/m^2/dose IM qwk; Info: individualize dose, frequency based on dz state, pt risk, concurrent drugs, tx phase, response to tx; admin. leucovorin rescue if high-dose (500 mg/m^2/dose or greater); consider leucovorin rescue if intermediate-dose regimen (100-500 mg/m^2/dose); use preservative-free formulation for neonates, low birth wt infants, high-dose regimen; alkalinize urine to maintain pH of 7 or higher, admin. fluids to maintain adequate hydration and UO before 1st dose and throughout high-dose tx; part of multi-drug chemo regimen
- [PO route, maintenance tx]
- Dose: individualize dose PO qwk; Start: 20 mg/m^2/dose PO qwk; Info: part of multi-drug chemo regimen
meningeal leukemia
- [treatment, <1 yo]
- Dose: 6 mg intrathecally q2-5 days up to 2x/wk; Info: use only preservative-free formulation; cont. until CSF normal, then give one additional dose; admin. leucovorin rescue in pts w/ Down syndrome
- [treatment, 1 yo]
- Dose: 8 mg intrathecally q2-5 days up to 2x/wk; Info: use only preservative-free formulation; cont. until CSF normal, then give one additional dose; admin. leucovorin rescue in pts w/ Down syndrome
- [treatment, 2 yo]
- Dose: 10 mg intrathecally q2-5 days up to 2x/wk; Info: use only preservative-free formulation; cont. until CSF normal, then give one additional dose; admin. leucovorin rescue in pts w/ Down syndrome
- [treatment, 3-8 yo]
- Dose: 12 mg intrathecally q2-5 days up to 2x/wk; Info: use only preservative-free formulation; cont. until CSF normal, then give one additional dose; admin. leucovorin rescue in pts w/ Down syndrome
- [treatment, 9 yo and older]
- Dose: 12-15 mg intrathecally q2-5 days up to 2x/wk; Info: use only preservative-free formulation; cont. until CSF normal, then give one additional dose; admin. leucovorin rescue in pts w/ Down syndrome
- [prophylaxis, <1 yo]
- Dose: 6 mg intrathecally no more frequently than qwk; Max: 1 dose/wk Info: use only preservative-free formulation; admin. leucovorin rescue in pts w/ Down syndrome
- [prophylaxis, 1 yo]
- Dose: 8 mg intrathecally no more frequently than qwk; Max: 1 dose/wk Info: use only preservative-free formulation; admin. leucovorin rescue in pts w/ Down syndrome
- [prophylaxis, 2 yo]
- Dose: 10 mg intrathecally no more frequently than qwk; Max: 1 dose/wk Info: use only preservative-free formulation; admin. leucovorin rescue in pts w/ Down syndrome
- [prophylaxis, 3-8 yo]
- Dose: 12 mg intrathecally no more frequently than qwk; Max: 1 dose/wk Info: use only preservative-free formulation; admin. leucovorin rescue in pts w/ Down syndrome
- [prophylaxis, 9 yo and older]
- Dose: 12-15 mg intrathecally no more frequently than qwk; Max: 1 dose/wk Info: use only preservative-free formulation; admin. leucovorin rescue in pts w/ Down syndrome
non-Hodgkin lymphoma
- [induction tx]
- Dose: 1000 mg/m^2/dose IV x1 on specific day of cycle per regimen; Alt: 3000 mg/m^2/dose IV x1 on specific day of cycle per regimen; Info: admin. leucovorin rescue; use preservative-free formulation; alkalinize urine to maintain pH of 7 or higher, admin. fluids to maintain adequate hydration and UO before 1st dose and throughout tx; part of multi-drug chemo regimen
CNS lymphoma
- [monotherapy]
- Dose: 8000 mg/m^2/dose IV x1 on specific day of cycle per regimen; Info: admin. leucovorin rescue; use preservative-free formulation; alkalinize urine to maintain pH of 7 or higher, admin. fluids to maintain adequate hydration and UO before 1st dose and throughout tx
- [combo tx]
- Dose: 3000 mg/m^2/dose IV x1 on specific day of cycle per regimen; Alt: 3500 mg/m^2/dose or 8000 mg/m^2/dose IV x1 on specific day of cycle per regimen; Info: admin. leucovorin rescue; use preservative-free formulation; alkalinize urine to maintain pH of 7 or higher, admin. fluids to maintain adequate hydration and UO before 1st dose and throughout tx
osteosarcoma
- [12 g/m^2/dose IV x1 at wk 4, 5, 6, 7, 11, 12, 15, 16, 29, 30, 44, 45]
- Start: 4wk after surgery; Max: 20 g/dose; Info: individualize dose, frequency based on peak serum MTX conc., pt comorbidities, dz, prior tx; if peak serum MTX conc. <10 mol/L at end of infusion, may incr. subsequent dose to 15 g/m^2/dose; admin. leucovorin rescue; use preservative-free formulation; alkalinize urine to maintain pH of 7 or higher, admin. fluids to maintain adequate hydration and UO before 1st dose and throughout tx; part of multi-drug chemo regimen
juvenile idiopathic arthritis
- [2 yo and older]
- Dose: 10-20 mg/m^2/dose PO/SC/IM qwk; Start: 10 mg/m^2/dose PO/SC/IM qwk; Max: 25 mg/wk; Info: use lowest effective dose; give w/ folic acid 1 mg qd or leucovorin 5 mg qwk
renal dosing
- [adjust dose amount]
- CrCl 10-50: decr. usual dose by 50%; CrCl <10: decr. usual dose by 70%
- HD: decr. usual dose by 70%, on dialysis days admin. after dialysis; no supplement; PD: decr. usual dose by 70%; no supplement
hepatic dosing
- [see below]
- hepatic impairment: not defined, caution advised; chronic hepatic dz: avoid use