methotrexate

Warnings and precautions

Black Box Warning: Pregnancy, bone marrow suppression Precautions: Breastfeeding, children, exfoliative dermatitis Black Box Warning: Renal disease, ascites, diarrhea, infection, intrathecal administration, lymphoma, pleural effu- sion, pulmonary toxicity, radiation ther- apy, stomatitis, tumor lysis syndrome, gastroenteritis, GI bleeding/perforation, hepatotoxicity, intrauterine fetal death, nephrotoxicity, requires an experienced clinician Black Box Warning: Use preservative- free sol, reconstitute with NS; dose should be drawn into 5- to 10-mL syringe after LP, vol of CSF should be withdrawn equal to vol of methotrexate; allow CSF to flow into syringe and mix, inject over 15-30 sec with bevel of needle upward • Use safe handling procedures for che- motherapeutic agents PO route • This route is  preferred for low-dose therapy • Methotrexate absorption is dose- dependent; absorption of single doses more than 40 mg/m2 is significantly less than that of lower doses • Weekly therapy with Rheumatrex Dose Packs is not intended for doses more than 15 mg PO/wk • Oral liquid formulations:  Mistaken daily use of the recommended dose has led to fatal toxicity • Measure using a calibrated oral mea- suring device • Storage:  store at room temperature (68°F-77°F) for up to 60 days Injectable route • Visually inspect parenteral products for particulate matter and discolor- M ation before use • The preserved solutions contain ben- zyl alcohol and should not be used for intrathecal, intermediate-, or high-dose therapy  • Reconstitution of lyophilized pow- ders: reconstitute each vial with sterile, preservative-free solution (D5W, 0.9% NaCl injection). Reconstitute the 25-mg vial to a concentration ≤25 mg/mL. The 1-g vial should be reconstituted with 19.4 mL to a concentration of 50 mg/mL; prepare immediately before use. Discard unused portions Intravenous route • Direct IV injection:    inject as a slow push via Y-site or 3-way stopcock into a free-flowing IV infusion  • Intermittent/continuous IV infusion:  further dilute in D5W, D5/0.8% NaCl, 0.9% NaCl injection before  infusion, check vein patency by flushing with 5 to 10 mL of 5% dextrose injection or 0.9% sodium chloride injection; infuse at pre- scribed rate. Following infusion, flush  IV tubing  IV infusion of intermediate- or high-dose methotrexate (500 mg/m2 over <4 hr or more than 1 g/m2 over >4 hr) • Before  use, the following laboratory parameters should be confirmed: WBC >1,500/mm3, neutrophil count >200/ mm3, platelet count >75,000/mm3, se- rum bilirubin <1.2 mg/dL, normal se- rum creatinine, and SGPT <450 U. Cre- atinine clearance should be >60 mL/ min. If serum creatinine has increased by 50% or more compared to a prior value, creatinine clearance should be measured and documented as more than  60 mL/ min even if the serum creatinine is still within normal limits • Give 1 L/m2 of IV fluids over 6 hr be- fore initiation of the methotrexate infu- sion; continue hydration at 125 mL/m2/ hr during the methotrexate infusion and for 2 days after the infusion has been completed • Alkalinize the urine using sodium bi- carbonate to maintain the urine pH more than 7 during the methotrexate infusion and leucovorin therapy • Repeat serum creatinine and metho- trexate serum level determinations 24 hr after starting methotrexate and at least daily until the methotrexate level is below 5 × 10–8 mol/L (0.05 micro-M) IM  route • Inject deeply into a large muscle • Aspirate before injection Subcut route • Otrexup and Rasuvo are methotrex- ate formulations for subcutaneous use only • Both Otrexup and Rasuvo are single- use auto-injectors. Otrexup is available in 5-mg increments for doses between 10 and 25 mg; Rasuvo is available in 2.5-mg increments for doses between 7.5 and 30 mg. Neither formulation should have lumps or particles floating in it • Administer Otrexup and Rasuvo in the abdomen or thigh; do NOT administer within 2 inches of the navel, on the arms, on any other areas of the body, or on skin that is tender, bruised, red, scaly, hard, or has scars or stretch marks • If self-injection is deemed appropriate, patients or caregivers should practice in- jections using a training device with guid- ance from a health care professional Use of Otrexup auto-injector • Immediately before use, twist cap to remove; flip the safety clip • Place needle end of Otrexup against thigh or stomach (abdomen) at a 90-degree angle and firmly push until you hear a click; hold for 3 sec before removing Use of Rasuvo auto-injector: • Pull the yellow cap straight off. Do not twist • Position the uncapped end of the auto- injector at a 90-degree angle to the skin. Without pressing the button, push firmly onto the skin until the stop point is felt, which will unlock the yellow injection button • Press the yellow injection button until a click is heard. Hold Rasuvo against the skin until all medication is injected. This can take up to 5 sec • Visually inspect the transparent con- trol zone to ensure there is no liquid left in the syringe Intrathecal administration • Use preservative-free solutions. The preserved solutions contain benzyl alco- hol and should NOT be used for intrathe- cal therapy • Reconstitute the preservative-free powder for injection with preservative-free 0.9% sodium chloride injection. The desired dose should be drawn into a 5- to 10-mL syringe • After lumbar puncture is complete, withdraw an amount of CSF equivalent to the volume of methotrexate injection to be administered. If puncture was traumatic, wait 2 days before attempting to administer methotrexate intrathecally • Allow CSF (approximately 10% of esti- mated CSF total volume) to flow into the syringe and mix with the product • Inject intrathecally over 15 to 30 sec with the bevel of the needle directed up- ward Black Box Warning: Infection: those with active infections should be treated for infection before product use; monitor temperature, fever may indicate begin- ning of infection; more common during neutropenia • Rheumatoid arthritis: ROM, pain, joint swelling before, during treatment • Psoriasis: skin lesions before, during treatment • Make sure drug–drug interacting products are discontinued before ther- apy, and do not resume until methotrex- ate level is safe M • Bone marrow suppression: CBC, dif- ferential, platelet count weekly; avoid use until WBC is >1500/mm3 or platelet count is >75,000/mm3, neutrophils >200/mm3; notify prescriber; WBC, platelet nadirs oc- cur on day 7 Black Box Warning: Nephrotoxicity: avoid use in renal failure; BUN, serum uric acid, urine CCr, electrolytes before, during therapy; I&O ratio; report fall in urine output to <30 mL/hr • Monitor vital signs during use; report changes if significant • Monitor for stomatitis, diarrhea, ab- dominal cramping or pain; if severe, product may need to be discontinued • Anemia:  extreme fatigue, increased heart rate, dyspnea, headache, dizziness, pale skin • Gout:  joint warmth, pain, edema, in- creased uric acid level; use of allopurinol and alkalinization of urine will decrease uric acid • Bleeding: bleeding time, coagulation time during treatment; bleeding: hematu- ria, guaiac, bruising, petechiae, he- matemesis, assess in mucosa or orifices; avoid IM injections, rectal temperature when platelets are low Black Box Warning: Pulmonary toxic- ity: may start with dry, nonproductive cough; those with ascites or pleural ef- fusion at greater risk for toxicity; fluid should be removed before treatment; monitor plasma methotrexate levels  Black Box Warning: Tumor lysis syndrome: hyperkalemia, hyperphos- phatemia, hyperuricemia, hypocalcemia, decreased urine output; use aggressive hydration, allopurinol to correct severe electrolyte imbalances, renal toxicity Black Box Warning: Hepatotoxicity: jaundiced skin and sclera, dark urine, clay-colored stools, pruritus, abdominal pain, fever, diarrhea, hepatic studies before and during therapy: bilirubin, alk phos, AST, ALT; liver biopsy should be done before start of therapy (psoriasis) • Monitor methotrexate levels; adjust leucovorin dose based on level • Buccal cavity for dryness, sores, ulcer- ation, white patches, oral pain, bleeding, dysphagia Black Box Warning: Serious skin re- action: Stevens-Johnson syndrome, exfoliative dermatitis, skin necrosis, ery- thema multiforme may occur within days of receiving product by any route; product should be discontinued • Stroke-like encephalopathy: com- mon in high-dose therapy; assess for confusion, hemiparesis, seizures, coma; usually transient • Increased fluid intake to 2-3 L/day to prevent urate deposits, calculi formation unless contraindicated • Rinsing of mouth tid-qid with water, club soda; brushing of teeth bid-tid with soft brush or cotton-tipped applicators for stomatitis; use unwaxed dental floss • Pregnancy/breastfeeding: do not use in pregnancy or breastfeeding Black Box Warning: To report any complaints, side effects to nurse or pre- scriber: black tarry stools, chills, fever, sore throat, bleeding, bruising, cough, shortness of breath, dark or bloody urine, seizures, rash • That hair may be lost during treat- ment; that wig or hairpiece may make patient feel better; that new hair may be different in color, texture (alopecia rare) • To avoid foods with citric acid, hot temperature, or rough texture if stomati- tis is present • To report stomatitis and any bleeding, white spots, ulcerations in mouth to pre- scriber; to examine mouth daily; to re- port symptoms to nurse; to use good oral hygiene Black Box Warning: Pregnancy: that contraceptive measures are recommend- ed during therapy and for at least 8 wk after cessation of therapy for women and men; to discontinue breastfeeding; that toxicity to infant may occur  • To drink 10-12 glasses of fluid/day • To avoid alcohol, salicylates, live vac- cines • To avoid use of razors, commercial mouthwash; to use soft-bristle tooth- brush • To use sunblock to prevent burns • To use good dental care to prevent overgrowth of infection in the mouth • How to use this product with leucovo- rin rescue • To continue leucovorin until told it is safe to stop • To report CNS symptoms, vision changes • To report fever, other symptoms of in- fection • To report decreased urine output • To avoid crowds, persons with known infections • To advise all health care providers that methotrexate is being taken; not to use Rx, OTC medications, herbs, or supple- ments unless approved by prescriber • Subcut route:  Teach patient self- injection technique and use and dis- posal of equipment HIGH ALERT

Source pages 858, 859, 860, 861, 862, 863