Pregnancy Category: C
ClassificationTherapeutic: orphan drugs
Lowering of toxic methotrexate levels (>1 micromole/L) associated with renal failure.
A carboxypeptidase enzyme that breaks methotrexate down into inactive metabolites that can be readily eliminated by non-renal pathways.
Prevention of damage associated with high levels of methotrexate including kidney and liver damage, mucusitis and bone marrow depression.
Absorption: IV administration results in complete bioavailability.
Distribution: Restricted to plasma volume.
Metabolism and Excretion: Unknown.
Half-life: 5.6 hr.
Time/action profile (reduction of methotrexate levels)
|IV||within 15 min||unknown||up to 8 days|
Contraindicated in: Patients with expected clearance of methotrexate (methotrexate levels within 2 standard deviations of the mean methotrexate excretion curve specific for the dose given) or those with normal or mildly impaired renal function.
Use Cautiously in: Lactation: Use cautiously; Obstetric: Use only if clearly needed.
Adverse Reactions/Side Effects
Central nervous system
- allergic reactions including anaphylaxis (life-threatening)
Drug-Drug interaction↓ effectiveness of leucovorin (should not be given within 2 hr before or after), similar effects may occur with other substrates of the enzyme including reduced folates and folate antimetabolites.
Intravenous (Adults and Children >1 mo) 50 Units/kg as a single dose.
Lyophilized powder for injection (requires reconstitution): 1,000 units/vial
- Assess for signs and symptoms of allergic reactions (fever, chills, flushing, feeling hot, rash, hives, itching, throat tightness or breathing problems, tingling, numbness, or headache) periodically following injection. Keep epinephrine, an antihistamine, and resuscitation equipment close by in the event of an anaphylactic reaction.
Potential Nursing DiagnosesDeficient knowledge, related to medication regimen (Patient/Family Teaching)
- Continue to administer leucovorin after glucarpidase. Do not administer leucovorin within 2 hrs before or after dose of glucarpidase. For the first 48 hrs administer same leucovorin dose as given prior to glucarpidase. Beyond 48 hrs after glucarpidase administer leucovorin dose based on methotrexate concentration. Do not discontinue leucovorin based on a single methotrexate concentration below leucovorin treatment threshold. Continue leucovorin until methotrexate concentration has been maintained below leucovorin treatment threshold for at least 3 days.
- Continue hydration and alkalinization of urine as needed.
- Reconstitute vial with 1 mL sterile saline for injection. Roll and tilt vial to mix; do not shake. Solution should be clear and colorless; do not administer if solution is discolored, cloudy or contains particulate matter. May be refrigerated for up to 4 hr if not used immediately. Discard unused product.
- Rate: Administer as a bolus over 5 min. Flush IV line before and after injection.
- Advise patient to notify health care professional if signs and symptoms of allergic reactions occur.
- Emphasize the importance of continued monitoring of methotrexate blood levels and renal status following hospital discharge.
- Advise female patient to notify health care professional if pregnancy is known or suspected.
- Maintenance of methotrexate level below the leucovorin treatment threshold for more than 3 days.