Generic Name: levoleucovorin (LEE voe LOO koe VOE rin)Brand Names: Fusilev
Levoleucovorin is used to treat or prevent toxic effects of methotrexate in people who have received methotrexate to treat bone cancer.
Levoleucovorin is also used to treat or prevent toxic effects of methotrexate in people whose bodies do not eliminate methotrexate properly after the drug is metabolized.
Levoleucovorin may also be used to treat toxic effects of an accidental overdose of methotrexate.Levoleucovorin should not be used to treat anemia that is caused by a lack of vitamin B12.
Levoleucovorin may also be used for other purposes not listed in this medication guide.
Tell your doctor if you are taking sulfa drugs, seizure medication, a cancer medication called fluorouracil (5FU), or a multivitamin or mineral supplement than contains folic acid.
In an emergency situation, it may not be possible before you are treated to tell your caregivers about any health conditions you have or if you are pregnant or breast-feeding. However, make sure any doctor caring for you afterward knows that you have received this medication.What should I discuss with my healthcare provider before I receive levoleucovorin?You should not receive this medication if you are allergic to levoleucovorin or to folic acid or folinic acid.
If possible, before you receive levoleucovorin, tell your doctor if you have:
if you are dehydrated.
In an emergency situation, it may not be possible to tell your caregivers that you are pregnant or breast-feeding before you are treated with levoleucovorin. However, make sure any doctor caring for your pregnancy or your baby knows that you have received the medication.
Levoleucovorin is given as an injection through a needle placed into a vein. You will receive this injection in a clinic or hospital setting. The medicine must be given slowly through an IV infusion, and can take up to 4 hours to complete.
Levoleucovorin is usually given every 6 hours for 10 doses. You will most likely receive your first dose 24 hours after the start of your methotrexate infusion, or as soon as possible within the first 24 hours after accidental overdose.
After treatment with levoleucovorin, you will be watched to make sure the medication has been effective and you no longer have any effects of methotrexate.
To be sure this medication is not causing harmful effects, your blood will need to be tested at least once daily for a short period of time while you are receiving levoleucovorin. This will help your doctor determine if your dose needs to be adjusted.
Since this medication is given by a healthcare professional, you are not likely to miss a dose.
Symptoms of a levoleucovorin overdose are not known.
Follow your doctor's instructions about any restrictions on food, beverages, or activity.
white patches or sores inside your mouth or on your lips;
urinating more or less than usual;
numbness or tingling;
Less serious side effects may include:
nausea, vomiting, diarrhea;
stomach pain, upset stomach;
mild skin rash; or
white patches or sores inside your mouth or on your lips.
This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.
Usual Adult Dose for Methotrexate Rescue:
Levoleucovorin Rescue After High-Dose Methotrexate Therapy:Dose: 7.5 mg (approximately 5 mg/m2) IV every 6 hours for 10 doses starts 24 hours after the beginning of the methotrexate infusion. (The recommendations for levoleucovorin rescue are based on a methotrexate dose of 12 grams/m2 administered by intravenous infusion over 4 hours.)Serum creatinine and methotrexate levels should be determined at least once daily. Levoleucovorin administration, hydration, and urinary alkalinization (pH of 7.0 or greater) should be continued until the methotrexate level is below 0.05 micromolar. The levoleucovorin dose should be adjusted or rescue extended based on the following guidelines:Guidelines for Levoleucovorin Dosage and AdministrationClinical Situation 1) Normal Methotrexate EliminationLaboratory Findings: Serum methotrexate level approximately 10 micromolar at 24 hours after administration, 1 micromolar at 48 hours, and less than 0.2 micromolar at 72 hours.Levoleucovorin Dosage and Duration: 7.5 mg IV every 6 hours for 60 hours (10 doses starting at 24 hours after start of methotrexate infusion).Clinical Situation 2) Delayed Late Methotrexate EliminationLaboratory Findings: Serum methotrexate level remaining above 0.2 micromolar at 72 hours, and more than 0.05 micromolar at 96 hours after administration.Levoleucovorin Dosage and Duration: Continue 7.5 mg IV every 6 hours, until methotrexate level is less than 0.05 micromolar.Clinical Situation 3) Delayed Early Methotrexate Elimination and/or Evidence of Acute Renal InjuryLaboratory Findings: Serum methotrexate level of 50 micromolar or more at 24 hours, or 5 micromolar or more at 48 hours after administration, or; a 100% or greater increase in serum creatinine level at 24 hours after methotrexate administration (e.g., an increase from 0.5 mg/dL to a level of 1 mg/dL or more).Levoleucovorin Dosage and Duration: 75 mg IV every 3 hours until methotrexate level is less than 1 micromolar; then 7.5 mg IV every 3 hours until methotrexate level is less than 0.05 micromolar.Patients who experience delayed early methotrexate elimination are likely to develop reversible renal failure. In addition to appropriate levoleucovorin therapy, these patients require continuing hydration, urinary alkalinization, and close monitoring of fluid and electrolyte status, until the serum methotrexate level has fallen to below 0.05 micromolar and the renal failure has resolved.Some patients will have abnormalities in methotrexate elimination or renal function following methotrexate administration, which are significant but less severe than the abnormalities described above. These abnormalities may or may not be associated with significant clinical toxicity. If significant clinical toxicity is observed, levoleucovorin rescue should be extended for an additional 24 hours (total of 14 doses over 84 hours) in subsequent courses of therapy. The possibility that the patient is taking other medications which interact with methotrexate (e.g., medications which may interfere with methotrexate elimination or binding to serum albumin) should always be reconsidered when laboratory abnormalities or clinical toxicities are observed.Delayed methotrexate excretion may be caused by accumulation in a third space fluid collection (i.e., ascites, pleural effusion), renal insufficiency, or inadequate hydration. Under such circumstances, higher doses of levoleucovorin or prolonged administration may be indicated.Although levoleucovorin may ameliorate the hematologic toxicity associated with high dose methotrexate, levoleucovorin has no effect on other established toxicities of methotrexate such as the nephrotoxicity resulting from drug and/or metabolite precipitation in the kidney.
Usual Adult Dose for Methotrexate Overdosage:
Dosing Recommendations for Inadvertent Methotrexate OverdosageDose: 7.5 mg (approximately 5 mg/m2) should be administered IV every 6 hours until the serum methotrexate level is less than 10^-8 M.Levoleucovorin rescue should begin as soon as possible after an inadvertent overdosage and within 24 hours of methotrexate administration when there is delayed excretion. As the time interval between antifolate administration (e.g., methotrexate) and levoleucovorin rescue increases, levoleucovorin's effectiveness in counteracting toxicity may decrease.Serum creatinine and methotrexate levels should be determined at 24 hour intervals. If the 24 hour serum creatinine has increased 50% over baseline or if the 24 hour methotrexate level is greater than 5 x 10^-6 M or the 48 hour level is greater than 9 x 10^-7 M, the dose of levoleucovorin should be increased to 50 mg/m2 IV every 3 hours until the methotrexate level is less than 10^-8 M. Hydration (3 L/day) and urinary alkalinization with NaHCO3 should be employed concomitantly. The bicarbonate dose should be adjusted to maintain the urine pH at 7.0 or greater.
The following drugs can interact with levoleucovorin. Tell your doctor if you are using any of these:
fluorouracil (5-FU, Adrucil, Efudex, Carac, Fluoroplex);
sulfa drugs (Bactrim, Gantanol, Gantrisin, Septra, SMX-TMP, and others);
seizure medication such as phenobarbital (Solfoton), phenytoin (Dilantin), or primidone (Mysoline); or
a multivitamin or mineral supplement than contains folic acid.
This list is not complete and there may be other drugs that can interact with levoleucovorin. Tell your doctor about all your prescription and over-the-counter medications, vitamins, minerals, herbal products, and drugs prescribed by other doctors. Do not start a new medication without telling your doctor.