Leucovorin 500mg/50ml Inj, 50ml
It is used with methotrexate to avoid side effects.It may lower the side effects of some drugs.It is used with fluorouracil to help fight colorectal cancer.It is used to help with some kinds of anemia.It may be given to you for other reasons. Talk with the doctor.
Drug Class
Antidote; Antineoplastic Adjuvant
Pharmacologic Class
Folic Acid Analog; Reduced Folate
Pregnancy Category
Category C
FDA Approved
Mar 1953
DEA Schedule
Not Controlled
Overview
What is this medicine?
Leucovorin is a type of vitamin (folic acid) that helps protect healthy cells from the harmful effects of certain cancer medicines, like methotrexate. It can also make another cancer medicine, 5-fluorouracil, work better against cancer cells. It's often called a 'rescue' medicine because it helps reduce side effects.
How to Use This Medicine
To use this medication correctly, follow your doctor's instructions and carefully read all accompanying information. Adhere to the dosage instructions provided by your healthcare team. This medication is administered via injection into a muscle or vein.
For proper storage and disposal, consult with your doctor, nurse, or pharmacist to determine the best approach if you need to store this medication at home.
If you miss a dose, contact your doctor promptly to receive guidance on the next steps to take.
For proper storage and disposal, consult with your doctor, nurse, or pharmacist to determine the best approach if you need to store this medication at home.
If you miss a dose, contact your doctor promptly to receive guidance on the next steps to take.
Lifestyle & Tips
- Follow all instructions from your doctor and nurse regarding timing and dose, especially for 'rescue' therapy.
- Maintain good hydration as instructed, especially during methotrexate treatment.
- Report any side effects or concerns immediately to your healthcare team.
Available Forms & Alternatives
Available Strengths:
- Leucovorin Calcium 5mg Tablets
- Leucovorin Calcium 10mg Tablets
- Leucovorin Calcium 15mg Tablets
- Leucovorin Calcium 25mg Tablets
- Leucovorin Calcium 50mg Inj, 1 Vial
- Leucovorin Calcium 100mg Inj, 1vial
- Leucovorin Calcium 350mg Inj, 1vl
- Leucovorin Calcium 500mg Inj, 1vial
- Leucovorin 10mg/ml Inj, 10ml
- Leucovorin 500mg/50ml Inj, 50ml
- Leucovorin Ca 200mg Inj, 1 Vial
Dosing & Administration
Adult Dosing
Standard Dose:
Highly variable depending on indication. For Methotrexate Rescue: Typically 10 mg/m2 IV/IM/PO every 6 hours for 10 doses, starting 24 hours after methotrexate initiation. Dosing adjusted based on methotrexate levels and renal function. For Colorectal Cancer (with 5-FU): 200 mg/m2 IV over 3 minutes, followed by 5-FU 370 mg/m2 IV, daily for 5 days; or 20 mg/m2 IV bolus followed by 5-FU 425 mg/m2 IV bolus, daily for 5 days. Weekly regimens also exist.
Dose Range:
10 - 500 mg
Condition-Specific Dosing:
Methotrexate Rescue:
Dose and duration depend on methotrexate serum concentrations, renal function, and clinical toxicity. May require higher doses (e.g., 50-100 mg/m2) or longer duration if methotrexate elimination is delayed.
Colorectal Cancer (with 5-FU):
Specific regimens vary (e.g., Mayo Clinic, Roswell Park). Doses are typically 20-200 mg/m2 IV, often given before or concurrently with 5-FU.
Pediatric Dosing
Neonatal:
Not established for routine use. Used in specific cases (e.g., methotrexate overdose) with careful monitoring.
Infant:
Dosing is typically extrapolated from adult or body surface area (BSA) based regimens, similar to adult methotrexate rescue protocols. E.g., 10 mg/m2 IV/IM/PO every 6 hours.
Child:
Dosing is typically extrapolated from adult or body surface area (BSA) based regimens, similar to adult methotrexate rescue protocols. E.g., 10 mg/m2 IV/IM/PO every 6 hours.
Adolescent:
Dosing is typically extrapolated from adult or body surface area (BSA) based regimens, similar to adult methotrexate rescue protocols. E.g., 10 mg/m2 IV/IM/PO every 6 hours.
Dose Adjustments
Renal Impairment:
Mild:
No specific adjustment for leucovorin itself, but careful monitoring of methotrexate levels and potential increase in leucovorin dose/duration is crucial if used for methotrexate rescue in patients with impaired methotrexate clearance.
Moderate:
Increased leucovorin dose/duration may be required for methotrexate rescue due to delayed methotrexate clearance. Monitor methotrexate levels closely.
Severe:
Increased leucovorin dose/duration may be required for methotrexate rescue due to severely delayed methotrexate clearance. Monitor methotrexate levels closely. Consider continuous infusion of leucovorin.
Dialysis:
Leucovorin itself is not significantly dialyzed. However, if used for methotrexate rescue, methotrexate is dialyzable, and leucovorin dosing must be adjusted based on post-dialysis methotrexate levels and clinical status.
Hepatic Impairment:
Mild:
No specific adjustment recommended for leucovorin itself.
Moderate:
No specific adjustment recommended for leucovorin itself.
Severe:
No specific adjustment recommended for leucovorin itself. However, if used with 5-FU, hepatic impairment may increase 5-FU toxicity, requiring dose adjustments of 5-FU.
Pharmacology
Mechanism of Action
Leucovorin is a reduced form of folic acid that does not require reduction by dihydrofolate reductase. It acts as a biochemical antidote to folic acid antagonists (e.g., methotrexate, trimethoprim, pyrimethamine) by providing the necessary reduced folates for purine and pyrimidine synthesis, thus protecting healthy cells from the cytotoxic effects of these antagonists. When used with 5-fluorouracil (5-FU), leucovorin is metabolized to 5,10-methylenetetrahydrofolate, which stabilizes the binding of 5-FU's active metabolite (5-fluorodeoxyuridine monophosphate, FdUMP) to thymidylate synthase, thereby enhancing the cytotoxic effect of 5-FU.
Pharmacokinetics
Absorption:
Bioavailability:
Oral bioavailability is variable and incomplete (e.g., ~97% for 25 mg, ~75% for 50 mg, ~37% for 100 mg due to saturable absorption). IV administration provides 100% bioavailability.
Tmax:
Oral: 1.7 hours (for parent drug); 2.7 hours (for active metabolite, 5-methyltetrahydrofolate). IV: Rapid.
FoodEffect:
Not significantly affected by food, but oral absorption can be saturable at higher doses.
Distribution:
Vd:
Not readily available for leucovorin itself, but its active metabolite (5-methyltetrahydrofolate) distributes widely.
ProteinBinding:
Not extensively protein bound.
CnssPenetration:
Limited penetration into the CNS, especially at standard doses. Higher doses or intrathecal administration may be required for CNS effects.
Elimination:
HalfLife:
Parent drug (leucovorin): ~0.5 hours. Active metabolite (5-methyltetrahydrofolate): ~6-7 hours.
Clearance:
Not precisely quantified, but rapid conversion to active metabolite.
ExcretionRoute:
Primarily renal (80-90%) and fecal (5-8%).
Unchanged:
<1% (parent drug)
Pharmacodynamics
OnsetOfAction:
Rapid (minutes) after IV administration.
PeakEffect:
Within 1-2 hours (for active metabolite).
DurationOfAction:
Dependent on dose and continued presence of active metabolite, typically several hours.
Safety & Warnings
Side Effects
Urgent Side Effects: Seek Medical Help Right Away
While rare, some people may experience severe and potentially life-threatening side effects when taking this medication. If you notice any of the following symptoms, contact your doctor or seek immediate medical attention:
Signs of an allergic reaction, which may include:
+ Rash
+ Hives
+ Itching
+ Red, swollen, blistered, or peeling skin with or without fever
+ Wheezing
+ Tightness in the chest or throat
+ Trouble breathing, swallowing, or talking
+ Unusual hoarseness
+ Swelling of the mouth, face, lips, tongue, or throat
Seizures
* Severe dizziness or fainting
Other Possible Side Effects
Like all medications, this drug can cause side effects. Although many people may not experience any side effects or only minor ones, it's essential to discuss any concerns with your doctor. If you experience side effects that bother you or persist, contact your doctor for guidance.
Reporting Side Effects
This list is not exhaustive, and you may have questions about other potential side effects. If you do, don't hesitate to reach out to your doctor. You can also report side effects to the FDA at 1-800-332-1088 or online at https://www.fda.gov/medwatch. Your doctor can provide medical advice about side effects and help you manage any concerns.
While rare, some people may experience severe and potentially life-threatening side effects when taking this medication. If you notice any of the following symptoms, contact your doctor or seek immediate medical attention:
Signs of an allergic reaction, which may include:
+ Rash
+ Hives
+ Itching
+ Red, swollen, blistered, or peeling skin with or without fever
+ Wheezing
+ Tightness in the chest or throat
+ Trouble breathing, swallowing, or talking
+ Unusual hoarseness
+ Swelling of the mouth, face, lips, tongue, or throat
Seizures
* Severe dizziness or fainting
Other Possible Side Effects
Like all medications, this drug can cause side effects. Although many people may not experience any side effects or only minor ones, it's essential to discuss any concerns with your doctor. If you experience side effects that bother you or persist, contact your doctor for guidance.
Reporting Side Effects
This list is not exhaustive, and you may have questions about other potential side effects. If you do, don't hesitate to reach out to your doctor. You can also report side effects to the FDA at 1-800-332-1088 or online at https://www.fda.gov/medwatch. Your doctor can provide medical advice about side effects and help you manage any concerns.
Seek Immediate Medical Attention If You Experience:
- Severe mouth sores or ulcers (mucositis)
- Severe diarrhea
- Unusual bleeding or bruising
- Signs of infection (fever, chills, sore throat)
- Severe fatigue or weakness
- Signs of kidney problems (decreased urination, swelling)
- Allergic reaction (rash, itching, swelling, severe dizziness, trouble breathing)
Before Using This Medicine
Before Taking This Medication: Important Information to Share with Your Doctor
It is essential to inform your doctor about the following:
Any allergies you have, including allergies to this medication, its components, or other substances, such as foods or drugs. Be sure to describe the allergic reaction you experienced, including any symptoms that occurred.
If you have anemia caused by a vitamin B12 deficiency.
If you have any stomach or bowel problems.
This list is not exhaustive, and it is crucial to discuss all your health concerns with your doctor. Additionally, tell your doctor and pharmacist about all the medications you are taking, including:
Prescription and over-the-counter (OTC) drugs
Natural products
Vitamins
Your doctor needs to be aware of all your medications and health problems to ensure it is safe for you to take this medication. Do not start, stop, or change the dose of any medication without first consulting your doctor.
It is essential to inform your doctor about the following:
Any allergies you have, including allergies to this medication, its components, or other substances, such as foods or drugs. Be sure to describe the allergic reaction you experienced, including any symptoms that occurred.
If you have anemia caused by a vitamin B12 deficiency.
If you have any stomach or bowel problems.
This list is not exhaustive, and it is crucial to discuss all your health concerns with your doctor. Additionally, tell your doctor and pharmacist about all the medications you are taking, including:
Prescription and over-the-counter (OTC) drugs
Natural products
Vitamins
Your doctor needs to be aware of all your medications and health problems to ensure it is safe for you to take this medication. Do not start, stop, or change the dose of any medication without first consulting your doctor.
Precautions & Cautions
It is essential to inform all your healthcare providers, including doctors, nurses, pharmacists, and dentists, that you are taking this medication. Regular blood work and laboratory tests should be conducted as directed by your doctor.
When used in combination with fluorouracil, this drug may increase the severity and frequency of side effects associated with fluorouracil, such as diarrhea, mouth irritation, and mouth sores. In older adults, the combination of this drug with fluorouracil has been linked to severe bowel problems, diarrhea, and dehydration, which can be life-threatening. If you have any questions or concerns, discuss them with your doctor.
If you are 65 years or older, exercise caution when using this medication, as you may be more susceptible to side effects.
Before taking this drug, inform your doctor if you are pregnant, planning to become pregnant, or breastfeeding. Your doctor will help you weigh the benefits and risks of using this medication during this time.
Some formulations of this drug contain benzyl alcohol, which can be hazardous to newborns and infants. If possible, avoid using products that contain benzyl alcohol in these age groups, as serious side effects can occur, particularly when combined with other medications containing benzyl alcohol. Consult your doctor to determine which fluids used to mix this drug contain benzyl alcohol.
When used in combination with fluorouracil, this drug may increase the severity and frequency of side effects associated with fluorouracil, such as diarrhea, mouth irritation, and mouth sores. In older adults, the combination of this drug with fluorouracil has been linked to severe bowel problems, diarrhea, and dehydration, which can be life-threatening. If you have any questions or concerns, discuss them with your doctor.
If you are 65 years or older, exercise caution when using this medication, as you may be more susceptible to side effects.
Before taking this drug, inform your doctor if you are pregnant, planning to become pregnant, or breastfeeding. Your doctor will help you weigh the benefits and risks of using this medication during this time.
Some formulations of this drug contain benzyl alcohol, which can be hazardous to newborns and infants. If possible, avoid using products that contain benzyl alcohol in these age groups, as serious side effects can occur, particularly when combined with other medications containing benzyl alcohol. Consult your doctor to determine which fluids used to mix this drug contain benzyl alcohol.
Overdose Information
Overdose Symptoms:
- While leucovorin itself has low toxicity, very high doses may rarely cause gastrointestinal upset or allergic reactions. The primary concern with 'overdose' is if it's given inappropriately with methotrexate, leading to methotrexate toxicity.
What to Do:
If you suspect an overdose or inappropriate administration, seek immediate medical attention. Call 911 or Poison Control at 1-800-222-1222. Management is supportive and depends on the specific context (e.g., if it led to methotrexate toxicity).
Drug Interactions
Major Interactions
- Methotrexate (antagonizes methotrexate's effect if given concurrently or before methotrexate, except in rescue therapy)
- 5-Fluorouracil (enhances 5-FU toxicity, requiring careful monitoring and dose adjustment of 5-FU)
- Trimethoprim (antagonizes antibacterial effect)
- Pyrimethamine (antagonizes antimalarial/antiparasitic effect)
Moderate Interactions
- Phenytoin (may decrease phenytoin levels, potentially increasing seizure risk due to increased folate metabolism)
- Phenobarbital (may decrease phenobarbital levels)
- Primidone (may decrease primidone levels)
Monitoring
Baseline Monitoring
Complete Blood Count (CBC) with differential
Rationale: To assess baseline hematologic status, especially when used with myelosuppressive agents like methotrexate or 5-FU.
Timing: Prior to initiation of therapy.
Renal Function (Serum Creatinine, BUN)
Rationale: To assess baseline kidney function, critical for methotrexate elimination and leucovorin rescue effectiveness.
Timing: Prior to initiation of therapy.
Liver Function Tests (LFTs)
Rationale: To assess baseline hepatic function, especially when used with other hepatotoxic agents.
Timing: Prior to initiation of therapy.
Routine Monitoring
Methotrexate Serum Levels
Frequency: As per protocol (e.g., 24, 48, 72 hours after methotrexate initiation) for high-dose methotrexate rescue.
Target: Specific to protocol (e.g., <0.1 micromolar at 48 hours, <0.01 micromolar at 72 hours).
Action Threshold: Levels above target require increased leucovorin dose/duration, hydration, and potentially urine alkalinization.
Complete Blood Count (CBC) with differential
Frequency: Daily or every 2-3 days, especially during methotrexate rescue or 5-FU combination therapy.
Target: Within normal limits, or as tolerated per chemotherapy protocol.
Action Threshold: Significant drops in WBC, ANC, platelets may indicate myelosuppression, requiring dose adjustment of concomitant chemotherapy or supportive care.
Renal Function (Serum Creatinine, BUN)
Frequency: Daily during high-dose methotrexate therapy and rescue.
Target: Within normal limits.
Action Threshold: Rising creatinine indicates impaired methotrexate clearance, requiring increased leucovorin and aggressive hydration/alkalinization.
Electrolytes (Potassium, Magnesium, Phosphate)
Frequency: Daily during high-dose methotrexate therapy.
Target: Within normal limits.
Action Threshold: Imbalances may occur due to renal toxicity or fluid shifts.
Symptom Monitoring
- Signs of methotrexate toxicity (mucositis, myelosuppression, renal dysfunction, hepatotoxicity)
- Signs of 5-fluorouracil toxicity (stomatitis, diarrhea, hand-foot syndrome, myelosuppression)
- Allergic reactions (rash, itching, swelling, dizziness, trouble breathing)
Special Patient Groups
Pregnancy
Leucovorin is Pregnancy Category C. It should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus. Its use is often in life-threatening situations (e.g., methotrexate overdose) where the benefit to the mother outweighs the theoretical risk.
Trimester-Specific Risks:
First Trimester:
Potential for fetal harm, especially if used with other teratogenic agents. Risk-benefit assessment is crucial.
Second Trimester:
Risk-benefit assessment is crucial.
Third Trimester:
Risk-benefit assessment is crucial.
Lactation
Leucovorin is excreted into breast milk. However, due to its low oral bioavailability and the fact that it is a naturally occurring vitamin, adverse effects on the breastfed infant are unlikely. Breastfeeding is generally considered compatible, but caution is advised, especially if the mother is receiving other cytotoxic agents.
Infant Risk:
Low risk. Monitor infant for any unusual symptoms.
Pediatric Use
Leucovorin is widely used in pediatric oncology, particularly for methotrexate rescue. Dosing is typically based on body surface area (BSA) and follows similar principles as adult dosing, with careful monitoring of methotrexate levels and renal function.
Geriatric Use
No specific dose adjustments are typically required for leucovorin based solely on age. However, elderly patients may have age-related decline in renal function, which can impact methotrexate clearance and thus necessitate closer monitoring and potential adjustments to leucovorin rescue therapy. Increased susceptibility to myelosuppression and other toxicities from concomitant chemotherapy should also be considered.
Clinical Information
Clinical Pearls
- Leucovorin is NOT a rescue for all chemotherapy agents; it is specific for folic acid antagonists like methotrexate.
- Timing is CRITICAL for methotrexate rescue. Leucovorin must be started within 24-42 hours of methotrexate administration to be effective.
- Ensure adequate hydration and urine alkalinization (if indicated) are maintained during high-dose methotrexate therapy, as these are crucial for methotrexate elimination and preventing toxicity, in addition to leucovorin.
- When used with 5-fluorouracil, leucovorin enhances 5-FU's toxicity, not reduces it. This combination requires careful monitoring for 5-FU-related side effects (e.g., mucositis, diarrhea, myelosuppression).
- Oral leucovorin absorption can be saturable at higher doses; IV administration is preferred for high-dose rescue or when absorption is critical.
Alternative Therapies
- Glucarpidase (Voraxaze): An enzyme that rapidly metabolizes methotrexate, used for rapid reduction of toxic methotrexate concentrations in patients with delayed methotrexate elimination due to renal dysfunction. It is a rescue agent, but works via a different mechanism than leucovorin.
Cost & Coverage
Average Cost:
Varies widely by dose and formulation (e.g., $50 - $500+ per vial) per 50mg/5ml or 500mg/50ml vial
Generic Available:
Yes
Insurance Coverage:
Typically covered by most medical and prescription drug plans (Medicare Part B, Part D, commercial insurance) as it is a critical oncology support drug. May fall under Tier 3 or specialty tiers depending on plan.
General Drug Facts
If your symptoms or health problems do not improve or worsen over time, it is essential to contact your doctor for further evaluation and guidance.
To ensure safe use, do not share your prescription medications with others, and never take medication that has been prescribed to someone else.
All medications should be stored in a secure location, out of the reach of children and pets, to prevent accidental ingestion.
When disposing of unused or expired medications, do not flush them down the toilet or pour them down the drain unless specifically instructed to do so by a healthcare professional or pharmacist. Instead, consult with your pharmacist to determine the best disposal method, as some communities may have designated drug take-back programs.
Some medications may come with an additional patient information leaflet; check with your pharmacist to see if this applies to your prescription.
If you have any questions or concerns about your medication, it is crucial to discuss them with your doctor, nurse, pharmacist, or other healthcare provider.
In the event of a suspected overdose, immediately contact your local poison control center or seek emergency medical attention. Be prepared to provide information about the medication taken, the amount, and the time it was taken, as this will aid in providing appropriate treatment.
To ensure safe use, do not share your prescription medications with others, and never take medication that has been prescribed to someone else.
All medications should be stored in a secure location, out of the reach of children and pets, to prevent accidental ingestion.
When disposing of unused or expired medications, do not flush them down the toilet or pour them down the drain unless specifically instructed to do so by a healthcare professional or pharmacist. Instead, consult with your pharmacist to determine the best disposal method, as some communities may have designated drug take-back programs.
Some medications may come with an additional patient information leaflet; check with your pharmacist to see if this applies to your prescription.
If you have any questions or concerns about your medication, it is crucial to discuss them with your doctor, nurse, pharmacist, or other healthcare provider.
In the event of a suspected overdose, immediately contact your local poison control center or seek emergency medical attention. Be prepared to provide information about the medication taken, the amount, and the time it was taken, as this will aid in providing appropriate treatment.