Leucovorin Ca 200mg Inj, 1 Vial
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 adjunct
Pharmacologic Class
Folic acid derivative; Folinic acid
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 derivative) that helps protect healthy cells from the harmful effects of certain cancer medications, like methotrexate. It can also boost the effectiveness of other cancer drugs, like fluorouracil. It's not a chemotherapy drug itself, but it's used alongside them to make treatments safer and more effective.
How to Use This Medicine
To use this medication correctly, follow your doctor's instructions and carefully read all accompanying information. Take this medication exactly as directed, and adhere to all guidelines provided. This medication is administered via injection into a muscle or vein.
For storage and disposal, consult with your doctor, nurse, or pharmacist to determine the best approach if you need to keep this medication at home.
If you miss a dose, contact your doctor promptly to receive guidance on the appropriate course of action.
For storage and disposal, consult with your doctor, nurse, or pharmacist to determine the best approach if you need to keep this medication at home.
If you miss a dose, contact your doctor promptly to receive guidance on the appropriate course of action.
Lifestyle & Tips
- Follow all instructions from your doctor regarding diet and hydration, especially when receiving high-dose methotrexate.
- Report any side effects promptly.
- Do not take additional folic acid supplements unless directed by your doctor.
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 based on indication. Examples: Methotrexate rescue: 10-15 mg/m2 IV/IM/PO every 6 hours for 10 doses, starting 24 hours after methotrexate. Fluorouracil modulation: 200 mg/m2 IV over 2 hours, followed by fluorouracil, or 20 mg/m2 IV bolus followed by fluorouracil.
Condition-Specific Dosing:
Methotrexate Rescue (High-Dose MTX):
Initial dose typically 10-15 mg/m2 IV/IM/PO every 6 hours for 10 doses, starting 24 hours after MTX. Dosing adjusted based on MTX levels and renal function. Duration and dose depend on MTX elimination. May require higher doses (e.g., 50-100 mg every 3-6 hours) for severe MTX toxicity.
Fluorouracil (5-FU) Modulation:
Typically 200 mg/m2 IV over 2 hours, followed by 5-FU, or 20 mg/m2 IV bolus followed by 5-FU. Regimens vary widely (e.g., weekly, bi-weekly, continuous infusion).
Trimethoprim/Pyrimethamine Toxicity:
5-15 mg/day orally, adjusted based on hematologic parameters.
Megaloblastic Anemia due to Folate Deficiency (unresponsive to oral folate):
1 mg/day IM.
Pediatric Dosing
Neonatal:
Not established for routine use; specific protocols for high-dose methotrexate rescue may exist.
Infant:
Dosing for methotrexate rescue is similar to adults on a mg/m2 basis, adjusted based on MTX levels and renal function.
Child:
Dosing for methotrexate rescue and 5-FU modulation is similar to adults on a mg/m2 basis, adjusted based on MTX levels and renal function.
Adolescent:
Dosing for methotrexate rescue and 5-FU modulation is similar to adults on a mg/m2 basis, adjusted based on MTX levels and renal function.
Dose Adjustments
Renal Impairment:
Mild:
No specific dose adjustment required for mild impairment, but close monitoring of methotrexate levels is crucial during MTX rescue.
Moderate:
For methotrexate rescue, higher doses and/or longer duration of leucovorin may be required due to delayed methotrexate clearance. Dosing guided by methotrexate levels.
Severe:
For methotrexate rescue, significantly higher doses and/or prolonged duration of leucovorin are often required. Close monitoring of methotrexate levels and aggressive hydration/alkalinization are critical. Leucovorin is not renally cleared, but its need is dictated by the impaired clearance of the antagonist (e.g., methotrexate).
Dialysis:
Leucovorin itself is not significantly dialyzable. For methotrexate rescue, leucovorin should be continued after dialysis sessions if methotrexate levels remain elevated. Hemodialysis can remove methotrexate, but leucovorin is still needed to counteract residual methotrexate effects.
Hepatic Impairment:
Mild:
No specific dose adjustment required.
Moderate:
No specific dose adjustment required.
Severe:
No specific dose adjustment required. Leucovorin is metabolized in the liver, but significant impairment is not typically a reason for dose adjustment, unless it impacts the metabolism of the co-administered drug (e.g., methotrexate).
Pharmacology
Mechanism of Action
Leucovorin (folinic acid) is a reduced form of folic acid that does not require reduction by dihydrofolate reductase. It is rapidly converted to 5-methyltetrahydrofolate, which is a coenzyme for various metabolic reactions, including purine and pyrimidine synthesis. In methotrexate rescue, leucovorin bypasses the metabolic block caused by methotrexate (which inhibits dihydrofolate reductase), providing the necessary reduced folates for DNA synthesis and repair, thereby protecting healthy cells from methotrexate toxicity. In combination with fluorouracil (5-FU), leucovorin enhances the cytotoxic effects of 5-FU by stabilizing the binding of 5-FU's active metabolite (5-FdUMP) to thymidylate synthase, thereby prolonging the inhibition of DNA synthesis.
Pharmacokinetics
Absorption:
Bioavailability:
Oral bioavailability is variable, generally lower than IV (e.g., ~97% for 25 mg dose, but decreases with higher doses due to saturation of active transport).
Tmax:
Oral: ~2 hours for parent compound, ~3 hours for active metabolite (5-methyltetrahydrofolate). IV: Rapid distribution.
FoodEffect:
Not significantly affected by food, but oral absorption can be saturated at higher doses.
Distribution:
Vd:
Not extensively reported, but distributes widely into body tissues, including CSF (though CSF levels are lower than plasma).
ProteinBinding:
Not extensively protein bound.
CnssPenetration:
Limited, but sufficient to provide some rescue in the CNS, though intrathecal administration of methotrexate often requires intrathecal leucovorin for CNS rescue.
Elimination:
HalfLife:
Parent compound: ~0.7 hours (IV). Active metabolite (5-methyltetrahydrofolate): ~6-7 hours (IV).
Clearance:
Not extensively reported, but primarily hepatic metabolism and renal excretion.
ExcretionRoute:
Primarily renal (80-90%) and fecal (5-8%).
Unchanged:
Minimal unchanged drug excreted.
Pharmacodynamics
OnsetOfAction:
Rapid, within minutes for IV administration.
PeakEffect:
Within hours, depending on route and conversion to active metabolite.
DurationOfAction:
Dependent on dose and elimination of active metabolite, typically several hours.
Safety & Warnings
Side Effects
Urgent Side Effects: Seek Medical Help Right Away
Although rare, this medication can cause severe and potentially life-threatening side effects. If you experience any of the following symptoms, contact your doctor or seek immediate medical attention:
Signs of an allergic reaction, including:
+ 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. While many people may not experience any side effects or only minor ones, it's essential to discuss any concerns with your doctor. If you have side effects that bother you or persist, contact your doctor for guidance.
Reporting Side Effects
This list is not exhaustive, and you may experience other side effects not mentioned here. If you have questions or concerns about side effects, consult 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 on managing side effects.
Although rare, this medication can cause severe and potentially life-threatening side effects. If you experience any of the following symptoms, contact your doctor or seek immediate medical attention:
Signs of an allergic reaction, including:
+ 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. While many people may not experience any side effects or only minor ones, it's essential to discuss any concerns with your doctor. If you have side effects that bother you or persist, contact your doctor for guidance.
Reporting Side Effects
This list is not exhaustive, and you may experience other side effects not mentioned here. If you have questions or concerns about side effects, consult 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 on managing side effects.
Seek Immediate Medical Attention If You Experience:
- Severe diarrhea
- Severe mouth sores (mucositis)
- Unusual bleeding or bruising
- Signs of infection (fever, chills, sore throat)
- Severe skin rash
- Signs of kidney problems (decreased urination, swelling)
- Allergic reaction (hives, difficulty breathing, swelling of face/lips/tongue/throat)
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 conditions and medications with your doctor. Please inform your doctor and pharmacist about:
All prescription and over-the-counter (OTC) medications you are taking
Any natural products or vitamins you are using
All your health problems
It is vital to verify that it is safe to take this medication with all your other medications and health conditions. Never 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 conditions and medications with your doctor. Please inform your doctor and pharmacist about:
All prescription and over-the-counter (OTC) medications you are taking
Any natural products or vitamins you are using
All your health problems
It is vital to verify that it is safe to take this medication with all your other medications and health conditions. Never 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, consult 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 discuss the potential benefits and risks of this medication to you and your baby.
Some formulations of this drug may contain benzyl alcohol, which can be hazardous to newborns and infants. Serious side effects can occur in these children, particularly when combined with other medications containing benzyl alcohol. Consult your doctor to determine which formulations contain benzyl alcohol and to discuss alternative options.
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, consult 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 discuss the potential benefits and risks of this medication to you and your baby.
Some formulations of this drug may contain benzyl alcohol, which can be hazardous to newborns and infants. Serious side effects can occur in these children, particularly when combined with other medications containing benzyl alcohol. Consult your doctor to determine which formulations contain benzyl alcohol and to discuss alternative options.
Overdose Information
Overdose Symptoms:
- While leucovorin itself has low toxicity, very high doses could theoretically mask the effects of antifolate drugs, leading to their toxicity. However, overdose is rare and typically not associated with direct toxicity from leucovorin itself.
What to Do:
In case of suspected overdose or adverse reaction, seek immediate medical attention. Call 911 or your local emergency number. For general poison control, call 1-800-222-1222.
Drug Interactions
Major Interactions
- Methotrexate (antagonistic effect, unless used for rescue)
- Fluorouracil (synergistic effect, intended interaction)
- Trimethoprim (antagonistic effect)
- Pyrimethamine (antagonistic effect)
Moderate Interactions
- Phenobarbital (may decrease anticonvulsant levels)
- Phenytoin (may decrease anticonvulsant levels)
- Primidone (may decrease anticonvulsant levels)
Monitoring
Baseline Monitoring
Complete Blood Count (CBC) with differential
Rationale: To establish baseline hematologic status, especially important when used with myelosuppressive agents or for toxicity rescue.
Timing: Prior to initiation of therapy.
Renal Function (BUN, Creatinine)
Rationale: Essential for methotrexate rescue, as impaired renal function delays methotrexate clearance, necessitating higher/prolonged leucovorin doses.
Timing: Prior to initiation of therapy, especially with high-dose methotrexate.
Liver Function Tests (ALT, AST, Bilirubin)
Rationale: To assess baseline hepatic function, though leucovorin itself is not highly hepatotoxic.
Timing: Prior to initiation of therapy.
Routine Monitoring
Methotrexate Plasma Levels
Frequency: At specific time points (e.g., 24, 48, 72 hours) after methotrexate administration, as per protocol.
Target: Protocol-specific, aiming for rapid decline below toxic thresholds (e.g., <0.1-0.05 micromolar by 48-72 hours).
Action Threshold: Elevated or persistently high methotrexate levels necessitate increased leucovorin dose and/or prolonged duration, along with aggressive hydration and urine alkalinization.
Complete Blood Count (CBC) with differential
Frequency: Daily or every few days, especially during methotrexate rescue or with 5-FU.
Target: Maintain adequate counts (e.g., ANC > 1500/mm3, platelets > 100,000/mm3).
Action Threshold: Significant myelosuppression (neutropenia, thrombocytopenia) may require dose modification of co-administered chemotherapy or supportive care.
Renal Function (BUN, Creatinine)
Frequency: Daily during high-dose methotrexate therapy.
Target: Maintain normal renal function.
Action Threshold: Rising creatinine indicates delayed methotrexate clearance, requiring intensified leucovorin rescue and supportive measures.
Electrolytes (Potassium, Magnesium, Phosphate)
Frequency: Daily during high-dose methotrexate therapy.
Target: Maintain within normal limits.
Action Threshold: Imbalances can occur with aggressive hydration and alkalinization, requiring correction.
Symptom Monitoring
- Signs of methotrexate toxicity (mucositis, diarrhea, rash, myelosuppression, renal dysfunction)
- Signs of fluorouracil toxicity (mucositis, 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 critical in cancer treatment where the underlying disease poses a greater risk.
Trimester-Specific Risks:
First Trimester:
Risk of fetal harm cannot be ruled out. Use only if clearly needed.
Second Trimester:
Risk of fetal harm cannot be ruled out. Use only if clearly needed.
Third Trimester:
Risk of fetal harm cannot be ruled out. Use only if clearly needed.
Lactation
Leucovorin is excreted into breast milk. Due to the potential for serious adverse reactions in the breastfed infant, a decision should be made whether to discontinue nursing or to discontinue the drug, taking into account the importance of the drug to the mother. Lactation Risk L3 (Moderately Safe).
Infant Risk:
Potential for adverse effects on the infant, though specific data are limited. The primary concern is the underlying condition being treated and co-administered drugs.
Pediatric Use
Leucovorin is widely used in pediatric oncology, particularly for methotrexate rescue. Dosing is typically based on body surface area (mg/m2) and adjusted based on methotrexate levels and renal function, similar to adult protocols. Close monitoring is essential.
Geriatric Use
No specific dose adjustments are generally required based solely on age. However, elderly patients may have reduced renal function, which can impact the clearance of co-administered drugs like methotrexate, necessitating careful monitoring and potential adjustment of leucovorin rescue protocols. Increased susceptibility to myelosuppression and other toxicities should be considered.
Clinical Information
Clinical Pearls
- Leucovorin is NOT a chemotherapy drug; it is a rescue agent or a modulator.
- Always verify the specific protocol for leucovorin administration, especially for methotrexate rescue, as timing and dosing are critical and depend on methotrexate levels.
- Ensure adequate hydration and urine alkalinization during high-dose methotrexate therapy to facilitate methotrexate excretion and reduce toxicity.
- Leucovorin can be given orally, intramuscularly, or intravenously. The IV route is preferred for high-dose methotrexate rescue due to rapid absorption and higher bioavailability.
- When used with 5-FU, leucovorin enhances 5-FU's toxicity; monitor for increased gastrointestinal and hematologic side effects.
- Leucovorin should not be mixed with 5-FU in the same syringe or infusion bag due to precipitation.
Alternative Therapies
- Glucarpidase (Voraxaze): An enzyme that rapidly metabolizes methotrexate, used for rapid reduction of toxic methotrexate concentrations in patients with delayed methotrexate clearance due to renal dysfunction. It is a rescue agent, not a direct alternative to leucovorin's mechanism, but an alternative strategy for methotrexate toxicity.
- Folic Acid: While leucovorin is a derivative of folic acid, folic acid itself cannot bypass the dihydrofolate reductase inhibition caused by methotrexate and is therefore not an effective rescue agent for methotrexate toxicity.
Cost & Coverage
Average Cost:
Varies widely by dose and formulation (e.g., 200mg vial can range from $50 to $200+). per 200mg vial
Generic Available:
Yes
Insurance Coverage:
Generally covered by most medical and pharmacy benefit plans, often under Tier 2 or 3, especially when used for oncology indications. Prior authorization may be required for specific uses.
General Drug Facts
If your symptoms or health problems persist or worsen, it is essential to contact your doctor for further guidance. To ensure safe use, never share your medication with others, and do not take medication prescribed to someone else. Store all medications in a secure location, out of reach of children and pets, to prevent accidental ingestion. Dispose of unused or expired medications properly. Unless instructed to do so by a healthcare professional, do not flush medications down the toilet or pour them down the drain. If you are unsure about the proper disposal method, consult your pharmacist for advice. Many communities have drug take-back programs, which your pharmacist can help you locate. 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, 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 to ensure prompt and effective treatment.