Leucovorin Calcium 5mg Tablets
It is used with methotrexate to avoid side effects.It may lower the side effects of some drugs.It may be given to you for other reasons. Talk with the doctor.
Drug Class
Antidote; Chemoprotectant; Folate Derivative
Pharmacologic Class
Reduced Folate; Folate Analog
Pregnancy Category
Not available (Historically Category C, but often used for specific indications where benefits outweigh risks, e.g., methotrexate rescue)
FDA Approved
Jan 1970
DEA Schedule
Not Controlled
Overview
What is this medicine?
Leucovorin is a form of folic acid, a B vitamin. It is used to protect healthy cells from the harmful effects of certain cancer medicines (like methotrexate) or to make other cancer medicines (like 5-fluorouracil) work better. It can also be used to treat certain types of anemia or to counteract the effects of other medications.
How to Use This Medicine
Taking Your Medication
To use this medication correctly, follow your doctor's instructions and read all accompanying information carefully. You can take this medication with or without food, but if it causes stomach upset, taking it with food may help. Continue taking this medication as directed by your doctor or healthcare provider, even if you start to feel better.
Storing and Disposing of Your Medication
Store this medication at room temperature, away from light and moisture. Keep it in a dry place, avoiding storage in a bathroom.
What to Do If You Miss a Dose
If you miss a dose or vomit after taking a dose, contact your doctor immediately for guidance on what to do next.
To use this medication correctly, follow your doctor's instructions and read all accompanying information carefully. You can take this medication with or without food, but if it causes stomach upset, taking it with food may help. Continue taking this medication as directed by your doctor or healthcare provider, even if you start to feel better.
Storing and Disposing of Your Medication
Store this medication at room temperature, away from light and moisture. Keep it in a dry place, avoiding storage in a bathroom.
What to Do If You Miss a Dose
If you miss a dose or vomit after taking a dose, contact your doctor immediately for guidance on what to do next.
Lifestyle & Tips
- Take exactly as prescribed by your doctor. Do not miss doses.
- If you are taking it for methotrexate rescue, it is critical to take it on time and for the full duration prescribed.
- Maintain good hydration, especially if undergoing chemotherapy.
- Report any new or worsening side effects promptly to your healthcare provider.
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. For megaloblastic anemia: 1 mg/day orally. For methotrexate rescue: 15 mg orally every 6 hours for 10 doses, adjusted based on methotrexate levels. For 5-fluorouracil modulation: Oral dosing less common, but may be used in some regimens (e.g., 20 mg/m2 orally daily for 5 days with 5-FU).
Dose Range:
1 - 500 mg
Condition-Specific Dosing:
Megaloblastic Anemia:
1 mg orally daily
Methotrexate Rescue (low-dose MTX):
15 mg orally every 6 hours for 10 doses, or as directed by MTX levels
Trimethoprim/Pyrimethamine Overdose:
5-15 mg orally daily
5-Fluorouracil Modulation:
Variable, e.g., 20 mg/m2 orally daily for 5 days with 5-FU
Pediatric Dosing
Neonatal:
Not established (use with caution, often IV in this age group)
Infant:
Dosing is weight-based and indication-specific, e.g., for MTX rescue, similar mg/m2 dosing as adults, but often IV.
Child:
Dosing is weight-based and indication-specific, e.g., for MTX rescue, 10-15 mg/m2 orally every 6 hours, adjusted based on MTX levels.
Adolescent:
Similar to adult dosing, adjusted based on body surface area and indication.
Dose Adjustments
Renal Impairment:
Mild:
Adjustment needed (monitor methotrexate levels closely if used for rescue)
Moderate:
Adjustment needed (monitor methotrexate levels closely if used for rescue)
Severe:
Adjustment needed (monitor methotrexate levels closely if used for rescue; consider higher doses or longer duration of leucovorin)
Dialysis:
Considerations: Leucovorin is dialyzable. Methotrexate is dialyzable. Dosing should be guided by methotrexate levels and clinical response.
Hepatic Impairment:
Mild:
Adjustment: Generally no specific dose adjustment, but monitor for increased toxicity if used with other hepatotoxic agents.
Moderate:
Adjustment: Generally no specific dose adjustment, but monitor for increased toxicity.
Severe:
Adjustment: Generally no specific dose adjustment, but monitor for increased toxicity.
Pharmacology
Mechanism of Action
Leucovorin is a reduced form of folic acid (5-formyltetrahydrofolate) that does not require reduction by dihydrofolate reductase. It is rapidly converted to 5-methyltetrahydrofolate, the primary active metabolite. In methotrexate (MTX) rescue, leucovorin bypasses the dihydrofolate reductase inhibition caused by MTX, providing the necessary reduced folates for purine and pyrimidine synthesis, thereby protecting healthy cells from MTX toxicity. In combination with 5-fluorouracil (5-FU), leucovorin enhances the binding of 5-fluorodeoxyuridine monophosphate (FdUMP), the active metabolite of 5-FU, to thymidylate synthase, forming a stable ternary complex that inhibits DNA synthesis and enhances the cytotoxic effects of 5-FU.
Pharmacokinetics
Absorption:
Bioavailability:
Variable and saturable at higher doses (e.g., 97% at 25 mg, 75% at 100 mg, 37% at 200 mg)
Tmax:
Parent compound: ~2 hours; Active metabolite (5-methyltetrahydrofolate): ~3 hours
FoodEffect:
Minimal effect on absorption
Distribution:
Vd:
Not well-defined
ProteinBinding:
Low
CnssPenetration:
Limited
Elimination:
HalfLife:
Parent compound: ~0.5 hours; Active metabolite (5-methyltetrahydrofolate): ~6-7 hours
Clearance:
Not well-defined
ExcretionRoute:
Primarily renal (80-90%), some biliary/fecal (5-8%)
Unchanged:
Minimal
Pharmacodynamics
OnsetOfAction:
Rapid (within minutes for IV, within hours for oral)
PeakEffect:
Variable depending on indication and route (e.g., peak plasma levels of active metabolite ~3 hours after oral dose)
DurationOfAction:
Several hours, depending on dose and elimination of active metabolite
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, 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. Although many people do not experience any side effects or only have mild ones, it is essential to discuss any concerns with your doctor. If you experience any 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, reach out to your doctor for advice. You can also report side effects to the FDA at 1-800-332-1088 or online at https://www.fda.gov/medwatch.
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, 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. Although many people do not experience any side effects or only have mild ones, it is essential to discuss any concerns with your doctor. If you experience any 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, reach out to your doctor for advice. You can also report side effects to the FDA at 1-800-332-1088 or online at https://www.fda.gov/medwatch.
Seek Immediate Medical Attention If You Experience:
- Fever, chills, or other signs of infection
- Unusual bleeding or bruising
- Severe diarrhea or vomiting
- Severe mouth sores or difficulty swallowing
- Signs of 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 a type of anemia caused by a lack of vitamin B12.
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, provide your doctor and pharmacist with a comprehensive list of all the medications you are taking, including:
Prescription medications
Over-the-counter (OTC) medications
Natural products
* Vitamins
It is vital to verify that it is safe to take this medication with all your existing medications and health conditions. Do not initiate, discontinue, or modify the dosage 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 a type of anemia caused by a lack of vitamin B12.
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, provide your doctor and pharmacist with a comprehensive list of all the medications you are taking, including:
Prescription medications
Over-the-counter (OTC) medications
Natural products
* Vitamins
It is vital to verify that it is safe to take this medication with all your existing medications and health conditions. Do not initiate, discontinue, or modify the dosage 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 to monitor your condition.
When used in combination with fluorouracil, this drug may increase the risk of side effects associated with fluorouracil, such as diarrhea, mouth irritation, and mouth sores. These side effects may occur more frequently, be more severe, and last longer. In rare cases, older adults taking this medication with fluorouracil have experienced severe bowel problems, diarrhea, and dehydration, which can be life-threatening. If you have any concerns or questions, 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 medication, 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, and help you make an informed decision.
When used in combination with fluorouracil, this drug may increase the risk of side effects associated with fluorouracil, such as diarrhea, mouth irritation, and mouth sores. These side effects may occur more frequently, be more severe, and last longer. In rare cases, older adults taking this medication with fluorouracil have experienced severe bowel problems, diarrhea, and dehydration, which can be life-threatening. If you have any concerns or questions, 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 medication, 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, and help you make an informed decision.
Overdose Information
Overdose Symptoms:
- Generally considered non-toxic in high doses, as it is a vitamin derivative. However, very high doses could potentially mask pernicious anemia if not properly diagnosed, leading to neurological damage.
What to Do:
Contact your healthcare provider or poison control center (1-800-222-1222) immediately. Treatment is generally supportive.
Drug Interactions
Major Interactions
- Methotrexate (when given concurrently for antineoplastic effect, leucovorin antagonizes MTX action)
- 5-Fluorouracil (enhances 5-FU toxicity, requiring careful monitoring and dose adjustment of 5-FU)
Moderate Interactions
- Phenytoin (may decrease phenytoin levels, increasing seizure risk)
- Phenobarbital (may decrease phenobarbital levels, increasing seizure risk)
- Primidone (may decrease primidone levels, increasing seizure risk)
- Trimethoprim (leucovorin can counteract the antibacterial effect of trimethoprim)
- Pyrimethamine (leucovorin can counteract the antimalarial/antiparasitic effect of pyrimethamine)
Monitoring
Baseline Monitoring
Complete Blood Count (CBC) with differential
Rationale: To establish baseline hematologic status, especially important when used with myelosuppressive agents.
Timing: Prior to initiation of therapy
Renal Function (Serum Creatinine, BUN)
Rationale: Renal impairment can affect methotrexate elimination, necessitating leucovorin dose adjustments.
Timing: Prior to initiation, especially if used for methotrexate rescue
Liver Function Tests (LFTs)
Rationale: To establish baseline hepatic status, though leucovorin is not primarily hepatotoxic.
Timing: Prior to initiation
Routine Monitoring
Methotrexate Plasma Levels
Frequency: As per methotrexate protocol (e.g., 24, 48, 72 hours post-MTX infusion)
Target: Levels should fall below specific thresholds (e.g., <0.1 micromolar at 48 hours, <0.01 micromolar at 72 hours) to discontinue leucovorin.
Action Threshold: Elevated or persistently high methotrexate levels necessitate increased leucovorin dose and/or extended duration.
Complete Blood Count (CBC) with differential
Frequency: Daily or every few days, depending on concomitant chemotherapy and clinical status
Target: Maintain adequate neutrophil and platelet counts.
Action Threshold: Significant myelosuppression (neutropenia, thrombocytopenia) may require supportive care or chemotherapy dose modification.
Renal Function (Serum Creatinine, BUN)
Frequency: Daily or every few days, especially during high-dose methotrexate therapy
Target: Maintain within normal limits or baseline.
Action Threshold: Rising creatinine may indicate impaired methotrexate clearance, requiring more aggressive leucovorin rescue.
Electrolytes (Potassium, Magnesium, Phosphate)
Frequency: Daily, especially during high-dose methotrexate therapy
Target: Maintain within normal limits.
Action Threshold: Imbalances can be associated with renal toxicity or other chemotherapy side effects.
Symptom Monitoring
- Signs of myelosuppression (fever, chills, unusual bleeding/bruising, fatigue)
- Signs of mucositis (sore mouth, difficulty swallowing, oral ulcers)
- Diarrhea
- Nausea/Vomiting
- Skin reactions (rash, itching)
- Signs of allergic reaction (hives, swelling, difficulty breathing)
Special Patient Groups
Pregnancy
Leucovorin is a folate derivative. While historically classified as Category C, its use in pregnancy is often considered when the benefits outweigh the risks, particularly for methotrexate rescue (where methotrexate is highly teratogenic) or for treating folate deficiency. Consult with an oncologist and obstetrician.
Trimester-Specific Risks:
First Trimester:
Risk: If used for methotrexate rescue, the primary concern is the methotrexate itself. Leucovorin is intended to mitigate this risk. If used for folate deficiency, it is generally considered beneficial.
Second Trimester:
Risk: Similar considerations as the first trimester. Generally considered safe when indicated.
Third Trimester:
Risk: Similar considerations as the first trimester. Generally considered safe when indicated.
Lactation
Leucovorin and its metabolites are excreted into breast milk. While it is a naturally occurring vitamin, the potential effects on a breastfed infant are not fully established. The decision to breastfeed should consider the need for leucovorin, the potential risks to the infant, and the benefits of breastfeeding. Monitor infant for adverse effects.
Infant Risk:
L3 (Moderately Safe - Limited data, potential for minor, non-serious adverse effects or no adverse effects)
Pediatric Use
Dosing is typically based on body surface area (mg/m2) or weight (mg/kg) and is highly dependent on the specific indication (e.g., methotrexate rescue, megaloblastic anemia). Close monitoring of drug levels (e.g., methotrexate) and clinical response is crucial.
Geriatric Use
No specific dose adjustments are generally required based on age alone. However, elderly patients may have reduced renal function, which can impact the elimination of co-administered drugs like methotrexate, necessitating careful monitoring and potential leucovorin dose adjustments based on renal function.
Clinical Information
Clinical Pearls
- Leucovorin is NOT interchangeable with folic acid for all indications; it is a reduced form that bypasses the need for dihydrofolate reductase.
- For methotrexate rescue, the timing and duration of leucovorin administration are critical. Delays or inadequate dosing can lead to severe, life-threatening toxicity.
- Oral leucovorin bioavailability can be saturable at higher doses; for very high-dose methotrexate rescue, IV leucovorin is often preferred or required.
- When used with 5-fluorouracil, leucovorin enhances both the efficacy and toxicity of 5-FU. Close monitoring for mucositis, diarrhea, and myelosuppression is essential.
- Patients on anticonvulsants (phenytoin, phenobarbital, primidone) should have their anticonvulsant levels monitored if leucovorin is initiated, as leucovorin may decrease their levels.
Alternative Therapies
- Folic acid (for some folate deficiency states, but not for methotrexate rescue or 5-FU modulation)
- Glucarpidase (Voraxaze): An enzyme that rapidly lowers plasma methotrexate levels in patients with delayed methotrexate elimination due to impaired renal function.
Cost & Coverage
Average Cost:
$10 - $50 per 30 tablets (5mg)
Generic Available:
Yes
Insurance Coverage:
Tier 1 or Tier 2 (Generic)
General Drug Facts
If your symptoms or health issues persist or worsen, it is essential to contact your doctor for further guidance. To ensure your safety, never share your medication with others or take someone else's medication. Some medications may come with an additional patient information leaflet, so it's a good idea to check with your pharmacist. If you have any questions or concerns about this medication, don't hesitate to discuss them with your doctor, nurse, pharmacist, or other healthcare provider. In the event of a suspected overdose, immediately call your local poison control center or seek emergency medical attention. When reporting the incident, be prepared to provide details about the medication taken, the amount, and the time it occurred.