Leucovorin Calcium 10mg 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, Antineoplastic Adjuvant
Pharmacologic Class
Folinic Acid Derivative
Pregnancy Category
C
FDA Approved
Aug 1953
DEA Schedule
Not Controlled
Overview
What is this medicine?
Leucovorin is a type of vitamin (folinic acid) that helps protect healthy cells from the harmful effects of certain cancer medicines, like methotrexate. It can also be used with other cancer medicines, like fluorouracil, to make them work better against cancer cells. It's not a cancer medicine itself, but it helps manage side effects or boost the effectiveness of other drugs.
How to Use This Medicine
Taking Your Medication
To use this medication correctly, follow your doctor's instructions and read all the information provided. Take your medication as directed, with or without food. If you experience stomach upset, taking it with food may help. Continue taking this medication as prescribed by your doctor or healthcare provider, even if you start feeling better.
Storing and Disposing of Your Medication
Store your 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 the information provided. Take your medication as directed, with or without food. If you experience stomach upset, taking it with food may help. Continue taking this medication as prescribed by your doctor or healthcare provider, even if you start feeling better.
Storing and Disposing of Your Medication
Store your 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, especially regarding timing for methotrexate rescue.
- Do not miss doses, as this can lead to serious side effects from other medications.
- Maintain good hydration as advised by your doctor, especially during high-dose methotrexate therapy.
- Report any new or worsening side effects immediately 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 depending on indication. For Methotrexate Rescue: Typically 10-15 mg/m2 orally every 6 hours for 10 doses, starting 24 hours after methotrexate initiation, adjusted based on methotrexate levels and renal function. For Colorectal Cancer (with 5-FU): 200 mg/m2 IV over 3-15 minutes, followed by 5-FU, or 20 mg/m2 IV followed by 5-FU. Oral dosing for 10mg tablets is typically for lower dose rescue or specific regimens.
Dose Range:
5 - 500 mg
Condition-Specific Dosing:
methotrexate_rescue:
Dose and duration depend on methotrexate dose, serum methotrexate levels, and renal function. Oral doses typically 10-25 mg every 6 hours.
colorectal_cancer_with_5fu:
Typically IV, but oral forms may be used in specific regimens or for maintenance. Oral doses are generally higher than IV due to bioavailability differences.
Pediatric Dosing
Neonatal:
Not established for routine use, but used off-label for specific conditions (e.g., pyrimethamine toxicity) with careful dosing.
Infant:
Dosing is highly individualized based on indication (e.g., methotrexate rescue, pyrimethamine toxicity) and body surface area or weight.
Child:
Dosing is highly individualized based on indication (e.g., methotrexate rescue, pyrimethamine toxicity) and body surface area or weight.
Adolescent:
Dosing is highly individualized based on indication (e.g., methotrexate rescue, pyrimethamine toxicity) and body surface area or weight, often similar to adult dosing based on BSA.
Dose Adjustments
Renal Impairment:
Mild:
No specific adjustment generally required, but monitor methotrexate levels closely if used for rescue.
Moderate:
Monitor methotrexate levels closely; higher or prolonged leucovorin doses may be required for rescue. Caution.
Severe:
Monitor methotrexate levels closely; higher or prolonged leucovorin doses may be required for rescue. Caution. Consult oncology protocol.
Dialysis:
Leucovorin is dialyzable. Methotrexate is dialyzable. Dosing for rescue should be guided by methotrexate levels and clinical status. Consult oncology protocol.
Hepatic Impairment:
Mild:
No specific adjustment generally required.
Moderate:
No specific adjustment generally required, but caution if severe liver dysfunction is present, as it may affect methotrexate clearance.
Severe:
No specific adjustment generally required, but caution if severe liver dysfunction is present, as it may affect methotrexate clearance.
Pharmacology
Mechanism of Action
Leucovorin is a reduced form of folic acid (folinic acid) that does not require the enzyme dihydrofolate reductase for its conversion to tetrahydrofolate. It acts as a biochemical rescue agent by providing the necessary coenzyme for purine and pyrimidine synthesis, thereby bypassing the inhibition caused by folic acid antagonists like methotrexate. In combination with fluorouracil, leucovorin enhances the binding of fluorodeoxyuridine monophosphate (FdUMP) to thymidylate synthase, thereby increasing the cytotoxic effects of fluorouracil.
Pharmacokinetics
Absorption:
Bioavailability:
Oral bioavailability is saturable and dose-dependent; generally 90% for 25 mg, decreasing to 37% for 200 mg. IV bioavailability is 100%.
Tmax:
Oral: 1.7 hours (for 5-methyltetrahydrofolate).
FoodEffect:
Food may delay absorption but does not significantly affect the extent of absorption.
Distribution:
Vd:
Not readily available for leucovorin itself, but for its active metabolite 5-methyltetrahydrofolate, it distributes widely.
ProteinBinding:
Not extensively protein bound.
CnssPenetration:
Limited penetration into the CNS, especially at standard doses. Higher doses may achieve therapeutic levels in CSF.
Elimination:
HalfLife:
Approximately 6.2 hours (for 5-methyltetrahydrofolate).
Clearance:
Not readily available for leucovorin, but for 5-methyltetrahydrofolate, it is primarily renal.
ExcretionRoute:
Primarily renal (80-90%), with some fecal excretion (5-8%).
Unchanged:
Less than 1% of the administered dose is excreted unchanged in urine.
Pharmacodynamics
OnsetOfAction:
Rapid (within minutes for IV, within an hour for oral).
PeakEffect:
Not directly applicable as it's a rescue agent or sensitizer; effect is sustained as long as adequate levels are maintained.
DurationOfAction:
Dependent on dose and continued administration, typically maintained for the duration of rescue therapy.
Safety & Warnings
Side Effects
Urgent Side Effects: Seek Medical Help Right Away
Although rare, some people may experience severe and potentially life-threatening side effects while 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
+ Difficulty 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 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 is available to provide medical advice about side effects, so don't hesitate to contact them if you have any concerns.
Although rare, some people may experience severe and potentially life-threatening side effects while 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
+ Difficulty 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 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 is available to provide medical advice about side effects, so don't hesitate to contact them if you have any concerns.
Seek Immediate Medical Attention If You Experience:
- Severe diarrhea
- Severe mouth sores (mucositis)
- Unusual bleeding or bruising
- Signs of infection (fever, chills, sore throat)
- Yellowing of skin or eyes (jaundice)
- Significant decrease in urine output
- Signs of allergic reaction (rash, hives, swelling of face/lips/tongue, difficulty 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, 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 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, 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 severity and frequency of side effects associated with fluorouracil, such as diarrhea, mouth irritation, and mouth sores. 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.
As you age, your sensitivity to this medication may increase. If you are 65 years or older, use this drug with caution, as you may be more prone to experiencing side effects.
If you are pregnant, planning to become pregnant, or breastfeeding, it is crucial to discuss the potential benefits and risks of this medication with your doctor. This will help you make an informed decision about your treatment and ensure the best possible outcome for you and your baby.
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 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.
As you age, your sensitivity to this medication may increase. If you are 65 years or older, use this drug with caution, as you may be more prone to experiencing side effects.
If you are pregnant, planning to become pregnant, or breastfeeding, it is crucial to discuss the potential benefits and risks of this medication with your doctor. This will help you make an informed decision about your treatment and ensure the best possible outcome for you and your baby.
Overdose Information
Overdose Symptoms:
- No specific symptoms of leucovorin overdose are well-documented, as it is a vitamin derivative. However, excessive doses could potentially interfere with the action of folic acid antagonists if not intended for rescue, or lead to imbalances if given inappropriately.
What to Do:
If overdose is suspected, contact a poison control center or emergency medical services immediately. Call 1-800-222-1222. Management is generally supportive.
Drug Interactions
Major Interactions
- Fluorouracil (enhances toxicity of fluorouracil, which is often desired in cancer therapy but requires careful monitoring for increased adverse effects)
- Methotrexate (antagonizes methotrexate's cytotoxic effects, which is the desired effect in rescue, but can reduce efficacy if given inappropriately)
Moderate Interactions
- Trimethoprim (antagonizes antibacterial effect)
- Pyrimethamine (antagonizes antimalarial/antiparasitic effect)
- Phenytoin (may decrease phenytoin levels, leading to loss of seizure control)
- Phenobarbital (may decrease phenobarbital levels)
- Primidone (may decrease primidone levels)
Monitoring
Baseline Monitoring
Complete Blood Count (CBC)
Rationale: To establish baseline hematologic status, especially important when used with myelosuppressive agents.
Timing: Prior to initiation of therapy.
Renal Function (BUN, Creatinine)
Rationale: To assess baseline kidney function, crucial for methotrexate elimination and leucovorin rescue.
Timing: Prior to initiation of therapy.
Liver Function Tests (ALT, AST, Bilirubin)
Rationale: To assess baseline liver function, as some co-administered drugs (e.g., methotrexate) are hepatotoxic.
Timing: Prior to initiation of therapy.
Routine Monitoring
Serum Methotrexate Levels
Frequency: As per protocol, typically 24, 48, 72 hours after methotrexate initiation, and as needed.
Target: Dependent on time point and protocol (e.g., <0.1-0.05 micromolar by 48-72 hours).
Action Threshold: Elevated levels require increased leucovorin dose and/or duration, and potentially other rescue measures.
Complete Blood Count (CBC)
Frequency: Daily or every other day during high-dose methotrexate therapy and rescue.
Target: Within normal limits or as tolerated per protocol.
Action Threshold: Significant drops in WBC, platelets, or hemoglobin may indicate myelosuppression requiring intervention.
Renal Function (BUN, Creatinine)
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 hydration.
Electrolytes (Potassium, Magnesium, Phosphate)
Frequency: Daily during high-dose methotrexate therapy and rescue.
Target: Within normal limits.
Action Threshold: Imbalances may occur with renal dysfunction or other therapies, requiring correction.
Symptom Monitoring
- Signs of myelosuppression (fever, chills, sore throat, unusual bleeding/bruising, fatigue)
- Signs of gastrointestinal toxicity (nausea, vomiting, diarrhea, mucositis, abdominal pain)
- Signs of renal dysfunction (decreased urine output, swelling)
- Signs of liver toxicity (jaundice, dark urine, right upper quadrant pain)
- Allergic reactions (rash, itching, swelling, dizziness, trouble breathing)
Special Patient Groups
Pregnancy
Pregnancy Category C. Animal reproduction studies have shown an adverse effect on the fetus and there are no adequate and well-controlled studies in humans, but potential benefits may warrant use of the drug in pregnant women despite potential risks. Use only if the potential benefit justifies the potential risk to the fetus.
Trimester-Specific Risks:
First Trimester:
Potential for fetal harm, especially if used with other teratogenic agents.
Second Trimester:
Potential for fetal harm, especially if used with other teratogenic agents.
Third Trimester:
Potential for fetal harm, especially if used with other teratogenic agents.
Lactation
Leucovorin is excreted in human milk. While generally considered compatible with breastfeeding due to its nature as a vitamin derivative, caution is advised. The decision to breastfeed should consider the potential for adverse reactions in the infant, the mother's need for the drug, and the underlying maternal condition.
Infant Risk:
Low risk, but monitor for any unusual effects in the infant. The amount transferred is likely small and unlikely to cause harm, especially given its role as a rescue agent.
Pediatric Use
Leucovorin is widely used in pediatric oncology, particularly for methotrexate rescue and in combination with fluorouracil. Dosing is typically based on body surface area (BSA) or weight and is highly individualized based on the specific protocol and indication. Close monitoring of drug levels (e.g., methotrexate) and toxicity is crucial.
Geriatric Use
No specific dose adjustments are generally required based solely on age. However, elderly patients may have reduced renal function, which can affect the clearance of co-administered drugs like methotrexate, necessitating closer monitoring of methotrexate levels and potential adjustments to leucovorin rescue doses. Monitor for increased susceptibility to adverse effects, especially gastrointestinal toxicity.
Clinical Information
Clinical Pearls
- Leucovorin is NOT a folic acid supplement and should not be used for pernicious anemia or megaloblastic anemia due to vitamin B12 deficiency, as it can mask the neurological symptoms of B12 deficiency while allowing hematologic abnormalities to improve.
- The timing of leucovorin administration is CRITICAL for effective methotrexate rescue. Delays can lead to severe, life-threatening toxicity.
- When used with fluorouracil, leucovorin enhances fluorouracil's cytotoxicity, which means increased efficacy but also increased risk of fluorouracil-related toxicities (e.g., mucositis, diarrhea, myelosuppression).
- Oral leucovorin bioavailability is saturable; for high-dose rescue or when absorption is a concern (e.g., severe mucositis), IV administration is preferred or required.
- Patients on leucovorin rescue should be well-hydrated and often receive urine alkalinization to promote methotrexate excretion.
Alternative Therapies
- Glucarpidase (Voraxaze): An enzyme that rapidly lowers plasma methotrexate levels in patients with delayed methotrexate elimination due to impaired renal function. Used in severe cases where leucovorin alone is insufficient.
- Folic acid (for folate deficiency, not for methotrexate rescue or 5-FU potentiation).
Cost & Coverage
Average Cost:
$10 - $50 per 30 tablets (10mg)
Generic Available:
Yes
Insurance Coverage:
Tier 1 or 2 (Generic)
General Drug Facts
If your symptoms or health issues persist or worsen, it's 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 be sure to check with your pharmacist for more information. If you have any questions or concerns about this medication, don't hesitate to reach out to your doctor, nurse, pharmacist, or other healthcare provider. In the event of a suspected overdose, immediately call your local poison control center or seek medical attention. When seeking help, be prepared to provide details about the overdose, including the medication taken, the amount, and the time it occurred.