Leucovorin Calcium 15mg 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; Antianemic
Pharmacologic Class
Folic acid derivative; Folinic acid
Pregnancy Category
Category C
FDA Approved
Aug 1981
DEA Schedule
Not Controlled
Overview
What is this medicine?
Leucovorin is a form of folic acid that helps protect healthy cells from the harmful effects of certain cancer medications, like methotrexate. It can also make other cancer medications, like 5-fluorouracil, work better. Sometimes, it's used to treat certain types of anemia.
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, protected from light, and in a dry place. Avoid storing it 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.
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, protected from light, and in a dry place. Avoid storing it 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.
Lifestyle & Tips
- Take exactly as prescribed by your doctor. Do not miss doses, especially if you are taking it as a 'rescue' medication after chemotherapy.
- Maintain good hydration, especially if you are receiving high-dose methotrexate.
- Report any side effects or concerns to your healthcare provider promptly.
- Store at room temperature, away from light and moisture.
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:
For Methotrexate Rescue: 15 mg orally every 6 hours for 10 doses, starting 24 hours after methotrexate administration. Dose and duration are highly variable based on methotrexate serum levels and renal function. For 5-Fluorouracil Modulation: 15 mg orally once daily, typically administered prior to or concurrently with 5-fluorouracil.
Dose Range:
1 - 25 mg
Condition-Specific Dosing:
Megaloblastic Anemia:
1 mg orally once daily
Pneumocystis Prophylaxis (with pyrimethamine/sulfadiazine):
5-10 mg orally once daily
Pediatric Dosing
Neonatal:
Not established
Infant:
Dosing is typically based on body surface area (BSA) or weight, similar to adult regimens for specific indications (e.g., methotrexate rescue).
Child:
Dosing is typically based on body surface area (BSA) or weight, similar to adult regimens for specific indications (e.g., methotrexate rescue). For Methotrexate Rescue: 15 mg/m² orally every 6 hours for 10 doses, starting 24 hours after methotrexate administration. Dose and duration are highly variable based on methotrexate serum levels and renal function.
Adolescent:
Dosing is typically based on body surface area (BSA) or weight, similar to adult regimens for specific indications (e.g., methotrexate rescue). For Methotrexate Rescue: 15 mg/m² orally every 6 hours for 10 doses, starting 24 hours after methotrexate administration. Dose and duration are highly variable based on methotrexate serum levels and renal function.
Dose Adjustments
Renal Impairment:
Mild:
No specific adjustment for leucovorin itself, but careful monitoring of methotrexate levels and leucovorin rescue duration is critical if used with high-dose methotrexate.
Moderate:
No specific adjustment for leucovorin itself, but careful monitoring of methotrexate levels and leucovorin rescue duration is critical if used with high-dose methotrexate. May require extended leucovorin rescue.
Severe:
No specific adjustment for leucovorin itself, but careful monitoring of methotrexate levels and leucovorin rescue duration is critical if used with high-dose methotrexate. May require extended leucovorin rescue and higher doses.
Dialysis:
Leucovorin is not significantly dialyzable. Methotrexate is dialyzable, so leucovorin rescue should continue after dialysis if methotrexate levels remain high.
Hepatic Impairment:
Mild:
No specific adjustment recommended.
Moderate:
No specific adjustment recommended, but caution advised due to potential impact on methotrexate metabolism and excretion.
Severe:
No specific adjustment recommended, but caution advised due to potential impact on methotrexate metabolism and excretion.
Pharmacology
Mechanism of Action
Leucovorin is a reduced form of folic acid, also known as folinic acid. It does not require reduction by dihydrofolate reductase, thus it can bypass the inhibitory action of folic acid antagonists (e.g., methotrexate, trimethoprim, pyrimethamine). Leucovorin is rapidly converted to 5-methyltetrahydrofolate, an active metabolite, which serves as a cofactor for enzymes involved in purine and pyrimidine synthesis. In methotrexate rescue, it replenishes intracellular folate stores, allowing normal cellular processes to resume and protecting healthy cells from methotrexate toxicity. In combination with 5-fluorouracil, leucovorin enhances the cytotoxic effects of 5-fluorouracil by stabilizing the binding of 5-fluorodeoxyuridine monophosphate (a 5-FU metabolite) to thymidylate synthase, thereby inhibiting DNA synthesis.
Pharmacokinetics
Absorption:
Bioavailability:
Approximately 90% (oral, variable)
Tmax:
Parent compound: 1-2 hours; Active metabolite (5-methyltetrahydrofolate): 2-3 hours
FoodEffect:
Not significantly affected by food.
Distribution:
Vd:
Not widely reported for leucovorin itself, but folates distribute widely into body tissues.
ProteinBinding:
Not extensively protein bound.
CnssPenetration:
Limited penetration into the central nervous system, especially with oral administration.
Elimination:
HalfLife:
Parent compound: Approximately 3-4 hours; Active metabolite (5-methyltetrahydrofolate): Approximately 6-7 hours
Clearance:
Not precisely quantified, primarily renal excretion.
ExcretionRoute:
Primarily renal (80-90%), with some fecal excretion (10-20%).
Unchanged:
Less than 1% of parent drug excreted unchanged.
Pharmacodynamics
OnsetOfAction:
Rapid (within minutes to hours, depending on route and indication)
PeakEffect:
Within hours, corresponding to peak metabolite levels.
DurationOfAction:
Several hours, depending on dose and indication.
Safety & Warnings
Side Effects
Urgent Side Effects: Seek Medical Help Right Away
While 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 medical attention immediately:
Signs of an allergic reaction, such as:
+ 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 passing out
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 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.
While 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 medical attention immediately:
Signs of an allergic reaction, such as:
+ 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 passing out
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 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 mouth sores or difficulty swallowing
- Unusual bleeding or bruising
- Signs of infection (fever, chills, sore throat)
- Severe diarrhea or vomiting
- Severe skin rash or itching
- Signs of an allergic reaction (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 in conjunction with all your other medications and health conditions. Never start, stop, or adjust 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 in conjunction with all your other medications and health conditions. Never start, stop, or adjust 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.
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 medication with fluorouracil has been linked to severe bowel problems, diarrhea, and dehydration, which can be life-threatening. If you have any concerns or questions, it is crucial to discuss them with your doctor.
Older adults (65 years and older) should exercise caution when using this medication, as they may be more susceptible to side effects.
If you are pregnant, planning to become pregnant, or breastfeeding, it is vital to consult with your doctor to discuss the potential benefits and risks of this medication to both 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 older adults, the combination of this medication with fluorouracil has been linked to severe bowel problems, diarrhea, and dehydration, which can be life-threatening. If you have any concerns or questions, it is crucial to discuss them with your doctor.
Older adults (65 years and older) should exercise caution when using this medication, as they may be more susceptible to side effects.
If you are pregnant, planning to become pregnant, or breastfeeding, it is vital to consult with your doctor to discuss the potential benefits and risks of this medication to both you and your baby.
Overdose Information
Overdose Symptoms:
- While leucovorin itself has low toxicity, an overdose is unlikely to cause severe symptoms directly. However, if taken in very large amounts, it could potentially mask symptoms of folate deficiency or interfere with the intended effects of other medications.
- The primary concern with 'overdose' is usually related to the chemotherapy drug it is rescuing from (e.g., methotrexate toxicity if leucovorin is insufficient or delayed).
What to Do:
In case of suspected overdose or adverse reaction, seek immediate medical attention or call a poison control center (1-800-222-1222). Management is generally supportive.
Drug Interactions
Major Interactions
- Methotrexate (Leucovorin is used to rescue cells from methotrexate toxicity, an intended interaction, but can antagonize its cytotoxic effect if given inappropriately)
- Fluorouracil (Leucovorin enhances the cytotoxic effect of fluorouracil, an intended interaction)
- Trimethoprim (Leucovorin can reduce the efficacy of trimethoprim by antagonizing its folate-depleting effects)
- Pyrimethamine (Leucovorin can reduce the efficacy of pyrimethamine by antagonizing its folate-depleting effects)
Moderate Interactions
- Phenytoin (Leucovorin may decrease serum concentrations of phenytoin, phenobarbital, and primidone, potentially increasing seizure frequency)
- Phenobarbital (Leucovorin may decrease serum concentrations of phenobarbital, potentially increasing seizure frequency)
- Primidone (Leucovorin may decrease serum concentrations of primidone, potentially increasing seizure frequency)
Monitoring
Baseline Monitoring
Complete Blood Count (CBC) with differential
Rationale: To assess baseline hematopoietic function, especially when used with myelosuppressive chemotherapy.
Timing: Prior to initiation of chemotherapy and leucovorin.
Renal Function (Serum Creatinine, BUN)
Rationale: Renal impairment can affect methotrexate elimination, necessitating adjustments in leucovorin rescue.
Timing: Prior to initiation of chemotherapy and leucovorin.
Liver Function Tests (LFTs)
Rationale: To assess baseline hepatic function, especially when used with hepatotoxic chemotherapy.
Timing: Prior to initiation of chemotherapy and leucovorin.
Routine Monitoring
Methotrexate Serum Levels
Frequency: As per high-dose methotrexate protocol (e.g., 24, 48, 72 hours post-MTX infusion)
Target: Protocol-specific (e.g., <0.1 µM at 48 hours, <0.05 µM at 72 hours)
Action Threshold: Levels above protocol-specific thresholds require continued or increased leucovorin rescue and supportive care.
Complete Blood Count (CBC) with differential
Frequency: Regularly during chemotherapy cycles (e.g., weekly or as clinically indicated)
Target: Within normal limits or as tolerated per chemotherapy protocol.
Action Threshold: Significant myelosuppression (e.g., ANC <500/mm³, platelets <50,000/mm³) may require dose modification of concomitant chemotherapy.
Renal Function (Serum Creatinine, BUN)
Frequency: Daily or every other day during high-dose methotrexate therapy and rescue.
Target: Within normal limits or stable baseline.
Action Threshold: Significant increase in creatinine may indicate delayed methotrexate clearance, requiring intensified leucovorin rescue.
Symptom Monitoring
- Signs of myelosuppression (fever, chills, sore throat, unusual bleeding/bruising)
- Signs of mucositis (mouth sores, difficulty swallowing)
- Gastrointestinal symptoms (nausea, vomiting, diarrhea)
- Skin reactions (rash, itching)
- Allergic reactions (hives, swelling, difficulty 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 situations where the mother's life is at risk (e.g., cancer treatment with methotrexate).
Trimester-Specific Risks:
First Trimester:
Potential risk to fetal development, especially if used in high doses or for prolonged periods. However, often used to mitigate risks of other essential medications.
Second Trimester:
Similar considerations as first trimester; benefits must outweigh risks.
Third Trimester:
Similar considerations as first trimester; benefits must outweigh risks.
Lactation
Leucovorin and its metabolites are excreted into breast milk. Due to the potential for serious adverse reactions in the nursing 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. Caution is advised.
Infant Risk:
L3 (Moderately Safe) - While generally considered low risk, potential for interference with infant's folate metabolism or masking of folate deficiency in the infant. Monitor infant for adverse effects.
Pediatric Use
Leucovorin is commonly used in pediatric oncology for similar indications as in adults, particularly for methotrexate rescue. Dosing is typically based on body surface area (BSA) or weight. Close monitoring of methotrexate levels and renal function is crucial in pediatric patients.
Geriatric Use
No specific dose adjustments are generally required for leucovorin in elderly patients. However, geriatric patients may have age-related decreases in renal function, which can affect the clearance of concomitant chemotherapy agents like methotrexate. Therefore, careful monitoring of renal function and methotrexate levels is important.
Clinical Information
Clinical Pearls
- Leucovorin is NOT folic acid. While both are folates, leucovorin is a reduced form that bypasses the need for dihydrofolate reductase, making it effective in rescuing cells from antifolate drugs.
- Timing of leucovorin administration is critical for effective methotrexate rescue. Delayed or inadequate leucovorin can lead to severe, life-threatening methotrexate toxicity.
- When used with 5-fluorouracil, leucovorin enhances the cytotoxic effect, which can increase the severity of 5-FU-related toxicities (e.g., mucositis, diarrhea).
- Oral leucovorin is generally well-absorbed, but IV administration is preferred for high-dose methotrexate rescue or in patients with impaired gastrointestinal absorption.
- Patients on leucovorin for methotrexate rescue should be well-hydrated and have urine alkalinized to promote methotrexate excretion.
Alternative Therapies
- Folic Acid (for folate deficiency not related to antifolate therapy)
- Glucarpidase (Voraxaze) (for rapid reduction of toxic methotrexate concentrations in patients with delayed methotrexate elimination due to impaired renal function)
Cost & Coverage
Average Cost:
$50 - $150 per 30 tablets (15mg)
Generic Available:
Yes
Insurance Coverage:
Tier 1 (Generic) or Tier 2 (Preferred Brand) on most formularies, especially when used for oncology indications.
General Drug Facts
If your symptoms or health issues persist or worsen, it is essential to contact your doctor for further evaluation and guidance. To ensure safe and effective treatment, never share your medication with others or take someone else's medication. Some medications may have additional patient information leaflets, so it is a good idea to consult with your pharmacist for more information. If you have any questions or concerns about this medication, do not 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 overdose, be prepared to provide details about the medication taken, the amount, and the time it occurred.