Leucovorin Calcium 100mg Inj, 1vial

Leucovorin is a reduced form of folic acid (folinic acid) that does not require reduction by the enzyme dihydrofolate reductase. It is rapidly converted to 5-methyltetrahydrofolate, an active metabolite. In methotrexate rescue, leucovorin bypasses the metabolic block of dihydrofolate reductase caused by methotrexate, providing the necessary reduced folates for purine and pyrimidine synthesis, thereby protecting healthy cells from methotrexate toxicity. In combination with fluorouracil, leucovorin enhances the cytotoxic effects of fluorouracil by stabilizing the binding of fluorodeoxyuridine monophosphate (FdUMP) to thymidylate synthase, thereby inhibiting DNA synthesis and repair.

Urgent Side Effects: Seek Medical Attention Immediately
If you experience any of the following symptoms, call your doctor or seek medical help right away, as they may be signs of a severe and potentially life-threatening side effect:
- 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, or 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 do not go away, contact your doctor for advice.

Reporting Side Effects
This list does not include all possible side effects. 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.

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 and its symptoms.
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 prescription and over-the-counter medications you are taking
Any natural products or vitamins you are using
Your overall health status, including any existing medical conditions

Before starting, stopping, or changing the dosage of any medication, including this one, consult with your doctor to ensure your safety. It is vital to verify that it is safe to take this medication in combination with your other medications and health conditions.

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 this medication is used in combination with fluorouracil, the risk of side effects associated with fluorouracil may increase. This may lead to more frequent, severe, or prolonged occurrences of 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 fatal. If you have any concerns or questions, it is crucial to discuss them with your doctor.

If you are 65 years or older, it is recommended to 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. It is necessary to discuss the potential benefits and risks of the medication to both you and your baby.

Some formulations of this medication may contain benzyl alcohol, which is used as a diluent. It is recommended to avoid products containing benzyl alcohol in newborns and infants, as high doses of benzyl alcohol can cause serious side effects in these age groups, particularly when combined with other medications containing benzyl alcohol. Consult your doctor to determine which formulations contain benzyl alcohol and to discuss alternative options.

• Fluorouracil (5-FU): Leucovorin significantly enhances the toxicity (e.g., severe diarrhea, mucositis, myelosuppression) and efficacy of 5-FU. This is a desired interaction in cancer therapy but requires careful monitoring.
• Trimethoprim/Sulfamethoxazole (Bactrim): Leucovorin may antagonize the antibacterial effects of trimethoprim, which is a dihydrofolate reductase inhibitor. Avoid concurrent use for antibacterial purposes.
• Pyrimethamine: Leucovorin may antagonize the antiprotozoal effects of pyrimethamine. Avoid concurrent use for antiprotozoal purposes.

• Phenytoin: Leucovorin may decrease plasma concentrations of phenytoin, potentially leading to loss of seizure control. Monitor phenytoin levels.
• Phenobarbital: Leucovorin may decrease plasma concentrations of phenobarbital.
• Primidone: Leucovorin may decrease plasma concentrations of primidone.
• Folic acid antagonists (e.g., methotrexate, raltitrexed): Leucovorin is used to counteract their effects, but inappropriate timing or dosing can lead to treatment failure or increased toxicity.

• Signs of methotrexate toxicity (e.g., mucositis, stomatitis, diarrhea, myelosuppression, skin rash, renal dysfunction)
• Signs of fluorouracil toxicity (e.g., severe diarrhea, mucositis, stomatitis, hand-foot syndrome, myelosuppression)
• Allergic reactions (rare, but possible: rash, itching, swelling, severe dizziness, trouble breathing)

Leucovorin is Pregnancy Category C. Animal studies have shown adverse effects on the fetus, but there are no adequate and well-controlled studies in pregnant women. It should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.

It is not known whether leucovorin is excreted in human milk. Because many drugs are excreted in human milk and because of the potential for serious adverse reactions in nursing infants from leucovorin, 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.

Leucovorin is used in pediatric patients, particularly for methotrexate rescue and in combination with fluorouracil for certain cancers. Dosing is typically based on body surface area or weight, similar to adult regimens, but requires careful monitoring and adjustment based on specific protocols and patient response.

No specific dose adjustments are generally required based solely on age. However, elderly patients may have reduced renal function, which could impact the clearance of co-administered drugs like methotrexate, necessitating closer monitoring and potential leucovorin dose adjustments in that context. Monitor for increased susceptibility to adverse effects, especially when used with fluorouracil.

• Leucovorin is NOT folic acid. They are different compounds and cannot be interchanged.
• The timing and dose of leucovorin are critical for its efficacy, especially in methotrexate rescue. Deviations from protocol can lead to severe toxicity or treatment failure.
• When used with fluorouracil, leucovorin enhances 5-FU's toxicity. This is an intended effect, but requires careful monitoring for severe diarrhea, mucositis, and myelosuppression.
• Always ensure adequate hydration and urinary alkalinization during high-dose methotrexate therapy to facilitate methotrexate excretion and reduce renal toxicity.
• Leucovorin can be given orally, intramuscularly, or intravenously. Oral administration is generally reserved for lower doses or maintenance, while IV is preferred for rescue or high-dose regimens due to more reliable absorption.

• Glucarpidase (Voraxaze): An enzyme that rapidly metabolizes methotrexate, used for rapid reduction of toxic methotrexate concentrations in patients with delayed methotrexate elimination due to impaired renal function.
• Folic acid (for folate deficiency anemia, but not for methotrexate rescue or fluorouracil modulation).

If your symptoms or health problems persist or worsen, it is essential to contact your doctor promptly. To ensure safe use, never share your medication with others, and do not take medication prescribed for 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 otherwise, avoid flushing medications down the toilet or pouring them down the drain. If you are unsure about the correct disposal method, consult your pharmacist for guidance. Many communities offer drug take-back programs, which your pharmacist can help you locate. Some medications may come with an additional patient information leaflet, so be sure to check with your pharmacist. 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.