Leucovorin Calcium 350mg Inj, 1vl

Leucovorin is a reduced form of folic acid (folinic acid) that does not require reduction by dihydrofolate reductase. It serves as a biochemical antidote to folic acid antagonists (e.g., methotrexate, pyrimethamine, trimethoprim) by providing the necessary cofactors for purine and pyrimidine synthesis, thus protecting healthy cells from the cytotoxic effects of these agents. When used with fluorouracil (5-FU), leucovorin enhances the cytotoxic effects of 5-FU by stabilizing the binding of fluorodeoxyuridine monophosphate (FdUMP) to thymidylate synthase, thereby inhibiting DNA synthesis and repair.

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, which may include:
+ 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 advice.

Please note that 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.

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 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, including any medical conditions or concerns.

To ensure your safety, it is vital to verify that this medication can be taken 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 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 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 older adults, the combination of this drug with fluorouracil has been linked to severe bowel problems, diarrhea, and dehydration, which can be fatal. 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 the medication to you and your baby.

Some formulations of this drug contain benzyl alcohol, which can be hazardous to newborns and infants. If possible, avoid using products that contain benzyl alcohol in these age groups, as high doses of benzyl alcohol can cause serious side effects, 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 enhances the toxicity of 5-FU, including severe diarrhea, mucositis, and myelosuppression. This is often a desired effect in cancer therapy, but requires careful monitoring.
• Methotrexate: Leucovorin is used to rescue cells from methotrexate toxicity, but if administered concurrently or inappropriately, it can antagonize the antineoplastic effect of methotrexate.

• Phenytoin, Phenobarbital, Primidone: Leucovorin may decrease plasma concentrations of these anticonvulsants, potentially increasing seizure frequency. This is due to increased hepatic metabolism of anticonvulsants, possibly by increasing folate levels.
• Co-trimoxazole (Trimethoprim/Sulfamethoxazole): Leucovorin can antagonize the antimicrobial effect of trimethoprim, which is a dihydrofolate reductase inhibitor. Used to mitigate toxicity, not for concurrent antimicrobial effect.
• Pyrimethamine: Leucovorin can antagonize the antiparasitic effect of pyrimethamine. Used to mitigate toxicity, not for concurrent antiparasitic effect.

• Diarrhea (especially with 5-FU)
• Mucositis/Stomatitis (especially with 5-FU)
• Nausea and vomiting
• Fatigue
• Fever or signs of infection (due to myelosuppression)
• Bleeding or bruising (due to thrombocytopenia)
• Allergic reactions (rash, itching, swelling, difficulty breathing)

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 clearly needed.

L3 (Moderately Safe). Leucovorin and its metabolites are excreted into breast milk. While generally considered safe due to its vitamin-like nature, caution is advised. The decision to breastfeed should consider the potential for infant exposure, the benefits of breastfeeding, and the mother's clinical need for leucovorin.

Dosing is typically weight- or body surface area-based. Used for methotrexate rescue, megaloblastic anemia, and to mitigate toxicity of other folate antagonists. Close monitoring of methotrexate levels is crucial in pediatric methotrexate rescue. Safety and efficacy are established for appropriate indications.

No specific dose adjustments are generally required based on age alone. However, elderly patients may have reduced renal function, which could impact methotrexate elimination and thus the need for leucovorin rescue. Monitor renal function and methotrexate levels closely. Increased susceptibility to adverse effects of co-administered chemotherapy (e.g., 5-FU) may necessitate careful monitoring.

• Leucovorin is NOT a chemotherapy drug; it is a rescue agent or modulator.
• NEVER administer leucovorin intrathecally for methotrexate overdose; fatal reactions have occurred.
• Always verify the dose and timing of leucovorin, especially in methotrexate rescue, as it is critical for efficacy and safety.
• Oral leucovorin is generally effective for doses up to 25 mg; higher doses or patients with malabsorption may require parenteral administration.
• When used with 5-FU, leucovorin enhances 5-FU's toxicity, which is the intended effect, but requires vigilant monitoring for severe diarrhea and mucositis.
• Ensure adequate hydration and urinary alkalinization during high-dose methotrexate therapy to prevent renal toxicity and facilitate methotrexate excretion.

• Glucarpidase (Voraxaze): An enzyme that rapidly metabolizes methotrexate, used for delayed methotrexate elimination due to renal dysfunction. Not a direct alternative to leucovorin, but an alternative rescue strategy for methotrexate toxicity.
• Folic Acid: While related, folic acid requires reduction by dihydrofolate reductase and cannot bypass the effects of folate antagonists like methotrexate. Not a substitute for leucovorin in rescue settings.

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. Properly dispose of unused or expired medications by checking with your pharmacist for guidance, as some communities have drug take-back programs. Unless instructed to do so, avoid flushing medications down the toilet or pouring them down the drain. If you have questions about disposing of your medication, consult your pharmacist, who can also provide additional patient information leaflets for certain medications. If you have any concerns or questions 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 occurred to ensure timely and effective treatment.