Leucovorin Calcium 50mg Inj, 1 Vial

Leucovorin is a reduced form of folic 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 allowing normal cellular function to resume. When used with 5-fluorouracil (5-FU), leucovorin enhances the cytotoxic effects of 5-FU by stabilizing the binding of 5-FU's active metabolite (5-fluoro-2'-deoxyuridine-5'-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 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.

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. Never start, stop, or change the dosage 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 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 questions or concerns, discuss them with your doctor.

If you are 65 years or older, exercise caution when using this medication, as you may be more susceptible to side effects.

Prior to initiating treatment, inform your doctor if you are pregnant, planning to become pregnant, or breastfeeding. It is crucial to discuss the potential benefits and risks of this medication to both you and your baby.

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

• Fluorouracil (5-FU): Leucovorin significantly enhances the cytotoxicity and toxicity (e.g., myelosuppression, mucositis, diarrhea) of 5-FU. This is an intended interaction in cancer therapy, but requires careful monitoring.
• Methotrexate: Leucovorin antagonizes the effects of methotrexate. This is the intended interaction for rescue therapy, but inappropriate timing or dosing can reduce methotrexate's efficacy.

• Folic acid antagonists (e.g., Trimethoprim, Pyrimethamine): Leucovorin can antagonize the antimicrobial effects of these drugs. This is the intended interaction for rescue from toxicity.
• Anticonvulsants (e.g., Phenytoin, Phenobarbital, Primidone): Leucovorin (folate) may decrease plasma concentrations of these drugs, potentially leading to increased seizure frequency. Monitor anticonvulsant levels.

• Signs of mucositis (oral sores, difficulty swallowing)
• Diarrhea (frequency, severity)
• Nausea and vomiting
• Skin rash
• Fever or signs of infection (due to myelosuppression)
• Signs of renal dysfunction (decreased urine output, edema)

Leucovorin is classified as Pregnancy Category C. However, its use is often critical in situations like high-dose methotrexate rescue, where the benefits of preventing severe maternal toxicity outweigh potential fetal risks. Folate is essential for fetal development, and leucovorin is a form of folate. The decision to use should be based on a careful risk-benefit assessment.

Leucovorin and its active metabolite (5-MTHF) are excreted into breast milk. However, as a folate derivative, it is generally considered compatible with breastfeeding, especially when used for short-term rescue. Caution is advised if the mother is receiving other cytotoxic agents in combination with leucovorin.

Dosing is typically based on body surface area (mg/m²) and adjusted based on specific protocols (e.g., methotrexate levels for rescue). Pediatric patients may be more susceptible to certain toxicities when leucovorin is combined with other chemotherapeutic agents. Close monitoring is essential.

No specific dose adjustments are generally required for leucovorin based on age alone. However, elderly patients may have age-related declines in renal function, which can impact the elimination of co-administered drugs like methotrexate, necessitating prolonged leucovorin rescue. Increased susceptibility to toxicities (e.g., myelosuppression, mucositis, diarrhea) when combined with 5-FU should be considered.

• Leucovorin is NOT a folate supplement for nutritional deficiency; it is a specific antidote or chemotherapy sensitizer.
• For methotrexate rescue, leucovorin must be started within the specified timeframe (usually 24 hours after MTX initiation) and continued until methotrexate levels are below toxic thresholds.
• Oral leucovorin may not be reliably absorbed in patients with significant gastrointestinal toxicity (e.g., mucositis, vomiting) or during high-dose methotrexate rescue; IV administration is preferred in these cases.
• Ensure adequate hydration and urine alkalinization during high-dose methotrexate therapy to facilitate methotrexate excretion and reduce renal toxicity.
• When used with 5-fluorouracil, leucovorin significantly increases 5-FU's toxicity; careful monitoring for myelosuppression, mucositis, and diarrhea is crucial.

• Glucarpidase (Voraxaze): Used for rapid reduction of toxic plasma methotrexate concentrations in patients with delayed methotrexate elimination due to impaired renal function.
• Folic acid: Not a direct substitute for leucovorin in rescue settings, as it requires reduction by dihydrofolate reductase, which is inhibited by methotrexate.

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, do not flush medications down the toilet or pour 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; check with your pharmacist for more information. 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 call 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.