Leucovorin Calcium 25mg Tablets

Leucovorin is a reduced form of folic acid (folinic acid) that does not require reduction by dihydrofolate reductase. It is rapidly converted to 5-methyltetrahydrofolate, which is the primary active metabolite. In methotrexate rescue, leucovorin competes with methotrexate for transport into cells and provides the necessary reduced folates to bypass the dihydrofolate reductase blockade, thereby protecting healthy cells from methotrexate's cytotoxic effects. In combination with fluorouracil (5-FU), leucovorin stabilizes the binding of 5-FU's active metabolite (FdUMP) to thymidylate synthase, enhancing the inhibition of DNA synthesis and increasing 5-FU's cytotoxicity.

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, 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 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 a type of anemia caused by a vitamin B12 deficiency.
If you have any stomach or bowel problems, as these conditions may affect how your body responds to the medication.

This list is not exhaustive, and it is crucial to discuss all your health concerns with your doctor. To ensure safe treatment, tell 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, as they may interact with this medication.

Before starting, stopping, or changing the dose of any medication, including this one, consult with your doctor to confirm it is safe for you to do so.

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 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 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, it is crucial to discuss them with your doctor.

As you age, your risk of experiencing side effects may increase. If you are 65 years or older, it is essential to use this medication with caution, as you may be more susceptible to adverse effects.

If you are pregnant, planning to become pregnant, or breastfeeding, you should notify your doctor. It is vital to discuss the potential benefits and risks of this medication to both you and your baby, allowing you to make an informed decision about your treatment.

• Fluorouracil (5-FU): Leucovorin enhances the toxicity of 5-FU, particularly gastrointestinal and hematologic toxicities. This is often an intended interaction in chemotherapy regimens, but requires careful monitoring.
• Methotrexate: Leucovorin is used to rescue cells from methotrexate toxicity, but if given concurrently or before methotrexate, it can reduce methotrexate's efficacy. Timing is critical.

• Trimethoprim/Sulfamethoxazole (Bactrim): May reduce the efficacy of leucovorin by competing for transport into cells.
• Pyrimethamine: May reduce the efficacy of leucovorin by competing for transport into cells.
• Phenytoin, Phenobarbital, Primidone: Leucovorin may decrease plasma concentrations of these anticonvulsants, potentially leading to increased seizure frequency. This is thought to be due to increased hepatic metabolism of the anticonvulsants, possibly by increasing folate levels.

• Signs of myelosuppression (fever, unusual bleeding/bruising, fatigue)
• Gastrointestinal toxicity (oral sores, difficulty swallowing, diarrhea, nausea, vomiting)
• Skin reactions (rash, redness)
• Allergic reactions (hives, swelling, difficulty breathing)

Leucovorin is 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. Its use in pregnancy is typically in the context of life-threatening conditions (e.g., cancer) where the benefit outweighs the risk, or to counteract the effects of folate antagonists.

Leucovorin is excreted into breast milk. The amount of leucovorin and its active metabolites transferred to breast milk is generally considered low. However, due to the potential for adverse effects on the nursing infant (especially if the infant has a folate deficiency or is exposed to other folate antagonists), caution is advised. The decision to breastfeed should consider the importance of the drug to the mother, the risk of infant exposure, and the risk of an untreated maternal condition. L3 (Moderately Safe).

Leucovorin is commonly used in pediatric oncology for methotrexate rescue and as a modulator for fluorouracil. Dosing is typically weight or body surface area-based. Close monitoring of methotrexate levels and renal function is crucial in pediatric patients.

No specific dose adjustments are generally required for elderly patients based on age alone. However, elderly patients may have reduced renal function, which can affect methotrexate clearance and thus the need for leucovorin rescue. Monitor renal function and methotrexate levels closely.

• Leucovorin is NOT a chemotherapy drug; it's a rescue agent or a sensitizer.
• Timing is critical for methotrexate rescue: Leucovorin must be started within 24-42 hours of methotrexate initiation to be effective in preventing severe toxicity.
• Oral leucovorin is generally effective for doses up to 25 mg; higher doses may require IV administration due to saturation of oral absorption.
• Always ensure adequate hydration and urinary alkalinization during high-dose methotrexate therapy to facilitate methotrexate excretion and reduce renal toxicity.
• When used with 5-FU, leucovorin significantly increases 5-FU's toxicity, particularly myelosuppression and mucositis/diarrhea. This is an intended effect, but requires vigilant monitoring.
• Leucovorin can mask the hematologic manifestations of pernicious anemia (vitamin B12 deficiency) while allowing neurological damage to progress. Always rule out B12 deficiency before using leucovorin for megaloblastic anemia.

• Glucarpidase (Voraxaze): An enzyme that rapidly breaks down methotrexate, used in cases of delayed methotrexate clearance due to renal dysfunction, where leucovorin alone may be insufficient.

If your symptoms or health issues persist or worsen, it is essential to contact your doctor for further guidance. To ensure safe and effective treatment, never share your medication with others or take someone else's medication. Some medications may come with an additional patient information leaflet, so it is a good idea to check with your pharmacist for more information. If you have any questions or concerns about your 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 seeking help, be prepared to provide detailed information about the overdose, including the medication taken, the amount, and the time it occurred.