Shilstine, containing the active ingredient Leucovorin, is a form of folinic acid used in combination with chemotherapy drugs to enhance their effectiveness or reduce their toxicity. It is also used to treat folic acid antagonist overdoses and certain types of anemia.

Uses

• Methotrexate Rescue Therapy: To reduce the toxicity of methotrexate in cancer treatment.

• Enhancement of Fluorouracil Therapy: In colorectal cancer to increase the efficacy of fluorouracil.

• Treatment of Folic Acid Antagonist Overdose: Such as methotrexate or trimethoprim.

• Megaloblastic Anemia: Due to folic acid deficiency.

Mechanism of Action

Leucovorin acts as a reduced form of folic acid that bypasses dihydrofolate reductase, replenishing folate stores in the body. This mechanism is vital for rescuing normal cells from methotrexate toxicity and enhancing fluorouracil activity by stabilizing its binding to thymidylate synthase.

Dosage and Administration

• Methotrexate Rescue: Dosage varies based on methotrexate levels. Typically, 15 mg every 6 hours for 10 doses.

• Fluorouracil Combination: 200 mg/m² IV daily for 5 consecutive days in a 28-day cycle.

• Overdose Management: Adjusted based on methotrexate concentration and renal function.

Administration can be oral or intravenous, depending on clinical conditions.

Side Effects

Common side effects:

• Nausea

• Vomiting

• Fatigue

• Diarrhea

Serious side effects:

• Seizures (in high doses)

• Allergic reactions

• Mouth sores

Precautions

• Regular monitoring of blood counts and renal function is essential.

• Use with caution in patients with pernicious anemia or vitamin B12 deficiency.

• Avoid overdose, as excessive leucovorin can counteract the antitumor effects of methotrexate.

Onset and Duration of Action

• Onset: Begins action within minutes to hours.

• Duration: Effects last several hours depending on the dosage and clinical context.

Storage

Store at room temperature, protected from light and moisture.