Levotonal (Calcium Levofolinate)

Levotonal is employed in oncology and supportive care to mitigate folate pathway disruption caused by antifolate chemotherapy.

• Rescue therapy after high‑dose methotrexate: reduces methotrexate toxicity and allows safe continuation of chemotherapy.
• Adjunct to 5‑fluorouracil‑based chemotherapy: enhances antitumor activity by stabilizing the active metabolite.
• Prevention/treatment of folate deficiency: restores folate levels in patients with chemotherapy‑induced depletion.

• Calcium levofolinate is a reduced form of folinic acid that enters cells via the reduced folate carrier and is converted to tetrahydrofolate derivatives. These derivatives serve as cofactors for enzymes in the purine and pyrimidine synthesis pathways, bypassing the block created by dihydrofolate reductase inhibition from antifolate drugs such as methotrexate, thereby rescuing normal cellular DNA synthesis while allowing antimetabolite activity to persist in tumor cells.

Calcium levofolinate may be associated with several adverse reactions, most of which are related to the injection process or underlying chemotherapy.

Common Side Effects

• Nausea: mild to moderate nausea.
• Fever: transient pyrexia.
• Injection site reactions: erythema or discomfort.
• Elevated liver enzymes: mild transaminase increase.

Serious or Rare Side Effects

• Anaphylaxis: severe allergic reaction requiring immediate treatment.
• Acute renal failure: rare kidney impairment.
• Thromboembolic events: rare clot formation.

Before using Levotonal, clinicians should consider several safety measures.

• Renal function: assess baseline creatinine and monitor during therapy.
• Hepatic function: evaluate liver enzymes before administration.
• Concurrent methotrexate: coordinate timing to avoid overlapping toxicity.
• Pregnancy and lactation: use only if benefits outweigh risks, as safety data are limited.
• Allergy history: screen for hypersensitivity to folate compounds.
• Store at 2-8°C: keep refrigerated, protect from light, do not freeze or shake.

Calcium levofolinate can interact with other medications that affect folate metabolism or methotrexate clearance.

Major Interactions (Avoid)

• High-dose methotrexate: simultaneous administration may reduce rescue efficacy; schedule appropriately.
• Antifolate agents (e.g., pemetrexed): may antagonize therapeutic effect.

Moderate Interactions (Monitor Closely)

• NSAIDs: can increase methotrexate toxicity, indirectly affecting calcium levofolinate rescue.
• Proton pump inhibitors: may alter renal clearance of methotrexate.
• Sulfonamides: potential additive bone marrow suppression.