Provider Briefing: The Leucovorin Shortage in 2026

Leucovorin Calcium remains a foundational component of multiple oncology regimens and a critical agent in methotrexate rescue therapy. Unfortunately, the drug's supply chain continues to be unreliable. This briefing provides an up-to-date overview of the shortage, its clinical implications, and practical strategies to ensure your patients maintain access to appropriate therapy.

Shortage Timeline and Current Status

Leucovorin's supply problems are not new. The drug has experienced recurring shortages since 2008, with three documented shortage events between 2008 and 2014. These disruptions directly contributed to the FDA's approval of Levoleucovorin (Fusilev) in 2008 as an alternative agent.

As of early 2026, the situation remains challenging:

• Injectable 500 mg vials: Multiple manufacturers, including Sagent and Fresenius Kabi, report ongoing back orders. Sagent has placed 500 mg vials on long-term back order with no estimated release date. Other manufacturers have projected availability in late 2025, but supply remains inconsistent.
• Oral tablets: Intermittent disruptions continue. The FDA has authorized temporary importation of Lederle Leucovorin (Calcium Folinate) 5 mg tablets from Canada, manufactured by Farmasierra in Spain for Pfizer.
• Other vial sizes (50 mg, 100 mg, 200 mg, 350 mg): Availability varies by manufacturer and changes frequently. Facilities should check with their wholesalers regularly.

Prescribing Implications

The Leucovorin shortage has direct consequences for treatment protocols across several clinical contexts:

Colorectal Cancer Regimens

Leucovorin is a standard component of FOLFOX (with Oxaliplatin) and FOLFIRI (with Irinotecan) — the backbone regimens for advanced colorectal cancer. Typical dosing in these protocols is 400 mg/m² IV over 2 hours, or 200 mg/m² depending on the specific protocol. When Leucovorin is unavailable, Levoleucovorin at half the dose (200 mg/m² or 100 mg/m², respectively) is the recommended substitution.

Methotrexate Rescue

In high-dose methotrexate therapy for osteosarcoma, leukemia, and lymphoma, Leucovorin rescue is not optional — it is essential to prevent life-threatening toxicity. Standard rescue dosing is approximately 15 mg (10 mg/m²) every 6 hours beginning 24 hours after methotrexate administration, continuing until serum methotrexate levels fall below 10⁻⁸ M.

If Leucovorin is unavailable for methotrexate rescue, Levoleucovorin should be substituted immediately. In cases of severely delayed methotrexate clearance, Glucarpidase (Voraxaze) may be considered as an adjunct — noting that Glucarpidase and Leucovorin/Levoleucovorin should not be administered within 2 hours of each other.

Other Uses

Providers in infectious disease (pyrimethamine toxicity prevention), OB/GYN (ectopic pregnancy protocols), and toxicology (methanol poisoning) should also be aware of the shortage and plan accordingly.

The Availability Picture

Supply is fragmented across manufacturers and formulations. Key points for procurement teams:

• Generic Leucovorin is manufactured by a small number of companies (Teva, Fresenius Kabi, Sagent, among others). Single-source vulnerability is high.
• The FDA importation of tablets from Canada provides limited relief for oral dosing needs.
• Levoleucovorin (generic and branded Fusilev/Khapzory) may have more stable supply at present, though at higher cost.
• Hospital and health-system pharmacies should consider maintaining par levels of both Leucovorin and Levoleucovorin to ensure continuity.

Cost and Access Considerations

The shortage has pricing implications that affect both institutions and patients:

• Generic Leucovorin oral tablets (5 mg, 12 ct): Cash price approximately $24-$36 with discount cards.
• Injectable vials: Pricing highly variable, from $30 to over $500 depending on vial size, manufacturer, and availability.
• Levoleucovorin: Generally more expensive than generic Leucovorin, which can create cost barriers for patients, particularly those with high-deductible plans or limited coverage.
• Insurance: Most plans cover Leucovorin under the medical benefit (injection) or pharmacy benefit (oral). Prior authorization may be required for brand Wellcovorin. Some payers may require documentation of Leucovorin unavailability before approving Levoleucovorin.

For patients facing financial barriers, resources include Prescription Hope ($70/month for Wellcovorin), NeedyMeds, RxAssist, and Pfizer RxPathways.

Tools and Resources for Providers

Several tools can help you and your patients navigate the shortage:

• Medfinder for Providers: Search for real-time pharmacy-level availability of Leucovorin. This can save significant time when coordinating with outpatient pharmacies and patients.
• ASHP Drug Shortage Resource Center: Tracks shortage status for both Leucovorin Calcium injection and tablets with manufacturer-level detail.
• FDA Drug Shortages Database: Official federal tracking of current and resolved shortages.
• Institutional formulary management: Consider dual-stocking Leucovorin and Levoleucovorin and establishing automatic substitution protocols.

For patient-facing resources, our blog offers practical guides including how to find Leucovorin in stock and how to save money on Leucovorin — resources you can share with patients directly.

Looking Ahead

The structural factors driving the Leucovorin shortage — limited manufacturing base, sterile injectable production complexity, and sustained oncology demand — are unlikely to resolve quickly. Providers should plan for continued supply variability through 2026 and beyond.

Proactive steps include:

1. Establishing Levoleucovorin substitution protocols in your practice or institution
2. Communicating proactively with patients about potential delays
3. Monitoring ASHP and FDA shortage databases regularly
4. Using tools like Medfinder to help patients locate supply

Final Thoughts

The Leucovorin shortage is a systemic issue that requires both institutional preparedness and individual problem-solving. By staying informed, maintaining flexible protocols, and connecting patients with the right resources, providers can mitigate the impact on treatment outcomes. For a patient-facing version of this information, see our Leucovorin shortage update for patients.

For guidance on helping patients navigate availability challenges, read our companion post: How to help your patients find Leucovorin in stock.