Treating cyanide poisoning or severe nitroprusside toxicity
Hydroxocobalamin 5 g IV
Only formulation FDA-approved for this indication.
Have chronic kidney disease and worry about added cyanide moiety
Either hydroxo- or methyl-…
They lack the cyanide ligand present in cyano; no large trials show harm, but many nephrologists prefer cyanide-free forms.
Practical take-aways for U.S. clinicians
Stock & coverage drive the default: most retail and mail-order pharmacies only carry cyanocobalamin MDVs, so it remains the path of least resistance (Cyanocobalamin - StatPearls - NCBI Bookshelf).
Hydroxocobalamin is superior for persistence, but you may need to special-order (McKesson, Cardinal) or use a compounding-outsourcing facility.
Methylcobalamin is perfectly safe when compounded to USP <797> standards, but quality varies—stick with PCAB-accredited 503A pharmacies (e.g., Empower, Belmar).
Dosing flexibility matters more than molecule choice: after deficiency is corrected, titrate injection spacing so that trough serum B-12 stays >400 pg/mL and methylmalonic acid normalizes—regardless of formulation.
Document the ICD-10 code and why you’re choosing a non-standard product to satisfy audits or prior authorizations.
Bottom line:
Most insured U.S. patients: cyanocobalamin monthly gets the job done.
Patients seeking convenience or with adherence issues: hydroxocobalamin every 2–3 months is worth the extra cost/effort.
Neuropathy or “biohacker” goals: compounded high-dose methylcobalamin is reasonable when evidence-based therapies are maximized and the patient is informed about regulatory status.
Need sample prescriptions, supplier contacts, or European (INFARMED, EMA) sourcing notes
No formal toxic (lethal) ceiling has ever been identified for injectable vitamin B-12. Because cobalamins are water-soluble and the kidneys excrete the excess, the U.S. National Academies declined to set a Tolerable Upper Intake Level (UL) for the nutrient.Office of Dietary Supplements (ODS) Doses orders of magnitude higher than those used for routine replacement have been given intravenously without organ damage, although idiosyncratic reactions can occur.
What the evidence shows
Scenario (form & context)
Highest dose studied or approved
Key safety findings
Hydroxocobalamin for cyanide poisoning (Cyanokit®)
5 g IV over 15 min; may repeat once → 10 g total
Transient hypertension, chromaturia, and two mild hypersensitivity reactions; no serious end-organ toxicity reported.FDA Access DataPubMed
Experimental volunteer studies
10 g IV bolus in healthy adults
Blood-pressure rise ≤25 mm Hg and reversible skin redness; no biochemical toxicity.PubMed
High-dose methylcobalamin for neuropathy
5–10 mg SC three times weekly for ≥6 months
No systemic toxicity; occasional acneiform eruption or injection-site pain (case reports only).NCBI
Repeated daily 1 mg injections (cyanocobalamin) in deficiency
Tachycardia, acne, anxiety reported after cumulative 12 mg; resolved on discontinuation—suggests intolerance, not systemic toxicity.PubMed
Why a numeric “LD₅₀” isn’t available
Renal clearance & binding limits: Only about 2–3 µg of each milligram injected remains in circulation once transport proteins are saturated; the remainder is rapidly filtered by the kidneys.
No cobalt overload: The cobalt in cobalamin is tightly chelated and is not released under physiologic conditions, so systemic cobalt toxicity—seen with hip prostheses—does not occur with B-12 injections.
Regulatory history: Hydroxocobalamin’s 10 g approval for cyanide poisoning effectively sets a clinically proven safe ceiling, far above replacement needs.
Routine maintenance: 1 mg IM/SC every 4 weeks (cyano- or hydroxo-).
Convenience dosing: Hydroxocobalamin 1 mg IM every 8–12 weeks once replete.
Neuropathy protocols (off-label): Methylcobalamin 5 mg SC up to three times weekly.
Monitor, don’t guess
Check serum B-12 or methylmalonic acid ≈ 3 months after any regimen change.
In severe baseline deficiency, add potassium and CBC 1–2 weeks after loading.
Reserve megadoses (>1 g) for special indications (e.g., cyanide poisoning) and hospital settings with cardiorespiratory monitoring.
Document & educate
Record the indication and chosen formulation in the chart.
Warn patients about harmless reddish urine after large hydroxocobalamin infusions.
Bottom line
Therapeutic ceiling: Up to 10 g IV hydroxocobalamin is FDA-approved and well tolerated; no lethal dose is known.
Clinical reality: For routine deficiency, anything above 1 mg per injection merely increases cost and wastes drug.
Risk management: Focus on allergy screening, electrolyte follow-up in profound deficiency, and patient education—rather than calculating a numeric “toxic dose.”
Always individualise dosing and monitoring to the patient’s renal function, comorbidities, and therapeutic goals.