Hydroxocobalamin (Cyanokit)

Emergency & Prehospital

• Smoke inhalation with suspected cyanide poisoning: an enclosed-space fire with altered mental status. Most empiric use starts here.
• Other known or suspected cyanide poisoning: hydrogen cyanide gas or cyanide salts (industrial, laboratory, electroplating, jewelry cleaning), cyanogenic plants, aliphatic nitriles; by inhalation, ingestion or skin contact
• Cardiac arrest, shock or coma after a possible cyanide exposure: Treat empirically. Don't wait for a cyanide level.

ED / ICU / Transport

• Nitroprusside-associated cyanide toxicity: A prolonged sodium nitroprusside infusion is a labeled source of cyanide.
• Refractory vasodilatory (vasoplegic) shock: A rescue adjunct after cardiopulmonary bypass or in septic shock, when norepinephrine and vasopressin are not enough (off-label).

Other Uses

• Vitamin B12 deficiency: A different product treats it: hydroxocobalamin 1,000 mcg/mL IM, not the Cyanokit antidote.

Recognizing Cyanide After Smoke Inhalation

• Screen before dosing: Ask about an enclosed-space fire, look for soot around the mouth, nose or oropharynx, and check for altered mental status. Low blood pressure is found in only a small share of victims.
• Lactate ≥10 mmol/L in a smoke victim also suggests cyanide (US label). Never delay the antidote for a result. See lactate and carbon monoxide.

Two sources set these numbers: AHA 2025 Part 10 and the Cyanokit label. Where the label differs, the "Differs from FDA label" note tells you.

Available Forms

• Cyanokit (US): One 250 mL glass vial holds 5 g of lyophilized hydroxocobalamin. Reconstitute it with 200 mL of diluent to reach 25 mg/mL (5 g in 200 mL). The kit includes a transfer spike and an IV set. The diluent is not in the kit.
• Outside the US (EU): You get one 5 g vial (200 mL) or two 2.5 g vials (100 mL each). Either way, 25 mg/mL.
• Hydroxocobalamin 1,000 mcg/mL IM: A vitamin B12 product. Far too dilute to treat cyanide poisoning.

Adult Dosing

Pediatric Dosing

Differs from FDA label: Pediatric safety and effectiveness aren't established on the US label. Outside the US, 70 mg/kg is the dose in use. The EU SmPC (section 4.2) lists the same per-dose amount for ages 0–18, plus the 140 mg/kg total cap. Quick check: 10 kg is 0.7 g (28 mL). Once a child passes about 71 kg, the 5 g adult dose applies. See weight-based dosing.

Preparation & Administration

• Reconstitution: Add 200 mL of 0.9% sodium chloride through the transfer spike. The line on the vial marks 200 mL. Reach for lactated Ringer's or D5W only when normal saline isn't readily available.
• Mixing: Invert or rock the vial for at least 60 seconds. Never shake it. Discard the solution if it isn't dark red or has particles.
• Line: Give it through a dedicated IV line that carries nothing else. Blood products go through another line, preferably on the opposite limb.
• IO: Neither the US nor the EU label includes IO. AHA 2025 Part 10 Table 4 lists IV or IO, so go IO when IV access fails.
• Baseline blood first: Draw lactate, a blood gas with co-oximetry and a cyanide level before you start, if this causes no delay.
• Stability: Use it within 6 hr of reconstitution. Keep it at 40 °C (104 °F) or below. Don't freeze it.
• Compatibility: Verify it with your institution's compatibility resource.

Contraindications

• None on the US or EU label. No contraindication is absolute in suspected cyanide poisoning.

Precautions

• Known anaphylaxis to hydroxocobalamin or cyanocobalamin (vitamin B12): Weigh benefit against risk with the poison center. In smoke inhalation, nitrite is hazardous. That leaves two options: hydroxocobalamin with epinephrine and airway support ready, or sodium thiosulfate alone, which acts slowly.
• Blood pressure rise: Systolic ≥180 mmHg or diastolic ≥110 mmHg shows up in about 18% of healthy volunteers at 5 g and 28% at 10 g. It peaks near the end of the infusion and is back to baseline within 4 hr. Watch closely in aortic dissection, intracranial hemorrhage or acute coronary syndrome. Don't hold it in life-threatening poisoning.
• Laboratory and device interference: Red plasma throws off many lab tests, pulse oximetry and dialysis alarms. See Monitoring.
• Burn assessment: Red skin can hide burn erythema. Skin lesions, edema and pain still point to burns.
• Photosensitivity: Tell the patient to avoid direct sun while the skin stays red.

Hold / Reassess If

• Stop for anaphylaxis (new bronchospasm, airway-threatening angioedema, or hypotension with urticaria): Stop the infusion and give IM epinephrine with standard anaphylaxis care. Then choose the next antidote with the poison center. Thiosulfate alone acts slowly. For isolated urticaria or pruritus, treat with an antihistamine and weigh whether to keep going (clinical judgment; label 5.2). Untreated cyanide poisoning is lethal, so that weighing matters. Red skin and flushing alone are expected. They are not allergy.
• Still no change after the first 5 g? Give the second dose and look for other causes: CO, burns, shock, trauma, other toxins.

Common

Expect red urine in 100% of volunteers at 5 g, lasting up to 5 weeks. Red skin appears in 94%, for up to 2 weeks. Urine oxalate crystals show up in 61%. Acneiform rash hits 20% on days 7–28, and it usually clears without treatment. Blood pressure rise: 18%. Nausea, headache and infusion-site reactions run 6% each.

Serious / Life-Threatening

Overdose & Toxicity Management

• Data: The US label has no overdose data. The EU label notes doses as high as 15 g given without specific dose-related reactions. In children, check every mL/kg calculation twice.
• Management: Treat the symptoms. Hemodialysis is indicated only for significant hydroxocobalamin toxicity. Red plasma can disrupt the machine.
• Methemoglobin: Raised MetHb has been reported after high-dose hydroxocobalamin. A reading taken after dosing can be analyzer interference. Confirm with clinical signs (cyanosis, an SpO₂–SaO₂ gap) and another method.

Clinically Significant Interactions

• Pediatrics: Not FDA-labeled in children. The dose is the AHA 2025 Part 10 Table 4 dose (IV or IO). In small children, count the fluid volume (2.8 mL/kg per dose).
• Neonates: No separate neonatal dosing is established.
• Pregnancy: Human data can't define a drug-associated risk. Animal studies at 0.5–2 times human exposure showed embryofetal loss and skeletal or soft-tissue anomalies at the high doses. Cyanide crosses the placenta, and untreated poisoning can kill mother and fetus. Never withhold treatment because of pregnancy.
• Lactation: Both hydroxocobalamin and cyanocobalamin show up in human milk. The US label advises against breastfeeding during treatment. No data say when to resume.
• Older Adults: About 50 patients aged 65 or older in the clinical studies responded like younger patients. No dose adjustment.
• Renal Impairment: Not studied. The kidneys clear both hydroxocobalamin and cyanocobalamin unchanged. The EU label gives no dose adjustment for this emergency use. Monitor renal function for 7 days.
• Hepatic Impairment: Not studied. The EU label gives no dose adjustment.
• Patients on Hemodialysis: Plan for blood-leak alarm shutdowns before the next session. See Monitoring.

• Scope: Paramedics, flight and critical-care transport, and ED and ICU clinicians, where the agency stocks it. It varies by state and agency protocol.
• Storage & Stability: Store at 25 °C (77 °F), with excursions allowed between 15–30 °C (59–86 °F). The label documents tolerance of 5–40 °C (41–104 °F) for 15 days, desert transport at 5–60 °C (41–140 °F) for 4 days, and freeze-thaw cycles from −20 to 40 °C (−4 to 104 °F) for 15 days.
• Carried Concentration: Each kit carries one 5 g vial and no diluent. Stock normal saline, for example a 250 mL bag, with every kit. Add the saline only to the vial's 200 mL fill line, which gives 25 mg/mL. Pediatric mL/kg volumes assume 25 mg/mL.
• Infusions in Transport: Keep a dedicated line, plus a second IV or IO for resuscitation drugs. For children, program the calculated volume, not the full vial.
• Scene: Remove the patient from smoke. Give oxygen and secure the airway first. The label says not to wait for the kit. Cyanide salts on skin or clothing need decontamination before transport.
• Handoff Essentials: Hand off the exposure time and source, the time and total grams (or mg/kg) of each dose, pre-dose tubes drawn and any pre-dose SpCO, the BP trend, and a warning about lab, co-oximetry, pulse oximetry and dialysis interference. Red skin and flushing are expected. They are not an allergic reaction. Look for urticaria, wheeze or angioedema.

Mechanism of Action

• Cobalt (Co³⁺) binds cyanide: each molecule swaps its hydroxo group for one cyanide ion and becomes cyanocobalamin (vitamin B12), which is then excreted in urine.
• Cytochrome c oxidase is freed: mitochondria can use oxygen again, so lactate falls and acidosis improves.
• No methemoglobin formation: oxygen-carrying capacity stays intact. That matters when CO is also present.
• Scavenges nitric oxide and hydrogen sulfide: With those gone, vessels constrict. That explains the transient BP rise and the rationale for vasoplegia use.

Pharmacokinetics

• Half-life: about 26–31 hr for free and total cobalamins at 5 g and 10 g.
• Metabolism: It isn't metabolized. Hydroxocobalamin binds plasma proteins and small molecules to form cobalamin complexes.
• Elimination: The kidneys clear it. About 60% of a 5 g dose is in the urine by 72 hr, most of it in the first 24 hr. Red urine can persist up to 35 days.

Generic Name

Hydroxocobalamin (hydroxocobalamin for injection)

Brand Names

Cyanokit (US 5 g vial; 2 × 2.5 g kit outside the US). Low-dose hydroxocobalamin 1,000 mcg/mL IM is generic vitamin B12

Pharmacologic Class

Cobalamin (vitamin B12a); cyanide-binding agent

Therapeutic Class

Cyanide antidote; off-label rescue adjunct in vasoplegic shock

Controlled Substance

Not controlled

ISMP High-Alert

No

Look-Alike / Sound-Alike

No ISMP-listed pair. Practical trap: the 5 g Cyanokit antidote vs 1,000 mcg/mL vitamin B12 products (hydroxocobalamin or cyanocobalamin), a 5,000-fold difference in dose