CYANOKIT
Clinical safety rating: caution
Comprehensive clinical and safety monograph for CYANOKIT (CYANOKIT).
Hydroxocobalamin, a form of vitamin B12, acts as a scavenger of cyanide ions by binding with them to form cyanocobalamin, which is then excreted in urine. It has a higher affinity for cyanide than cytochrome c oxidase, thereby restoring mitochondrial function.
| Metabolism | Hydroxocobalamin is not metabolized; it forms complexes with cyanide (cyanocobalamin) and other ligands, which are excreted in urine. |
| Excretion | Primarily renal elimination as hydroxocobalamin and cyanocobalamin; >90% of an intravenous dose is excreted in urine within 72 hours, with the remainder eliminated in feces via biliary excretion. |
| Half-life | The terminal elimination half-life of hydroxocobalamin is approximately 24-28 hours in healthy adults; in cyanide poisoning, the half-life may be prolonged due to reversible binding to cyanide. |
| Protein binding | Hydroxocobalamin is extensively bound to plasma proteins, primarily transcobalamin II and haptocorrin; binding is >90%. |
| Volume of Distribution | Volume of distribution (Vd) is approximately 0.3-0.5 L/kg, indicating distribution mainly in extracellular fluid; higher Vd in poisoning reflects tissue binding. |
| Bioavailability | Not applicable for oral route; intravenous administration yields 100% bioavailability. No other routes are clinically used. |
| Onset of Action | Intravenous administration: Clinical effect (reversal of cyanide toxicity) is observed within minutes; peak plasma concentrations are achieved immediately after infusion. |
| Duration of Action | Duration of effect is variable, typically lasting 24-72 hours based on cyanide re-exposure or redistribution; repeat dosing may be required for severe poisonings. |
| Molecular Weight | 1382.82 |
5 g intravenous infusion over 15 minutes for adults and pediatric patients weighing >=40 kg. A second dose of 5 g may be administered if needed based on clinical response.
| Dosage form | INJECTABLE |
| Renal impairment | No specific dose adjustment for renal impairment; use caution in patients with pre-existing renal disease due to sodium nitrite content. |
| Liver impairment | No specific dose adjustment for hepatic impairment; monitor for adverse effects as hepatic metabolism may be altered. |
| Pediatric use | For pediatric patients weighing <40 kg: 0.2 mL/kg (equivalent to 0.24 g/kg) of a 2.5% solution (25 mg/mL) intravenously over 15 minutes, not to exceed 5 g. A second dose at same rate may be given if needed. |
| Geriatric use | No specific dose adjustment; monitor renal function and vital signs closely due to potential age-related changes in hemodynamics and renal function. |
| 1st trimester | Hydroxocobalamin is generally considered safe in the first trimester for life-threatening cyanide poisoning, as the benefits of treating cyanide poisoning outweigh potential risks. Animal studies have not shown teratogenicity at clinically relevant doses. |
| 2nd trimester | Use for life-threatening cyanide poisoning in the second trimester is justified. No fetal harm known from limited human data. |
| 3rd trimester | Third trimester use is acceptable for cyanide poisoning. No adverse fetal effects reported, but caution due to possible transient maternal hypertension. |
Clinical note
Comprehensive clinical and safety monograph for CYANOKIT (CYANOKIT).
| Placental transfer | Hydroxocobalamin crosses the placenta, but transfer is limited due to its large molecular size. Fetal exposure is expected to be low. |
| Breastfeeding | Hydroxocobalamin is excreted into breast milk in low amounts. It is considered compatible with breastfeeding due to its high molecular weight and poor oral bioavailability, minimizing infant exposure. However, caution is advised if used repeatedly. |
■ FDA Black Box Warning
None
| Serious Effects |
Known hypersensitivity to hydroxocobalamin or any component of the formulation
| Precautions | Allergic reactions: Anaphylaxis, angioedema, rash, and urticaria have been reported., Blood pressure increase: Transient hypertension may occur., Laboratory interference: May cause falsely elevated red co-oximetry readings for carboxyhemoglobin and methemoglobin; also interferes with clinical chemistry tests (e.g., creatinine, bilirubin)., Skin and urine discoloration: Red discoloration of skin, mucous membranes, and urine may occur and last up to 35 days., Renal impairment: Use with caution in patients with pre-existing renal impairment due to potential for decreased elimination of cyanocobalamin. |
| Food/Dietary | No known food interactions. |
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| Lactation Rating | L2 (Safer) |
| Teratogenic Risk | Cyanokit (hydroxocobalamin) is classified as FDA Pregnancy Category C. Animal studies have shown adverse effects on fetal development at high doses, but no adequate human studies exist. In the first trimester, theoretical risk from cyanide poisoning itself outweighs drug risk; use if clearly needed. Second and third trimesters: no known teratogenicity, but maternal cyanide poisoning poses significant fetal hypoxia risk; antidote administration is recommended. |
| Fetal Monitoring | Monitor maternal vital signs, ECG, oxygen saturation, and cyanide levels if available. Fetal heart rate monitoring should be performed if gestational age permits. Observe for maternal allergic reactions, hypertension, and infusion site reactions. In neonates exposed in utero, monitor for methemoglobinemia and cyanide toxicity signs. |
| Fertility Effects | No human data on fertility effects. Animal studies have not reported impaired fertility at clinically relevant doses. |
| Clinical Pearls | CYANOKIT (hydroxocobalamin) is indicated for known or suspected cyanide poisoning. Administer intravenously as a 5 g dose over 15 minutes. May cause red discoloration of skin, urine, and mucous membranes. Monitor blood pressure; hypertension may occur. Can interfere with colorimetric lab tests (e.g., bilirubin, creatinine) for up to 72 hours. Not effective for cyanide poisoning due to smoke inhalation without co-existing carbon monoxide toxicity if hypoxia is severe. |
| Patient Advice | This medication is only used in hospital for cyanide poisoning. · Your skin, urine, and eyes may turn red for up to several days. · Report any allergic reactions such as rash or swelling. · You may feel flushing or warmth during infusion. · Blood tests may be affected for a few days after treatment. |