Hydroxocobalamin

Renal Impairment The safety and effectiveness of CYANOKIT have not been studied in patients with renal impairment. Hydroxocobalamin and cyanocobalamin are eliminated unchanged by the kidneys.

Hepatic Impairment The safety and effectiveness of CYANOKIT have not been studied in patients with hepatic impairment.

Important Dosage and Administration Instructions If clinical suspicion of cyanide poisoning is high, administer CYANOKIT without delay. Comprehensive treatment of acute cyanide intoxication requires support of vital functions. Airway, ventilatory and circulatory support, oxygen administration, and management of seizures should not be delayed to administer CYANOKIT [see Warnings and Precautions] .

The expert advice of a regional poison control center may be obtained by calling 1-800-222-1222. Identifying Patients with Cyanide Poisoning Cyanide poisoning may result from inhalation, ingestion, or dermal exposure to various cyanide-containing compounds, including smoke from closed-space fires. Sources of cyanide poisoning include hydrogen cyanide and its salts, cyanogenic plants, aliphatic nitriles, and prolonged exposure to sodium nitroprusside.

The presence and extent of cyanide poisoning are often initially unknown. There is no widely available, rapid, confirmatory cyanide blood test. Treatment decisions must be made on the basis of clinical history and signs and symptoms of cyanide intoxication. Table 1 Common Signs and Symptoms of Cyanide Poisoning Symptoms Headache Confusion Dyspnea Chest tightness Nausea Signs Altered Mental Status (e.g., confusion, disorientation) Seizures or Coma Mydriasis Tachypnea / Hyperpnea (early) Bradypnea / Apnea (late) Hypertension (early) / Hypotension (late) Cardiovascular collapse Vomiting Plasma lactate concentration ≥8 mmol/L In some settings, panic symptoms including tachypnea and vomiting may mimic early cyanide poisoning signs.

The presence of altered mental status (e.g., confusion and disorientation) and/or mydriasis is suggestive of true cyanide poisoning although these signs can occur with other toxic exposures as well. Smoke Inhalation Not all smoke inhalation victims will have cyanide poisoning and may present with burns, trauma, and exposure to other toxic substances making a diagnosis of cyanide poisoning particularly difficult.

Prior to administration of CYANOKIT, smoke-inhalation victims should be assessed for the following: Exposure to fire or smoke in an enclosed area Presence of soot around the mouth, nose or oropharynx Altered mental status Although hypotension is highly suggestive of cyanide poisoning, it is only present in a small percentage of cyanide-poisoned smoke inhalation victims.

Also indicative of cyanide poisoning is a plasma lactate concentration ≥10 mmol/L (a value higher than that typically listed in the table of signs and symptoms of isolated cyanide poisoning because carbon monoxide associated with smoke inhalation also contributes to lactic acidemia). If cyanide poisoning is suspected, treatment should not be delayed to obtain a plasma lactate concentration.

Use with Other Cyanide Antidotes The safety of administering other cyanide antidotes simultaneously with CYANOKIT has not been established. If a decision is made to administer another cyanide antidote with CYANOKIT, these drugs should not be administered concurrently in the same intravenous line [see Dosage and Administration].

Preparation of Solution for Infusion Reconstitute the 5 g vial of hydroxocobalamin with 200 mL of diluent (not provided with CYANOKIT) using the supplied sterile transfer spike. The recommended diluent is 0.9% Sodium Chloride injection (0.9% NaCl). Lactated Ringers injection and 5% Dextrose injection (D5W) have also been found to be compatible with hydroxocobalamin and may be used if 0.9% NaCl is not readily available.

The line on the vial label represents 200 mL volume of diluent. Following the addition of diluent to the lyophilized powder, the vial should be repeatedly inverted or rocked, not shaken, for at least 60 seconds prior to infusion. Visually inspect hydroxocobalamin solutions for particulate matter and color prior to administration.

If the reconstituted solution is not dark red or if particulate matter is observed after the solution has been appropriately mixed, the solution should be discarded.

Incompatibility Information Physical incompatibility (particle formation) and chemical incompatibility were observed with the mixture of hydroxocobalamin in solution with selected drugs that are frequently used in resuscitation efforts. Hydroxocobalamin is also chemically incompatible with sodium thiosulfate and sodium nitrite and has been reported to be incompatible with ascorbic acid.

Therefore, these and other drugs should not be administered simultaneously through the same intravenous line as hydroxocobalamin. Simultaneous administration of hydroxocobalamin and blood products (whole blood, packed red cells, platelet concentrate and/or fresh frozen plasma) through the same intravenous line is not recommended.

However, blood products and hydroxocobalamin can be administered simultaneously using separate intravenous lines (preferably on contralateral extremities, if peripheral lines are being used).

Storage of Reconstituted Drug Product Once reconstituted, hydroxocobalamin is stable for up to 6 hours at temperatures not exceeding 40°C (104°F). Do not freeze. Any reconstituted product not used by 6 hours should be discarded.