Emergency Patient Management In addition to Cyanokit, treatment of cyanide poisoning must include immediate attention to airway patency, adequacy of oxygenation and hydration, cardiovascular support, and management of any seizure activity. Consideration should be given to decontamination measures based on the route of exposure. Allergic Reactions Use caution in the management of patients with known anaphylactic reactions to hydroxocobalamin or cyanocobalamin. Consideration should be given to use of alternative therapies, if available. Allergic reactions may include: anaphylaxis, chest tightness, edema, urticaria, pruritus, dyspnea, and rash. Allergic reactions including angioneurotic edema have also been reported in postmarketing experience. Blood Pressure Increase Many patients with cyanide poisoning will be hypotensive; however, elevations in blood pressure have also been observed in known or suspected cyanide poisoning victims. Elevations in blood pressure ( ≥ 180 mmHg systolic or ≥ 110 mmHg diastolic) were observed in approximately 18% of healthy subjects (not exposed to cyanide) receiving hydroxocobalamin 5 g and 28% of subjects receiving 10 g. Increases in blood pressure were noted shortly after the infusions were started; the maximal increase in blood pressure was observed toward the end of the infusion. These elevations were generally transient and returned to baseline levels within 4 hours of dosing. Use of Blood Cyanide Assay While determination of blood cyanide concentration is not required for management of cyanide poisoning and should not delay treatment with Cyanokit, collecting a pretreatment blood sample may be useful for documenting cyanide poisoning as sampling post-Cyanokit use may be inaccurate. Interference with Clinical Laboratory Evaluations and Clinical Methods Clinical Laboratory Evaluations Because of its deep red color, hydroxocobalamin has been found to interfere with colorimetric determination of certain laboratory parameters (e.g., clinical chemistry, hematology, coagulation, and urine parameters). In-vitro tests indicated that the extent and duration of the interference are dependent on numerous factors such as the dose of hydroxocobalamin, analyte, methodology, analyzer, hydroxocobalamin concentration, and partially on the time between sampling and measurement. Based on in-vitro studies and pharmacokinetic data obtained in healthy volunteers, the following table (Table 2) describes laboratory interference that may be observed following a 5 g dose of hydroxocobalamin. Interference following a 10 g dose can be expected to last up to an additional 24 hours. The extent and duration of interference in cyanide-poisoned patients may differ. Results may vary substantially from one analyzer to another; therefore, caution should be used when reporting and interpreting laboratory results. Table 2 : Laboratory Interference Observed with In-Vitro Samples of Hydroxocobalamin
Laboratory Parameter No Interference Observed Artificially Increased * Artificially Decreased * Unpredictable Duration of Interference Clinical Chemistry Calcium Creatinine ALT Phosphate 24 hours with the exception of bilirubin (up to 4 days) Sodium Bilirubin Amylase Uric Acid Potassium Triglycerides AST Chloride Cholesterol CK Urea Total protein CKMB GGT Glucose LDH Albumin Alkaline phosphatase Hematology Erythrocytes Hemoglobin 12 - 16 hours Hematocrit MCH MCV MCHC Leukocytes Basophils Lymphocytes Monocytes Eosinophils Neutrophils Platelets Coagulation aPTT PT (Quick or INR) 24 - 48 hours Urinalysis pH (with all doses) pH (with equivalent doses of < 5 g) 48 hoursup to 8 days; color changes may persist up to 28 days Glucose Protein erythrocytes Leukocytes Ketones Bilirubin Urobilinogen Nitrite * ≥ 10% interference observed on at least 1 analyzer
Analyzers used: ACL Futura (Instrumentation Laboratory),
AxSYM®/Architect™ (Abbott), BM Coasys110 (Boehringer Mannheim),
CellDyn 3700® (Abbott), Clinitek® 500 (Bayer), Cobas Integra® 700, 400 (Roche), Gen-S Coultronics, Hitachi 917, STA® Compact, Vitros® 950 (Ortho Diagnostics) Clinical Methods Because of its deep red color, hydroxocobalamin may cause hemodialysis machines to shut down due to an erroneous detection of a “blood leak”. This should be considered before hemodialysis is initiated in patients treated with hydroxocobalamin. Photosensitivity Hydroxocobalamin absorbs visible light in the UV spectrum. It therefore has potential to cause photosensitivity. While it is not known if the skin redness predisposes to photosensitivity, patients should be advised to avoid direct sun while their skin remains discolored. Patient Counseling Information Cyanokit is indicated for cyanide poisoning and in this setting, patients will likely be unresponsive or may have difficulty in comprehending counseling information. Erythema and Chromaturia Patients should be advised that skin redness may last up to 2 weeks and urine coloration may last for up to 5 weeks after administration of Cyanokit. While it is not known if the skin redness predisposes to photosensitivity, patients should be advised to avoid direct sun while their skin remains discolored. Rash In some patients an acneiform rash may appear anywhere from 7 to 28 days following hydroxocobalamin treatment. This rash will usually resolve without treatment within a few weeks. Pregnancy and Breast Feeding Patients should be advised that maternal cyanide poisoning results in fetal cyanide poisoning. Treatment for cyanide poisoning may be lifesaving for both mother and fetus. Patients should notify their physician if they were pregnant during therapy with Cyanokit [see Use In Specific Populations]. It is not known whether hydroxocobalamin is excreted in human milk. Nonclinical Toxicology Carcinogenesis, Mutagenesis, Impairment of Fertility Long-term animal studies have not been performed to evaluate the carcinogenic potential of hydroxocobalamin. Hydroxocobalamin was negative in the following mutagenicity assays: in vitro bacterial reverse mutation assay using Salmonella typhimurium and Escherichia coli strains, an in-vitro assay of the tk locus in mouse lymphoma cells, and an in-vivo rat micronucleus assay. The effect of hydroxocobalamin on fertility has not been evaluated. Use In Specific Populations Pregnancy Pregnancy Category C There are no adequate and well controlled studies of Cyanokit in pregnant women. In animal studies, hydroxocobalamin caused skeletal and visceral (soft tissue) abnormalities at exposures (based on AUC) similar to human exposures at the therapeutic dose. Cyanokit should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus. Because cyanide readily crosses the placenta, maternal cyanide poisoning results in fetal cyanide poisoning. Timely treatment of the pregnant mother may be lifesaving for both mother and fetus. In animal studies, pregnant rats and rabbits received Cyanokit (75, 150, or 300 mg/kg/d) during the period of organogenesis. Following intraperitoneal dosing in rats and intravenous dosing in rabbits, maternal exposures were equivalent to 0.5, 1, or 2 times the human exposure at the therapeutic dose (based on AUC). In the high dose groups for both species, maternal toxicity occurred, and there was a reduced number of live fetuses due to embryofetal resorptions. In addition, decreased live fetal weight occurred in high dose rats, but not in rabbits. Incomplete skeletal ossification occurred in both rats and rabbits. In rats, two fetuses of the high dose group and two fetuses of the mid dose group (each from a different litter) had short, rudimentary or small front or hind legs. Rabbit litters and fetuses exhibited a dose dependant increase in various gross soft tissue and skeletal anomalies. The main findings in rabbits were flexed, rigid flexor or medially rotated forelimbs or hindlimbs and domed heads at external examination; enlarged anterior or posterior fontanelles of the ventricles of the brain and flat, bowed or large ribs at skeletal examination; and dilated ventricles of the brain, and thick wall of the stomach at visceral examination. Labor and Delivery The effect of Cyanokit on labor and delivery is unknown. Nursing Mothers It is not known whether hydroxocobalamin is excreted in human milk. Cyanokit may be administered in life-threatening situations, and therefore, breast-feeding is not a contraindication to its use. Because of the unknown potential for adverse reactions in nursing infants, the patient should discontinue nursing after receiving Cyanokit.. Pediatric Use Safety and effectiveness of Cyanokit have not been established in this population. In non-US marketing experience, a dose of 70 mg/kg has been used to treat pediatric patients. Geriatric Use Approximately 50 known or suspected cyanide poisoning victims aged 65 or older received hydroxocobalamin in clinical studies. In general, the safety and effectiveness of hydroxocobalamin in these patients was similar to that of younger patients. No adjustment of dose is required in elderly patients. 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. Oxalate crystals have been observed in the urine of both healthy subjects given hydroxocobalamin and patients treated with hydroxocobalamin following suspected cyanide poisoning. Hepatic Impairment The safety and effectiveness of Cyanokit have not been studied in patients with hepatic impairment.Last reviewed on RxList: 5/26/2011
This monograph has been modified to include the generic and brand name in many instances.