ThisiscontentfromElsevier'sDrugInformation
Hydroxocobalamin
Learn more about Elsevier's Drug Information today! Get the drug data and decision support you need, including TRUE Daily Updates™ including every day including weekends and holidays.
NOTE: Administer hydroxocobalamin without delay if clinical suspicion of cyanide poisoning is high. Administer in conjunction with airway, ventilatory, and circulatory support as well as management of seizures.[33229]
5 g IV infused over 15 minutes. A second 5 g dose infused over 15 minutes to 2 hours (depending on patient status), for a total to 10 g, may be administered based on clinical response and severity of cyanide poisoning.[33229]
70 mg/kg/dose (Max: 5 g/dose) IV infused over 15 minutes. A second 70 mg/kg/dose (Max: 5 g/dose) infused over 15 minutes to 2 hours (depending on patient status), for a total of 140 mg/kg (Max: 10 g), may be administered based on clinical response and severity of cyanide poisoning.[67134] [67135]
1,000 mcg IM once daily or every other day for 1 week, then once weekly for 4 to 8 weeks, then monthly until recovery.[43996] [43997] [60922] 30 mcg IM once daily for 5 to 10 days followed by 100 to 200 mcg IM once monthly is the FDA-approved dosage.[33665]
1,000 mcg IM once daily or every other day for 1 week, then once weekly for 4 to 8 weeks, then monthly until recovery.[43997] [60922] 100 mcg IM once daily over a period of 2 or more weeks (total of 1 to 5 mg) then 30 to 50 mcg IM every 4 weeks is the FDA-approved dosage.[33665]
Dosing is not well established in pediatric patients; guide by clinical response and laboratory measurements.[60926] [60930] 1,000 mcg IM once daily for 2 to 7 days, then 100 mcg IM once weekly for 4 weeks, then 100 mcg IM once monthly until recovery has been recommended and used in children.[60922] [60925] [60928] [60929] [60930] The adult dosage (1,000 mcg IM once daily or every other day for 1 week, then once weekly for 4 to 8 weeks, then monthly) has also been used in children.[60922] [60939] [62570] 100 mcg IM once daily over a period of 2 or more weeks (total of 1 to 5 mg) then 30 to 50 mcg IM every 4 weeks is the FDA-approved dosage.[33665]
Dosing is not well established in pediatric patients; guide by clinical response and laboratory measurements.[60926] [60930] 250 to 1,000 mcg IM once daily for 4 to 10 days then 100 to 1,000 mcg IM once weekly or monthly until recovery has been recommended and used in infants.[60922] [60923] [60924] [60925] [60937] [60942] [62570] 100 mcg IM once daily over a period of 2 or more weeks (total of 1 to 5 mg) then 30 to 50 mcg IM every 4 weeks is the FDA-approved dosage.[33665]
1,000 mcg IM once daily or every other day for 1 week, then once weekly for 4 to 8 weeks, then monthly for life is the usual dosage.[43996] [43997] [60922] 30 mcg IM once daily for 5 to 10 days then 100 to 200 mcg IM once monthly is the FDA-approved dosage. Administer with folic acid, if needed.[33665]
1,000 mcg IM once daily or every other day for 1 week, then once weekly for 4 to 8 weeks, then monthly for life is the usual dosage.[43997] [60922] 100 mcg IM once daily over a period of 2 or more weeks (total of 1 to 5 mg) then 30 to 50 mcg IM every 4 weeks is the FDA-approved dosage. Administer with folic acid, if needed.[33665]
Dosing is not well established in pediatric patients; guide by clinical response and laboratory measurements.[60926] [60930] 1,000 mcg IM once daily for 2 to 7 days, then 100 mcg IM once weekly for 4 weeks, then 100 mcg IM monthly has been recommended and used in children.[60922] [60925] [60928] [60929] [60930] The adult dosage (1,000 mcg IM once daily or every other day for 1 week, then once weekly for 4 to 8 weeks, then monthly) has also been used in children.[60922] [60926] [60939] [60941] [62570] 100 mcg IM once daily over a period of 2 or more weeks (total of 1 to 5 mg) then 30 to 50 mcg IM every 4 weeks is the FDA-approved dosage. Administer with folic acid, if needed.[33665]
Dosing is not well established in pediatric patients; guide by clinical response and laboratory measurements.[60926] [60930] 250 to 1,000 mcg IM once daily for 4 to 10 days then 100 to 1,000 mcg IM once weekly or monthly has been recommended and used in infants in case reports.[60922] [60923] [60924] [60925] [60937] [60942] [62570] 100 mcg IM once daily over a period of 2 or more weeks (total of 1 to 5 mg) then 30 to 50 mcg IM every 4 weeks is the FDA-approved dosage. Administer with folic acid, if needed.[33665]
1,000 to 2,000 mcg/day IM initially. Adjust dosage and frequency based on clinical and laboratory response.[33666] [33667] [33668] [33669]
1,000 to 2,000 mcg/day IM initially, with infants and children started at the lower end of the dosage range. Adjust dosage and frequency based on clinical and laboratory response.[33666] [33667] [33668] [33669]
1,000 mcg IM once is the flushing dose for Schilling test/vitamin B12 absorption test.[33665]
30 mcg/day IM, followed by 200 mcg/month IM is FDA-approved maximum; however, doses up to 2,000 mcg/day IM are used off-label; 10 g IV (total dose) for cyanide poisoning.
30 mcg/day IM, followed by 200 mcg/month IM is FDA-approved maximum; however, doses up to 2,000 mcg/day IM are used off-label; 10 g IV (total dose) for cyanide poisoning.
100 mcg/day IM, followed by 50 mcg/month IM is FDA-approved maximum; however, doses up to 2,000 mcg/day IM are used off-label; 140 mg/kg (Max: 10 g) IV total dose has been used off-label for cyanide poisoning.
100 mcg/day IM, followed by 50 mcg/month IM is FDA-approved maximum; however, doses up to 2,000 mcg/day IM are used off-label; 140 mg/kg (Max: 10 g) IV total dose has been used off-label for cyanide poisoning.
100 mcg/day IM, followed by 50 mcg/month IM is FDA-approved maximum; however, doses up to 2,000 mcg/day IM are used off-label; 140 mg/kg (Max: 10 g) IV total dose has been used off-label for cyanide poisoning.
Specific guidelines for dosage adjustments in hepatic impairment are not available; it appears that no dosage adjustments are needed.
Hydroxocobalamin and cyanocobalamin are excreted unchanged in the urine. In studies, oxalate crystals have been found in the urine of both healthy patients and those being treated for cyanide poisoning. Specific guidelines for dosage adjustments in renal impairment are not available; it appears that no dosage adjustments are needed.
Hemodialysis
Specific guidelines are not available; it appears that no dosage adjustments are needed.
† Off-label indication
Hydroxocobalamin is a parenteral preparation of vitamin B12; specifically, it is the hydroxylated active form of vitamin B12. Hydroxocobalamin is used to treat known or suspected cyanide toxicity. Cyanide toxicity can occur from inhalation, ingestion, or exposure of the skin to various cyanide-containing compounds, including smoke inhalation from confined space fires. Sources of cyanide toxicity include hydrogen cyanide and its salts, cyanogenic plants, aliphatic nitriles, and prolonged therapy with sodium nitroprusside. Unlike other treatments for cyanide toxicity, amyl nitrite and sodium nitrite, hydroxocobalamin does not cause methemoglobinemia or hypotension. In addition, hydroxocobalamin has been shown to bind both intra- and extracellular cyanide. Hydroxocobalamin is also used to treat megaloblastic anemia, pernicious anemia, and other states of vitamin B12 deficiencies. Vitamin B12 is essential to growth, cell reproduction, hematopoiesis, and nucleoprotein and myelin synthesis. Vitamin B12 is an essential vitamin found in foods such as meat, eggs, and dairy products. Deficiency in healthy individuals is rare; the elderly, strict vegetarians (i.e., vegan), and patients with malabsorption problems are more likely to become deficient. If vitamin B12 deficiency is not treated with a vitamin B12 supplement, then anemia, intestinal problems, and irreversible nerve damage may occur. Oral therapy is not always effective, as some persons lack intrinsic factor, an endogenous substance produced by the stomach and necessary for oral B12 absorption. Other patients may not be able to absorb oral vitamin B12 due to surgical removal or dysfunction of the intestines in the area where absorption of vitamin B12 occurs. Thus, parenteral therapy may be required. Hydroxocobalamin was FDA-approved in 1975. Cyanokit was FDA approved December 2006.[33229]
For storage information, see the specific product information within the How Supplied section.
Reconstitution of Cyanokit
IV Infusion of Cyanokit
Hydroxocobalamin 1,000 mcg/mL injection
Among healthy adults enrolled in a double-blind study conducted to assess the safety, tolerability, and pharmacokinetics of intravenous hydroxocobalamin, the 2 most commonly reported adverse reactions among patients who received hydroxocobalamin were urine discoloration (red colored urine or chromaturia) and erythema or red skin discoloration. Urine discoloration occurred in all patients that received hydroxocobalamin and lasted from 7 to 35 days after administration; there were no occurrences among the placebo patients. In patients who received hydroxocobalamin, red skin discoloration occurred in 94% who received a 5 g dose and 100% of those who received either a 7.5 g or 10 g dose. The skin redness was noted to begin to appear approximately 11 to 13 minutes after the start of the infusion and lasted for an average of 4 to 9 days.[33229] [33670]
In a double-blind study of healthy adults conducted to assess the safety, tolerability, and pharmacokinetics of intravenous hydroxocobalamin, 2 patients developed an allergic reaction, 1 each with the 5 g and 10 g dosages.[33229] [33670] The allergic reactions occurred within 5 to 10 minutes after the start of the infusion with symptoms including pruritus, facial erythema, facial papulae, eye swelling and reddening, shivering, dyspnea, facial edema, spontaneous exanthema, urticaria, and wheals. The patient receiving the 10-gram dose was unable to complete the infusion secondary to the allergic reaction and only received 3.9 g of hydroxocobalamin.[33670] It should be noted that in the trial pruritus was reported in 2% of patients who received the 5 g dose and in 17% of patients who received the 10 g dose.[33229] [33670] Anaphylactoid reactions (anaphylaxis) and pruritus have also been reported with intramuscular administration of hydroxocobalamin.[33665]
In a double-blind study of healthy adults conducted to assess the safety, tolerability, and pharmacokinetics of intravenous hydroxocobalamin, nausea and vomiting were reported as an adverse reaction in the 5 g dose group (nausea 6%; vomiting frequency not reported) and in the 10 g dose group (nausea 11%; vomiting frequency not reported). Dysphagia was reported in 22% of patients who received the 10 g dose; it was not reported in patients who received the 5 g dose. Abdominal pain or discomfort, diarrhea, and dyspepsia were also reported.[33229] [33670]
In a double-blind study of healthy adults conducted to assess the safety, tolerability, and pharmacokinetics of intravenous hydroxocobalamin, headache was reported in 6% of patients who received the 5 g dose and in 33% of patients who received the 10 g dose. Dizziness and restlessness were also reported.[33229] [33670]
In a double-blind study of healthy adults conducted to assess the safety, tolerability, and pharmacokinetics of intravenous hydroxocobalamin, lymphopenia was reported in 8% of patients who received the 5 g dose and in 17% of patients who received the 10 g dose.[33229] [33670]
In a double-blind study of healthy adults conducted to assess the safety, tolerability, and pharmacokinetics of intravenous hydroxocobalamin, injection site reaction was reported in 6% of patients who received the 5 g dose and in 39% of patients who received the 10 g dose.[33229] [33670] Pain at the injection site has been reported with intramuscular administration of hydroxocobalamin.[33665]
In a double-blind study of healthy adults conducted to assess the safety, tolerability, and pharmacokinetics of intravenous hydroxocobalamin (Cyanokit), hot flashes or flushes were reported.[33229] [33670]
In a double-blind study of healthy adults conducted to assess the safety, tolerability, and pharmacokinetics of intravenous hydroxocobalamin (Cyanokit), rash was reported in 13 (20%) and 8 (44%) patients in the hydroxocobalamin 5 gram and 10 gram groups, respectively. Of the 21 patients who developed a rash with either dose, 14 (11 with 5 gram and 3 with 10 gram) developed a pustular rash that was primarily located on the face and neck. The pustular rash typically occurred 7 to 25 days after the infusion and lasted for 6 to 38 days. Three patients (17%) who received 10 grams of hydroxocobalamin developed a papular rash.[33670]
In a double-blind study of healthy adults conducted to assess the safety, tolerability, and pharmacokinetics of intravenous hydroxocobalamin, hypertension was reported with clinically significant increases in diastolic blood pressure reported in 12 (18%) and 5 (28%) of patients who received hydroxocobalamin doses of 5 grams and 10 grams, respectively. Of these 17 patients, only 2 patients also had clinically relevant increases in systolic pressure; no patient had only elevated systolic blood pressure. Clinical significance was defined as a systolic blood pressure greater than 179 mmHg or diastolic blood pressure greater than 109 mmHg. A majority of these events occurred during the infusion, ranging from 5 to 25 minutes after the start of the infusion. Four patients experienced increased blood pressure after the infusion had ended, occurring 10 minutes to 72 hours after the infusion. Of those patients who developed hypertension during the hydroxocobalamin infusion, blood pressures were found to return to baseline within 20 minutes to 4 hours post-infusion. The maximum mean increase was 14.3 to 25.4 mmHg and 22.6 to 27 mmHg for diastolic blood pressure and systolic blood pressure, respectively. Pulse rates were found to decrease in correspondence with the increased blood pressure. The maximum mean change from baseline pulse rate was -12.6 with the 5 gram dose and -14.2 with the 10 gram dose. Pulse rates returned to baseline within 2 to 3 hours post-infusion.[33670]
Adverse reactions reported in uncontrolled, clinical studies of hydroxocobalamin, involving patients being treated for cyanide poisoning (frequency not reported) included: ventricular tachycardia or extrasystoles, electrocardiogram repolarization abnormality, increased heart rate, and pleural effusion.[33229] In a double-blind study of healthy adults conducted to assess the safety, tolerability, and pharmacokinetics of intravenous hydroxocobalamin, chest discomfort was reported in 5% of patients who received the 5 g dose and in 11% of patients who received the 10 g dose. Peripheral edema was also reported.[33229] [33670]
Postmarketing reports have associated intravenous hydroxocobalamin therapy with the development of renal failure (unspecified) and renal tubular necrosis, renal impairment, and crystalluria (i.e., urine calcium oxalate crystals). In some of these cases, hemodialysis was required to achieve recovery.[33229]
Hydroxocobalamin is contraindicated in patients with a known hydroxocobalamin hypersensitivity, in patients with hypersensitivity, allergy, or anaphylactic reaction to the drug or to any of the formulation components, or in patients who have known cyanocobalamin or cobalt hypersensitivity.[33229][33665]
Following reconstitution, hydroxocobalamin forms a deep red solution, which has greatest absorption at wavelengths routinely used in colorimetric assays.[33229][33672] Secondary to this deep red color and wavelength absorption, hydroxocobalamin administration may interfere with the colorimetric interpretation of certain laboratory assays for 2—3 days or longer after administration. Based on results of both in vitro and pharmacokinetic studies, falsely elevated levels of creatinine, triglycerides, cholesterol, total protein, glucose, albumin, and alkaline phosphatase have been observed for 24 hours after administration of hydroxocobalamin 5 g or 10 g.[33229] Falsely elevated levels of bilirubin have been found to occur up to 4 days after hydroxocobalamin administration. Levels of hemoglobin, MCH, MCHC, and basophils were observed to be falsely increased for 12—16 hours after hydroxocobalamin administration. Falsely decreased levels of ALT and amylase were noted within 24 hours of hydroxocobalamin use. Hydroxocobalamin had an unpredictable impact, lasting 24—48 hours, on the following assays: phosphate, uric acid, AST, CK, CKMB, LDH, aPTT, and PT. Hydroxocobalamin has been found to interfere with urinalysis resulting in falsely elevated pH, glucose, protein, erythrocytes, leukocytes, ketones, bilirubin, urobiliongen, and nitrite. Urinary pH has also been found to be falsely decreased with hydroxocobalamin doses < 5 g. These interferences with urinalysis may occur 8 to 28 days after hydroxocobalamin administration. It is important to note that there are some factors that may influence the extent and duration of these interferences, which include hydroxocobalamin dose, type of analyzer used, and time between sampling and measurement. Utilize caution when reporting and interpreting laboratory results. Based on the results of one experimental study performed on rabbits, hydroxocobalamin may have the potential to interfere with cooximetry blood gas measurements; specifically carboxyhemoglobin, methemoglobin, and oxyhemoglobin.[33673] Practitioners may want to be aware of this potential interaction when treating victims of smoke inhalation who may be suffering from both cyanide and carbon monoxide poisoning.
It is important to start treatment early in patients with cyanide poisoning; thus, supportive care and hydroxocobalamin (Cyanokit) therapy should be initiated in patients with known or suspected cyanide poisoning prior to obtaining blood cyanide assay results. Prior to administration of the antidote, a blood sample should be taken and sent for assay to determine the cyanide concentration. Treatment of cyanide poisoning includes supportive therapy, such as cardiovascular support, airway/ventilation management, control of seizure activity, and hydration in addition to the use an antidote, such as hydroxocobalamin (Cyanokit).[33229]
Hydroxocobalamin therapy is associated with the development of erythema. Hydroxocobalamin has been found to absorb visible UV light; thus, therapy with this medication may cause photosensitivity. It is unknown whether the hydroxocobalamin-induced erythema increases the risk for photosensitivity; however, it is recommended that patients avoid direct sunlight until the redness has resolved.[33229]
Vitamin B12 deficiency can suppress the symptoms of polycythemia vera. Treatment with hydroxocobalamin, or cyanocobalamin, may unmask this condition.[33665]
It may be prudent to carefully monitor patients with hypertension during intravenous (IV) administration of hydroxocobalamin, as hypertension or increases in blood pressure have been reported.[33229] In a study conducted to evaluate the safety of hydroxocobalamin in healthy patients, 18% of patients who received 5 grams IV and 28% of patients who received 10 grams IV were found to have an elevation in blood pressure. The blood pressure began to elevate soon after the infusion was started and peaked near the end of the infusion.[33670] Blood pressures were typically found to return to baseline approximately 4 hours after the end of the infusion.
Postmarketing reports have associated intravenous hydroxocobalamin therapy with the development of acute renal failure with tubular necrosis, renal impairment, and urine calcium oxalate crystals. In some of these cases, hemodialysis was required to achieve recovery. Healthcare providers are advised to monitor the drug recipients renal function during and for 7 days following administration of hydroxocobalamin. Hydroxocobalamin and cyanocobalamin are excreted unchanged in the urine; therefore, cause is advised when administering the drug to patients with preexisting renal impairment. Also, the presence of uremia or renal failure may blunt or impede therapeutic response to hydroxocobalamin therapy; the mechanism appears to be interference with erythropoiesis. Caution is also advised when administering the drug to patients receiving dialysis, as the deep red color of hydroxocobalamin may cause dialysis machines to shut down due to erroneous detection of a blood leak.[33229] [33665]
Certain conditions may blunt or impede therapeutic response to hydroxocobalamin therapy, such as serious infection or drugs with bone marrow suppression properties (e.g., chloramphenicol).[33665] The mechanism appears to be interference with erythropoiesis.
Folic Acid, vitamin B9 is not a substitute for hydroxocobalamin in the treatment of vitamin B12 deficiency. While it may improve vitamin B12 megaloblastic anemia, exclusive use of folic acid in treating vitamin B12 deficient megaloblastic anemia could result in progressive and irreversible neurologic damage.[33665] Before receiving folic acid or hydroxocobalamin, patients should be assessed for deficiency and appropriate therapy started concurrently. Concurrent iron-deficiency anemia and folic acid deficiency may result in a blunted or impeded response to hydroxocobalamin therapy. Secondary to an increase in red cell production with hydroxocobalamin therapy there is a corresponding increase in iron requirements; thus, patients should be closely monitored for the development of iron deficiency and treated accordingly.[33671]
Concurrent undiagnosed anemia due to folate deficiency may blunt or impede therapeutic response to hydroxocobalamin therapy.[33665] The mechanism appears to be interference with erythropoiesis. Additionally, hydroxocobalamin, vitamin B12 is not a substitute for folic acid, vitamin B9 in the treatment of folate deficiency. While it may improve folic acid megaloblastic anemia, exclusive use of hydroxocobalamin in treating folate deficient megaloblastic anemia could delay or mask the real diagnosis.[33665]
Treatment of severe megaloblastic anemia with hydroxocobalamin results in the conversion to normal erythropoiesis. The change to normal erythropoiesis may cause secondary development of hypokalemia and thrombocytosis, therefore, potassium levels and platelet counts should be closely monitored.[33665]
Safety and efficacy of hydroxocobalamin therapy in the treatment of cyanide poisoning in children has not been adequately studied.[33229] In France, hydroxocobalamin 70 mg/kg has been used for the treatment of children with cyanide poisoning.[33662] Use of hydroxocobalamin in children for certain vitamin B12 deficiency states has been established; see dosage.
Adequate and well-controlled studies have not been conducted regarding the use of hydroxocobalamin during human pregnancy; data are insufficient to adequately assess the risk of birth defects, miscarriages, or adverse maternal or fetal outcomes. Hydroxocobalamin should only be administered during pregnancy when the benefit outweighs the potential for fetal risk.[33229] [33665] If an antidote is indicated for treatment of poisoning, the antidote should generally not be withheld because of pregnancy. Toxicity to the mother is a major determinant of fetal risk after cyanide exposure. For vitamin B12 supplementation, cyanocobalamin has been used within the recommended dietary intakes (RDIs) for pregnancy without harmful effects noted, and should be considered a preferred alternative for that indication. Vitamin B12 is an essential vitamin and requirements are increased during pregnancy. Amounts of vitamin B12 that are recommended by the Food and Nutrition Board, National Academy of Science-National Research Council for pregnant women should be consumed during pregnancy.[49235]
Hydroxocobalamin and cyanocobalamin are excreted in human breast milk. The manufacturer recommends mothers who receive hydroxocobalamin to treat cyanide poisoning avoid breast-feeding their infants. There are no data to determine when nursing can be reinitiated after administration of hydroxocobalamin.[33229] Cyanocobalamin is usually the preferred form of vitamin B12 supplementation if a patient is vitamin deficient; follow current recommendations for recommended dietary intakes (RDIs) during lactation for patients who are not deficient. There are no known harmful effects of vitamin B12 products during breast-feeding that have been reported.[27500] [49235]
Hydroxocobalamin, vitamin B12 is essential to growth, cell reproduction, hematopoiesis, and nucleoprotein and myelin synthesis. Cells characterized by rapid division (epithelial cells, bone marrow, myeloid cells) appear to have the greatest requirement for vitamin B12. Vitamin B12 can be converted to coenzyme B12 in tissues; in this form it is essential for conversion of methylmalonate to succinate and synthesis of methionine from homocysteine (a reaction which is also accompanied by the conversion of methyltetrahydrofolate to tetrahydrofolate). In the absence of coenzyme B12, tetrahydrofolate cannot be regenerated from its inactive storage form, 5-methyl tetrahydrofolate, resulting in functional folate deficiency. Vitamin B12 also may be involved in maintaining sulfhydryl (SH) groups in the reduced form required by many SH-activated enzyme systems. Through these reactions, vitamin B12 is associated with fat and carbohydrate metabolism and protein synthesis. Vitamin B12 deficiency results in megaloblastic anemia, GI lesions, and neurologic damage (which begins with an inability to produce myelin and is followed by gradual degeneration of the axon and nerve head). Vitamin B12 requires an intrinsic factor-mediated active transport for absorption, therefore, lack of or inhibition of intrinsic factor results in pernicious anemia.
Cyanide binds to the ferric ion on the cytochrome oxidase enzyme, cytochrome a3; thus, inhibiting the function of the enzyme and preventing cellular use of oxygen.[33229][33661][33662][33663] Secondary to the inhibition of cytochrome a3 and inability of the cell to utilize oxygen, it switches from aerobic to anaerobic production of adenosine triphosphate (ATP). Anaerobic metabolism favors lactate production over ATP leading to cellular hypoxia and metabolic acidosis. Hydroxocobalamin combines with cyanide to form cyanocobalamin, which is nontoxic and excreted in the urine. Specifically, the cyanide ion replaces the hydroxo ligand to form cyanocobalamin. Each hydroxocobalamin molecule binds one molecule of cyanocobalamin. Based on the molecular weight ratio of 50:1, 5 g hydroxocobalamin will bind 250 mg cyanide.[33229][33661] Patients receiving hydroxocobalamin therapy for the treatment of known or suspected cyanide poisoning should also receive aggressive supportive care (ventilatory support, oxygen, and cardiovascular support).
Revision Date: 01/11/2024, 04:54:00 PMHydroxocobalamin is administered intravenously or intramuscularly. For the treatment of cyanide poisoning, hydroxocobalamin is administered as an intravenous infusion (IV). For the treatment of pernicious anemia, megaloblastic anemia, and vitamin B12 deficiencies and related syndromes, hydroxocobalamin is administered as an intramuscular injection (IM). Hydroxocobalamin significantly binds to plasma proteins.
Following IV administration, the mean volume of distribution was 0.19—0.3 L/kg in healthy volunteers and 0.45 L/kg in smoke inhalation victims.[33661][33664] The mean half-life following IV administration was 1.6—5.4 hours in healthy volunteers compared to 26—31 hours in smoke inhalation victims.[33229][33661][33664] Following administration during in vitro studies, a 75% reduction of intracellular cyanide was observed along with the intracellular formation of cyanocobalamin; thus, hydroxocobalamin is thought to also work intracellularly.[33661][33663] Hydroxocobalamin was found to cross the blood-brain barrier and enter the cerebrospinal fluid of animals utilized in an experimental study.[33661] Following IV infusion, the primary route of hydroxocobalamin excretion was found to be in the urine with 60% of the 5 g dose and 50% of the 10 g dose appearing in the urine within 72 hours of administration; urinary excretion accounts for a total of 60—70% of the administered dose. A majority of the urinary excretion occurs within the first 24 hours after administration.
Following IM administration, approximately 50% of the dose remains at the injection site 2.5 hours after administration.[33665] Once absorbed, hydroxocobalamin (vitamin B12) is highly bound to transcobalamin II, a specific B-globulin carrier protein and is distributed and stored primarily in the liver as coenzyme B12. The bone marrow also stores a significant amount of the absorbed vitamin B12. This vitamin crosses the placenta and is distributed into breast milk. Enterohepatic recirculation conserves systemic stores. Hydroxocobalamin is excreted in both the bile and urine. Following the IM administration of 500—1000 mcg, 16—66% of the dose was excreted in the urine within 72 hours. Similar to IV administration, a majority of the urinary excretion occurs within the first 24 hours after IM administration.
Adequate and well-controlled studies have not been conducted regarding the use of hydroxocobalamin during human pregnancy; data are insufficient to adequately assess the risk of birth defects, miscarriages, or adverse maternal or fetal outcomes. Hydroxocobalamin should only be administered during pregnancy when the benefit outweighs the potential for fetal risk.[33229] [33665] If an antidote is indicated for treatment of poisoning, the antidote should generally not be withheld because of pregnancy. Toxicity to the mother is a major determinant of fetal risk after cyanide exposure. For vitamin B12 supplementation, cyanocobalamin has been used within the recommended dietary intakes (RDIs) for pregnancy without harmful effects noted, and should be considered a preferred alternative for that indication. Vitamin B12 is an essential vitamin and requirements are increased during pregnancy. Amounts of vitamin B12 that are recommended by the Food and Nutrition Board, National Academy of Science-National Research Council for pregnant women should be consumed during pregnancy.[49235]
Hydroxocobalamin and cyanocobalamin are excreted in human breast milk. The manufacturer recommends mothers who receive hydroxocobalamin to treat cyanide poisoning avoid breast-feeding their infants. There are no data to determine when nursing can be reinitiated after administration of hydroxocobalamin.[33229] Cyanocobalamin is usually the preferred form of vitamin B12 supplementation if a patient is vitamin deficient; follow current recommendations for recommended dietary intakes (RDIs) during lactation for patients who are not deficient. There are no known harmful effects of vitamin B12 products during breast-feeding that have been reported.[27500] [49235]
Cookies are used by this site. To decline or learn more, visit our cookie notice.
Copyright © 2024 Elsevier, its licensors, and contributors. All rights are reserved, including those for text and data mining, AI training, and similar technologies.
