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Hidroksikobalamin

Clinical Effects:

HYDROXOCOBALAMIN
  • USES: Hydroxocobalamin is an antidote approved for the treatment of known or suspected cyanide poisoning. This product is not to be confused with commercially available hydroxocobalamin preparation (1000 mcg/mL for intramuscular injection) used for the treatment of cobalamin deficiency. This product is not intended for use in the treatment of cyanide poisoning. It would require 4 to 5 liters of this preparation for an adequate antidote dose, and therefore this product should NOT be used. PHARMACOLOGY: Hydroxocobalamin is a vitamin B12a precursor. This cobalt-centered metalloprotein complexes with cyanide on a one-to-one molar ratio to form cyanocobalamin (vitamin B12), which is excreted renally. Hydroxocobalamin reactivates the mitochondrial enzymes involved in the respiratory process. EPIDEMIOLOGY: Overdose is rare. OVERDOSE: Limited overdose data available. Overdose effects are expected to be an extension of adverse effects reported with therapeutic use. ADVERSE EFFECTS: MOST COMMON (greater than 5%): Transient chromaturia, erythema, rash, increased blood pressure, nausea, headache, and injection site reactions. OTHER EFFECTS: Peripheral edema, dizziness, allergic reactions, urticaria, pruritus, and pink or reddish discoloration of skin and mucous membranes.

Range of Toxicity:

HYDROXOCOBALAMIN
  • TOXICITY: Overdose data are limited. No lethal human doses have been reported. Range of toxicity is not well described. Up to 15 grams have been given with no adverse effects reported. THERAPEUTIC DOSES: ADULT: 5 g IV over 15 min (approximately 15 mL/min), may repeat an additional 5 g IV over 15 min to 2 hours as needed, for a total dose of 10 g. PEDIATRIC: In a non-US marketing experience, hydroxocobalamin 70 mg/kg was used to treat pediatric patients with cyanide toxicity. Additional doses may be given in cases of severe cyanide poisoning.

Treatment:

HYDROXOCOBALAMIN
  • Support: MANAGEMENT OF MILD TO MODERATE TOXICITY: Treatment is symptomatic and supportive. Hypertension associated with infusion is generally mild and resolves within 4 hours of completion of infusion. Therapy is generally not necessary. MANAGEMENT OF SEVERE TOXICITY: Treatment is symptomatic and supportive. In patients with acute allergic reaction, oxygen therapy, bronchodilators, diphenhydramine, corticosteroids, vasopressors and epinephrine may be required. Refer to “Cyanide” management for further information on the treatment of cyanide exposures.
  • Decontamination: Administered intravenously; ingestion is unlikely; decontamination is not necessary.
  • Airway management: Ensure adequate ventilation and perform endotracheal intubation early in patients with severe allergic reactions.
  • Antidote: None
  • Acute allergic reaction: Mild to moderate allergic reactions may be treated with antihistamines with or without inhaled beta agonists, corticosteroids or epinephrine. Treatment of severe anaphylaxis also includes oxygen supplementation, aggressive airway management, epinephrine, ECG monitoring, and IV fluids.
  • Monitoring of patient: No specific laboratory tests are needed in patients exposed to hydroxocobalamin who are NOT also cyanide poisoned. Monitor blood pressure and heart rate during infusion of hydroxocobalamin. Laboratory tests should include serum electrolytes for assessment of renal function and hydration status. In suspected cyanide exposures, initial laboratory tests should include CBC, arterial and venous blood gases, serum electrolytes and lactate, assessment of renal function, chest x-ray (following inhalation exposure or if the patient has abnormal respiratory signs and symptoms), and whole blood cyanide levels. Refer to “Cyanide” management for further information on the treatment of cyanide exposures.
  • Enhanced elimination procedure: Hemodialysis may be effective in the event of significant toxicity from hydroxocobalamin or overdose; however, hydroxocobalamin has a deep red color which can interfere with the performance of hemodialysis machines.
  • Patient disposition: HOME CRITERIA: There is no role for home management of patients with hydroxocobalamin overdose after cyanide exposure. A patient with an inadvertent exposure to just hydroxocobalamin (without cyanide exposure), that remains asymptomatic can be managed at home. OBSERVATION CRITERIA: Patients with a deliberate overdose, and those who are symptomatic, need to be monitored for several hours. Any exposure to cyanide salts or cyanide gas should be referred to a healthcare facility. Patients who remain asymptomatic with normal laboratory studies can be discharged after 6 hours. ADMISSION CRITERIA: Patients who remain symptomatic despite treatment should be admitted. Any patient with symptomatic poisoning should be admitted to an intensive care unit. CONSULT CRITERIA: Consult a regional poison center or medical toxicologist for assistance in managing symptomatic patients.
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