Details
Stereochemistry | ACHIRAL |
Molecular Formula | C62H88N13O14P.Co.HO |
Molecular Weight | 1346.3551 |
Optical Activity | UNSPECIFIED |
Additional Stereochemistry | Yes |
Defined Stereocenters | 14 / 14 |
E/Z Centers | 0 |
Charge | 0 |
Stereo Comments | Octahedral trans |
SHOW SMILES / InChI
SMILES
[OH-].[Co+3].[H][C@]12[N-]C(=C(C)C3=NC(=CC4=NC(=C(C)C5=N[C@]1(C)[C@@](C)(CC(N)=O)[C@@H]5CCC(N)=O)[C@@](C)(CC(N)=O)[C@@H]4CCC(N)=O)C(C)(C)[C@@H]3CCC(N)=O)[C@](C)(CCC(=O)NC[C@@H](C)OP([O-])(=O)O[C@@H]6[C@@H](CO)O[C@@H]([C@@H]6O)N7C=NC8=C7C=C(C)C(C)=C8)[C@H]2CC(N)=O
InChI
InChIKey=YOZNUFWCRFCGIH-WZHZPDAFSA-K
InChI=1S/C62H90N13O14P.Co.H2O/c1-29-20-39-40(21-30(29)2)75(28-70-39)57-52(84)53(41(27-76)87-57)89-90(85,86)88-31(3)26-69-49(83)18-19-59(8)37(22-46(66)80)56-62(11)61(10,25-48(68)82)36(14-17-45(65)79)51(74-62)33(5)55-60(9,24-47(67)81)34(12-15-43(63)77)38(71-55)23-42-58(6,7)35(13-16-44(64)78)50(72-42)32(4)54(59)73-56;;/h20-21,23,28,31,34-37,41,52-53,56-57,76,84H,12-19,22,24-27H2,1-11H3,(H15,63,64,65,66,67,68,69,71,72,73,74,77,78,79,80,81,82,83,85,86);;1H2/q;+3;/p-3/t31-,34-,35-,36-,37+,41-,52-,53-,56-,57+,59-,60+,61+,62+;;/m1../s1
Molecular Formula | C62H88N13O14P |
Molecular Weight | 1270.4146 |
Charge | -2 |
Count |
|
Stereochemistry | ABSOLUTE |
Additional Stereochemistry | No |
Defined Stereocenters | 14 / 14 |
E/Z Centers | 0 |
Optical Activity | UNSPECIFIED |
Molecular Formula | HO |
Molecular Weight | 17.0073 |
Charge | -1 |
Count |
|
Stereochemistry | ACHIRAL |
Additional Stereochemistry | No |
Defined Stereocenters | 0 / 0 |
E/Z Centers | 0 |
Optical Activity | NONE |
Molecular Formula | Co |
Molecular Weight | 58.9332 |
Charge | 3 |
Count |
|
Stereochemistry | ACHIRAL |
Additional Stereochemistry | No |
Defined Stereocenters | 0 / 0 |
E/Z Centers | 0 |
Optical Activity | NONE |
DescriptionSources: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=39de0239-a4f6-45b0-a3cf-c6fba941c08ehttp://www.accessdata.fda.gov/drugsatfda_docs/label/2011/022041s008s009lbl.pdfCurator's Comment: description was created based on several sources, including
Sources: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=39de0239-a4f6-45b0-a3cf-c6fba941c08ehttp://www.accessdata.fda.gov/drugsatfda_docs/label/2011/022041s008s009lbl.pdf
Curator's Comment: description was created based on several sources, including
Hydroxocobalamin (also hydroxycobalamin, OHCbl) is a natural form, or vitamer, of vitamin B12. It is a member of the cobalamin family of compounds. Hydroxocobalamin, the active ingredient in Cyanokit, is cobinamide dihydroxide dihydrogen phosphate (ester), mono (inner salt), 3’-ester with 5,6-dimethyl-1-α-D-ribofuranosyl-1H-benzimidazole. The drug substance is the hydroxylated active form of vitamin B12 and is a large molecule in which a trivalent cobalt ion is coordinated in four positions by a tetrapyrol (or corrin) ring. It is a hygroscopic, odorless, dark red, crystalline powder that is freely soluble in water and ethanol, and practically insoluble in acetone and diethyl ether. Cyanokit contains hydroxocobalamin, an antidote indicated for the treatment of known or suspected cyanide poisoning. Cyanide is an extremely toxic poison. In the absence of rapid and adequate treatment, exposure to a high dose of cyanide can result in death within minutes due to the inhibition of cytochrome oxidase resulting in arrest of cellular respiration. Specifically, cyanide binds rapidly with cytochrome a3, a component of the cytochrome c oxidase complex in mitochondria. Inhibition of cytochrome a3 prevents the cell from using oxygen and forces anaerobic metabolism, resulting in lactate production, cellular hypoxia and metabolic acidosis. In massive acute cyanide poisoning, the mechanism of toxicity may involve other enzyme systems as well. Signs and symptoms of acute systemic cyanide poisoning may develop rapidly within minutes, depending on the route and extent of cyanide exposure. The action of Cyanokit is based on its ability to bind cyanide ions. Each hydroxocobalamin molecule can bind one cyanide ion by substituting it for the hydroxo ligand linked to the trivalent cobalt ion, to form cyanocobalamin, which is then excreted in the urine.
CNS Activity
Sources: https://www.ncbi.nlm.nih.gov/pubmed/2117062https://www.ncbi.nlm.nih.gov/pubmed/14668053
Curator's Comment: Acetic acid was shown to cross the blood brain barrier in rats.
Approval Year
Targets
Primary Target | Pharmacology | Condition | Potency |
---|---|---|---|
Target ID: cyanide ions |
Conditions
Condition | Modality | Targets | Highest Phase | Product |
---|---|---|---|---|
Curative | CYANOKIT Approved UseCyanokit contains hydroxocobalamin, an antidote indicated for the treatment of known or suspected cyanide poisoning. (1.1) If clinical suspicion of cyanide poisoning is high, Cyanokit should be administered without delay. (1.2) The expert advice of a regional poison control center may be obtained by calling 1-800-222-1222. (1.2) 1.1 Indication Cyanokit is indicated for the treatment of known or suspected cyanide poisoning. 1.2 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. If clinical suspicion of cyanide poisoning is high, Cyanokit should be administered without delay. Table 1 Common Signs and Symptoms of Cyanide Poisoning Symptoms Signs Headache Altered Mental Status (e.g., confusion,disorientation) Confusion Seizures or Coma Dyspnea Mydriasis Chest tightness Tachypnea / Hyperpnea (early) Nausea 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. The expert advice of a regional poison control center may be obtained by calling 1-800-222-1222. 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. 1.3 Use with Other Cyanide Antidotes Caution should be exercised when administering other cyanide antidotes simultaneously with Cyanokit, as the safety of co-administration 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 (2.3) Launch Date2006 |
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Curative | VOSOL Approved UseFor the treatment of superficial infections of the external auditory canal caused by organisms susceptible to the action of the antimicrobial. Launch Date1960 |
AUC
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
4511.6 μM × h EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/8699553 |
5 g single, intravenous dose: 5 g route of administration: Intravenous experiment type: SINGLE co-administered: |
HYDROXOCOBALAMIN plasma | Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN |
T1/2
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
26.2 h EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/8699553 |
5 g single, intravenous dose: 5 g route of administration: Intravenous experiment type: SINGLE co-administered: |
HYDROXOCOBALAMIN plasma | Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN |
Doses
Dose | Population | Adverse events |
---|---|---|
20 mg 1 times / day multiple, intramuscular Dose: 20 mg, 1 times / day Route: intramuscular Route: multiple Dose: 20 mg, 1 times / day Sources: |
unhealthy, 13 years n = 1 Health Status: unhealthy Age Group: 13 years Sex: M Population Size: 1 Sources: |
|
20 g single, intravenous Highest studied dose Dose: 20 g Route: intravenous Route: single Dose: 20 g Sources: |
unhealthy, 26.9 years n = 1 Health Status: unhealthy Age Group: 26.9 years Sex: M Population Size: 1 Sources: |
|
5 g single, intravenous Overdose |
unhealthy, 3 years n = 1 Health Status: unhealthy Condition: cyanide toxicity Age Group: 3 years Sex: F Population Size: 1 Sources: |
|
5 g single, intravenous |
unhealthy, 62 years n = 1 Health Status: unhealthy Condition: Vasoplegic Syndrome Age Group: 62 years Sex: M Population Size: 1 Sources: |
|
2000 ug 2 times / day multiple, oral Dose: 2000 ug, 2 times / day Route: oral Route: multiple Dose: 2000 ug, 2 times / day Sources: |
unhealthy, adult n = 8 Health Status: unhealthy Condition: pernicious anaemia Age Group: adult Population Size: 8 Sources: |
PubMed
Title | Date | PubMed |
---|---|---|
Subcellular localization of Rab17 by cryo-immunogold electron microscopy in epithelial cells grown on polycarbonate filters. | 2001 |
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Evaluation of copper availability to plants in copper-contaminated vineyard soils. | 2001 |
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Fully automated on-line determination of olanzapine in serum for routine therapeutic drug monitoring. | 2001 Feb |
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Exploring infection of wheat and carbohydrate metabolism in Mycosphaerella graminicola transformants with differentially regulated green fluorescent protein expression. | 2001 Feb |
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In vivo (13)C NMR measurement of neurotransmitter glutamate cycling, anaplerosis and TCA cycle flux in rat brain during. | 2001 Feb |
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Analgesic and anti-inflammatory effects of Mangifera indica L. extract (Vimang). | 2001 Feb |
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Structure of manganese diacetate tetrahydrate and low-temperature methyl-group dynamics. | 2001 Feb |
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Pharmacodynamic effects and plasma pharmacokinetics of single doses of cetrorelix acetate in healthy premenopausal women. | 2001 Feb |
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Biodistribution of radiolabeled [(3)H] CMT-3 in rats. | 2001 Feb |
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Lipase-catalyzed irreversible transesterification of 1-(2-furyl)ethanol using isopropenyl acetate. | 2001 Feb |
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Effect of acetate on glycogen replenishment in liver and skeletal muscles after exhaustive swimming in rats. | 2001 Feb |
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Development of xylose-fermenting yeast Pichia stipitis for ethanol production through adaptation on hardwood hemicellulose acid prehydrolysate. | 2001 Feb |
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Screening for cervical neoplasia in a developing country utilizing cytology, cervicography and the acetic acid test. | 2001 Feb |
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Physiological responses to mixing in large scale bioreactors. | 2001 Feb 13 |
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Computational studies on nonenzymatic and enzymatic pyridoxal phosphate catalyzed decarboxylations of 2-aminoisobutyrate. | 2001 Feb 6 |
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Clostridium hungatei sp. nov., a mesophilic, N2-fixing cellulolytic bacterium isolated from soil. | 2001 Jan |
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Long-term stability characterization of a controlled release gastrointestinal therapeutic system coated with a cellulose acetate pseudolatex. | 2001 Jan |
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A survey of lipolytic and glycolytic end-products in commercial Cheddar enzyme-modified cheese. | 2001 Jan |
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Cation-exchange purification of mutagenized bovine beta-casein expressed in transgenic mouse milk: its putative Asn68-linked glycan is heterogeneous. | 2001 Jan |
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In vitro mixed ruminal microorganism fermentation of whole cottonseed coated with gelatinized corn starch and urea. | 2001 Jan |
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Teprenone promotes the healing of acetic acid-induced chronic gastric ulcers in rats by inhibiting neutrophil infiltration and lipid peroxidation in ulcerated gastric tissues. | 2001 Jan |
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Effect of ruminal vs postruminal administration of degradable protein on utilization of low-quality forage by beef steers. | 2001 Jan |
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Determination of cilostazol and its metabolites in human urine by high performance liquid chromatography. | 2001 Jan |
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Measurement of myocardial blood flow with PET using 1-11C-acetate. | 2001 Jan |
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Expression of alpha-amylase gene in rat liver: liver-specific amylase has a high affinity to glycogen. | 2001 Jan |
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Immunobiology of the reproductive tract in a female baboon. | 2001 Jan |
|
Physical stability of the blue pigments formed from geniposide of gardenia fruits: effects of pH, temperature, and light. | 2001 Jan |
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N(delta)-(5-hydroxy-4,6-dimethylpyrimidine-2-yl)-l-ornithine, a novel methylglyoxal-arginine modification in beer. | 2001 Jan |
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Structure and dynamics of high molecular weight glutenin subunits of durum wheat (Triticum durum) in water and alcohol solutions studied by electron paramagnetic resonance and circular dichroism spectroscopies. | 2001 Jan |
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The metal binding properties of the CCCH motif of the 50S ribosomal protein L36 from Thermus thermophilus. | 2001 Jan |
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New analogues of bradykinin containing a conformationally restricted dipeptide fragment in their molecules. | 2001 Jan |
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Purification and characterization of a cellulase from the ruminal fungus Orpinomyces joyonii cloned in Escherichia coli. | 2001 Jan |
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Peripheral and preemptive opioid antinociception in a mouse visceral pain model. | 2001 Jan |
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Three types of K(+) currents in murine osteocyte-like cells (MLO-Y4). | 2001 Jan |
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Analgesic activity of Peperomia pellucida aerial parts in mice. | 2001 Jan |
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Control of electrochemical reactions at the capillary electrophoresis outlet/electrospray emitter electrode under CE/ESI-MS through the application of redox buffers. | 2001 Jan 15 |
|
Inactivation of infective larvae of Angiostrongylus costaricensis with short time incubations in 1.5% bleach solution, vinegar or saturated cooking salt solution. | 2001 Jan 15 |
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Modelling the influence of pH and organic acid types on thermal inactivation of Bacillus cereus spores. | 2001 Jan 22 |
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Identification of lactic acid bacteria constituting the predominating microflora in an acid-fermented condiment (tempoyak) popular in Malaysia. | 2001 Jan 22 |
|
Acetate as a carbon source for hydrogen production by photosynthetic bacteria. | 2001 Jan 23 |
|
Di-tert-butyl phosphate complexes of cobalt(II) and zinc(II) as precursors for ceramic M(PO3)2 and M2P2O7 materials: synthesis, spectral characterization, structural studies, and role of auxiliary ligands. | 2001 Jan 29 |
|
[DOTA-bis(amide)]lanthanide complexes: NMR evidence for differences in water-molecule exchange rates for coordination isomers. | 2001 Jan 5 |
|
Optimised determination of clobazam in human plasma with extraction and high-performance liquid chromatography analysis. | 2001 Jan 5 |
|
[Acetyl starch as volume substitute, a possible alternative to HES]. | 2001 Jan 5 |
|
Evaluation of a novel vitamin E coated cellulosic membrane hollow fiber dialyzer. | 2001 Jan-Feb |
|
S-methyl-N,N-diethylthiocarbamate sulfoxide elicits neuroprotective effect against N-methyl-D-aspartate receptor-mediated neurotoxicity. | 2001 Jan-Feb |
|
Salt accumulation resulting from base added for pH control, and not ethanol, limits growth of Thermoanaerobacteriumthermosaccharolyticum HG-8 at elevated feed xylose concentrations in continuous culture. | 2001 Jan-Feb |
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Conversion of sugars to 1,2-propanediol by Thermoanaerobacterium thermosaccharolyticum HG-8. | 2001 Jan-Feb |
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Production of ethanol and xylitol from corn cobs by yeasts. | 2001 Mar |
|
Measurement of low picomolar levels of triamcinolone acetonide in human bronchoalveolar lavage fluid by gas chromatography-electron-capture negative-ion mass spectrometry. | 2001 Mar 1 |
Patents
Sample Use Guides
To promote continuous contact, insert a wick of cotton saturated with the drug solution (Vosol). Keep the wick in for at least 24 hours and keep it moist by adding 3 to 5 drops of solution every 4 to 6 hours. The wick may be removed after 24 hours but the patient should continue to instill 5 drops of the drug solution 3 or 4 times daily thereafter, for as long as indicated.
Route of Administration:
Otic (auricular)
In Vitro Use Guide
Sources: https://www.ncbi.nlm.nih.gov/pubmed/11420658
Curator's Comment: Hydroxocobalamin (OH-Cbl), when used to treat vitamin B12 deficiency, is better retained by the body than is cyanocobalamin (CN-Cbl), but the availability to cells has not been studied systematically. In a series of experiments, were compared the uptake and internalization of OH-Cbl and CN-Cbl bound to transcobalamin II (TCII) by a human cell model, the HeLa cell. TCII-OH-Cbl was: (1) taken up in larger amounts per unit time, (2) the greater uptake was not a consequence of more effective attachment to receptors of TCII-Cbl nor to a more rapid regeneration of receptors, (3) the difference was expressed during the phase of internalization of TCII-Cbl, (4) with CN-Cbl, the stages of binding to receptors plus internalization were more readily reversed, and (5) larger amounts of OH-Cbl were internalized and converted to active coenzyme forms of Cbl.
Acetic acid inhibited Saccharomyces cerevisiae growth. The minimum inhibitory concentration (MIC) of acetic acid for yeast growth was 0.6% w/v (100 mM).
Substance Class |
Chemical
Created
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Record UNII |
Q40X8H422O
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Record Status |
Validated (UNII)
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Record Version |
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Classification Tree | Code System | Code | ||
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WHO-ATC |
B03BA03
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LOINC |
55883-3
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DSLD |
3479 (Number of products:24)
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WHO-VATC |
QB03BA03
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NCI_THESAURUS |
C26017
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WHO-ATC |
V03AB33
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WHO-VATC |
QV03AB33
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FDA ORPHAN DRUG |
9585
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NDF-RT |
N0000175429
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EMA ASSESSMENT REPORTS |
CYANOKIT (AUTHORIZED: POISONING)
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LOINC |
55882-5
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LOINC |
55884-1
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WHO-ESSENTIAL MEDICINES LIST |
10.1
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LOINC |
2440-6
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WHO-ATC |
B03BA53
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LIVERTOX |
488
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LOINC |
55885-8
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LOINC |
55881-7
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FDA ORPHAN DRUG |
177403
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FDA ORPHAN DRUG |
137600
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3342
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C65868
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5514
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27786
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m6116
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PRIMARY | Merck Index | ||
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44475014
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D006879
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HYDROXOCOBALAMIN
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PRIMARY | Description: Dark red crystals or a red, crystalline powder; odourless. Solubility: Sparingly soluble in water and ethanol (~750 g/l) TS; practically insoluble in acetone R. Category: Antianaemia drug. Storage: Hydroxocobalamin should be kept in a tightly closed container, protected from light and stored at a temperature between 2? and 8?C.Labelling: The designation on the container should state whether the substance is in the anhydrous or hydrated form. Additional information: In aqueous solution, Hydroxocobalamin exists as hydroxocobamide in equilibrium with the hydrated ionic form. The anhydrous form of Hydroxocobalamin is very hygroscopic. Even in the absence of light, it is gradually degraded on exposure to a humid atmosphere, the decomposition being faster at higher temperatures. | ||
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4309
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Q40X8H422O
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HYDROXOCOBALAMIN
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SUB08074MIG
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100000091430
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Q40X8H422O
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236-533-2
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DB00200
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13422-51-0
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1043
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CHEMBL2103737
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SALT/SOLVATE -> PARENT |
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SALT/SOLVATE -> PARENT |
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IMPURITY -> PARENT |
NMT 1.0%
USP
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IMPURITY -> PARENT |
NMT 1.0%
USP
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ACTIVE MOIETY |
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