Tetradecyl hydrogen sulfate (ester)

Identification

Name
Tetradecyl hydrogen sulfate (ester)
Accession Number
DB11328
Type
Small Molecule
Groups
Approved
Description

Sodium tetradecyl sulfate is an anionic surface-active agent which is used for its wetting properties in the industry and is also used in medicine as a blood vessel irritant and sclerosing agent for hemorrhoids and varicose veins [2].

Sodium tetradecyl sulfate has been widely used since the 1950s, and in 1978 the first successful report of injecting a 1% solution into spider angiomas in 144 patients was made. Also noted was an unspecified number of episodes of epidermal necrosis without significant long-term effects and a 30% incidence of post-sclerosis pigmentation that resolved within a few months [3].

Structure
Thumb
Synonyms
  • 7-Ethyl-2-methyl-4-undecanol sulfate
  • Tetradecyl hydrogen sulfate
Generic Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
SotradecolInjection, solution30 mg/1mLIntravenousMylan Institutional2013-04-29Not applicableUs
SotradecolInjection, solution10 mg/1mLIntravenousAngiodynamics2004-12-012015-09-30Us
SotradecolInjection, solution10 mg/1mLIntravenousMylan Institutional2013-04-29Not applicableUs
SotradecolInjection, solution30 mg/1mLIntravenousAngiodynamics2004-12-012015-09-30Us
International/Other Brands
Fibro-vein (Australasian Medical and Scientific Limited) / Fibro-Vein 3% (STD) / Fibrovein (Craveri) / Veinfibro (STD Pharmaceutical Products)
Categories
Not Available
UNII
6326W0DRHY
CAS number
300-52-7
Weight
Average: 294.45
Monoisotopic: 294.18648062
Chemical Formula
C14H30O4S
InChI Key
GROJOWHVXQYQGN-UHFFFAOYSA-N
InChI
InChI=1S/C14H30O4S/c1-5-7-8-13(6-2)9-10-14(11-12(3)4)18-19(15,16)17/h12-14H,5-11H2,1-4H3,(H,15,16,17)
IUPAC Name
[(7-ethyl-2-methylundecan-4-yl)oxy]sulfonic acid
SMILES
CCCCC(CC)CCC(CC(C)C)OS(O)(=O)=O

Pharmacology

Indication

Sotradecol (sodium tetradecyl sulfate injection) is indicated in the treatment of small, uncomplicated varicose veins of the legs showing simple dilation, with competent valves [1].

Sodium tetradecyl sulfate has been designated as an orphan drug by the FDA for the treatment of gastrointestinal bleeding due to esophageal varices [8].

Associated Conditions
Pharmacodynamics

Telangiectasias or varicose veins occur in about 33% of adult women and about 15% of adult men. Sclerotherapy with sotradecol is widely used in the treatment of varicose veins [7].

Sotradecol (sodium tetradecyl sulfate injection) is a sclerosing agent. Intravenous (IV) injection of this agent causes blood vessel intima inflammation and thrombus formation. This normally occludes the injected vein, leading to a series of events. Subsequent formation of fibrous tissue results in partial or complete vein obliteration that may be temporary or permanent [1].

Mechanism of action

When injected directly into a vein, sodium tetradecyl sulfate causes intimal inflammation and venous thrombus formation, which then results in occlusion of the vein. Following this sequence of events, fibrous tissue forms and causes partial to complete obliteration of the vein, which may be temporary or permanent. An important role of this drug, as well as other sclerosing agents, is to control active hemorrhage and encourage hemostasis. This may be due to the esophageal and vascular smooth muscle spasm induced by the sclerosing agent [5].

During acute and active bleeding, the sodium tetradecyl sulfate injected directly into the esophageal varices may dissipate rapidly, as the varices have a much higher blood volume/flow rate and no functioning valves [5].

The mechanical compression effect of submucosal edema, created by the injection of sclerosing agents, may also be responsible for acute hemostasis [5].

TargetActionsOrganism
AEndothelial protein C receptor
antagonist
Human
Absorption
Not Available
Volume of distribution

In humans, a large proportion (75%) of an injected dose of radiolabelled 3% sodium tetradecyl sulfate rapidly disappeared from the empty varicose vein injection site into communicating blood vessels with rapid entry into the deep veins of the calf [9].

In rats, at 72 hours after intravenous dosing of radiolabelled sodium tetradecyl sulfate, tissue levels of radiolabelled matter found in sample tissues (liver, kidney, lipid and skeletal muscle) were measured as very low. Although there was some evidence of radiolabel associated with the injection site, the levels were negligible [9].

Protein binding
Not Available
Metabolism
Not Available
Route of elimination

After an intravenously administered radiolabelled dose, 70% of the drug was recovered in the urine of rats within 24 hours post-dosing [9].

At the end of the 72 hour post-dose period, 73.5% of the radiolabel had been recovered from the urine and 18.2% recovered from the faeces [9].

Half life
Not Available
Clearance
Not Available
Toxicity

The intravenous LD50 of sodium tetradecyl sulfate in mice is 90 ± 5 mg/kg [1].

In the rat, the acute intravenous LD50 of sodium tetradecyl sulfate is estimated at 72 mg/kg and 108 mg/kg [1].

Adverse events are below:

Deep venous thrombosis

Because of the risk of deep vein thrombosis, patients must be evaluated for valvular competency and deep venous patency before treatment is initiated and slow injections of a small volume (< 2 mL) should be injected. It is recommended that patients be monitored post-treatment for both deep vein thrombosis and pulmonary embolism [12].

Air embolism

Stroke, transient ischemic attack, myocardial infarction, and impaired cardiac function have been associated with tetradecyl sulfate administration. Such sequelae may be caused by air embolism [5].

Local reaction

Local reactions including pain, itching or ulceration at the site of injection with permanent discoloration may remain along the path of the treated/sclerosed vein segment. Sloughing and/or necrosis of surrounding tissue may occur following extravasation from the injection site [1].

Allergic reactions

Hives, asthma, hay fever and anaphylactic shock have been reported with use of this drug [1].

*Mild systemic reactions *

Headache, nausea and vomiting [1].

Death A minimum of 6 deaths have reported with the use of Sotradecol. Four incidences of anaphylactic shock resulting in death have been reported in patients who received this drug [1].

One death has been reported in a patient who received Sotradecol while receiving an anti-ovulatory agent [1]

Another death (from lethal pulmonary embolism) has been reported in a 36-year-old female treated with sodium tetradecyl acetate and was not taking oral contraceptive therapy [1]

Affected organisms
  • Humans and other mammals
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
DrugInteraction
AcetaminophenAcetaminophen may decrease the excretion rate of Tetradecyl hydrogen sulfate (ester) which could result in a higher serum level.
Acetylsalicylic acidAcetylsalicylic acid may decrease the excretion rate of Tetradecyl hydrogen sulfate (ester) which could result in a higher serum level.
AlprazolamAlprazolam may decrease the excretion rate of Tetradecyl hydrogen sulfate (ester) which could result in a higher serum level.
AmilorideAmiloride may increase the excretion rate of Tetradecyl hydrogen sulfate (ester) which could result in a lower serum level and potentially a reduction in efficacy.
AmitriptylineTetradecyl hydrogen sulfate (ester) may decrease the excretion rate of Amitriptyline which could result in a higher serum level.
AmlodipineAmlodipine may decrease the excretion rate of Tetradecyl hydrogen sulfate (ester) which could result in a higher serum level.
AmoxicillinAmoxicillin may decrease the excretion rate of Tetradecyl hydrogen sulfate (ester) which could result in a higher serum level.
AmphetamineAmphetamine may decrease the excretion rate of Tetradecyl hydrogen sulfate (ester) which could result in a higher serum level.
AmpicillinAmpicillin may decrease the excretion rate of Tetradecyl hydrogen sulfate (ester) which could result in a higher serum level.
AuranofinAuranofin may decrease the excretion rate of Tetradecyl hydrogen sulfate (ester) which could result in a higher serum level.
Food Interactions
Not Available

References

General References
  1. SOTRADECOL- tetradecyl hydrogen sulfate (ester) injection, solution [Link]
  2. Sotradecol, PubChem [Link]
  3. Sodium tetradecyl sulfate [Link]
  4. Sodium Tetradecyl Sulfate [Link]
  5. PDR Sotradecol [Link]
  6. Evaluation of sodium tetradecyl sulfate and polidocanol as sclerosants for leg telangiectasia based on histological evaluation with clinical correlation [Link]
  7. Anaphylactoid Reaction After the Use of Sodium Tetradecyl Sulfate: A Case Report [Link]
  8. Drug Approval Package [Link]
  9. NZ Drug Safe Fibrovein [Link]
  10. Intralesional 3% Sodium Tetradecyl Sulfate for Treatment of Cutaneous Kaposi's Sarcoma [Link]
  11. Sodium tetradecyl sulfate actions [Link]
  12. Sotradecol [Link]
External Links
ChemSpider
8441
ChEBI
75275
ChEMBL
CHEMBL1201345
MSDS
Download (253 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
1, 2CompletedTreatmentHereditary Haemorrhagic Telangiectasia (HHT) / Nasal Bleeding1
4RecruitingTreatmentVenous Malformations1

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage forms
FormRouteStrength
Injection, solutionIntravenous10 mg/1mL
Injection, solutionIntravenous30 mg/1mL
Prices
Not Available
Patents
Not Available

Properties

State
Not Available
Experimental Properties
PropertyValueSource
melting point (°C)199MSDS
Predicted Properties
PropertyValueSource
Water Solubility0.0104 mg/mLALOGPS
logP1.98ALOGPS
logP5.04ChemAxon
logS-4.4ALOGPS
pKa (Strongest Acidic)-1.1ChemAxon
Physiological Charge-1ChemAxon
Hydrogen Acceptor Count3ChemAxon
Hydrogen Donor Count1ChemAxon
Polar Surface Area63.6 Å2ChemAxon
Rotatable Bond Count11ChemAxon
Refractivity77.77 m3·mol-1ChemAxon
Polarizability33.53 Å3ChemAxon
Number of Rings0ChemAxon
Bioavailability0ChemAxon
Rule of FiveNoChemAxon
Ghose FilterYesChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleNoChemAxon
Predicted ADMET features
Not Available

Spectra

Mass Spec (NIST)
Not Available
Spectra
Not Available

Taxonomy

Classification
Not classified

Targets

Kind
Protein
Organism
Human
Pharmacological action
Yes
Actions
Antagonist
General Function
Receptor activity
Specific Function
Binds activated protein C. Enhances protein C activation by the thrombin-thrombomodulin complex; plays a role in the protein C pathway controlling blood coagulation.
Gene Name
PROCR
Uniprot ID
Q9UNN8
Uniprot Name
Endothelial protein C receptor
Molecular Weight
26671.245 Da
References
  1. Sodium tetradecyl sulfate actions [Link]

Drug created on December 03, 2015 09:52 / Updated on August 02, 2018 06:23