Guaifenesin

198.22

198.22

2049375

202-222-5

757052|62112

DTXSID5023114

Minute rhombic prisms from ether|WHITE TO SLIGHTLY GRAY, CRYSTALLINE POWDER

R05CA03|R - Respiratory system

2909499000

58.9

1.4

Solid

1.2±0.1 g/cm3

78.5-79 °C

215 °C @ Press: 19 Torr

215°C/19mm

1.538

H2O: 5 g/100 mL (25 ºC)

Refrigerator

1.52X10-6 mm Hg at 25 deg C (est)

LD50 oral in rabbit: 2553mg/kg

SLIGHT CHARACTERISTIC ODOR

Slightly bitter aromatic taste

Henry's Law constant = 4.44X10-11 atm-cu m/mole at 25 °C (est)

Hydroxyl radical reaction rate constant = 4.10X10-11 cu cm/molec-sec at 25 °C (est)|NONHYGROSCOPIC

NONH for all modes of transport

1

22-36/37/38

26-36

TY8400000

Xn

Stable in light and heat.

P261-P305 + P351 + P338

H302-H315-H319-H335

SRP: At the time of review, criteria for land treatment or burial (sanitary landfill) disposal practices are subject to significant revision. Prior to implementing land disposal of waste residue (including waste sludge), consult with environmental regulatory agencies for guidance on acceptable disposal practices.

The Approved Drug Products with Therapeutic Equivalence Evaluations List identifies currently marketed over-the-counter drug products, incl guaifenesin, approved on the basis of safety and effectiveness by FDA under sections 505 of the Federal Food, Drug, and Cosmetic Act.|Cold, cough, allergy, bronchodilator, and antiasthmatic drug products for over-the-counter human use. Expectorant active ingredient. The active ingredient of the product is guaifenesin when used within the dosage limits established in §341.78(d).|Implantation or injectable dosage form new animal drugs. Guaifenesin sterile powder. ... It is indicated for intravenous use as a muscle relaxant in horses. ... Not to be used in horses intended for food. ... Federal law restricts this drug to use by or on the order of a licensed veterinarian.|Implantation or injectable dosage form new animal drugs. Guaifenesin injection. ... The drug is used intravenously in horses as a skeletal muscle relaxant. ... Not to be used in horses intended for food. ... Federal law restricts this drug to use by or on the order of a licensed veterinarian.

|Warning|H302 (100%): Harmful if swallowed [Warning Acute toxicity, oral]|P264, P270, P301+P312, P330, and P501|Aggregated GHS information provided by 727 companies from 10 notifications to the ECHA C&L Inventory.

Guaifenesin was detected at a concentration range of 21-52 ng/L in the waters of the Las Vegas Bay of Lake Mead, Nevada, sampled from 1997 through 1998. This study detected several pharmacteuticals and personal care products which were entering the Bay through the discharge of the Las Vegas Wash(1).

The most prevalent signs and symptoms associated with an overdose of guaifenesin have been nausea and vomiting. Although adequate and well-controlled studies in pregnant women have not been performed, the Collaborative Perinatal Project monitored 197 mother-child pairs exposed to guaifenesin during the first trimester. An increased occurrence of inguinal hernias was found in the neonates. However, congenital defects were not strongly associated with guaifenesin use during pregnancy in 2 large groups of mother-child pairs. Moreover, guaifenesin is excreted in breast milk in small quantities. Subsequently, caution should be exercised by balancing the potential benefit of treatment against any possible risks. Additionally, an LD50 value of 1510 mg/kg (rat, oral) has been reported for guaifenesin [MSDS].

Enzyme induction due to barbiturates has recently been shown to significantly reduce biological t/2 of...glyceryl guaiacolate ether...

Information regarding the protein binding of guaifenesin is not readily available or accessible.

Guaifenesin's production and use as a veterinary and human expectorant(1) for the treatment of respiratory tract infections(2) and as a centrally acting muscle relaxant in animals(3) may result in its release to the environment through various waste streams(SRC).

TERRESTRIAL FATE: Based on a classification scheme(1), an estimated Koc value of 140(SRC), determined from a log Kow of 1.39(2) and a regression-derived equation(3), indicates that guaifenesin is expected to have high mobility in soil(SRC). Volatilization of guaifenesin from moist soil surfaces is not expected to be an important fate process(SRC) given an estimated Henry's Law constant of 4.4X10-11 atm-cu m/mole(SRC), using a fragment constant estimation method(4). Guaifenesin is not expected to volatilize from dry soil surfaces(SRC) based upon an estimated vapor pressure of 1.52X10-6 mm Hg(SRC), determined from a fragment constant method(5). Biodegradation data were not available(SRC, 2007).|AQUATIC FATE: Based on a classification scheme(1), an estimated Koc value of 140(SRC), determined from a log Kow of 1.39(2) and a regression-derived equation(3), indicates that guaifenesin is not expected to adsorb to suspended solids and sediment(SRC). Volatilization from water surfaces is not expected(3) based upon an estimated Henry's Law constant of 4.4X10-11 atm-cu m/mole(SRC), developed using a fragment constant estimation method(4). According to a classification scheme(5), an estimated BCF of 7.0(SRC), from its log Kow(2) and a regression-derived equation(6), suggests the potential for bioconcentration in aquatic organisms is low(SRC). Biodegradation data were not available(SRC, 2007).|ATMOSPHERIC FATE: According to a model of gas/particle partitioning of semivolatile organic compounds in the atmosphere(1), guaifenesin, which has an estimated vapor pressure of 1.5X10-6 mm Hg at 25 °C(SRC), determined from a fragment constant method(2), will exist in both the vapor and particulate phases in the ambient atmosphere. Vapor-phase guaifenesin is degraded in the atmosphere by reaction with photochemically-produced hydroxyl radicals(SRC); the half-life for this reaction in air is estimated to be 9.4 hours(SRC), calculated from its rate constant of 4.1X10-11 cu cm/molecule-sec at 25 °C(SRC) that was derived using a structure estimation method(3). Particulate-phase guaifenesin may be removed from the air by wet or dry deposition(SRC). Guaifenesin does not contain chromophores that absorb at wavelengths >290 nm(4) and therefore is not expected to be susceptible to direct photolysis by sunlight(SRC).

The rate constant for the vapor-phase reaction of guaifenesin with photochemically-produced hydroxyl radicals has been estimated as 4.1X10-11 cu cm/molecule-sec at 25 °C(SRC) using a structure estimation method(1). This corresponds to an atmospheric half-life of about 9.4 hours at an atmospheric concentration of 5X10+5 hydroxyl radicals per cu cm(1). Guaifenesin is not expected to undergo hydrolysis in the environment due to the lack of functional groups that hydrolyze under environmental conditions(2). Guaifenesin does not contain chromophores that absorb at wavelengths >290 nm(2) and therefore is not expected to be susceptible to direct photolysis by sunlight(SRC).

An estimated BCF of 7.0 was calculated for guaifenesin(SRC), using a log Kow of 1.39(1) and a regression-derived equation(2). According to a classification scheme(3), this BCF suggests the potential for bioconcentration in aquatic organisms is low(SRC).

The Koc of guaifenesin is estimated as 140(SRC), using a log Kow of 1.39(1) and a regression-derived equation(2). According to a classification scheme(3), this estimated Koc value suggests that guaifenesin is expected to have high mobility in soil.

The Henry's Law constant for guaifenesin is estimated as 4.4X10-11 atm-cu m/mole(SRC) using a fragment constant estimation method(1). This Henry's Law constant indicates that guaifenesin is expected to be essentially nonvolatile from water surfaces(2). Guaifenesin is not expected to volatilize from dry soil surfaces(SRC) based upon an estimated vapor pressure of 1.5X10-6 mm Hg(SRC), determined from a fragment constant method(3).

NIOSH (NOES Survey 1981-1983) has statistically estimated that 25,427 workers (21,545 of these are female) are potentially exposed to guaifenesin in the US(1). Occupational exposure to guaifenesin may occur through dermal contact with this compound at workplaces where guaifenesin is produced or used(SRC). Exposure to guaifenesin among the general population may be limited to those administered the drug, an expectorant(SRC).

Guaifenesin is an expectorant that is indicated for providing temporary symptomatic relief from congested chests and coughs which may be due to a cold, bronchitis, and/or other breathing illnesses.|FDA Label

Expectorants|Guaifenesin is indicated as an expectorant in the temporary symptomatic management of cough due to minor upper respiratory infections and related conditions, such as sinusitis, pharyngitis, and bronchitis, when these conditions are complicated by viscous mucus and congestion. However, because supporting data are very limited, there is some controversy about its effectiveness. /Included in US product label/|VET: Guaifenesin (glyceryl guaiacolate) is a centrally acting muscle relaxant that is believed to depress or block nerve impulse transmission at the internuncial neuron level of the subcortical areas of the brain, brain stem, and spinal cord. It also has mild analgesic and sedative actions. Guaifenesin is given IV to induce muscle relaxation as an adjunct to anesthesia for short procedures. It relaxes both laryngeal and pharyngeal muscles, allowing easier intubation, but has little effect on diaphragm and respiratory function. It may cause transient increases in cardiac rate and decreases in blood pressure. It is also used in treatment of horses with exertional rhabdomyolysis and in dogs with strychnine intoxication.|VET: The drug is used intravenously as a skeletal muscle relaxant in horses. /Gecolate, Glycodex Injection/

The Centers for Disease Control and Prevention (CDC) issued a Morbidity and Mortality Weekly Report (MMWR) article describing three deaths in U.S. infants aged less than 12 months associated with cough and cold medications /including guaifenesen/. These medications were determined by medical examiners or coroners to be the underlying cause of death. The cases described in this report underscore the need for clinicians to use caution when prescribing and caregivers to use caution when administering cough and cold medications to children aged less than 2 years.|Doses of guaifenesin larger than those required for expectorant action may produce emesis, but GI upset at ordinary dosage levels is rare.|For self-medication, unless directed by a physician, guaifenesin should not be used for persistent or chronic cough such as that occurring with smoking, asthma, chronic bronchitis, or emphysema, or for cough accompanied by excessive phlegm. A persistent cough may be indicative of a serious condition. If cough persists for more than one week, is recurrent, or is accompanied by fever, rash, or persistent headache, a physician should be consulted.|Adverse effects ... indicating need for medical attention only if they continue or are bothersome ... occurring at an incidence less frequent or rare /include/: diarrhea; dizziness; headache; nausea or vomiting; skin rash; stomach pain; urticaria (hives).|For more Drug Warnings (Complete) data for GUAIFENESIN (7 total), please visit the HSDB record page.

2(?). 2= SLIGHTLY TOXIC: PROBABLE ORAL LETHAL DOSE (HUMAN) 5-15 G/KG, BETWEEN 1 PINT & 1 QT FOR 70 KG PERSON (150 LB).

Guaifenesin is categorized as an expectorant that acts by enhancing the output of phlegm (sputum) and bronchial secretions via decreasing the adhesiveness and surface tension of such material. Furthermore, guaifenesin elicits an increased flow of less viscous gastric secretions that subsequently promote ciliary action - all actions that ultimately change dry, unproductive coughing to coughs that are more productive and less frequent. Essentially, by decreasing the viscosity and adhesiveness of such secretions, guaifenesin enhances the efficacy of mucociliary activity in removing accumulated secretions from the upper and lower airway.

Agents that increase mucous excretion. Mucolytic agents, that is drugs that liquefy mucous secretions, are also included here. (See all compounds classified as Expectorants.)

Studies have shown that guaifenesin is well absorbed from and along the gastrointestinal tract after oral administration.|After administration, guaifenesin is metabolized and then largely excreted in the urine.|The geometric mean apparent volume of distribution of guaifenesin determined in healthy adult subjects is 116L (CV=45.7%).|The mean clearance recorded for guaifenesin is about 94.8 L/hr (CV=51.4%).|Readily absorbed from the gastrointestinal tract.|It is not known whether guaifenesin is distributed into breast milk.|Elimination /is/ renal, as inactive metabolites.|Five donkeys and three horses were given guaifenesin, intravenously, by gravity administration, until recumbency was produced. The time and dose required to produce recumbency, recovery time to sternal and standing were recorded. Blood samples were collected for guaifenesin assay at 10, 20, 30, 40, 50, 60 min, and 2, 3, 4 and 6 hr after guaifenesin administration. Serum was analysed for guaifenesin using HPLC and pharmacokinetic values were calculated using a computer software package. In donkeys, heart and respiratory rates and blood pressures were recorded before and at 5-min intervals during recumbency. Arterial blood samples were collected before and at 5 and 15 min intervals during recumbency for analysis of pH, CO2, and O2. ANOVA was used to evaluate dynamic data, while t-tests were used for kinetic values. Respiratory rate was decreased significantly during recumbency, but no other significant changes from baseline occurred. The mean (+/- SD) recumbency dose of guaifenesin was 131 mg/kg (27) for donkeys and 211 mg/kg (8) for horses. Recovery time to sternal (min) was 15 (SD, 11) for donkeys and 34 (SD, 1.4) for horses. Time to standing was 32 min for donkeys and 36 min for horses. Calculation of AUC (area under the concentration-time curve) microgram/mL) (dose-dependent variable) was 231 (SD, 33) for donkeys and 688 (SD, 110) for horses. The clearance (CL) (mL/hr.kg) was 546 (SD, 73) for donkeys, which was significantly different from 313 (SD, 62) for horses. Mean residence time (MRT) (hr) was 1.2 (SD, 0.1) for donkeys and 2.6 (SD, 0.5) for horses. Volume of distribution Vd(area) (mL/kg) was 678 (SD, 92) for donkeys and 794 (SD, 25) for horses. At the rate of administration used in this study, donkeys required less guaifenesin than horses to produce recumbency, but cleared it more rapidly.

After the oral administration of 400 mg guaifenesin, the agent experiences rapid hydrolysis (more than 60% of the dose hydrolyzed over a range of seven hours) with β-(2-methoxyphenoxy)-lactic acid found as the major urinary metabolite but no parent drug detectable in the urine. Moreover, it has been observed that guaifenesin also experiences both oxidation and demethylation. In particular, the medication is quickly metabolized hepatically by way of oxidation to β-(2-methoxyphenoxy)-lactic acid. Furthermore, guaifenesin is also demethylated by O-demethylase in liver microsomes to the point where about 40% of an administered dose is excreted as this metabolite in the urine within 3 hours. In fact, O-demethylase appears to be the primary enzyme for the metabolism of guaifenesin and the primary metabolites of the substance are β-(2-methoxyphenoxy)-lactic acid and the demethylated hydroxyguaifenesin, both of which are themselves inactive moieties.|The major urinary metabolite is beta-(2-methoxyphenoxy) lactic acid.|It is excreted in urine principally as glucuronates & sulfates.|Oxidative o-demethylation of glyceryl guaiacolate ether occurred much more rapidly in ip injected male rats than in females. This sex difference in metabolism was paralleled by corresponding difference in o-demethylase activity between male & female animals.

The half-life in plasma observed for guaifenesin is approximately one hour.|Guaifenesin has a plasma half-life of one hour.|Centrally acting muscle relaxant glyceryl guaiacolate ether was found to have t/2 of 56.5 min in male rats and 88.5 min in female rats following ip administration.

Although the exact mechanism of action of guaifenesin may not yet be formally or totally elucidated, it is believed that expectorants like guaifenesin function by increasing mucus secretion. Moreover, it is also further proposed that such expectorants may also act as an irritant to gastric vagal receptors, and recruit efferent parasympathetic reflexes that can elicit glandular exocytosis that is comprised of a less viscous mucus mixture. Subsequently, these actions may provoke coughing that can ultimately flush difficult to access, congealed mucopurulent material from obstructed small airways to facilitate a temporary improvement for the individual. Consequently, while it is generally proposed that guaifenesin functions as an expectorant by helping to loosen phlegm (mucus) and thin bronchial secretions to rid the bronchial passageways of bothersome mucus and make coughs more productive, there has also been research to suggest that guaifenesin possesses and is capable of demonstrating anticonvulsant and muscle relaxant effects to some degree possibly by acting as an NMDA receptor antagonist.|Guaifenesin is thought to act as an expectorant by increasing the volume and reducing the viscosity of secretions in the trachea and bronchi. Thus it may increase the efficiency of the cough reflex and facilitate removal of the secretions; however, objective evidence for this is limited and conflicting.|By increasing respiratory tract fluid, guaifenesin reduces the viscosity of tenacious secretions and acts as an expectorant.|Guaifenesin, a commonly used agent for the treatment of cough, is termed an expectorant since it is believed to alleviate cough discomfort by increasing sputum volume and decreasing its viscosity, thereby promoting effective cough. Despite its common usage, relatively few studies, yielding contrasting results, have been performed to investigate the action and efficacy of guaifenesin. To evaluate the effect of guaifenesin on cough reflex sensitivity. Randomized, double-blind, placebo-controlled trial. Fourteen subjects with acute viral upper respiratory tract infection (URI) and 14 healthy volunteers. On 2 separate days, subjects underwent capsaicin cough challenge 1 to 2 hr after receiving a single, 400-mg dose (capsules) of guaifenesin or matched placebo. Measurements and results: The concentration of capsaicin inducing five or more coughs (C(5)) was determined. Among subjects with URI, mean (+/- SEM) log C(5) after guaifenesin and placebo were 0.92 +/- 0.17 and 0.66 +/- 0.14, respectively (p = 0.028). No effect on cough sensitivity was observed in healthy volunteers. /The/ results demonstrate that guaifenesin inhibits cough reflex sensitivity in subjects with URI, whose cough receptors are transiently hypersensitive, but not in healthy volunteers. Possible mechanisms include a central antitussive effect, or a peripheral effect by increased sputum volume serving as a barrier shielding cough receptors within the respiratory epithelium from the tussive stimulus.

2-methoxyphenol (guaiacol); 2-(2-methoxyphenoxy)propane-1,3-diol (beta-isomer); 1,1'-oxybis[3-(2-methoxyphenoxy)propan-2-ol] (bisether); 1,3-bis(2-methoxyphenoxy)propan-2-ol

Basic treatment: Establish a patent airway (oropharyngeal or nasopharyngeal airway, if needed). Suction if necessary. Watch for signs of respiratory insufficiency and assist ventilations if needed. Administer oxygen by nonrebreather mask at 10 to 15 L/min. Monitor for pulmonary edema and treat if necessary ... . Monitor for shock and treat if necessary ... . Anticipate seizures and treat if necessary ... . For eye contamination, flush eyes immediately with water. Irrigate each eye continuously with 0.9% saline (NS) during transport ... . Do not use emetics. For ingestion, rinse mouth and administer 5 mL/kg up to 200 mL of water for dilution if the patient can swallow, has a strong gag reflex, and does not drool ... . Cover skin burns with dry sterile dressings after decontamination ... . /Poisons A and B/|Advanced treatment: Consider orotracheal or nasotracheal intubation for airway control in the patient who is unconscious, has severe pulmonary edema, or is in severe respiratory distress. Positive-pressure ventilation techniques with a bag valve mask device may be beneficial. Consider drug therapy for pulmonary edema ... . Consider administering a beta agonist such as albuterol for severe bronchospasm ... . Monitor cardiac rhythm and treat arrhythmias as necessary ... . Start IV administration of D5W /SRP: "To keep open", minimal flow rate/. Use 0.9% saline (NS) or lactated Ringer's if signs of hypovolemia are present. For hypotension with signs of hypovolemia, administer fluid cautiously. Watch for signs of fluid overload ... . Treat seizures with diazepam or lorazepam ... . Use proparacaine hydrochloride to assist eye irrigation ... . /Poisons A and B/|Immediate first aid: Ensure that adequate decontamination has been carried out. If patient is not breathing, start artificial respiration, preferably with a demand valve resuscitator, bag-valve-mask device, or pocket mask, as trained. Perform CPR if necessary. Immediately flush contaminated eyes with gently flowing water. Do not induce vomiting. If vomiting occurs, lean patient forward or place on the left side (head-down position, if possible) to maintain an open airway and prevent aspiration. Keep patient quiet and maintain normal body temperature. Obtain medical attention. /Poisons A and B/

/HUMAN EXPOSURE STUDIES/ ... 197 mother-child pairs exposed to guaifenesin during the first trimester /were monitored/. An increased occurrence of inguinal hernias was found in the neonates. However, congenital defects were not strongly associated with guaifenesin use during pregnancy in 2 large groups of mother-child pairs.|/SIGNS AND SYMPTOMS/ Nausea and drowsiness may occur rarely. ...May produce false positive test for urinary 5-hydroxyindoleacetic acid (5-HIAA).|/CASE REPORTS/ Guaifenesin is a commonly used expectorant whose use may lead to the occasional formation of guaifenesin urinary stones. /Investigators/ herein describe a patient who was taking 2400 mg Guaifenesin per day as part of his treatment for asthma. He had a past history of a guaifenesin stone removed ureteroscopically. His current presentation was with a 9 mm by 6 mm stone in the upper left ureter, seen on CT scan, and treated initially with a ureteral stent and hydration. After 3 weeks, the stone had disappeared, as confirmed by repeat CT scan.|/CASE REPORTS/ ...This paper reviews the reported cases of ephedrine- and guaifenesin-induced nephrolithiasis, as well as the diagnostic techniques and treatments that have been successfully used for these stones. A systematic review of the literature pertaining to nephrolithiasis and the compounds ephedrine and guaifenesin was conducted. Ephedrine and guaifenesin use results in over 35% of urinary stones that are related to pharmaceutical metabolites, and collectively are present in 0.1% of all urinary stones. These calculi are radiolucent, requiring the use of computerized tomography (CT scan) for diagnosis. Alkalinization therapy offers an alternative to surgical intervention and may have a role in prevention of recurrence. ...|For more Human Toxicity Excerpts (Complete) data for GUAIFENESIN (6 total), please visit the HSDB record page.

Breonesin

Essentally 100% in human and veterinary medicine (1976)

Oral /formulations/: Capsules 200 mg Hytuss-2X,(Hyrex); Capsules, extended-release 300 mg Humibid Pediatric, (Celltech); Solution 100 mg/5 mL Phanasin Diabetic Choice ( with parabens and propylene glycol), (Pharmakon); 200 mg/5 mL Naldecon Senior EX, (Bristol-Myers Squibb); Tablets 100 mg Hytuss (scored), (Hyrex); 200 mg guaifenesin Tablets, (United Research); Tablets, extended-release 600, 1200 mg Mucinex, (Adams).|Capsules: 100 & 200 mg; syrup NF: 100 mg/5 mL; tablets: 100 & 200 mg.

1,2-Propanediol, 3-(2-methoxyphenoxy)-: ACTIVE

GAS CHROMATOGRAPHY METHOD FOR QUANTITATIVE DETERMINATION OF GLYCERYL GUAIACOLATE IN COUGH MIXTURE.|QUANTITATIVE DETERMINATIONS OF GUAIFENESIN IN EXPECTORANT BY HIGH PRESSURE LIQ CHROMATOGRAPHY.|SAMPLE WAS SEPARATED BY SILICA GEL CHROMATOGRAPHIC PLATES & CONC DETERMINED AT 274 NM BY UV ABSORPTION.|RAPID, STABILITY-INDICATING, REVERSED-PHASE HIGH-PRESSURE LIQ CHROMATOGRAPHIC DETERMINATION OF GUAIFENESIN IN LIQ & SOLID PHARMACEUTICAL DOSAGE FORMS WITHOUT INTEREFERENCE FROM ACTIVE &/OR VEHICLE DECOMP.|For more Analytic Laboratory Methods (Complete) data for GUAIFENESIN (14 total), please visit the HSDB record page.

Analyte: guaifenesin; matrix: blood (whole), urine; procedure: high-performance liquid chromatography with ultraviolet detection at 200.5 nm|Analyte: guaifenesin; matrix: blood (plasma); procedure: high-performance liquid chromatography with fluorescence detection at 280 nm (excitation) and 315 nm (emission); limit of detection: 30 ng/mL|Analyte: guaifenesin; matrix: blood (plasma); procedure: high-performance liquid chromatography with ultraviolet detection at 272 nm

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