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GUAIFENESIN

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Classification   |    Detailed evidence-based information

Substances Included Synonyms

Therapeutic Toxic Class

    A) Guaifenesin is an expectorant used to loosen mucus and thin bronchial secretions to make a cough more productive. It is available as an over-the-counter (OTC) medication and can be combined with a cough suppressant that may be available OTC or by prescription. This topic is limited to the effects of guaifenesin only.

Specific Substances

    1) Guaifenesiini
    2) Guaifenesina
    3) Guaifenesine
    4) CAS 93-14-1
    5) Molecular Formula: 10H14O4

Available Forms Sources

    A) FORMS
    1) The following is a list of formulations for guaifenesin only:
    a) TABLETS: Immediate release: 400 mg orally (OTC Product Information, as posted to the DailyMed site 11/01/2012).
    b) EXTENDED-RELEASE TABLETS: 600 mg orally (OTC Product Information, as posted to the DailyMed site 10/01/2013a).
    c) SYRUP: 100 mg/5 mL oral solution (OTC Product Information, as posted to the DailyMed site 10/01/2013).
    d) GRANULES: 100 mg orally per packet (OTC Product Information, as posted to the DailyMed site 06/01/2012).
    e) ORAL, DISINTEGRATING (SOFT CHEW): 100 mg soft chew formulation (OTC Product Information, as posted to the DailyMed site 04/01/2011).
    B) USES
    1) Guaifenesin is an expectorant used to loosen mucus and thin bronchial secretions to make a cough more productive. It is available as a single ingredient over-the-counter (OTC) medication and in combination with cough suppressants, antihistamines or decongestants that are available as both an OTC or prescription medication. It has been combined with dextromethorphan bromide, codeine, hydrocodone and carbetapentane citrate to suppress cough. This topic is limited to the effects of guaifenesin only. See the following managements for information regarding other products: Dextromethorphan, Codeine, and Hydrocodone.
    2) COMBINATION COUGH AND COLD MEDICATIONS: Reports of infant deaths have been associated with over-the-counter (OTC) cough and cold medications (Centers for Disease Control, 2007), and guaifenesin is commonly used as an expectorant in combination with a cough suppressant, a decongestant, and/or an antihistamine in the OTC cough and cold products. In January 2008, the US Food and Drug Administration issued a public health advisory recommending that cough and cold products not be used in children younger than 2 years because of the risk of serious and life-threatening effects (US Food and Drug Administration, 2008; US Food and Drug Administration, 2008).

Overview

Life Support

    A) This overview assumes that basic life support measures have been instituted.

Clinical Effects

    0.2.1) SUMMARY OF EXPOSURE
    A) USES: Guaifenesin, an expectorant, is used to loosen mucus and thin bronchial secretions to make a cough more productive. It is available as a single ingredient over-the-counter (OTC) medication and in combination with cough suppressants, antihistamines or decongestants that are available as both an OTC or prescription medication. This topic is limited to the effects of guaifenesin only.
    B) PHARMACOLOGY: As an expectorant it promotes the removal of secretions from the respiratory tract. It increases sputum volume and makes sputum less viscous, and promotes expectoration of retained secretions. During clinical trials, guaifenesin has been shown to stimulate the cholinergic pathway and increase mucus secretions from the airway submucosal glands; however, its effectiveness has not been determined.
    C) EPIDEMIOLOGY: As an OTC drug, guaifenesin is widely available, but significant toxicity is not anticipated.
    D) WITH THERAPEUTIC USE
    1) ADVERSE EFFECTS: There have been very few reports of adverse clinical effects with guaifenesin use. COMMON: Nausea, vomiting and gastrointestinal discomfort are the most commonly reported clinical events with therapy. Other symptoms have included rash, urticaria, headache and dizziness.
    E) WITH POISONING/EXPOSURE
    1) TOXICITY: Clinical effects are anticipated to be an extension of adverse effects reported with therapeutic use. Little information is available regarding toxicity. Overall, significant toxicity has not been reported with OTC guaifenesin. At high doses, it may cause CNS depression. In veterinary medicine, guaifenesin has been used as a muscle relaxant with sedative effects.
    2) CASE REPORT: A young woman died several hours after intentional guaifenesin exposure along with nonlethal amounts of sertraline, cetirizine and ethanol. She initially developed CNS depression followed by significant bradycardia followed by asystole that was unresponsive to resuscitation efforts; no physical cause of death could be found.
    0.2.20) REPRODUCTIVE
    A) There are limited studies examining the use of guaifenesin during pregnancy.

Laboratory Monitoring

    A) No specific laboratory studies (eg, CBC, electrolytes, urinalysis) are needed unless otherwise clinically indicated.
    B) Monitor fluids and electrolyte balance following significant vomiting.
    C) Monitor neurologic status following a significant exposure or a possible mixed ingestion.

Treatment Overview

    0.4.2) ORAL/PARENTERAL EXPOSURE
    A) MANAGEMENT OF MILD TO MODERATE TOXICITY
    1) Limited overdose experience. Treatment is symptomatic and supportive. Nausea and vomiting may develop following exposure; monitor fluids and electrolytes as indicated. Replace fluids and electrolytes as needed.
    B) MANAGEMENT OF SEVERE TOXICITY
    1) Treatment is symptomatic and supportive. Significant CNS depression may develop at high doses, especially if coingested with other agents. Initially monitor mental status; assess airway. Based on limited data, significant bradycardia followed by dysrhythmias developed in one adult. Obtain a baseline ECG and institute continuous cardiac monitoring as needed.
    C) DECONTAMINATION
    1) PREHOSPITAL: Toxicity after an acute ingestion is unlikely and has rarely been reported. Gastrointestinal decontamination is generally unnecessary unless a significant or mixed ingestion has occurred.
    2) HOSPITAL: Toxicity after an acute ingestion is unlikely and has rarely been reported. Gastrointestinal decontamination is generally unnecessary. Consider activated charcoal only if a significant or mixed ingestion with significant toxicity are involved.
    D) AIRWAY MANAGEMENT
    1) Airway support is unlikely to be necessary following a minor to moderate exposure. Monitor and support airway if a patient develops evidence of significant CNS depression.
    E) ANTIDOTE
    1) No known antidote.
    F) ENHANCED ELIMINATION
    1) It is unknown if hemodialysis would be effective in overdose.
    G) PATIENT DISPOSITION
    1) HOME CRITERIA: A patient with an inadvertent exposure, that remains asymptomatic can be managed at home.
    2) OBSERVATION CRITERIA: Patients with a deliberate overdose, and those who are symptomatic, need to be monitored until they are clearly improving and clinically stable.
    3) ADMISSION CRITERIA: Patients with severe symptoms (ie, CNS depression, cardiac arrhythmias) despite treatment, should be admitted.
    4) CONSULT CRITERIA: Consult a regional poison center or medical toxicologist for assistance in managing patients with severe toxicity or in whom the diagnosis is not clear.
    H) PHARMACOKINETICS
    1) Guaifenesin is readily absorbed from the GI tract. It is rapidly metabolized and excreted in the urine and its major urinary metabolite is beta-(2-methoxyphenoxy) lactic acid. The plasma half-life is one hour.

Range Of Toxicity

    A) TOXICITY: Severe toxicity is not anticipated following a guaifenesin exposure. Very little information is available to describe possible toxic or fatal concentrations of guaifenesin.
    B) THERAPEUTIC DOSE: ADULT: IMMEDIATE RELEASE: 200 to 400 mg orally every 4 hours; max 2400 mg/day. EXTENDED RELEASE: 600 to 1200 mg orally every 12 hours; max 2400 mg/day. PEDIATRIC: Dosing varies by product type (ie, disintegrating, syrup). In general, guaifenesin is not indicated in children younger than 2 years especially when used in combination cough and cold medications.

Clinical Effects

Summary Of Exposure

    A) USES: Guaifenesin, an expectorant, is used to loosen mucus and thin bronchial secretions to make a cough more productive. It is available as a single ingredient over-the-counter (OTC) medication and in combination with cough suppressants, antihistamines or decongestants that are available as both an OTC or prescription medication. This topic is limited to the effects of guaifenesin only.
    B) PHARMACOLOGY: As an expectorant it promotes the removal of secretions from the respiratory tract. It increases sputum volume and makes sputum less viscous, and promotes expectoration of retained secretions. During clinical trials, guaifenesin has been shown to stimulate the cholinergic pathway and increase mucus secretions from the airway submucosal glands; however, its effectiveness has not been determined.
    C) EPIDEMIOLOGY: As an OTC drug, guaifenesin is widely available, but significant toxicity is not anticipated.
    D) WITH THERAPEUTIC USE
    1) ADVERSE EFFECTS: There have been very few reports of adverse clinical effects with guaifenesin use. COMMON: Nausea, vomiting and gastrointestinal discomfort are the most commonly reported clinical events with therapy. Other symptoms have included rash, urticaria, headache and dizziness.
    E) WITH POISONING/EXPOSURE
    1) TOXICITY: Clinical effects are anticipated to be an extension of adverse effects reported with therapeutic use. Little information is available regarding toxicity. Overall, significant toxicity has not been reported with OTC guaifenesin. At high doses, it may cause CNS depression. In veterinary medicine, guaifenesin has been used as a muscle relaxant with sedative effects.
    2) CASE REPORT: A young woman died several hours after intentional guaifenesin exposure along with nonlethal amounts of sertraline, cetirizine and ethanol. She initially developed CNS depression followed by significant bradycardia followed by asystole that was unresponsive to resuscitation efforts; no physical cause of death could be found.

Cardiovascular

    3.5.2) CLINICAL EFFECTS
    A) ASYSTOLE
    1) WITH POISONING/EXPOSURE
    a) CASE REPORT: In a rare report, a 23-year-old woman intentionally ingested multiple drug agents including sertraline, cetirizine, guaifenesin and ethanol. A partner contacted medical services about 1 hour after exposure and stated that the patient was slurring her words. Once EMTs arrived, she was found to be unresponsive but was breathing on her own. During transport her heart rate dropped to the 30s and she was given atropine and intubated in the field. Upon arrival to the ED, ventricular fibrillation occurred. She was defibrillated and her rhythm showed asystole. She was given epinephrine followed by lidocaine with a short period of bradycardia followed by asystole which did not respond to further interventions. Postmortem laboratory analysis detected small, nonlethal amounts of sertraline (0.0038 mcg/mL) and cetirizine (0.14 mcg/mL) in femoral blood. In addition, an ethanol level of 0.120 g/100 mL (femoral blood) was consistent with intoxication but not considered a lethal concentration. With further laboratory analysis, guaifenesin was detected as follows: 25 mcg/mL in femoral blood, 17 mcg/g in the brain and 25 mcg/g in the liver. No physical cause of death could be found (Okic et al, 2013).

Neurologic

    3.7.2) CLINICAL EFFECTS
    A) HEADACHE
    1) WITH THERAPEUTIC USE
    a) Headache has been reported in patients using guaifenesin (Prod Info Humibid LA(R), 2003)(Prod Info ORGANIDIN(R) NR oral tablets, oral liquid, 2003).
    B) DIZZINESS
    1) WITH THERAPEUTIC USE
    a) Dizziness has been reported in patients using guaifenesin (Prod Info Humibid LA(R), 2003)(Prod Info ORGANIDIN(R) NR oral tablets, oral liquid, 2003).
    C) CENTRAL NERVOUS SYSTEM FINDING
    1) WITH THERAPEUTIC USE
    a) CNS DEPRESSION
    1) SUMMARY: At high doses, guaifenesin may cause CNS depression (Okic et al, 2013).
    2) CASE REPORT: In a rare report, a 23-year-old woman intentionally ingested multiple drug agents including sertraline, cetirizine, guaifenesin and ethanol. A partner contacted medical services about 1 hour after exposure and stated that the patient was slurring her words. Once EMTs arrived, she was found to be unresponsive but was breathing on her own. During transport her heart rate dropped to the 30s and she was given atropine and intubated in the field. Upon arrival to the ED, ventricular fibrillation occurred. She was defibrillated and her rhythm showed asystole. She was given epinephrine followed by lidocaine with a short period of bradycardia followed by asystole which did not respond to further interventions. Postmortem laboratory analysis detected small, nonlethal amounts of sertraline (0.0038 mcg/mL) and cetirizine (0.14 mcg/mL) in femoral blood. In addition, an ethanol level of 0.120 g/100 mL (femoral blood) was consistent with intoxication but not considered a lethal concentration. With further laboratory analysis, guaifenesin was detected as follows: 25 mcg/mL in femoral blood, 17 mcg/g in the brain and 25 mcg/g in the liver. No physical cause of death could be found (Okic et al, 2013).

Gastrointestinal

    3.8.2) CLINICAL EFFECTS
    A) NAUSEA AND VOMITING
    1) WITH THERAPEUTIC USE
    a) Nausea, vomiting and gastrointestinal discomfort are the most commonly occurring side effects of guaifenesin (Prod Info Humibid LA(R), 2003) (Prod Info ORGANIDIN(R) NR oral tablets, oral liquid, 2003).

Genitourinary

    3.10.2) CLINICAL EFFECTS
    A) UROLITHIASIS
    1) WITH POISONING/EXPOSURE
    a) Abuse of medications containing guaifenesin may produce urolithiasis. Laboratory analysis of the chemical composition of several renal calculi found that they were composed of a calcium salt of beta-(2-methoxyphenoxy)-lactic acid, a metabolite of the antitussive product, guaifenesin. It was found that 11 of 24 patients with kidney stones containing the guaifenesin metabolite, were using excessive amounts of over-the-counter stimulants and bronchodilators (stated dosages of 3 to 120 tablets per day, amounting to 600 to 24,000 mg of guaifenesin per day); of the other patients, some were suspected by their physicians of abusing drugs or other substances (Pickens et al, 1999).
    b) Laboratory analysis showed that renal calculi from 7 patients contained high amounts of a guaifenesin metabolite (beta-2- methoxyphenoxy-lactic acid) and, in some cases, small amounts of ephedrine. The stones were radiolucent on standard x-rays, but could be seen on unenhanced CT images. Data (available for 5 of 7 patients) indicated that 3 had a history of chemical dependency. Four patients admitted taking excessive amounts of over-the-counter products, including 50 to 100 tablets daily containing guaifenesin 200 mg and ephedrine 25 mg. The stones were easily fragmented by shockwave lithotripsy (Assimos et al, 1999).
    B) OCCLUSION OF URETER
    1) WITH POISONING/EXPOSURE
    a) CASE REPORT: A 23-year-old man with a history of alcohol abuse, intentionally ingested 10 tablets of guaifenesin 600 mg (total 6 grams) with dextromethorphan 30 mg (Mucinex DM) to reportedly "get high" and presented to the ED with acute onset of bilateral flank pain radiating to the scrotum along with hematuria and dysuria. His initial creatinine was 2.5 mg/dL. A CT of the abdomen and pelvis showed significant bilateral hydroureteronephrosis with perinephric edema. An indwelling double-J ureteral sent was emergently placed. Upon inspection of the bladder flocculent, whitish debris protruding from the ureteral orifices was found. Specimens were obtained from both the ureters and bladder and tested using Fourier transform infrared spectroscopy. The findings were consistent with guaifenesin metabolites. The stents were removed 6 weeks laster and a follow-up IV pyelogram showed no evidence of residual obstruction (Cockerill et al, 2013).

Dermatologic

    3.14.2) CLINICAL EFFECTS
    A) ERUPTION
    1) WITH THERAPEUTIC USE
    a) Rash, including urticaria has been reported with the use of guaifenesin (Prod Info Humibid LA(R), 2003)(Prod Info ORGANIDIN(R) NR oral tablets, oral liquid, 2003).

Reproductive

    3.20.1) SUMMARY
    A) There are limited studies examining the use of guaifenesin during pregnancy.
    3.20.3) EFFECTS IN PREGNANCY
    A) TRENDS IN USE
    1) Data were collected in 2 case-control studies of birth defects (Slone Epidemiology Center Birth Defects Study (BDS) and the National Birth Defects Prevention Study (NBDPS)) to assess the patterns of over-the-counter medication(s) use among pregnant women. From 1976 to 2004, women enrolled in the BDS study had an increased use in pregnancy of ibuprofen, pseudoephedrine, diphenhydramine, dextromethorphan, and guaifenesin, while women in the NBDPS study had higher use of guaifenesin and other OTC medications during pregnancy than before pregnancy(Werler et al, 2005). However, this study did not provide any information regarding guaifenesin use in pregnant women and potential risk to the fetus.
    B) INGUINAL HERNIA
    1) In a review, information gathered from the Collaborative Perinatal Project from 1958 to 1965, 132,500 women participated in a multicenter study; however, selection and exclusion criteria were not consistent. Of this group, 50282 mother-child pairs were identified and women were interviewed 4 times during their infant's first 2 years and annually until age 8 years. Of 197 women who took guaifenesin during their first trimester of pregnancy, 7 children with inguinal hernias were identified and 20 children were diagnosed with inguinal hernias among mothers that took guaifenesin any time during their pregnancy. Potential reporting bias among the participating centers limited any conclusions that could be drawn from the data (Silva et al, 2007).
    A) NEURAL TUBE DEFECTS
    1) In a review, information from a case-control study conducted from 1989 and 1991, 538 fetuses or live births with neural tube deficits were identified. Twelve cases of neural tube defects were reported following exposure to guaifenesin compared to 6 cases in the control group that reported exposure. Because the results were not statistically significant, it was concluded that guaifenesin did not contribute to neural tube defects. In another study, pregnant women exposed to guaifenesin during their first trimester reported no significant association between guaifenesin use and malformations (Silva et al, 2007).
    RISK SUMMARY
    2) Until more information is available, guaifenesin should only be used during pregnancy if the maternal condition justifies the potential risk to the fetus.

    3.20.4) EFFECTS DURING BREAST-FEEDING
    A) LACK OF INFORMATION
    1) No reports describing the use of guaifenesin during human lactation or measuring the amount, if any, of the drug excreted into milk have been located.
    B) BREAST MILK
    1) It is not known if guaifenesin affects the quantity and composition of breast milk. Until more data is available, use caution when considering the use of guaifenesin in lactating women.
    3.20.5) FERTILITY
    A) LACK OF INFORMATION
    1) It is not known if guaifenesin affects male or female reproduction.
    B) SPERM MOTILITY
    1) CASE REPORT: A 32-year-old, healthy nonsmoking man was being evaluated for infertility following the inability of his wife to conceive after 18 months of unprotected, regular intercourse. A sperm evaluation was completed and initially showed a low sperm count and decreased motility. He was treated with guaifenesin 600 mg twice daily for 2 months and motility improved from 10% to 61% and his sperm count increased from 2.4 to 34.7 million/mL. No other lifestyle changes were reported. Despite these laboratory changes, the patient's wife was not pregnant at the time of this report (Means et al, 2011). The authors suggested it may improve both male and female infertility related to mucus production; however, further studies are suggested.

Laboratory Monitoring

Monitoring Parameters Levels

    4.1.1) SUMMARY
    A) No specific laboratory studies (eg, CBC, electrolytes, urinalysis) are needed unless otherwise clinically indicated.
    B) Monitor fluids and electrolyte balance following significant vomiting.
    C) Monitor neurologic status following a significant exposure or a possible mixed ingestion.

Treatment

Life Support

    A) Support respiratory and cardiovascular function.

Patient Disposition

    6.3.1) DISPOSITION/ORAL EXPOSURE
    6.3.1.1) ADMISSION CRITERIA/ORAL
    A) Patients with severe symptoms (ie, CNS depression, cardiac arrhythmias) despite treatment, should be admitted.
    6.3.1.2) HOME CRITERIA/ORAL
    A) A patient with an inadvertent exposure, that remains asymptomatic can be managed at home.
    6.3.1.3) CONSULT CRITERIA/ORAL
    A) Consult a regional poison center or medical toxicologist for assistance in managing patients with severe toxicity or in whom the diagnosis is not clear.
    6.3.1.5) OBSERVATION CRITERIA/ORAL
    A) Patients with a deliberate overdose, and those who are symptomatic, need to be monitored until they are clearly improving and clinically stable.

Monitoring

    A) No specific laboratory studies (eg, CBC, electrolytes, urinalysis) are needed unless otherwise clinically indicated.
    B) Monitor fluids and electrolyte balance following significant vomiting.
    C) Monitor neurologic status following a significant exposure or a possible mixed ingestion.

Oral Exposure

    6.5.1) PREVENTION OF ABSORPTION/PREHOSPITAL
    A) SUMMARY
    1) Toxicity after an acute ingestion is unlikely and has rarely been reported. Gastrointestinal decontamination is generally unnecessary unless a significant or mixed ingestion has occurred.
    B) ACTIVATED CHARCOAL
    1) PREHOSPITAL ACTIVATED CHARCOAL ADMINISTRATION
    a) Consider prehospital administration of activated charcoal as an aqueous slurry in patients with a potentially toxic ingestion who are awake and able to protect their airway. Activated charcoal is most effective when administered within one hour of ingestion. Administration in the prehospital setting has the potential to significantly decrease the time from toxin ingestion to activated charcoal administration, although it has not been shown to affect outcome (Alaspaa et al, 2005; Thakore & Murphy, 2002; Spiller & Rogers, 2002).
    1) In patients who are at risk for the abrupt onset of seizures or mental status depression, activated charcoal should not be administered in the prehospital setting, due to the risk of aspiration in the event of spontaneous emesis.
    2) The addition of flavoring agents (cola drinks, chocolate milk, cherry syrup) to activated charcoal improves the palatability for children and may facilitate successful administration (Guenther Skokan et al, 2001; Dagnone et al, 2002).
    2) CHARCOAL DOSE
    a) Use a minimum of 240 milliliters of water per 30 grams charcoal (FDA, 1985). Optimum dose not established; usual dose is 25 to 100 grams in adults and adolescents; 25 to 50 grams in children aged 1 to 12 years (or 0.5 to 1 gram/kilogram body weight) ; and 0.5 to 1 gram/kilogram in infants up to 1 year old (Chyka et al, 2005).
    1) Routine use of a cathartic with activated charcoal is NOT recommended as there is no evidence that cathartics reduce drug absorption and cathartics are known to cause adverse effects such as nausea, vomiting, abdominal cramps, electrolyte imbalances and occasionally hypotension (None Listed, 2004).
    b) ADVERSE EFFECTS/CONTRAINDICATIONS
    1) Complications: emesis, aspiration (Chyka et al, 2005). Aspiration may be complicated by acute respiratory failure, ARDS, bronchiolitis obliterans or chronic lung disease (Golej et al, 2001; Graff et al, 2002; Pollack et al, 1981; Harris & Filandrinos, 1993; Elliot et al, 1989; Rau et al, 1988; Golej et al, 2001; Graff et al, 2002). Refer to the ACTIVATED CHARCOAL/TREATMENT management for further information.
    2) Contraindications: unprotected airway (increases risk/severity of aspiration) , nonfunctioning gastrointestinal tract, uncontrolled vomiting, and ingestion of most hydrocarbons (Chyka et al, 2005).
    6.5.3) TREATMENT
    A) SUPPORT
    1) MANAGEMENT OF MILD TO MODERATE TOXICITY
    a) Limited overdose experience. Treatment is symptomatic and supportive. Nausea and vomiting may develop following exposure; monitor fluids and electrolytes as indicated. Replace fluids and electrolytes as needed.
    2) MANAGEMENT OF SEVERE TOXICITY
    a) Treatment is symptomatic and supportive. Significant CNS depression may develop at high doses, especially if coingested with other agents. Initially monitor mental status; assess airway. Based on limited data, significant bradycardia followed by dysrhythmias developed in one adult. Obtain a baseline ECG and institute continuous cardiac monitoring as needed.
    B) MONITORING OF PATIENT
    1) No specific laboratory studies (eg, CBC, electrolytes, urinalysis) are needed unless otherwise clinically indicated. Monitor fluids and electrolyte balance following significant vomiting. Monitor neurologic status following a significant exposure or a possible mixed ingestion.

Enhanced Elimination

    A) SUMMARY
    1) It is unknown if hemodialysis would be effective in overdose.

Range Of Toxicity

Summary

    A) TOXICITY: Severe toxicity is not anticipated following a guaifenesin exposure. Very little information is available to describe possible toxic or fatal concentrations of guaifenesin.
    B) THERAPEUTIC DOSE: ADULT: IMMEDIATE RELEASE: 200 to 400 mg orally every 4 hours; max 2400 mg/day. EXTENDED RELEASE: 600 to 1200 mg orally every 12 hours; max 2400 mg/day. PEDIATRIC: Dosing varies by product type (ie, disintegrating, syrup). In general, guaifenesin is not indicated in children younger than 2 years especially when used in combination cough and cold medications.

Therapeutic Dose

    7.2.1) ADULT
    A) IMMEDIATE RELEASE
    1) SYRUP/TABLETS: 200 to 400 mg orally every 4 hours; MAX 2400 mg/day (OTC Product Information, as posted to the DailyMed site 10/01/2013; OTC Product Information, as posted to the DailyMed site 11/01/2012).
    B) EXTENDED RELEASE
    1) EXTENDED RELEASE TABLET: 600 to 1200 mg orally every 12 hours; MAX 2400 mg/day (OTC Product Information, as posted to the DailyMed site 10/01/2013a).
    7.2.2) PEDIATRIC
    A) IMMEDIATE-RELEASE
    1) TABLETS
    a) Children 12 Years or Older: Usual dose: 400 mg orally every 4 hours; maximum 2400 mg/day (OTC Product Information, as posted to the DailyMed site 11/01/2012).
    b) Do NOT use in children less than 12 years (OTC Product Information, as posted to the DailyMed site 11/01/2012).
    2) SOFT CHEWS, ORALLY DISINTEGRATING
    a) Children 12 years and Older: Usual dose: 200 to 400 mg every 4 hours; maximum 2400 mg/day (OTC Product Information, as posted to the DailyMed site 04/01/2011).
    b) Children 6 to Under 12 Years of Age: Usual dose: 100 to 200 mg orally every 4 hours; maximum 1200 mg/day (OTC Product Information, as posted to the DailyMed site 04/01/2011).
    c) Children less than 6 years: Check with a physician for dosing orally disintegrating formulation (ie, soft chews) in children less than 6 years of age (OTC Product Information, as posted to the DailyMed site 04/01/2011).
    3) ORAL SOLUTION
    a) SYRUP: 12 Years of Age and Older: Usual dose: 200 to 400 mg (1 tsp (5 mL) = 100 mg) orally every 4 hours; maximum 2400 mg/day (OTC Product Information, as posted to the DailyMed site 10/01/2013).
    b) Do NOT use in children less than 12 years (OTC Product Information, as posted to the DailyMed site 10/01/2013).
    4) GRANULES
    a) Children 12 Years or Older: Usual dose: 200 to 400 mg every 4 hours; maximum 2400 mg/day (OTC Product Information, as posted to the DailyMed site 06/01/2012).
    b) Children 6 to Under 12 Years of Age: Usual dose: 100 to 200 mg orally every 4 hours; maximum 1200 mg/day (OTC Product Information, as posted to the DailyMed site 06/01/2012).
    c) Children 4 to Under 6 Years of Age: Usual dose: 100 mg orally every 4 hours; maximum 600 mg/day (OTC Product Information, as posted to the DailyMed site 06/01/2012).
    d) Do NOT use in children less than 4 years (OTC Product Information, as posted to the DailyMed site 06/01/2012).
    B) EXTENDED-RELEASE
    1) Children 12 Years or Older: Usual dose: 600 to 1200 mg orally every 12 hours; maximum 2400 mg/day (OTC Product Information, as posted to the DailyMed site 10/01/2013a).
    2) Do NOT use in children less than 12 years (OTC Product Information, as posted to the DailyMed site 10/01/2013a).

Minimum Lethal Exposure

    A) SUMMARY
    1) A minimum lethal dose has not been established.
    B) CASE REPORT
    1) CASE REPORT: In a rare report, a 23-year-old woman intentionally ingested multiple drug agents including sertraline, cetirizine, guaifenesin and ethanol. A partner contacted medical services about 1 hour after exposure and stated that the patient was slurring her words. Once EMTs arrived, she was found to be unresponsive but was breathing on her own. During transport her heart rate dropped to the 30s and she was given atropine and intubated in the field. Upon arrival to the ED, ventricular fibrillation occurred. She was defibrillated and her rhythm showed asystole. She was given epinephrine followed by lidocaine with a short period of bradycardia followed by asystole which did not respond to further interventions. Postmortem laboratory analysis detected small, nonlethal amounts of sertraline (0.0038 mcg/mL) and cetirizine (0.14 mcg/mL) in femoral blood. In addition, an ethanol level of 0.120 g/100 mL (femoral blood) was consistent with intoxication but not considered a lethal concentration. With further laboratory analysis, guaifenesin was detected as follows: 25 mcg/mL in femoral blood, 17 mcg/g in the brain and 25 mcg/g in the liver. No physical cause of death could be found (Okic et al, 2013).

Maximum Tolerated Exposure

    A) SUMMARY
    1) A maximum tolerated exposure has not been determined.
    2) In general, guaifenesin is well tolerated and has a wide margin of safety. Adverse events are usually mild and infrequent; nausea and vomiting are the most common side effects (Prod Info ORGANIDIN(R) NR oral tablets, oral liquid, 2003).
    B) CASE REPORT
    1) CASE REPORT: A 23-year-old man with a history of alcohol abuse, intentionally ingested 10 tablets of guaifenesin 600 mg (total 6 grams) with dextromethorphan 30 mg (Mucinex DM) to reportedly "get high" and presented to the ED with acute onset of bilateral flank pain radiating to the scrotum along with hematuria and dysuria. His initial creatinine was 2.5 mg/dL. A CT of the abdomen and pelvis showed significant bilateral hydroureteronephrosis with perinephric edema. An indwelling double-J ureteral sent was emergently placed. Upon inspection of the bladder flocculent, whitish debris protruding from the ureteral orifices was found. Specimens were obtained from both the ureters and bladder and tested using Fourier transform infrared spectroscopy. The findings were consistent with guaifenesin metabolites. The stents were removed 6 weeks laster and a follow-up IV pyelogram showed no evidence of residual obstruction (Cockerill et al, 2013).

Pharmacology Toxicology

Pharmacologic Mechanism

    A) Guaifenesin is an expectorant which promotes the removal of secretions from the respiratory mucus tract. It increases sputum volume and makes sputum less viscous, and promotes expectoration of retained secretions (Prod Info ORGANIDIN(R) NR oral tablets, oral liquid, 2003).
    B) As an expectorant it can be ciliotoxic when applied directly to respiratory epithelium. During clinical trials, guaifenesin has been shown to stimulate the cholinergic pathway and increase mucus secretions from the airway submucosal glands; however, its effectiveness in therapy has not been determined (Rubin, 2007)

References

General Bibliography

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    3) Centers for Disease Control: Infant deaths associated with cough and cold medications--two states, 2005. MMWR Morb Mortal Wkly Rep 2007; 56(1):1-4.
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    14) None Listed: Position paper: cathartics. J Toxicol Clin Toxicol 2004; 42(3):243-253.
    15) OTC Product Information: Adult Tussin oral syrup, guaifenesin oral syrup. Rite Aid Corp., Camp Hill, PA, as posted to the DailyMed site 10/01/2013.
    16) OTC Product Information: BIDEX(R)-400 oral tablets, guaifenesin oral tablets. SJ Pharmaceuticals, Atlanta, GA, as posted to the DailyMed site 11/01/2012.
    17) OTC Product Information: CareOne(R) Mucus ER(TM) oral extended-release tablets, guaifenesin oral extended-release tablets. American Sales Company, Lancaster, NY, as posted to the DailyMed site 10/01/2013a.
    18) OTC Product Information: Children's Mucinex(R) Mini-Melts Chest Congestion oral granules, guaifenesin oral granules. Reckitt Benckiser, Parsippany, NJ, as posted to the DailyMed site 06/01/2012.
    19) OTC Product Information: Kids-EEZE(R) Chest Relief oral disintegrating tablets, guaifenesin oral disintegrating tablets. ProPhase Labs, Inc., Doylestown, PA , as posted to the DailyMed site 04/01/2011.
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    21) Pickens CL, Milliron AR, Fussner AL, et al: Abuse of guaifenesin-containing medications generates an excess of a carboxylate salt of beta-(2-methoxyphenoxy)-lactic acid, a guaifenesin metabolite, and results in urolithiasis. Urology 1999; 54:23-27.
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    23) Product Information: OBREDON oral solution, hydrocodone bitartrate guaifenesin oral solution. Sovereign Pharmaceuticals, LLC (per FDA), Fort Worth, TX, 2014.
    24) Product Information: ORGANIDIN(R) NR oral tablets, oral liquid, guaifenesin oral tablets, oral liquid. MedPointe Pharmaceuticals, Somerset, NJ, 2003.
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    30) US Food and Drug Administration: Nonprescription Cough and Cold Medicine Use in Children : FDA Recommends that Over-the-Counter (OTC) Cough and Cold Products not be used for Infants and Children under 2 Years of Age. US Food and Drug Administration. Rockville, MD. 2008. Available from URL: http://www.fda.gov/cder/drug/advisory/cough_cold_2008.htm.
    31) US Food and Drug Administration: Using Over-the-Counter Cough and Cold Products in Children. US Food and Drug Administration. Silver Spring, MD. 2008a. Available from URL: http://www.fda.gov/downloads/forconsumers/consumerupdates/ucm048524.pdf. As accessed 2013-10-06.
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