These described symptoms such as severity of chest congestion, mucus thickness and cough. Some of these 11 exploratory parameters showed strong trends or statistically significant differences between guaifenesin and placebo. A PRO validation process served to qualify more focused subsets of 4 and 8 questions. To explore effects on sputum as objective endpoints, laboratory analyses were performed on patient mucus samples from the pilot study.
The laboratory analyses could not demonstrate differences in mucus properties with guaifenesin compared to placebo; however, it should be noted that methodological issues with mucus sample collection and shipping were present, raising some questions about the interpretation of the laboratory results [ 44 ]. Guaifenesin was reported to be effective for improving symptomatic rhinitis and sinusitis by decreasing nasal congestion and postnasal discharge in immunocompromised HIV positive patients [ 45 , 46 ].
Despite some conflicting data available, some patients with rhinitis benefit from using guaifenesin [ 12 ]. As a single agent, guaifenesin has a well-established and favorable safety and tolerability profile.
Its safety record is supported by data from published clinical studies and a history of post-marketing surveillance safety reports covering more than 50 years in the US and around the world. Common side effects reported for the drug include dizziness, headache, and gastrointestinal disturbances at high doses [ 17 ]. Guaifenesin had the lowest frequency of mentions for non-fatal AEs by system organ class SOC at estimated supra-therapeutic and even at estimated unknown dosing; and the second lowest frequency of mentions for non-fatal AEs by SOC at estimated therapeutic dosing.
The few published reports of serious adverse events related to the use of guaifenesin have mostly been in the context of overdose and use as part of multiple-drug combinations for various cough and cold indications. Published reports include renal stone formation with chronic guaifenesin overdose [ 49 ], and acute fatal intoxication by a combination of guaifenesin, diphenhydramine, and chlorpheniramine, although the relative contribution of guaifenesin to the fatality could not be determined [ 50 ].
Pregnancy category C status for GGE was determined by the FDA based on the absence of definitive studies assessing potential risks to the fetus [ 3 , 51 ]. Results of a recently published study in female, pregnant rats, after testing very high doses of guaifenesin, suggest that the risk of fetal abnormalities cannot be ruled out [ 52 ].
The medical literature and safety databases do not show meaningful signals suggesting a significant risk of fetal development issues after pregnant women used guaifenesin. Thus, caution regarding the use of GGE in pregnant women is warranted [ 51 ]. Immediate-release IR and extended-release ER guaifenesin are available in single-agent formulations Table 7. There are also many popular guaifenesin-containing combination OTC and prescription products available on the market, but these are outside the scope of this article.
The dual dosing range of guaifenesin in the US allows patients the flexibility to titrate doses to achieve optimal efficacy. In the US, adults and children above 12 years old may take guaifenesin in oral doses of to mg every 4 h, up to a maximum of mg over 24 h [ 17 ]. Pediatric doses cater to children aged 2—12 years, and differ according to age groups, i. In Canada, guaifenesin is not recommended for children aged 12 years and below.
Dosing regimens and daily maximum doses for adults and children above 12 years old in Canada daily dose of mg maximum also differ from those in the US [ 53 ]. Examples of currently available over-the-counter guaifenesin formulations and recommended doses in the US and Canada.
Because of guaifenesin short half-life, frequent dosing with IR guaifenesin is required to maintain therapeutic levels of the drug in the body Fig. Subsequently h extended release form of guaifenesin were designed to provide bioequivalent pharmacokinetic characteristics to generic IR guaifenesin products [ 20 ] and are currently approved as h tablet ER guaifenesin formulation in the US market.
An example of such ER products is a bi-layer tablet formulation containing mg of guaifenesin and comprising an IR layer that allows rapid release of guaifenesin to achieve an early C max , and an ER layer that allows sustained release of guaifenesin to produce a steady plasma concentration over a h period Fig. Following approval of this extended release form of guaifenesin NDA in , the FDA required the removal of all marketed, but unapproved, timed-release guaifenesin products from the market by Schematic pharmacokinetic profile of extended-release ER vs immediate-release IR guaifenesin formulations.
Extended-release ER guaifenesin blue line attained bioequivalent plasma concentrations to those obtained with 3 immediate-release IR guaifenesin doses orange line. The unique bi-layer tablet formulation comprises an IR layer that permits immediate release of guaifenesin to rapidly attain maximum plasma concentrations C max , and an ER layer that permits sustained release of guaifenesin to maintain prolonged blood plasma levels of guaifenesin over 12 h.
Figure adapted from Vilson and Owen, [ 20 ]. This review provides an updated and comprehensive perspective on the use of guaifenesin in treating respiratory disorders in which excessive mucus is an important clinical feature.
Excessive mucus secretion and local accumulation in the airway occurs in both acute URTIs and chronic respiratory disorders with an underlying inflammatory etiology such as chronic bronchitis and COPD. The expectorant properties of guaifenesin, which help to thin bronchial secretions and promote mucus clearance, were demonstrated in studies involving patients with chronic bronchitis or other chronic respiratory conditions.
Studies in symptomatic chest congestion and acute cough, as well as in acute rhino-sinusitis indications, have yielded mixed results. This may be understandable, given the context of rapidly changing symptoms in acute URTIs, which are challenging to study under standard clinical trial conditions. Some studies showed evidence of efficacy based on improvements in subjective measures as patients assessed their cough, mucus clearance, or chest congestion symptoms. However, in many cases the methods were not validated or results were not confirmed by subsequent studies.
For this reason, the effects of guaifenesin have been more consistently demonstrated in stable chronic respiratory disease models. Further research is needed to clarify the antitussive effectiveness of guaifenesin and its ability to relieve chest congestion in acute URTIs in children and adults, and the utility of the drug in improving symptoms of rhino-sinusitis.
To date, the approved indications for guaifenesin have not changed from those included in the Final Monograph. Interestingly, the secondary indication for stable chronic bronchitis remains largely underutilized or unrecognized even among US medical professionals. A large body of AE reporting data supports the safety of guaifenesin for adult and pediatric use. Well-established as a safe expectorant drug, guaifenesin has achieved common usage for the relief of mucus-related symptoms of acute URTIs and for patients with mucus-related symptoms in the context of stable chronic bronchitis.
Additional, up-to-date, and high-quality data are needed to explore the full potential of this compound in established uses, and in new respiratory indications associated with mucus hypersecretion. The authors would like to thank the subjects, clinicians, and scientists who participated in the design, conduct, and analysis of the studies described in this review paper.
Medical writing and editorial support in the preparation of this review article was funded by Reckitt Benckiser, LLC. There are no other sources of funding to declare. All authors participated in drafting the manuscript, and have read and approved the final manuscript.
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations. Helmut H. Albrecht, Email: ude. UIF hcerblAH. Peter V. Dicpinigaitis, Email: moc. Eric P. Guenin, Email: moc. National Center for Biotechnology Information , U. Journal List Multidiscip Respir Med v.
Multidiscip Respir Med. Published online Dec Albrecht , 1 Peter V. Dicpinigaitis , 2 and Eric P. Guenin 3. Author information Article notes Copyright and License information Disclaimer. Corresponding author. Received May 3; Accepted Nov This article has been cited by other articles in PMC. Abstract Guaifenesin, a mucoactive drug, acts by loosening mucus in the airways and making coughs more productive.
Background Respiratory conditions have been known throughout most of recorded medical history, and today mortality and morbidity associated with respiratory conditions represent a substantial global health burden.
Table 1 Brief history of guaifenesin and its regulatory path in the US. Time Key events Pres Used as natural remedy by Native Americans s Guaiac extract used as stimulant remedies, e. From , the FDA removed all marketed, but unapproved, timed-release guaifenesin products from the market. Open in a separate window. Mucus in airway function and disease The respiratory tract is covered with a layer of mucus, which maintains airway humidification and acts as a protective barrier to inhaled particles and microorganisms.
Guaifenesin: multiple effects on pathological mucus Therapy with mucoactive drugs is an important factor in the treatment of respiratory conditions in which mucus hypersecretion is prevalent. Keep from freezing. There is a problem with information submitted for this request. Sign up for free, and stay up-to-date on research advancements, health tips and current health topics, like COVID, plus expert advice on managing your health.
Error Email field is required. Error Include a valid email address. To provide you with the most relevant and helpful information and to understand which information is beneficial, we may combine your e-mail and website usage information with other information we have about you. If we combine this information with your PHI, we will treat all of that information as PHI, and will only use or disclose that information as set forth in our notice of privacy practices.
You may opt-out of e-mail communications at any time by clicking on the Unsubscribe link in the e-mail. Our Housecall e-newsletter will keep you up-to-date on the latest health information. Also tell your health care professional if you have any other types of allergies, such as to foods, dyes, preservatives, or animals. For non-prescription products, read the label or package ingredients carefully.
Although there is no specific information comparing use of guaifenesin in children with use in other age groups, this medicine is not expected to cause different side effects or problems in children than it does in adults. However, check with your doctor before using this medicine in children who have a chronic cough, such as occurs with asthma, or who have an unusually large amount of mucus or phlegm with the cough.
Children with these conditions may need a different kind of medicine. Also, guaifenesin should not be given to children and infants younger than 2 years of age unless you are directed to do so by your doctor. Many medicines have not been studied specifically in older people. Therefore, it may not be known whether they work exactly the same way they do in younger adults. Although there is no specific information comparing use of guaifenesin in the elderly with use in other age groups, this medicine is not expected to cause different side effects or problems in older people than it does in younger adults.
There are no adequate studies in women for determining infant risk when using this medication during breastfeeding. Weigh the potential benefits against the potential risks before taking this medication while breastfeeding. Although certain medicines should not be used together at all, in other cases two different medicines may be used together even if an interaction might occur. In these cases, your doctor may want to change the dose, or other precautions may be necessary.
Tell your healthcare professional if you are taking any other prescription or nonprescription over-the-counter [OTC] medicine. Stacy Wiegman, PharmD.
Kathleen Handal, MD. What side effects does Guaifenesin with Dextromethorphan cause? Based on information from iGuard. How does fexofenadine treat allergy symptoms? Since fexofenadine is an antihistamine, it blocks the effects of histamine, namely allergy symptoms.
0コメント