Joseph P. Nathan, MS, PharmD

Cough is the most common symptom prompting patients to seek health care in the ambulatory care setting. Although a cough can be secondary to a variety of medical conditions, the most common etiology is a viral upper respiratory infection (URI).

 A nonprescription drug commonly used to manage a cough is guaifenesin which is labeled for use as an expectorant. According to a 2019 survey of pharmacists, Mucinex and Robitussin, 2 branded formulations of guaifenesin, were recommended close to 2.5 million times per month during that year.

Guaifenesin’s use as a medicinal substance dates back to as early as the 1500s when Native Americans used an extract of the guaiac tree as a natural remedy for various ailments.Today, guaifenesin is an FDA-approved drug that is sold in a variety of oral formulations, including liquid dosage forms as well as immediate- and extended-release solid dosage forms. The recommended adult dose of guaifenesin is 200 mg to 400 mg every 4 to 6 hours, as needed, for the immediate-release formulations and 600 mg to 1200 mg every 12 hours, as needed, for the extended-release formulations. Although guaifenesin’s mechanism of action is not fully understood, it is thought to act by irritating the gastric mucosa and stimulating respiratory tract secretions. This, in turn, increases the volume and decreases the viscosity of bronchial secretions.

 In addition to being an expectorant, guaifenesin has also been proposed to act as an antitussive by inhibiting cough-reflex sensitivity in patients with URI.

 Guaifenesin is generally well tolerated with the most commonly reported adverse effects being nausea, vomiting, and gastrointestinal discomfort.

Despite its popularity and its status as an FDA-approved expectorant, evidence to support guaifenesin’s efficacy is limited and conflicting. The purpose of this article is to present the reader with data from clinical trials which were designed primarily to evaluate the use of guaifenesin in the management of cough associated with URI.

In 1977, Robinson et al. described a double-blind trial that examined whether guaifenesin was superior to placebo in facilitating the coughing up of sputum and ameliorating dry cough in patients with an acute URI.

 Two hundred and thirty-nine adult patients with moderate-to-severe cough were randomly assigned to receive 200 mg of guaifenesin syrup or placebo 4 times per day for 3 days. Efficacy was evaluated subjectively through patients’ assessments of symptoms and of the quality and quantity of sputum as well as through physicians’ assessments of patients’ symptoms at different time points throughout the study. The investigators reported that, overall, in patients with dry or productive cough, guaifenesin decreased cough frequency, cough intensity, and chest discomfort, and resulted in a significantly thinner sputum. Likewise, in patients with productive cough, guaifenesin was found to facilitate raising sputum. Notably, these findings were not consistent across all the assessment parameters and time points at which they were measured.

In 1982, Kuhn et al. described a double-blind study that evaluated the effect of guaifenesin on cough frequency in young adults with a cough secondary to a cold.

 Sixty-five patients were randomly assigned to receive 400 mg of guaifenesin syrup or placebo every 6 hours for a total of 6 doses. Guaifenesin’s efficacy was evaluated subjectively through a completion of a patient self-assessment questionnaire throughout the course of the study and objectively through a cough count using an audio recording of the patients (performed on 42 of the study participants). The investigators reported that in the subjective evaluation, guaifenesin was associated with a statistically significant decrease in sputum thickness in patients who experienced a productive cough; however, guaifenesin failed to significantly reduce the number of coughs when assessed by objective cough counts. 

In 2003, Dicpinigaitis and Gayle described a randomized, double-blind trial that evaluated guaifenesin’s effect on cough reflex sensitivity in 14 healthy volunteers and 14 patients with acute viral URI.

On 2 separate days, each participant received a 400-mg guaifenesin capsule or placebo. A capsaicin cough challenge test, which involves the inhalation of capsaicin, a known tussive agent, was performed 1 to 2 hours after the ingestion of guaifenesin or placebo. Guaifenesin’s efficacy was determined by the concentration of capsaicin needed to induce 5 or more coughs (C5). The investigators reported that in the participants with URI, mean log C5 afterguaifenesin was significantly higher than after placebo; in the healthy volunteers, such a difference was notnoted. The investigators concluded that a single, 400-mg dose of guaifenesin inhibits cough reflex sensitivity to inhaled capsaicin in individuals with acute viral URI.

In 2009, Dicpinigaitis et al. described a study that assessed the antitussive effect of guaifenesin and benzonatate, alone and in combination, in 30 adult patients with acute URI.

 In this double-blind, placebo-controlled, crossover study, patients were randomized to receive capsules containing benzonatate 200 mg, guaifenesin 600 mg, benzonatate 200 mg plus guaifenesin 600 mg, or placebo. Patients received a single dose of 3 of the 4 aforementioned treatments on 3 separate days within a 7-day period. The study utilized the capsaicin cough challenge and its main efficacy measure was C5. The investigators reported that mean log C5 was significantly greater with guaifenesin as compared with placebo; mean log C5 with benzonatate plus guaifenesin was also significantly greater than with guaifenesin alone. The authors noted that guaifenesin and the combination of guaifenesin and benzonatate inhibited cough-reflex sensitivity in patients with acute URI.

In 2014, Hoffer-Schaefer et al. described a study that evaluated the impact of guaifenesin on sputum properties associated with a productive cough secondary to an acute URI.

 In this double-blind, placebo-controlled, multicenter study, 378 adolescent and adult patients were randomized to receive 1200 mg of extended-release guaifenesin or placebo every 12 hours for 7 days. No significant differences were found in the any of the sputum measures in the guaifenesin group as compared with the placebo group.

In 2015, Bennett et al. described a study assessing the effect of guaifenesin on mucociliary clearance and cough clearance as measured by the rate of removal of inhaled radioactive tracer particles; other sputum properties were also assessed.

Participants were also asked to subjectively rate the severity of the chest congestion, mucus thickness, and cough. In this double-blind, placebo-controlled study, 38 adult patients with acute URI were randomized to receive a single 1200-mg dose of extended release guaifenesin or placebo. Assessments were conducted at several time points over the course of the post-dose period. Guaifenesin use did not result in significant improvements in any of the objective outcome measures as compared with placebo. A statistically significant difference favoring guaifenesin was noted in the subjective assessment of mucus thickness at one of the evaluation time points.

Few clinical trials have been conducted to assess guaifenesin’s efficacy in the management of cough secondary to URI. The trials varied in their methodologies (eg, dosage forms, dosage regimens, outcome measures) and generally included a small number of participants. In these trials, guaifenesin was found to be effective in some, but not all, of the assessments of efficacy. Given these mixed results, drawing firm conclusions about guaifenesin’s efficacy is challenging. Nonetheless, given its overall safety profile, the use of guaifenesin may be considered on a case-by-case basis for patients who are bothered greatly by their cough.

Dr Nathan is the director at the International Drug Information Center and associate professor at Arnold & Marie Schwartz College of Pharmacy and Health Sciences, Long Island University.

Dr Grossman is a drug information specialist at the International Drug Information Center and adjunct assistant professor at Arnold & Marie Schwartz College of Pharmacy and Health Sciences, Long Island University.

1. Frei CR, Frei BL. Upper Respiratory Tract Infections. In: DiPiro JT, Yee GC, Posey L, Haines ST, Nolin TD, Ellingrod V, eds. 

Pharmacotherapy: A Pathophysiologic Approach, 11e

2. Contemporary Clinic. Pharmacy Recommendations. 

https://www.contemporaryclinic.com/otcguide/coughcoldallergy/expectorants

3. Albrecht HH, Dicpinigaitis PV, Guenin EP. Role of guaifenesin in the management of chronic bronchitis and upper respiratory tract infections. 

. 2017;12:31. Published 2017 Dec 11. doi:10.1186/s40248-017-0113-4.

4. Guaifenesin. In: IBM Micromedex® DRUGDEX® (electronic version). IBM Watson Health, Greenwood Village, Colorado, USA. Accessed August 27, 2020.

5. Robinson RE, Cummings WB, Deffenbaugh ER. Effectiveness of guaifenesin as an expectorant: a cooperative double-blind study. 

6. Kuhn JJ, Hendley O, Adams KF, Clark JW, Gwaltney JM. Antitussive effects of guaifenesin in young adults with natural colds. 

7. Dicpinigaitis PV, Gayle YE. Effect of guaifenesin on cough reflex sensitivity. 

8. Dicpinigaitis PV, Gayle YE, Solomon G, Gilbert RD. Inhibition of cough-reflex sensitivity by benzonatate and guaifenesin in acute viral cough. 

. 2009;103(6):902-906. doi:10.1016/j.rmed.2008.12.008.

9. Hoffer-Schaefer A, Rozycki HJ, Yopp MA, Rubin BK. Guaifenesin has no effect on sputum volume or sputum properties in adolescents and adults with acute respiratory tract infections. 

 2014;59(5):631-636. doi: 10.4187/respcare.02640.

10. Bennett WD, Kala A, Duckworth H, et al. Effect of a single 1200 mg dose of Mucinex on mucociliary and cough clearance during an acute respiratory tract infection. 

 2015;109(11):1476-1483. doi: 10.1016/j.rmed.2015.09.017.

Articles

Despite its popularity and its status as an FDA-approved expectorant, evidence to support guaifenesin’s efficacy is limited and conflicting. 

Reevaluating the Use of Guaifenesin in the Management of Acute Cough Associated With the Common Cold

Some patients affected by the coronavirus disease 2019 (COVID-19) may be concerned about hyposmia (reduced ability to smell) or anosmia (loss of smell) that they experience after contracting the virus. Although the exact prevalence of olfactory disturbances in patients with COVID-19 is not known, various studies reported the rates to be as low as 5% and as high as 98%.

 In a telephone survey of Italian patients diagnosed with COVID-19, the investigators found that olfactory disturbances were reported early on in the course of the disease and that severe disturbances were more likely to be reported by female patients.

 Likewise, the investigators found that patients who reported severe olfactory disturbances were significantly younger than patients with no or mild olfactory disturbances.

Reports of olfactory disturbances are not unique to the COVID-19 pandemic. Patients with other viral upper respiratory infections (URIs) may develop olfactory loss as a result of nasal inflammation, mucosal edema, and obstruction of airflow into the olfactory cleft.

 Episodes of olfactory loss secondary to URIs are usually self-limiting and generally do not persist beyond the resolution of URI symptoms. At times, however, the loss of smell may persist for an extended period of time (months to years) and is thought to result from a more direct injury to the olfactory system that is induced by the viral infection. With respect to patients with COVID-19, unpublished data and anecdotal reports suggest that the resolution of olfactory symptoms usually occurs within approximately 2 weeks. At the present time, it is unknown what proportion of patients with COVID-19 develop persistent olfactory loss.4 When these symptoms do persist for an extended period of time, they may be troubling and concerning to the affected individuals. In such cases, patients or their caregivers may turn to health care professionals for advice and guidance on management strategies.

Numerous drugs and supplements have been studied for the management of viral-associated olfactory loss.

 Oral and intranasal steroids have been used for post-infectious olfactory loss, but they are not recommended because of the risks associated with their use.

 Intranasal sodium citrate, intranasal vitamin A, or systemic omega-3 have shown some efficacy but definitive evidence to support their use in patients with COVID-19 is lacking.4 In the absence of proven pharmacotherapy, olfactory training (OT) has been recommended as a primary treatment strategy for viral-associated olfactory loss.3 Through OT, the brain is re-trained to correctly interpret the neurologic signals received from various odorants. The training consists of smelling 4 different odors twice per day, every day. Specifically, patients are advised to smell 1 odor at a time for 15 seconds while trying to recall what it previously smelled like. Patients are then advised to rest for 10 seconds and repeat the process until all 4 odors have been sampled. While specific scents have been suggested for OT (eg, rose, eucalyptus, lemon, clove), patients can select specific scents that they wish to incorporate into their training. Many individuals purchase essential oils containing the odors that are selected for inclusion in their training. The training process continues with the same 4 odors for a 3 month period, after which training begins with a new set of odors. Olfactory training has been shown to be effective in multiple clinical studies but results vary.

 The improvement in smell is often slow and occurs over many months or even years.

In summary, olfactory loss is frequently reported by patients with COVID-19. Although in some patients, the condition is self-limiting, in others it may persist for an extended period of time. In the absence of proven pharmacotherapy, OT is recommended as a primary management strategy.

1. Chung TWH, Sridhar S, Zhang AJ, et al. Olfactory dysfunction in coronavirus disease 2019 patients: observational cohort study and systematic review. 

2. Mercante G, Ferreli F, De Virgilio A, et al. Prevalence of taste and smell dysfunction in coronavirus disease 2019 [published online ahead of print, 2020 Jun 18]. 

. 2020;e201155.doi:10.1001/jamaoto.2020.1155.

3. Soler ZM, Patel ZM, Turner JH, et al. A primer on viral‐associated olfactory loss in the era of COVID‐19. 

. 2020;10.1002/alr.22578.doi:10.1002/alr.22578.

4. Whitcroft KL, Hummel T. Olfactory dysfunction in COVID-19: diagnosis and management. 

 2020;323(24):2512–2514.doi:10.1001/jama.2020.8391.

Some patients affected by COVID-19 may be concerned about hyposmia (reduced ability to smell) or anosmia (loss of smell) that they experience after contracting the virus. 

Smell Disturbances in the Era of COVID-19

) is a common condition that is estimated to affect approximately 10% to 20% of the population in the Western world.

The most common symptom of GERD is heartburn, which can be described as a burning sensation in the middle of the chest or in the middle of the abdomen. Other symptoms that may be suggestive of GERD include bad breath, nausea, vomiting, painful and/or difficult swallowing, respiratory complaints, and wearing away of the teeth.

 An important element in the etiology of GERD is the abnormal reflux of gastric contents from the stomach into the esophagus, oral cavity, and/or the lung.

 Gastroesophageal reflux may be associated with defective lower esophageal sphincter (LES) pressure or function, which may be due to spontaneous transient LES relaxations, transient increases in intra-abdominal pressure, or an atonic LES; other etiologies may also contribute to the development of GERD.

The first step in managing GERD includes nonpharmacologic interventions/lifestyle modification. Patients presenting with GERD symptoms should be counseled on strategies that may address their symptoms. Patients who are overweight or those who have recently gained weight should be counseled about the importance of weight loss. It is important to note that GERD symptoms may develop even in those individuals with a normal body mass index who experienced recent weight gain.

The weight loss goal in patients suffering from GERD should be at least 10%.

 Patients, especially those who suffer from nocturnal GERD, should also be counseled about the benefits of elevating the head of the bed and avoiding meals 2 to 3 hours before bedtime.1 Head of bed elevation can be achieved by inserting a foam wedge under the mattress such that the head of the bed will be elevated by 6 to 8 inches. Traditionally, patients suffering from GERD have been counseled about the need to quit smoking and eliminate foods that are believed to trigger reflux, including chocolate, caffeine, alcohol, acidic and/or spicy foods, as these may decrease LES pressure or act as direct irritants to the esophageal mucosa. However, because clinical evidence to support the global avoidance of “trigger” foods is lacking, guidelines published in the 

 note that this strategy is not recommended in the management of GERD.

Pharmacologic management should be reserved for patients in whom non-pharmacologic interventions/lifestyle modifications were unsuccessful. The pharmacologic management of GERD is primarily aimed at acid suppression, which at times may be accompanied by adjunctive treatment with promotility agents.

 Acid suppression may be achieved with the use of non-prescription antacids, which are appropriate for treating milder intermittent GERD symptoms. Patients suffering from more severe or chronic symptoms usually require treatment with proton pump inhibitors (PPIs) or with H2 receptor antagonists (H2RAs).

 The various PPIs on the market are similar to one another in efficacy, useful in the management of moderate-to-severe symptoms, and generally produce long-lasting effects over the course of the day. When treatment is initiated, PPIs are typically dosed once daily, with the dose administered prior to the first meal of the day. Traditional delayed-release PPIs should be administered 30 to 60 minutes before a meal, but dexlansoprazole can be dosed more flexibly relative to the timing of the meal. Patients that only respond partially to PPI therapy may benefit from adjusting the timing of the dose, twice daily dosing, and/or switching to another PPI. In patients with mild-to-moderate disease, H2RAs may be appropriate. These agents, which are also similar in their efficacies to one another, are usually dosed in divided doses, but often produce suboptimal results.

 Promotility agents, such as metoclopramide, may be used as adjuncts to acid suppression therapy in patients with a known motility defect; however, these agents generally have undesirable adverse effects and their efficacy is limited.

1. Katz PO, Gerson LB, Vela MF. Guidelines for the Diagnosis and Management of Gastroesophageal Reflux Disease. 

. 2013;108(3):308-328. doi: 10.1038/ajg.2012.444.

2. The National Institute of Diabetes and Digestive and Kidney Diseases. Symptoms & Causes of GER & GERD. November 2014. Accessed June 30, 2020.

https://www.niddk.nih.gov/health-information/digestive-diseases/acid-reflux-ger-gerd-adults/symptoms-causes

3. May D, Thiman ML, Rao SSC. Gastroesophageal Reflux Disease. In: DiPiro JT, Yee GC, Posey L, Haines ST, Nolin TD, Ellingrod V, eds. Pharmacotherapy: A Pathophysiologic Approach, 11e. McGraw-Hill; 2020.

Pharmacists can counsel patients with GERD on strategies to address their symptoms. 

Gastroesophageal Reflux Disease: A Focus on Management and Patient Education

Constipation is a common disorder that has a prevalence of approximately 20% in the general population and occurs even more frequently in the elderly.

 Constipation is generally characterized by infrequent bowel movements (BMs) over the course of a week (generally fewer than 3 BMs weekly), but patients may have a wide range of symptoms, including hard stools, a feeling of incomplete evacuation, abdominal discomfort, bloating, and distention, as well as other symptoms (eg, excessive straining and a sense of anorectal blockage during defecation).

 Constipation may be secondary to other disorders, lifestyle factors, or drug therapy, and these situations may be managed by addressing the underlying cause(s). Alternatively, an identifiable cause may not be known and in such instances, the condition is referred to as primary or idiopathic constipation.

 Regardless of the etiology, pharmacologic intervention may be necessary to manage the associated symptoms.

 Pharmacological agents used in the management of constipation fall within a variety of laxative classes, such as bulk forming agents (eg, psyllium), osmotic agents (eg, polyethylene glycol), stimulants (eg, bisacodyl, senna), lubricants (eg, mineral oil), chloride channel activator (lubiprostone), guanylate cyclase activator (linaclotide), and serotonergic agents (eg, tegaserod).

 An additional class of agents used to manage constipation includes emollient laxatives. Docusate, a commonly used member of this class, is believed to act as a stool softening agent by increasing the amount of water and lipids the stool absorbs in the gut, resulting in a softer, easier-to-pass stool.

Docusate, formerly known as dioctyl sulfosuccinate (DSS), was approved for use in the United States in 1957 and is available in 2 different salt forms: docusate sodium (Colace and others) and docusate calcium (Surfak and others).

 Docusate is available over the counter in numerous oral dosage forms as well as a rectal enema. The usual recommended adult dose of oral docusate is 100-300 mg/day for the sodium salt and 240 mg/day for the calcium salt.

In its 2013 Position Statement on Constipation, the American Gastroenterological Association (AGA) recommends that constipation be initially managed with a gradual increase in fiber intake (through dietary means and/or via supplementation) and/or with inexpensive osmotic agents, such as milk of magnesia or polyethylene glycol. The AGA recommends that low-cost stimulant laxatives be added to the initial agents when needed, and that newer, more costly agents be reserved for patients who do not respond to less costly laxatives.

 Docusate is not included in the aforementioned recommendations, however, its use is common, with greater than 3.5 million prescriptions for docusate dispensed in the US in 2017.

 Moreover, docusate is listed on the World Health Organization’s 

the safest and most effective medicines needed in a health system

 Despite its popularity, evidence to support its use is limited.

The earliest identified data on the clinical use of docusate dates back to 1956. At that time, Cass and Frederikdescribed a study involving 74 hospitalized patients who were treated for chronic constipation.

 In this randomized, double-blind, placebo-controlled, crossover study, patients were randomized to receive docusate sodium 60 mg daily for 20 days or placebo for 10 days. The investigators reported differences in the outcomes of stool consistency (3.64 vs 4.0, respectively [with 1 = watery and 5 = extremely hard]) and frequency of BM (4.55/patient/week vs 3.5/patient/week, respectively) in the docusate group as compared with placebo group. It is unclear whether these differences were statistically significant.

A 1968 article by Hyland and Foran describes a study involving 34 geriatric hospitalized patients who were being treated for chronic constipation.

 In this placebo-controlled, crossover study, patients were randomized to receive docusate sodium 100 mg or placebo 3 times daily for 4 weeks. The investigators reported that docusate increased stool frequency by a mean of 1 BM per week compared with placebo; this difference was found to be statistically significant.

In another article, published in 1976, Goodman et al. described a study that examined the use of docusate for the prophylaxis of constipation in 34 elderly hospitalized patients.

 Patients were randomized to receive docusate sodium (100 mg twice daily) or placebo. Outcome measures included the frequency and quality of BMs; no significant between-group differences were found in the aforementioned outcome measures over the course of the study. The authors concluded that routine prophylaxis with docusate at a dose of 100 mg twice daily is not effective in altering the incidence of constipation in a hospital setting.

In a 1978 article, Fain et al. described a study that assessed the use of 2 docusate salts in 46 elderly patients with chronic constipation who were residing in a retirement center.

 Patients were randomized to 1 of 3 arms: docusate sodium 100 mg daily, docusate sodium 100 mg twice daily, or docusate calcium 240 mg daily. All patients underwent a 2-week placebo run-in period followed by 3 weeks of treatment. At the conclusion of the treatment period, a statistically significant increase in the frequency of BMs was noted in the docusate calcium arm compared with that observed at the conclusion of the placebo run-in period (2.83/week vs 1.75/week). In contrast, no such differences were noted with the 2 regimens of docusate sodium. 

A 1991 article by Castle et al. describes a randomized, double-blind, crossover study involving 15 elderly nursing home residents, all of whom were on a bowel regimen before the onset of the study.7,8 Subjects were randomized to receive docusate calcium 240 mg twice daily or placebo for 3 weeks followed by a 2-week washout period before crossing over to the other arm. Outcome measures included stool frequency, stool consistency, the need for additional laxatives, and patients’ subjective experience. The investigators reported no significant differences in any of these outcome measures.

In the largest study to date involving the use of docusate, McRorie et al. assessed the comparative efficacy of psyllium and docusate sodium in the management of chronic idiopathic constipation.10 In this multi-site, double-blind study, 170 adult patients were randomized to receive psyllium 5.1 g twice daily (along with docusate placebo) or docusate sodium 100 mg twice daily (along with psyllium placebo). The study began with a 2-week placebo phase (baseline) followed by a 2-week treatment phase. Outcome measures included BM frequency, stool weight, total stool output, dry stool weight, stool water weight, stool water content, and a combined score of the aforementioned outcome measures. The investigators reported that in treatment week 2, BM frequency was significantly greater with psyllium than with docusate (3.5/week vs 2.9/week, respectively). Increases in total stool output (359.9 g/week vs 271.9 g/week, respectively) and stool water weight (84.0 g/BM vs 71.4 g/BM, respectively) were also significantly greater with psyllium than with docusate. Likewise, when compared with baseline values, psyllium resulted in a significantly greater increase in stool water content vs. docusate (2.33% vs 0.01%, respectively). The combined score of objective measures of constipation was also significantly greater with psyllium than with docusate.

Other outcomes measures were not statistically different. Notably, the focus of this study was a comparison of psyllium with docusate, and as such, the investigators did not report whether docusate resulted in significant improvements in the study’s outcomes when compared with baseline measures.

In the most recent study, Tarumi et al. assessed the efficacy of docusate sodium in hospice patients.11 In this prospective, randomized, double-blind, placebo-controlled trial, 74 patients were randomized to receive 1 to 3 sennoside tablets (8.6 mg/tablet) plus docusate sodium 200 mg twice daily or 1 to 3 sennoside tablets (8.6 mg/tablet) plus placebo for 10 days. The primary outcome measures were stool frequency, volume, and consistency. The investigators reported no significant differences between the 2 groups in regards to the primary outcome measures. The authors concluded that docusate plus sennosides was not more efficacious than sennosides alone in managing constipation in hospice patients.

In addition to the clinical studies reported above, 2 systematic reviews were identified which examined the clinical efficacy of docusate in the management of constipation. In a review of literature spanning the period of 1940-1997, Hurdon et al. identified 4 eligible prospective controlled trials which evaluated the efficacy of oral docusate in adults with chronic illness and identifiable risk factors for constipation, as well as in those with preexisting constipation.

Based on their review, the authors concluded that treatment of constipation with docusate in chronically ill and terminally ill patients is based on inadequate experimental evidence. Notably, the 4 trials included in the Hurdon review have been previously summarized in this article.

Similarly, in 2005, Ramkumar and Rao conducted a systematic review of the efficacy and safety of medical therapies for the management of chronic constipation.

 In this review, the authors searched for randomized studies published between 1966 and 2003 that included adult patients. The search yielded 4 studies that examined the efficacy of docusate, all of which have been summarized in the current review. Based on the evidence, Ramkumar and Rao concluded that “[t]he efficacy of docusate in the treatment of constipation is modest at best”.

Although the use of docusate remains common, evidence to support its use is based on a small number of clinical trials which often carried significant limitations. Pharmacists should be mindful of the lack of robust evidence to support the use of docusate for the management of constipation. Considering its OTC status, pharmacists can and must play an active role in guiding patients on the selection of laxatives which are supported by sound evidence. Likewise, such guidance should be provided to other health care practitioners caring for patients who require the use of laxatives.

At the time of writing, Dr Chattah was a student at The Arnold & Marie Schwartz College of Pharmacy and Health Sciences, Long Island University. 

Dr Grossman is a drug information specialist at the International Drug Information Center and adjunct assistant professor at Arnold & Marie Schwartz College of Pharmacy and Health Sciences, Long Island University. 

1. Vazquez Roque M, Bouras EP. Epidemiology and management of chronic constipation in elderly patients. 

 2015;10:919-930. doi:10.2147/CIA.S54304.

2. Bharucha AE, Dorn SD, Lembo A, Pressman A. American Gastroenterological Association medical position statement on constipation. 

 2013;144(1):211-217. doi:10.1053/j.gastro.2012.10.029.

3. Fabel PH, Shealy KM. Diarrhea, Constipation, and Irritable Bowel Syndrome. In: DiPiro JT, Talbert RL, Yee GC, Matzke GR, Wells BG, Posey L. eds. 

Pharmacotherapy: A Pathophysiologic Approach,

 10e New York, NY: McGraw-Hill. Accessed April 28, 2020.

 [database online]. Elsevier Inc. Accessed April 28, 2020.

5. Medical Expenditure Panel Survey summary tables – Prescribed drugs. Agency for Healthcare Research and Quality. U.S. Department of Health and Human Services. Accessed April 28, 2020.https://meps.ahrq.gov/mepstrends/hc_pmed/.

6. Model List of Essential Medicines. 21st List 2019. World Health Organization. Accessed April 28, 2020. https://apps.who.int/iris/bitstream/handle/10665/325771/WHO-MVP-EMP-IAU-2019.06-eng.pdf?ua=1.

7. Hurdon V, Viola R, Schroder C. How useful is docusate in patients at risk for constipation? A systematic review of the evidence in the chronically ill. 

 2000;19(2):130-136. doi:10.1016/s0885-3924(99)00157-8.

8. Ramkumar D, Rao SS. Efficacy and safety of traditional medical therapies for chronic constipation: systematic review. 

 2005;100(4):936-971. doi:10.1111/j.1572-0241.2005.40925.x.

9. American College of Gastroenterology Chronic Constipation Task Force. An evidence-based approach to the management of chronic constipation in North America. 

 2005;100 Suppl 1:S1-4. DOI:10.1111/j.1572-0241.2005.50613_1.x.

10. McRorie JW, Daggy BP, Morel JG, Diersing PS, Miner PB, Robinson M. Psyllium is superior to docusate sodium for treatment of chronic constipation. 

 1998;12(5):491-497. doi:10.1046/j.1365-2036.1998.00336.x.

11. Tarumi Y, Wilson MP, Szafran O, Spooner GR. Randomized, double-blind, placebo-controlled trial of oral docusate in the management of constipation in hospice patients. 

 2013;45(1):2-13. doi:10.1016/j.jpainsymman.

Pharmacists can and must play an active role in guiding patients on the selection of laxatives which are supported by sound evidence. 

Reevaluating the Use of Docusate in the Management of Constipation

As pharmacists, we know that the use of a medication before its expiration date ensures maximum potency if it was stored under proper conditions. Once a medication has been dispensed, the original manufacturer's expiration date cannot always be relied upon and 22 states and the District of Columbia (see table) require the pharmacist to place on the Rx label a "use-by date" or an "expiration date." The "use-by date" is one year from the date of dispensing or the expiration date on the manufacturer's container, whichever is earlier. This "use-by date"  required  by states is  similar to the requirements  of the 2007 USP/NF, which  indicates that in the absence of stability data for a drug product in a repackaged container, the beyond-use dating period is one year from the date of dispensing or the time remaining of the expiration date, whichever is shorter. 

All prescription drugs should have a sell-by date for consistency and patient protection.

Viewpoint: Should an RX label require a use-by date or an expiration date?

Scanning the pharmacy shelves, one can be overwhelmed by the variety of treatment options. The obvious question is, Are all of these options effective, and, if not, which should be recommended and which should be avoided in adult patients?

When self-treatment of acute cough due to the common cold is acceptable, pharmacists have traditionally recommended drugs such as dextromethorphan as an antitussive and guaifenesin as an expectorant for the management of cough, as well as zinc-containing products for the management of the common cold and its associated symptoms, including cough. The ACCP guidelines provide insight into the effectiveness of these preparations in adult patients.  

Using a review of literature published in the English language on human subjects from 1960 to 2004, the authors evaluated agents that have been utilized for the management of cough due to upper respiratory tract infections (URTI). Dextromethorphan was found to have limited efficacy for symptomatic relief of cough, and the authors therefore concluded that it is not recommended for such use until further evidence becomes available to support its efficacy. The guidelines review studies by Lee et al. and Tukainen et al., which showed no difference in cough frequency and severity when patients were treated with dextromethorphan. On the other hand, the authors note that meta-analyses by Pavesi et al. and Parvez et al. showed some efficacy of dextromethorphan in reducing cough frequency. This inconsistency could be due to the limited efficacy of dextromethorphan (<20% cough suppression), which would require large numbers of study participants to determine its efficacy. 

The ACCP review of trials on guaifenesin also yielded mixed results where, in one study by Robinson et al., the substance was found to improve cough severity and frequency, yet the study by Kuhn et al. showed no significant effect. The authors of the guidelines do not make any specific recommendations concerning the use of guaifenesin in patients with acute cough secondary to URTI. 

The guidelines also address the use of zinc-containing products for the management of the common cold. Such preparations were found to provide mixed results in the management of URTI; and, as a result, the authors suggest that the use of zinc-containing products for treating acute cough due to the common cold is not justified and should not be recommended. 

In contrast, the guidelines identify several products that may be effective. According to the guidelines, the combination of the first-generation antihistamine brompheniramine and a sustained-release formulation of the decongestant pseudoephedrine has proven effective in reducing acute cough as well as postnasal drip (PND) and throat-clearing associated with URTI. This recommendation is based on a study by Curley et al., who demonstrated that the use of this combination led to a more rapid improvement in those three symptoms.  

It is that time of the year when consumers flock to their local drugstores seeking the "long-trusted" remedies for the common cold and its associated symptoms-particularly cough. In response, pharmacists will be called upon to make therapy recommendations that suit the needs of each individual patient.