maker of MiraLAX (PEG 3350) and Phillips' laxatives.

Constipation is a widespread condition that affects an estimated 16% of all adults in the United States.

 Chronic constipation is defined by the ROME IV criteria, and it is characterized by symptoms such as infrequent bowel movements, difficult passage of stool, straining, and the feeling of incomplete evacuation.

 There is no formal definition for occasional constipation, although the symptoms of occasional and chronic constipation are common to both conditions. The differences between occasional constipation (an acute condition) and chronic constipation are the underlying cause and the length of time for which symptoms have existed.

The burden of constipation symptoms can substantially affect quality of life and cause the interruption of daily activities.

 Unresolved constipation can lead to various consequences, such as hemorrhoids, anal fissures, rectal prolapse, and fecal impaction.

THERAPEUTIC CLASSES OF OTC OPTIONS AVAILABLE

There are many OTC products with different mechanisms of action and formulations available for the management of occasional constipation. Laxatives are a popular selection for the relief of occasional constipation; in fact, approximately 40% of Americans self-treat with OTC laxatives.

 It is important to increase awareness of effective and safe options available to those in the pharmacy to aid consumers in choosing among the available OTC products and provide pharmacists' evidence-based recommendations if requested.

Five OTC classes of treatment options commonly used to treat constipation include osmotic laxatives, saline laxatives, stimulant laxatives, bulk-forming (fiber) laxatives, and stool softeners.

 Notably, there is variability in both the quality and quantity of evidence supporting the use of these various agents (

As there may be mixed perceptions regarding the relative evidence supporting the different OTC options,

 pharmacists have an important opportunity to familiarize themselves with the levels of evidence supporting the use of each so that they can educate both patients and health care practitioners.

EVIDENCE SUPPORTING THE USE OF OTC PRODUCTS

A systematic review published in 2005 evaluated the efficacy and safety of treatment options available for the management of constipation based on data published between 1966 and 2004.

 The review provided evidence-based recommendations for the use of these agents; however, it identified a lack of robust supporting evidence for many agents.

Polyethylene glycol (PEG) was the sole OTC preparation that received a strong recommendation based on high levels of evidence.

 PEG 3350, marketed in the United States under the brand name MiraLAX, is an osmotic laxative FDA approved for the treatment of occasional constipation.

 Within the 15 years since the initial review, additional high-quality trial data have been published for many of the agents.

An updated systematic review of efficacy and safety data generated in the 15 years since the initial analysis was published in the 

This analysis was designed to review the body and quality of evidence of all classes of OTC agents to provide up-to-date treatment recommendations.

The analysis included 41 studies published between 2004 and 2020 that evaluated 8 classes of OTC products for constipation.

 Updated evidence-based recommendations were provided and graded from A (good evidence in support) to I (insufficient evidence) based on the level of evidence from I (good) to III (poor).

 ­for a summary of the evidence-based recommendations.

The osmotic laxative, PEG, had the most robust clinical evidence supporting its efficacy and safety. PEG received a grade A recommendation for its use based on level I evidence that was evaluated from 9 trials, of which 3 were placebo controlled. PEG also demonstrated high levels of tolerance across the studies reviewed. Most adverse events (AEs) were mild to moderate in severity and included abdominal distention, diarrhea, loose stools, flatulence, and nausea.

The only other OTC agent with a similar level of evidence and recommendation (see 

) was the stimulant laxative senna, based on the results from 2 short-term placebo-controlled trials.It should be noted that 1 of those trials used substantially higher doses of senna than normally used in clinical practice. Of the other stimulant laxatives assessed, bisacodyl received a grade B recommendation based on the results from 3 trials, 1 of which was placebo controlled.

Based on the safety data, bisacodyl and sennosides are both associated with the potential for dose reduction and intolerance due to AEs. Common gastrointestinal-related AEs reported in clinical studies were diarrhea and abdominal pain, which are believed to be due to the mechanism of action of the stimulant class.

Bulk-forming (fiber-containing) agents demonstrated more modest efficacy based on the findings from placebo-controlled and comparative studies. In 2 trials, the soluble fiber psyllium did not show a significant benefit compared with placebo, and head-to-head trials revealed that psyllium is less effective than several comparator agents, including PEG. This yielded psyllium a grade B recommendation based on level II evidence. Other fibers (polydextrose and inulin) showed inconsistent benefits over placebo, and no trials were identified that assessed the efficacy of methylcellulose for the treatment of constipation.

There were no studies evaluating the efficacy of magnesium hydroxide that were published after 2004, which met the inclusion criteria for this review. A single trial demonstrated the superiority of magnesium oxide over placebo and noninferiority versus senna (level I evidence, Grade B recommendation). Magnesium-rich water preparations received a similar recommendation. However, the lack of standardized preparations and dosages evaluated in the studies were noted as limitations of the review.

Docusate is an OTC stool softening agent that is frequently used for relief of constipation; however, its efficacy has been questioned previously due to inconsistent clinical data. Despite docusate being one of the most used agents for constipation, no studies conducted after 2004 were identified for inclusion in this analysis. The authors concluded that there is insufficient evidence to make a recommendation to support its use.

Overall, a substantial amount of higher-quality evidence is currently available to support the use of OTC products in the treatment of constipation; however, there remains considerable variability in clinical trial design and the clinical definitions of constipation and efficacy end points.

 Based on the findings of this review, the authors concluded that there was good evidence to recommend PEG and senna as first-line options for the treatment
of constipation.

EFFICACY OF PEG 3350 USING MODERN CONSTIPATION END POINTS

Given the lack of evidence assessing the response to OTC laxative treatment using modern, standardized end points, a reanalysis of previously published data from a 6-month double-blind, placebo-controlled trial evaluating the efficacy of PEG 3350 was conducted using the FDA–recommended end point for chronic idiopathic constipation (CIC) treatment response.

 This stringent end point is more relevant to today’s clinicians. It is generally recognized within the medical community that a laxative product that provides relief from chronic constipation will also be effective in occasional constipation. There is also the problem of feasibility in conducting research in subjects with occasional constipation. Thus, it is sensible to conduct trials in the CIC population and extrapolate the results to occasional constipation.

The reanalysis focused on the current FDA-recommended CIC responder end point, defined as at least 3 complete spontaneous bowel movements (CSBMs) per week and an increase of at least 1 CSBM from baseline during at least 9 of 12 treatment weeks, including 3 of the last 4 weeks of this period. Patients with CIC, as defined by modified ROME I criteria, who had fewer than 3 satisfactory bowel movements per week during the 14-day baseline observation period were randomized (2:1) to receive 17 g of PEG 3350 or placebo daily for 24 weeks. CSBMs and spontaneous bowel movements (SBM) responses were evaluated weekly throughout the study period.

In the reanalysis, the weekly CSBM response rate defined by the FDA-recommended end point indicated a more than 3-fold increased likelihood of response to PEG 3350 compared with placebo (42% vs 13% CSBM response rate; 

 < .0001), which was durable over 6 months of treatment. Multiple additional analyses evaluating CSBMs and SBMs demonstrated substantial efficacy in patients with CIC, and responses were sustained throughout the 6-month study period.

To assess the efficacy of PEG during its FDA-approved duration of use (7 days), CSBM and SBM data were also analyzed over the first week of treatment. After initiation of treatment, the number of CSBMs and SBMs increased rapidly in the PEG 3350 group. PEG 3350 increased the mean number of CSBMs from baseline by more than 2.5 times that observed with placebo (2.1 vs 0.8 CSBM increase; 

The significant efficacy observed across multiple time intervals for multiple end points demonstrates the overall consistency in the clinical benefits of PEG 3350 for patients with constipation.

As pharmacists are readily accessible health care professionals in community settings, they are a helpful resource to provide additional education for consumers with constipation symptoms, and they can support physicians with questions about treatment options for optimal management.

 Pharmacists can recognize common OTC, complementary, and prescription medications that may potentially cause or worsen constipation symptoms (eg, antipsychotics, diuretics, opioids, antihypertensives, iron supplements).

When educating on available OTC agents, pharmacists should highlight the body of evidence supporting the relative effectiveness among different options to support selection. PEG and senna are the only OTC laxatives with substantially favorable evidence to support their use in occasional constipation. However, only PEG is supported by robust short-term and long-term clinical evidence, including the evaluation of treatment response using stringent, standardized trial end points. Moderate evidence supports the use of psyllium, bisacodyl, and magnesium for the treatment of constipation. Docusate lacks well-controlled trials demonstrating its efficacy and thus has poor evidence to support its use in clinical practice.

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

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

Lacy BE, Mearin F, Chang L, et al. Bowel disorders. Published online February 18, 2016. 

 2016;150(6):1393-1407. doi:10.1053/j.gastro.2016.02.031

Johanson JF, Kralstein J. Chronic constipation: a survey of the patient perspective. 

. 2007;25(5):599-608. doi:10.1111/j.1365-2036.2006.03238.x

Werth BL, Christopher SA. Laxative use in the community: a literature review. 

. 2021;10(1):143. Published online January 4, 2021. doi:10.3390/jcm10010143

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

Rao SSC, Brenner DM. Efficacy and safety of over-the-counter therapies for chronic constipation: an updated systematic review. Published online March 17, 2021. 

. 2021;10.14309/ajg.0000000000001222. doi:10.14309/ajg.0000000000001222

MiraLAX (drug facts). Bayer Consumer Health. Accessed May 7, 2021. https://labeling.bayercare.com/omr/online/MiraLAX-Bottles.pdf

Metamucil Fiber, 4-in-1 psyllium fiber supplement, sugar-free powder single-serve packets, orange flavored drink (supplement facts). Procter & Gamble; 2021. Updated April 15, 2021. Accessed May 7, 2021. https://smartlabel.pg.com/00037000741084.html

Citrucel-methylcellulose powder, for solution (drug facts). GlaxoSmithKline Consumer Healthcare Holdings (US) LLC. Updated April 14, 2021. Accessed May 7, 2021. https://dailymed.nlm.nih.gov/dailymed/fda/fdaDrugXsl.cfm?setid=9d5f2244-a610-4d45-b6e8-e79bb17a558f&type=display

Senokot-standardized senna concentrate tablet (drug facts). Avrio Health L.P. Updated August 17, 2020. Accessed May 7, 2021. https://dailymed.nlm.nih.gov/dailymed/fda/fdaDrugXsl.cfm?setid=c18dd7fa-993b-440b-8cdd-f1551abb99ca&type=display

Dulcolax-bisacodyl tablet, film coated (drug facts). Chattem, Inc. Updated February 12, 2021. Accessed May 7, 2021. https://dailymed.nlm.nih.gov/dailymed/fda/fdaDrugXsl.cfm?setid=d285651b-7ccc-4ae5-a862-7a38dffefa28&type=display

Phillips’ Milk of Magnesia – Cherry (drug facts). Bayer HealthCare LLC. Accessed May 7, 2021. https://www.phillipsdigestive.com/sites/g/files/vrxlpx15496/files/2021-02/phillips-milk-of-magnesia-cherry.pdf

Phillips’ Caplets Laxative Dietary Supplement (facts). Bayer HealthCare, Consumer Care. Accessed May 7, 2021. https://www.phillipsdigestive.com/sites/g/files/vrxlpx15496/files/2021-03/phillips-caplets_0.pdf

Colace-docusate sodium capsule (drug facts). Avrio Health L.P.Updated November 2020. Accessed May 7, 2021. https://dailymed.nlm.nih.gov/dailymed/fda/fdaDrugXsl.cfm?setid=7793fced-e8ee-44e2-b212-dd2a59a5f462&type=display

Di Palma JA, Cleveland MV, McGowan J, Herrera JL. A randomized, multicenter comparison of polyethylene glycol laxative and tegaserod in treatment of patients with chronic constipation. 

. 2007;102(9):1964-1971. doi:10.1111/j.1572-0241.2007.01365.x

Menees SB, Lembo AJ, Chey WD. Six-month efficacy of polyethylene glycol (PEG) 3350 in the treatment of chronic idiopathic constipation: analysis using FDA endpoints. P1094 (S0457).Poster presented at: American College of Gastroenterology Annual Meeting; October 23-28, 2020; virtual. Accessed May 12, 2021. https://www.eventscribe.com/2020/ACG/fsPopup.asp?efp=RElCSUFHUk02NDI2%20&PosterID=298978%20&rnd=0.6476836&mode=posterinfo

Articles

Clinical Evidence for OTC Products for Constipation

Atopic dermatitis (AD), commonly referred to as eczema, is a common chronic inflammatory skin condition characterized by its hallmark feature of pruritus (itching), which causes painful skin irritation, soreness, and difficulty sleeping.

 Although symptoms often first present during childhood, AD is recurrent and can persist into adulthood, requiring long-term management.

 Patients with AD can experience overall impairments to daily activities and emotional comorbidities as result of their condition.

AD can be classified by severity based on objective clinical observations and subjective patient reports on itching and sleep impairment. Clinical manifestations can include inflamed, dry, scaly, oozing, or crusty skin.

 Symptoms typically fluctuate between flares (periods of skin worsening) and dormancy with treatment.

The prevention and management of flares can be a challenge for many patients. It may require a combination of nonpharmacologic (eg, IgE-mediated allergy avoidance and daily moisturizers) and pharmacologic (eg, topical corticosteroids, topical calcineurin inhibitors, oral antihistamines) strategies, depending on severity.

OTC and prescription topical corticosteroids are a mainstay option for the temporary relief and prevention of flares; however, long-term use for more than twice-weekly application is not recommended.

 Prolonged daily use is associated with risks of corticosteroid withdrawal after discontinuation.

 Other treatment-related adverse effects (AEs) of topical corticosteroids can include telangiectasia, striae, skin atrophy, and systemic effects such as suppression of the hypothalamic-pituitary-adrenal axis, which can be more pronounced in children due to their higher body surface to weight ratio.

There is a need for safe and effective complementary strategies that can provide an alternative option to topical corticosteroid treatments to help patients achieve improvements in eczema severity and clear skin outcomes. Pharmacists have an opportunity to increase awareness of the complementary options available, such as Florajen

 Eczema, a medical food that contains a unique blend of probiotics that have been specifically studied for the dietary management of eczema.

Emerging evidence has highlighted the potential role for probiotics as a nutritional adjunctive management strategy to address gut microflora imbalances that may contribute to the pro-inflammatory state in AD.

A combination of factors involving genes, the immune system, and the environment can contribute to dysfunction of the skin barrier and immunity, causing the hallmark AD characteristics of red, itchy, and painful skin.

 The exact mechanism is not fully understood; however, there appears to be an association between the gastrointestinal (GI) system and skin, called the gut-skin axis, in the development of AD.

Changes in gut flora can compromise gut wall integrity and increase GI permeability, resulting in the passage of inflammatory products, bacteria, and toxins from the GI tract into the circulatory system. The presence of gut microbiota and their metabolites within the circulation can trigger an immune response, resulting in systemic inflammation. These components can also accumulate in the skin and disrupt normal epidermal barrier function.

Analyses of Bacterial Species in Patients With AD

Patients with AD have distinct differences in their gut microbiome composition that may contribute to disease manifestation.

 Compared with non-AD populations, those with AD have reduced levels of certain beneficial bacteria and their metabolites, such as short-chain fatty acid (SCFA)—producing bacteria (eg, 

 Certain SCFAs suppress inflammatory responses and help maintain gut barrier integrity; therefore, reduced levels of SCFA-producing bacteria may result in a pro-inflammatory state in the gut.

Those with AD may have specific nutritional needs in order to balance their gut microbiome.

 Results from separate studies have shown elevated levels of 

in the general AD population, a higher prevalence of 

species among children, greater colonization with 

 in adults and infants, and a lack of bacterial diversity in infants with AD.

 Therefore, probiotics may help address gut microbiome imbalances.

Because different probiotic strains provide different health benefits, it is important to increase awareness of probiotic formulas that have clinical evidence supporting their use.

 Eczema is the first and only probiotic medical food available for the dietary management of eczema.

Each packet of this medical food contains 1 billion colony-forming-units of 
3 probiotic strains: 

 Eczema is intended to be used under the supervision of a health care professional.

The effectiveness of the probiotic blend in Florajen

 Eczema was investigated in a 12-week, randomized, placebo-controlled clinical study of 50 children aged 4 to 17 years with moderate AD as assessed on the SCORing Atopic Dermatitis (SCORAD) index. Patients received topical methylprednisolone aceponate, a moisturizer, and an oral antihistamine in combination with either 
Florajen

From baseline to 12 weeks of follow-up, patients in the probiotic group achieved an 83% reduction in overall eczema severity, as measured by a reduction in the SCORAD index score, compared with a 24% reduction in the placebo group (relative difference, −59%; 95% CI, −72% to −46%; 

 < .001). Moreover, 91% of patients in the probiotic group achieved clear or almost clear skin on the Investigator Global Assessment scale compared with 21% in the placebo group over the 12-week study period.

Over the study period, there was a significant reduction in topical corticosteroid use for the treatment of flares in the probiotic group compared with the placebo group at 161 versus 220 patient-days of use, respectively (odds ratio, 0.63; 
95% CI, 0.51-0.78; 

Findings from this clinical study suggest that the mixture of 3 probiotic strains in Florajen

 Eczema may be an effective adjuvant management option that can reduce overall eczema severity and the use of topical corticosteroids during flares.

 In a separate published review of probiotic strains for pediatric AD, the probiotic blend in Florajen

 Eczema was noted to reduce AD symptoms with “high certainty evidence.”

Eczema can be difficult to manage and may require a combination of strategies.

 As accessible health care professionals, pharmacists have an important role in supporting the management of eczema from the pharmacy. For children and their caregivers, pharmacists may consider alternatives to topicals and recommend options that are easy to administer, appropriate for daily use, and eliminate AEs associated with topical corticosteroid use. When asked for a product recommendation, pharmacists can provide education on the different products available, including Florajen

 Eczema, highlighting its clinical effectiveness for flare management, skin clearance, and reduction in topical corticosteroid use.

Along with other available probiotics, Florajen

 Eczema should be stored in the pharmacy refrigerator to maintain the product’s freshness and potency through its expiration date.

 Eczema is available behind the pharmacy counter, pharmacists have the opportunity to review the labeled information, counsel patients on key storage and administration information, and provide them with education and resources for Florajen

Eichenfield LF, Tom WL, Chamlin SL, et al. Guidelines of care for the management of atopic dermatitis: section 1: diagnosis and assessment of atopic dermatitis.

. 2014;70(2):338-351.doi:10.1016/j.jaad.2013.10.010

Chiesa Fuxench ZC, Block JK, Boguniewicz M, et al. Atopic Dermatitis in America study: a cross-sectional study examining the prevalence and disease burden of atopic dermatitis in the US adult population. 

. 2019;139(3):583-590. doi:10.1016/j.jid.2018.08.028

Sidbury R, Tom WL, Bergman JN, et al. Guidelines of care for the management of atopic dermatitis: section 4: prevention of disease flares and use of adjunctive therapies and approaches. 

. 2014;71(6):1218-1233. doi:10.1016/j.jaad.2014.08.038

Eichenfield LF, Tom WL, Berger TG, et al. Guidelines of care for the management of atopic dermatitis: section 2: management and treatment of atopic dermatitis with topical therapies. 

. 2014;71(1):116-132. doi:10.1016/j.jaad.2014.03.023

Education announcement: use of topical steroids for eczema. 
National Eczema Association. Updated April 14, 2015. Accessed February 3, 2021. https://nationaleczema.org/warnings-for-topical-steroids-eczema/

 Eczema. Prescribing information. American Lifeline, Inc; 2021.

Navarro-López V, Ramírez-Bosca A, Ramón-Vidal D, et al. Effect of oral administration of a mixture of probiotic strains on SCORAD index and use of topical steroids in young patients with moderate atopic dermatitis: a randomized clinical trial. 

 2018;154(1):37-43. doi:10.1001/jamadermatol.2017.3647

Ellis SR, Nguyen M, Vaughn AR, et al. The skin and gut microbiome and its role in common dermatologic conditions. 

. 2019;7(11):550. doi:10.3390/microorganisms7110550

Salem I, Ramser A, Isham N, Ghannoum MA. The gut microbiome as a major regulator of the gut-skin axis. 

. 2018;9:1459. doi:10.3389/fmicb.2018.01459

Reddel S, Del Chierico F, Quagliariello A, et al. Gut microbiota profile in children affected by atopic dermatitis and evaluation of intestinal persistence of a probiotic mixture. 


 2019;9(1):4996. doi:10.1038/s41598-019-41149-6

Tan-Lim CSC, Esteban-Ipac NAR, Mantaring JBV 3rd, et al. Comparative effectiveness of probiotic strains for the treatment of pediatric atopic dermatitis: a systematic review and network meta-analysis. 

Emerging Evidence in the Dietary Management of Eczema With Probiotics 

This article was sponsored by SK Life Science, Inc.

Many medications require dose titration to minimize adverse drug reactions (ADRs) or to reach a desired clinical effect or both.

 Titrating doses with slow escalation over time allows for a customized regimen based on patient-specific treatment responses.

From 2013 to 2017, the FDA approved several agents deemed amenable to titration, with those for metabolic or endocrine conditions (eg, antidiabetic agents) being the most titrated agents.

 Pharmacologic agents commonly encountered in community settings and for which titration is recommended include anticoagulants,

Titration allows for personalizing treatment, maximizing outcomes, and reducing ADRs.

 Titration starts with a generally well-tolerated low dose and the dose is increased until a particular outcome is achieved.

Titration can achieve the desired pharmacologic effect while avoiding toxicities.

 At times, titration may achieve a benefit with doses below the recommended target dose.

 Also, titration may be influenced by available formulations. Certain medications are available in liquid formulations and subcutaneous injections, allowing for titrations with precise dosing, versus tablets or capsules that are available in limited or fixed dosages.

Compared with standard care, titration improves outcomes, particularly when patients are being closely monitored by providers. For example, patients with diabetes showed improvements in their A1C levels with pharmacist-facilitated titration of insulin.

 Similarly, a pharmacist-run warfarin titration led to an increased duration of target international normalized ratio and decreased thromboembolic events.

Slowly acclimating a patient to a dose helps minimize potential treatment-related ADRs.

 A slow uptitration can provide insight into individual dose responses and may help prevent serious ADRs, especially in patients with a new diagnosis or when introducing a new medication into a regimen.

 Slow titration may help mitigate risk and may allow the clinician or patient to identify potentially serious idiosyncratic immune-related hypersensitivity reactions (eg, drug-related rash with eosinophilia and systemic symptoms [DRESS] and Stevens-Johnson syndrome [SJS]) before they become severe.

 Titration and monitoring are especially important for medications with a narrow therapeutic index, where there is a small difference between the dose that provides benefit versus toxicity (eg, digoxin, insulin, opioids, phenytoin, warfarin).

Titrating antidepressants (eg, nefazodone, paroxetine) has been shown to reduce ADRs such as sexual dysfunction, nausea, and sedation.

 With ASMs (eg, cenobamate, lamotrigine), slow titration may reduce the risk of idiosyncratic immune-related hypersensitivity reactions when initiating therapy.

 Uptitration of one medication may also allow for downtitration of concomitant medications used for similar indications, thereby reducing additive ADRs associated with combination therapy. Conversely, when discontinuing medications, downtitration may prevent withdrawal or discontinuation syndromes.

 A gradual decrease in the dose over 2 weeks may reduce the risk of recurrent seizures and status epilepticus when discontinuing uptitrated ASMs.

Titration may provide benefits for at-risk patients, such as those with genetic variants or those with comorbidities who are being treated with multiple medications. With appropriate titration, patients with genetic polymorphisms that impact a medication’s metabolism (eg, warfarin) or ADR profile (eg, HLA-B*1502 haplotype) may be less likely to develop supratherapeutic concentrations or certain ADRs.

 Titration also allows for close monitoring of the onset of ADRs in patients at risk for drug-drug interactions due to polypharmacy.

 Elderly, frail, or malnourished patients may also benefit from a more cautious titration, especially when nutrition status and albumin concentrations impact a medication’s pharmacokinetics (eg, phenytoin, warfarin).

Pharmacists are ideally positioned to help patients understand titration.

 They can counsel patients on titration goals and expectations, titration schedules, eventual target maintenance dose, and adherence strategies.

Pharmacists can help to ensure that patients understand that titrated medications are started at low doses and escalated upwards, reiterating that this can provide the flexibility to achieve a maintenance dose that is best suited for their individual needs.

 Pharmacists can also provide patients with detailed titration instructions, stressing the importance of following the directions to achieve the therapeutic outcome.

Setting treatment expectations is especially important for titrated medications. Pharmacists can educate patients on therapeutic goals, particularly when those goals may not be tangible or when objective measures objective measures of the medication’s efficacy are not readily seen.

 Advising patients on the potential timing of clinical benefits can help manage expectations. Dose escalation is done slowly, with increases occurring every few days, weekly, or even biweekly, as many medications may take several days or weeks to reach steady state. As such, the full therapeutic benefit may not be realized for several weeks or months.

Prescriptions change as medications are titrated over time. Some titration schedules may seem overwhelming and can cause confusion, for example, when instructions include splitting tablets or taking different tablet strengths from one week to the next.

 Pharmacists can emphasize that adhering to the titration schedule can help patients achieve their treatment goals.

 They should also encourage patience and staying the course to achieve optimal results.

Finally, pharmacists should discuss the potential benefits and risks with patients upon initiation of any new therapy, including common ADRs, and how to recognize their early signs and symptoms and what to do if they occur. Pharmacists can help patients understand that slow uptitration is intended to help minimize potential ADRs while maximizing therapeutic effectiveness.

Caffrey AR, Borrelli EP. The art and science of drug titration. 

Maxwell S. Therapeutics and good prescribing. In: Walker BR, Colledge NR, Ralston SH, Penman ID, eds. 

Davidson’s Principles and Practice of Medicine

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Schuck RN, Pacanowski M, Kim S, Madabushi R, Zineh I. Use of titration as a therapeutic individualization strategy: an analysis of Food and Drug Administration-approved drugs. 

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Lantus. Prescribing information. Sanofi-Aventis U.S. LLC; 2019.

Prozac. Prescribing information. Eli Lilly and Company; 2016.

Xcopri. Prescribing information. SK Life Science, Inc; 2020.

Cramer JA, Mintzer S, Wheless J, Mattson RH. Adverse effects of antiepileptic drugs: a brief overview of important issues. 

 2010;10(6):885-891. doi:10.1586/ern.10.71

Perucca P, Gilliam FG. Adverse effects of antiepileptic drugs. 

Ielmini M, Poloni N, Caselli I, et al. Efficacy and tolerability of two different kinds of titration of paroxetine hydrochloride solution: an observational study. 

Weidman-Evans E, Evans J, Eastwood R, Fort A. Implementation of a pharmacist-run telephonic insulin titration service. 

 2012;52(6):e266-e272. doi:10.1331/JAPhA.2012.11225

Bungard TJ, Gardner L, Archer SL, et al. Evaluation of a pharmacist-managed anticoagulation clinic: improving patient care. 

Zaccara G, Franciotta D, Perucca E. Idiosyncratic adverse reactions to antiepileptic drugs. 

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Lamictal. Prescribing information. GlaxoSmithKline; 2019.

Increasing Awareness and Counseling on the Importance of Titration Schedules

This article was sponsored by Bayer and produced by Pharmacy Times® with Bayer.

With the onset of cold and flu season, pharmacists have an opportunity to support the management of symptoms. Given the wide variety of active ingredients available to treat cold, cough, and flu symptoms—and the even wider variety of OTC products that feature combinations of these ingredients&mdash;it may be a daunting task for some consumers when they navigate the product selection in the pharmacy. However, pharmacists are in a position to help.

If a pharmacist is asked for a recommendation or guidance when a consumer is selecting an OTC cough and cold product, there are a number of factors to consider, including identifying their most bothersome symptom, product preference, and the presence of any comorbid medical conditions. A common medical condition shared by many Americans is hypertension, which is defined as blood pressure at or above 130/80 mm Hg according to the 2017 American College of Cardiology and American Heart Association (ACC/AHA) hypertension management guidelines.

 Hypertension affects an estimated 108 million adults in the United States (or 45% of the adult population).

Due to the high prevalence of hypertension, it is important for pharmacists to increase the awareness of ingredients in cold and flu OTC medications that can raise blood pressure or interfere with the effectiveness of prescription antihypertensive agents.

 Pharmacists are well positioned to provide information to those with high blood pressure who seek out recommendations on options available to them.

Considerations of High Blood Pressure in the Selection Of an OTC Medication

According to the AHA, those with high blood pressure should avoid products that include systemic nasal decongestants and nonsteroidal anti-inflammatory drugs (eg, ibuprofen and naproxen) as these agents can increase blood pressure.

Several cold and flu OTC products contain pseudoephedrine or phenylephrine decongestants that stimulate α-adrenergic receptors on vascular smooth muscle, causing vasoconstriction of the blood vessels within the nose and providing temporary relief of nasal edema. However, the vasoconstriction is nonspecific systemically and may cause elevated blood pressure.

 HBP products are specially formulated to provide safe and effective symptom relief for those with high blood pressure.

provides the FDA-approved indications and features for each of the 7 Coricidin

 HBP products available on pharmacy shelves.

These products contain combinations of several active ingredients to provide temporary relief from cold, cough, and flu symptoms. All products are free of α-adrenergic agonist systemic decongestants and therefore will not increase blood pressure. Depending on the specific product, ingredients may include acetaminophen (pain reliever and fever reducer), dextromethorphan hydrobromide (cough suppressant), guaifenesin (expectorant), chlorpheniramine maleate (antihistamine), and doxylamine succinate (antihistamine).

Information For The Pharmacist

Clinical Evidence for OTC Products for Constipation

Emerging Evidence in the Dietary Management of Eczema With Probiotics

Increasing Awareness and Counseling on the Importance of Titration Schedules

Cough, Cold, and Flu Symptom Relief For Those with High Blood Pressure