Director, International Drug Information Center

Joseph P. Nathan, PharmD, MS

Diarrhea is a common adverse effect of antibiotics, affecting 11% to 40% of children treated with broad-spectrum antibiotics.

 Antibiotic-associated diarrhea (AAD) may occur when anti biotics disrupt the normal balance of the gut flora, causing harmful bacteria to multiply and destroy the gut microflora.

 Probiotics restore the natural balance of gut flora through the introduction of nonpathogenic bacterial or yeast microbiota and have been used in clinical trials and in practice to manage AAD in children.

Probiotics are generally well tolerated in healthy children, with minor adverse effects being dyspepsia, abdominal pain, nausea, and bloating.

 Probiotics should be avoided in children who are immunocompromised or severely debilitated.

 Likewise, probiotics must be used with caution in specific populations such as premature infants, critically ill patients, and patients with a central venous catheter, cardiac valvular disease, and short-gut syndrome.

 Although evidence supporting a clinically meaningful interaction between probiotics and antibiotics is lacking, the use of antibiotics could theoretically eradicate the microorganisms contained in the probiotics. Therefore, it has been suggested to space the administration of probiotics from antibiotics by 2 hours.

Because antibiotics are commonly used in the pediatric population, we sought to examine the evidence concerning the use of probiotics for the prevention of pediatric AAD. After applying search criteria, 7 relevant articles were identified, which are summarized below.

Shan et al described an open label, randomized, controlled trial involving 333 hospitalized children who were being treated with intravenous antibiotics.

 The study’s objective included an assessment of the efficacy of 

, dosed at 500 mg per day, for the prevention of AAD. Patients were followed during and 2 weeks after antibiotic therapy. The primary outcomes related to the prevention of AAD were the frequency and duration of AAD. In this study, the use of 

 resulted in statistically significant fewer occurrences of AAD. The investigators concluded that using 

 was effective for the prevention of AAD in children.

Georgieva et al described a randomized, controlled study that examined the efficacy of 

 In this study, 100 hospitalized children aged 3 to 12 years were randomly assigned to receive a probiotic tablet containing 1 × 10

 or placebo once daily during the antibiotic treatment period and for an additional 7 days. The primary study end point was the incidence of diarrhea during and up to 21 days post antibiotic treatment. The investigators found no statistically significant difference between the 2 groups but noted that because of the low incidence of AAD in both groups, no conclusion can be made about the efficacy of 

Fox et al described a randomized, double-blind, placebo-controlled study that examined the efficacy of a yogurt containing probiotics (

) for the prevention of AAD.9 In this study, 72 outpatients aged 1 to 12 years were randomly assigned to receive active yogurt or pasteurized yogurt (placebo) for the duration of their antibiotic treatment. The primary outcome was stool frequency and consistency. There were significantly fewer occurrences of diarrhea in the children who were given the probiotic-rich yogurt as compared with those receiving placebo. Also, more adverse events, including abdominal pain, loss of appetite, and nausea, were reported in the placebo group compared with the active group. The investigators concluded that the specific probiotic-rich yogurt used in the trial was an effective intervention for reducing the incidence of antibiotic-associated gastrointestinal disturbance in children.

Olek et al described a randomized, double-blind, placebo-controlled study that examined the efficacy of probiotics for the prevention of AAD in 438 outpatient children aged 1 to 11 years.

 Patients were assigned to receive a probiotic capsule containing 1 × 10

 or placebo once daily for the duration of antibiotic therapy and for 1 week after completion of treatment. The primary outcome was the incidence of antibiotic-associated loose/watery stools; the investigators found no statistically significant differences between the groups regarding this outcome. Furthermore, the incidence of children with at least 1 adverse event was significantly higher in the placebo group compared with the probiotic group. The investigators concluded that there was no beneficial effect of 

Kołodziej and Szajewska assessed the efficacy of 

 for the prevention of diarrhea and AAD in hospitalized children.

 The investigators randomly assigned 250 children younger than 18 years to receive 

 CFU or placebo twice daily for the duration of antibiotic treatment. Primary outcome measures were the occurrences of diarrhea and AAD. The investigators found no statistically significant differences between the 2 groups in the primary outcome measures. Additionally, there were no statistically significant differences in adverse effects. The investigators concluded that the study provided no evidence to support the use of 

Wronowski et al described a prospective, randomized, double-blind, placebo-controlled study in a pediatric hospital.12 In this study, 156 children aged 1 to 18 years were randomly assigned to receive 100-mg bovine lactoferrin or placebo twice daily for the duration of antibiotic therapy. The primary outcome was the occurrence of AAD during treatment and up to 2 weeks after antibiotic therapy. The investigators found no statistically significant benefit for the probiotic and concluded that bovine lactoferrin was not effective for the prevention of AAD.

Esposito et al described a placebo-controlled study designed to evaluate the effectiveness of 

 for the prevention of AAD in children receiving antibiotic therapy postoperatively.13 The study consisted of 3 groups (probiotic, no treatment, and placebo), with 30 boys in each group. The overall incidence of AAD was statistically significantly lower in the probiotic group compared with the other groups. Also, the duration of AAD was statistically significantly longer in the control groups than the probiotic group. The investigators concluded that the use of 

 significantly reduced the incidence and duration of AAD in children.

Clinical trials evaluating the use of probiotics for the prevention of AAD in children yielded varying results. A systematic review that assessed the results of 33 randomized, controlled studies concluded that probiotics produced

a moderate reduction in the incidence of pediatric AAD, with a larger effect noted with high-dose probiotics (≥ 5 billion CFUs/day).1 Furthermore, probiotics reduced the duration of diarrhea by almost 1 day. Among the various probiotics evaluated, 

 (eg, Florastor) at 5 to 40 billion CFUs per day appeared to be most appropriate for preventing AAD in children. The authors of the systematic review also stated that it is pre- mature to draw firm conclusions about other probiotic agents.

Notably, there does not seem to be a consensus concerning the use of probiotics to prevent AAD in children as a standard of care. When making recommendations concerning the use of probiotics, pharmacists should follow evidence-based practices.

Guo Q, Goldenberg JZ, Humphrey C, El Dib R, Johnston BC. Probiotics for the prevention of pediatric antibiotic-associated diarrhea. 

. 2019;4(4):CD004827. doi:10.1002/14651858.CD004827.pub5

Schrezenmeir J, de Vrese M. Probiotics, prebiotics, and synbiotics—approaching a definition. 

. 2001;73(suppl 2):361S-364S. doi:10.1093/ajcn/73.2.361s

Probiotics. Natural Medicines. Updated March 10, 2022. Accessed May 31, 2022. 

Salminen MK, Rautelin H, Tynkkynen S, et al. Lactobacillus bacteremia, clinical significance, and patient outcome, with special focus on probiotic 

Hojsak I, Fabiano V, Pop TL, et al. Guidance on the use of probiotics in clinical practice in children with selected clinical conditions and in specific vulnerable groups. 

. 2018;107(6):927-937. doi:10.1111/apa.14270

. 2010;67(6):449-458. doi:10.2146/ajhp090168

​​Shan LS, Hou P, Wang ZJ, et al. Prevention and treatment of diarrhoea with 

 in children with acute lower respiratory tract infections. 

. 2013;4(4):329-334. doi:10.3920/BM2013.0008

Georgieva M, Pancheva R, Rasheva N, Usheva N, Ivanova L, Koleva K. Use of the probiotic 

 DSM 17938 in the prevention of antibiotic-associated infections in hospitalized Bulgarian children: a randomized, controlled trial. 

. 2015;21(4):895-900. doi:10.5272/jimab.2015214.895

Fox MJ, Ahuja KD, Robertson IK, Ball MJ, Eri RD. Can probiotic yogurt prevent diarrhoea in children on antibiotics? A double-blind, randomised, placebo-controlled study. 

. 2015;5(1):e006474. doi:10.1136/bmjopen-2014-006474

Olek A, Woynarowski M, Ahrén IL, et al. Efficacy and safety of 

 DSM 9843 (LP299V) in the prevention of antibiotic-associated gastrointestinal symptoms in children-randomized: double-blind, placebo-controlled study. 

. 2017;186:82-86. doi:10.1016/j.jpeds.2017.03.047

DSM 17938 in the prevention of antibiotic-associated diarrhoea in children: a randomized clinical trial. 

. 2019;25(6):699-704. doi:10.1016/j.cmi.2018.08.017

Wronowski MF, Kotowska M, Banasiuk M, Kotowski A, Kuzmicka W, Albrecht P. Bovine lactoferrin in the prevention of antibiotic-associated diarrhea in children: a randomized clinical trial. 

. 2021;9:675606. doi:10.3389/fped.2021.675606

Esposito C, Roberti A, Turrà F, et al. Frequency of antibiotic-associated diarrhea and related complications in pediatric patients who underwent hypospadias repair: a comparative study using probiotics vs placebo. 

. 2018;10(2):323-328. doi:10.1007/s12602-017-9324-4

Articles

Evidence of the relationship between probiotics and antibiotics is lacking.

Probiotics for the Prevention of Pediatric Antibiotic-Associated Diarrhea

Vaccines are a critical means of preventing disease-related morbidity and mortality,

 providing individual and herd immunity, and decreasing the burden of certain diseases.

 While vaccination is important at every age, it is especially important for older adults: As people age, their immune system weakens, making them more vulnerable to infections. Likewise, age-related comorbidities may increase the risk of complications from illnesses.


Preventive medicine is the most effective strategy to protect the health of older adults, and vaccination is one of the most feasible approaches.

 Read on for an overview of current vaccination recommendations for adults 65 years and older and strategies to ensure the effective vaccination of this population.

The CDC provides recommendations for immunization practices, which are available on the CDC website.

 Specific recommendations are made based on age group as well as on medical condition and other indications. A summary of the CDC recommendations for those 65 years and older is presented in the 

Table. Routine Vaccinations for Individuals 65 Years and Older

The COVID-19 vaccine reduces the risk of contracting and spreading SARS-CoV-2 and decreases the risk of serious illness. The dosing regimen differs based on the specific product that is used. The CDC updated its recommendations in late December 2021 to include a clinical preference for the Pfizer-BioNTech or Moderna mRNA vaccines over the Johnson & Johnson vaccine.

 The CDC also recommends a single booster dose of the COVID-19 vaccine.

At press time, individuals who received the Pfizer-BioNTech vaccine are eligible to receive a booster dose 5 months after their completed series,9 and those who received the Moderna vaccine, after 6 months. Individuals who received the Johnson & Johnson vaccine are eligible to receive a booster dose beginning 2 months after their initial vaccination.

Because of the uncertainty about the duration of protection and the emergence of new variants of the virus, recommendations for booster doses of the COVID-19 vaccine may change.


All individuals 65 years and older should receive an annual influenza vaccine, ideally by the end of October but no earlier than September because of concerns of waning immunity.

 During the 2017-2018 flu season, nearly 80% of influenza-related deaths were in individuals 65 years or older.12 The CDC recommends the influenza inactivated vaccine (IIV) or the influenza recombinant vaccine (RIV4) in adults over 50 years; the influenza live attenuated vaccine (LAIV4) is not recommended in this population.

A tetanus and diphtheria (Td) booster, with or without pertussis, is recommended every 10 years. Individuals who have not been previously vaccinated with tetanus, diphtheria, and pertussis (Tdap) at or after the age of 11 should receive 1 dose of Tdap followed by Td or Tdap boosters every 10 years.

The risk for developing herpes zoster increases with age.13 As such, it is recommended that adults 50 years and older receive a 2-dose series of the recombinant zoster vaccine (Shingrix) spaced 2 to 6 months apart, regardless of previous herpes zoster infection or previous administration of a live zoster vaccine (Zostavax, ZVL).

The overall case-fatality rate for pneumococcal bacteremia is about 20% among adults; this rate may be as high as 60% among older patients.14 The CDC currently recommends 1 dose of the pneumococcal polysaccharide vaccine (PPSV23) for all adults 65 and older. If PPSV23 was administered prior to age 65, the dose of PPSV23 should be administered at least 5 years after the previous dose. A dose of PCV13 may also be considered in addition to PPSV23 in those who did not receive PCV13 previously; a determination concerning its administration should be based on shared clinical decision-making. In patients requiring both vaccines, PCV13 should be administered first, at least 1 year before the PPSV23 vaccine.

In addition to the aforementioned vaccines recommended for most adults 65 years and older, the CDC recommends other vaccines—including varicella, hepatitis A, hepatitis B, MenACWY (meningococcal A, C, W, Y), MenB (meningococcal B), and 

 type b5—for those with certain risk factors or other indications.


There are several reasons elderly adults may not be vaccinated according to CDC recommendations. Patient-related factors include lack of awareness of declining immunity or the importance of vaccines in this age group, lack of familiarity with vaccine recommendations, the belief that a healthy lifestyle can take the place of vaccines, worries about vaccine safety, underestimation of the impact of vaccine-preventable diseases on health, concerns about cost, and mobility issues preventing the individual from getting to a vaccination site.

Provider-related issues and other systematic issues include lack of familiarity with vaccine recommendations, lack of promotion of vaccination to patients, limited access to immunization records, and availability of a vaccine at the provider’s practice site.

Overcoming barriers to vaccination among older individuals means addressing patient-level, provider-level, and systematic issues. Key to the success of vaccination efforts is buy-in from the patient; effective patient education and encouragement can help facilitate this. Health care professionals should identify knowledge gaps and patient concerns, achieved via motivational interviewing that alleviates concerns. Inform patients that Medicare Part B covers influenza and pneumococcal vaccines, as well as other vaccines for those who are at increased risk. Vaccines may also be covered by Medicare Part D, Medicaid, or private insurers.

At the provider level, attaining the proper education and training necessary to effectively address vaccination needs in the community can help. Keeping current with the CDC’s recommendations is essential. Providers must maintain complete and up-to-date patient records, ensure sufficient supply of properly stored vaccines. Providers must also be proactive in examining patient history and screening for immunization needs. Although this should be an ongoing process, it may be instrumental to designate a particular visit to ensure that an overall assessment of patient immunization status is performed.

armacists are uniquely positioned to play a significant role in vaccination efforts. Community pharmacies are convenient vaccination sites, staffed with trusted professionals who are knowledgeable and trained.

On a systemic level, government and social agencies and the health care community should work to facilitate successful vaccination programs. Those who live in community-based group homes or who receive home health care should be included in vaccination outreach programs. Involving caregivers is also important. Vaccines should be offered at convenient locations: senior centers, community centers, or independent living facilities for older adults. Pay special attention to those who are homebound, and to people living in rural or remote areas. Lastly, create effective communication material specifically geared for this population; this is likely to be instrumental in maximizing the impact of these efforts.

Older adults are among the most vulnerable populations. By leveraging expertise to advocate for and facilitate vaccine administration, pharmacists are poised to ensure widespread vaccination in this cohort.


View the rest of our February 2022 issue here

Weinberger B. Vaccines for the elderly: current use and future challenges. 

. 2018;15:3. doi:10.1186/s12979-017-0107-2

Why vaccinate? The history of vaccines. The College of Physicians of Philadelphia. Updated January 25, 2018. Accessed January 3, 2022. 

https://www.historyofvaccines.org/content/articles/why-vaccinate

Adults age 65 and older. US Department of Health & Human Services. Updated April 29, 2021. Accessed January 3, 2022. 

https://www.hhs.gov/immunization/who-and-when/adults/seniors/index.html

Ciabattini A, Nardini C, Santoro F, Garagnani P, Franceschi C, Medaglini D. Vaccination in the elderly: the challenge of immune changes with aging. 

. 2018;40:83-94. doi:10.1016/j.smim.2018.10.010

Adult immunization schedule. CDC. Updated February 12, 2021. January 3, 2022. 

https://www.cdc.gov/vaccines/schedules/hcp/imz/adult.html

Types of vaccines available. CDC. Updated December 29, 2021. Accessed January 3, 2022. 

https://www.cdc.gov/coronavirus/2019-ncov/vaccines/different-vaccines.html

CDC endorses ACIP’s updated COVID-19 vaccine recommendations. News release. CDC. December 16, 2021. Accessed January 3, 2022. https://www.cdc.gov/media/releases/2021/s1216-covid-19-vaccines.html

CDC expands eligibility for COVID-19 booster shots. News release. CDC. October 21, 2021. Accessed January 3, 2022. 

https://www.cdc.gov/media/releases/2021/p1021-covid-booster.html

CDC recommends Pfizer booster at 5 months, additional primary dose for certain immunocompromised children. CDC. News release. January 4, 2022. Accessed January 4, 2022. https://www.cdc.gov/media/releases/2022/s0104-Pfizer-Booster.html

COVID-19 vaccine booster shots. CDC. Updated December 28, 2021. Accessed January 3, 2022. 

https://www.cdc.gov/coronavirus/2019-ncov/vaccines/booster-shot.html

Key facts about flu vaccines. CDC. Updated November 18, 2021. Accessed January 3, 2022. 

https://www.cdc.gov/flu/prevent/keyfacts.htm

Frank T. Flu deaths rising for Americans over 65. AARP. October 2, 2018. Accessed January 3, 2022. 

https://www.aarp.org/health/conditions-treatments/info-2018/older-flu-deaths-rising.html

Shingles. Mayo Clinic. September 17, 2021. Accessed January 3, 2022. 

https://www.mayoclinic.org/diseases-conditions/shingles/symptoms-causes/syc-20353054

Pneumococcal vaccines (PCV13 and PPSV23). Immunization Action Coalition. Updated October 22, 2020. Accessed January 3, 2022. 

https://www.immunize.org/askexperts/experts_pneumococcal_vaccines.asp

Aging and immunity: the important role of vaccines. American College of Physicians. Accessed January 3, 2022. 

https://www.acponline.org/system/files/documents/clinical_information/resources/adult_immunization/aging_and_immunity_guide.pdf

Ventola CL. Immunization in the United States: recommendations, barriers, and measures to improve compliance: part 2: adult vaccinations. 

Tak CR, Marciniak MW, Savage A, Ozawa S. The essential role of pharmacists facilitating vaccination in older adults: the case of herpes zoster. 

. 2020;16(1):70-75. doi:10.1080/21645515.2019.1637218

Jurisdictions: Vaccinating older adults and people with disabilities. CDC. Reviewed August 26, 2021. Accessed January 3, 2022. 

https://www.cdc.gov/vaccines/covid-19/clinical-considerations/older-adults-and-disability/access.html

Vaccines are important for everyone, but they’re critical for adults older than 65 years. 

Review: Vaccine Guidelines for Older Adults

Obesity is a worldwide major public health concern. In the US, approximately 74% of adults are either overweight (BMI 25-29.9 kg/m2) or obese (BMI > 30 kg/m2).

Obesity is associated with serious health complications including type 2 diabetes, hypertension, dyslipidemia, and cardiovascular disease.

 As such, obesity is considered a multi-faceted chronic disease that requires appropriate management. According to the American Association of Clinical Endocrinologists and the American College of Endocrinology, lifestyle modification, consisting of a reduced-calorie diet and physical activity, is the first-line management strategy for overweight and obesity.

 Pharmacotherapy is recommended as an adjunct to lifestyle modifications in patients with a BMI > 30 kg/m2 or in patients with a BMI > 27 kg/m2 in the presence of weight-related comorbidities, such as diabetes, hypertension, and dyslipidemia.

 The recent FDA approval of semaglutide for weight management presents an important advancement in the pharmacotherapy options available to the practitioner as well as to the patient. The aim of this article is to provide a brief overview of the agents that are FDA-approved for chronic weight management.

Pharmacological Agents Approved for Chronic Weight Management

Five medications are currently approved by the FDA for chronic weight management (see 

); these include semaglutide (Wegovy; Novo Nordisk), liraglutide (Saxenda; Novo Nordisk), naltrexone extended-release (ER)/bupropion ER (Contrave; Orexigen Therapeutics Inc), phentermine/topiramate ER (Qsymia; Vivus, Inc), and orlistat (Xenical and Alli).

 Notably, semaglutide, naltrexone ER/bupropion ER, and phentermine/topiramate ER are approved for adult use only, whereas liraglutide and orlistat are also approved for children aged 12 and older.

 None of the approved agents are recommended in pregnancy or in patients planning a pregnancy.

 An additional medication, setmelanotide (Imcivree; Rhythm Pharmaceuticals), is approved for the treatment of obesity caused by 3 rare genetic conditions and is not indicated for weight management in the general patient population.

 The choice of which medication to use in a given patient is influenced by patient comorbidities and patient preferences including the route of administration and dosing frequency, as well as cost.

FDA Approved Medication for Chronic Weight Management

In addition to the aforementioned medications indicated for chronic weight management, several agents are approved for short-term (<12 weeks) use. Clinical guidelines, though, recommend weight loss medications to be used chronically for a sustained effect.

 When comparing the efficacy of weight-loss agents, it is important to note that even a sustained 5% weight loss has been shown to produce a clinically meaningful reduction in triglycerides, blood glucose, blood pressure, and the risk of developing type 2 diabetes.

The most recently approved medication, semaglutide, is a glucagon-like peptide-1 (GLP-1) agonist that is also approved for use in type 2 diabetes. Compared with the other approved agents, semaglutide resulted in the greatest weight loss among patients who used it. Animal studies showed that semaglutide activates neurons in brain regions involved in the regulation of appetite, thus decreasing food intake.

The recommended initial dose is 0.25 mg injected subcutaneously once weekly for 4 weeks with dose increments every 4 weeks to a maintenance dose of 2.4 mg once weekly. The rationale behind this titration is to decrease gastrointestinal adverse effects (AEs) that are associated with the GLP-1 agonist drug class. AEs reported with the use of semaglutide in clinical trials at the rate of > 5% and with frequencies greater than placebo included nausea (44%), diarrhea (30%), vomiting (24%), constipation (24%), abdominal pain (20%), headache (14%), fatigue (11%), dyspepsia (9%), dizziness (8%), abdominal distension (7%), eructation (7%), hypoglycemia in patients with type 2 diabetes (6%), flatulence (6%), gastroenteritis (6%), and gastroesophageal reflux disease (5%). Semaglutide carries a black box warning for thyroid C-cell tumors; a warning that is based on data from animal studies. Semaglutide is contraindicated in patients with a personal or family history of medullary thyroid carcinoma or multiple endocrine neoplasia syndrome type 2. Additional warnings include acute kidney

injury, mostly due to volume depletion, as well as acute pancreatitis, acute gallbladder disease, increase in heart rate, and suicidal ideation. Patients with type 2 diabetes, who use semaglutide for weight loss, are at an increased risk for hypoglycemia, especially if they are using insulin or an insulin secretagogue (eg, sulfonylurea), and for diabetic retinopathy complications.

Pharmacists should advise the patient to stay hydrated, rotate injection sites with each injection, and use semaglutide on the same day each week. Patients should not use semaglutide with other GLP-1 agonists.

Like semaglutide, liraglutide is a GLP-1 agonist with similar pharmacology and AE profile. Liraglutide is administered as a subcutaneous injection. The dose is initiated at 0.6 mg daily which is titrated in weekly intervals to a maintenance dose of 3 mg daily. AEs reported with the use of liraglutide in clinical trials at the rate of > 5% and with frequencies greater than placebo included nausea (39.3%), diarrhea (20.9%), constipation (19.4%), vomiting (15.7%), injection site reactions (13.9%), headache (13.6%), hypoglycemia in patients with type 2 diabetes (12.6%), dyspepsia (9.6%), fatigue (7.5%), dizziness (6.9%), abdominal pain (5.4%), increased lipase (5.3%), and upper abdominal pain (5.1%). Liraglutide carries a black box warning for thyroid C-cell tumors; a warning that is based on data from animal studies. Liraglutide is contraindicated in patients with a personal or family history of medullary thyroid carcinoma or multiple endocrine neoplasia syndrome type 2, as well as in pregnancy. Additional warnings include acute pancreatitis, acute gallbladder disease, hypoglycemia, especially if used with insulin or an insulin secretagogue, increase in heart rate, renal impairment, mostly due to volume depletion, and suicidal ideation. Caution should be used when initiating liraglutide in patients with renal dysfunction or hepatic impairment. In addition to counseling on injection techniques and AEs, pharmacists should counsel patients to discontinue liraglutide if they have not achieved 4% weight loss from baseline by 16 weeks, as it is not likely that continued treatment would result in clinically meaningful weight loss. Patients should not use liraglutide with other GLP-1 agonists.

Naltrexone is an opioid antagonist which is also indicated for opioid use disorder, and bupropion is a dopamine and norepinephrine reuptake inhibitor which is also indicated for depression and smoking cessation. The 2 medications work synergistically by stimulating 2 areas of the brain involved with the regulation of food intake: the hypothalamus and the mesolimbic dopamine circuit. This medication is available as ER tablets containing 8 mg of naltrexone and 90 mg of bupropion. The recommended initial dose is 1 tablet once daily orally with weekly increments to a maintenance dose of 2 tablets in the morning and 2 tablets in the evening.

AEs reported with the use of naltrexone ER/bupropion ER in clinical trials at the rate of > 5% and with frequencies greater than placebo included nausea (32.5%), constipation (19.2%), headache (17.6%), vomiting (10.7%), dizziness (9.9%), insomnia (9.2%), dry mouth (8.1%), and diarrhea (7.1%). Because bupropion is an antidepressant, naltrexone ER/bupropion ER carries a black box warning for an increased risk of suicidal thoughts and behaviors. Naltrexone ER/bupropion ER is contraindicated in patients with uncontrolled hypertension, chronic opioid use, seizure disorders, anorexia nervosa or bulimia, patients undergoing abrupt discontinuation of alcohol, benzodiazepines, barbiturates, or antiepileptic drugs, patients using other bupropion products, and patients who have taken monoamine oxidase inhibitors (MAOIs) within the last 14 days. Other precautions include neuropsychiatric events, which were reported in patients who used bupropion for smoking cessation, hepatotoxicity associated with naltrexone, activation of mania, increase in blood pressure and heart rate, angle-closure glaucoma, and hypoglycemia in patients with type 2 diabetes who are on insulin or an insulin secretagogue.

This medication should also not be used in patients with end-stage renal disease or severe hepatic impairment. Pharmacists should counsel patients to avoid taking this medication with a high-fat meal, since doing so increases systemic exposure to the medication, and to avoid drinking alcohol. If after 12 weeks at the maintenance dose, the patient does not achieve at least 5% weight loss from baseline, naltrexone ER/ bupropion ER should be discontinued.

Phentermine’s mechanism in weight loss is believed to involve the release of catecholamines in the hypothalamus, leading to decreased appetite and food intake. It is also available as monotherapy for short-term weight management.

 Topiramate produces weight loss by suppressing appetite and enhancing satiety, which is achieved by several possible pharmacological mechanisms.

Phentermine/topiramate ER is taken orally once daily in the morning to avoid insomnia. The initial dose is 3.75 mg/23 mg daily and titrated up to 7.5 mg/46 mg daily after 14 days. After 12 weeks on the latter dose, the patient’s weight loss is evaluated and if the patient does not achieve at least 3% weight loss from baseline, the medication may be discontinued as continued use on this dose is not likely to produce clinically meaningful weight loss. Alternatively, at that point, the dose may be increased to 11.25 mg/69 mg daily for 14 days followed by 15 mg/92 mg daily, which is the maximum recommended dose. If the patient does not achieve at least 5% weight loss from baseline after 12 weeks on the maximum dose, the medication should be discontinued. AEs reported with the use of phentermine/topiramate ER in clinical trials at the rate of > 5% and with frequencies greater than placebo included paresthesia (19.9%), dry mouth (19.1%), constipation (16.1%), upper respiratory tract infection (13.5%), headache (10.6%), dysgeusia (9.4%), insomnia (9.4%), nasopharyngitis (9.4%), dizziness (8.6%), sinusitis (7.8%), nausea (7.2%), back pain (6.6%), fatigue (5.9%), diarrhea (5.6%), blurred vision (5.4%), bronchitis (5.4%), and urinary tract infection (5.2%).

Because it contains phentermine, an amphetamine-like stimulant, this medication is classified as a schedule IV controlled substance. Phentermine/topiramate ER is contraindicated in pregnancy, glaucoma, hyperthyroidism, and within 14 days of MAOI use. Due to teratogenic risk, this medication is available through a Risk Mitigation and Evaluation Strategy (REMS) program. Warnings associated with the use of the medication include an increase in heart rate, suicidal ideation, acute myopia and secondary angle closure glaucoma, cognitive impairment, mood and sleep disorders, metabolic acidosis, elevation in creatinine, kidney stones, oligohidrosis and hyperthermia, and hypokalemia. Patients should have their laboratory chemistry profiles analyzed periodically throughout the treatment. 

Additionally, patients should discontinue the medication gradually, since abrupt discontinuation of topiramate can precipitate a seizure. The medication has been shown to increase the risk for hypoglycemia in patients who take antidiabetic medications, the risk for hypotension in patients who use antihypertensive medications, and it may potentiate central nervous system (CNS) depression in patients who drink alcohol or use any other CNS depressants. This agent should not be used in patients with end-stage renal disease or severe hepatic impairment. Pharmacists should advise patients to avoid driving or operating heavy machinery while using this medication, since it may cause dizziness or confusion. Patients should also avoid drinking alcohol and be aware of the medication’s teratogenic risk and potential for drug-drug interactions.

Orlistat is the only chronic weight management medication available both over the counter (60 mg capsules) and by prescription (120 mg capsules). This agent acts by inhibiting gastrointestinal lipases, resulting in decreased fat absorption.

The recommended dose of the OTC product is 60 mg 3 times daily while the prescription product is dosed at 120 mg 3 times daily. Orlistat must be taken within 1 hour of a meal containing fat. The patient should be on a reduced-calorie diet that contains approximately 30% of calories from fat. If the patient’s meal is skipped or does not contain fat, the dose of the medication can be omitted. AEs reported within the first year of using prescription orlistat in clinical trials at the rate of > 5% and with incidence which was at least twice seen with placebo were oily spotting (26.6%), flatus with discharge (23.9%), fecal urgency (22.1%), fatty/oily stool (20%), oily evacuation (11.9%), increased defecation (10.8%), and fecal incontinence (7.7%). Orlistat is contraindicated in pregnancy, chronic malabsorption syndrome, and cholestasis. Warnings include decreased absorption of fat-soluble vitamins, rare cases of severe liver injury, increased levels of urinary oxalate, increased risk of cholestasis in patients who achieve substantial weight loss, and increased gastrointestinal AEs in patients who have a diet high in fat (>30% total daily calories from fat).

The OTC orlistat also contains a warning for organ transplant recipients noting that orlistat can interact with immunosuppressants (eg, cyclosporine).

Pharmacists should advise patients to take a multivitamin containing fat-soluble vitamins at least 2 hours before or after taking orlistat.

 Furthermore, pharmacists should monitor for drug-drug interactions with this medication.

Medications for chronic weight management differ in their mechanisms, efficacy, safety, and dosing profiles, as well as in their cost of therapy. Patient-specific factors should be considered when choosing a weight loss agent and, once therapy is initiated, it is necessary to monitor the patient’s response and tolerability. Pharmacists should discuss the expected benefits and risks of weight loss agents with their patients, emphasizing that these medications need to be taken long-term for a sustained effect and should be used in conjunction with a healthy lifestyle.

1. Obesity and overweight. CDC. Updated March 1, 2021. Accessed June 24, 2021. https://www.cdc.gov/nchs/fastats/obesity-overweight.htm

2. Garvey WT, Mechanick JI, Brett EM, et al. American Association of Clinical Endocrinologists and American College of Endocrinology Comprehensive Clinical Practice Guidelines for Medical Care of Patients with Obesity. Endocr Pract. 2016;22 Suppl 3:1-203. doi:10.4158/EP161365.GL

3. Prescription medications to treat overweight and obesity. National Institute of Diabetes and Digestive and Kidney Health. Updated June 2021. Accessed June 18, 2021. https://www.niddk.nih.gov/health-information/weight-management/prescription-medications-treat-overweight-obesity#available

4. FDA approves first treatment for weight management for people with certain rare genetic conditions. US Food and Drug Administration. Published November 27, 2020. Accessed June 18, 2021. https://www.fda.gov/drugs/drug-safety-and-availability/fda-approves-first-treatment-weight-management-people-certain-rare-genetic-conditions#:~:text=%5B11%2F27%2F2020%5D,POMC

5. Wegovy. Prescribing information. Novo Nordisk; 2021. Accessed June 11, 2021. https://www.novo-pi.com/wegovy.pdf

6. Saxenda. Prescribing information. Novo Nordisk; 2020. Accessed June 14, 2021. https://www.novo-pi.com/saxenda.pdf

7. Contrave. Prescribing information. Nalpropion Pharmaceuticals LLC; 2021. Accessed June 17, 2021. https://contrave.com/contrave-pi/

8. Qsymia. Prescribing information. Vivus, Inc.; 2020. Accessed June 17, 2021. https://qsymia.com/patient/include/media/pdf/prescribing-information.pdf

9. Xenical. Prescribing information. H2-Pharma LLC; 2020. Accessed June 17, 2021. https://xenical.com/pdf/PI_Xenical-brand_FINAL.PDF

10. Alli. Drug label information. GlaxoSmithKline Consumer Healthcare Holdings (US) LLC; 2020. Accessed June 17. 2021. https://dailymed.nlm.nih.gov/dailymed/lookup.cfm?setid=a2d3bd73-f3af-4ea5-a57c-66b0004cfe4f

Five medications are currently approved by the FDA for chronic weight management.

A Review of FDA-Approved Medications for Chronic Weight Management

Since the onset of the COVID-19 pandemic, emphasis has been placed on monitoring health status, screening for disease states, and ensuring that the general public is not exposed to the virus and/or exhibiting signs and symptoms of COVID-19. One of the methods used to detect illness and prevent the spread of the disease is monitoring for fever with the use of thermometers. According to IRI, a Chicago-based market research firm, the sale of personal thermometers increased by 297% during the 4-week period ending March 22, 2020, compared to the same time period 1 year earlier.

 Since COVID-19 remains a public concern, it is important for pharmacists to be familiar with the various types of thermometers available on the market and to provide proper guidance on their use.

The body maintains a state of homeostasis regulated by the hypothalamic thermoregulatory center. The center balances excess heat production from metabolic activity in the muscle and liver by allowing heat to be released from the skin and lungs to maintain a mean oral temperature of 36.8

 0.7o F). Fluctuations in body temperature occur throughout the day, with temperature being lower in the morning and higher in the evening.

 Furthermore, the temperature considered to be fever differs based on the measurement site (

Body Temperature per Site of Measurement

Considerations When Selecting a Thermometer

Various thermometers are available on the US market. When selecting a thermometer, identifying one that will provide an accurate reading is most important. Since the FDA regulates thermometers as medical devices, all approved thermometers are considered accurate and reliable, when used appropriately.

 To do so, considerations must be given to the ease of use, which may be a function of the site of temperature measurement. Thus, consideration should be given to the versatility afforded by certain thermometers, allowing for measurements to be obtained in more than one body site. The following is a discussion of various types of thermometers. 

Rectal thermometers have been generally accepted as the “gold standard” for measuring temperature in very young children; however, some caregivers refrain from using them due to their intrusive nature and associated risks. These risks may include the development of peritonitis, rectal or intestinal perforation, and retaining of the thermometer inside the rectum.

 Rectal temperature measurements should not be taken in patients with obstructive hemorrhoids or diarrhea, as well as in patients with neutropenia due to their increased susceptibility to infection. Other considerations when measuring rectal temperature are that it is cumbersome and time consuming and that rapid changes in body temperature may not be detected due to the large muscle mass and poor blood flow to the rectal area.

 Notably, rectal temperatures tend to run higher than oral temperatures.

Oral thermometers are commonly used in medical offices and within households. However, to obtain accurate readings, certain factors must be kept in mind. For instance, oral temperature readings should be obtained at least 20 to 30 minutes after drinking and/or eating and should not be taken in patients who have a difficult time keeping the thermometer under their tongue and/or difficulty creating a tight seal around the thermometer.

 For younger patients who may struggle with these issues, pacifier thermometers are an alternative option to measure temperature. To obtain a proper reading with a pacifier thermometer, patients should wait 30 minutes after eating or drinking and should hold the pacifier in their mouth without moving it for 2 to 6 minutes.

 Lastly, oral temperatures should not be obtained in patients who are hyperventilating, uncooperative, lethargic, confused, and/or those who have had recent oral surgery.

Tympanic thermometers are usually used in pediatric offices to take the temperature via the ear. These provide a relatively quick and accurate measurement because the ear is close to the hypothalamus which allows for an accurate reading of core body temperature.

 However, proper positioning of the thermometer is extremely important to ensure an accurate reading. Other factors such as inflammation of the ear canal, age (children younger than 6 months do not have fully developed ear canals), and earwax buildup may also affect temperature readings.

 Additionally, cold or hot weather can affect temperature readings so it is recommended to wait at least 15 minutes after being exposed to extreme temperatures before using the thermometer.

Proper technique requires the user to pull the ear backward to help straighten the ear canal and to aim the tip of the probe towards the patient's eye on the opposite side of his or her head.

Temporal touch thermometers use an infrared scanner to scan the temporal artery in the forehead. This task is completed by placing the thermometer on 1 side of the forehead and then moving it across the forehead; the process usually takes a few seconds. This method of measuring temperature can be very sensitive in detecting fever but the scanner needs to be in contact with the skin at all times. Overall, this method provides an easy and accurate temperature reading in most patients.

 Yet, one must keep in mind that direct sunlight, cold temperature, sweaty forehead, and poor technique can impact the accuracy of the reading.

Noncontact temporal thermometers also use infrared technology but these do not require direct contact with the skin. Thermometers are generally held between 1.2 and 6 inches from the skin.

 Using a forehead noncontact infrared thermometer is quick, convenient, noninvasive, and carries a low risk of disease transmission. Studies suggest that taking temperature immediately after coming in from the cold underestimates body temperatures and as such, infrared temporal thermometers are not ideal for screening for diseases during cold weather.

 To ensure accuracy, measurements should be taken at least 10 minutes after coming in from the cold.

 These thermometers should also be used in environments free from secondary infrared sources, such as direct sunlight and incandescent lamps.

Axillary temperatures usually run lower than oral temperatures. Compared with the rectal and oral methods of measuring temperature, axillary thermometers are less reliable at detecting fevers.

 Although they may be favored because of their ease of use and noninvasive nature, their use should be discouraged because of concerns with accuracy.

 When used, temperatures should not be taken directly after vigorous activity or bathing since these can alter body temperature.

Basal thermometers are used to monitor basal body temperature for the purpose of tracking ovulation in women who are trying to conceive or prevent pregnancy.

Pharmacists must be familiar with the different thermometers so they can ensure proper use by the consumer. 