In acute-patient-care settings, injectable drugs are used ubiquitously. Injectables offer several advantages over other administration routes, including precise and adjustable dosing, predictable bioavailability, and fast onset of action. Intravenous administration is particularly crucial for critically ill patients and others undergoing anesthesia in whom the onset of drug action is required in seconds.

The average number of injectable drugs administered to patients during a typical hospitalization in the United States has not been formally quantified, but a recent analysis of the QuintilesIMS National Sales Perspective pharmacy database found that the majority of nonfederal US hospital drug spending in 2016 was for injectables ($25.8 billion), with 31.7% of that spending for generically marketed preparations.

Two hospital care areas that rely heavily on generic injectables are operating rooms and intensive care units (ICUs). An adult patient undergoing an uneventful general anesthetic for a variety of surgical procedures may reasonably receive no fewer than 5 different classes of injectable drugs (

). Clinicians working in these settings require several other classes of injectables, including vasopressors and anti-arrhythmics, to be immediately available for the management of potential complications of anesthesia and surgery. For more complex or lengthy procedures, the number of required drugs may reach 30 or more, to be delivered in potentially hundreds of incremental doses.

In the ICU, the vast majority of critically ill patients are likely to require treatment with crystalloid solutions, anticoagulants, acid suppressive agents, sedatives, analgesics, electrolytes, and antibiotics. The results of a 2015 multicenter observational study showed that the most common classes of typically injectable medications used in medical ICU patients were anti-infectives, opioids, antihypertensives, and insulin.

Hospitals’ and physicians’ reliance on generic injectables for routine clinical care exposes 2 key vulnerabilities of these formulations: shortages and cost increases.

One generic injectable drug in shortage and used commonly in hospitalized patients is sodium bicarbonate.

 Sodium bicarbonate is used by clinicians to treat life-threatening metabolic acidosis. It is also used for the management of select drug overdoses and a major component of dialysate solutions used in the treatment of renal failure. Several clinical reviews describe injectable drug shortages with implications for treatment of infectious diseases,

 Drug shortages require hospitals and clinicians to alter drug purchasing, dispensing, and prescription practices, with consequences for patient care and its outcomes.

 There is some observational evidence that national shortages of generic injectable medications are associated with patient harm.

Dramatic cost increases may be related to drug shortages but can also be caused by rebranding or manufacturer restructuring. A 2016 report sponsored by the American Hospital Association and Federation of American Hospitals identified 10 drugs with price increases of 300% or more between 2013 and 2015. The list included 6 generic injectables used in the operating room and ICU: hydralazine (776%), nitroprusside (672%), isoproterenol (480%), neostigmine (446%), glycopyrrolate (316%), and ephedrine (300%).

In a recent review article, the authors argued that unique market forces and manufacturing practices inextricably link the problems of drug shortage and significant price increases for generic injectable medications.

 For example, recent rebranding of vasopressin, commonly used alongside norepinephrine for the management of patients with septic shock, increased its cost more than 200% and led to a modification of institutional protocols to reduce use.

Drug manufacturers are not required to reveal which factories produce each drug they manufacture.

 Therefore, Hurricane Maria’s impact on drug manufacturing facilities in Puerto Rico, which produces 10% of all drugs consumed in the United States, remains to be seen.

  Even in the absence of devastating natural disasters, supply instability of generic injectable drugs has significant consequences for the US health care system. Further work by pharmaceutical manufacturers, the FDA, and legislators to address these issues is necessary to ensure that the sickest patients receive the treatments they need.

Emily A. Vail, MD, MSc, is an assistant clinical professor of anesthesiology at the University of Texas Health Science Center at San Antonio. Mona K. Patel, PharmD, BCCCP, is a clinical pharmacy manager, critical care, in the surgical intensive care unit at NewYork-Presbyterian Hospital/Columbia University Medical Center.

De Oliveira Jr. GS, Theilken LS, McCarthy RJ. Shortage of perioperative drugs: implications for anesthesia practice and patient safety. 

 2011;113(6):1429-1435. doi: 10.1213/ANE.0b013e31821f23ef.

Fox ER, Sweet BV, Jensen V. Drug shortages: a complex health care crisis. 

 2014;89(3):361-373. doi: 10.1016/j.mayocp.2013.11.014.

Fox ER, Tyler LS. Potential association between high-cost medications and drug shortages. 

2017;37(1):36-42. doi: 10.1002/phar.1861.

NORC at the University of Chicago. Trends in hospital inpatient drug costs: issues and challenges. Presented at: American Hospital Association and the Federation of American Hospitals; October 11, 2016; Washington, DC. http://aha.org/content/16/aha-fah-rx-report.pdf. Accessed October 18, 2017.

Quadri F, Mazer-Amirshahi M, Fox ER, et al. Antibacterial drug shortages from 2001 to 2013: implications for clinical practice. 

 2015;60(12):1737-1742. doi: 10.1093/cid/civ201. 

Schumock GT, Li EC, Wiest MD. National trends in prescription drug expenditures and projections for 2017. 

. 2017;74(15):1158-1173. doi: 10.2146/ajhp170164. 

Smithburger PL, Buckley MS, Culver MA, et al. A multicenter evaluation of off-label medication use and associated adverse drug reactions in adult medical ICUs.

2015;43(8):1612-1621. doi: 10.1097/CCM.0000000000001022.

Statement from FDA commissioner Scott Gottlieb, M.D. on FDA’s continued assistance following the natural disaster in Puerto Rico [news release]. FDA. October 6, 2017. fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm579493.htm. Accessed October 9, 2017.

accessdata.fda.gov/scripts/drugshortages/dsp_ActiveIngredientDetails.cfm?AI=Sodium%20Bicarbonate%20Injection,%20USP&st=c&tab=tabs-1

. Published March 1, 2017. Accessed October 10, 2017.

Vail E, Gershengorn HB, Hua M, Walkey AJ, Rubenfeld G, Wunsch H. Association between US norepinephrine shortage and mortality among patients with septic shock

. 2017;317(14):1433-1442. doi: 10.1001/jama.2017.2841.

Wiggins BS, Nappi J, Fortier CR, Taber DJ. Cardiovascular drug shortages: predominant etiologies, clinical implications, and management strategies. 

Wu JY, Stollings JL, Wheeler AP, Semler MW, Rice TW. Efficacy and outcomes after vasopressin guideline implementation in septic shock. 

 September 14, 2016. doi: 10.1177/1060028016669163.

Articles

Health System Information

In acute-patient-care settings, injectable drugs are used ubiquitously. Injectables offer several advantages over other administration routes, including precise and adjustable dosing, predictable bioavailability, and fast onset of action.

Clinical Use of Generic Injectable Drugs in Hospitalized Patients

Fosfomycin (Monurol) is an antibiotic that uses a unique mechanism of action to establish its bactericidal activity. It inactivates the enzyme, enolpyruvyl transferase, irreversibly blocking the condensation of uridine diphosphate-N-acetylglucosamine with p-enolpyruvate, one of the first steps in bacterial cell wall synthesis. It also reduces the adherence of bacteria to uroepithelial cells.

There is generally no cross-resistance between fosfomycin and other classes of antibacterial agents, such as beta-lactams and aminoglycosides.

 Fosfomycin has a broad spectrum of in vitro activity covering gram-positive pathogens, including methicillin resistant 

, and gram-negative pathogens, including 

, extended-spectrum beta-lactamase (ESBL) pathogens, and carbapenem-resistant 

 Although a relatively old and “forgotten”

 antibiotic (discovered in 1969 and FDA-approved in 1996), fosfomycin can be safe and potentially useful in an era of increasing prevalence of multi-drug—resistant bacteria.

The poor bioavailability of oral fosfomycin (37%) limits its use in patients who are critically ill. Intravenous (IV) fosfomycin is approved for use outside the United States and can be imported to the United States from Europe on a compassionate-use basis under the aegis of the emergency investigational new drug application process. A small number of case studies from the United States have reported the use of IV fosfomycin as an adjunctive agent in successful treatment of blood and disseminated infections due to extensively drug-resistant 

 In a recent multi-center, phase 2, placebo-controlled trial, fosfomycin was used in an experimental inhalation system, along with amikacin, as an adjunct agent to standard IV antibiotics to treat gram-negative bacterial ventilator-associated pneumonia.

 The remainder of this article will focus on the use of oral fosfomycin for both FDA-approved and unapproved indications.

Oral fosfomycin is FDA approved at a single 3-g dose to treat uncomplicated urinary tract infection (UTI) (ie, acute cystitis) in women due to susceptible strains of 

 Fosfomycin is listed as one of the first-line treatment options, along with trimethoprim-sulfamethoxazole and nitrofurantoin, in the Infectious Diseases Society of America (IDSA) guidelines for uncomplicated cystitis.

 Fosfomycin has been shown to be effective for uncomplicated UTIs as a single dose (see 

 Additionally, it is recommended for the treatment of uncomplicated cystitis in elderly individuals.

 Primarily because of increasing bacterial resistance to other agents, the use of fosfomycin in the United States is starting to increase for both FDA-approved and non—FDA-approved indications.

Every 48-to-72 hours dosing in complicated UTIs

Only 1 clinically appreciable drug interaction (metoclopramide)

Development of resistance with increased use, including while on therapy for 

Broad spectrum of activity (may cover most organisms associated with UTIs) including resistant pathogens such as ESBLs, some CRE, VRE, and MRSA

Not recommended to use in pyelonephritis, and limited data in prostatitis

Potential for treatment failure regardless of in vitro susceptibilities

UTI = urinary tract infection; ESBL = extended spectrum beta-lactamases; CRE = carbapenem-resistant enterobacteriaceae; VRE = vancomycin-resistant enterococci; MRSA = methicillin-resistant staphylococcus

Although not an FDA-approved indication, fosfomycin is used to treat complicated UTIs, excluding pyelonephritis, perinephric abscess, or UTI associated with bacteremia. It is important for providers to realize that the dosing of fosfomycin in these instances is different for complicated infections. For complicated UTIs, fosfomycin is commonly given in 3-g doses every 48 to 72 hours for 6 to 21 days. Three doses are usually sufficient, but the total duration is guided by clinical improvement.

There are data available supporting the use of fosfomycin for complicated UTIs. According to the results of a recent single-center, retrospective study from the Henry Ford Health System, outpatient therapy with fosfomycin (including as a step-down agent) was noninferior to IV ertapenem (Invanz) for outpatient treatment of ESBL UTI, mostly attributed to ESBL 

 Fosfomycin and amoxicillin-clavulanate were shown to be equally effective for cystitis caused by susceptible isolates with cure rates of 93%.

 However, another retrospective analysis on the use of fosfomycin to treat complicated UTIs due to multidrug-resistant organisms demonstrated a notable discordance between in vitro susceptibility (overall 86%) and microbiological cure (overall 59%). The largest discordance occurred for carbapenem-resistant 

 (92% in vitro susceptibility vs 46% microbiological cure rate). Microbiological failure was more common in patients who underwent solid organ transplant and in patients with ureteral stents.

is relatively common, and resistance can emerge while on therapy, regardless of in

 It is important for providers to note that even patients with susceptible organisms may fail fosfomycin therapy.

Another complicated UTI for which fosfomycin cannot be used is pyelonephritis. The IDSA guidelines do not recommend fosfomycin use to treat pyelonephritis due to less than optimal serum and renal tissue concentrations after oral dosing.

 Ode and colleagues studied fosfomycin in patients with fosfomycin and found a success rate of just 44% and considerably lower concentrations in the renal tissues compared with the urine.

 Therefore, fosfomycin should be avoided if there are concerns about upper urinary tract (ie, kidney) involvement.

Prostatitis is another disease state in which oral fosfomycin has been used. Fosfomycin achieves reasonable intraprostatic tissue levels

 and is active against extended-spectrum beta-lactamase—producing organisms.

 For these reasons, the consensus guidelines by the Prostatitis Expert Guidance Group in the United Kingdom state that fosfomycin can be considered in patients with chronic bacterial prostatitis due to multi-drug-resistant gram-negative infections, based on susceptibility results and discussion with local microbiologists.

 However, studies have been small or consist of case studies, and there is limited clinical experience and outcome data.

Fosfomycin may be an attractive option to treat UTIs for many reasons. First, it achieves urinary concentrations well above typical minimum inhibitory concentrations (~1000-4000 mcg/mL) and is able to sustain them for long periods of time (>100 mcg/mL at 48 hours and greater than the minimum inhibitory concentration of 

 Thus, it is an attractive single-dose regimen for uncomplicated UTIs.

 Second, there is no hepatic or renal adjustment.

 Third, there is only 1 clinically relevant drug interaction with metoclopramide that decreases absorption of fosfomycin listed in the package insert.

 Interestingly, fosfomycin may actually decrease the nephrotoxicity and ototoxicity of aminoglycosides and cisplatin if administered together.

 Fourth, due to relatively low use and an unshared mechanism of action, resistance to fosfomycin remains relatively low even among some multi-drug—resistant organisms.

 Some studies even suggest that fosfomycin may still cover up to 97% of ESBL-producing 

 Fifth, patients with multiple allergies could use fosfomycin when treatment options become severely limited. Finally, from a patient perspective, oral outpatient treatment may be favorable for quality of life and avoiding the risk of catheter-related infections or thrombosis in patients who would otherwise require IV antibiotics due to organisms resistant to other oral options.

Fosfomycin use does not come without drawbacks, in addition to the previously mentioned diseases states where it cannot be used. As previously mentioned, patients may fail therapy even if their organism is sensitive.

 In addition, fosfomycin has an average wholesale price of $79 per dose, which is substantially costlier than most other oral options, especially if treating complicated UTIs where longer treatments may be needed. Insurance coverage can be variable, so patients may pay out of pocket. Subsequently, given its cost and limited use, many retail pharmacies do not stock it. Therefore, patients may have difficulty getting their prescriptions filled. In addition, increasing use of fosfomycin has been shown to increase resistance. The results of a study conducted in Spain showed increasing rates of fosfomycin resistance from 2005 to 2009 in both ESBL-producing and non-ESBL—producing 

 In the time span of the study, resistance rates among non-ESBL—producing 

 increased from 1.5% in 2005 to 2.9% in 2009. Similarly, the rates of fosfomycin resistance in ESBL-producing 

 increased from 4.4% in 2005 to 11.4% in 2011. The authors, in part, linked the increasing resistance rates to increasing use of fosfomycin to treat UTIs.

 There are not many antibiotics left to treat drug-resistant pathogens, and therefore increased resistance to fosfomycin is very worrisome.

In addition, most microbiology labs are not able to test susceptibilities for fosfomycin, so most providers will not be able to immediately confirm that the isolate is sensitive and may end up using it without knowing if it is effective in vitro. Fosfomycin can also be difficult to use in clouded clinical pictures. If there is any suspicion that a UTI involves the upper urinary tract, fosfomycin should be avoided. Finally, patients must be counseled as to how to properly take the fosfomycin to avoid decreasing efficacy. Fosfomycin comes as powder in a sachet. The sachet must be opened and the contents mixed in liquid before consumed. Patients must also be told not to mix it with hot water.

Fosfomycin can be an attractive option to treat UTIs due to its broad spectrum and general ease of use, but it should be used with caution. In line with the basic principles of antimicrobial stewardship, other treatment options should be considered first when choosing empiric treatment based upon local susceptibility patterns to preserve fosfomycin’s spectrum of activity against multi-drug—resistant pathogens. Fosfomycin should be reserved for use in uncomplicated UTIs and the appropriate complicated UTIs, with multi-drug–resistant pathogens, when the risk outweighs the benefit of using alternative agents. Use of fosfomycin can also be considered in patients with multiple allergies that preclude other options. Providers and patients must be aware of the considerable cost, potential lack of availability, appropriate dosing for uncomplicated versus complicated UTIs, and recommendations for administration to maximize the potential for positive outcomes. Providers also must be aware of the potential for treatment failure despite in vitro susceptibility.

Michael Wankum, PharmD, BCPS, is a clinical pharmacy specialist in infectious diseases at North Healthcare. Christina Koutsari, PharmD, PhD, is a PGY2 infectious diseases pharmacy resident at Abbott Northwestern Hospital in Minneapolis. Krista Gens, PharmD, BCPS-AQ ID, is an infectious diseases clinical pharmacy coordinator and a PGY2 infectious diseases pharmacy residency program coordinator at Abbott Northwestern Hospital in Minneapolis.

MONUROL [prescribing information]. St. Louis, MO: Forest Pharmaceuticals, Inc; 2007. www.accessdata.fda.gov/drugsatfda_docs/label/2008/050717s005lbl.pdf. Accessed 9/7/2017September 7, 2017.

Reffert JL, Smith WJ. Fosfomycin for the treatment of resistant gram-negative bacterial infections. Insights from the Society of Infectious Diseases Pharmacists. 

 2014;34(8):845-857. doi: 10.1002/phar.1434. 

Vardakas KZ, Legakis NJ, Triarides N, Falagas ME. Susceptibility of contemporary isolates to fosfomycin: a systematic review of the literature. 

. 2016;47(4):269-285. doi: 10.1016/j.ijantimicag.2016.02.001.

Michalopoulos AS, Livaditis IG, Gougoutas V. The revival of fosfomycin. 

 2011;15(11):e732-e739. doi: 10.1016/j.ijid.2011.07.007.

Raz R. Fosfomycin: an old—new antibiotic. 

. 2012;18(1): 4-7. doi: 10.1111/j.1469-0691.2011.03636.x

ESCMID Study Group for Antibiotic Policies

. Forgotten antibiotics: an inventory in Europe, the United States, Canada, and Australia. 

. 2012;54(2):268-274. doi: 10.1093/cid/cir838.

Nathan C, Cars O. Antibiotic resistance--problems, progress, and prospects. 

. 2014;371(19):1761-1763. doi: 10.1056/NEJMp1408040.

Simkins J, Fan J, Camargo JF, Aragon L, Frederick C. Intravenous fosfomycin treatment for carbapenem-resistant 

 2015;49(10):1177-1178. doi: 10.1177/1060028015598326.

Mills JP, Wilck MB, Weikert BC, et al. Successful treatment of disseminated infection with extensively drug-resistant 

in a liver transplant recipient with a fosfomycin-based multidrug regimen. 

. 2016;18(5):777-781. doi: 10.1111/tid.12578.

Kollef MH, Ricard JD, Roux D, et al. A randomized trial of amikacin fosfomycin inhalation system for the adjunctive therapy of gram-negative ventilator-associated pneumonia. 

. 2017;151(6):1239-1246. doi: 10.1016/j.chest.2016.11.026.

European Society for Microbiology and Infectious Diseases

. International clinical practice guidelines for the treatment of acute uncomplicated cystitis and pyelonephritis in women: a 2010 update by the Infectious Diseases Society of America and the European Society for Microbiology and Infectious Diseases. 

. 2011;52(5): e103-e120. doi: 10.1093/cid/ciq257.

Stein GE. Comparison of single-dose fosfomycin and a 7-day course of nitrofurantoin in female patients with uncomplicated urinary tract infection. 

Schaeffer AJ, Nicolle LE. Urinary tract infections in older men. 

. 2016;374(22):2192. doi: 10.1056/NEJMc1603508.

Mody L, Juthani-Mehta M. Urinary tract infections in older women: a clinical review. 

. 2014;311(8):844-854. doi: 10.1001/jama.2014.303.

Veve MP, Wagner JL, Kenney RM, Grunwald JL, Davis SL. Comparison of fosfomycin to ertapenem for outpatient or step down therapy of extended-spectrum β-lactamase urinary tract infections. 

 2016;48(1):56-60. doi: 10.1016/j.ijantimicag.2016.04.014.

Rodríguez-Baño J, Alcalá JC, Cisneros JM, et al. Community infections caused by extended-spectrum beta-lactamase-producing Escherichia coli. 

. 2008;168(17):1897-1902. doi: 10.1001/archinte.168.17.1897.

Neumer EA, Sekeres J, Hall GS, van Duin D. Experience with fosfomycin for treatment of urinary tract infections due to multidrug-resistant organisms. 

. 2012;56(11):5744-5748. doi: 10.1128/AAC.00402-12.

Walsh CC, Ladnersdorfer CB, McIntosh MP, et al. Clinically relevant concentrations of fosfomycin combined with polymyxin B, tobramycin or ciprofloxacin enhance bacterial killing of Pseudomonas aeruginosa, but do not suppress the emergence of fosfomycin resistance. 

. 2016;71(8):2216-2229. doi: 10.1093/jac/dkw115.

Gardiner BJ, Mahony AA, Ellis AG, et al. Is fosfomycin a potential treatment alternative for multidrug-resistant gram-negative prostatitis? 

. 2014;58(4):e101-e105. doi: 10.1093/cid/cit704.

Rees J, Abrahams M, Doble A, Cooper A; Prostatitis Expert Reference Group (PERG). Diagnosis and treatment of chronic bacterial prostatitis and chronic prostatitis/chronic pelvic pain syndrome: a consensus guideline. 

. 2015;116(4):509-525. doi: 10.1111/bju.13101.

Grayson ML, Macesic N, Trevillyan J, et al. Fosfomycin for treatment of prostatitis: new tricks for old dogs. 

. 2015;61(7):1141-1143. doi: 10.1093/cid/civ436.

Ode B, Haidl S, Hoffstedt B, Walder M, Ursing J. Fosfomycin versus ampicillin in the treatment of acute pyelonephritis. 

Zhanel GG, Walkty AJ, Karlowsky JA. Fosfomycin: a first-line oral therapy for acute uncomplicated cystitis. 

. 2016;2016:2082693. doi: 10.1155/2016/2082693.

Hirsch EB, Raux BR, Zucchi PC, et al. Activity of fosfomycin and comparison of several susceptibility testing methods against contemporary urine isolates

2015;46(6):642-647. doi: 10.1016/j.ijantimicag.2015.08.012.

. Parallel increase in community use of fosfomycin and resistance to fosfomycin in extended-spectrum beta-lactamase (ESBL)-producing Escherichia coli. 

. 2010;65(11):2459-2463. doi: 10.1093/jac/dkq346.

Infectious Diseases Focus

Fosfomycin (Monurol) is an antibiotic that uses a unique mechanism of action to establish its bactericidal activity.

Fosfomycin Use

The 340B Drug Pricing Program was enacted in 1992. Through this program, eligible health care providers, or covered entities, are able to purchase certain manufacturers’ covered outpatient drugs at discounted prices, with a program goal “to stretch scarce federal resources as far as possible, reaching more eligible patients and providing more comprehensive services.”

 There are several primary components of 340B compliance, including accuracy of covered entity registration/recertification, and the prohibitions on diversion, duplicate discounts, and use of a group purchasing organization (GPO) or arrangement for certain hospital covered entities.

 Each compliance component may be best understood by specific covered entity stakeholders. Implementation of a 340B Oversight Committee (340B OC) creates a mechanism for content experts and stakeholders within an organization to discuss important program administration topics. This concept has been identified as a best practice by Apexus, the designated prime vendor for the program and various 340B stakeholder groups.

It is recommended that the 340B OC meet on a regular basis and involve a diverse group of covered entity stakeholders. An example list of 340B OC members is below. If unable to attend, an appropriate replacement attendee may be designated. It is important to note that different covered entities have varying levels of 340B dedicated and shared resources. Therefore, the composition of the 340B OC will vary based on organizational needs.

Chief executive officer Chief financial officer Chief pharmacy officer or director of pharmacy

Chief information technology officer and/or pharmacy informatics support

Manager(s) of pharmacy area(s) purchasing 340B-priced drugs

The 340B OC should be used to ensure the proper functioning and regulatory compliance of the covered entity. The committee may be charged with the following functions to accomplish this goal:

Setting the general direction for 340B drug purchasing and compliance framework

Establishing and maintaining policies and procedures

Maintaining a plan for self-audits and external audits

Reviewing reports, trends, and audit results

Reviewing regulatory and legislative updates

Providing compliance and oversight direction

Establishing corrective action plans, when necessary

Preparing for a Health Resources and Services Administration and/or manufacturer audit, when necessary

Preparing responses for manufacturer good-faith evaluations, when necessary

Determining self-disclosure appropriateness

Regular, scheduled meetings of the 340B OC may be supplemented by meetings of ad-hoc groups, including task forces or subcommittees. Task forces may focus on the operational impact of 340B regulations/policy changes or other areas, such as GPO exclusion compliance, material breach, contract pharmacy, etc. An example 340B OC organizational structure, with reporting relationships, is highlighted in the 

Figure. An Example 340B OC Organizational Structure

Establishing a mechanism for stakeholders to provide perspective and expertise during administration of the covered entity’s 340B program, through implementation of a 340B OC, is an effective method in the program administration process that can be used to ensure continued compliance.

Grayson K. Peek, PharmD, MS, BCPS, is the manager of business development and integrity at the Duke University Hospital (DUH) Department of Pharmacy in Durham, North Carolina. He completed the 2-year health-system pharmacy administration residency at DUH in conjunction with a master of science in health-system pharmacy administration at the University of North Carolina at Chapel Hill. Dr. Peek is a PharmD graduate of the University of Tennessee Health Science Center. Alexandra M. Williams, BA, CPHT, is the 340B program manager at the University of North Carolina Hospitals in Chapel Hill, North Carolina. She completed her undergraduate degree in biology and health sciences at Guilford College. She is a certified pharmacy technician and has been involved in a 340B-related role for more than 4 years. She serves as a member of the Apexus Education Advisory Council.

Health Resources and Services Administration. 340B Drug Pricing Program. hrsa.gov/opa/index.html. Updated May 2017. Accessed July 30, 2017.  

Health Resources and Services Administration. 340B Drug Pricing Program: program requirements. hrsa.gov/opa/programrequirements/index.html. Accessed July 30, 2017.

Health Resources and Services Administration. 340B Peer-to-Peer Program: 340B Compliance Improvement Guide. hrsa.gov/opa/educationalresources/compliance-improvement-guide.pdf. October 1, 2015:14-17. Accessed August 15, 2017.

Apexus. Sample 340B program policy and procedures manual: disproportionate share hospital (DSH). docs.340bpvp.com/documents/public/resourcecenter/DSH_PolicyManual.docx. 2016:21-22. Accessed July 30, 2017.

Viewpoints

The 340B drug pricing program was enacted in 1992.

340B Oversight: Interdisciplinary Approach Ensures Continuous Compliance

In 2016, the National Institute for Occupational Safety and Health (NIOSH) published an updated list of antineoplastic and other hazardous drugs (HDs). This list, which is updated periodically, is crucial to the implementation of USP <800>, as the regulation requires institutions to identify all HDs dispensed in their facility. USP <800> will eventually be implemented by all boards of pharmacy and nursing throughout the United States.

The NIOSH list groups HDs into 3 categories. Group 1 products encompass antineoplastic drugs, group 2 products encompass nonantineoplastic drugs that meet other criteria for potential hazards, and group 3 products include drugs that may harm human reproduction. Importantly, group 3 is not the only group that may pose reproductive risk. Criteria for qualification of nonantineoplastic drugs as HDs include the potential for carcinogenicity, genotoxicity, organ toxicity, or other product-specific properties.

It is important to recognize that not all HDs pose a major risk during occupational exposure. 

For instance, HDs that are supplied in solid, intact dosage forms—such as coated tablets or capsules&mdash;generally do not pose a risk to workers.

However, products such as uncoated tablets that shed dust may result in exposure, skin contact, or inhalation of hazardous materials. Due to these risks, uncoated tablets should never be placed in automated counting machines; they should be counted manually and poured carefully to minimize the risk of exposure. Avoid activities involved in compounding HDs, such as crushing tablets or opening capsules.

Certain products may be more likely to be crushed or compounded in a community or specialty pharmacy setting. These include progesterone, which may be compounded into suppositories; any compounded formulations or hormones, such as testosterone, estradiol, or progesterone combinations; and compounded oral syrup formulations of finasteride to provide low-dose daily treatment for prevention or mitigation of alopecia. Other dosage forms, such as uncoated forms of warfarin tablets, colchicine tablets, or cyclophosphamide tablets, may pose a risk of exposure.

When handling hazardous medications, several precautions should be taken in terms of using personal protective equipment and engineering controls; it is also important to realize when protective gear is not required. For instance, when cleaning up a spill or leak of hazardous medication, wearing 2 layers of chemotherapy gloves, donning a protective gown, and using respiratory protection are all recommended practices.

NIOSH also recommends wearing 1 layer of chemotherapy gloves during unpacking or storage activities. However, wearing 2 layers of gloves, protective gowns, eye or face protection, or respiratory protection are not required under most circumstances.

Although many products that are on the NIOSH HD list are hazards well known to all pharmacists, some included products may not be thought of as hazardous medications in most contexts. For instance, 39 products on the list are classified as pregnancy category C: of this list, 13 are category 3 medications that have no toxicity other than a reproductive hazard (Table1). In addition, many medications that are classified as category X in pregnancy are not included on the list, such as all statins.

Although the NIOSH list is an important guide for pharmacists and other health care professionals when developing an institution-specific list of HDs, per USP <800> requirements, it is important to analyze all potential hazards regarding medication exposure. In developing a list, it is important to consider the perspectives of all stakeholders, including those handling medications. Even if medications are not listed by NIOSH, the concerns of staff with regard to any specific medication or class of medication should be considered.

Michael R. Page, PharmD, RPh, has worked as a community pharmacist at CVS Pharmacy and is clinical editor in clinical and scientific affairs at 

Safe Handling

in 2016, the National Institute for Occupational Safety and Health (NIOSH) published an updated list of antineoplastic and other hazardous drugs.

Considerations Regarding the National Institute for Occupational Safety and Health 2016 Hazardous Drug List

Between 1999 and 2014, lung cancer was the leading cause of cancer-related deaths in the United States and the third most prevalent type of cancer in the country.

In 2017, lung cancer is projected to be the second most prevalent type of cancer in the United States, with about 222,500 new cases and is estimated to still be the leading cause of cancer-related death, with 155,870 deaths (see figure).

This would make up 13.2% of all new cancer cases and 25.9% of all deaths caused by cancer in 2017.

 From 2007 to 2013, the percentage of patients who survived lung cancer for 5 years was 18.1%, which decreased from 19.6% in 2009.

 illustrates the breakdown of lung cancer cases by the stage of cancer, as well as the 5-year relative survival for each group.

 highlights the risk factors linked to increased lung cancer incidence. Tobacco smoking remains the leading cause of lung cancer, despite the overall decline in smoking among both genders.

Non—small cell lung cancer (NSCLC), small cell lung cancer (SCLC), and mesothelioma are among the most common types of lung cancer. There are also a few less prevalent lung cancer types that originate in the lung and chest wall. Most rare lung cancers are secondary to metastasis. These lung cancer types vary according to size, rate of metastasis, and recommended treatment options.

 for the prevalence and characteristics of the various subcategories of lung cancer. NSCLC is the most common type of lung cancer and is further characterized by the histology of cells involved. NSCLC is relatively unresponsive to chemotherapy and/or radiation treatment, compared with SCLC.

In general terms, risk factors such as smoking may cause damage to the epithelial cells that line the bronchioles. This damage causes the host’s normal repair system to activate to remove damaged cells and replace them with new, healthy cells. The repair system is inactivated when the restoration process is complete. The network of enzymes involved in this process may not activate or may not recognize the cells as being abnormal, thus allowing for continuation of tumor cell replication, which may eventually spread beyond where it originated. Depending on the type of enzymes involved, this may be a slow or rapid process. Lung cancer may metastasize to distant organs, and tumors originating in breast tissue or in the pancreas can disseminate to the lungs.

Lung cancer is the second most prevalent type of cancer, behind breast cancer.

In 2017, lung cancer is projected to be the second most prevalent type of cancer in the United States, with about 222,500 new cases and is estimated to still be the leading cause of cancer-related death, with 155,870 deaths. 

November 2017

Clinical Use of Generic Injectable Drugs in Hospitalized Patients

Fosfomycin Use

340B Oversight: Interdisciplinary Approach Ensures Continuous Compliance

Considerations Regarding the National Institute for Occupational Safety and Health 2016 Hazardous Drug List

Lung Cancers: Facts, Causes, and Types

The Skinny on Weight-Loss Medications

Updates in Heart Failure Drug Therapy

Neonatal Abstinence Syndrome

Breakthrough Cancer Pain