Clinical Medicine Insights: Endocrinology
`and Diabetes
`
`REVIEW
`
`Libertas Academica
`
`FRECDDM TD RCSEARCII
`
`OPEN ACCESS
`Full open access to this and
`thousands of other papers at
`http://www.la-press.com.
`
`A Review of Insulin Pen Devices and Use in the Elderly
`Diabetic Population
`
`Bradley M. Wright, Jessica M. Bellone and Emily K. McCoy
`Auburn University Harrison School of Pharmacy, Mobile, Alabama, 36849, USA
`Corresponding author email: ekm001 O@auburn.edu
`
`Abstract: The prevalence of diabetes mellitus (DM) in the elderly population currently represents almost one-half of the overall
`diabetic population. Treatment of DM often requires a multidrug regimen that includes insulin therapy; however, due to concomitant
`comorbidities such as dementia, vision loss, neuropathies, poor mobility, and poor manual dexterity, elderly patients may be at increase
`risk for hypoglycemia and other dosing errors that are associated with insulin administration. Insulin pen devices have been shown to
`provide more reliable, accurate, and simplified dosing, and therefore may be a safer, easier, and more acceptable method of insulin deliv(cid:173)
`ery in the elderly population. This review will describe the various insulin pen devices available today, as well as discuss the potential
`advantages of these devices in the elderly population.
`
`Keywords: insulin, pen device, elderly
`
`Clinical Medicine Insights: Endocrinology and Diabetes 2010:3 53-63
`
`doi: 10.4137/CMED.S5534
`
`This article is available from http://www.la-press.com.
`
`© the author(s), publisher and licensee Libertas Academica Ltd.
`
`This is an open access article. Unrestricted non-commercial use is permitted provided the original work is properly cited.
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`Introduction
`The number of patients diagnosed with diabetes mel(cid:173)
`litus (DM) in the United States in 2007 totaled almost
`18 million people. An additional 5. 7 million people
`are considered undiagnosed, which brings the total to
`8% of the US population considered to have DM. 1
`While this disease affects a large percentage of the
`overall population, it also affects a large number of
`elderly patients. The prevalence of DM in patients
`60 years of age or older was estimated to be greater
`than 12 million in 2007, which represents almost one(cid:173)
`quarter of the elderly population and over one-half of
`the overall DM population. 1 This number will almost
`surely continue to rise as a result of several factors,
`most notably the increase in the size of the elderly
`population. In 2000, an estimated 12% of the US
`population was 65 years of age or older. This number
`is projected to grow to over 16% by the year 2020. 2
`Additionally, an estimated 35% of the elderly popula(cid:173)
`tion has impaired fasting glucose, which could later
`progress to DM. 1
`The treatment of Type 2 DM often requires a multi
`drug regimen that includes insulin in order to maintain
`glycemic control. The American Diabetes Association
`(ADA) consensus algorithm lists basal insulin as a
`possible option in step 2 therapy after lifestyle changes
`and metformin have inadequately controlled glucose
`levels, as well as in patients with an HbAlc >8.5%. 3
`Statistics in 2007 showed that 14% of those diagnosed
`with DM are on insulin alone, and 13% are on a com(cid:173)
`bination of insulin and oral medications. 1 Additionally,
`a 2006 survey found that nearly 32% of the elderly
`population who were diagnosed in their middle-age
`were on insulin, and almost 7% of those who were
`classified as elderly when diagnosed were on insulin. 4
`These numbers will continue to rise not only as the
`proportion of the elderly population increases, but also
`as the role of insulin in treatment of DM continues to
`evolve and guidelines continue to place more of an
`emphasis on insulin therapy.
`While many patients of all ages are treated with
`insulin for DM, concerns arise over the safety and
`efficacy of this high-alert medication in the elderly
`population. The use of insulin in this population is
`often complicated by multiple comorbidities such as
`dementia, vision loss, neuropathies, poor mobility,
`and poor manual dexterity. These factors can affect
`the patient's ability to self-inject insulin, increase
`
`reliability on caregivers, and ultimately may limit the
`use of insulin in treatment of DM in this population.
`Safety, especially hypoglycemia, is always a con(cid:173)
`cern when using insulin, and individual studies have
`shown that the overall incidence of hypoglycemia in
`the elderly may be between 21 %-27%. 3 Additionally,
`it has been shown that many patients, including the
`elderly, may make significant errors in drawing up the
`correct insulin dose for injection, furthering safety
`and efficacy concerns.
`As a result of these complications and concerns,
`there is a need to simplify insulin regimens and dos(cid:173)
`ing in the elderly population. One option for doing
`this is through the administration of insulin with a
`pen device rather than the traditional vial and syringe
`method of delivery. Insulin pen devices were first
`marketed in the mid-1980s, and since that time the
`design of these devices has continued to evolve. The
`result is a device which may allow for more elderly
`patients to be treated with insulin as administration
`of insulin is possibly made safer, easier, and more
`acceptable.
`The purpose of this review is to describe the vari(cid:173)
`ous insulin pen devices available today, as well as dis(cid:173)
`cuss the potential advantages of these devices in the
`elderly population. The safety, efficacy, patient pref(cid:173)
`erence, and overall patient satisfaction with regards
`to ease of use will be reviewed in order to determine
`the role of these devices in the utilization of insulin
`therapy in the elderly population.
`
`Insulin Pens versus Insulin Vials
`and Syringes
`In order to determine if insulin pen devices have a role
`in the treatment of elderly DM patients, it is impor(cid:173)
`tant to understand the advantages these devices offer
`over traditional vials and syringes. Many patients find
`that these devices are more convenient as they elimi(cid:173)
`nate the need for drawing up a dose. 5 The ability to
`dial up the desired dose may lead to greater accuracy
`and reliability, especially for low doses which are
`often needed in the elderly. 7
`8 The sensory and audi(cid:173)
`•
`tory feedback associated with the dial mechanism on
`many pens may also benefit those with visual impair(cid:173)
`ments. Pen devices are also more compact, portable
`and easier to grip, which may benefit those with
`impairments in manual dexterity. Finally, less pain(cid:173)
`ful injections and overall ease of use may contribute
`
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`to the increased patient preference seen with the pen
`6
`devices. 5
`•
`Despite the advantages associated with pen devices
`there are potential disadvantages. Most importantly
`the devices are more costly than the insulin vial,
`and this may be difficult for many elderly patients.
`It should be noted, however, that most insurance
`plans, including Medicare part D, charge the patient
`the same amount for a month supply of insulin in the
`pen device as insulin in the vial. Patients may also
`find that pen devices take longer to use, as they must
`remain in the subcutaneous tissue for 5-10 seconds
`after dose release. 5 Lastly, not all forms of insulin are
`available in the pen device; this is discussed in more
`detail below.
`
`Dosing and Safety
`An important consideration with insulin administra(cid:173)
`tion in the elderly population is the possibility of dos(cid:173)
`ing errors. 9 Correct administration and accurate dosing
`is important in order to prevent serious complica(cid:173)
`tions, such as hypoglycemia and hyperglycemia. The
`traditional vial and syringe method of insulin admin(cid:173)
`istration involves several steps, including injecting
`air into the vial, drawing an amount out of the vial
`into a syringe with small measuring increments, and
`verifying the correct dose visually. 10 In addition to the
`complexity of insulin administration, visual impair(cid:173)
`ment, joint immobility, and peripheral neuropathy in
`elderly patients with diabetes may contribute to inac(cid:173)
`curate dosing, and insulin pen devices may be ben(cid:173)
`eficial in terms of safety for elderly patients due to
`these visual or physical disabilities. 7 Additionally,
`insulin pens may provide ease in setting and reading
`the amount of insulin to be injected and are also pre(cid:173)
`ferred for smaller doses of insulin due to improved
`dose accuracy. 7
`Studies have demonstrated that patients using a
`traditional vial and syringe method of delivery have
`a higher risk of inaccurately drawing up the insulin
`dose, with a relative error of approximately 19% seen
`in accuracy of dosing. 11 Higher inaccuracies may be
`seen in the elderly population. Puxty and colleagues
`found that a 12% variation in drawing up and expel(cid:173)
`ling 20 units was seen with syringe users (average
`age 66 years). 12 These errors in administration could
`lead to either an increased risk of hypoglycemia or an
`increased risk of inadequate glycemic control.
`
`Insulin pen devices in the elderly
`
`The occurrence of hypoglycemia is one of the most
`important barriers to achieving tight glycemic con(cid:173)
`trol, and rates of hypoglycemia may be more common
`in the elderly patient. However, use of insulin pen
`devices may actually improve rates of hypoglycemia
`often seen with the traditional vial and syringe method
`of delivery. One observational study demonstrated
`that patients treated with insulin pens experienced
`a significant improvement in rates of hypoglycemia
`(P < 0.05), and another analysis of third party claims
`found that the initiation or addition of a pen device
`both increased medication adherence while decreas(cid:173)
`ing hypoglycemic events. 13
`14 In Korytkowski et al
`•
`two serious hypoglycemic events occurred in those
`patients using the vial/syringe method. There were
`no cases of hypoglycemic events in those patients
`who used the pen device. 15 In contrast, Coscelli et al
`reported no significant difference in the incidence of
`hypoglycemic episodes in patients 60 years of age or
`older using the vial/syringe compared to the pen. 9
`Dose accuracy may be an advantage to insulin pen
`devices over the traditional vial and syringe method
`especially with smaller doses ( <5 units). 7 Some prod(cid:173)
`ucts also allow for dosage correction, and if too many
`units are dialed, the dose can be corrected by dial(cid:173)
`ing backwards. According to Korytkowski et al 73%
`of patients reported more confidence in injecting the
`correct dose with the insulin pen device compared to
`19% of patients using the vial/syringe method. 15 When
`assessing dose accuracy in the Humalog® KwikPen™
`compared to the vial/syringe method, Ignaut et al
`found that moderate to high doses (30-60 units) pre(cid:173)
`pared with the pen were more accurate than vial and
`syringe. 16
`Insulin pen devices may also be especially advan(cid:173)
`tageous for those patients with visual impairment or
`dexterity issues due to the availability oflarger digits
`in a dose window or digital dose display. Some of the
`pens also provide audible clicking with dosage selec(cid:173)
`tion and injection completion which can help with
`accurate dosing. In a trial assessing safety and effi(cid:173)
`cacy of the prefilled disposable pen compared to vial
`and syringe administration, 85% of patients reported
`they found the dose scale on the prefilled pen easier to
`read. 15 The patient questionnaire reflected that 82% of
`patients reported greater confidence with setting the
`required dose when using the insulin pen device. 15
`Additional studies note that patients find selection of
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`Wright et al
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`the correct insulin dose easier compared to the vial
`and syringe method of insulin administration. 9
`17
`18
`•
`•
`Other considerations for safety in choosing an
`insulin pen device for an elderly patient may include
`the type of device. The device types and features will
`be discussed in further detail later in this review;
`however, when discussing the dosing accuracy of
`pen devices, it should be noted that minimum and
`maximum dosage, as well as the minimum dosage
`increments, should be considered when individualiz(cid:173)
`ing therapy. Many elderly patients may only require
`small doses of insulin, and therefore pen devices
`allowing 0.5 unit adjustments may be advantageous.
`Digital dose displays and memory features are also
`available with specific products such as the OptiClik®
`and HumaPen® Memoir™ and may help the patient
`obtain a more accurate dose. 19
`20 It should also be
`•
`noted that pen devices need to be primed prior to use.
`The insulin pen devices require an "air shot", "safety
`shot", or priming in order to prevent the injection of
`air and ensure accurate dosage for delivery. This is
`an important area of education for elderly patients in
`order to ensure dose accuracy.
`
`Efficacy
`It is estimated that less than half of patients with dia(cid:173)
`betes achieve a HbAlc goal of <7% as set forth by
`the ADA, and this amount is even higher when con(cid:173)
`sidering a HbAlc goal of :::=:6.5% as set forth by the
`American Association of Clinical Endocrinologists
`(AACE); up to two thirds of patients do not reach
`this level of glucose control. 21
`22 As diabetic com(cid:173)
`•
`plications are often the result of inadequate glucose
`control, it is important to also consider the efficacy
`of available insulin pen devices in comparison to the
`traditional vial and syringe method. Few studies have
`evaluated an objective direct association between
`glycemic control and the use of pen devices; often
`it is the patient's perception of efficacy and dosing
`accuracy that lead to an assumption of improved gly(cid:173)
`cemic control. However, several studies have evalu(cid:173)
`ated both the perceived and actual clinical efficacy of
`insulin pen devices in the overall population as well
`as the elderly.
`In one 12 week crossover study in patients
`with an average age of 57 years, the use of bipha(cid:173)
`sic 70% insulin aspart protamine suspension and
`30% insulin aspart in both the prefilled insulin pen
`
`device (FlexPen)® and the vial/syringe method was
`compared. 15 In this study, there was an overall sta(cid:173)
`tistically significant improvement in glycemic con(cid:173)
`trol, with a mean reduction in HbAlc values of 0.3%
`(P < 0.05), regardless of which method of insulin
`delivery was used. 15 Another 12 week crossover study
`conducted in patients who were over the age of 60
`compared the NovoLet pen device to the vial/syringe
`method. 9 Investigators found that pre-lunch glucose
`levels were significantly lower in the patients who
`used the pen device (P < 0.01); however, no signifi(cid:173)
`cant differences were found in HbAlc values or other
`prandial glucose levels. 9
`A study involving 25 elderly patients who were
`suboptimally controlled on two doses of NPH alone
`found significant decreases in HbAlc, from 7.8% to
`7.6%, preprandial breakfast and lunch glucose levels,
`and postprandial breakfast and dinner glucose levels
`(P < 0.05 for all values) when subjects were given
`an alternate pen device. Interestingly, a decrease was
`seen in the total daily insulin dose when patients
`received therapy with the pen device. Although no
`patients were optimally controlled at study entry,
`29% of patients were able to reach HbAlc goals at
`the end of the three month period. 23
`Patient perception of clinical efficacy may also
`impact use of insulin therapy. A comparison of
`the FlexPen® device and the vial/syringe method
`found that patient perception of clinical efficacy
`was found to be higher with the FlexPen®,with the
`greatest improvement seen in insulin-narve patients
`(P < 0.001). 24
`While insulin has been shown to decrease compli(cid:173)
`cations that may arise from uncontrolled hyperglyce(cid:173)
`mia, the method of injection should be considered.
`Insulin pen devices have shown comparable efficacy
`to the traditional vial/syringe method, and some evi(cid:173)
`dence exists to suggest that this efficacy is also similar
`and potentially better in the elderly population. Addi(cid:173)
`tionally, the perception of efficacy has been shown to
`be higher in patients using pen devices.
`
`Ease of Use
`Ease of use is an important aspect to consider when
`choosing insulin delivery devices for all patients, but
`particularly in the elderly as older patients may need
`more time than younger patients to learn the vari(cid:173)
`ous functions of the different available pen devices. 25
`
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`Diabetic patients often experience age-related
`complications such as poor vision or impaired man(cid:173)
`ual dexterity, which can lead to inaccuracies in
`dosing. 12
`26 Visual impairment in particular is com(cid:173)
`7
`,1
`,
`mon in the aging diabetic population; 16 to 27% of
`diabetic patients ages 65 to 75 have a visual acuity
`of approximately 20/40 feet or worse, respectively. 27
`Pen devices offer several features, such as single-unit
`dosing increments, an easy-to-push release button, an
`audible click when dialing doses, large dose selec(cid:173)
`tors, and a dial that clearly shows the selected dose
`that make pen devices easier to use than the traditional
`vial/syringe method. 28
`In one 12 week study of elderly diabetic patients
`age 60 years and older, patients were assessed on their
`ability to use a pre-filled insulin pen device compared
`to the vial/syringe method. Patients were randomly
`assigned to either the vial/syringe or the pen device
`for 6 weeks and were then switched to the other deliv(cid:173)
`ery system for an additional 6 weeks. At weeks 2 and
`6 of pen device insulin delivery, patients were asked
`to complete a questionnaire that assessed the patients'
`ability to use the pen device versus the vial/syringe
`method of delivery; 90% of patients rated the pen
`device either very easy or easy to understand. 9 Like(cid:173)
`wise, Korytkowski et al found that 85% of patients
`found it easier to read the insulin dose scale with the
`pen device in comparison to the 10% of patients using
`the vial/syringe; overall 74% of patients found that
`the pen device was easier to use than the vial/syringe
`method of insulin delivery. 15
`Shelmet et al followed 79 elderly diabetic patients
`who had visual and/or motor disabilities severe enough
`that they experienced ongoing difficulties with insulin
`injection with the vial/syringe method of insulin deliv(cid:173)
`ery or required the assistance of a caregiver. Patients
`were randomized to receive either the vial/syringe
`method or the InnoLet® pen device for six weeks and
`then were switched to the alternate regimen for an
`additional six weeks. The study also found that while
`60% and 36% of patients required assistance in draw(cid:173)
`ing up the appropriate dosage and injecting insulin,
`respectively, over half of the study population (53%)
`were able to independently administer insulin with the
`pen device. 17 Another interesting aspect of this study
`is that costs associated with daily nursing assistance
`were significantly reduced as a result of the increase in
`independence found with the pen device. 17
`
`Insulin pen devices in the elderly
`
`Despite the above findings, ease of use cannot
`necessarily be considered equal with all pen device
`delivery systems. Haak et al assessed usability and pen
`features for Solostar®, Humulin/Humalog® (Lilly pen),
`and the FlexPen® device. 19 Usability involved com(cid:173)
`pleting such tasks including removing the cap, attach(cid:173)
`ing the needle, activation of the dose knob, delivering
`a safety dose, dialing a 40 unit dose, and delivering the
`dose. A comparison of the SoloStar, FlexPen®, and the
`Lilly Disposable pen in patients 60 years of age and
`older found that a higher percentage of patients were
`able to correctly complete the assessed steps with the
`SoloStar (90%) and FlexPen® (83%) versus the Lilly
`Disposable pen (47%). Likewise, patients with visual
`and manual dexterity impairments were more able to
`complete the steps when using either SoloStar (94%
`and 91 %) or FlexPen® (84% and 89%); in comparison,
`only about 50% of patients using the Lilly Disposable
`pen were found able to complete the assessed steps. 18
`Lower injection force associated with the Solostar®
`pen may contribute to the success of this device in
`those with dexterity issues and this finding has been
`seen in other studies as well. 29 Additionally, several
`studies have found that patients prefer the ease of use
`associated with the FlexPen® device in comparison
`with other insulin pen devices. One simulation study
`comparing the Humalog Pen to the FlexPen® demon(cid:173)
`strated that patients scored the FlexPen® significantly
`higher in overall ease of use, including ease of dose
`setting (P < 0.001 ), ease in pressing the release button
`(P < 0.01), and simplicity (P < 0.01); the higher rating
`for the FlexPen® was consistent for patients with both
`visual and manual dexterity impairments as well. 30
`Similarly, another study comparing the FlexPen® to
`the Humalog pen device found that 74% of patients
`preferred the FlexPen® for overall ease of use, includ(cid:173)
`ing the following parameters: ease ofreading the dose
`scale, ease of feeling the click for each unit increment,
`ease of depressing the injection button, ease of turning
`the dose selector, and ease of determining that push
`button was completely depressed. 31 Health care profes(cid:173)
`sionals have also expressed a preference for the ease
`of use of the FlexPen® device when compared to both
`the Humulin Pen and the OptiSet; of 102 health care
`professionals supervising patients initiating therapy,
`85% thought that it would be easy to teach patients to
`use the FlexPen®, and 71 % thought that less induction
`time would be required for FlexPen®. 32
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`Preference
`As patient adherence plays an important role in
`glycemic control, it is important to consider fac(cid:173)
`tors that may impact patient preference and therefore
`adherence with insulin therapy. Barriers to insulin ther(cid:173)
`apy are both practical and psychological, and patients
`may worry that insulin injections will be painful, dif(cid:173)
`ficult to administer, adversely affect their indepen(cid:173)
`dence, or cause a social embarrassment or stigma. 6
`28
`•
`Several studies have demonstrated that these barriers
`can be overcome and patient preference and accept(cid:173)
`ability improved when insulin is delivered through a
`pen device, with up to 90% of elderly patients express(cid:173)
`ing a preference for insulin pen devices in certain
`instances. 9
`When the pre-filled disposable FlexPen® was com(cid:173)
`pared to the conventional vial/syringe method, 74%
`of patients indicated a preference for the pen device
`versus 20% of patients who preferred the vial/syringe
`method, and more patients reported an increase in
`confidence with the insulin pen method, confidence
`in dosing accuracy and ability to maintain glycemic
`control, and felt that the pen device was more discreet
`for public use (Table 1 ). 15
`A study in which 44% of diabetic patients were
`age 56 or older compared the Novolin Prefilled® pen
`device to the traditional vial/syringe delivery method
`and found that a higher percentage of patients reported
`less pain with the pen device than with the vial/syringe
`method. 8 More patients were also likely to take their
`insulin at home or while away, reported a better social
`life, and stated that they were more active with the
`pen device. 8 Patients also felt that the Novolin pen had
`greater convenience and flexibility, and a larger percent-
`
`Table 1. Patient preference with the FlexPen® device. 15
`
`Patient
`preference
`questionnaire
`
`Confidence with
`method
`Confidence in dosing
`accuracy
`Confidence in ability
`to maintain glycemic
`control
`Discreet to use
`in public
`
`FlexPen
`N (%)
`
`Vial/syringe
`N (%)
`
`86/105 (82%)
`
`12/105 (11%)
`
`77/105 (73%)
`
`20/105 (19%)
`
`63/103 (61%)
`
`16/103 (16%)
`
`88/104 (85%)
`
`9/104 (9%)
`
`age of patients reported that they preferred that method
`of delivery (79% vs. 7%), felt a positive impact on well(cid:173)
`being (75% vs. 47%), were willing to continue using
`the pen device (88% versus 32%), and would recom(cid:173)
`mend that treatment to someone else (91 % vs. 39%). 8
`In a comparison trial of the InnoLet® pen device to
`the vial/syringe method, significantly more patients
`indicated preference for the InnoLet® pen (82%,
`P < 0.001), and a higher proportion of patients indi(cid:173)
`cated that they felt the InnoLet® pen was more reliable
`than the vial/syringe method. 17 Seventy-three percent
`of patients also reported "no pain at all" when judging
`the pain of injections with the pen device. 17 Finally,
`in a study of 25 elderly patients with type 2 diabe(cid:173)
`tes previously treated with the vial/syringe method,
`a significant increase in patient satisfaction was seen
`with the pen device (P < 0.05). 23
`
`Availability
`When considering insulin pen use in the elderly it is
`important to understand what products are available and
`the differences in the various devices. Many of the cur(cid:173)
`rently available insulins are available in both insulin vials
`and insulin pen devices. All available formulations are
`available in vial formulation, and all insulins other than
`regular human insulin (Humulin® Rand Novolin® R),
`NPH (Novolin® N and Humulin® N), and the regular
`mix insulins (Novolin® 70/30 and Humulin® 70/30)
`are available in pen devices. 33
`6 The latter 2 Novolin
`--4
`products were previously available in a device called
`the Innolet®, however this device was recently discon(cid:173)
`tinued by Novo Nordisk. 47 The latter Humulin products
`were available in the Original Prefilled Pen Device, but
`this device is currently being discontinued by Eli Lilly
`and Company. 48 Table 2 describes the type of insulins
`available in pen devices and vials.
`Insulin pen devices can be divided into 2 categories:
`durable ( or reusable) pens and prefilled pen devices.
`Durable pen devices combine the reusable syringe
`and insulin container with a disposable insulin car(cid:173)
`tridge that houses the actual insulin. These devices
`are designed to be reused by the patient as only the
`insulin cartridge and pen needles need to be replaced,
`which allows a single device to be used for several
`years. Some of these devices are available with a
`digital display and require batteries with the aver(cid:173)
`age lifespan of the battery being around 3 years. 19
`20
`•
`
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`• Table 2. Cost and availabilty. 19-20 -33- 56
`
`Insulin pen devices in the elderly
`
`Insulin
`
`Insulin type
`
`Cost
`
`Durable pen device
`
`Flexible pen device
`
`Vial
`
`Glulisine-Apridra®
`
`Rapid
`
`Asparte-Novolog®
`
`Rapid
`
`Lispro-Humalog®
`
`Rapid
`
`Regular-Humulin® R
`Regular-Novolin® R
`NPH-Humulin® N
`NPH-Novlolin® N
`Detemir-Levemir®
`
`Short
`Short
`Intermediate
`Intermediate
`Long
`
`Glargine-Lantus®
`
`Long
`
`Novolog® Mix 70/30
`
`Mixed
`
`Novolin® 70/30
`Humalog® Mix 75/25
`
`Humulin® 70/30
`Humalog® Mix 50/50
`
`Mixed
`Mixed
`
`Mixed
`Mixed
`
`Vial-$105.95
`Cartridges-$203.64
`Solostar-$201.01
`Vial-$120.69
`Cartridges-$216. 99
`FlexPen-$239.99
`Vial-$125.99
`Cartridges-$215.99
`Kwikpen-$225.99
`Vial-$66.99
`Vial-$73.18
`Vial-$66.99
`Vial-$73.18
`Vial-$110.49
`FlexPen-$205.10
`Vial-$111.88
`Cartridges-$206. 09
`Solostar-$202. 71
`Vial-$119.97
`FlexPen-$226. 00
`Vial-$73.18
`Vial-$119.05
`KwikPen-$219.99
`Vial-$68.00
`Vial-$
`KwikPen-$219.99
`
`OptiClik
`
`SoloSTAR
`
`NovoPen® Junior
`NovoPen® 3
`
`HumaPen® Memoir
`HumaPen® Luxura HD
`Autopen Classic
`
`FlexPen
`
`KwikPen
`
`OptiClik
`
`FlexPen
`
`SoloSTAR
`
`FlexPen
`
`Kwikpen
`
`KwikPen
`
`X
`
`X
`
`X
`
`X
`X
`X
`X
`X
`
`X
`
`X
`
`X
`X
`
`X
`X
`
`Although overall use of the pen devices may be easier
`for older patients, loading an insulin cartridge into a
`durable pen device may be especially difficult for
`older patients with visual and dexterity impairments.
`The durable devices hold 3 ml cartridges contain(cid:173)
`ing 300 units of insulin per cartridge. These devices
`can deliver insulin in 0.5, 1, or 2 unit increments up to
`a maximum of 80 units depending on the actual device
`20
`49
`50
`being used. 19
`52 Most of the durable pens are
`•
`•
`•
`•
`designed with special features that may benefit certain
`patient populations including the elderly (Table 3).
`However, it should also be noted that many manufac(cid:173)
`turers are planning to move away from certain durable
`pen devices as they are more expensive and difficult to
`manufacture than the prefilled devices. 19
`47
`48
`•
`•
`Prefilled pen devices are also available, and these
`tend to be more commonly used than the durable pen
`devices. These devices are disposable, and unlike the
`durable devices, these prefilled pens are designed
`with a built-in and prefilled insulin reservoir. Once
`these devices are empty, the patient must discard the
`device and obtain a new device. Like the durable
`
`devices, these pens are designed prefilled with 3 ml
`(300 units) of insulin, and many patients may find that
`these devices are easier to use than durable devices as
`there is no need to install a new cartridge when the
`device is empty. All of these devices feature audible
`clicks to help with dosing. Some of these devices may
`also have special features related to dosing (Table 3).
`The prefilled devices include the FlexPen® (Novo
`Nordisk), the Humalog Kwikpen and Original pre(cid:173)
`filled pen device (Eli Lilly and Company), and the
`SoloSTAR device (Sanofi-Aventis). 47
`55 As men(cid:173)
`48
`51
`54
`•
`-
`-
`-
`tioned previously the Original prefilled pen device is
`being phased out by the manufacturer. 48
`
`Cost
`Pen devices generally are associated with a higher cost
`per unit insulin than traditional vials and syringes;
`however one box of pen devices (5 pens) contain
`1500 units of insulin as compared to 1000 units in one
`10 mL vial of insulin. As individual pen devices are
`smaller and contain only 300 units, one advantage of
`this delivery method is the possibility of less insulin
`
`Clinical Medicine Insights: Endocrinology and Diabetes 2010:3
`
`59
`
`Sanofi Exhibit 2113.007
`Mylan v. Sanofi
`IPR2018-01675
`
`

`

`~I Table 3. Characteristics of pen devices. 19-20-47- 55
`Pen device
`Dose
`Min
`adjustments
`units
`(units)
`
`Max
`units
`
`Comments and special
`features for elderly patients
`
`Durable devices
`NovoPen® Jr
`
`NovoPen® 3
`
`0.5
`
`1
`
`HumaPen® Memoir
`
`1
`
`HumaPen®
`Luxura HD
`
`0.5
`
`OptiClik®
`
`1
`
`Autopen® Classic
`
`Autopen® 24
`
`1
`2
`
`1
`2
`
`1
`
`2
`
`1
`
`1
`
`1
`
`1
`2
`
`1
`2
`
`35
`
`70
`
`60
`
`30
`
`80
`
`21
`42
`
`21
`42
`
`• Dosage adjustments in 0.5 unit increments
`• Dose indicator window shows full units as numbers and half
`units as long lines between numbers
`• Requires air shot (2 units) prior to each injection
`• Easy to read dosing window and easy-dial dosing mechanism
`• Dose indicator window shows even numbers
`• Odd numbers are indicated by long lines
`• Requires air shot (2 units) prior to each injection
`• Digital display window
`• Memory function stores time, date, and amount of 16 most
`recent doses
`. • Must be primed (2 units) prior to each injection
`• Note: A new cartridge may need to be primed up to 4 times
`• Dose can be corrected by dialing backwards.
`• Dosage adjustments in 0.5 unit
`increments
`• Half units indicated by smaller lines between numbers
`• Must be primed (2 units) prior to each injection
`• Dose can be corrected by dialing backwards.
`• Digital display
`• Clicks when properly loaded with insulin cartridge, when insulin
`dose is locked in and when full dose of insulin is injected
`• Safety test (1 unit) should be performed prior to each injection
`• Dose can be corrected by dialing backwards
`• N