Katie Eder, Director of Content

The FDA has just approved Shire’s immune globulin subcutaneous (human), 20% solution (Cuvitru) for primary immunodeficiency (PI) in patients 2 years and older.

PI is a group of more than 300 genetic disorders where part of the body’s immune system is missing or functions improperly. It affects as many as 6 million individuals worldwide.

Cuvitru is the only 20% subcutaneous immunolglobulin (IG) treatment option without proline and with the ability to infuse up to 60 mL (12 g) per site and 60 mL per hour per site as tolerated, resulting in fewer infusion sites and shorter infusion durations compared with other conventional subcutaneous IG treatments. Regardless of infusion rate or volume per site, the drug was generally associated with a low incidence of local adverse and systemic reactions in a phase 2/3 study among North American patients that was recently published in the 

“The availability of Cuvitru as a high-concentration, subcutaneous IG provides PI patients with the dosing flexibility that allows them to customize their therapy to best fit their individual needs,” stated Richard L. Wasserman, MD, PhD, Medical Director of Pediatric Allergy and Immunology at Medical City Children's Hospital, in a press release about the product’s approval.

Shire expects to launch Cuvitru in the United States in the coming weeks. The treatment was approved in 17 European countries in June 2016, and Shire expects to initiate additional global regulatory submissions for it in late 2016 and 2017.

Like other IG products, Cuvitru carries a Boxed Warning for thrombosis. For those at risk of thrombosis, health care professionals should administer the drug at the minimum dose and infusion rate practicable, and then monitor for signs and symptoms of thrombosis and assess blood viscosity in those at risk of hyperviscosity.

Other warnings and precautions include renal dysfunction/failure, aseptic meningitis syndrome, transfusion-related acute lung injury, transmittable infectious agents, and interference with laboratory tests. The most common adverse reactions observed in clinical trials were headache, nausea, fatigue, diarrhea, and vomiting.

Articles

The FDA has just approved Shire's Cuvitru for primary immunodeficiency in patients 2 years and older.


Cuvitru Approved for Primary Immunodeficiency

Although it’s difficult to determine exactly how many patients experience opioid-induced constipation (OIC), the large quantities of prescribed opioids in circulation create widespread potential for this bothersome adverse effect.

OIC is preventable and manageable, but prescribing clinicians often fail to anticipate, identify, or treat it. For that reason, pharmacists should know the following things about OIC:

1. OIC Isn’t the Same as Regular Constipation

Many clinicians are surprised to learn that OIC is 

 than functional constipation. Regular constipation usually occurs subsequent to poor dietary choices, inactivity, or dehydration, while OIC follows interrupted receptor activity.

OIC develops when exogenous opioids create several changes—slower motility, altered fluid balance, sluggish mental status (leading to hampered mobility), and increased luminal fluid absorption&mdash;when opioid agonists bind to mu-opioid receptors in the enteric nervous system. Notably, this may cause abdominal pain that can rival the pain caused by the conditions for which opioids are prescribed.

2. Certain OTC Products Can Serve as OIC Prophylaxis

At PAINWeek 2016, pain expert Jeffrey Gudin, MD, advised that an OTC stool softener and a stimulant laxative— particularly docusate sodium and a senna product&mdash;should always be coprescribed or codispensed with an opioid to help prevent OIC.

“If someone comes to the pharmacy to fill their opioid prescription, the pharmacist should reflexively say, ‘What are you taking for stool softener and laxative?’ ” Dr. Gudin said. “…The pharmacist can play a role to make sure that at least there’s a regimen in place to address the constipation that comes from opioids.”

In addition to recommending a concomitant stool softener and laxative as prophylaxis, pharmacists can suggest lifestyle interventions, such as increasing fluid intake and dietary fiber consumption. Although bulk-forming laxatives are considered a cornerstone for managing chronic constipation, these fiber supplements should generally be avoided in OIC patients because they’re “not only likely to be ineffective, but they also can result in bowel obstruction,” according to Mary M. Bridgeman, PharmD.

3. If Prophylaxis Doesn’t Work, There Are Pharmacologic Options Available

When traditional laxatives are inadequate, clinicians should consider adding a prescriptive-strength agent specifically indicated for treating OIC. Available agents include the chloride channel activator lubiprostone, the subcutaneously administered methylnaltrexone bromide, and the orally administered naloxogol, which can reverse OIC symptoms in the gut without affecting analgesia or causing withdrawal.

“There aren’t too many places in medicine where we have an antidote or antivenom for a problem, but this is one of them,” Dr. Gudin explained. “This is…a novel class of drug to change an age-old problem of OIC.”

There are also some new agents on the horizon, including serotonin receptor agonists and other formulations of methylnaltrexone.

4. OIC Treatment Options Have Some Drug Interactions and Contraindications

Pharmacists should know that methadone is thought to interfere with the chloride channel receptor that lubiprostone serves to activate, so “it’s not likely that patients with OIC related to methadone use would respond to that particular therapy,” Dr. Bridgeman explained. For that reason, lubiprostone hasn’t been studied in patients on methadone and its effectiveness in this population hasn’t been established.

Meanwhile, naloxogol is contraindicated when strong CYP34A inhibitors are used, and all 3 previously described agents are contraindicated in patients with known or suspected mechanical gastrointestinal obstruction.

Although it's difficult to determine exactly how many patients experience opioid-induced constipation, the large quantities of prescribed opioids in circulation create widespread potential for this bothersome adverse effect.

4 Things Pharmacists Should Know About Opioid-Induced Constipation

The opioid overdose death toll has been steadily increasing for more than a decade, making it a leading cause of accidental death in the United States.

, the FDA approved naloxone auto-injector (Evzio) and naloxone nasal spray (Narcan) for take-home use for the emergency treatment of opioid overdose (

 can reverse the effects of opioids, including respiratory depression, sedation, and hypotension.

				·  Audio directions guide caregivers on proper administration

				·  Trainer device accompanies each carton

				·  Manufacturer has offered a free carton to all US high schools

				·  Ease of administration + low cost

				·  Audio directions only available in English

				·  Potential absorption concern in users whose nasal mucosa may be damaged from drug snorting, obstructed by vomit during overdose, or experiencing severe rhinitis

Notably, naloxone has been used for more than 40 years to reverse respiratory depression during opioid-related emergencies. Prior to the approval of Evzio and Narcan, the medication had to be administered as an intravenous (IV) injection, which was problematic for 2 reasons: 1) peripheral venous access may be difficult to obtain in IV drug abusers, making the medication difficult to administer, and 2) exposure to the affected patient’s blood could mean exposure to a blood-borne disease like hepatitis or HIV.

All forms of naloxone carry a warning of causing withdrawal in opioid-dependent patients, but as Juliana Zschoche, PharmD, emergency medicine clinical pharmacy specialist at Johns Hopkins Hospital, put it during PAINWeek 2016, “I would rather a patient be in withdrawal than not breathing.”

Pharmacists can use validated risk assessment tools, such as the Risk Index for Overdose or Serious Opioid-Induced Respiratory Depression (

), to identify patients who may be at risk for opioid overdose and could benefit from keeping naloxone handy. They could also access their state’s Prescription Drug Monitoring Program to check whether patients are obtaining opioid prescriptions from multiple prescribers or pharmacies, and then consult with the patients’ providers to determine whether they’re good candidates for naloxone.

“The pharmacist [should be] willing to have a conversation with a provider, and if they’re noticing anything odd, to alert the prescriber and maybe recommend that they think the patient is at risk [for opioid overdose] and may benefit from [naloxone] intervention,” Dr. Zschoche told 

When providing patients with naloxone—which, depending on state laws, could be accomplished 

 or through collaborative practice agreements with physicians or 

—pharmacists should make a point to demonstrate how to administer the product.

“Some [naloxone products] require assembly, and some patients may not feel comfortable in an emergency situation to have to flip a top off a vial or…put a needle or whatever else is necessarily prior to administration,” Dr. Zschoche explained. “So, walking a patient through the exact type [of naloxone] that they’re going to get is really important to patient education.”

Dr. Zschoche has also found that patients are sometimes reluctant to administer naloxone when they’re unsure whether the affected individual has overdosed on heroin, opioids, or something else entirely. Therefore, it’s important for pharmacists to assure patients that the benefits of naloxone greatly outweigh its risks, so patients should still administer the product even if they’re not sure what the individual took because it could potentially save a life.

Key Considerations for Providing Naloxone

There are many misconceptions surrounding pain management, especially when it comes to opioids with abuse-deterrent properties (OADPs).

To help pharmacists and other health care professionals separate the myths from the facts about OADPs, J. David Haddox, DDS, MD, and Ellen Battista, NP, led an interactive session with live audience polling on the subject at PAINWeek 2016.

Here are 7 myths and misconceptions pharmacists should debunk for their colleagues and patients:

Most current nonmedical users of opioids obtain the drug they abuse from a dealer.

Poll results: 93% said myth, 7% said fact

The fact is that most nonmedical opioid users obtain the drug from a friend or relative. According to combined data from the 2013-2014 National Survey on Drug Use and Health (NSDUH), half of nonmedical users received opioids from friends or relatives for free, while another 15% bought or stole them from a friend or relative. In other words, two-thirds of nonmedical opioid users obtained the drug from friends or family.

“What that tells me, as a physician and a pharmaceutical executive, is that there is a lot of unaccounted for medicine out there in our collective medicine chest just waiting to be diverted, possibly with disastrous consequences,” Dr. Haddox told 

Meanwhile, 22% nonmedical users reported obtaining opioids from one doctor. Just 0.1% said they bought them on the Internet.

Myth #2: The number of individuals abusing opioids is at an epidemic level.

Poll results: 88% said fact, 12% said myth

Believe it or not, opioid abuse is not an epidemic, but an endemic. The devil is in the definitions, as epidemic relates to a rapid spread of disease to a large population over a short period time, while endemic means a disease or condition is regularly growing or existing among a particular population or certain area.

By definition, opioid abuse is at an endemic level because the number of individuals abusing opioids has not changed much in over 12 years, according to NSDUH statistics.

“That doesn’t mean the problem isn’t serious, because there are about 4.3 million people who are doing this in any given month, but that is endemic,” Dr. Haddox explained. “What is an epidemic is the deaths that are involving opioids often with other substances. That is really an epidemic curve that is taking off in the wrong direction.”

Myth #3: Fatal overdoses involving opioid analgesics grew from 2010-2013 at a rate similar to the rate they grew from 2000-2005.

Poll results: 50% said myth, 50% said fact.

In the past decade, death resulting from unintentional prescription drug overdoses has increased steeply in the United States and is now widely recognized as a major public health problem. As Dr. Haddox put it, “This is the true epidemic with opioids.”

According to CDC figures, 18,893 deaths were related opioid analgesics in 2014, compared with just 4400 in the year 2000.

Myth #4: The most common method of abusing an opioid involves crushing.

Poll results: 50% said myth, 50% said fact

As it turns out, abuse of intact medicine by the oral route is the most prevalent method of choice for opioid abusers.

If that’s the case, then why didn’t opioid manufacturers try to deter the swallowing method first, rather than turning their attention to crushing and other manipulation methods?

“The answer is…it is the most prevalent, but it’s also exactly how patients are supposed take their medications. That makes it extremely challenging,” Dr. Haddox said. “…[Instead], let’s focus on trying to deter intranasal and intravenous abuse because those give you the most rapid rise and the highest blood levels in the shortest amount of time and therefore have the most risk of immediate lethal outcome.”

Myth #5: One approved product received ADP designation on the basis of Category 1 studies alone.

Poll results: 64% said fact, 36% said myth

Actually, no currently approved OADP received this designation on that basis alone.

 on OADPs to assist pharmaceutical manufacturers in creating such formulations. Within that guidance, the FDA specified that any development program for studying abuse-deterrent technologies should include data from 3 categories of premarket studies:

Category 1: Laboratory-based in vitro manipulation and extraction studies

Category 3: Clinical abuse potential studies

 received the designation on the basis of all 3 category premarket studies, with multiple studies in each category.

Furthermore, the FDA currently recognizes 7 general approaches to formulating OADPs:

		Physical/chemical barrier: drugs with physical barriers that can prevent chewing, crushing, cutting, grating, or grinding of the dosage form. Dosage forms with chemical barriers should resist extraction of the opioid through use of common solvents including water, alcohol or other organic solvents.

		Agonist/antagonist combinations: An opioid antagonist is added to the formulation to interfere with the release of the opioid if the medication is taken in any other way than it was intended.

		Aversion: Substances are added to the dosage form to produce an unpleasant effect if the dosage form is manipulated prior to ingestion or if a higher dosage than directed is used.

		Delivery system: Alternative delivery systems such as a depot injectable or an implant that is more difficult to manipulate.

		Prodrug: Medication contains a prodrug that lacks opioid activity until it has been transformed in the gastrointestinal tract.

		Combination: 2 or more of the above methods can be combined to deter abuse.

Myth #6: If an opioid is an extended-release (ER) formulation, it is by definition abuse deterrent.

The audience at PAINWeek got this one absolutely right: Just because an opioid is an ER formulation doesn’t guarantee it’s abuse-deterrent.

There are 2 ways pharmacists can quickly determine whether an opioid is abuse-deterrent:

		Section 9.2 (Drug Abuse and Dependence) of the drug label will list a summary of ADP claims approved by the FDA, though it notably does not mention that the drug is abuse proof.

		The opioid’s listing at Drugs@FDA will have a bullet stating that the FDA has determined that the drug has ADPs.

There are many misconceptions surrounding pain management, especially when it comes to opioids with abuse-deterrent properties.

7 Myths About Opioids with Abuse-Deterrent Properties

Mylan has just announced that it will launch the first generic EpiPen auto-injector at a price of $300 per generic epinephrine 2-pack carton in both 0.15 mg and 0.30 mg strengths. This amounts to a greater than 50% discount to the wholesale acquisition cost of the brand-name product.

The authorized generic will be identical to the brand-name product, including device functionality and drug formulation. Mylan expects to launch the product in several weeks, pending completion of labeling revisions.

The company also intends to continue to market and distribute brand-name EpiPen.

“We understand the deep frustration and concerns associated with the cost of EpiPen to the patient, and have always shared the public’s desire to ensure that this important product be accessible to anyone who needs it,” Mylan CEO Heather Bresch stated in a press release. “Generic drugs have a long, proven track record of delivering significant savings to both patients and the overall health care system. The launch of a generic EpiPen…will offer a long-term solution to further reduce costs and ease the burden and complexity of the process on the patient.”

This generic launch follows the augmented patient assistance program and $300 savings card for the brand-name version that Mylan put in place last week. The company intends to initiate a direct ship program in conjunction with the launch of the generic at the $300 list price. It also continues to fight for enhanced access to epinephrine auto-injectors through other measures, such as inclusion of the product on the federal and private insurance preventive drug lists, which could potentially eliminate all co-pays.

Mylan's actions come amid public outcry over brand-name EpiPen's high cost. Today, the price is about $600 for a 2-pack carton, compared with $100 in 2008.

Mylan is the latest manufacturer to get caught up in growing public criticism of drug price hikes, following Valeant and 

Mylan has just announced that it will launch the first generic EpiPen auto-injector at a price of $300 per generic epinephrine 2-pack carton in both 0.15 mg and 0.30 mg strengths.

Mylan Launches First Generic EpiPen Amid Pricing Pressure

Customer satisfaction with drugstore chain, mass-merchandiser, supermarket, and mail-order pharmacies has improved across the board in the last year, according to the J.D. Power 2016 US Pharmacy Study released today.

Chain drugstores’ overall customer satisfaction scores improved from 842 points out of a possible 1000 in 

 to 863 on the same 1000-point scale in this year’s. Health Mart (898 points) scored slightly higher than Good Neighbor Pharmacy (896 points) to rank highest overall among brick-and-mortar chain drugstores, performing particularly well on the store, nonpharmacist staff, cost competitiveness, and pharmacist factors.

In the mass-merchandiser pharmacies category, Sam’s Club (883 points) nabbed the top spot, performing particularly well on nonpharmacist staff, pharmacist, and prescription ordering/pick-up process, though it was closely followed by Costco (880 points). After dropping in ratings from 830 points 

 to 822 in 2015, overall customer satisfaction scores for this category increased to 851 points in 2016.

Meanwhile, supermarket pharmacies’ overall scores improved from 851 points last year to 874 this year. Publix (912) earned the highest score overall, as well as in its category, where it was followed by Wegmans (891).

The higher scores for all brick-and-mortar pharmacy categories reflects an increased focus on customers and the growing trend of pharmacy-based convenient care clinics, as those choosing to visit a pharmacy are often finding more wellness services being provided today.

“Increasingly, customers are turning 2 errands into one when, for example, they need to pick up a prescription and get a flu shot,” said Rick Johnson, director of the health care practice at J.D. Power. “Pharmacies that are cognizant of their customers’ needs—and their time&mdash;will likely continue to achieve high satisfaction.”

At the same time, more customers are turning to mail-order pharmacies because of convenience and cost effectiveness. In this category, Kaiser Permanente Pharmacy ranked highest (906 points), followed by Humana RightSourceRx (890 points). Average overall satisfaction in the mail-order segment was 869.

All results are based on responses from 14,789 pharmacy customers who filled a new prescription or refilled a prescription during the 3 months prior to the survey period of June 2016. Customer satisfaction with brick-and-mortar pharmacies was measured across 5 factors: 1) prescription ordering/pick-up process, 2) store, 3) cost competitiveness, 4) nonpharmacist staff, and 5) pharmacist. Satisfaction with mail-order pharmacies was measured across prescription ordering process, prescription delivery, nonpharmacist staff, cost competitiveness, and pharmacist.

Customer satisfaction with drugstore chain, mass-merchandiser, supermarket, and mail-order pharmacies has improved across the board in the last year.