November/December 2016

Combating Counterfeit Drugs
By Mark D. Coggins, PharmD, CGP, FASCP
Today's Geriatric Medicine
Vol. 9 No. 6 P. 10

Many older adults, unable to afford necessary medications, access unregulated drug suppliers that provide impure or unsafe drugs to unsuspecting patients. Providers must counsel patients to make wise choices, offering guidance on avenues likely to represent safe alternative drug sources.

Counterfeit drugs present a global threat to the health and safety of millions of patients, many of whom reside in the United States. An estimated 10% of the drugs worldwide are counterfeit, with some countries experiencing a drug supply of 50% or more that is counterfeit, meaning of questionable origin, uncertain purity, and unknown safety. Counterfeit drugs are being manufactured overseas in countries such as China, India, Russia, Nigeria, Egypt, and Turkey, with few or no prohibitions against the exportation of counterfeit drugs.1-3

According to the Organization for Economic Co-operation and Development, 75% of counterfeit drugs come from India, which has no prohibition on their export. The counterfeit drug supply of developed countries such as the United States is estimated to be less than 1%.2 However, the fact that 40% of the world's prescription drug sales occur in the United States, coupled with the fact that 80% of their active ingredients originate from countries with counterfeiting problems,1 makes it increasingly clear that America is at significant risk for pervasive counterfeit medications.

Annual profits of $200 billion generated from counterfeit drugs now represent more than the world's combined heroin and cocaine markets, which total $160 billion.3 Counterfeit drug profits are estimated to be from 10 to 20 times more profitable than heroin. For example, crime syndicates investing $1,000 can return $20,000 through counterfeit currency or heroin distribution, $43,000 from counterfeit cigarettes, or $200,000 to $450,000 from counterfeit drugs.4

Organized Crime and Terrorist Threats
The International Institute of Research Against Counterfeit Medications (IRACM) has labeled counterfeit medications as "the new face of organized crime." Well funded organized global crime syndicates produce counterfeit drugs from all major therapeutic classes of medications, and they are doing so in more than 100 countries.4

Of equal concern is counterfeit drugs' threat to national security. The United States Drug Enforcement Agency (DEA) and other international law enforcement agencies acknowledge that terrorist groups are funding their operations in part from revenues generated by counterfeit drug operations. Groups such as Hezbollah, Hamas, and Al Qaeda manufacture counterfeit drugs that are distributed and sold by criminal networks throughout the Middle East and Latin America.5

Health Safety Concerns
Counterfeiters are not motivated to ensure the safety and efficacy of their products. Therefore, these criminals take whatever steps are necessary to turn a profit. Counterfeit drugs are often manufactured under unsafe conditions and may contain too little, too much, or no active pharmaceutical ingredients. Floor wax, rat poison, concrete, chalk, boric acid, road tar, paint, and antifreeze are only a few of the dangerous or toxic ingredients found in counterfeit drugs.6 Hence, patients taking counterfeit drugs are at risk of dangerous health consequences ranging from unexpected side effects to allergic reactions to worsening of their medical conditions. In the most severe cases, patients may experience serious injury and even death.

Counterfeit drug manufacturers are indiscriminate when it comes to targeting both the rich and poor, preying upon vulnerable patients in developing countries and wealthy countries alike. In fact, counterfeit drug makers have made fakes of inexpensive malaria and tuberculosis medications, which kill an estimated 700,000 people in developing countries each year.7

Patients in the United States often fall victim to counterfeit medications after being lured to unlicensed pharmacy websites by the promise of savings, a desire for anonymity, easy access, or the lack of or need for a prescription. A number of instances, such as the one reported by the FDA involving the weight loss medication, Alli, can be cited as examples. Patients ordering Alli online from an unlicensed pharmacy received fake drugs containing dangerous levels of the controlled substance, sibutramine. Patients experienced serious consequences, including elevated blood pressure, heart attack, and stroke.8

As noted earlier, all classes of medications have been counterfeited, with lifestyle medications such as Viagra believed to be the most frequently counterfeited drug ever made. Other commonly counterfeited drugs include those manufactured to mimic drugs prescribed to treat chronic diseases such as high cholesterol (eg, Lipitor), hypertension, cancer, and HIV/AIDS, as well as antibiotics and pain medications.

Counterfeit drugs are not limited to brand name medications, as counterfeiters often create fake versions of generic drugs, over-the-counter medications, and herbal remedies. In 2015, the New York attorney general, along with the FDA, targeted supplement companies selling fake or dangerous products. Authorities tested top-selling herbal supplements at four retail giants—GNC, Target, Walgreens, and Walmart—and found that 80% of the tested products did not contain the medicinal herbs listed on their labels.9

Opioid Counterfeit Crisis
Fentanyl is a synthetic opioid used to treat severe pain. Counterfeit fentanyl and fentanyl-related substances are being mass-produced in China and then marketed by drug trafficking groups in the United States. As reports of fake fentanyl compounds have increased, so have the reports of seizures and death. Between late 2013 and 2014, there were more than 700 fentanyl-related deaths reported in the United States. During this same period, the Centers for Disease Control and Prevention (CDC) reported that deaths from synthetic opioids (including fentanyl) increased by 79% from 3,097 to 5,544.10

Since 2014, US law enforcement agencies have been seizing a new form of fentanyl—counterfeit prescription opioid pills containing fentanyl or fentanyl-related compounds. The counterfeit pills closely resemble the authentic medications, with the presence of fentanyl detectable only upon laboratory analysis.10

In March 2016, law enforcement officers in Lorain County, Ohio, seized 500 pills that looked like oxycodone. However, analysis showed the pills contained no oxycodone but instead contained the research chemical U-47700, which is an unscheduled synthetic opioid unstudied for human use that has caused at least 17 overdoses and multiple deaths in the United States.10

Reports of deaths from counterfeit opioids often portray the victims as street drug addicts looking for a high. While no person deserves to die from counterfeit opioids, we need to better understand all of the issues that may lead to patients seeking these opioid medications through the black market. Concerns for opioid drug abuse, legal issues, time constraints, and increased scrutiny by licensing boards and the DEA may lead prescribers to refuse treatment with opioids. Other factors putting patients at increased risk for seeking counterfeit drugs are inappropriate weaning off long-term opioid medication and, in some cases, turning away by the same prescribers who prescribed patients opioids for months or years. As scenarios like this occur, more patients are likely to turn to risky online pharmacies and street dealers in an attempt to obtain relief.

Greed Over Patient Safety
Counterfeit drugs can enter safe drug supplies in cases where health care providers allow their pursuit of profits to supersede the safety of their patients. Physicians, pharmacists, and other health care professionals have placed patients at risk of harm by knowingly using counterfeit medications. Although the extent of this issue is unknown, there are reports of physicians and pharmacists knowingly purchasing counterfeit drugs from unlicensed distributors. These distributors realize a profit by selling drugs that have been illegally imported, have expired, have been stolen, have been damaged by poor handling, or are outright counterfeits. Physicians and pharmacists who purchase these discounted drugs generate a profit for themselves by billing insurance companies, Medicare, and patients at the same prices charged for legitimate treatments. This introduction of unsafe drugs into legitimate drug supplies causes patients to lose trust in the integrity of their treatments and the health care system.

One notable case occurred in 2012 when the FDA sent letters to 19 US cancer clinics believed to have purchased unapproved cancer therapies, including counterfeit Avastin (bevacizumab). Patients received a cocktail of starch, salt, paint thinner, and other common chemicals. In 2015, as indictments were unsealed, The Partnership for Safe Medicines reported that the fake Avastin warning letters and initial prosecutions were just the tip of the iceberg for what is now unfolding into one of the most convoluted counterfeit medication incidents ever uncovered. The supply of fake cancer medication was traced to internet pharmacy giant CanadaDrugs and its shell companies. In the past year, four physicians have been prosecuted for purchasing and administering the fake cancer drugs to their unsuspecting patients.11

Protecting Patients From Rogue Online Pharmacies
The rapid growth of internet commerce has led to an explosion of counterfeit drugs sold around the world, with China and India acting as two of the world's biggest sources of fake medicines.

A survey of more than 6,000 consumers revealed the following patterns:12

• Twenty-three percent say they've purchased prescription medicine online. Of those, almost 1 in 5 chose sites not associated with a local pharmacy or health insurance plan.

• Twenty-one percent of those who reported buying from an online pharmacy reported using one based outside of the United States.

• Fifteen percent of all respondents would consider purchasing from an online pharmacy based outside of the United States.

• Forty-seven percent of those who reported buying from an online pharmacy not associated with a local pharmacy or health insurance plan searched online for comments and ratings before making the purchase.

The National Association of Boards of Pharmacy (NABP) reviewed more than 11,000 websites and found 96% of those sites to be out of compliance. Those sites engage in various activities that put patient safety at risk, including the following:13

• Twenty-four percent have a physical address located outside of the United States (though most rogue sites do not post any address).

• Eighty-eight percent do not require a valid prescription.

• Fifty-eight percent issue prescriptions per online consultation or questionnaire only.

• Fifty percent offer foreign or non-FDA-approved drugs.

• Seventeen percent do not have secure sites.

• Forty-two percent have server locations in foreign countries.

• Twelve percent dispense controlled substances.

Furthermore, 62% of medicines purchased online are fake or substandard.13

The FDA and other groups such as the NABP note that foreign and unlicensed drug sellers are unmotivated to ensure the safety and efficacy of their products. The FDA indicates these pharmacies are not operating under appropriate regulatory oversight and, therefore, no authority can guarantee the authenticity of the medication they sell.

Assisting Patient Consumers
The Center for Safe Internet Pharmacies (CSIP) is a nonprofit organization founded by a diverse group of internet service providers and technology companies. CSIP works with its 11 member organizations and partners to address the global problem of consumer access to illegitimate pharmaceuticals from illegal online pharmacies and other sources. Through its partnership with LegitScript.com, CSIP provides resources to verify the website addresses of online pharmacies to determine their legitimacy.

The NABP, the FDA, and other agencies and individuals suggest the safest way to purchase drugs online is through pharmacies accredited through the Verified Internet Pharmacy Practice Sites (VIPPS) program by NABP. These certified online pharmacies ensure prescriptions are acquired from a trustworthy provider, which can help eliminate risks associated with sites that fail to comply with federal and state laws and regulations. One issue of concern with VIPPS is that not all legitimate online pharmacies have registered and paid the credentialing fees necessary to be accredited, so patients may not find the access to affordable medications they are seeking.

The NABP has launched its ".pharmacy" Top-Level Domain Program, which provides an even easier way for consumers to find safe and legal online pharmacies. Unlike .com and other domains, only legitimate internet pharmacies and pharmacy-related websites are awarded ".pharmacy" domains. Applicants are vetted by the NABP and, where applicable, local authorities, to prove legitimacy of the online pharmacy.

The Canadian Personal Importation Dilemma
Nearly every patient advocacy group and law enforcement agency agrees there is no such thing as a safe rogue online pharmacy. These pharmacies illegally sell counterfeit and substandard medications with no regard for patient safety. Educating patients and health care professionals as to how rogue online pharmacies operate is essential to reducing risk.

While it's technically illegal to import medications from other countries, the FDA has chosen not to enforce the law for personal importation in smaller quantities of medications. In fact, the CDC reports that due to cost advantages, about 5 million Americans import medication for personal use.14

There is division among patient advocacy, government agencies, and pharmaceutical companies as to whether US citizens should be permitted to purchase medications online from other countries, including Canada. The issue is complex due to the risk of counterfeit medications, especially from illegal rogue internet pharmacy sites. However, consideration must also be given to the realities patients face due to rising medication costs and frequent inability to afford necessary medications.

An estimated 35 million patients in 2014 did not fill a prescription because of cost.15 Additionally, a survey by the Harvard School of Public Health and Kaiser Health Foundation found that 50% of Americans who could not afford medication said they became sicker.16 With millions of Americans already using online pharmacy sites to purchase their medications, providers must give consideration to making patients' purchase of medications not only safer but also affordable.

Avoiding Rogue Online Pharmacies
Educating patients on criminal enterprises operating rogue online pharmacy sites is a priority. Remind patients never to buy medications from an online pharmacy site that engages in any of the following practices:

• does not require a prescription—these sites are dangerous and operate illegally;

• does not provide verifiable contact information;

• sells prescriptions after a patient answers only a few health questions;

• does not fill orders through licensed pharmacies;

• does not have a licensed pharmacist dispensing prescriptions;

• offers to sell controlled substances; or

• does not protect personal and financial information, as rogue pharmacies are increasingly stealing information for identity theft.

Recommend that patients buying from online pharmacies use one of the verification services. These services help to ensure the pharmacy is licensed, a prescription is required, pharmacy contact information is confirmed, privacy policies protect patients' personal information, and personal/financial data transmission is encrypted.

These verification services include VIPPS for online pharmacies in the United States. If a patient is insistent on purchasing from a pharmacy outside of the United States, recommend patients purchase medications only if the pharmacy is accredited by a credentialing authority such as PharmacyChecker.com or the Canadian International Pharmacy Association (CIPA), both of which verify and certify online pharmacies outside of the United States.

Health care professionals should take steps to minimize patient risk from counterfeit drugs and rogue online pharmacies. Work with patients to identify cost-saving alternatives such as generic medications. Consider switching to less costly but therapeutically equivalent alternatives within a drug class. Evaluate patients' medication regimens for possible polypharmacy, and discontinue unnecessary medications. Discuss options such as pharmaceutical company assistance and other discount pharmacy programs. Encourage price shopping among pharmacies, as prices vary tremendously. Urge patients to check into cost-saving possibilities first by reviewing online pharmacies in the United States accredited by VIPPS.

After exhausting the recommendations above, be mindful that patients unable to afford their medications are at increased health risk. Remember that many patients will purchase medications online from sources outside of the United States regardless of what health care professionals' views may be. Educate patients on the risks associated with illegal rogue pharmacies. Consider informing patients about sources such as PharmacyChecker.com and CIPA.

Significant problems associated with counterfeit drugs and rogue online pharmacies exist in the United States, and it is unlikely a perfect solution will be developed in the near future. While the dilemma is real, all health care professionals have the opportunity to take a much larger role in working with patients. Doing so can guide patients toward a safer solution that takes into consideration each patient's individual health care and economic needs.

— Mark D. Coggins, PharmD, CGP, FASCP, is vice president of pharmacy services for Diversicare, which operates skilled nursing centers in 10 states, and is a director on the board of the American Society of Consultant Pharmacists. He was nationally recognized by the Commission for Certification in Geriatric Pharmacy with the 2010 Excellence in Geriatric Pharmacy Practice Award.

References
1. US House of Representatives, The Committee on Energy and Commerce. Hearing on counterfeit drugs. http://docs.house.gov/meetings/IF/IF02/20140227/101804/HHRG-113-IF02-20140227-SD002.pdf. Published February 25, 2014. Accessed September 20, 2016.

2. World Health Organization. Counterfeit medications: an update on estimates. http://www.who.int/medicines/services/counterfeit/impact/TheNewEstimatesCounterfeit.pdf. Published November 15, 2006.

3. Sample I. Surge in illegal sales of drugs as gangs exploit 'phenomenal market' online. The Guardian. https://www.theguardian.com/society/2014/dec/28/drugs-medicines-sold-illegally-online-internet. Published December 28, 2014. Accessed September 28, 2016.

4. IRACM publishes a study report on counterfeit medicines and criminal organisations. International Institute of Research Against Counterfeit Medicine website. http://www.iracm.com/en/study-report-2013/. Published September 25, 2013. Accessed September 27, 2016.

5. Braun MA; US House of Representatives, Committee on Homeland Security. Iran, Hezbollah and the threat to the homeland. https://homeland.house.gov/files/Testimony-Braun.pdf. Published March 21, 2012. Accessed September 30, 2016.

6. Battling the epidemic of illegal online drug sellers and counterfeit medicines. Quality Matters website. http://qualitymatters.usp.org/battling-epidemic-illegal-online-drug-sellers-and-counterfeit-medicines. Published June 30, 2015. Accessed September 18, 2016.

7. Fake drugs kill over 700,000 people every year — new report. International Policy Network website. http://archive.today/ipW8i. Accessed September 22, 2016.

8. Warning: counterfeit Alli. US Food and Drug Administration website. http://www.fda.gov/ForConsumers/ConsumerUpdates/ucm198557.htm. Updated April 7, 2016. Accessed September 30, 2016.

9. Kaplan S. GNC, Target, Wal-Mart, Walgreens accused of selling adulterated 'herbals'. The Washington Post. February 3, 2015. https://www.washingtonpost.com/news/morning-mix/wp/2015/02/03/gnc-target-wal-mart-walgreens-accused-of-selling-fake-herbals/. Accessed September 21, 2016.

10. Drug Enforcement Administration. Counterfeit prescription pills containing fentanyls: a global threat. https://www.dea.gov/docs/Counterfeit%20Prescription%20Pills.pdf. Published July 2016. Accessed September 30, 2016.

11. Imber S. U.S. doctors prosecuted for buying fake medication from CanadaDrugs. The Partnership for Safe Medicines website. http://www.safemedicines.org/2016/03/u-s-doctors-prosecuted-for-buying-fake-cancer-medication-from-canadadrugs.html. Updated March 14, 2016. Accessed September 23, 2016.

12. FDA. Buying medicines online? Be wary, FDA says. www.fda.gov/downloads/consumers/consumerupdates/ucm321495.pdf. Published September 2012. Accessed September 17, 2016.

13. National Association of Boards of Pharmacy. Internet Drug Outlet Identification Program progress report for state and federal regulators: July 2015. http://safeonlinerx.com/wp-content/uploads/2015/08/NABP-Internet-Drug-Outlet-Report_July-2015.pdf. Published July 2015.

14. Levitt G; PharmacyChecker.com. Online pharmacies, personal drug importation and public health: ill-considered enforcement prevents access to safe and affordable medication. http://www.pharmacychecker.com/online-pharmacies-personal-drug-importation-public-health.pdf. Published February 12, 2015.

15. Collins SR, Rasmussen PW, Doty MM, Beutel S. The rise in health care coverage and affordability since health reform took effect: findings from the Commonwealth Fund Biennial Health Insurance Survey, 2014. http://www.commonwealthfund.org/~/media/files/publications/issue-brief/2015/jan/1800_collins_biennial_survey_brief.pdf. Published January 2015. Accessed September 30, 2016.

16. USA Today; Kaiser Family Foundation; Harvard School of Public Health. Health care costs survey. https://kaiserfamilyfoundation.files.wordpress.com/2013/01/7371.pdf. Published August 2005.