Negative Consequences of the Widespread and Inappropriate Easy Access to Purchasing Prescription Medications on the Internet

Abstract

Background

The purchase of prescription medications via the Internet is a global phenomenon with significant economic, social, and health-related impacts. The growth of online purchasing of prescription medicines is significant and has been amplified by social isolation related to the COVID-19 pandemic, with many patients unable to obtain medicines as they normally would. By contrast, there are licensed, certified, legitimate retail pharmacies that provide significant and vital services to patients.

Objective

To review the major public health threat from illegal entities that sell any type of prescription medicines to individuals without proper physician oversight.

Discussion

Rogue and inappropriate online vendors are providing counterfeit and substandard medications fraudulently with untold impacts on morbidity and mortality globally. This article presents the differentiation between the types of legal and illegal Internet pharmacies, as well as the actions that are currently in play to affect the illegal online purchase of prescription medicines. Much must be done in a collaborative, global effort to address the public health threat of obtaining prescription drugs via the Internet.

Conclusion

Global, federal, state, health professional, societal, and patient-specific collaborations are necessary to affect the significant threat that is now present via the increasing ease of access to online medication purchases.

In many ways, all of us are living in the age of the Internet. Where purchases are made and will be made have changed and will continue to evolve in the US marketplace and worldwide. Online shopping via the Internet in the United States is expected to double between 2018 and 2023 to a total spending of more than $6.5 trillion.1 Virtually anything can be purchased online, including controlled and regulated pharmaceuticals.2

Precipitating conditions are influencing individuals to purchase prescription and over-the-counter medications via the Internet. With disruptions in obtaining medications from pharmacies because of social isolation during the COVID-19 pandemic, the appeal of obtaining prescription drugs via the Internet has increased dramatically. The US Food and Drug Administration (FDA) has recently confiscated batches of drugs obtained via mail order from rogue Internet pharmacies in Canada.3

Mackey and Nayyar have defined rogue pharmacies as “those pharmacies that either fail to meet national or international pharmacy regulations or have not been subjected to the requisite regulatory review, licensure and/or certification.”4

Twenty years ago, Mills referred to obtaining prescription medications without a proper physician prescription as “cybermedicine” and “an affront to traditional medicine, as well as potentially dangerous to consumers.”5

The Figure outlines the 3 types of online consumer drug purchasing sites. The 3 types of Internet pharmacies are:

Figure. The 3 Internet Consumer Drug Purchasing Entities.

• 1.Traditional pharmacy sites, which dispense a prescription drug only after the submission of a legal prescription order by the patient or a physician
• 2.Prescribing-based sites, which provide prescriptions to patients after online or telephone interactions with prescribers. In these sites, there is no person-to-person physical interaction. The criticism of these sites focuses on the reliance of questionnaires or surveys for assessment of the patient. For example, many websites provide drugs for erectile dysfunction to consumers only after a questionnaire is filled out online by the consumer.
• 3.Online drug shops, which sell prescription drugs after consumers indicate what drugs they wish to purchase online and submit payment. No physician is involved in those sites.

KEY POINTS

• ▸The purchasing of substandard or counterfeit prescription medications on the Internet can have economic, social, and health-related effects.
• ▸Online illegitimate shops are a global public health threat in that they provide counterfeit, substandard drugs with an untold impact on morbidity and mortality.
• ▸The use of online-procured medications may make the drug appear ineffective on drug and/or medical histories, when in actuality the drug is a substandard counterfeit.
• ▸Unrestricted access to medications online allows people to engage in illegal and deviant drug use, which can legitimize unacceptable health practices.
• ▸Internet pharmacies must be validated and legitimized, and patients need education on the drugs they are taking and on where to obtain them optimally.
• ▸Collaborations among global, federal, and state agencies, health professionals, and patients are needed to regulate the online purchasing of medications.

Table 1 lists 4 websites from the United States that allow for the assessment of the legitimate validity and certification of online pharmacies. Table 1 also includes 1 Canadian site, Canadian International Pharmacy Association (CIPA) website, which should not be used. The CIPA website claims to list “certified” Internet drug access sites; however, the pharmacies listed on that site have not been verified by independent and valid inspections because drugs shipped from Canada are not subject to Canadian regulatory authority.6

Table 1.

Websites Useful to Ascertain the Validity of Online Pharmacies

Website address	Sponsoring entity	Human prescription	Veterinary prescription
https://safe.pharmacy/buy-safely	NABP	Yes	Yes
https://nabp.pharmacy/programs/dotpharmacy	Pharmacy websites that end in “.pharmacy” are NABP-verified	Yes	Yes
https://nabp.pharmacy/programs/digital-pharmacy/accredited-facilities	NABP-accredited digital pharmacies	Yes	No
https://buysaferx.pharmacy	Independent verification entity	Yes, international checking options	Yes
https://napra.ca/online-pharmacies	National Association of Pharmacy Regulatory Authorities	Yes	Yes
Site not to use		Problems	Problems
www.cipa.com	Canadian International Pharmacy Association	Listing of “pharmacies” that have not been verified by independent and valid inspections; some formulations offered via websites sell drugs without any FDA approval	Many of the websites on this site use foreign entities to process and complete processing prescriptions; these are not legitimate

FDA indicates US Food and Drug Administration; NABP, National Association of Boards of Pharmacy.

This article focuses on these online drug shops, which are, in effect, rogue operations and pose a significant public health threat. When detailing the impact of the Internet on medication purchasing, Sugiura has noted, “The Web is changing how people manage their healthcare choices and obtain medicine. In providing unrestricted accessibility to medicine, the Web has democratised consumerist opportunities and allows more people than ever before to engage in illegal and deviant activities.”7 Sugiura has also suggested that when purchasing Internet medications outside of the medical sphere, consumers are “engaging in unauthorised behaviour…[which] challenges societal norms about acceptable health practices.”7

According to the 2018 US National Survey on Drug Use and Health, prescription pain relievers were the most frequently misused illicit drugs by people aged ≥12 years.8 According to that survey, in 2018, of the estimated 16.9 million Americans who misused psychotherapeutic prescription drugs in the previous year, 9.9 million misused prescription pain relievers.8

Medication insecurity in the United States has been previously noted with precipitating factors, which include deficient economic and therapeutic medication outcomes, Internet access to illegal prescription medications without a valid prescription, and the prevalence of counterfeit medicines.9

Many Internet-based pharmacies have a domain name that is indicative of a specific country, but a lot of these names are specious. For example, “Internet pharmacies” in Canada have a dedicated website (www.cipa.com/certified-safe-online-pharmacies); however, the pharmacies listed on this website may dispense medications from other international sources via prescriptions. Many of the pharmacies listed as members sell drugs that are sourced from unreliable countries, such as India and Turkey, and have never had to pass through Health Canada's (Canada's equivalent of the FDA) regulatory process for assurance of safety and efficacy.

None of the pharmacies listed on the CIPA website and claimed to be certified by the National Association of Boards of Pharmacy (NABP) are indeed certified by NABP. Carmen A. Catizone, MS, RPh, DPh, Executive Director, NABP, sent a letter to the US Congress stating: “In NABP's nearly 20 years of experience, US consumers buying medications from Canadian online pharmacies rarely, if ever, receive the Health Canada-approved products afforded to Canadian customers. Instead, these Canadian pharmacy websites sell US patients medicines manufactured in places where buyers would not even drink the water, e.g., India, Turkey, or Southeast Asia. NABP and many other patient safety advocates have found that the dangers of drugs dispensed outside of FDA's or Health Canada's drug approval process are significant. Outside these closed and tightly regulated drug supply chains, the safeguards put in place to ensure the identity, efficacy, and safety of prescription medications no longer apply.”10

Furthermore, Mr Catizone states, “It is NABP's understanding that Congress is contemplating legislation that would amend the US Food, Drug, and Cosmetic Act to allow US consumers to buy Health Canada-approved medicines from ‘legitimate’ Canadian online pharmacies. Based on our experience, for the following reasons NABP believes this action would have grave consequences.”10

Mr Catizone lists 3 reasons why NABP believes this is not a wise step. First, he says, suggesting that there are safe sites is a gamble that could cost lives. “Even finding a legitimate online pharmacy that sells US FDA-approved medicines to US consumers is tricky, given there are 35,000 active online pharmacies operating today and 96% of them violate applicable laws.”10

Second, he adds, “NABP is unaware of any Canadian online pharmacies that consistently dispense Health Canada-approved medicines to US consumers.”10 Therefore, US consumers who shop online for medicines approved by Health Canada will likely “receive unapproved, substandard, and counterfeit drugs from unknown foreign sources.”10

Finally, he asks, “Even if there were Canadian online pharmacies that consistently dispensed Health Canada-approved medicines to US patients (which is not the case today), how would a US consumer distinguish these sites from the thousands of other, dangerous sites selling counterfeit, adulterated, and unapproved products?”10

The 2020 NABP ROGUE RX Activity Report suggested that, “If significant action is not taken voluntarily by internet intermediaries, then NABP supports legislation that would require registrars to validate domain name registration information and make registration data accessible, as well as legislation that would require domain name registrars to immediately lock and suspend any domain name used to facilitate illegal activities that harm public health.”11

Shakour and colleagues have detailed counterfeit medications as drugs that may include12:

• 1.Incorrect or wrong ingredients
• 2.Insufficient or inactive ingredients
• 3.Fake packaging
• 4.Active ingredients that are different from those described on the package
• 5.Medicines that have expired or have no expiration date
• 6.Different quantity of impurities.

Counterfeit drug purchases can readily cause significant harm and health problems for patients when healthcare professionals and patients do not know or cannot be ensured of the reliability of the source of prescription medications.13

When viewing medications that patients have been prescribed and dispensed on drug and/or medical histories, it may seem that there are problems with the drug's efficacy. The medication may be therapeutically deficient for the condition for which it has been prescribed, but the deficiency may be a result of the substandard potency of the drug's active ingredients, a total lack of active ingredients, or even because it is counterfeit. These counterfeit components of a medication may cause the drug to have no effect, a negative effect, or a deleterious impact on the patient's medical condition.

Extent of the Problem

The World Health Organization (WHO) maintains the WHO Substandard and Falsified Medical Products Group.14 The European Commission has defined falsified drugs as “fake medicines that pass themselves off as real, authorised medicines.”15 Between 2013 and 2017, there was a total of 1112 substandard or fake medicines reported in the WHO database.14

Analysis showed that some of the fake medicines contained only chalk, impurities, and different drugs from what was on the label.13 Some of these fake drugs were purchased over the Internet and included so-called lifestyle medications (eg, for cosmetic purposes, weight loss, or erectile dysfunction); anesthetics, pain medications, contraceptives and fertility treatments, diabetes medications, heart medications, HIV and hepatitis treatments, malaria medications, psychotropics, cancer medications, antibiotics, and vaccines.14

Inappropriate Internet access to prescription medications is not unique to the United States. A study of the nonmedical use of prescription drugs in Europe showed that across 5 countries (ie, Denmark, Germany, Great Britain, Spain, and Sweden), Internet pharmacies, without physician oversight, were a source of obtaining stimulants (7.6%), opioids (4.1%), and sedatives (2.7%).16

In the United Kingdom, the sophisticated packaging and appearance of counterfeit medications purchased via the Internet through legitimate trade routes have resulted in these drugs being distributed in retail pharmacies and in hospitals.17

According to a study conducted in the Netherlands, at least 10.2% of the Dutch population has purchased prescription drugs online.18 Koenraadt and van de Ven added that, “Illicit lifestyle drugs are mainly purchased through e-commerce sites and online pharmacies, and users report high satisfaction rates” with their purchases.18

In a nationally representative sample in Hungary, frequent purchasers of general items on the Internet were more likely than infrequent users to purchase drugs online.19 Fittler and colleagues found that variables in age and level of education were significant determinants of medication purchasing behavior.19

Risks Associated with Easy Access to Drugs Online

The following small sample from the literature details the dangerous and problematic concerns and the outcomes that can occur with the ease of purchasing potent drugs online.

In 2011, Jena and Goldman published an analysis of the rise of prescription drug abuse in the United States between 2000 and 2007 and its relationship with the online availability of abused drugs.20 When searching for easy access to 4 classes of prescription drugs (ie, narcotic painkillers, stimulants, anxiolytics, and sedative-hypnotics), the study showed that for every 10% rise in high-speed Internet use at the state level, the associated admissions for prescription drug abuse increased by 1%.20

Monteith and Glenn studied the ease of purchasing psychiatric drugs online. They used the search term “buy [drug name] online” to examine 38 frequently used medications, 13 of which have a high abuse potential.21 The search resulted in 167 pharmacies offering medications for sale, of which 147 (88%) did not require any type of prescription.

The controlled substance drugs with high risk for abuse that were included in the search are shown in Table 2; each of these drugs harbors serious abuse potential.21 To ascertain the legitimacy of the sites, Monteith and Glenn used the NABP Digital Pharmacy Accreditation22 and LegitScript verification websites.23

Table 2.

High-Risk Controlled-Substance Psychiatric Drugs Accessible via the Internet

Drug (brand name)	Generic
Adderall	Amphetamine and dextroamphetamine
Ambien CR	Zolpidem
Ativan	Lorazepam
Concerta ER	Methylphenidate
Focalin	Dexmethylphenidate
Klonopin	Clonazepam
Lunesta	Eszopiclone
Restoril	Temazepam
Seroquel	Quetiapine
Valium	Diazepam
Xanax	Alprazolam

CR indicates controlled release; ER, extended release.

Source: Monteith S, Glenn T. Psychiatry Res. 2018;260:248–254.

LegitScript is an independent Internet source verification entity aimed at providing transparency when evaluating the veracity of Internet pharmacy operations. Monteith and Glenn concluded that when searching for online access to psychiatric medications, the Internet consumer is presented with rogue Internet pharmacies that do not require a prescription and present suspect accreditation documentation.21

A 2016 study by Monteith and colleagues examined the ease of online purchasing of drugs for bipolar disorder.24 The availability of the brand-name drugs Seroquel XR and Abilify and the generic drugs lamotrigine, lithium carbonate, and bupropion SR were chosen to determine their availability on the Internet. Of the 30 online pharmacies examined in the study, 17 (57%) were rated as rogue by LegitScript.24 Some of the sites listed credentials that were false. All the bipolar drugs were available online as either a brand-name or a generic pharmaceutical, with or without a prescription. The study showed that many of the drugs contained substitutions and/or formulations that were not approved by the FDA.24

Brühl and colleagues examined the availability and use of modafinil, a drug that is used to promote wakefulness and is often used by patients with sleep disorders, such as chronic obstructive sleep apnea.25,26 Modafinil is a federally controlled substance, available by prescription only in the United States. These researchers expressed concern that users of modafinil often report purchasing these drugs from the Internet.25

Cheng and Gedeon examined the impact of online access to counterfeit diabetes drugs and supplies.27 They note that the increasing costs of diabetes medicines and supplies has resulted in patients looking for cheaper alternatives, which often may be counterfeit, to manage their diabetes. Counterfeiters are now entering the mainstream pharmaceutical and device markets with more sophistication, which makes these drugs and devices harder to detect. These drugs and devices may include adulterated oral or injectable diabetes medications, and blood glucose test strips and measuring devices.27

Fittler and colleagues analyzed the availability of oncology drugs affected by shortages, using drugs identified via the European Association of Hospital Pharmacists survey drug shortages.28 The researchers simulated Internet search techniques that consumers would use when searching online for oncology medications. They determined that 100% of oncology medications affected by shortages were available online, with most (approximately 76%) available without a physician-written prescription. None of the online vendors were classified as legitimate or accredited by the NABP22 or LegitScript23 online pharmacy verification databases.28

This is only a limited list of disease states and drug types, but every drug available could have been inserted into this discussion with the same results. There is a widespread inappropriate use of the unregulated online purchasing of medications in the United States and worldwide.

A Call to Action: Much-Needed Next Steps

The means to ameliorate inappropriate Internet access to counterfeit and substandard medications will require significant actions from many entities. These efforts must come from international cooperative agreements between countries, individual country actions, health professional involvement, and individual consumers and patients.

In an article about the fake pharmaceuticals pandemic, Perks has stated, “a unified authentication system is needed to combat the massive trade in counterfeit medicines.”29 The International Criminal Police Organization (INTERPOL) is coordinating operations in the field to disrupt criminal networks, training crime-fighting agency personnel globally, and working to build partnerships across various entities.30 In 2008, INTERPOL created Operation Pangea, a specialized division that “targets the online sale of counterfeit and illegal medicines and medical devices.”31 In March 2020, Pangea XII shut down more than 2500 illegally operating websites.31

Attaran has crafted the Model Law on Medicine Crime.32,33 This model law is offered free of charge under the Creative Commons License to any government that wishes to implement some or all of it. The Model Law on Medicine Crime contains provisions pertaining to criminal activities that include32,33:

• The prohibition of manufacturing, trafficking, or selling poor-quality medications

• Principles for punishing offenders appropriately

• Special segments for Internet-based criminal actions

• Inducements for encouraging the cooperation of whistleblowers with law enforcement

• Incentives for third-world governments to strengthen drug regulatory capacities.

Nayyar and colleagues have echoed the call for the implementation of the Model Law on Medicines and Crime, but also have suggested the implementation of a Sustainable Development Goal, as well as an international convention to ensure drug quality and safety.34

Peltier-Rivest and Pacini have noted that “the detection of drug counterfeiting is extremely difficult after fake medicines have been ingested by patients.”35 They suggest the early discovery of counterfeiting via the use of reliable tracking technologies, well-controlled and required inventory management restrictions in the supply chain, the conduction of effective regulatory and legitimate customs inspections, and increasing consumer awareness of the problems and true negative outcomes of drug counterfeiting.35

The researchers point to the problem that online counterfeit medicines are usually sold through traditional drug distribution channels. The problem with Internet access to counterfeit and substandard medicines, they note, is that, “a Web address may be licensed in Belarus, the server in Thailand, the firm payee for the credit charge in Ireland, the payment processing in New Zealand, and the product mailed from Minneapolis, using a return address of a website customer.”35

The European Union has funded a research project entitled CONPHIRMER.36 The result of this project is a handheld digital fingerprint detection scanner that can easily identify counterfeit medications. The use of radio waves detects digital fingerprints on the packaging of suspected illegal drugs.36

The creation and use of sophisticated devices and techniques have been very useful in identifying substandard, illegal medications and shows promise for identifying illegal counterfeit drugs. Bhunia and Mandal describe the collaborative research of groups from Case Western Reserve in Cleveland, OH; the University of Florida; and King's College in London, United Kingdom.37 The result of their research is the use of nuclear quadruple resonance that allows for a medicine to be tested for authenticity and still be safely consumable. The tester that has been developed facilitates the finding of a unique fingerprint for reliable medications that other substandard drugs can then be compared with and identified as counterfeit. The researchers hope that one day, the device could be used safely and inexpensively in hospitals, health clinics, community pharmacies, and individual patients' homes.37

In 2005, researchers at the FDA developed the handheld Counterfeit Detection (CD) device (current version is CD-3) that uses alternative light sources to identify suspect medications rapidly.38–40 The CD-3 device has been proved to identify counterfeit medications quickly.40

There is a substantial need to train healthcare personnel regarding consumers' online access and ease of access in obtaining counterfeit medications. This need is global in nature. The Royal Pharmaceutical Society of Great Britain has produced a guidance for pharmacists and dispensing doctors titled “Counterfeit Medicines Advice for Healthcare Professionals.”41

The 4-page guidance presents the problem of ease of access to counterfeit medications, details the counterfeit drug situation in the United Kingdom, presents data on the consequences of counterfeiting, and proposes actions to be taken, suggests tips for evaluation of drug sources and detection of counterfeit medications, describes the logo that was created to help patients identify medications sold by legitimate British pharmacies, and encourages health professionals to counsel patients regarding the online purchase of medications.41

Ferrario and colleagues have described the need for comprehensive and multidisciplinary training concerning counterfeit and falsified medications.42 They emphasize the need for the cooperation of multiple stakeholders, including various government bodies, such as customs, law enforcement, legislature, judiciary, and regulatory agencies; health professionals, including pharmacists and public health professionals; patients; and the general public to address this urgent issue.42

Conclusion

The ease of access to Internet pharmacies that sell substandard and illegal medications is problematic and globally widespread. New and emerging efforts to stem the negative outcomes from access to substandard and illegal medications are promising. A concerted effort is required to provide advice on which Internet pharmacies are legitimate and to educate consumers consistently on vigilance concerning the medications they take, and from whom they obtain these drugs.