Federal regulations provide as follows:
A prescription for a controlled substance to be effective must be issued for a legitimate medical purpose by an individual practitioner acting in the usual course of his professional practice. The responsibility for the proper prescribing and dispensing of controlled substances is upon the prescribing practitioner, but a corresponding responsibility rests with the pharmacist who fills the prescription. An order purporting to be a prescription issued not in the usual course of professional treatment or in legitimate and authorized research is not a prescription within the meaning and intent of Section 309 of the Act (21 U.S.C. § 829) and the person knowingly filling such a purported prescription, as well as the person issuing it, shall be subject to the penalties provided for violations of the provisions of law relating to controlled substances (21 C.F.R. § 1306.04(a)).
The preceding regulation, referred to as the corresponding responsibility doctrine, clearly indicates that both the prescriber and the pharmacist are legally responsible for the proper prescribing and dispensing of controlled substances. Therefore, pharmacists must be particularly alert that the controlled substance prescriptions they receive and dispense are for a legitimate medical purpose and are issued by a lawful practitioner in the usual course of professional practice.
The corresponding responsibility doctrine is not absolute because the regulation states that a violation occurs when the pharmacist "knowingly" dispenses an improper prescription. Thus, the definition of "knowingly" is critical because a pharmacist who does not know a prescription is not for a legitimate medical purpose cannot have violated the regulation. In other words, a pharmacist should not be accountable for filling an invalid prescription that the pharmacist could not have known was invalid.
In United States v. Hayes, 595 F.2d 258 (5th Cir. 1979), included in the case studies section of this chapter, a pharmacist challenged the constitutionality of the corresponding responsibility doctrine, contending that the doctrine imposes an unfair burden on pharmacists because they cannot prescribe and do not have the means of knowing if a prescription is really valid. The most that a pharmacist can do, argued the pharmacist, is to call the physician and seek verification of the prescription, which he did. The facts of the case indicate that the pharmacist dispensed a tremendous number of prescriptions from a single physician for massive quantities of drugs to patients who admitted selling the drugs. The court rejected the constitutional argument, essentially finding that the regulation does not impose an unattainable obligation on pharmacists. However, the court added, verification of a prescription may not in itself be enough to establish that the pharmacist has met the knowledge requirement in situations such as this where the prescriptions are obviously false. Thus, the court disagreed with the pharmacist and affirmed his conviction.
In a similar case, United States v. Lawson, 682 F.2d 480 (4th Cir. 1982), a physician who operated a diet clinic, created medical records for fictitious patients and sold all the prescriptions written for Preludin and Tuinal for these fictitious patients to one obese patient. The patient would then present the prescriptions to the defendant pharmacist, Lawson. Initially, Lawson had contacted the physician to ascertain the validity of the prescriptions, but he subsequently dispensed the prescribed drugs without question.
Lawson was charged with dispensing schedule II drugs that he knew were not for a legitimate medical purpose. He contended that he did not know the prescriptions were not for a legitimate medical purpose. The court, however, convicted Lawson, finding that he should have known for a number of reasons. First, one person was presenting a large number of prescriptions, all written by one physician. Second, the prescriptions were uniform in dosages and quantities. Third, the sudden surge in the quantity of prescriptions for the controlled substances should have been suspect. The appellate court confirmed Lawson's conviction.
The court's opinion in a California case, Vermont and 110th Medical Arts Pharmacy v. State Board of Pharmacy, 177 Cal. Rptr. 807 (Cal. Ct. App. 1981), states the pharmacist's responsibility very well. In this case, over a 45-day period, the pharmacy filled 10,000 prescriptions written by a small group of physicians for four controlled substances. All together, these prescriptions accounted for 748,000 dosage units. Many of these prescriptions were filled in consecutively numbered batches for the same prescriber and for the same person with different addresses, although many of the addresses were nonexistent. Many of the names were suspect as well (e.g., Henry Ford, Fairlane Ford, Glenn Ford, Pearl Harbor). In response to the pharmacist's argument that he did not know the prescriptions were not valid, the court replied:
The statutory scheme plainly calls upon pharmacists to use their common sense and professional judgment. When their suspicions are aroused as reasonable professional persons by either ambiguities in the prescriptions, the sheer volume of controlled substances prescribed by a single practitioner for a small number of persons or, as in this case, when the control inherent in the prescription process is blatantly mocked by its obvious abuse as a means to dispense an inordinate and incredible amount of drugs under the color and protection of the law, pharmacists are called upon to obey the law and refuse to dispense (177 Cal. Rptr. at 810).
These cases indicate that whether a pharmacist knew that prescriptions were not for a legitimate medical purpose can be inferred from strong circumstantial evidence. Thus, for criminal purposes, "knowingly" could be defined as when a pharmacist should have known based on obvious facts but rather consciously chose to disregard them. Stated another way, the pharmacist recognized the possibility of wrongdoing but consciously refused to conduct a proper investigation. A pharmacist is expected to exercise professional judgment when suspicions should arise and should take action to determine if the prescription is valid. In these situations, verification with the prescriber is a critical first step; this step may not be enough, however, when facts indicate that the pharmacist should have investigated further.
In 2018, the DEA issued multiple decisions that revoked the DEA registrations for various pharmacies. These decisions help further clarify the "knowingly" requirement standard necessary for a finding that a pharmacy violated its corresponding responsibility. (See Trinity Pharmacy II, 83 Fed. Reg 7304 (Feb. 20, 2018) and Zion Clinic Pharmacy, 83 Fed. Reg. 10,876 (Mar. 13, 2018)). From these cases, for the DEA to show that the pharmacist acted with the required degree of knowledge to prove a corresponding responsibility violation, it needs to show either that "(1) the pharmacist filled a prescription notwithstanding her actual knowledge that the prescription lacked a legitimate medical purpose; or (2) the pharmacist was willfully blind or deliberately ignorant to the fact that the prescription lacked a legitimate medical purpose." Furthermore, "to establish willful blindness, the DEA must prove that the pharmacist had a subjective belief that there was a high probability that a fact existed and she took deliberate actions to avoid learning of that fact."
On the other hand, although pharmacists must be ever vigilant for invalid prescriptions, they also must guard against being overly suspicious. In the case of Ryan v. Dan's Food Stores, Inc., 972 P.2d 395 (Utah 1998), reported in the case studies section of this chapter, a pharmacist contended that he was wrongfully discharged for questioning the validity of controlled substance prescriptions. The court, however, found the discharge to be valid because the discharge was based on the pharmacist's behavior of being suspicious of most of the patients with controlled substance prescriptions and of being rude to those patients. Likewise, the Gordon v. Frost case, 388 S.E.2d 362 (Ga. 1989), reported in the case studies section, demonstrates the civil liability consequences of a pharmacist who was overly suspicious and "jumped to the conclusion" that a regular patient was attempting to fraudulently obtain a refill of a controlled substance prescription. The Ryan and Gordon cases are good examples that a pharmacist should not be suspicious of a patient unless the pharmacist has a reason to be suspicious. Without any indication to the contrary, a pharmacist should presume that a controlled substance is legitimate. Although having a proper balance regarding this may be hard to accomplish in light of the national drug abuse epidemic and increased scrutiny over dispensing practices, pharmacists should have a good understanding of the importance of their role in dispensing valid controlled substance prescriptions.
Only prescriptions written for a "legitimate medical purpose" in the "usual course of professional practice" are valid under the law. Although these terms are not specifically defined, at least one court has found the term to mean acting "in accordance with a standard of medical practice generally recognized and accepted in the United States" (United States v. Moore, 423 U.S. 122, 139 (1975)). Some examples of invalid controlled substance prescriptions not written for a legitimate medical purpose include:
Fraudulent or forged prescriptions written by persons not authorized to issue drug orders
Prescriptions written by individual practitioners for office use
Prescriptions written by individual practitioners:
For fictitious patients
For patients not named on the prescription
When the individual practitioner has not performed a good faith medical examination
When there is no medical reason for the prescription
Narcotic prescriptions written by individual practitioners to maintain an addiction or to detoxify an addict (excluding approved MAT under DATA)
Prescriptions written by individual practitioners that exceed the usual course of their professional practice; for example, a dentist who prescribes a controlled drug for a patient's back pain unrelated to dental diagnosis
This list clearly demonstrates that facial validity of a prescription does not in itself make a prescription valid. A controlled substance prescription must be based on a legitimate prescriber-patient relationship, where the prescriber has taken a patient history, conducted an assessment, developed a treatment plan, and documented these steps. As discussed under "Internet Pharmacy Prescriptions" the CSA was amended to provide that when controlled substances are dispensed via the Internet, a valid prescription requires the practitioner to have conducted at least one in-person medical evaluation of the patient. This means a good faith examination in compliance with standards of practice. Although this amendment applies to Internet pharmacy, the requirement is no less applicable to every controlled substance prescription in any practice setting. Courts will consider if a situation violates "legitimate medical purpose" and "usual course of professional practice" on a case-by-case basis. However, cases where courts have determined that violations occurred have been based on blatant or glaring misconduct, not merely questionable legality (United States v. Rosen, 582 F.2d 1032 (5th Cir. 1978)).
The DEA 2022 Pharmacist's Manual included an Appendix D, A Pharmacist's Guide to Prescription Fraud and Identifying Out of Scope Prescriptions to help pharmacists ensure that controlled substance prescriptions are available for legitimate medical purposes while preventing diversion. In addition to sharing various kinds of fraudulent or forged prescriptions that may be presented for dispensing, the Guide also lists examples of criteria that may indicate that a prescription was forged or not issued for a legitimate medical purpose.
For identifying forged prescriptions, these include:
Prescriptions that look "too good." A prescriber's handwriting is too legible.
Quantities, directions, or dosages differ from usual medical usage.
Prescriptions do not comply with the acceptable standard abbreviations or appears to be textbook presentation.
Prescriptions appear to be photocopied.
Directions are written in full with no abbreviations. Prescriptions are written in different color ink or written in different handwriting.
For identifying out-of-scope prescriptions, these include:
The prescriber writes significantly more prescriptions (or in larger quantities) compared with other practitioners in your area.
The prescriber writes for antagonistic drugs, such as depressants and stimulants, at the same time. Drug abusers often request prescription orders for "uppers and downers" at the same time.
Patients appear to be returning too frequently. For example, a prescription that should have lasted for a month in legitimate use is being refilled on a biweekly, weekly, or even a daily basis.
The prescriber writes prescriptions for antagonistic drugs, such as depressants and stimulants, at the same time. Drug abusers often request prescriptions for "uppers and downers" at the same time.
Patients appear presenting prescription orders written in the names of other people.
A number of people appear simultaneously or within a short time, all bearing similar prescription orders from the same prescriber.
People who are not regular patrons or residents of the community show up with prescription orders from the same prescriber.
The Guide also provides common prevention techniques, including the pharmacist getting to know patients and prescribers, as well as requiring proper patient identification. Furthermore, pharmacists are to contact prescribers for verification and clarification when there is a question about any aspect of a prescription order. The Guide also urges pharmacists to contact the local police for forged or altered prescriptions, and the state board of pharmacy or local DEA office when a pattern of prescription abuse is discovered.
In addition to the above information, pharmacists should also understand that their corresponding responsibility surrounding dispensing of controlled substances also requires being alert for "red flags." Red flags are considered circumstances surrounding the presentation of a controlled substance prescription that should raise reasonable suspicion about the validity of that prescription. Although "red flags" are not spelled out in DEA regulations, there have been a variety of sources, including past DEA administrative decisions and presentations and letters to the pharmacy industry, which have indicated specific red flags. In 2018, the DEA issued a decision, revoking the registration of Zion Clinic Pharmacy (83 Fed. Reg. 10,876 (Mar. 13, 2018)). From this decision, the DEA provided a non-exhaustive list of red flags that would support a finding of the required knowledge necessary for a corresponding responsibility violation. This list includes:
Multiple customers filling prescriptions written by the same prescriber for the same drugs in the same quantities
Customers with the same last name and street address presenting similar prescriptions on the same day or within a short time span
Two short-acting opiates prescribed together
Patients traveling long distances to fill opioid prescriptions
Drug cocktails
Payment by cash
Unusually large quantity of controlled substance
Pattern prescribing
Irregular dosing instructions
Lack of individualized therapy or dosing
Early fills/refills
Other pharmacies' refusals to fill the prescriptions
In addition to being alert for "red flags" it is also important that pharmacists resolve and document the resolution of identified "red flags." Although DEA rules do not specifically require documentation surrounding the resolution of "red flags" one recent DEA case determined it is a pharmacy practice standard. (See Gulf Med Pharmacy, 86 Fed. Reg. 72694 (Dec. 22, 2021)).
Pharmacists who do not meet their corresponding responsibility, including not resolving "red flags" may face legal action under the CSA. According to the DEA, a pharmacist is required to exercise sound professional judgment and to adhere to professional standards when determining whether a controlled substance prescription is legitimate. Furthermore, not only is this decision required to be made prior to dispensing a prescription, pharmacists are not required or permitted to dispense prescriptions of questionable or suspicious medical legitimacy. When a pharmacist dispenses invalid prescriptions that were not issued for a "legitimate medical purpose" in the "usual course of professional practice" the pharmacist as well as the pharmacy could be subject to criminal and/or civil actions. The DEA could revoke a pharmacy's registration based on its pharmacists corresponding responsibility violations, and both the pharmacy and pharmacists may also face administrative actions against their state licenses.
The treatment of pain with controlled substances is unquestionably a legitimate medical purpose. Pharmacists must take care that the legitimate medical purpose rule not be misapplied to determining the appropriateness of the drug therapy. In some instances, controlled substances may not be the best treatment, the amount prescribed may seem excessive, or the patient may have become addicted as a result of treatment.
For example, a frequently seen patient who complains of back pain may be using opioids to relieve that pain. There are medical alternatives, some invasive and some conservative, to the use of opioids, but the patient refuses these alternatives in favor of treatment with opioids. The patient may develop dependence to these drugs, but sees the dependence as the price that must be paid to avoid the alternative treatments that do not appeal to the patient. Controlled substances are not strictly necessary for this patient because alternative treatments are available. However, the patient really does suffer pain, and controlled substances are rationally related to the control of pain. Thus, although it might not be the best medical treatment, the prescribing of controlled substances for this patient is certainly both legitimate and medical. It does not matter that some physicians may treat the patient without prescribing opioids.
If the patient in this hypothetical case receives other controlled substances, not just for pain but also for anxiety and insomnia, the prescribed dosages of each drug may be extremely high. Some may say that the prescriptions then become nonlegitimate. This position is not consistent with the federal framework, however. Under federal interpretations of the legitimate medical purpose rule, the objective is to prevent the diversion of medications to the illicit market without impeding the legitimate use of medications. The DEA is a law enforcement agency that does not have the expertise to make medical judgments, and there is nothing to suggest that anyone other than the patient is using the prescribed drugs or that the drugs are being used for anything other than conditions requiring the medical treatment for which they are indicated. Even though the dosages may be high and the combination risky, the use is legitimate because patients differ in their need for drugs and in their attitudes toward risk.
This is not to say that the pharmacist should not question the prescriber's choice of drug therapy when professional judgment warrants. For example, if one drug has been shown more effective than another for a particular type of pain or the dosage selected raises significant safety or efficacy issues, the pharmacist should intervene as appropriate. Perhaps the pharmacist, under certain circumstances, may make a decision not to dispense the medication. Decisions to intervene and/or not dispense in these types of situations, however, should be based on patient safety, weighing all clinical factors, and current practice standards instead of the legitimate medical purpose rule.
Federal regulations specifically state that it is illegal to prescribe and dispense narcotic drugs for the purpose of maintaining an addiction or detoxifying an addict (21 C.F.R. § 1306.04(c)). The intent of the regulation is to ensure that addicts are treated for their addiction in registered opioid treatment programs (OTPs). DATA does allow office-based practitioners to prescribe schedule III, IV, and V opioid drugs specifically approved by the U.S. Food and Drug Administration (FDA) for the purpose of treating addicts. Thus, it may be simply stated that, absent legal exceptions (most notably DATA), it is not a legitimate use or a legitimate medical purpose of a controlled substance prescription to maintain an addiction or detoxify an addict.
The application of this principle in pharmacy practice is often not simple. For example, assume that the patient with back pain has taken the medication for several months and the pharmacist has reason to believe that the patient really does not have pain any longer. The pharmacist suspects that the patient is addicted to the drug and that is the only reason the patient is taking the drug. In this situation, the pharmacist should try to determine if the medical condition for which the drug was prescribed still exists or if the drug is being issued for the illegal purpose of maintaining a narcotic addiction. At this point, the pharmacist has a duty to contact the prescriber and inquire. If the prescriber can substantiate that the patient still has the back pain and the use of the drug is still necessary for this purpose, the pharmacist should continue to dispense the drug. The regulations support this action because they state that a physician may administer or dispense narcotic drugs to persons with intractable pain in which no relief or cure is possible or has been found after reasonable efforts (21 C.F.R. § 1306.07(c)). On the other hand, the prescriber might share the pharmacist's concern that the purpose of the prescription is really the addiction and not the pain. In this situation, the prescriber might seek to enter the patient into an OTP or treat the patient under the requirements of DATA.
Situations get even more complicated when a pharmacist receives an opioid prescription with directions to gradually taper down the dosage. This complex situation requires the pharmacist to differentiate addiction from dependence. Addiction is generally characterized as psychological dependence characterized by compulsive use of the drug despite harm, a loss of control, and a preoccupation with obtaining opioids. Physical dependence is a state of adaptation in which withdrawal occurs when the drug is stopped or quickly decreased. Physical dependence is normal and expected with long-term opioid use. Thus, if the purpose of the opioid prescription is to gradually withdraw the pain patient from dependence, the prescription is legitimate. If the purpose is detoxification of an addict, the prescription is not legitimate. If the patient has been a regular pain patient of the pharmacy, the pharmacist can likely presume the dosage tapering is withdrawal from dependence. If, however, the patient is new or a stranger, the pharmacist would likely need to query the prescriber and learn more.
There are exceptions under federal law that, other than DATA, allow for the limited treatment of addicts outside of OTPs. Under CSA regulations (21 C.F.R. § 1306.07(b)), it is permissible for the prescriber to administer from his or her office supply, but not prescribe, narcotic drugs to an addict for a maximum of 3 days for the purpose of relieving acute withdrawal symptoms while arrangements are being made for referral for treatment. Not more than 1 day's medication may be administered to the person at one time. (Note that the pharmacist may not dispense the medication pursuant to a prescription, as discussed under "Treatment of Addicts Outside of OTPs (DATA).") The regulations also permit a physician or authorized hospital staff member to administer or dispense narcotic drugs to maintain or detoxify a hospitalized patient incidental to treating a condition other than the addiction (21 C.F.R. § 1306.07(c)).
One of the most difficult situations pharmacists encounter is when a prescriber or prescribers issue several prescriptions to chronic pain patients for very large quantities and very large doses of opioids. Large quantities and doses are sometimes necessary to treat severe chronic pain patients. The DEA provides, in Appendix D of the 2022 Pharmacists Manual, that the quantity of drugs prescribed and frequency of prescriptions filled are not lone indications of fraud or improper prescribing, especially if a patient is being treated for pain management. However, because pharmacists are held to a corresponding responsibility with the prescriber, these situations can be uncomfortable if the pharmacist fears the patient might not be a legitimate pain patient. General DEA tips on determining the validity of prescriptions were mentioned earlier and should be considered.
More specifically to pain treatment, pharmacists should be aware of the standards of practice for treating pain. If a pharmacist is concerned about the legitimacy of a pain patient, the pharmacist should not hesitate to contact the prescriber and ascertain if he or she is complying with practice standards. Physicians should have no problem sharing medical records or developing a collaborative practice arrangement with the pharmacy.
Absent medical record documentation or a collaborative practice situation when uncertainty exists, pharmacists should consider interviewing the patient when appropriate with such questions as: What causes the pain? What past treatments has the patient attempted for the pain? What is the nature and intensity of the pain? What is the duration of the pain? What effect is the pain having on the patient's quality of life? The pharmacist should then ask the same questions of the prescriber and should receive the same answers from both the prescriber and the patient. If available, pharmacists should also use additional resources, including the state's prescription monitoring program, to evaluate a chronic pain patient's behavior.
In 2021, there were more than 107,000 overdose deaths in the United States. According to the CDC, most overdose deaths involve opioids, with the vast majority specifically involving illicitly manufactured fentanyl, heroin, and/or cocaine. While the pattern of drugs involved in overdose deaths has changed over time, overdose deaths due to prescription opioids remains a national concern. For those interested in learning more about the epidemic, reports, data, and educational information are available from various federal agencies on a regular basis, including the CDC, SAMHSA, FDA, National Institute on Drug Abuse (NIDA), and DEA. Most states have their own reports and data available as well.
To help address patient safety concerns, as well as potentially inappropriate prescribing and/or dispensing of controlled substances, there have been a number of national and state initiatives to assist providers in improving the way opioids are prescribed and dispensed for the treatment of chronic pain. One example of clinical practice guidelines includes the 2016 CDC Guideline for Prescribing Opioids for Chronic Pain, available at https://www.cdc.gov/mmwr/volumes/65/rr/rr6501e1.htm. However, in 2019, the CDC advised that some policies and practices attributed to the 2016 Guideline were inconsistent with its recommendations, potentially risking patient health and safety. The CDC continues to stress that the guidelines provide voluntary recommendations that do not require mandatory compliance. Furthermore, the recommendations were intended to be flexible and support clinical judgment and individualized, patient-centered decision making, and were not intended to be applied as inflexible standards of care. In an effort to improve patient access to safe and effective pain management, the CDC released an updated guidance in November of 2022. The 2022 CDC Clinical Practice Guideline for Prescribing Opioids for Pain provides 12 recommendations for clinicians treating pain patients in the outpatient setting age 18 years and older with acute pain (less than 1 month), subacute pain (1-3 months), or chronic pain (more than 3 months). One important 2022 update relevant to pharmacy practice included the removal of specific dosing and duration limits for opioids. With numerous state and federal efforts based on the CDC 2016 Guideline regarding quantity and dosing limits on opioids, these may have to be adjusted.
There have been many other federal and state efforts to help address the opioid epidemic as well as patient safety concerns, some of which have been mentioned in other sections of the text. Most of these initiatives can be categorized into prevention, treatment, or enforcement efforts. For example, a few of the federal efforts have included the Comprehensive Addiction and Recovery Act (CARA) of 2016 (which included partial fills of CII medications and expansion of addiction treatment), the Substance Use-Disorder Prevention that Promotes Opioid Recovery and Treatment (SUPPORT) Act of 2018, FDA REMS for long-acting and immediate-release opioids, mandatory electronic prescribing for controlled substance prescriptions covered under Medicare Part D, FDA approval of an OTC naloxone product, DEA rules expanding disposal options, DEA rescheduling of hydrocodone combination products, DEA decreasing yearly manufacturing quotas for various opioids, and increased enforcement actions and inspections by the DEA.
Additional state-level initiatives (which have been mentioned in other sections) include PDMPs, security prescription blanks, and electronic prescribing mandates. Other state efforts that involve pharmacy practitioners may include naloxone access and distribution, required continuing education on opioid prescribing and dispensing, and prescribing and dispensing guidance documents for specific practice areas. As changes and updates have occurred often and will continue to do so in the future, pharmacists need to keep up to date on the federal and state laws, rules, and guidance that have been implemented to not only help address the opioid epidemic but also improve patient safety while maintaining access to legitimate medications.