Controlled Substances- MPJE

Reporting In-Transit Losses

*DEA Form 106* is also used to report *in-transit losses* of controlled substances. The *supplier* is responsible for reporting this loss to the DEA. The pharmacy is only responsible for making the report if the registrant has already signed for the delivery and subsequently notices that some or all of the controlled substances are missing. When a central-fill pharmacy contracts with carriers (e.g., couriers, delivery services) to transport filled prescriptions to a retail pharmacy, the central-fill pharmacy is responsible for filling out Form 106 and reporting the in-transit loss upon discovery. Alternatively, when a retail pharmacy contracts with carriers to retrieve filled prescriptions from a central-fill pharmacy, the retail pharmacy is responsible for reporting in-transit losses upon discovery.

DEA Form 222- Overview

*DEA Form 222* is available as both a *single-sheet* and a *triplicate* form with three carbon copies (Copy 1, Copy 2, Copy 3). The single-sheet Form 222 was released in 2019 to replace the triplicate form. The DEA is allowing a two-year transition period to the single-sheet form. During this time, triplicate forms can still be used to order CI and CII drugs, but any registrant who requests additional order forms will be issued single-sheet forms. The triplicate form will not be accepted after October 31, 2021, requiring all registrants to use the single-sheet form or CSOS from that point forward.

FDA-Approved Products of CBD and THC

*Epidiolex* (Cannabidiol), the first FDA approved *CBD-derived* product is indicated for seizures associated with several disorders: Lennox-Gastaut Syndrome, Dravet Syndrome, and Tuberous Sclerosis Complex. Initially, the DEA placed Epidiolex in a new classification of Schedule V that would include FDA-approved CBD drugs containing no more than 0.1% (w/w) residual THC. However, in 2020, the DEA descheduled Epidiolex, so it is now considered *non-controlled* according to federal law. There are also two FDA-approved *cannabis-related* drugs (i.e., not cannabis-derived, like Epidiolex): - *Dronabinol*: A synthetic delta-9-tetrahydrocannabinol (synthetic THC) approved for AIDS-associated anorexia and chemotherapy-induced NV (CINV). It is available as an oral capsule (*Marinol, schedule III*) and an alcohol-containing oral solution (*Syndros, schedule II*). - *Nabilone (Cesamet, schedule II)*: A synthetic cannabinoid with a chemical structure similar to THC that is indicated in CINV.

Controlled Substances Registrants

*Individual persons* must *register* with the *DEA* for authorization to *prescribe* controlled substances. An exception is medical residents in a healthcare facility, who can prescribe controlled substances for patients within the institution by using the facility's DEA number. *Facilities* participating in the manufacture, distribution, research, *prescribing*, and *dispensing* of controlled substances must also register with the DEA. The registration form used depends on the manner in which the applicant will manage controlled substances. After approval of the registration, the DEA will assign the individual or facility a *unique DEA number*. This DEA number will allow a physician to prescribe controlled substances or authorize a pharmacy to order and dispense controlled substances.

Ordering CIII-CV Medications

*Schedule III - V drugs* can be obtained from a supplier/wholesaler by using a *purchase order* or through the *Controlled Substance Ordering System (CSOS)*. The invoice or a packing slip (e.g. receipt) is used to record the delivery date and to confirm that the correct items are received. The *receipts* must be readily retrievable in the pharmacy and *should contain* the following information: - *Name* of each controlled substance in the order - Drug *formulation* (e.g. oral solution) - *Number of dosage units* in each container - *Number of packages* ordered and delivered

Transferring CIII - CV Prescriptions- Overview

*Schedule III - V prescriptions* are only allowed *one transfer* that may be communicated directly between *two licensed pharmacists* (some states may permit interns or certified pharmacy technicians to transfer). The only *exception* is if the pharmacies share a *real-time, online database* of the prescription recordkeeping system (such as stores in the same chain). Pharmacies with a shared database can transfer up to the maximum number of refills on the prescription. The prescription transfer information may be documented electronically. Federal law requires *records* to be *kept* for *two years*. AZ requires *seven years*.

State-Specific Controlled Substances

*States* can choose to classify drugs into *stricter* scheduling categories than the DEA. When state and federal law differ, the *stricter law* should be *followed*. For example, Fioricet (Butalbital + Acetaminophen + Caffeine) is not federally controlled as a CS, but a handful of states (e.g. Maryland, Georgia, Utah, Florida, New Mexico, California) classify Fioricet as a Schedule III. Gabapentin is another example of a drug not federally scheduled, but numerous states have placed into schedule V.

DEA Number- Letter for Each Registrant Type

- *A/B/F/G*: Hospital, clinic, teaching institution, pharmacy - *M*: Mid-level practitioner (e.g., NP, PA, OD) - *P/R*: Manufacturer, distributor, researcher, analytical lab, importer, exporter, reverse distributor, Narcotic Treatment Program - *X*: DATA-waived practitioner

Common Schedule I Drugs

- 3,4-Methylenedioxymethamphetamine or MDMA - Gamma-Hydroxybutyric Acid or GHB (the Sodium Oxybate salt form [Xyrem], is Schedule III) - Heroin (Diacetylmorphine) - Lysergic Acid Diethylamide or LSD - Marijuana (Cannabis Sativa), per the DEA; legalized in some states - Mescaline - Peyote

Common Schedule II Drugs- Opioids

- Alfentanil - Codeine, single ingredient - Fentanyl (*Actiq, Duragesic*, Fentora, Lazanda, Sublimaze, Subsys) - Hydrocodone, single ingredient (*Hysingla ER, Zohydro ER*) - Hydrocodone, combination products (*Lortab, Norco, TussiCaps, Tussionex, Vicodin, Vicoprofen*) - Hydromorphone (*Dilaudid*) - Levorphanol - Meperidine (*Demerol*) - Methadone (*Methadone HCl Intensol, Methadose*) - Morphine (*Kadian, MS Contin*, Duramorph, Infumorph, Mitigo) - Oxycodone, single ingredient (*OxyContin, Roxicodone*, Oxaydo, Xtampza ER) - Oxycodone, combination products (*Endocet, Percocet, Percodan*) - Oxymorphone (*Opana*) - Sufentanil - Tapentadol (*Nucynta, Nycynta ER)

Common Schedule IV Drugs- Benzodiazepines

- Alprazolam (*Alprazolam Intensol, Xanax, Xanax XR*) - Chlordiazepoxide (*Librium*) - Clobazam (*Onfi*, Sympazan) - Clorazepate (*Tranxene-T*) - Diazepam (*Diastat AcuDial, Diazepam Intensol, Valium*) - Estazolam - Flurazepam - Lorazepam (*Ativan, Lorazepam Intensol*) - Midazolam (*Versed*, Nayzilam, Seizalam) - Quazepam (Doral( - Oxazepam - Remimazolam (*Byfavo*) - Temazepam (*Restoril*) - Triazolam (*Halcion*)

Common Schedule II Drugs- ADHD Stimulants

- Amphetamine (Adzenys ER, Adzenys ER-ODT, Dyanavel XR, Evekeo, Evekeo ODT) - Amphetamine/Dextroamphetamine (*Adderall, Adderall XR*, Mydayis) - Dexmethylphenidate (*Focalin, Focalin XR*) - Dextroamphetamine (*Dexedrine*) - Lisdexamfetamine (*Vyvanse*) - Methamphetamine (Desoxyn) - Methylphenidate (*Concerta, Daytrana, Ritalin, Ritalin LA*, Adhansia XR, Aptensio XR, Cotempla XR-ODT, Jornay PM, Metadate CD, Methylin, QuilliChew ER, Quillivant XR)

Common Schedule IV Drugs- Other Important Medications

- Armodafinil (*Nuvigil*) - Butorphanol (*Stadol*) - Carisoprodol (*Soma*) - Difenoxin/Atropine (Motofen) - Eluxadoline (Viberzi) - Modafinil (*Provigil*) - Phenobarbital - Tramadol (*Ultram*, ConZip) - Tramadol/Acetaminophen (*Ultracet*)

Refill Limits and Expiration Dates- Federal Law and AZ Law

Federal Law: - Non-Scheduled: Expiration- Never; Refill Limit- No limit - Schedule V: Expiration- Never, Refill Limit- No limit - Schedule III and IV: Expiration- 6 months, Refill Limit- 5 Refills - Schedule II: Expiration- Never, Refill Limit- No refills Arizona Law: - Non-Scheduled: Expiration- 1 year, Refill Limit- No limit - Schedule V: Expiration- 1 year, Refill Limit- No limit - Schedule III and IV: Expiration- 6 months, Refill Limit- 5 Refills - Schedule II: Expiration- 90 days, Refill Limit- No refills

Common Schedule III Drugs

- Benzphetamine - Buprenorphine, single ingredient (*Butrans*, Belbuca, Buprenex, Probuphine, Sublocade) - Buprenorphine/Naloxone (*Suboxone*, Zubsolv) - Butabarbital - Butalbital (*Fioricet w/ Codeine, Fiorinal, Fiorinal w/ Codeine*, Allzital, Bupap) - Codeine/Acetaminophen (*Tylenol #3, Tylenol #4) - Dronabinol *capsules (Marinol)*; Solution (Syndros) is a CII - Ketamine (Ketalar) - Paregoric - Perampanel (*Fycompa*) - Phendimetrazine - Sodium Oxybate (*Xyrem*); GHB is a CI - Testosterone and all anabolic steroids [look for "Andro" in the drug name, such as Androstenedione] (*Androderm, AndroGel*, Aveed, Depo-Testosterone, Fortesta, Jatenzo, Natesto, Testim, Testopel, Vogelxo, Xyosted)

Common Schedule V Drugs

- Brivaracetam (Briviact) - Codeine containing cough syrups (Codeine + Promethazine, Codeine + Promethazine + Phenylephrine, Codeine + Guaifenesin, others) (*Cheratussin AC, G Tussin AC, Robitussin AC, Virtussin A/C*) - Diphenoxylate/Atropine (*Lomotil*) - Lacosamide (*Vimpat*) - Pregabalin (*Lyrica, Lyrica CR*)

Common Mid-Level Practitioners

- Certified Nurse Midwives (CNMs) - Certified Registered Nurse Anesthetists (CRNAs) - Nurse Practitioners (NPs) - Physician Assistants (PAs) - Registered Pharmacists (RPhs)

Common Schedule II Drugs- Other Important Drugs

- Cocaine - Dronabinol *solution (Syndros)*; capsules (Marinol) are schedule III - Levo-Alpha-Acetyl-Methadol (LAAM) - Pentobarbital, single ingredient (excluding suppository formulation, which is CIII) - Secobarbital, single ingredient (excluding suppository formulation, which is CIII) - Amobarbital, single ingredient (excluding suppository formulation, which is CIII)

DEA Forms for Controlled Substances

- DEA 224: Registration form for retail pharmacies, hospitals/clinics, teaching institutions, practitioners, or mid-level practitioners. - DEA 225: Registration form for drug manufacturers, distributors (e.g. supplier/wholesaler) and researchers. - DEA 363: Registration form for narcotic (opioid) treatment clinics - DEA 510: Registration form for bulk chemical manufacturers and distributors - DEA 222: Ordering form for Schedule I and II drugs - DEA 106: Reporting form for theft or significant loss of controlled substances - DEA 41: Record of controlled substances destroyed

NABP Ref Flags

- Frequent requests for early refills - Prescriber and/or patient located an unusual distance from pharmacy - Patient profile reveals multiple prescribers for duplicate therapy (e.g., "doctor shopping") - Similar or identical prescriptions for multiple patients from the same prescriber (e.g., "pill mill") - Prescription is not within prescriber's scope of practice (e.g., opioid analgesic from a psychiatrist) - Patients presenting to the pharmacy in groups - Unusual patient behavior (e.g., nervous demeanor) - Patient pays cash for an opioid prescription - Use of street slang to refer to a medication (e.g., "Zannies" for Xanax) - Patient is prescribed a "drug cocktail" (e.g., opioid + benzodiazepine + muscle relaxant) - A pending federal or state action against the prescriber

POA Use

- It can be granted to *licensed or unlicensed* pharmacy personnel. - The registrant can grant *multiple POAs*. - The registrant may *terminate* a POA at any time by *executing a notice of revocation*. - A new POA is only needed if a *different person* signs the *renewal application*. - The POA should be *filed* at the *pharmacy* with the executed DEA Form 222 and must be *readily retrievable* (it is *not submitted* to the DEA).

Paper vs. Electronic Ordering- CSOS

- Method of Submission: Electronic - Limit of items per order: No limit - Ordered Drugs: Schedules I - V - Typical Turnaround Time: 1 to 2 business days - Type of Signature Used: Digital signature - Endorsing to another supplier: No - Supplier Reporting to DEA: Within 2 business days of filling the order

Paper vs. Electronic Ordering- DEA Form 222

- Method of Submission: Paper - Limit of items per order: 10 items (triplicate form), 20 items (single-sheet form) - Ordered Drugs: Schedule I and II - Typical Turnaround Time: 2 to 5 business days - Type of Signature Used: Handwritten signature - Endorsing to another supplier: Yes (if a supplier cannot fill all or part of the order, then the order can be endorsed to another supplier for filling. Only the initial supplier can endorse the order to another supplier). - Supplier Reporting to DEA: By the end of the month during which the order was filled

Advantages of CSOS

- Reduces ordering errors - Decreased paperwork - Reduces administrative costs - Faster drug delivery (potential for next day delivery) - Easy to use, allowing for more frequent ordering

Considerations to Determine Loss or Theft is Significant

- The specific substances lost or stolen and their likelihood for diversion. - The quantity lost in relation to the type of business. - The individuals with access to the lost or stolen drug. - History or pattern of losses or local diversion issues. - Unique circumstances surround the loss or theft.

Determining the Validity of a DEA Number

1. Add the 1st, 3rd, and 5th digits together. 2. Add the 2nd, 4th, and 6th digits together then multiply the sum by 2. 3. Add the results of Step 1 and Step 2 together. The last digit of this sum should match the last digit of the prescriber's DEA number. This is called the "*check digit*".

Schedule II Prescriptions- Emergency Filling of CIIs, Criteria

1. Dispense the *minimum necessary* amount (must use professional judgement) 2. Prescriber must provide the *original* prescription *within 7 days* of oral authorization. The original may be *written or electronic*. The written prescription can be *hand-delivered* or *mailed* (must be postmarked by seventh day). The face of the original must include the statement, "*Authorization for Emergency Dispensing*" and the *date* of the *oral prescription*. 3. Pharmacist must attach the written prescription to the emergency oral prescription. If the original sent is electronic, the pharmacist must annotate the electronic prescription record with the emergency authorization and the date of the oral order. 4. If the original prescription is not received within 7 days, the pharmacist must *report* the breach to the *local DEA office*.

Schedule II Prescriptions- Allowable Partial Filling Scenarios

1. If the *pharmacy cannot supply* the full quantity, a portion of the prescription can be dispensed to hold the patient over until the remaining balance can be obtained. - This partial fill can be provided pursuant to a *written* or an *emergency oral prescription*. - The *quantity supplied* must be *documented* on the face of the hard copy or in the electronic prescription record. - The remaining portion must be filled *within 72 hours* of the first partial filling. After 72 hours, a *new prescription is required*. - If the *remaining portion* is *not or cannot be filled* within the 72 hours of the first partial filling, the pharmacist must *notify the prescriber*. 2. Under the 2016 Comprehensive Addiction and Recovery Act (CARA), pharmacists can partially fill CII drugs at the *request* of the *patient or prescriber*. This was enacted to help prevent stockpiling of unused CII drugs, which can lead to misuse or abuse. Currently, not all states have added this amendment to their legal statutes. - *Additional partial fills* can only be dispensed up to *30 days* from the *date* the *prescription* was *issued*. - There is *no limit* on the *number of partial fills* a patient can receive pursuant to one prescription, as long as the total quantity dispensed does not exceed the total quantity prescribed. 3. CII prescriptions can be partially filled for patients residing in *LTCFs* or patients diagnosed with a *terminal illness (e.g., hospice patients). This is to reduce drug diversion and waste that can occur if the patient expires before the medication is finished. - The *pharmacist must document* "terminally ill" or "LTCF patient" on the prescription. - Partial fills can be dispensed for up to *60 days* from the *issue date* of the prescription.

Triplicate Form 222 For Schedule II Drug Transactions

1. Pharmacy orders drug from supplier: Copy 1- Supplier, Copy 2- DEA, Copy 3- Pharmacy 2. Pharmacy returns unused drugs back to a supplier: Copy 1- Pharmacy, Copy 2- DEA, Copy 3- Supplier 3. Pharmacy sends unused drugs back to reverse distributor for disposal: Copy 1- Pharmacy, Copy 2- DEA, Copy 3- Reverse Distributor 4. Pharmacy sells or lends drugs to another pharmacy: Copy 1- Supplying Pharmacy, Copy 2- DEA, Copy 3- Receiving Pharmacy 5. Pharmacy sells or lends drugs to a physician for administration or dispensing: Copy 1- Pharmacy, Copy 2- DEA, Copy 3- Physician

Requirements for Legit Online Pharmacies to Sell CS

1. Register with the DEA as a pharmacy and complete the Application for Modification for Online Pharmacies. 2. *Notify* the *DEA and state boards of pharmacy* in each state in which it intends to conduct business *30 days before dispensing* through the internet. 3. Submit a monthly report to the DEA of the total quantity of CS dispensed if one of the following criteria is met: - > 100 CS prescriptions were filled in the last month - ≥ 5,000 CS dosage units were dispensed in the last month 4. The website must list the following information: - The name and address (as it appears on the DEA registration) of the pharmacy's physical location. - The list of states in which the pharmacy is licensed to dispense controlled substances. - The name, professional degree, and state/s of licensure for the PIC and the phone number where the PIC can be reached. - The name, address, phone number, professional degree, and states of licensure of any practitioner who is contracted with the pharmacy to provide medical examinations or issue prescriptions for controlled substances. 5. The website must list the following statements: - "In accordance with the Controlled Substances Act and the DEA regulations, this online pharmacy has made the notifications to the DEA Administrator required by 21 U.S.C. 831 and 21 C.F.R. 1304.40." - "This online pharmacy is obligated to comply fully with the Controlled Substances Act and DEA regulations. As part of this obligation, this online pharmacy has obtained a modified DEA registration authorizing it to operate as an online pharmacy. ln addition, this online pharmacy will only dispense a controlled substance to a person who has a valid prescription issued for a legitimate medical purpose based upon a medical relationship with a prescribing practitioner. This includes at least one prior in-person medical evaluation in accordance with section 309 of the Controlled Substances Act (21 U.S.C. 829), or a medical evaluation via telemedicine in accordance with section 102(54) of the Controlled Substances Act (21 U.S.C. 802(54))."

Pharmacy Requirements for CS Prescription Transfers

1. Transferring Pharmacy: - Write "VOID" on the front of the original hard copy. Write the receiving pharmacy's information on the back of the voided prescription: - Pharmacy name - Business address - DEA number - Name of transferring pharmacist - Name of receiving pharmacist - Date of transfer 2. Receiving Pharmacy - Reduce the prescription to writing and write, "TRANSFER" on the face of the prescription. Record the following information on the prescription: - Date of original prescription issuance - Original number of refills - Date it was first dispensed - Number of refills remaining - Transferring pharmacy's name, address, DEA number, and prescription number - Name of transferring pharmacist - Pharmacy's name, address, DEA number, and prescription number from which the prescription was originally filled, if different.

Cancelling or Voiding CS Orders

A *purchaser* can *cancel* all or part of a controlled substance order by *notifying* the *supplier* in writing. The supplier must *indicate the cancellation* on Form 222 (Copies 1 and 2 of the triplicate form) by drawing a line through the canceled item/s and writing *"canceled"* in the space for the number of items shipped. A *supplier* can *void* part or all of an order by *notifying* the *purchaser* in writing. The supplier must draw a line though the cancelled items on Form 222 (Copies 1 and 2 of the triplicate form) and print *"void"* in the space for the number of items shipped. Alternatively, if the supplier cannot fulfill an order, they can *endorse* (i.e., transfer) the order to *another supplier* that can fulfill it. This only applies if the order was placed using a paper Form 222. If the Form 222 is illegible, incomplete, or altered, the supplier *returns Copies 1 and 2* to the purchaser with the rationale for not filling the order. The purchaser must keep the original Form 222 (all three copies of the triplicate form). An electronic order is invalid if any required data field is empty, if it is not signed with a DEA-sanctioned digital certificate, if the digital certificate is expired or if the purchaser's digital signature is not validated. The supplier can refuse to fill an order for any reason and must provide the purchaser with a statement of the occurrence. The *purchaser* must *electronically link* this *statement* to the original order. Invalid electronic orders cannot be corrected; the purchaser must submit a new order. The supplier is not required to keep a record of unfilled orders, but the purchaser must keep an electronic copy of the voided order. If a supplier partially voids an order, the supplier must indicate nothing was shipped for each voided item in the linked record.

Disposal of CS Wastage in an Institutional Setting

A CS dispensed for immediate administration in a hospital or other institutional facility remains under the control of that institution at all times. In some instances, a single-dose vial or syringe may be dispensed for a patient, and only a portion of the drug is administered, leaving some drug remaining in the vial or syringe. The remaining portion cannot be used and is referred to as "drug wastage" or "pharmaceutical wastage." *Drug wastage* is not reported with DEA Form 41, but is must be properly *recorded in a logbook* or electronic recordkeeping system.

Concentration-Dependent Scheduling- Schedule IV

A drug will be classified as *Schedule IV* if the *opioid quantity is NMT*: - 1 mg of Difenoxin and not less than 25 mcg of Atropine Sulfate per dosage unit.

Concentration-Dependent Scheduling- Schedule V

A drug will be classified as *Schedule V* if the *opioid quantity is NMT*: - *200 mg* of *Codeine per 100 mL/grams* when combined with one or more active non-narcotic ingredients (e.g., Robitussin AC, Promethazine w/ Codeine) - *100 mg* of *Dihydrocodeine per 100 mL/grams* when combined with one or more active non-narcotic ingredient (such as Dihydrocodeine/Chlorpheniramine/Phenylephrine cough syrup) - 100 mg of Ethylmorphine per 100 mL/grams when combined with one or more non-narcotic ingredient - *2.5 mg* of *Diphenoxylate* and *not less than 25 mcg of Atropine Sulfate per dosage unit* (e.g., Lomotil) - 100 mg of Opium per 100 mL/grams when combined with one or more active non-narcotic ingredient - 0.5 mg of Difenoxin and not less than 25 mcg of Atropine Sulfate per dosage unit

Pharmacy Selling Controlled Substances

A pharmacy can *sell controlled substances* to other pharmacies or prescribers without registering as a distributor, provided both parties are *registered* with the DEA *to dispense controlled substances*. The total *quantity sold cannot exceed 5%* of the total quantity *dispensed each year* by the selling pharmacy.

Distribution of CS Between DEA Registrants

A pharmacy can transfer CS to another pharmacy, the original supplier, or the manufacturer. A DEA *Form 222* of CSOS must be used to *transfer CI and CII drugs*. An *invoice* or CSOS is used to *transfer CIII - CV drugs* and must contain the following information: - Drug name, dosage form, strength, and quantity - Date of controlled substance transfer - Recipient's name, address, and DEA number All records of these transfers (inventory, Form 222, invoice) should be *kept for at least two years*, and some states require paperwork to be maintained for a longer period.

Controlled Substance Loss or Theft

A pharmacy must report a *significant* loss or theft of controlled substances to the *local DEA office*, in writing, within *one business day* of the discovery. After initially notifying the DEA, the pharmacy must conduct an investigation and submit *Form 106* to the *DEA* with the findings. If the investigation determines that theft or loss did not occur, then Form 106 does not need to be submitted. Instead, the registrant must *notify* the *DEA* in writing that there was *no theft or loss*. While not required by federal law, some states may also require the theft or loss to be submitted to local law enforcement and the state board of pharmacy.

Schedule III - V Prescriptions- Partial Filling

A prescription for CS can be filled for *less than* the quantity prescribed, which is called a *partial fill*. Partial filling is generally done at the patient's request due to cost issues or to help *decrease* the amount of *excess or unused medication* in the patient's home. A patient with acute pain may pick up a partial fill of pain medication, and would be able to pick up the remaining quantity later if they continue to have pain after using the initial supply received. *Partial fills* of *CIII - CV drugs* are *permitted* by the DEA if each fill is *recorded* in the same manner as a refill, and the *total quantity dispensed* in all the fills *does not exceed* the *total quantity prescribed*. For example: - A prescription written for Ultram #60 with 2 refills is equivalent to 180 tablets. As a C-IV drug, this can be dispensed over a 6-month period from the date of issuance. Theoretically, the patient could come into the pharmacy every day for 90 days and receive two tablets, or come in daily for 180 days and receive 1 tablet. Partial fills are *not considered refills*. The *refill quantity* is the same as the *initially quantity prescribed*. For example: - If a C-III prescription is written for 30 tablets with 5 refills, but a patient only receives 15 tablets at a time, then the patient could receive up to 12 partial fills. - The initial written quantity of 30 dispensed (even if dispensed as two partial fills of 15 tablets) would be considered the initial fill, which does not count as one of the five refills. - After the initial 30 tablets are dispensed, the subsequent partial fills will not subtract from the remaining refills until another full refill quantity of 30 has been dispensed.

Disposal of Controlled Substances

A registrant (e.g., pharmacy or dispensing prescriber) should not send drugs to the DEA for disposal unless they have received prior approval from the local DEA field office. Otherwise, controlled substances should be disposed of using one of the following methods: 1. Return to Supplier 2. Reverse Distributor

Disposal of Controlled Substances- Return to Reverse Distributor

A reverse distributor is a company that disposes of CS. A pharmacy can send CS to a reverse distributor for disposal, provided the reverse distributor is registered with the DEA. The *reverse distributor* must *issue Form 222* or the electronic equivalent to a pharmacy that is transferring *CII drugs* for disposal. If the triplicate form is used, the reverse distributor will keep Copy 3 and send Copies 1 and 2 to the pharmacy, which is acting as the "supplier." The pharmacy will forward Copy 2 to the DEA. If the pharmacy is transferring *CIII - CV drugs*, then a record (e.g., receipt or invoice) must be maintained with the following information: - Drug name, strength, dosage form, quantity - Date transferred. *DEA Form 41* is used to document the *destruction* of controlled substances. The *reverse distributor* will submit Form 41 to the *DEA* once the CS have been destroyed.

Electronic Controlled Substance Ordering System

AKA CSOS, this system is the *electronic equivalent* to the *Form 222* and allows for electronic ordering of *CI and CII drugs*. CSOS can be used to order CIII - CV drugs as well, but it is not required. Each person authorized to place orders for CI - CII drugs must obtain a *personal digital certificate* to sign orders (e.g., the registrant and any individuals granted POA). Digital *certificates cannot be shared*. When using *CSOS*, the purchaser creates an electronic order using *DEA-approved software*. When the order is complete, the *purchaser signs* it with their *digital certificate* and electronically transmits it to the supplier. The *supplier* receives the order, *verifies the certificate* and fills the order. The *supplier* must *report the transaction* to the *DEA* within *two business days* from the date the order was filled.

Cannabis Products: CBD and Hemp DEA Changes

According to *federal law*, CBD derived from any source (including Hemp) cannot be used in dietary supplements or as a food additive since CBD is available as a prescription drug (Epidiolex). However, the DEA has made two recent changes pertaining to cannabis products: 1. In 2018, the Farm Bill was signed into federal law, which removed hemp from the definition of marijuana in the CSA. Since hemp products are legal, *CBD* can be extracted from hemp and used in *topical products* (e.g. creams, ointments, oils, sprays). 2. The *FDA* still *regulates hemp and hemp-derived products*, but they are no longer classified as schedule I. This has allowed *retail pharmacies* to begin selling *CBD-containing topical products* in select states.

Schedule III - V Prescriptions- Expiration Dates

According to *federal law*, prescriptions for *non-scheduled* and *schedule V drugs do not expire*, whereas prescriptions for *schedule III and IV* drugs are only valid for *six months* from the *issue date*. Individual states may have stricter regulations regarding the expiration dates of prescriptions. Some states may also impose a quantity or days' supply limit on certain prescriptions (e.g., limits on opioids for acute pain).

Schedule III - V Prescriptions- Recordkeeping

According to federal law regulations, the pharmacist must document the following information on the back of the prescription for each *refill* of CIII - CV drugs: - Dispensing pharmacist's *initials* - *Date* dispensed - *Quantity* dispensed If an electronic recordkeeping system is utilized, the pharmacist must verify and document that the refill data entered into the system is correct using one of the following methods: - A *daily, hard copy printout* of refills for CS. Each pharmacist involved must sign and date the printout to indicate the printout is correct and includes the refills for that day. Printouts can be long and may come from a central "computer room" location. This is more common in pharmacies that fill a large number of prescriptions. The printout must be provided to the pharmacy within 72 hours of the date when the refills were dispensed. - A *bound logbook or separate file* documenting each day's refills. Each dispensing pharmacist on duty must sign a statement saying that what they dispensed is correctly listed in the logbook or file. The electronic system must provide online retrieval of *original prescription information* for those prescriptions currently authorized for refill. The information must include: - Original Rx Number - Date of Issue - Patient full name and address - Prescriber name, business address, and DEA number - The name, strength, dosage form, and quantity of the CS prescribed (and quantity dispensed if different from the quantity prescribed). - Total number of refills authorized. The electronic system must also be able to print out *refill information*, which must include: - Original Rx Number - Date of each refill - Patient full name and address - Prescriber name - Name or ID code of dispensing pharmacist - Quantity dispensed

Paper CS Prescription Recordkeeping

According to federal law, pharmacies have *two options* for filing paper prescriptions: 1. Option 1: Three separate files - A file for CII prescriptions - A file for CIII - CV prescriptions - A file for all non-controlled drug prescriptions 2. Option 2: Two separate files - A file for CII prescriptions - A file for other drugs dispensed (CIII - CV and non-controlled drugs). *Schedule III to V prescriptions* must be made readily retrievable by stamping a *red "C"* that is at least *one inch* high in the *lower right corner*. The letter "C" is waived if the pharmacy has an electronic prescription recordkeeping system, which can identify the controlled drugs by the prescription number.

Schedule III - V Prescriptions- Downtime Processing of Refills

Although computers offer an efficient method for managing workflow, electronic recordkeeping systems are susceptible to downtime. Downtime occurs when the computer system is unavailable to the pharmacy staff. This can occur due to power outages, system crashes, or scheduled software maintenance. The DEA requires pharmacies to develop a *back-up procedure* to *document* the *dispensing* of refills of *CIII - CV drugs* in the event of a system downtime. The back-up procedure must ensure that refills have been *authorized* by the *original prescription*, and that the *maximum* number of *refills* is *not exceeded*. The prescription itself can be prepared using a tabletop label printer if the power is down entirely, or with hand-written labels. However, the pharmacist must use caution that all required information is documented during a system downtime. Since pharmacies are required to maintain a daily record of CIII - CV drug refills as a printout or in a bound logbook, refill information should be accessible during a system downtime. Federal regulations also mandate that any electronic system employed by a pharmacy must have a central recordkeeping location that can provide a printout of the refill information to the requesting pharmacy within 48 hours. Once the computer system is functioning properly, all the dispensing information must be *entered* into the *electronic system* as soon as possible. Although not addressed by federal regulations, the pharmacy should also have a back-up procedure in place to document the dispensing of all other prescriptions (new fills and refills). Individual states may have stricter downtime policies.

Dispensing Controlled Substances- Patient Identification Prior to Dispensing

As part of a recent initiative to reduce drug diversion, the federal government has *recommended* pharmacies require *identification* before dispensing a CS *If the patient is not known* to the pharmacy staff. While not required by federal law, some states require a valid photo identification at pick-up or drop-off. Some states require pharmacies to submit a patient's identification number to the PDMP, which is a unique number located on the form of identification. Commonly accepted valid forms of photo ID include: - State driver's license - State or Federal-issued ID card - Military ID card - U.S. Passport In states where ID is not required, it can be requested at the pharmacist's discretion, especially if diversion or fraud is suspected. Alternatively, a pharmacy may ask the patient to verify specific identifiers when dropping off or picking up a prescription. Common identifiers include patient name, date of birth, home address. AZ does not require ID for CS prescription pickup.

Faxed Controlled Substance Prescriptions

Faxed prescriptions are acceptable for *CIII - CV drugs* as long as they contain all the required prescription elements, and the *prescriber* has *signed* the *prescription* form. After the prescriber signs it, the designated agent or the prescriber can transmit the fax to the pharmacy. A prescriber may write the prescription on a tamper-evident security form and fax it to the pharmacy as well. This however may cause the text "void" to appear on the face of the prescription, due to the effect of the fax machine on the thermochromic ink. This is a security feature intended to prevent the creation of fake prescriptions or faxing the same prescription to multiple pharmacies. The pharmacist should exercise professional judgment in determining the validity of the prescription and contact the prescriber for verification if there are any doubts.

Ordering CI and CII Medications

Before ordering schedule I and II drugs, the *pharmacist-in-charge* (i.e., the registrant) must first *register* with the DEA *using Form 224*. CSOS can be used to order Schedule I - V drugs, while the DEA Form 222 is limited to ordering Schedule I and II drugs. Schedule I drugs have no currently accepted medical use, but they may be ordered for use in investigational research. The DEA registrant can request copies of Form 222 or CSOS access on the initial DEA Form 224 or through the DEA website. Each pharmacy location has *one designated registrant*. This is the only pharmacist authorized to order CI and CII drugs, unless the registrant grants a *Power of Attorney (POA)* to another individual, allowing them to place orders for CI and CII medications in his/her absence. A *POA* is a legal document that *authorizes* a designated individual to *act in the registrant's place*. Each time a schedule I or II drug changes location, DEA Form 222 or the electronic alternative documents the movement. A copy of the DEA Form 222 will accompany the drug during *distribution, purchase, or transfer*. If CSOS is used, the electronic system will trace the drug's movement. A record is needed when a schedule II drug moves from a wholesaler/supplier to a pharmacy, from a pharmacy to another pharmacy, or to a reverse distributor for destruction. This documentation is required for every drug movement, except in two situations: - When the drug is dispensed or administered to a patient. - When a central-fill pharmacy associated with a retail chain is filling schedule II drugs for one of the chain's retail stores.

Steps to Order CII Drugs with the DEA Form 222- Purchaser Steps

Both Triplicate and Single-Sheet Form 1. Fill out the name and address of the supplier 2. Enter the # of packages, size of the package, drug name, and strength. Each item must be on a separate line. Do not skip any lines. 3. Write the number of the last line used into the space on the bottom left of the form. This field must be completed. 4. The DEA registrant or the person with the POA must sign/date the form (handwritten signature and date is required) 5. If a mistake is made, write "VOID" on Form 222 and start over with a new Form 222 Triplicate Form 222 Differences 1. There are *10 lines* on each form; a maximum of 10 lines can be ordered. 2. *Keep Copy 3 (blue)* and send Copies 1 and 2 (brown and green) to the supplier. 3. The first two Copies must stay attached; the supplier cannot fill the order if they are separated. Single-Sheet Form 222 Differences 1. There are *20 lines* on each form; a maximum of 20 items can be ordered. 2. Make a *copy* of the form (*readily-retrievable* electronic copies are allowed) and keep for *two years*. 3. Send the form to the supplier.

Steps to Order CII Drugs with the DEA Form 222- Supplier Steps

Both Triplicate and Single-Sheet Form 1. If any required fields are missing, or if the form is sloppy and not legible, return the form to the purchaser. Minor errors can be corrected. 2. Fill in the NDC, number of containers for each item and the date shipped. 3. If unable to provide the entire quantity, provide a partial shipment, and *supply the balance* within *60 days* or endorse (i.e., send) the order to another supplier. 4. Shipments can only be delivered to the DEA-registered address. 5. Deliver the scheduled drugs to the purchaser in a separate container from non-controlled drugs or OTC products. Triplicate DEA Form 222 Differences 1. *Keep Copy 1* (brown) and send *Copy 2* (green) to the *DEA* by the end of the month in which the order was filled. Single-Sheet Form 222 Differences 1. Keep the *original copy* for *two years*.

Steps to Order CII Drugs with the DEA Form 222- Purchaser Receives Shipment Steps

Both Triplicate and Single-Sheet Forms 1. When the order arrives at the pharmacy, it must be *checked in* by a *pharmacist*, who records the *number* of *packaged* and the *date received* by comparing the delivery to the order. Triplicate Form 222 1. The *number of packages* and the *date received* should be recorded on Copy 3 (blue). 2. Keep Copy 3 for *two years* (federally, AZ law is *3 years*). Single-Sheet Form 222 1. Part 5 of the form can be completed once the drugs arrive from the supplier. Fill in the number of packages and date received on the pharmacy's photocopy of the form.

Written Controlled Substance Prescriptions

CS prescriptions must be written in ink, indelible pencil (i.e., unable to be erased) or typewritten by the prescriber or by an agent of the prescriber (such as an office assistant or nurse). The prescription *must include*: - Patient full name and address - Prescriber full name, business address, and DEA number - Drug name, strength, dosage form, quantity prescribed, and directions for use - Number of refills authorized According to the CSA, a CS prescription must be *signed and dated* by the prescriber on the *date it is issued to the patient*. If a MLP is prescribing under a physician-directed protocol, the *MLP must sign* the prescription. The supervising physician does not need to sign the prescription. *Pre-signing* prescription blanks for *non-controlled* and *controlled drugs* is *illegal*. This practice can result in disciplinary action and license suspension. Pharmacists should not fill prescriptions that are suspected to have been pre-signed. Orders written for *direct administration* to patients in facilities such as clinics or hospitals are not considered prescriptions, they are referred to as *Medication Orders or Chart Orders*. Medication Orders are not subject to the same requirements as prescriptions. Some states may have additional restrictions, such as limiting the number of CS written on a single prescription form or prohibiting the writing of non-CS and CS on the same prescription form. This may be due to the need to file CS prescriptions separately.

Recordkeeping of CS- Required Records

Every pharmacy must maintain current, complete, and accurate records of each CS purchased, received, stored, distributed, dispensed, or disposed of. The DEA requires *all records* of CS be kept for *two years*, but individual states may have longer requirements. The records that must be kept by the pharmacy include: - Completed and blank *DEA Form 222 or CSOS* equivalents - *POA* forms - *Receipts and/or invoices* for CIII - CV drugs - Initial and biennial *inventory records* for CS - *Records of transfers* of CS between pharmacies - *Records of distribution* (e.g., sales to other registrants, returns to vendors, distribution to reverse distributors) - *Records of dispensing* (e.g., prescriptions, schedule V logbook) - *Reports of theft or significant loss* (DEA Form 106) - Inventory of *drugs surrendered for disposal* (DEA Form 41) - *DEA registration certificate* - Self-certification certificate and paper/electronic *logbook for pseudoephedrine* sales

Providers Authorized to Prescribe Controlled Substances

Controlled Substance prescriptions can be issued by a physician (MD/DO), dentist (DDS/DMD), podiatrist (DPM), veterinarian (DVM), mid-level practitioner (MLP), or another practitioner who is: - *Authorized to prescribe* controlled substances by the *jurisdiction or state* in which the practitioner is licensed to practice. - *Registered with the DEA* or *exempt* from DEA registration. - An agent or employee of a hospital or institution acting in the normal course of business *under* the *hospital's or institution's registration*. The license to practice medicine and prescribe is granted by the individual states. After approval by the state, the practitioner can register with the DEA to prescribe CS. Physicians are the only providers with unlimited, independent prescribing authority. Despite this independence, many states stipulate that physicians must only prescribe within their scope of practice. In all states, all other practitioners are limited to prescribing within their *scope of practice*. For example, Naturopathic Doctors (NMDs) are generally limited to "natural" compounds such as amino acids, vitamins, or natural hormones (e.g., Armor Thyroid). Individual states define which practitioners are considered mid-level practitioners and regulate what/how they can prescribe. The state will also define whether MLPs can prescribe independently or if they require a *collaborative practice agreement* with a supervising physician. The DEA maintains a list of the different types of MLPs and the controlled substance prescribing authority for each within a state. An *employee or agent* (e.g., nurse or office assistant), under the direct supervision of a prescriber, may *communicate prescription* information to a *pharmacist*. The agent can also *prepare a prescription* for the prescriber to sign and date.

Schedule II Prescriptions- Expiration Dates and Refills

Despite CII drugs having the *highest abuse potential* of all FDA-approved drugs, there is *no expiration date* or *quantity limit* set by *federal law* for *CII prescriptions*. Some states may impose an expiration date, quantity limit, or days' supply limits. Federal law *does not allow refills* for *CII* drugs. Patients requiring additional quantities must obtain a new prescription. Prescriptions for CII drugs *cannot be refilled* even though some patients may require CII drugs as maintenance therapy. While there are no federal quantity limits, providers generally avoid prescribing more than a 30-day supply for CII drugs due to the risk of abuse and misuse. The inability to provide refills for patients requiring chronic treatment (such as stimulants for ADHD) necessitates frequent office visits, which can become costly and inconvenient for the patient. In 2007, the DEA authorized prescribers to issue *multiple prescriptions* at *one time* for *CII drugs*. These prescriptions can be *filled sequentially* but *cannot exceed a 90-day supply*. The prescription *cannot be post-dated*. Instead, the prescriber must include two dates on the prescription: the *written date* (i.e., the issue date), and the *earliest acceptable fill date*. The prescriber can write any phrase to indicate the earliest fill date, such as "Do not fill before," or "Do not fill until." This is necessary to prevent a patient from filling a prescription at the same time at multiple pharmacies.

Valid DEA Numbers

Each DEA number is unique and is assigned to an individual HCP or an institution. The DEA number permits the individual to write CS prescriptions and authorizes an institution to order and manage CS. Each DEA number is randomly generated and consists of the following: 1. Starts with *two letters* - *First Letter*: Identifies the *type* of practitioner or institution (i.e., registrant type) - *Second Letter*: First letter of the *prescriber's last name*. 2. Letters are followed by *seven numbers*, with the last number being the *"check digit."* If a practitioner is authorized to *prescribe narcotics* (such as Buprenorphine) for *opioid addiction treatment*, the practitioner will receive a *DATA 2000 Waiver* Unique Identification Number (UIN). The number is the same as the practitioner's DEA number, except that the letter "*X*" replaces the *first letter*. Prescribers in a hospital or other institution, including medical *interns, residents*, and visiting physicians, can prescribe medication under the *DEA registration* of that *hospital or institution*. The hospital or institution will assign a specific internal code number to each practitioner authorized to prescribe. The internal code number will follow the last number of the hospital's DEA number.

Label Requirements of Controlled Substance Prescriptions

Each controlled substance prescription dispensed must include the following items on the container: - Date of initial fill - Date of current fill (if it is a refill) - Pharmacy name and address - Prescription serial number - Name of patient - Name of prescriber - Directions for use - Cautionary statements Central Fill Pharmacies must include the *retail pharmacy's name and address* on the label and a *unique identifier* (such as the *Central Fill* Pharmacy's DEA number) to indicate that is was centrally filled. The DEA also requires a warning statement on all CII - CIV prescription labels that reads: - "Caution: Federal law prohibits the transfer of this drug to any person other than the person for whom it was prescribed." Federal law does not require this statement on CV prescription labels, but some states require it for all controlled substances.

Cannabidiols and Tetrahydrocannabinols

Federal law designates marijuana as a Schedule I controlled substance. *Cannabidiol (CBD)* and *Tetrahydrocannabinol (THC)* are natural compounds found in the *Cannabis Sativa* (marijuana) plant. *THC* has a *psychoactive effect* (a "high"). *CBD* does not cause a high, but can have an *anxiolytic (relaxing)* effect. *Hemp* is derived from a type of Cannabis Sativa plant with levels of *THC (<0.3%)* incapable of causing a psychoactive effect. Both THC and CBD are used for a variety of medical conditions, with and without proof of efficacy. The ratio THC:CBD contributes to a product's therapeutic efficacy and psychoactive effect.

Schedule II Prescriptions- Documentation of Partial Fills for LTCF or Terminally Ill Patients

For *each partial fill*, the *pharmacist* must *document* the following information on the back of the prescription: - Date of partial filling - Amount dispensed - Amount remaining - Name of dispensing pharmacist If an *electronic recordkeeping system* is used, the following information must be maintained and be updated in real time when a partial fill is dispensed: - Original Rx Number - Date of Issue - Drug name, dose, formulation, strength, and quantity - Quantity authorized - Patient name - Prescriber name - Address of the LCTF, hospital, or patient's home - List of partial fills dispensed

Faxed CII Prescriptions

Generally, *faxed* prescriptions for *CII drugs cannot* serve as the original prescription. Some prescribers will fax a prescription and provide the patient with the written one to bring to the pharmacy. The purpose of faxing the written one is to permit the pharmacy to begin processing the prescription to reduce the patient's wait time. The *CII drug cannot be dispensed* to the patient until the pharmacy receives the *written prescription*. The written prescription is then verified against the faxed prescription prior to dispensing. It is not acceptable for a patient to fax the prescription to the pharmacy. The faxed prescription can serve as the *original copy* for a CII drug in only three scenarios: 1. A drug *compounded* for administration to a patient by *parenteral, intravenous, intramuscular, subcutaneous, or intraspinal route*. 2. A prescription for a resident of a *Long-Term Care Facility (LTCF)*. 3. A prescription for a patient enrolled in a *hospice program*. The prescriber or agent of the prescriber must note on the face of the prescription that the patient is a hospice patient.

Schedule II Prescriptions- Emergency Filling of CIIs

Generally, *prescribers cannot call in* prescriptions for *CII* drugs. However, the DEA *permits dispensing* a CII drug pursuant to an *oral prescription* of the drug's *immediate administration* is *necessary to avoid patient harm*, and there is no reasonable alternative. *Central fill* pharmacies are *prohibited* from preparing emergency fills of CII drugs under any circumstance. If the *pharmacist* is not familiar with the prescriber, they must *make a good faith effort* to determine that the oral prescription came from a DEA-registered practitioner. This can be done by calling the prescriber using the phone number listed in a public directory (i.e., not the number provided, as it could be fake). The pharmacist must reduce the prescription to writing immediately and it must contain all the necessary information for CS prescriptions, except for the prescriber's signature.

Exempt Providers from DEA Registration

Healthcare providers practicing at the following facilities can *prescribe, administer, or dispense* controlled substances *without registering with the DEA*: - Federal Bureau of Prisons - Indian Health Service - U.S. Armed Forces (Air Force, Army, Coast Guard, Navy, Marines, Space Force) - U.S. Public Health Service However, providers that *purchase or procure* controlled substances (e.g. pharmacists) at these facilities are *not eligible* for this exemption and *must register* with the DEA.

Common Schedule IV Drugs- Hypnotics, Weight Loss Drugs

Hypnotics - Eszopiclone (*Lunesta*) - Lemborexant (DayVigo) - Suvorexant (Belsomra) - Zaleplon (*Sonata*) - Zolpidem (*Ambien, Ambien CR, Edluar, Zolpimist*) Weight Loss Drugs - Diethylpropion - Phentermine (*Adipex-P*, Lomaira) - Phentermine/Topiramate (*Qsymia*)

Electronic Controlled Substance Prescriptions- Transmission Failure

If *transmission* of an electronic prescription for *CIII - CV drugs fails*, the prescriber must *send it* to the pharmacy *by another method*, such as a written prescription, by fax, or by phone. If *transmission fails* for a *CII drug*, the prescriber must *provide a handwritten prescription*. If an electronic prescription was not received in a timely manner, it may be due to a lag in the electronic delivery. To ensure the prescription is not filled twice, the replacement must specify that the initial electronic transmission has failed, with the date, time, and pharmacy where the electronic prescription was sent. The pharmacy must verify the initial electronic prescription was not received or dispensed. If the initial prescription was received and dispensed, the second prescription is voided. If the initial prescription was received but not dispensed, then the initial prescription is voided and the pharmacy uses the replacement to provide the drug to the patient.

Lost or Stolen DEA Form 222 or Electronic Orders

If a completed *Form 222 is lost or stolen*, the purchaser must *resubmit* the order with a *new Form 222* and submit it to the supplier. The pharmacy must provide a *statement* to the distributor with the new Form 222 that contains the following information: - The *serial number* of the original form - The *date* of the *initial order* - A *statement* that the controlled substances *were not received* The *pharmacy* must *keep a copy* of the statement with a copy of the *initial order* and the *second order*. If *unused forms* are discovered to be *lost or stolen*, the pharmacy must *immediately notify* the *local DEA* Diversion Field Office. The *serial number* for each lost or stolen form must be *provided* unless an entire book or multiple books are missing, and the serial numbers are unknown. If the numbers are unknown, then the pharmacy must provide the approximate date that the DEA issued the forms. If an *electronic order is lost*, the *purchaser* must provide a *signed statement* to the supplier stating that the fulfilled order was not received. This statement must contain the *unique tracking number* and the *date of the lost order*. If a replacement order is created, the *purchaser* must *electronically link* the *new order* with the record of the *lost order* and the *signed statement*.

Transferring CII Prescriptions

If a pharmacy cannot fill an *electronic prescription* for a CII drug, the pharmacy has two options: 1. *Contact the prescriber* to have them send the electronic prescription to a different pharmacy. 2. *Transfer* the *unfilled original* electronic prescription to another pharmacy. This practice is allowed for all controlled substances and is generally less time consuming than contacting the prescriber. If a pharmacy is unable to fill a written prescription for a CII drug, the pharmacy can return the prescription to the patient for filling elsewhere. The pharmacy cannot transfer a written prescription for a CII drug to another pharmacy, it must be physically delivered to a different pharmacy.

Pharmacy Going Out of Business

If a pharmacy goes out of business or is acquired by new ownership, the *pharmacy can transfer* controlled substances to the new pharmacy, once the DEA number is confirmed. A *complete inventory* is taken and used as the transferring registrant's *final inventory* and as the *initial inventory* for the acquiring registrant. The inventory is not sent to the DEA. *Each pharmacy* must *maintain* a copy of the inventory *records* for at least *two years*. The inventory must be taken before the dispensing for the day as started, or at the end of the day.

Electronic CS Prescription Recordkeeping

If a prescription is *received electronically*, the record must be *kept electronically*. The system must be able to sort by prescriber name, patient name, drug dispensed, and date filled. Federal law requires keeping electronic records for *two years*, but individual states can require longer periods.

Electronic Controlled Substance Prescriptions- Software Pending DEA Approval

If the prescriber's *software* is still *pending DEA approval*, it *cannot be used to transmit prescriptions*. If a prescription is sent from software that is pending DEA approval, the pharmacy will need to print out the prescription and contact the prescriber for verification. If the prescriber was contacted by phone, then the prescription is considered an oral prescription. If the prescriber was contacted by fax, then the prescription is considered a faxed prescription (as long as the fax has been manually signed by the prescriber prior to transmission).

Errors or Omissions on CS Prescriptions

In most states, a pharmacist can amend minor misspellings, fill in the patient's address, and add the prescriber's DEA number to a controlled substance prescription. The pharmacist can amend the dosage form, strength, quantity, directions for use, after consultation with the prescriber. This includes making any quantity changes required for insurance coverage. All significant changes must be documented on the prescription and the pharmacist will write his/her name or initials to indicate who made the call to the prescriber. However, for *all controlled substance prescriptions*, there are *three items* that *cannot be changed*: 1. *Patient name* 2. The *prescribed drug* (except for generic substitutions) 3. *Prescriber signature* If any of these three items above need to be changed, or if the prescriber did not sign the prescription, the prescription is invalid. Minor spelling mistakes in the patient's name, or drug name can be corrected at the pharmacist's discretion. It is unlikely the prescriber misspelled his or her own name, although it may be difficult for the pharmacy staff to decipher the correct spelling. If the prescriber's signature is obviously misspelled, the pharmacist *should be wary of forgery*. For major errors or omissions on CIII - CV drugs, the pharmacist can simply call the prescriber, note any authorized modification and document that the prescriber was contacted. The prescriber would need to provide a new written or electronic prescription if major modifications need to be made to a CII prescription. Some states may have more strict limitations on what modifications are permitted for CS prescriptions.

Corresponding Responsibility and Red Flags

In order for a prescription to be considered *valid*, it must be issued in the *usual course of professional treatment* for a *legitimate medical purpose*. The condition being treated must be one that the prescriber would be expected to treat. The *pharmacist* has *corresponding responsibility* to ensure a *CS prescription* is *valid* prior to filling. A pharmacist is *not required to dispense* a prescription if he/she has any concerns about the legitimacy. If a pharmacist dispenses a CS prescription that he/she suspects has not been issued for a legitimate medical purpose, then the pharmacist and prescriber may both be prosecuted. Pharmacists should be aware of potential "Red Flags" when filling CS prescriptions to help prevent drug abuse and diversion. The National Association of Boards of Pharmacy (NABP) has published examples of Red Flags that should be reconciled before dispensing a CS prescription. Other signs of drug abuse or misuse may include: - Irregularities on the face of the prescription - Prescriptions for unusually large quantities or an initial prescription for a strong opioid

Schedule III - V Prescriptions- Emergency Refilling

Limitations on emergency filling without the prescriber's authorization will vary from state-to-state. Some states allow emergency filling for non-CS drugs and CIII - CV drugs while other may only allow emergency refilling on non-CS drugs. The emergency days supply to be dispensed will also vary, but is commonly limited to 72 hours. The emergency refill must be properly documented and an original prescription for the emergency fill must be obtained in a timely manner. In AZ, according to the law, emergency fills are allowed for CIII - CVs without prescriber authorization if it is during a declared state of emergency (natural disaster or terrorist attack). The pharmacist is allowed to dispense up to 30 days, and if the emergency lasts for 21 days, the pharmacist may dispense one additional 30-day supply. The pharmacist must make a good faith effort to reduce the emergency fill to writing (as a prescription), mark it "emergency prescription" and file it as required by law.

Formulation-Specific Controlled Substances

Most controlled substances in the *same pharmacological class* or containing the same active ingredient will be classified in the same schedule (e.g. all Benzodiazepines are Schedule IV). Some controlled substances that are available as single-entity and combination products (e.g. Oxycodone) are Schedule II in all formulations due to their abuse potential. Other drugs (e.g. Barbiturates, Codeine, Dronabinol) may have varying schedules based on the formulation.

Recordkeeping of CS- Location of Records

Original *prescriptions*, executed copies of *Form 222* and *inventory records* must be kept *on-site* at the pharmacy location. *Shipping and financial* records can be stored at a *central location* after submitting written notification to the local DEA office. States may also require pharmacies to request permission to store records off-site. Unless the DEA denies the request to store records off-site, the registrant can begin storing the records at a central location *14 days* after the DEA receives this request. Upon request, the pharmacy must provide the DEA with the central records within *48 hours*. All *CII drug records* must be kept *separate* from all other records. All records of *CIII - CV drugs* must either be kept *separately* from all other records or stored in such a way that the information is *readily retrievable* from other records.

Disposal of Controlled Substances- Return to Supplier

Pharmacies can return CS to the drug supplier or manufacturer. The pharmacist must maintain a written record of the return showing: - The date of the transaction - The name, strength, dosage form, and quantity of the CS - The supplier or manufacturer's name, address, and registration number. A new Form 222 or its electronic equivalent must accompany the return of the CII drugs. The supplier or manufacturer receiving the CS must initiate the order. If the triplicate form is used, the supplier or manufacturer will keep Copy 3 and send Copies 1 and 2 to the pharmacy, which is acting as the "supplier." The pharmacy will forward Copy 2 to the DEA.

Oral Controlled Substance Prescriptions

Pharmacists can receive prescriptions over the phone (verbally, over the phone) for *CIII - CV* drugs only. The pharmacist must immediately *reduce* the prescription to *writing* (i.e., transcribe the prescription information onto the pharmacy's prescription form). The transcribed prescription must include all the required equivalents for a valid prescription, with the *exception* of the *prescriber's signature. Oral* prescriptions for *CII drugs* are not valid except in *emergency situations*. Federal law permits prescribers to designate an *agent* (e.g., *office staff* or a *nurse*) to communicate new and refill information to pharmacists by telephone or fax. The communication must be under the *supervision* of the *prescriber*. The prescriber is ultimately responsible for their designated agent's actions and medication orders.

DEA Controlled Substance Inventory Requirements

Prior to opening a new pharmacy, there must be a complete inventory of all CS. The registrant needs a record showing a *zero inventory* if there are *no CS* at the time of opening. After the initial inventory, a complete inventory of the *current stock* on hand is taken minimally on a biennial basis (i.e., *every two years*). The inventory should be counted at either the *beginning or close of business*. This avoids CS being pulls from the stock during the time the inventory is being taken and provides a more accurate count. An inventory should also be taken if a loss or theft is suspected. Pharmacies must maintain an inventory record at each location. The inventory records of *CII drugs* must be kept *separate* from all other CS. The records must be maintained in written, typewritten, or printed format. Inventory taken with a recording device must be reduced to writing promptly. The record must include: - *Date* of the inventory - If the inventory was taken at the *beginning or close of business* - *Names* of CS - *Dosage form* - *Strength, quantity*, or *volume* in each container. - *Number* of commercial *containers* There is no requirement to submit a copy of the inventory to the DEA. For *sealed, unopened* containers of all CS, an *exact count* is needed. There is no need to open a sealed container to perform a count, since the count is listed on the manufacturer's drug container. For *opened containers* of CS: - CI and CII containers require an exact count. - CIII - CV containers holding 1,000 dosage units or less can be *estimated*. - CIII - CV containers holding >1,000 dosage units require an *exact count*.

Controlled Substance Schedules- Definitions

Schedule I: - No currently accepted medical use. High potential for abuse and lack of accepted safety under medical supervision. Schedule II: - High potential for abuse. Abuse may cause severe psychological or physical dependence. Schedule III: - Lower abuse potential than Schedules I and II. Abuse may cause moderate or low potential for physical dependence or high psychological dependence. Schedule IV: - Low potential for abuse compared to Schedule III. Abuse may cause limited physical or psychological dependence relative to Schedule III. Schedule V: - Low potential for abuse relative to Schedule IV. Abuse may cause limited physical or psychological dependence relative to Schedule IV.

Formulation-Specific Controlled Substances- Dronabinol

Schedule II: - *Oral solution (Syndros)*, which is 50% alcohol Schedule III: - *Oral capsules (Marinol)*

Formulation-Specific Controlled Substances- Barbiturates

Schedule II: - *Single-entity* oral formulations of Amobarbital, *Pentobarbital*, and *Secobarbital*. Schedule III: - Amobarbital, *Pentobarbital*, and *Secobarbital* formulated as a *suppository*. - Amobarbital, *Pentobarbital*, and *Secobarbital* in *combination* with a *non-controlled substance*. - Butabarbital - Butalbital + Acetaminophen + Caffeine + Codeine (*Fioricet with Codeine*) - Butalbital + Aspirin + Caffeine (*Fiorinal*) - Butalbital + Aspirin + Caffeine + Codeine (*Fiorinal with Codeine*) Schedule IV: - *Phenobarbital* *Non-Controlled* (federally) - Butalbital + Acetaminophen + Caffeine (*Fioricet*)

Formulation-Specific Controlled Substances- Codeine

Schedule II: - *Single-entity* products Schedule III: - *Combination tablets/capsules* that contain Codeine (e.g. Tylenol #3, Acetaminophen/Codeine 300/30 mg) Schedule V: - *Combination cough syrups* that contain Codeine (e.g., Promethazine/Phenylephrine HCl/Codeine syrup)

Dispensing Non-Prescription Controlled Substances

Some *CV drugs*, including select Codeine-containing cough syrups (e.g., G Tussin AC), are not considered prescription drugs as defined by the FDA. These drugs do not meet the criteria for toxicity potential or require prescriber supervision, as outlined in the Durham-Humphrey Amendment of 1951. Therefore, some states permit the pharmacist to sell select CV drugs directly to patients *without a prescription*. Many states have elected to keep these products behind the counter, while others have stricter rules and require prescriptions for all CS, even those categorized as non-prescription by the FDA. These non-prescription CS products may contain Opium and Codeine, which have abuse potential when used in excessive amounts. For this reason, there are federal *limits* on the amount of drug that can be *dispensed* every *two days*: 1. *240 mL (8 ounces)* or *48 dosage units* of any CS containing *Opium*. 2. *120 mL (4 ounces)* or *24 dosage units* of any *other CS*. Only a *pharmacist can dispense* a non-prescription CS to a patient, who must be *at least 18 years of age*. If the pharmacist does not know the patient, the patient must provide proper ID. The pharmacist must record the following information in a *bound record book*: - Patient *name and address* - *Drug* name and *quantity* purchased - *Date* of purchase - *Pharmacist's name or initials*. After the pharmacist dispenses the drug, the payment and delivery may be completed by a non-pharmacist staff member.

Legalized Marijuana

Some states have legalized marijuana for consumption or inhalation. These states require cannabis products or edibles to be obtained from a state-approved dispensary. Cannabis products may be limited to the treatment of certain medical conditions or may be allowed for recreational use. If limited to medical use, states generally require patients to obtain a certificate or medical marijuana card in order to obtain products from a licensed dispensary. A prescriber authorized by the state to recommend medical marijuana must grant approval based on state-approval indication for use. Since pharmacies are registered with the DEA, they must operate within the confines of the federal law regarding marijuana. As such, *pharmacies are not permitted to sell marijuana* or drug paraphernalia (e.g. rolling papers). Even though marijuana is not dispensed in pharmacies, pharmacists should add marijuana to a patient's medication profile, and be aware of potential *drug interactions*. CBD and THC are *CNS depressants* which can cause additive side effects. Both are also *substrates* of several *CYP 450 enzymes*.

Written Controlled Substance Prescriptions- Tamper-Resistant Security Forms

States can require the use of *tamper-resistant security forms* for all prescriptions, for all scheduled drugs, or for CII drugs only. Prescribers can use both security and non-security forms, but some choose to use security forms for all prescriptions for simplicity.

Prescription Drug Monitoring Programs

The *DEA highly recommends* using a state-wide *Prescription Drug Monitoring Program (PDMP)* to help *prevent drug abuse and diversion*. A PDMP is a *state-administered* electronic database that *collects prescription information*. This database can help pharmacists identify patients receiving controlled substance prescriptions from multiple prescribers ("doctor shoppers") and filling multiple CS at multiple pharmacies ("pharmacy hopping"). *Data collection frequency* varies by the state, but is most commonly collected in real-time, daily, every 72 hours, or weekly. Each state can determine what information is collected, such as prescriptions for all drugs (non-controlled and controlled), CS only, CII drugs only, or CII - CIV drugs only. Some states choose to collect prescription information for non-controlled drugs only if they have shown abuse potential (e.g., Gabapentin). Each PDMP is *regulated* by a specified *state-wide* administrative, regulatory, or law enforcement agency, *not by the DEA*. The agency that collects the prescription data makes it available to authorized individuals, which may include out-of-state HCPs (e.g., from neighboring states). In some states there may be specific criteria for checking the PDMP. For example, a pharmacist may be required to check the PDMP when a patient receives a prescription for a new CS or anytime the patient or prescriber is outside of the usual geographic area served by the pharmacy.

Breakage, Spillage, or Damage of Controlled Substances

The *breakage, damage, or spillage* of CS is *not considered a "loss"* of CS. Any *drug* that is *recoverable* from the breakage, damage, or spillage *must be disposed of* according to DEA requirements. *DEA Form 41* must be submitted to the DEA to *document this disposal*. If the breakage or spillage is *not recoverable*, the registrant must *document* the incident in the *inventory record*, and two witnesses to the breakage or spillage must sign the record. DEA Form 41 does not need to be filled out for non-recoverable scheduled drugs.

Prescribing Controlled Substances for Oneself or Immediate Family Members

The American Medical Association (AMA) does not recommend self-prescribing or treating immediate family members. The prescribing of CS for oneself or immediate family members is not addressed by the DEA, but individual state medical boards and boards of pharmacy can prohibit this practice. Some states prohibit prescribing certain categories of drugs, such as CII drugs or all controlled drugs.

Schedule II Prescriptions- Partial Filling Overview

The DEA allows for scenarios in which a CII prescription may be partially filled. Similar to partial filling of any other drug, the total *quantity dispensed* from all partial fills *cannot exceed* the *total quantity prescribed*. When a pharmacist fills less than the full amount prescribed, he or she must document the quantity dispensed on the prescription. The remaining balance must be filled within a specific time frame or the remaining balance is forfeited. There are three circumstances in which a *CII prescription may be partially filled*.

Schedule Changes

The DEA can reclassify a drug schedule when the perceived risk of abuse or dependence associated with the drug changes. When a scheduling change occurs, a pharmacy must complete an *inventory* of the drug on the *date the change becomes effective*. After the initial inventory, subsequent inventories are conducted according to the requirements of the new schedule.

Schedule III - V Prescriptions- Refills

The DEA does not provide a limit on the number of refills for CV prescriptions. Some states permit refills on CV drugs in a manner similar to non-CS drugs, whereas other states provide stricter refill limitations. *CIII - CIV drugs* may be refilled up to a maximum of *five times* within *six months* of the date written. After five refills or six months, whichever occurs first, a new prescription is required. The *original fill* is *not counted as a refill*, so a prescription with 5 refills would allow a total of six fills. A pharmacy may use a paper or electronic system for storage and retrieval of prescription refill information.

Controlled Substance Schedules- Overview

The Drug Enforcement Administration (DEA), under the US Department of Justice (DOJ), enforces the requirements of the Controlled Substances Act (CSA). The DEA publishes the Pharmacist's Manual, which includes the details needed to comply with the CSA. The DEA determines which drugs should be classified as CS and places them into one of five schedules (I to V). The schedule is determined based on whether the drug has a currently *accepted medical use*, its relative *abuse potential*, and the potential for it to cause *dependence when abused*. The *higher the abuse potential*, the *lower the schedule number. Schedule I* drugs have the *highest abuse potential* and are considered to have *no accepted medical use*. Drugs in this category (such as Heroin and LSD) may be used for research purposes, but are most commonly used illicitly (illegally/unlawfully). *Schedule II - V* drugs are considered to have *currently accepted medical uses*, with varying degrees of abuse and dependence potential.

Electronic Controlled Substance Prescriptions

The documentation of medical care in most healthcare settings is conducted electronically. This includes electronic medical records, computer-based prescribing systems, and networks to transmit and receive prescriptions. When prescriptions are electronically transmitted entirely through software, safeguards must be in place to prevent unauthorized persons from hacking into the system and illegally transmitting CS prescriptions. In 2010, the DEA released final rules that *permit electronic prescriptions* for CS (EPCS) for *CII - CV drugs*. Prescribers and pharmacies must use *DEA-approved software* that has passed a DEA-sanctioned audit by a third-party in order to send and receive EPCS. Prescribers must use a *two-factor authentication* method to sign and transmit EPCS. The credentials that are permitted for DEA-sanctioned validation include two of the following: - Something you *know* (e.g., *password* or *response to a question*) - Something you *have* (e.g., *hard token* containing a cryptographic key stored on a hardware device separate from the computer being accessed) - Something you *are* (e.g., biometric information, such as a *retinal or fingerprint scan*) As an alternative to using two-factor authentication to sign the EPCS, the prescriber can use a *digital certificate*. A digital certificate contains the user's credentials and is issued by the DEA. A prescriber can use a single digital signature to *sign multiple* electronic *prescriptions* at one time for the same patient. A single digital signature *cannot* be used to sign prescriptions for *different patients*. If a prescriber needs to issue a prescription for a different patient, the prescriber must repeat the process for a new digital signature.

DEA Form 222- Format

The following items are *preprinted* on the Form 222: - A *serial number*, in a consecutive number series - The *pharmacy name and address* - The *pharmacy DEA number* - The drug *schedules* that the pharmacy is *permitted to order* (i.e., schedules II, III, IV, V) Each copy of the triplicate form must be retained by the appropriate parties. *Copy 1 (Brown sheet)* is filled out by the purchaser. The purchaser *retains Copy 3 (Blue sheet)* and sends off Copy 1 and Copy 2 to the supplier. The supplier then fills in their portion (if they need to fill in the NDCs being provided) then *keeps Copy 1 (Blue sheet)* and sends *Copy 2 (Green sheet) to the DEA*. When using a single-sheet form, each entity involved in the transfer of CII drugs must retain a copy of Form 222 (e.g., by making a photocopy of the form).

Exemptions to CS Prescription Label Requirements

The labeling requirements do not apply to CS ordered for an institutionalized patient when a healthcare provider will administer the medications. The amount dispensed must be a short-term supply, and the drug cannot be in the user's possession prior to administration. The maximum amount dispensed is a seven-day supply for CII drugs and no more than a 34-day supply or 100 dosage units (whichever is less) for CIII - CV drugs. The institution must have appropriate safeguards in place for the safe distribution of controlled substances.

Concentration-Dependent Scheduling

The scheduling of some opioid-containing combinations depends on the *opioid concentration* compared to other non-narcotic active ingredients. If a drug *exceeds* the NMT ("not more than") quantity for a Schedule V, look at the *next most restrictive Schedule* criteria. If is exceeds the NMT for Schedule III, then the opioid would be considered a Schedule II. Schedule III: - Codeine - Dihydrocodeine - Ethylmorphine - Opium - Morphine Schedule IV: - Difenoxin Schedule V: - Codeine - Dihydrocodeine - Ethylmorphine - Diphenoxylate - Opium - Difenoxin

Internet Pharmacies and the Ryan Haight Amendments

There are two types of internet pharmacies: legitimate mail order pharmacies and rogue internet pharmacies. Legitimate mail order pharmacies dispense medications pursuant to a prescription from a prescriber who has performed a good faith medical exam. Rogue online pharmacies sell drugs for non-medical purposes (e.g., recreational use) and do not require legitimate prescriptions. These illegally operating pharmacies have contributed to the increase in CS abuse and drug overdoses. In 2008, the Ryan Haight Online Pharmacy Consumer Protection Act was signed into law to *prevent illegal sales of CS via the internet*. Now, there are requirements that must be met in order for online pharmacies to sell CS.

Concentration-Dependent Scheduling- Schedule III Opioids

Typically these are calculated based on the *"Rule of Three"* as many of these numbers are divisible by 3. A drug will be classified as *Schedule III* if the *opioid quantity is NMT*: - *1.8 grams* of *Codeine per 100 mL* or *90 mg per dosage unit* when combined with an equal or greater quantity of an isoquinoline alkaloid of Opium. - *1.8 grams* of *Codeine per 100 mL* or *90 mg per dosage unit* when combined with one or more active non-narcotic ingredients. - *1.8 grams* of *Dihydrocodeine per 100 mL* or *90 mg per dosage unit* when combined with one or more active non-narcotic ingredients. - 300 mg of Ethylmorphine per 100 mL or 15 mg per dosage unit when combined with one or more active non-narcotic ingredients. - 500 mg of Opium per 100 mL or grams or 25 mg per dosage unit when combined with one or more active non-narcotic ingredients. - *50 mg* of *Morphine per 100 mL or grams* when combined with one or more active non-narcotic ingredients.

Electronic Controlled Substance Prescriptions- Recordkeeping Requirements

When a prescription is received electronically, federal law requires that the prescription and all required annotations (i.e., prescription corrections) must be *stored electronically* for at least *two years*. Some states have stricter requirements. The longest is Arizona, which requires keeping prescription records for seven years.