1. UConn Health John Dempsey Hospital
Methadone therapy for detoxification in medically ill hospitalized patients
Sylvia M. Cavero, PharmD
PGY1 Pharmacy Resident
UConn Health John Dempsey Hospital
May 8th, 2018

2. Disclosure I have no conflict of interest to report
I intend to reference unlabeled/unapproved uses of drugs or products in my presentation

3. Learning Objective
Clarify the FDA regulations regarding methadone prescribing and dispensing in acutely ill hospitalized patients not currently on maintenance therapy
Apply understanding of FDA regulations regarding methadone prescribing and dispensing to a patient case

4. Opioid Epidemic
In 2015 over 20 million Americans had a substance use disorder
Approximately 2 million involved prescription opioids
Approximately 591,000 involved heroin
Many of these patients may become hospitalized for reasons unrelated to illicit drug use
First I would like to briefly review the root cause of the problem that causes this question to be asked.
According to the American Society of Addiction Medicine, in 2015 there were more than 20 million Americans who had a substance use disorder.
Of that statistic, about 2 million Americans abuse prescription opioids, and nearly 600,000 abuse heroin.
Many of these patients will become hospitalized for reasons that are unrelated to their illicit drug use.
In addition, not all patients are forthcoming with their drug use history.
Some patients may even present in such critical condition that they are unable to disclose their history and thus, may go into withdrawal
American Society of Addiction Medicine 2016

5. At this time, I would like to introduce a patient case from a case based review published in the Journal of Addictive Behaviors, Therapy & Rehabilitation.
The title of the case based reviews is shown for you here.

6. Patient Case 40 y/o female presented to the ED via ambulance
History of present illness:
Low back pain
Fever and chills
Left upper extremity redness, swelling and pain
Past medical history:
HIV
Hepatitis B
IVDU x 15 years
A 40 year old female presented to the emergency room complaining of 3 days of low back pain, fever, chills, and left upper extremity redness, swelling, and pain.
Her past medical history consists of HIV, hepatitis B and a 15 year history of IV drug use.

7. Patient Case
Vitals:
The final diagnosis is cellulitis with probable evolving abscess
Temp 37.9°C (100.2°F)
Pulse 82
BP 97/54
Admit for treatment with IV antibiotics
RR 17
Physical exam:
Erythema and swelling
1.5 x 1.5 cm induration
Extending to distal forearm
The patient was febrile on presentation with low pressures approaching hypotensive. On physical exam a 1.5x1.5 centimeter indurated area was noted on the right antecubital fossa with erythema extending to the distal half of the forearm. This area was tender to palpation and slightly warmer than the rest of her.
Ultimately, she was diagnosed with cellulitis and probable evolving abscess in the antecubital fossa and was admitted to the general medicine service for IV antibiotics.
Her past medical history was well known to the facility, as she was considered a “frequent flyer” who often left AMA due to poor control of withdrawal symptoms.
It is important to make note of the fact that in this current hospitalization, the patient did not disclose her active drug use to the attending physician.

8. Fifth Edition (DSM-5), American Psychiatric Association, 2013
Withdrawal Syndrome
May begin within 3-6 hours of last use
May last between 7-10 days
DSM-V diagnostic criteria:
Presence of 3 or more recognized symptoms following:
Cessation of prolonged heavy use
Administration of opioid antagonist
Cause clinically significant distress or impairment
Not attributable to another medical condition
Withdrawal management is part of comprehensive medical care, and with that being said I would like to briefly review what withdrawal syndrome is.
Symptoms of withdrawal may begin within 3-6 hours of last known drug use and can last for 7-10 days. It can be a very uncomfortable situation for the patient.
The DSM-V has specific diagnostic criteria for diagnosing withdrawal syndrome.
Fifth Edition (DSM-5), American Psychiatric Association, 2013

9. Withdrawal Syndrome DSM-V Symptoms: Other possible symptoms:
Dysphoric mood
Nausea/vomiting
Muscle aches
Lacrimation/rhinorrhea
Pupillary dilation, piloerection, sweating
Diarrhea
Yawning
Fever
Insomnia
Other possible symptoms:
Drug cravings
Flu-like symptoms
Restlessness
Mild hypertension
Low grade fever
Listed for you here are the recognized signs and symptoms per the DSM – V criteria for withdrawal syndrome.
Not all patient's experience withdrawal syndrome the same. There is no defined progression of symptoms because it is very patient specific.
Some patients experience only mild symptoms such as a flu-like syndrome which can include a low grade fever.
Others can go on to experience more bothersome symptoms like GI distress and even mild hypertension.
Any of these symptoms may be masked by other conditions…such as an infection
As I said, withdrawal management is considered part of comprehensive medical care, and should NOT be ignored or under-estimated due to unease of using effective therapy outside of a narcotic treatment program.
Addiction. 1994; 89(11):
Fifth Edition (DSM-5), American Psychiatric Association, 2013

10. Current Therapeutic Options
Non-narcotic
Clonidine
Naltrexone
Narcotic
Methadone
Current therapeutic options for withdrawal syndrome related to opioid use disorder fall into 1 of 2 categories:
The first category includes non-narcotic options which are typically used as targeted symptom management
One of the most commonly utilized non-narcotic option is clonidine.
Another is naltrexone
We will not go into to much detail regarding these
The second category includes narcotic options which are typically used as a bridge to maintenance therapy once in an outpatient setting.
One of the most well known and effective narcotic options is methadone.
Pharmacists can play an important role in selecting appropriate therapy to manage a patient in withdrawal. .
Expert Opin Pharmacother, 2009; 10(11):

11. Methadone Full opioid agonist Dose: 10-30 mg daily upon initiation
Limiting factors:
Patient variability
Potential lethality if not initiated correctly
Misunderstanding of regulations outside a narcotic treatment program

12. Patient Case Review 40 y/o female admitted for treatment of cellulitis
Discovered to be in withdrawal
Cannot tolerate clonidine
Threatening to leave AMA prior to therapy completion
A 40 y/o female is admitted to the general medicine service for treatment of a cellulitis with evolving abscess. During her hospitalization it is discovered that she is an active heroin user, and is now undergoing withdrawal. It is determined that she cannot tolerate clonidine, and she is threatening to leave AMA prior to therapy completion.

13. Attending physician recommends initiating a three day methadone taper and referral to an outpatient narcotic treatment program
One of the attending physicians has an idea that he suggests to the team.
He recommends starting a methadone taper over 3 days, and referring the patient to an outpatient narcotic treatment program.

14. What is the correct response to this recommendation?
Assessment Question 1:
What is the correct response to this recommendation?
This action is inappropriate and considered illegal
This requires someone with the correct DEA license to complete
This action is considered appropriate and legal
The patient should first complete antibiotic therapy outpatient
My question for you is as follows:
What is the correct response to this recommendation?...
In order to answer this question, we need to review and clarify the law

15. Title 21 Code of Federal Regulations
§ Administering or dispensing of narcotic substances
Requires two conditions be met:
Separate registration with the DEA
Compliance with DEA regulations pursuant to the Act
Not prohibited from relieving acute withdrawal when necessary
Maintain/detoxify a person
Incidental to medical or surgical treatment
No more than three days of therapy – Three Day Rule
Title 21 of the Code of Federal Regulations subsection 1300 and on provides guidance on the rules and regulations regarding narcotic substances. This includes registration requirements, handling, prescribing and dispensing, scheduling, etc.
Subsection is specific to rules regarding administration and dispensing of narcotic substances.
The regulations say two conditions MUST be met in order for a practitioner to administer or dispense a narcotic drug in any schedule for the purpose of maintenance OR detoxification. Those are that the practitioner is separately registered with the DEA as a narcotic treatment program. And that the practitioner is in compliance with the regulations regarding treatment qualifications, security, records, and unsupervised use of the drugs pursuant to the Act.
Paragraph B further goes on to state that nothing in this section shall prohibit a physician who does not meet the aforementioned requirements from administering narcotic drugs to a person for the purpose of relieving acute withdrawal symptoms when necessary while arrangements are being made for referral for treatment.
Paragraph C states that this section of the law is not intended to impose any limitations on a physician or hospital staff to administer or dispense narcotics in a hospital setting. As long as it is to maintain or detoxify a person as an incidental adjunct to medical or surgical treatment of conditions other than addiction.
The regulations also state that no more than one day’s medication may be administered at one time, and emergency treatment can be carried out for no more than 3 days and this is called the three day rule.
US Drug Enforcement Administration Office of Diversion Control

16. What is the correct response to this recommendation?
Answer:
What is the correct response to this recommendation?
This action is inappropriate and considered illegal
This requires someone with the correct DEA license to complete
This action is considered appropriate and legal
The patient should first complete antibiotic therapy outpatient
So, with all that in mind, what is the correct response to the attending physicians recommendation to start methadone therapy.

17. What is the correct response to this recommendation?
Answer 1:
What is the correct response to this recommendation?
This action is inappropriate and considered illegal
This requires someone with the correct DEA license to complete
This action is considered appropriate and legal
The patient should first complete antibiotic therapy outpatient
According to the Code of Federal Regulations subsection ,
It is perfectly legal to administer methadone therapy for detoxification purposes, in a medically ill hospitalized patients who cannot tolerate non-narcotic options. This is because of the “Three Day Rule” established by Title 21 of the Code of Federal Regulations Part paragraph B

18. Assessment Question 2: Fill in the blank:
The “three day rule” allows a practitioner who is not separately registered as a narcotic treatment program to, but not , narcotic drugs to a patent for the purpose of relieving acute withdrawal symptoms.
Administer, prescribe
Dispense, refill
Recommend, prescribe
Prescribe, administer

19. Answer 2: Fill in the blank:
The “three day rule” allows a practitioner who is not separately registered as a narcotic treatment program to, but not , narcotic drugs to a patent for the purpose of relieving acute withdrawal symptoms.
Administer, prescribe
Dispense, refill
Recommend, prescribe
Prescribe, administer

20. Case Based Review Conclusions
A review of the medical and legal literature was conducted
Methadone for opioid withdrawal and maintenance
Critically ill hospitalized patients
Conclusion:
Methadone is effective AND legal for acutely ill hospitalized patients

21. Pearls in Summary
Managing opioid withdrawal is part of the comprehensive care
Methadone is an appropriate choice when:
A patient is hospitalized for reasons other than their use disorder
Cannot tolerate non-narcotic options
No more than one day’s supply may be administered at a time
Three day rule applies to inpatient management
Outpatient referral should be arranged for these patients

22. UConn Health John Dempsey Hospital
Methadone therapy for detoxification in medically ill hospitalized patients
Sylvia M. Cavero, PharmD
PGY1 Pharmacy Resident
UConn Health John Dempsey Hospital
May 8th, 2018