The approach to tapering depends on the patient history, current status, financial/coverage resources, and provider access/resources. Patients should be well-supported throughout and the taper carefully designed for the individual patient. Patients on chronic opioids experience physical dependence leading to withdrawal symptoms during tapering. Providers must be aware of patient overall health status and substance use including substances of abuse as well as other prescribed medications. The interprofessional team should be involved. Resources beyond medication therapy should be engaged liberally and to all extent possible.

Motivational Interviewing: a start for tapering conversations

Ask about the positives and negatives from the patient's perspective
Reflect any responses and emotions
Listen carefully and then link together positives and negatives
- "On one hand, you still are not able to do all the things you want to and you are worried about the risks related to opioids but, you are also scared about withdrawal and not having anything to manage your pain"
Ask - Tell - Ask
- Ask permission to provide information: "I have some information that I would like to share with you about opioids. Would today be a good day to discuss this?"
- Tell individualized benefits and risks (sleep apnea, hormonal changes, mood, risk of death, hyperalgesia, interdose withdrawal), recommend specific tapering strategies, and discuss withdrawal management including how other patients have fared
- Ask what patient thinks of the information you have shared and engage them in the plan

Tapering with abuse/addiction

The focus of this online module is primarily tapering of opioids in the context of chronic pain treatment. When determining to taper and realizing that a patient is abusing or addicted to opioids, a full regimen for treatment of opioid use disorder should be initiated. The individualized regimen should include psychological support and interventions, medication assisted therapy, family engagement, employment support, and measures to reformulate the individual's life, support network, and treatment of underlying physical, emotional, and psychological disease states. Managing future pain in this context should avoid all potentially addictive substances and the individual should strive to avoid all other addictive substances whether legal (i.e. alcohol, nicotine) or otherwise as they progress through treatment.

Tapering for chronic pain treatment

Goal is to prevent significant withdrawal symptoms while reducing or discontinuing opioids. Gradual tapers often take 1-6 months but may take as long as 18-24 months for patients at higher risk of adversity from tapers, higher starting doses, or longer history of chronic use.

Many patients will experience improvement in functionality and significant reduction of pain after tapering off or to a lower dose of opioid even if their pain increases at first.

Start by answering a few questions

How long has the patient been on the opioid?
What is their current total daily dose in MME?
What else are they doing for chronic pain management at this time?
Are they more likely to have difficulty with tapering? (taper more slowly if ...)
- Multiple comorbidities
- Polysubstance abuse (see left column)
- Female (if so, are they pregnant?)
- Older age
- Long history of chronic opioid use
Goal of dose reduction or discontinuation?
Inpatient or outpatient setting?
What agent will you use for the taper?
What format will you follow?
What will your first step be and when will you follow-up?

1. Setting?

Inpatient

The opioid taper may be done with more significant reductions at a more rapid pace (i.e. 25-50% every 4 days)
Monitor carefully utilizing an opioid withdrawal scale such as the Clinical Opiate Withdrawal Scale (COWS) and actively manage the more severe withdrawal symptoms that will occur
Select if patient is already admitted for a related or non-related indication, patient has significant concerns related to adverse effects and/or abuse/addiction that necessitate a rapid detoxification, patient is not appropriate for outpatient tapering, patient desires more rapid taper and withdrawal, or patient/provider agreement

Outpatient

Often, the outpatient setting is appropriate and a more patient-centered approach
Utilize with a therapeutic relationship
Most appropriate for chronic pain patients where alternative treatments will need to be explored concurrently

2. Agent?

The agent to use is patient and situation-dependent. If a patient is on a lower dose of a short-acting (immediate release) agent then simply tapering off of that agent in a few steps may be done. If a patient is on a single long-acting or extended-release opioid then simply tapering off of that agent based on available dosage forms may be done.

Switching to fixed dose regimen of a longer half-life or extended release formulation may be considered if a patient is having side effects on their current opioid, is on a high dose of short-acting opioids, or is on a combination of multiple agents. Commonly utilized agents include MS Contin(R), Oxycontin(R), or methadone. In a patient on multiple opioids at the initiation of a taper, you can either transition to one opioid, or start by tapering the opioid that is thought to be providing the least amount of relief to build patient confidence. See Tapering Tools below to learn how to conduct the switch.

Short acting, as needed, medication use should be stopped as variation in dosing will adversely impact a tapering plan.

Acetaminophen from combination products should be accounted for and provided separately from the tapering opioid.

When tapering off of an extended release product, some patients may not be able to discontinue directly from the lowest dosage form available. At this point, switching to a shorter acting formulation of the same opioid may allow for more tapering steps. Knowledge of available dosage forms, the option to half certain tablets, and/or the availability of a liquid formulation is important. Additionally, patient comorbidities must be considered in selecting an opioid such as avoiding morphine in renal impairment.

3. Format?

Decrease dose by 10% per week
- 5-10% every 2 to 4 weeks or 10-20% every 1 to 3 weeks are alternative options
- Decrease dose first then increase interval
- An initial reduction of up to 20-25% may be done however additional caution, time, and monitoring are required. Alternative medications and modalities must be explored concurrently
- With short term chronic use, such as post-procedure, a reduction of one tablet per day every 3 days may be done
Educate on increased overdose risk if returning to old higher dose abruptly
- Tolerance is lost within1 to 2 weeks of a taper step
- Patients are at high risk for overdose if they resume their pre-taper dose
- Provide access to and education on naloxone use to patient and family
Provide close follow-up with the interprofessional team
- Engage patient, family, pharmacist, behavioral health professionals, support groups, and other clinic and local resources
- Provide alternative therapies and modalities
- Adjust rate and duration of taper based on patient response
- Do not reverse the taper; slow down or pause the taper to manage withdrawal symptoms
- Provide patient education on opioid withdrawal symptoms and incorporate treatment to relieve emergent withdrawal symptoms
- Encourage patient throughout process
Once a third of the original dose is reached ... smaller dose reductions such as 5% with longer intervals between reductions (every 2 to 8 weeks) may be more optimal for a successful taper
Once the smallest available dose is reached ... extend the interval a step at a time then, stop after patient is on a once a day bedtime dose

Tapering Tools

Calculate Morphine Milligram Equivalents (MME)

Stepwise approach to calculate MME:

Determine the total daily doses of current opioid medications (including as needed use)
Convert each dose into MMEs by multiplying the dose by the conversion factor
If more than one opioid medication, add together

Now switch to an alternative opioid if desired:

Determine equivalent daily dose of new opioid by dividing the calculated MMEs of current opioid by new opioid’s conversion factor
Reduce this amount by 25-50% for incomplete cross tolerance
Utilize an available dosage form and divide into appropriate intervals to obtain new dosing regimen

Resources: Opioid Conversion Table and Calculating Total Daily Dosage of Opioids for Safer Dosage

Online option to double check yourself: Opioid Calculator

Manage opioid withdrawal symptoms

Utilize the below table compiled by the American Academy of Family Physicians (AAFP) as a part of their Chronic Pain Management Toolkit to provide assistance to patients with management of patient withdrawal symptoms.

Educate patients that most patients have improved function without worse pain after tapering opioids even if the pain gets worse at first.

Lucemrya (lofexidine hydrochloride)

Structural analog of Clonidine with clinical trials showing comparable efficacy. Lofexidine is a little more selective for the alpha2 receptor which may reduce side effects. FDA approved May 2018 for the mitigation of withdrawal symptoms to facilitate abrupt discontinuation of opioids in adults. First FDA approved non-opioid for managing withdrawal symptoms .
Central alpha-2 adrenergic agonist that works by binding to receptors on adrenergic neurons, decreasing sympathetic tone and reducing the release of norepinephrine.
- Chronic opioid use suppresses noradrenergic outflow and thus norepinephrine release.
- During acute withdrawal adrenergic outflow is restored and causes many of the symptoms associated with withdrawal including diaphoresis, hypertension, nausea, tachycardia, and vomiting.
- Lofexidine does NOT suppress cravings.
Dosing is three 0.18mg tablets four times daily for the first 5-7 days following last opioid use during peak symptoms and then it is continued for up to 14 days with symptom-guided dosing. Maximum total daily dose is 2.88mg (16 tablets), maximum single dose is 0.72mg (4 tablets). Discontinue gradually over 2 to 4 days to mitigate its own withdrawal symptoms. Reduce by 1 tablet per dose every 1 to 2 days.
Renal dose adjustments if CrCl < 90 mL/min and Hepatic dose adjustments in moderate to severe impairment. Consult drug information resource.
Adverse effects: Orthostatic hypotension (29-42%), Bradycardia (24-32%), Hypotension (30%), Insomnia (51-55%), Dizziness (19-23%), Sedation (12-13%), Drowsiness (11-13%), Xerostomia (10-11%)
Pricing: $24.83 per tablet (generic Clonidine 0.1mg tablets are ~$0.30 each)
Counsel on risk of hypotension and monitor for low blood pressure and/or pulse. Can be taken with or without food.

LexiComp. Lofexidine. Accessed 3/5/2019.; Lucemyra Webpage.; Pharmacy Times Article.

Morphine Milligram Equivalents (MME) that a patient is taking in a 24 hour period is a tool to utilize at the start of and throughout the taper process. Make sure in calculating this amount to include all formulations of opioid being used and to verify actual use of any as needed (PRN) medications to get an accurate calculation.

Utilize available opioid formulations

Utilize information on available dosage forms, strengths, and common dosing intervals to assist with tapering plans.

For conversion to/from as well as titration/tapering of any fentanyl product you consult fentanyl product-specific labeling.

Methadone dosing interval varies and requires specific care and unique dosing when initiating use. Consult labeling.

Practice Constructing Tapers ...

Kara is a 40-year-old female patient on Kadian (morphine ER) 80mg po daily and Oxycodone/Acetaminophen 10/325mg po q6h PRN for chronic noncancer pain. She is taking 4 doses of the supplemental each day. Review of controlled substances database supports her self-report and does not raise any red flags. She states that the opioids are not working as well anymore and is interested in alternative regimens or medications. Pregnancy test is negative and intrauterine device (IUD) is in place.

What is her current daily MME and current daily Acetaminophen dose?
- Kadian 80mg (Morpine ER) daily = 80 MME
- Oxycodone/Acetaminophen 40/1,300mg/day = 40 * 1.5 = 60 MME
- Total daily MME = 140 *** Incomplete cross tolerance has NOT been accounted for ***
- 325mg acetaminophen * 4 doses per day = 1,300mg acetaminophen per day
- Total daily acetaminophen dose = 1,300mg
What acetaminophen dose do you recommend?
- Equivalent: Regular strength 325 mg po four times daily (same dose) OR
- Nearly equivalent but easier to obtain/take: Extra strength 500mg three times daily OR
- Maximized regimen: Extra strength 500mg two tablets four times daily
- Choose regimen based on patient preference, comorbidities, and considering pain management optimization
She is ready and willing to taper to a lower opioid dose. What do you recommend?
- She could stay on current medications and taper the supplemental first. If doing this, the acetaminophen will be tapered as well so will need to be reconsidered along the way. Oxycodone/Acetaminophen will likely need to be switched to plain Oxycodone or supplemented with Acetaminophen separately along the way to maximize Acetaminophen benefit. Doses of the supplemental should be fixed, not as needed.
- Switch to a single opioid and taper. Separate out Acetaminophen and provide separately as above.
  - If going to only Morphine ER reduce by 25-50% to account for incomplete cross tolerance.
    - 140mg MME * 0.75 = 105mg MME
    - 140mg MME * 0.50 = 70mg MME
    - 70-105mg morphine for new regimen
    - Kadian 100mg po daily for for 2 weeks (already reduced with switch) and then reduce by 10% to Kadian 90mg po daily for 2 weeks ... reevaluate at each step. Is the goal dose reduction or discontinuation?

60 year old male patient had orthopedic surgery 2 months ago and is doing well but is concerned about running out of his pain medications though he knows they are not forever. He did not take any opioids prior to the procedure. He has been taking two tablets of Hydrocodone/Acetaminophen 5/325 mg every 6 hours. How can you help him taper off?

What is his current MME and current Acetaminophen dose?
- Hydrocodone/Acetaminophen 40/2,600 mg daily = 40 * 1 = 40 MME
- Total daily MME = 40
- Total daily acetaminophen dose = 2,600 mg
What taper do you recommend?
- Note that use is shorter term so tapering may be able to be done more rapidly than with long-term chronic users
- Reduce by one tablet per day every 3 days until he is off which will take about 3 weeks. Last dose stopped is bedtime dose. See below example for tablets/time of day.
  - 1/2/2/2 for 3 days
  - 1/2/1/2 for 3 days
  - 1/1/1/2 for 3 days
  - 1/1/1/1 for 3 days
  - 1/0/1/1 for 3 days
  - 1/0/0/1 for 3 days
  - 0/0/0/1 for 3 days
  - No more

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