Opioid Conversion Calculations

Opioid Conversion Calculations

Mary Lynn McPherson, Pharm.D., BCPS Professor, University of Maryland School of Pharmacy mmcphers@rx.umaryland.edu

Disclosure • Nothing to Disclose

Learning Objectives • At the conclusion of this lecture, the participant will be able to: – Describe the rationale for rotating patients from one opioid to another when treating chronic pain.

– Explain the appropriate use of Equianalgesic Opioid Dosing chart to include the limitations of the data.

– Outline conversion protocols for alternative opioid therapies (such as routes of administration, oral dosages, and controlled release delivery systems).

– Describe how to reduce barriers and address concerns regarding opioids and opioid rotation so that the patient and family/caregiver can make more informed decisions about pain management, improve patient outcomes and adherence to therapy.

Reasons for Changing Opioids • • • •

Lack of therapeutic response Development of adverse effects Change in patient status Other considerations – Opioid/formulation availability – Formulary issues – Patient/family health care beliefs

• Opioid rotation, substitution, switching • Opioid Conversion Calculations!

Seizing the Teachable Moment • Explaining WHY to patients, families, caregivers (and other practitioners): – Improved pain management • Less troughs/valleys – LA oral, transdermal fentanyl and buprenorphine

– Enhanced adherence to opioid therapy – Improved patient outcomes • Better analgesic effects • Better functional status • Fewer adverse effects

Equianalgesic Dosing Terminology • Opioid responsiveness – The degree of analgesia achieved as the dose is titrated to an endpoint defined either by intolerable side effects or the occurrence of acceptable analgesia

• Potency – Intensity of the analgesic effect of a given dose – Dependent on access to the opioid receptor and binding affinity

• Equipotent doses = equianalgesic • Equianalgesic Opioid Dosing

Converting Among Routes: Same Opioid • Bioavailability – The rate and extent to which the active ingredient or active moiety is absorbed from a drug product and becomes available at the site of action

• Oral bioavailability – – – –

Morphine 30-40% (range 16-68%) Hydromorphone 50% (29-95%) Oxycodone 80% Oxymorphone 10%

Equianalgesic Opioid Dosing Equianalgesic Doses (mg) Parenteral Oral

Drug Morphine Buprenorphine Codeine Fentanyl Hydrocodone Hydromorphone Meperidine Oxycodone Oxymorphone Tramadol *Not available in the US

10 0.3 100 0.1 NA 1.5 100 10* 1 100*

30 0.4 (sl) 200 NA 30 7.5 300 20 10 120

McPherson ML. Demystifying Opioid Conversion Calculations: A Guide For Effective Dosing. Amer Soc of Health-Systems Pharm, Bethesda, MD, 2010. Copyright ASHP, 2010. Used with permission.

NOTE: Learner is STRONGLY encouraged to access original work to review all caveats and explanations pertaining to this chart.

The Problem with “Those Charts” • Source of equianalgesic data • Patient-specific variables • Unidirectional vs. bidirectional equivalencies

5-Step OCC Process 1. Globally assess pain complaint (PQRSTU) 2. Determine TDD current opioid (LA and SA) 3. Decide which opioid analgesic will be used for the new agent and consult established conversion tables to determine new dose 4. Individualize dosage based on assessment information gathered in Step 1 5. Patient follow-up and continual reassessment (7-14 days) Gammaitoni AR, et al. Clinical J Pain 2003;19:286-297

BJ is a 42 year old man with chronic low back pain, receiving LA oral morphine 45 mg by mouth q12h around the clock. He was admitted to the hospital for back surgery. What would be an EQUIVALENT dosage regimen of IV morphine?

A. B. C. D. E.

Morphine 5 mg IV every 4 hours Morphine 10 mg IV every 4 hours Morphine 15 mg IV every 4 hours Morphine 30 mg IV every 4 hours Morphine 45 mg IV every hours

Conversion Conversations • Same opioid, from one oral dosage formulation to a different oral dosage formulation • Same opioid, from one route of administration to another route of administration • From one opioid to a different opioid, regardless of dosage formulation • Conversions to/from transdermal opioids

Same Opioid (PO → PO): Case 1 • HW is an 84 year old man in a LTC facility with general debility on oxycodone 5 mg/acetaminophen 325 mg tabs, six per day, pain well controlled.

• He can no longer swallow the tablets and his physician asks you convert him to an oral solution of oxycodone 5 mg/acetaminophen 325 mg per 5 ml.

Case 1 1. Pain assessed; stable and controlled 2. Six tabs x 5 mg oxycodone per day = 30 mg TDD oral oxycodone 3. Switching to 5 ml oral oxycodone/acetaminophen solution (5/325 per 5 ml); also dosed every 4 hours. Dose is 5 ml (5 mg oxycodone/325 mg acetaminophen per 5 ml) q4h 4. Individualization – oxycodone is oxycodone; no need to change dose 5. Monitor response

Case 2 • GV is a 48 year old man with rectal cancer, referred to hospice for palliative care. He is receiving hydromorphone 2 mg every 4 hours, and the best his pain gets on this regimen is a 6 or 7 (on a 0-10 scale).

• He also tells you the every 4 hour dosing is very inconvenient and the hydromorphone doesn’t seem to last the full four hours.

• You decide to recommend switching him to EXALGO, the once a day hydromorphone ER tablet. It is available as 8, 12, 16 mg tablets.

Case 2 • Patient on hydromorphone 2 mg po q4h, pain not controlled.

• Switch to EXALGO (8, 12, 16 mg tablets).

• What do you recommend: – – – –

A. 8 mg once a day B. 12 mg once a day C. 16 mg once a day D. 20 mg once a day

Same Opioid (∆ ROA): Case 3 • WP is a 62 year old man with multiple myeloma and diffuse bony mets admitted to hospice.

• Current analgesic regimen extended-release oral morphine 30 mg po q12h plus oral morphine solution 10 mg prn (takes six times per day), plus dexamethasone.

• Admitted to inpatient to switch to IV morphine due to continued pain.

• Oral to IV morphine – divide or multiply by 3?

• TDD oral morphine = 30 mg po q12h = 60 • MS soln 10 mg x 6 = 60 mg; TDD = 120 mg oral morphine • Consult equianalgesic dosing chart for equivalency

Case 3 TDD current opioid X EAF new opioid = EAF current opioid 120 mg oral morphine X 10 mg IV morphine = 30 mg oral morphine 40 mg TDD IV morphine 25-50% increase - MS 7.5 or 10 IV q4h (TDD 45-60 mg) EAF – equianalgesic factor

Case 4 • BJ is an 82 year old woman with severe osteoarthritis of the knees. She has been receiving morphine 5 mg po q4h (during waking hours) for the past several years.

Unfortunately she suffered a stroke recently and she cannot swallow tablets or even oral solution.

• Her physician wants to switch her to rectal morphine suppositories.

• Available as 5, 10, 20, 30 mg suppositories.

• What do you recommend?

– – – –

A. 2.5 mg pr q4h during waking hours B. 2.5 mg pr q6h during waking hours C. 5 mg pr q4h during waking hours D. 10 mg pr q4h during waking hours

Case 5 • Mrs. Claytor is a 62 year old woman with pancreatic cancer.

• Her pain is well controlled, but she is unable to swallow the LA morphine tablets (200 mg po q12h) or even the oral morphine solution (40 mg q3h prn breakthrough pain, she uses about one dose per day).

• Her physician would like to switch her to a parenteral SQ morphine infusion.

Recommendation?

Case 5 “x” mg SQ morphine = 440 mg oral morphine

10 mg SQ morphine 30 mg oral morphine

• Cross multiply and solve for “x” as follows: – – – – – –

(30)(x) = (10)(440) 30x = 4400 x = 146.7 mg SQ morphine per day 146.7 / 24 hours = 6.1 mg/hour Recommend 5 mg/hour What about a bolus? What do you recommend?

Case 5 • Bolus dose?

– 50-100% of hourly infusion rate – 2.5-5 mg every 30 minutes SQ (could extend dosing interval once stable)

• When should the continuous infusion start relative to the last dose of LA morphine?

– A. Take one last dose LA morphine and start infusion – B. Take one last dose LA morphine and start infusion 812 hours later – C. Start infusion and take one last dose LA morphine 6 -8 hours later

∆ Opioid (and Route/Formulation): Case 6 • Mrs. Smith is a 92 year old woman with breast cancer, currently receiving LA morphine 60 mg po q12h, plus oral morphine solution 20 mg po q4h prn, taking on average 3 doses per day.

• She has been on this dose for about 2 weeks, and her pain is well controlled, but she has developed visual hallucinations which she finds quite frightening.

• She has significant renal impairment (serum creatinine of 2.0 mg/dl) and this adverse effect may be due to accumulation of morphine metabolites.

• Her physician would like to switch her to LA oxycodone.

What are the steps necessary to make this conversion?

Setting up the Conversion Equation 1.

2.

Calculate total daily dose of current opioids.

Set up conversion ratio between old opioid (and route of administration) and new opioid (and route of administration) as follows:

“x” mg new opioid/route = mg of current opioid/route “x” mg oral oxycodone = 180 mg oral morphine

equivalent mg new opioid/route equivalent mg current opioid/route 20 mg oral oxycodone 30 mg oral morphine

(x)(30) = (20)(180) X = 120 mg oral oxycodone per day

Solving the Equation • Individualize dose for patient – Pain controlled; developed adverse effect; reduce 25-50% – Calculated oxycodone 120 mg po qd – Reduce to 60-90 mg po qd

• Decide how many times per day you’re going to dose the new opioid; divided by the appropriate dosing interval, and select a dosage that is available in that strength.

• LA oxycodone 30 mg po q12h with oxycodone IR 10 mg po q2h prn, or • LA oxycodone 40 mg po q12h with oxycodone 10 mg po q2h prn

∆ To/From Transdermal Formulation: Case 7 • Mr. Johnson is a 62 year old cancer pain patient who is unable to swallow tablets or oral solution.

• He refuses rectal administration of medications, and is not interested in a parenteral infusion.

• He is currently receiving LA oral morphine 30 mg po q8h with oral morphine solution 10 mg po q3h prn (taking about 4 doses per day).

• His pain is well controlled on this regimen.

• What do you need to consider before converting him to transdermal fentanyl (TDF)?

– Opioid tolerance, body habitus, fever, pain intensity/stability

• How do you make this conversion?

Case 7 • Calculate total daily dose of morphine: – LA morphine 30 mg po q8h = 90 – IR morphine 10 mg x 4 per day = 40 – TDD = 130 mg oral morphine

• Generally give 50% of total daily morphine dose as transdermal fentanyl – 65 mcg – need to round up or down – TDF 12, 25, 50, 75, 100 – Transdermal fentanyl 50 mcg q3days

• Considerations? Timing?

Case 8 • MR is a 91 year old woman with an end-stage malignancy.

• She had been maintained on transdermal fentanyl 50 mcg every 3 days.

• Her pain progressed, and the fentanyl was increased to 75 mcg, and then 100 mcg.

• Unfortunately, the recent dosage increases did not appreciably result in pain relief.

• MR is 5’4”, and weighs 78 pounds.

• She is hypotensive and bed-bound.

• She can swallow tablets and capsules, and the physician would like to switch her to oral long-acting oxycodone.

• What do you recommend?

Case 8 • Transdermal fentanyl 100 mcg is approximately equal to 200 mg oral morphine per day.

• HOWEVER, she is very thin, and has not achieved appreciable pain relief with the dosage increase from the 50 mcg patch (equivalent to 100 mg oral morphine per day).

• Total daily dose of morphine = 100 mg • Total daily dose of oxycodone = 66 mg • LA oxycodone 30 mg po q12h with IR oxycodone10 mg po q2h prn breakthrough pain.

• Or, oxycodone 10 mg po q4h with an additional 10 mg q2h prn breakthrough pain.

Case 9 • AL is a 62 year old man with a history of prostate cancer admitted to the hospital for a course of palliative radiation.

• Patient on TDF 50 mcg/h; you have been asked to switch him to a continuous IV infusion of fentanyl.

• He has oral morphine 15 mg po q2h prn for breakthrough pain available.

• AL is not in pain at this time.

Case 9 • At time zero, remove TDF patch, establish IV access • Provide bolus dose option, fentanyl 25 mcg every 20 minutes for the first 6 hours • At 6 hours, the continuous infusion of fentanyl should begin at 25 mcg/h, keep bolus option • At 12 hours increase IV infusion of fentanyl to 50 mcg/h and bolus option remains in place. Adjust as needed.

Case 10 • AL, our 62 year old man with prostate cancer admitted for palliative radiation has completely his course and is ready for discharge home.

• His current fentanyl infusion is 70 mcg/h, and he has only used his 35 mcg bolus once in the past 24 hours.

• He would like to resume TDF therapy.

• What do you suggest and how?

Case 10 • 70 mcg/h infusion – round to closest TDF strength – 75 mcg/h • 8 am – apply 75 mcg/hr TDF patch, continue infusion and bolus option • 2 pm (6 hours later) – reduce continuous infusion to 35 mcg/h and maintain bolus option • 8 pm (12 hours later) – discontinue continuous infusion, maintain bolus option or switch to oral rescue analgesia at this time • 8 am – discontinue infusion and discharge

Case 11 • ET is a 68 year old woman with severe osteoarthritis of the hips and knees, for which she takes acetaminophen and a NSAID. • This therapy has not adequately reduced her pain, and she continues to complain of dyspepsia from the NSAID. • She also complains that taking medication multiple times per day makes her feel like a “druggie” and she hates the reminder of her pain.

• She heard about a pain patch that was new on the market – what is she referring to, and what do you recommend?

Case 11 • Butrans – transdermal buprenorphine, every 7 days • Approved for moderate to severe chronic pain in patients requiring a continuous, around-the-clock opioid for an extended period of time • Available in three strengths: – 5 mcg/hour – 10 mcg/hour – 20 mcg/hour

• May begin opioid-naïve patients at 5 mcg/hour • Do not increase for at least 72 hours

Case 12 • JK is a 64 year old man with cervical and lumbar back pain that is fairly response to oxycodone/acetaminophen therapy (5/325), using about six tablets per day (when he remembers to take them). • When he gets busy and forgets to take his analgesic the pain overwhelms him and he has to stop everything and lie down. • His neighbor ET told him about this new pain patch (Butrans) that works well for her, so he wants to know if he can switch to this as well.

Butrans (BU-tranz) • Transdermal buprenorphine indicated for the management of moderate to severe chronic pain in patients requiring a continuous, around-the-clock opioid analgesic for an extended period of time – Osteoarthritis, low back pain, Schedule III

• Advantages over TDF: – Lower abuse potential – Less dangerous in an overdose – Causes fewer withdrawal symptoms

• Contraindications and Precautions – Significant respiratory depression, asthma, paralytic ileus – Acute post-op, mild, or intermittent pain

Butrans • Each patch is meant to be worn for 7 days • Apply to upper outer arm, upper chest, upper back or the side of the chest. Do not re-use site for 21 days.

• In opioid-naïve patients the initial dose should always be 5 mcg/h • Converting to Butrans:

www.butrans.com; Prescribing Information

Case 12 • Patient receiving 30 mg oral oxycodone per day (equivalent to about 45 mg oral morphine per day).

• Reduce patient’s oxycodone to 20 mg per day over the next week – Supplement with acetaminophen as needed, NSAID

• Switch to Butrans 10 mcg/hour

WOF Statements is TRUE? A. Opioid-na誰ve patients may start transdermal fentanyl or buprenorphine as their first opioid B. Twenty milligrams a day of oral morphine is equivalent to 60 mg a day of parenteral morphine C. Oral morphine is more potent than oral oxycodone D. EXALGO is dosed once a day

Final Thoughts 1. Be alert for clinical scenarios that may indicate opioid switching should be recommended 2. Understand/consider principles of opioid responsiveness, potency, equivalence and bioavailability 3. Follow approved labeling for switching in opioid tolerant patients 4. Use the five step process 5. Use a fair balance equianalgesic dosing chart and understand limitations 6. Consider timing of switches 7. Document your interventions and EDUCATE patients and practitioners

Opioid Conversion Calculations

Mary Lynn McPherson, Pharm.D., BCPS Professor, University of Maryland School of Pharmacy mmcphers@rx.umaryland.edu