1. Opioid therapy for pain
Elizabeth Whiteman M.D.

2. Goals and objectives Understand appropriate opioid use for pain
Understand side effects of opioids
Learn to treat and prevent side effects
Routes of administration
Equianalgesic dosing
Develop competence in treating pain and use of opioids

3. Opioid Dosing Opioid starting dose depends on:
Patient’s age, weight, cachexia
Total doses of previous analgesics
Frequency and severity of pain

4. Starting opioids Opioid naive patient start slow
Oral first line if patient can swallow
Short acting prn, or around the clock if constant pain
Can then calculate long acting needs
Convert to long acting PO and make sure patient has breakthrough short acting for prn

5. Sublingual formulas not good bioavailability
But can use liquid morphine orally
Rectal dosing if patient able
Routine dosing around the clock (q4-6hr)
IV or Subcutaneous infusion if need rapid titration or unable to take other route

6. Opioid titration Titration for increases in pain
Oral morphine: 4 hr duration, 2hr peak
IV/SC morphine min peak
Titrate prn: ½ of the 4hr dose
(about 10% of the 24 hr dose)
eg: 10mg q4hr ATC with 5mg prn q2hr

7. Opioids Tolerance Dependence Addiction
pharmacologic property, less drug effect over time
Dependence
pharmacological response, uncomfortable side effects when drug is withheld
Addiction
Behavior problem, compulsive use and craving for psychological gain

8. Opioid side effects Constipation Nausea Sedation and confusion
Always start laxatives with opioids
Fluid intake
Nausea
Sedation and confusion
Urinary retention
Myoclonic jerks
Pruitis

9. Myoclonic Jerking Often seen in: Treatments
renal or hepatic insufficiency
Treatments
Benzodiazepines
Control electrolytes
Opioid rotation
Progressive Myoclonis-seizures
Reduce or rotate opioid

10. Delirium Can be both hypoactive or hyperactive Often seen in:
Renal or hepatic insufficiency
Elderly
Alcohol or benzodiazepine withdrawal
Patients with underlying dementia
Brain metastasis
Treatment
Decrease or rotate opioid
Assess other medication which can contribute
Antipsychotic medications

11. Respiratory Depression
Often seen in:
COPD
Chronic lung disease
Upper airway compromise
Pneumonia
Treatment
Reduce opioid
Switch to short acting agents
Avoid drug with active metabolite
Use diluted naloxone (only if indicated)

12. Treatment of side effects
Reduce opioid dose
Add adjuvant drug if indicated
Treat symptoms (may be temporary)
Hold medicine if feel patient got too much and reassess
Opioid rotation- try other agents

13. Special populations Frail elderly Liver patients Dementia
Renal failure
Drug users
Pediatrics
HIV patients

14. Drugs to avoid / caution
Meperidine (Demerol)
Butorphanol(Stadol)
Propoxyphene(Darvon)
Pentazocine(Talwin)
Caution, case by case
Methadone(Dolophine)
Transdermal Fentanyl(Duragesic)

15. Duragesic patch Use if no other route po or rectal
If patient is on it, assess if really working
Need to have some subcutaneous fat
Drug is lipophilic, distributed in fat
Remember takes hours to work
Also slow to get out of system, cant just pull off patch
Not for use on opioid naive patients
Patient should be already on 45mg/day or more Morphine Sulfate

16. Methadone Good for both nociceptive and neuropathic pain
Patient need to have time to titrate
Lasts longer, but may need q 8 hr titration
Long action hours
Need to use case by case
Not as appropriate in patients with short life expectancy or risk side effects

17. Equianalgesic dosing
When changing routes of administration be familiar with an equianalgesic table
Equivalent dosing are guides, individual patients may require more dose adjustment
Calculate for incomplete cross tolerance, start with 50-75% of the equianalgesic dose

18. Converting oral to parenteral
Always calculate back to morphine/24hr
Drug PO SC or IV
Morphine 20mg (divide by 3) = 7mg
Hydromorphone 5mg (divide by 5) = 1mg

19. EQUIANALGESIC DOSES OF OPIOIDS (EPEC Project 1999, Module 4)
ORAL/RECTAL DOSE (MG) ANALGESIC PARENTERAL DOSE (MG)
Codeine 60
– Fentanyl
15 Hydrocodone –
4 Hydromorphone 1.5
2 Levorphanol 1
Meperidine 50
10 Methadone 5
15 Morphine 5
10 Oxycodone –

20. Fentanyl Patch conversion
TABLE 1: DOSE CONVERSION GUIDELINES
Current Analgesic Daily Dosage (mg/day)
Oral morphine
IM or IV morphine
Oral oxycodone
Oral codeine
Oral hydromorphone
Intravenous hydromorphone
Intramuscular meperidine
Oral methadone
DURAGESIC recommended 25mcg/hr 50mcg/hr 75mcg/hr 100 mcg/hour
Source: Ortho-McNeil, Inc All rights reserved. 
1 Table 1 should not be used to convert from DURAGESIC to other therapies because this conversion to DURAGESIC is conservative. Use of Table 1 for conversion to other analgesic therapies can overestimate the dose of the new agent. Overdosage of the new analgesic agent is possible [see Dosage and Administration (2.3)].

21. Fentanyl patch Key Considerations
All equianalgesic ratios/formulas are approximations; clinical judgment is needed when making dose or drug conversions.
The risk of sedation/respiratory depression with transdermal fentanyl is probably increased in the elderly or patients with liver and renal impairment due to its long half-life, thus, choose the lower end of the dosing spectrum.
When in doubt, go low and slow, using prn breakthrough doses generously while finding the optimal dosage of a long-acting drug.
Other teaching points about Duragesic:
Start at the lowest dose, 12 mcg/hr, in an opioid naïve patient; there is no maximum dose.
Therapeutic blood levels are not reached for hours after patch application and drug will be continue to be released into the blood for at least 24 hours after patch removal.
Opioid withdrawal symptoms can occur during dose conversions—care must be taken to avoid this by use of breakthrough opioids.
Some patients will need to have their patches changed every 48 hours.
The recommended upward dose titration interval is no more frequently than every 72 hours.
Place patches on non-irradiated, hairless skin.
Direct heat applied over the patch can increase drug absorption with increased toxic effects.
(FAST FACTS AND CONCEPTS #2, David E Weissman MD, EPERC, 2008.

22. Cases
Case 1
Mrs. D is a 45-year-old attorney who has breast cancer metastatic to bone. She is comfortable on a continuous infusion of morphine at 6 mg/h SC. Your goal is to change to oral medications before discharging her home. What should your oral morphine prescription be?
Calculate a 10% prn breakthrough dose as well.
cases: adapted from EPEC Project , Train the Trainer course

23. Case 2 Mr. T is a 73-year-old man with lung cancer, a malignant pleural effusion, and chronic chest pain. He has undergone therapeutic thoracentesis and pleurodesis. He is currently receiving meperidine, 75 mg IM q 6 h, for pain. You want to change to oral morphine. Without adjusting for cross-tolerance, what dose and schedule would you choose? Calculate a 10% prn breakthrough dose also.

24. Case 3 Ms. M is a 41-year-old teacher who has ovarian cancer with ascites and has been taking 2 tablets of acetaminophen/hydrocodone (500 mg/5 mg) every 4 hours and 1 tablet of acetaminophen/oxycodone (325 mg/5 mg) every 6 hours for pain relief. Morphine makes her nauseated. You are concerned about acetaminophen toxicity and want to change to an alternative oral approach. Without adjusting for partial cross-tolerance, what dose of hydromorphone would you choose?

25. Case 4 Mrs. A is hospitalized post op head and neck ca surgery
Case 4 Mrs. A is hospitalized post op head and neck ca surgery. She is receiving adequate pain control with hydromorphone 0.4mg/hr PCA pump. She is unable to take nutrition and medications by mouth. What dose and schedule fentanyl patch would you prescribe to provide her with an approximately equal amount of analgesia?

26. Cases
Case 5
Mr. B has been taking 3 capsules containing oxycodone (5 mg per capsule) and acetaminophen every 3 hours at home for relief of bone pain from metastatic lung cancer. He is now admitted to the hospital with a chemotherapy-induced aplasia. You do not want him taking an antipyretic (acetaminophen). Without correcting for partial cross-tolerance, how much oral morphine elixir would you prescribe to provide analgesia similar to that which he received from the oxycodone?

27. Case 6 Mrs. C has been taking codeine, 60 mg by mouth every 4 hours, and methadone, 40 mg orally every 6 hours, to adequately control abdominal pain from bulky retroperitoneal metastases. She is now admitted with a chemotherapy-induced stomatitis. Your attending physician suggests that you place her on a constant infusion of intravenous morphine. Without adjusting for partial cross-tolerance, what hourly rate of intravenous morphine will you choose to continue to keep her pain well controlled?

28. Answers
Case 1
Morphine Sulfate ER 200mg PO bid or Morphine sulfate IR 70mg PO q4hr ATC
Don’t forget breakthrough dose (10% daily dose)
Morphine sulfate IR 40mg PO q1hr prn breakthrough pain

29. Case 2 Morphine sulfate SR 45mg PO BID Breakthrough:
Morphine Sulfate 10 mg IR q1hr prn breakthrough
NOTE: use equianalgesic conversion chart for conversion of meperidine. Based on EPEC table, slide 19.

30. Case 3 Case 4 Case 5 Hydromorphone 4mg po q4hr ATC
Hydromorphone 1-2mg po q1hr prn breakthrough
Case 4
Fentanyl transdermal patch 100mcg/hr q 72 hr
Case 5
Morphine 30mg PO q4hr ATC

31. Case 6 Total morphine in 24hr= 98mg, so
Morphine sulfate IV 4mg/hr continuous

32. Resources
Ballantyne,J, Mao,J, Opiod Therapy for chronic pain, NEJM 349:20, Nov 13, 2003.
Moryl,N, Coyle,N, Foley,K, Managing an Acute Pain Crisis in a patient with Advanced Cancer, JAMA, Vol 299, no 12, March 26,2008.
EPEC Module 4, Pain Management, EPEC Project, 1999.
UNIPAC 3, Assessment and Treatment of Pain in the Terminally Ill, AAHPM,
Weissman,D, Fast fact #2 Converting to/from Transdermal fentanyl, 2nd ed, EPERC Medical College of Wisconsin, (