Opioid Pain Management

By Carla Alexander, 4th Year Pharmacy StudentMarch 15, 2011

Pain management in the elderly differs from that for younger people:

Clinical manifestations are often complex and multi-factorial

Underreport pain Concurrent illnesses make pain evaluation and

treatment more difficult More likely to experience medication-related side

effects and have higher potential for complications

However, despite these challenges, pain can usually be effectively managed in this age group.

Obstacles With Geriatric Pain Control

Elderly may see an increased sensitivity to analgesics◦ Start low and go slow ◦ Reassess pain scale frequently◦ Monitor side effects◦ Consider renal and hepatic function as well as

concurrent medications

Pain is dynamic◦ Consider IR dosing as well as scheduled◦ Treatment should be tailored to the level of pain

Dosing Tips:

Relaxation, refocus

Physical Manipulation (physiotherapy)

Thermal therapy (heating pad, ice packs)

Physical Stimulation (massage)

Behavioural (support groups)

Nonpharmacological

High alert medications◦ Heightened risk of causing significant harm if used in

error

Morphine and Hydromorphone (Dilaudid) are the most frequent high alert medications to cause patient harm.◦ Dilaudid is 5x more potent than morphine

Serious adverse events over-sedation, respiratory depression, seizures,

myoclonus, death.

Pharmalogical --Opioids

Note: not to be used for neuropathic pain

Step #1: Non-opioid such as acetaminophen, NSAID

Step#2: Opioid such as codeine, oxycodone, tramadol (in combination with acetaminophen)

Percocet (oxycodone + acet.) Tramacet (tramadol + acet.) T#2, T#3 (codeine + acet.)

Step#3: Opioid such as Morphine, oxycodone, hydromorphone, fentanyl, methadone (used as monotherapy)

Note: ◦ Steps 1 and 2 have a ceiling dose due to the combination with non-opioids

(example: acetaminophen (4g/day)).◦ Step 3 has no ceiling dose◦ Must be on at least 60mg oral morphine equivalents for one week before

started on fentanyl.◦ Adjunct treatment include: NSAIDS, antidepressants, anticonvulsants,

dexamethasone

WHO Analgesic Ladder

Mild-to-Moderate Pain Severe Pain

First Line codeine or tramadol morphine, oxycodone or hydromorphone

Second Line morphine, oxycodone or hydromorphone

fentanyl

Third Line   methadone

Canadian Guideline for Safe and Effective Use of Opioids for Chronic Non-Cancer Pain

Note: trial non-opioid options first (acetaminophen, NSAID)

Immediate Release (IR)◦ Duration 4-6 hrs◦ Used for acute pain “breakthrough” pain or when

initiating someone on chronic therapy

Sustained Release (SR)◦ Usually lasts for 12 hrs ◦ Up to 72 hrs for fentanyl patches◦ Unique once daily formulations

Morphine, hydromorphone, tramadol

Immediate and Sustained Release Opioids

More consistent pain relief

More convenient for the patient◦ Dosing OD or BID

Do not crush, chew or dissolve SR products◦ Can lead to rapid absorption of the entire 12-24hr

dose leading to sedation, respiratory depression and potentially fatal dose.

Sustained Release Opioids

1/10th the potency of morphine◦ 200mg po codeine = 20mg po morphine

Increased risk of constipation & GI upset Lower risk of overdose & addiction

Converted to morphine through CYP 2D6 metabolism in our body. ◦ Some people are rapid metabolizers, therefore

increased side effects because can convert faster◦ Some people do not have CYP 2D6 therefore no

metabolism takes place, no morphine formed, no pain relief.

Codeine

Combination products with non-opioids◦ Acetaminophen (ex. T#1, #2, #3)- watch ceiling

dose of 4g/day of acetaminophen when dosing 3g/day limit with elderly?

◦ Combination products also contain caffeine

IR: tablets, syrup, injectable (IM)

SR: tablets, can be halved on score line but patients must swallow half tablet intact

Exception: 50mg tablet cannot be halved EDS criteria discussed later

Codeine

Lower risk of addiction & abuse Increased risk of seizures and nausea

◦ Watch for patients with history of seizure or on concurrent medications that lower seizure threshold

Combination products◦ Tramacet (tramadol 37.5mg + acet. 325mg) max 8 tabs/day

◦ IR: tablets- BID to QID◦ SR: tablets- daily

◦ Note: none of the products are covered by SK Drug Plan

Tramadol

2x more potent than morphine◦ 10mg oxycodone po = 20mg morphine po

Equianalgesia with chronic dosing

Used for mild to moderate pain when in combination with non-opioid

Used for severe pain when used as single agent

Increased risk of abuse potential

Oxycodone

Combination products (not on SK formulary)

◦ Percocet (acet. 325mg + oxycodone 5mg)

IR: tablets, suppository (not on SK formulary)

SR: tablets (oxycontin)

No parenteral formulation available

Oxycodone

Used as a standard for comparing potency Available as:

◦ IR: tablets, solution, suppository, injectable

◦ SR: tablets, may be given rectally

◦ Unique SR: 24 hr coverage Kadian capsules- not interchangeable with other SR

products Should not be started in opioid naïve patients

Morphine

5x more potent than morphine Available as:

◦ IR: tablet, liquid, suppository, injectable

◦ SR: capsule

◦ Unique SR: 24hr coverage Tablet Not listed in SK formulary

Hydromorphone

Potency is variable◦ The higher the dose of the original opioid, the

more potent the methadone is.

Used for moderate to severe chronic pain as well as opioid addiction

Long acting and complicated dosing◦ Duration of pain relief: initially 4-8 hrs, increases

to 24-48 hrs with repeated doses◦ Takes 3-5 days to reach plasma steady state

Methadone

Peak respiratory depressant effects occur later, and persist longer than its peak analgesic effects

Risk of QT prolongation Many drug interactions

Available as:◦ Tablets, oral solution, powder (all which can be

administered rectally)

Methadone

Continue to be inappropriately prescribed, dispensed and administered to opioid naïve patients with acute pain.

Indicated for the management of persistent, moderate to severe chronic pain that can not be managed by other opioids.

Only to be used in patients:◦ who require continuous around the clock opioid analgesia

for extended periods of time.◦ who are already receiving opioid therapy at a total daily

dose of at least 60mg/day morphine equivalents for a minimun of 7 days (no longer considered opioid naïve).

Fentanyl Patches

100x more potent than morphine!◦ 100mg po morphine/day = 25mcg fentanyl patch

Available as ◦ Duragesic MAT and generic duragesic

Required EDS for SK drug plan (later discussed)◦ Parenteral solution (not on SK formulary)

Fentanyl Patches

Less constipation, nausea, vomiting and itchiness compared to morphine

Very effective

Convenient dosing schedule (every 72 hrs)

No ceiling dose

Fentanyl Patch Advantages:

Opioid naïve patients◦ Need to be on at least 60mg of morphine

equivalents per day for a week or longer before initiating fentanyl patch.

Acute pain management◦ Takes 12-24hrs for analgesia to take effect

Unstable or poorly controlled pain◦ Pain controlled for at least 48 hrs

Fentanyl Patch Contraindications:

Not appropriate for patients with:

◦ Fever- heat activated absorptive system

◦ Diaphoresis- difficult to adhere

◦ Cachexia- lipophilic drug, won’t absorb

◦ Morbid obesity- increased absorption, lose patch

◦ Ascites

Fentanyl Patch Precautions:

Continuous delivery of opioid for 72 hrs◦ Breakthrough” doses may still be required

Blood levels reach steady state between 12-24 hrs

Absorption is: ◦ 47% complete after 24hrs◦ 88% complete after 48hrs◦ 94% complete after 72hrs

Therefore a used patch contains residual drug

Fentanyl Patch

Apply patch to a non-hairy area on chest, back, flank or upper arm

◦ Avoid areas of excessive movement◦ If necessary, clip hair as close to skin as possible◦ Do not shave as this irritates skin and increases

absorption

If patch falls off, discard it and put a new patch on at a different site.

If the gel contacts your skin, wash with water. Do not use soap as it can increase the drug’s ability to go through the skin

Fentanyl Patch Application

Remove patch after 3 days New patch should be applied to different

site Avoid sources of heat (hot tub, waterbeds,

electric blankets)

Disposal:◦ Fold sticky sides together and flush down toilet or

discard in safe place (sharps container)

Application continued

Recommended to not cut as this will disrupt the reservoir membrane and the entire dose will be available immediately.

Future: Duragesic-MAT patches may be cut, check with pharmacy first!

If only need ½ strength of patch use an occlusive barrier to cover half.

Cutting Fentanyl Patches--NO

Pain Medication

Elderly Dosing Considerations

Acetaminophen Clcr 10-50ml/min: administer q6hrs; if Clcr <10ml/min: administer q8hrs.

Ibuprofen NSAIDS can compromise existing renal function especially when Clcr is <30ml/min. Be aware of comorbidities: GERD/PUD, GI bleed, Asthma, Renal failure, Heart failure.

Codeine Clcr 10-50ml/min: administer 75% of dose; if Clcr <10ml/min: administer 50% of dose.

Tramadol Elderly >65 yrs old use with caution and initiate at the lower end of dosing range. Elderly >75 years old, do not exceed 300mg/day for IR formulation and use with great caution.•IR formulation: Clcr <30ml/min: administer 50-100mg dose q12rs (max 200mg/day). •ER formulation: should not be used in patients with Clcr<30ml/min because experience more adverse effects: constipation, fatigue, weakness, postural hypotension, dyspepsia.

Pain Medication

Elderly Dosing Considerations

Morphine Clcr 10-50ml/min: administer 75% or normal dose; if Clcr <10ml/min: administer 50% of normal dose.

Oxycodone serum concentrations increase ~50% in patients with Clcr <60ml/min, adjust dose based on clinical situation.

Hydromorphone Moderate renal impairment: start with a reduced dose and monitor closely. Severe renal impairment: consider use of an alternate analgesic with better dosing flexibility.

Methadone Clcr <10-ml/min: administer 50-75% of normal dose. Because of its long half life and risk of accumulation, methadone is difficult to titrate and is not considered a drug of first choice.

Fentanyl Elderly have been found to be twice as sensitive as younger patients to the effects of Fentanyl. A wide range of doses may be used. No renal adjustment necessary.

Potency varies by agent and route

Oral/rectal doses ≠ parenteral doses (IM, SC, IV)

Parenteral route is 2x more potent than oral/rectal route

morphine 5mg po = morphine 2.5mg SC

Routes of Administration

Onset 30-60mins

Advantages: Preferred and easier to administer Maintain patient independence Portable Less expensive

Disadvantages: Caution with patients suffering form vomiting,

difficulty swallowing or pain with swallowing

Oral Route

IR formulations can be crushed SR formulation CANNOT be crushed

◦ Open capsule and sprinkle contents onto small amount of soft, cold food.

◦ Ensure patient does not chew the spheres◦ Take within 30mins of sprinkling◦ Mouth should be rinsed to ensure all medication

has been swallowed

Or switch formulation/route/opioid Suppository, oral solution, injectable

Unable to Swallow??

Onset varies depending on opioid Use concentrated parenteral formulations

Advantages: Rapid onset of action

Disadvantages: Maximum of 2ml Must retain volume in mouth for 10-15mins Not all meds have good transmuscosal absorption

(morphine) Thrush, mucositis & dry mouth may impact absorption

Buccal / Sublingual Route

Onset similar to oral

Advantages: Used if unable to swallow pills Can administer controlled release oral opioids rectally

Disadvantages: Not easy to administer Patients feel uncomfortable Limited commercial preparations Avoid in patients with diarrhea, colostomy, hemorrhoids Suppositories may be expelled before absorbed High degree of inter-individual absorption variability

Rectal Route

Not recommended due to:

Painful, unreliable absorption

Nerve injury, sterile abscess formation and muscle/soft tissue fibrosis with chronic injections

30-60min lag time until peak effect

Intramuscular (IM) Route

Subcutaneous Intravenous Transdermal Topical Nebulized Patient controlled analgesia (PCA) Etc.

Other Routes of Administration

Defn: transient pain not controlled by around-the-clock analgesia

Use immediate release products

Used the same opioid for both scheduled and prn, when possible

Exception: fentanyl patch

Breakthrough Pain

1. Idiopathic unpredictable, unknown cause

2. End of dose failure pain at the end of a scheduled interval

3. Incident pain Secondary to stimulus

Types of Breakthrough Pain

Nausea/vomiting Constipation

Laxative should always be used when on opioid Dizziness/orthostatic hypotension Respiratory depression Urinary Retention

Improves within 1 week Delirium/confusion

Usually resolves in 3-4 days Sedation

Tolerance develops in 2-4 days Pruritis Dry mouth

Opioid Side Effects

Codeine, controlled release tablet, 50mg, 100mg, 150mg, 200mg

For treatment of : (a) Palliative and chronic pain patients as an alternative to

ASA/codeine combination products or acetaminophen/codeine combination

products. (b) Palliative and chronic pain patients as an alternative to

regular release tablet when large doses are required. In non-palliative patients, coverage will only be approved for a 6

month course of therapy, subject to review.

*Fentanyl Patch For treatment of patients: (a) Intolerant to, or unable to take, oral sustained-release strong

opioids. (b) As an alternative to subcutaneous narcotic infusion therapy. *These brands of products have been approved as

interchangeable.

Exceptional Drug Status

Lecture Notes Pharmacy 557

Saskatchewan Formulary

RX Files

Exceptional Drug Status Program

American Geriatrics Society

Therapeutic Choices, 5th edition

References

Questions?