Pharmacology Pearls – Chronic Opioid Use
Renal and Hepatic Dysfunction (www.practicalpainmanagement.com/treatments/pharmacological/opioids)
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General recommendations for opioids in patients with renal insufficiency
Drug Name
Meperidine
Codeine
Recommendation
Not Recommended
Not Recommended
Morphine
Use cautiously
Oxycodone
Use cautiously
Hydromorphone
Use cautiously
Fentanyl
Appears safe
Methadone
Appears safe

General recommendations for opioids in patients with liver insufficiency
Drug Name
Meperidine
Codeine
Recommendation
Not Recommended
Not Recommended
Morphine
Use cautiously
Oxycodone
Use cautiously
Hydromorphone
Use cautiously
Fentanyl
Appears safe
Methadone
Not Recommended
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Notes
Accumulation of toxic metabolite, normeperidine, may cause CNS toxicity.
Impaired conversion of codeine to the active compound, morphine, in the liver to be
active.
Recommended to decrease frequency of administration and dosage because of
decreased clearance and increased t1/2 and oral bioavailability.
Risk of accumulation of parent drug due to decreased conversion to metabolites and
decreased elimination. Recommended to reduce dose by 1/2 to 1/3 of the usual amount
and avoid in severe cirrhosis.
Risk of accumulation of parent drug due to decreased conversion to metabolites and
decreased elimination. Recommended to decrease dose by 50% of the usual amount.
Pharmacokinetics were not altered in patients with cirrhosis. With continued use, recovery
time after termination of infusion may be longer.
Risk of accumulation with severe liver disease.
Fentanyl
o
o
o
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Notes
Accumulation of toxic metabolite, normeperidine, may cause CNS toxicity
Accumulation of active metabolites in renal failure.5 Case reports of toxicity and serious
adverse effects which can be delayed
Metabolite morphine-6-glucuronide, a more potent analgesic, may accumulate causing
more sedation.4 If morphine must be used, it is recommended to use cautiously and
adjust dose appropriately
Insufficient evidence available for strong recommendation. Reports of accumulation of
both parent compound and active metabolite, free oxymorphone, leading to CNS toxicity
and sedation.
Metabolite, hydromorphone-3-glucuronide can accumulate and cause CNS
toxicity. Careful monitoring of patients on dialysis and avoid use in patients with GFR <
30mL/min.
Some reports of parent compound accumulating in renal failure, but no increase in
adverse effects. The metabolites are considered inactive. A dose reduction may be
necessary. With long term use, careful monitoring of pharmacodynamic effects is advised.
Recommended to be used only by experienced clinicians. No active metabolites are
formed and limited plasma accumulation of the drug observed in renal failure. Dose
reduction may be necessary in severe renal failure.
Never start in an opioid naïve patient
Transdermal delivery offers unique benefits, but results in delayed action and may not last 72
hours in all patients
Refer to product labeling for guidance on fentanyl conversions and use more conservative
approaches than are typically used with long acting opioids
Methadone
o
o
o
o
o
Too rapid of titration can result in unintentional overdoses
Little cross tolerance with other opioids making conversations complicated
Highly variable metabolism; must titrate slowly (no sooner than every 5 days)
Consult with a provider who has experience with using methadone prior to use
EKG testing needed due to Qtc prolongation, and might need to be avoided in high risk patients
Red Flag Regimens
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Violating terms of provider-patient opioid agreement
Use of more than one short acting opioid
High quantity of short acting opioids per prescription in relation to the long acting opioid
Patterns of early filling that are frequent or not explained
Multiple providers of opioid prescriptions identified on PDMP reports
Consider the Morphine Equivalent (ME) of an Opioid Regimen
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Evidence has convincingly demonstrated that higher opioid doses are associated with an increased risk
of harm, specifically overdose and related mortality, bone fracture, and emergency department visits
Morphine equivalent dosing is now an explicit criteria singled out by DORA for judging monitoring
intensity and prescribing appropriateness. The increased risk of fatal overdose significantly increases in
patients receiving opioid therapy consisting of 100-mg of morphine equivalents (ME) or higher. Per the
state board “Opioid doses >120 mg morphine equivalents per day is a dosage that the Boards agree is
more likely dangerous for the average adult (chances for unintended death are higher) over which
prescribers should use clinical judgment, put in place additional safeguards for the treatment plan (such
as utilizing a treatment agreement), consult a specialist or refer the patient; and dispensers should be
more cautious.”
Several calculators are available to allow clinicians to determine a patient’s ME
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Example Regimens:
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Patient 1:
o Oxycontin (oxycodone SR) 20 mg po Q12h
o Norco (hydrocodone/APAP) 10/325 mg po q4-6h prn (average 4 daily)
Total daily use is equal to 100 ME
Patient 2:
o Dilaudid (hydromorphone) 4 mg 1 to 2 tablets q3-4h prn (average 7 daily)
Total daily use is equal to 112 ME
Patient 3:
o MS Contin (morphine SR) 30 mg po Q12h
o Roxicodone (oxycodone) 10 mg po q3-4h prn (average 4 daily)
Total daily use is equal to 120 ME
Naloxone Rescue for Overdoses (http://prescribetoprevent.org/wp-content/uploads/2012/11/one-pager_22.pdf,
http://stopoverdose.org/docs/NaloxoneBrochure.pdf )
Intranasal Spray
 Given with a foam tip (nebulizer, adapter, or atomizer) that is put on a syringe then placed into the
nostril
 Intranasal naloxone has not been approved by the FDA (i.e., it is an "off-label" delivery method), but
can be legally prescribed by a physician or approved pharmacists
 First responders often give naloxone intranasally
Intramuscular Injection
 Evzio™ is a 0.4 mg auto-injector that is commercially available (similar to an EpiPen ®)