Download Levorphanol Tartrate

Levorphanol Tartrate
RATIONALE FOR INCLUSION IN PA PROGRAM
Background
Levorphanol tartrate is a potent synthetic opioid analgesic for the management of moderate to
severe pain where an opioid analgesic is appropriate. Levorphanol is 4 to 8 times as potent as
morphine and has a longer half-life, which may have some advantages in the management of
chronic pain. Because there is incomplete cross-tolerance among opioids, when converting a
patient from morphine to levorphanol, the total daily dose of levorphanol should be approximately
1/15 to 1/12 of the total daily dose of oral morphine that the patient was receiving, and then the
dose should be adjusted to the patient’s clinical response. To avoid excessive sedation due to drug
accumulation, adequate time should be allowed after each dose change (approximately 72 hours)
if a patient is to be placed on a fixed-dosing schedule with this drug (1).
Regulatory Status
FDA-approved indication: Levorphanol Tartrate Tablets USP are indicated for the management of
moderate to severe pain where an opioid analgesic is appropriate (1).
Limitations of Use:
Levorphanol, like morphine, may produce serious or potentially fatal respiratory depression if the
patient is given an excessive dose or given a dose too frequently. Doses required to produce
analgesia may cause serious respiratory depression in vulnerable patients. Safe usage of this drug
requires individualized dosing for the patient based on the severity of pain, weight, age, diagnosis,
and other medications the patient is taking concurrently (1).
The initial dose of levorphanol should be reduced by 50% or more in patients with conditions
affecting their respiratory reserve or in patients taking other drugs that might affect their respiratory
reserve. Subsequent doses can be titrated per patient response. Respiratory depression caused
by levorphanol tartrate can be reversed by naloxone (1).
Levorphanol tartrate carries several warnings regarding addiction, abuse, misuse, severe
respiratory depression, cardiovascular effects, and interaction with alcohol (1).
CDC guidelines find that concurrent use of benzodiazepines and opioids might put patients at
greater risk for potentially fatal overdose. Three studies of fatal overdose deaths found evidence of
concurrent benzodiazepine use in 31%–61% of decedents (2)
Levorphanol FEP Clinical Rationale
Levorphanol Tartrate
CDC guidelines finds that given uncertain benefits and substantial risks that opioids should not be
considered first-line or routine therapy for chronic pain (i.e., pain continuing or expected to continue
longer than 3 months or past the time of normal tissue healing) outside of active c ancer, palliative,
and end-of-life care (2).
FDA warns that opioids can interact with antidepressants and migraine medicines to cause a
serious central nervous system reaction called serotonin syndrome, in which high levels of the
chemical serotonin build up in the brain and cause toxicity (see Appendix 1 for list of drugs) (3).
Levorphanol is not recommended in pediatric patients below the age of 18 years as the safety and
efficacy of the drug in this population has not been established (1).
Summary
Levorphanol tartrate is an opioid analgesic used for the management of moderate to severe pain.
The potential for developing substance abuse and addiction is extreme. Patients should be
thoroughly assessed for their risk of developing severe respiratory depr ession, as well as
substance abuse prior to being prescribed levorphanol and should be routinely monitored for signs
of misuse, abuse and addiction during therapy. Levorphanol is not recommended in pediatric
patients below the age of 18 years as the safety and efficacy of the drug in this population has not
been established (1).
Prior approval is required to ensure the safe, clinically appropriate and cost effective use of
levorphanol while maintaining optimal therapeutic outcomes.
References
1. Levorphanol tartrate [package insert]. Columbus, OH: Roxane Laboratories, Inc.;
September 2015.
2. Dowell D, Haegerich T, Chou R. CDC Guideline for Prescribing Opioids for Chronic Pain.
CDC Guidelines 2016.
3. FDA Safety Release. FDA Drug Safety Communication: FDA warns about several safety
issues with opioid pain medicines; requires label changes. March 22, 2016.
Levorphanol FEP Clinical Rationale
Levorphanol Tartrate
Appendix 1 - List of Serotonergic Medications
Selective Serotonin Reuptake Inhibitors (SSRIs)
paroxetine
Paxil, Paxil CR, Pexeva, Brisdelle
fluvoxamine
Luvox, Luvox CR
fluoxetine
Prozac, Prozac Weekly, Sarafem, Selfemra, Symbyax
sertraline
Zoloft
citalopram
Celexa
escitalopram
Lexapro
Serotonin-Norepinephrine Reuptake Inhibitors (SNRIs)
venlafaxine
Effexor XR
desvenlafaxine
Pristiq, Khedezla
duloxetine
Cymbalta
milnacipran
Savella
Tricyclic Antidepressants (TCAs)
amitriptyline
No brand name currently marketed
desipramine
Norpramin
clomipramine
Anafranil
imipramine
Tofranil, Tofranil PM
nortriptyline
Pamelor, Aventyl
protriptyline
Vivactil
doxepin
Zonalon, Silenor
trimipramine
Surmontil
Monoamine Oxidase Inhibitors (MAOIs)
isocarboxazid
Marplan
phenelzine
Nardil
selegiline
Emsam, Eldepryl, Zelapar
tranylcypromine
Parnate
Other Psychiatric Medicines
amoxapine
No brand name currently marketed
maprotiline
No brand name currently marketed
nefazodone
No brand name currently marketed
trazodone
Oleptro
buspirone
No brand name currently marketed
vilazodone
Viibryd
mirtazapine
Remeron, Remeron Soltab
llthium
Lithobid
Levorphanol FEP Clinical Rationale
Levorphanol Tartrate
Migraine Medicines
almotriptan
Axert
frovatriptan
Frova
naratriptan
Amerge
rizatriptan
Maxalt, Maxalt-MLT
Imitrex, Imitrex Statdose, Alsuma, Sumavel Dosepro, Zecuity,
sumatriptan
Treximet
zolmitriptan
Zomig, Zomig-ZMT
Antiemetics
ondansetron
granisetron
dolasetron
palonosetron
Zofran, Zofran ODT, Zuplenz
Kytril, Sancuso
Anzemet
Aloxi
Other Serotonergic Medicines
dextromethorphan Bromfed-DM, Delsym, Mucinex DM, Nuedexta
linezolid
Zyvox
cyclobenzaprine
Amrix
methylene blue
St. John’s wort
tryptophan
Levorphanol FEP Clinical Rationale