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Created Sep 2019 | Updated Oct 2020



DEA CODE 9220: Schedule 2 Narcotic

Levorphanol is used to relieve pain severe enough to require opioid treatment and when other pain medicines did not work well enough or cannot be tolerated. It belongs to the group of medicines called narcotic analgesics (pain medicines). It acts on the central nervous system (CNS) to relieve pain. When levorphanol is used for a long time, it may become habit-forming, causing mental or physical dependence.

Appropriate studies have not been performed on the relationship of age to the effects of levorphanol in the pediatric population.

Safety and efficacy have not been established.

Appropriate studies performed to date have not demonstrated geriatric-specific problems that would limit the usefulness of levorphanol in the elderly. However, elderly patients are more likely to have age-related liver, kidney, heart, or lung problems, which may require caution and an adjustment in the dose for patients receiving levorphanol.

Other Interactions:

  • Ethanol

Other Medical Problems:
Make sure you tell your doctor if you have any other medical problems, especially:

  • Addison's disease (adrenal gland problem)
  • Alcohol abuse, history of
  • Brain tumor
  • Breathing or lung problems (eg, chronic obstructive pulmonary disease [COPD], hypoxia)
  • Congestive heart failure
  • Cor pulmonale (serious heart condition)
  • Drug dependence, especially narcotic abuse or dependence, or history of
  • Enlarged prostate (BPH, prostatic hypertrophy)
  • Gallbladder problems
  • Head injuries
  • Hypothyroidism (an underactive thyroid)
  • Increased pressure in your head
  • Infection, severe
  • Mental illness, history of
  • Problems with passing urine
  • Stomach or bowel problems - Use with caution. May increase risk for more serious side effects
  • Gallbladder surgery
  • Lung or breathing problems (eg, asthma, respiratory depression), severe
  • Stomach or bowel blockage (eg, paralytic ileus), known or suspected - Should not be used in patients with these conditions
  • Heart disease
  • Hypotension (low blood pressure)
  • Myocardial infarction (heart attack)
  • Pancreatitis (swelling of the pancreas)
  • Seizures, history of - Use with caution. May make these conditions worse
  • Kidney disease
  • Liver disease - Use with caution. The effects may be increased because of slower removal of the medicine from the body

Levorphanol acts by binding to opioid receptors. Of the several types of opioid receptors that exist, levorphanol specifically binds to the mu, delta, and kappa receptors, inhibiting the excitability of nerve cells and, consequently, the transmission of pain signals to the brain. Levorphanol also acts as an antagonist, or a molecule that inhibits the normal action of NMDA receptors, which are involved in the transmission of electric signals between nerve cells. Levorphanol reduces the activity of these receptors.

Sickle Cell Anemia Patients
It was initially developed as a more potent and longer-acting alternative to morphine. In sickle cell anemia patients, levorphanol is used for the treatment of moderate to severe chronic pain. For acute pain relief, it should be used in combination with short-acting opioids. Levorphanol has not been tested in clinical trials specifically for sickle cell anemia patients. One study suggests, however, that levorphanol might be of benefit in cases of chronic neuropathic pain, which is common in sickle cell anemia patients.

Levorphanol is a fully synthetic opioid that has full agonist activity to the u type opiate receptors which are found in the central nervous system, but also in the heart, lungs, intestine and skin. Levorphanol is similar to morphine in effect, but is 4 to 8 times as potent and somewhat longer acting. Levorphanol was first approved for use in the United States in 1953. Indications are for moderate-to-severe pain that is that is not responsive to nonnarcotic analgesia and for perioperative sedation and analgesia.

Levorphanol has not been linked to serum enzyme elevations during therapy or to clinically apparent liver injury.

The forgotten opioid may be a "new" treatment for chronic pain syndromes that are refractory to other opioids, as well as a favored alternative to methadone, as it has a lower potential for drug-drug interactions, and has no reports of QT interval prolongation. Levorphanol's multimodal profile is unique amongst the class, and may make it an optimal agent both for initial use, as well as for opioid rotation. Levorphanol may address pain that is refractory to other opioid analgesics, such as central and neuropathic pain syndromes, and may also play a role in addressing opioid-induced hyperalgesia (OIH). This review will discuss some of the benefits of levorphanol over other opioids and its potential use in difficult-to-treat pain syndromes.

Although levorphanol is an effective treatment for pain, many clinicians remain unfamiliar with its use. Levorphanol has a longer half-life (11 to 16 hours) than many opioids and therefore is best suited for treating chronic pain; an interval of approximately 72 hours should pass to allow the patient to achieve steady-state before being assessed for a dose adjustment. Because levorphanol is not metabolized by CYP enzymes and is not dependent on p-glycoprotein for absorption, there is less potential for the adverse drug-drug and drug-food reactions observed with many opioids. Further investigations of the clinical utility of levorphanol, especially in the areas of chronic complex pain, OIH, and as a substitute for methadone, are warranted.

Back when I was a novice nurse, in 1980, I worked at a community hospital in Washington, DC. The favorite analgesic of one of our oncologists was Levo-Dromoran (levorphanol). The reason was that it was a little more potent than morphine, but more importantly it had a longer duration of action. I have only a vague recollection of how frequently we dosed it, but I think it was every 6 hours. I moved on from that hospital after 3 years, and haven't seen levorphanol ordered in all those intervening years (of course, extended release morphine became available in the '80's).

In a very small nutshell, the advantages and disadvantages of levorphanol:

  • Has been shown to be responsive in both peripheral and central neuropathic pain syndromes
  • Multiple analgesic mechanisms: strong affinity for mu, delta, and kappa receptors; NMDA antagonist; serotonin & norepinephrine reuptake inhibitor
  • 4-8 times more potent than morphine
  • Oral to parenteral ratio of 2:1
  • Can be administered via oral, intravenous, subcutaneous, and intramuscular routes; not sublingual
  • Not metabolized via cytochrome system, so relatively smaller risk of drug-drug interactions, especially compared to methadone
  • Relatively long acting, dosing every 6 hours, possibly longer in some patients
  • Accumulates, so all the usual precautions, including waiting 3 days between dose changes
  • Anticholinergic properties similar to morphine
  • Neurotoxic 3-glucuronide metabolite with symptoms (sedation, irritability) seen in the higher dose ranges
  • Relatively slow onset, so not a good choice for breakthrough pain

Levorphanol, brand name Levo-Dromoran, is an opioid medication used to treat moderate to severe pain. Levorphanol is indicated for the management of moderate to severe pain where an opioid analgesic is appropriate. It is a potent synthetic opioid mu-receptor agonist similar in action to morphine. Like other opioid mu-receptor agonists, it is believed to act at receptors in both the brain and spinal cord to alter the transmission and perception of pain. The onset and peak analgesic effects following administration of levorphanol are similar to morphine when administered at equal analgesic doses. Levorphanol produces a degree of respiratory depression similar to that produced by morphine at equal analgesic doses, and like many opioid mu-receptor agonists, levorphanol produces euphoria or has a positive effect on mood in many individuals.

What are racemorphan and levorphanol?
These are both highly potent opioid (narcotic-)analgesics, chemically related to morphine, but produced synthetically. They are part of a small group of opioids in the morphine series known as morphinans, and are lacking certain chemical groupings of the original opium alkaloid, though still containing the fundamental, biologically active, portion of the molecule, known as N-methyl-morphinan, which is related to the narcotic opium alkaloids in a way analogous to that in which tropane is related to cocaine and the atropa belladonna alkaloids, such as atropine. Morphinan analgesic agonists are typically analgesically superior to morphine. Racemorphan is a racemate of levorphanol and dextrorphan. That is, it is an equal mixture of two optical isomers, one of which is the highly potent opioid levorphanol, and the other the compound dextrorphan, which is dissociative in higher doses, and resembles ketamine in it's actions.

Levorphanol may be habit forming, especially with prolonged use. Take levorphanol exactly as directed. Do not take more of it, take it more often, or take it in a different way than directed by your doctor. Levorphanol may cause serious or life-threatening breathing problems, especially during the first 24 to 72 hours of your treatment and any time your dose is increased. Taking certain other medications during your treatment with levorphanol may increase the risk that you will experience breathing problems or other serious, life-threatening breathing problems, sedation, or coma. Tell your doctor if you are taking or plan to take any of the following medications: benzodiazepines such as alprazolam (Xanax), diazepam (Diastat, Valium), estazolam, flurazepam, lorazepam (Ativan), and triazolam (Halcion); other narcotic pain medications; medications for mental illness or nausea; muscle relaxants; sedatives; sleeping pills; or tranquilizers. Do not drink alcohol, take any prescription or nonprescription medications that contain alcohol, or use street drugs during your treatment with other levorphanol products.

Levo Dromoran (levorphanol)
Side Effects:
Get emergency medical help if you have signs of an allergic reaction: hives; difficult breathing; swelling of your face, lips, tongue, or throat.
Opioid medicine can slow or stop your breathing, and death may occur. A person caring for you should seek emergency medical attention if you have slow breathing with long pauses, blue colored lips, or if you are hard to wake up.
Call your doctor at once if you have:
  • noisy breathing, sighing, shallow breathing, breathing that stops during sleep
  • a slow heart rate or weak pulse
  • a light-headed feeling, like you might pass out
  • mood changes, unusual thoughts or behavior
  • severe stomach pain, severe constipation
  • low cortisol levels - nausea, vomiting, loss of appetite, dizziness, worsening tiredness or weakness
Seek medical attention right away if you have symptoms of serotonin syndrome, such as: agitation, confusion, fever, sweating, fast heart rate, chest pain, feeling short of breath, muscle stiffness, trouble walking, or feeling faint.
Serious side effects may be more likely in older adults and those who are overweight, malnourished, or debilitated.
Long-term use of opioid medication may affect fertility (ability to have children) in men or women. It is not known whether opioid effects on fertility are permanent.
Common side effects may include:
  • nausea, vomiting, stomach pain
  • constipation
  • dizziness, drowsiness
  • tiredness
  • headache
This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

Levorphanol Tartrate
Maximum Dosage:
Prescribers Digital Reference
Adults:With appropriate dosage titration, there is no maximum dose of levorphanol.
Geriatric:With appropriate dosage titration, there is no maximum dose of levorphanol.
Adolescents:Safety and efficacy have not been established.
Children:Safety and efficacy have not been established.
Infants:Safety and efficacy have not been established.
Neonates:Safety and efficacy have not been established.

Important Information:

MISUSE OF OPIOID MEDICINE CAN CAUSE ADDICTION, OVERDOSE, OR DEATH. Keep the medication in a place where others cannot get to it.

Taking opioid medicine during pregnancy may cause life-threatening withdrawal symptoms in the newborn.

Fatal side effects can occur if you use opioid medicine with alcohol, or with other drugs that cause drowsiness or slow your breathing.

Do not drink alcohol. Dangerous side effects or death could occur.

Avoid driving or hazardous activity until you know how levorphanol will affect you. Dizziness or drowsiness can cause falls, accidents, or severe injuries.


Drug Interactions (326) Alcohol/Food Interactions (1) Disease Interactions (17)

What other drugs will affect Levorphanol?
Opioid medication can interact with many other drugs and cause dangerous side effects or death. Be sure your doctor knows if you also use:
  • cold or allergy medicines, bronchodilator asthma/COPD medication, or a diuretic ("water pill")
  • medicines for motion sickness, irritable bowel syndrome, or overactive bladder
  • other narcotic medications - opioid pain medicine or prescription cough medicine
  • a sedative like:
  • drugs that make you sleepy or slow your breathing - a sleeping pill, muscle relaxer, medicine to treat mood disorders or mental illness
  • drugs that affect serotonin levels in your body - a stimulant, or medicine for depression, Parkinson's disease, migraine headaches, serious infections, or nausea and vomiting
This list is not complete. Other drugs may affect levorphanol, including prescription and over-the-counter medicines, vitamins, and herbal products. Not all possible interactions are listed here.

A total of 326 drugs are known to interact with Levorphanol.

  • 115 major drug interactions
  • 210 moderate drug interactions
  • 1 minor drug interaction

Levorphanol is an old opioid, but it doesn't get a lot of use. It's a relative of DXM. It has NMDA activity like Methadone, which makes it a useful analgesic in certain situations (nerve/neuropathic pain patients and several other illnesses react much better to opioids with NMDA activity vs those without), plus the lack of complete cross tolerance with other opioids (like Morphine) make it potentially useful in specific situations. It has a long half-life compared to other opioids of similar strength (Wiki lists it as 11-16 hours, compared to like 6 with Morphine).

It is nearly as effective orally as by injection.

It is one of four enantiomers of the compound racemorphan. It was first described in Germany in 1946. The drug has been in medical use in the United States since 1953. The duration of action is generally long compared to other comparable analgesics and varies from 4 hours to as much as 15 hours. For this reason levorphanol is useful in palliation of chronic pain and similar conditions. Levorphanol has an oral to parenteral effectiveness ratio of 2:1, one of the most favorable of the strong narcotics.

Pharma company pays $750K to settle federal opioid kickback accusations - A California pharmaceutical company settled claims they paid kickbacks to a physician by hiring his girlfriend as a sales representative.
Thursday February 15, 2024 - nj.com

The Safety of Dextromethorphan in Pregnancy: Results of a Controlled Study - Background: Dextromethorphan (DM), the d-isomer of the codeine analog levorphanol ... to suggest that pregnant women should not use this drug because of the risk of birth defects.
Saturday February 17, 2024 - medscape.com

Promethazine Dm - Promethazine HCl 6.25mg, dextromethorphan HBr 15mg; per 5mL; liq; contains alcohol 7%. Dextromethorphan is an antitussive agent and, unlike the isomeric levorphanol, it has no analgesic or ...
Thursday December 01, 2011 - empr.com

Should You Take Opioids to Treat Pain? - In addition, using the drugs longer term or taking higher doses can also lead to addiction, overdose, and even death. Because of these factors, Consumer Reports Best Buy Drugs has not chosen any ...
Thursday July 31, 2014 - consumerreports.org

Abuse-Deterrent Dosage Formulations - The 2009 Peabody Award-winning television documentary, titled The Oxycontin Express, reported on the human toll of America’s prescription drug abuse epidemic. [1] In the same year, the FDA ...
Friday March 30, 2012 - medscape.com

Escitalopram Interaction with other Drugs - Escitalopram is an antidepressant of the selective serotonin reuptake inhibitor (SSRI) class, prescribed for major depressive disorder, generalized anxiety disorder, social anxiety disorder, or ...
Wednesday August 29, 2018 - medindia.net

Painful Sensory Neuropathy - If a three-drug regimen is ineffective, it is reasonable to substitute a narcotic analgesic. Oxycodone or levorphanol can be used, but we prefer sustained-release oral morphine. Methadone ...
Tuesday August 01, 2023 - nejm.org

Flunarizine Interaction with other Drugs - Flunarizine is a calcium channel blocker, prescribed for migraine occlusive peripheral vascular disease, vertigo of central and peripheral origin and as an adjuvant in the therapy of epilepsy.
Thursday October 21, 2021 - medindia.net

Frequency of Use Increases Risk for Depression Among Long-Term Prescription Opioid Users - Reserved for members of the media. ST. LOUIS, MO - Reducing the frequency of opioid use in chronic opioid therapy may limit the risk for depression, a Saint Louis University School of Medicine study ...
Wednesday November 02, 2022 - slu.edu

SLU Research: Long-Term Opioid Use Associated with Increased Risk of Depression - Opioid drugs in the study included codeine, fentanyl, hydrocodone, hydromorphone, levorphanol, meperidine, oxycodone, oxymorphone, morphine and pentazocine. Other authors include Joanne Salas, MPH, of ...
Wednesday April 05, 2017 - slu.edu

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