Levorphanol

Levorphanol is a full opioid agonist and is relatively selective for the mu-opioid receptor, although it can bind to other opioid receptors at higher doses. The principal therapeutic action of levorphanol is analgesia.

• Levorphanol Tartrate Tablets are indicated for the management of pain severe enough to require an opioid analgesic and for which alternative treatments are inadequate. Limitations of Use Because of the risks of addiction, abuse, and misuse with opioids, which can occur at any dosage or duration [see WARNINGS ], reserve Levorphanol Tartrate Tablets for use in patients for whom alternative treatment options (e.g., non-opioid analgesics): • Have not been tolerated or are not expected to be tolerated, • Have not provided adequate analgesia or are not expected to provide adequate analgesia Levorphanol Tartrate Tablets should not be used for an extended period of time unless the pain remains severe enough to require an opioid analgesic and for which alternative treatment options continue to be inadequate.

• Levorphanol Tartrate Tablets are contraindicated in patients with: • Significant respiratory depression [see WARNINGS ] • Acute or severe bronchial asthma in an unmonitored setting or in the absence of resuscitative equipment [see WARNINGS ] • Known or suspected gastrointestinal obstruction, including paralytic ileus [see WARNINGS ] • Hypersensitivity to levorphanol or any of the formulation excipients (e.g., anaphylaxis) [see WARNINGS ]contraindicated

Important Dosage and Administration Instructions Levorphanol Tartrate Tablets should be prescribed only by healthcare professionals who are knowledgeable about the use of opioids and how to mitigate the associated risks. Use the lowest effective dosage for the shortest duration of time consistent with individual patient treatment goals [see WARNINGS ]. Because the risk of overdose increases as opioid doses increase, reserve titration to higher doses of Levorphanol Tartrate Tablets for patients in whom lower doses are insufficiently effective and in whom the expected benefits of using a higher dose opioid clearly outweigh the substantial risks. Many acute pain conditions (e.g., the pain that occurs with a number of surgical procedures or acute musculoskeletal injuries) require no more than a few days of an opioid analgesic. Clinical guidelines on opioid prescribing for some acute pain conditions are available. There is variability in the opioid analgesic dose and duration needed to adequately manage pain due both to the cause of pain and to individual patient factors. Initiate the dosing regimen for each patient individually, taking into account the patient’s underlying cause and severity of pain, prior analgesic treatment and response, and risk factors for addiction, abuse, and misuse [see WARNINGS ]. Respiratory depression can occur at any time during opioid therapy, especially when initiating and following dosage increases with Levorphanol Tartrate Tablets. Consider this risk when selecting an initial dose and when making dose adjustments [see WARNINGS ].

Addiction, Abuse, and Misuse Levorphanol Tartrate Tablets contains levorphanol, a Schedule II controlled substance. As an opioid, Levorphanol Tartrate Tablets exposes users to the risks of addiction, abuse, and misuse [see DRUG ABUSE AND DEPENDENCE ]. Although the risk of addiction in any individual is unknown, it can occur in patients appropriately prescribed Levorphanol Tartrate Tablets. Addiction can occur at recommended dosages and if the drug is misused or abused. Assess each patient’s risk for opioid addiction, abuse, or misuse prior to prescribing Levorphanol Tartrate Tablets, and reassess all patients receiving Levorphanol Tartrate Tablets for the development of these behaviors and conditions. Risks are increased in patients with a personal or family history of substance abuse (including drug or alcohol abuse or addiction) or mental illness (e.g., major depression). The potential for these risks should not, however, prevent the proper management of pain in any given patient. Patients at increased risk may be prescribed opioids such as Levorphanol Tartrate Tablets, but use in such patients necessitates intensive counseling about the risks and proper use of Levorphanol Tartrate Tablets along with frequent reevaluation for signs of addiction, abuse and misuse. Consider prescribing naloxone for the emergency treatment of opioid overdose (see WARNINGS, Life-Threatening Respiratory Depression ; DOSAGE AND ADMINISTRATION, Patient Access to Naloxone for the Emergency Treatment of Opioid Overdose ).

In approximately 1400 patients treated with Levorphanol Tartrate Tablets in controlled clinical trials, the type and incidence of side effects were those expected of an opioid analgesic, and no unforeseen or unusual toxicity was reported. Drugs of this type are expected to produce a cluster of typical opioid effects in addition to analgesia, consisting of nausea, vomiting, altered mood and mentation, pruritus, flushing, difficulties in urination, constipation, and biliary spasm. The frequency and intensity of these effects appears to be dose related. Although listed as adverse events these are expected pharmacologic actions of these drugs and should be interpreted as such by the clinician. The following adverse events have been reported with the use of Levorphanol Tartrate Tablets: Body as a Whole: abdominal pain, dry mouth, sweating Cardiovascular System: cardiac arrest, shock, hypotension, arrhythmias including bradycardia and tachycardia, palpitations, extra-systoles Digestive System: nausea, vomiting, dyspepsia, biliary tract spasm Nervous System: coma, suicide attempt, convulsions, depression, dizziness, confusion, lethargy, abnormal dreams, abnormal thinking, nervousness, drug withdrawal, hypokinesia, dyskinesia, hyperkinesia, CNS stimulation, personality disorder, amnesia, insomnia Respiratory System: apnea, cyanosis, hypoventilation Skin & Appendages: pruritus, urticaria, rash, injection site reaction Special Senses: abnormal vision, pupillary disorder, diplopia Urogenital System: kidney failure, urinary retention, difficulty urinating Postmarketing Experience The f…

Pregnancy Neonatal Opioid Withdrawal Syndrome Inform female patients of reproductive potential that use of Levorphanol Tartrate Tablets for an extended period of time during pregnancy can result in neonatal opioid withdrawal syndrome, which may be life-threatening if not recognized and treated [see WARNINGS , PRECAUTIONS; Pregnancy ]. Embryo-Fetal Toxicity Inform female patients of reproductive potential that Levorphanol Tartrate Tablets can cause fetal harm and to inform the prescriber of a known or suspected pregnancy [see WARNINGS , PRECAUTIONS; Pregnancy ].

Metabolism

The pharmacokinetics of levorphanol have been studied in a limited number of cancer patients following intravenous (IV), intramuscular (IM) and oral (PO) administration. Following IV administration plasma concentrations of levorphanol decline in a triexponential manner with a terminal half-life of 11 to 16 hours and a clearance of 0.78 to 1.1 L/kg/hr.

Clinical Presentation Acute overdose with Levorphanol Tartrate Tablets can be manifested by respiratory depression, somnolence progressing to stupor or coma, skeletal muscle flaccidity, cold and clammy skin, constricted pupils, and, in some cases, pulmonary edema, bradycardia, hypotension, hypoglycemia, partial or complete airway obstruction, atypical snoring, and death. Marked mydriasis rather than miosis may be seen with hypoxia an overdose situations. Treatment of Overdose In case of overdose, priorities are the reestablishment of a patient and protected airway and institution of assisted or controlled ventilation, if needed. Employ other supportive measures (including oxygen and vasopressors) in the management of circulatory shock and pulmonary edema as indicated. Cardiac arrest or arrhythmias will require advanced life-support measures. Opioid antagonists, such as naloxone, are specific antidotes to respiratory depression resulting from opioid overdose. For clinically significant respiratory or circulatory depression secondary to resulting from opioid overdose.

• Mar 31, 2000ANDAANDA074278Hikma
• Dec 13, 2018ANDAANDA211484Acertis Pharms
• Dec 13, 2019ANDAANDA212024Specgx Llc
• Jul 1, 2020ANDAANDA213479Novitium Pharma
• Jun 17, 2021ANDAANDA213906Sun Pharm Inds Inc

1. 1Product Dose Omission Issue369.9%
2. 2Pain297.9%
3. 3Drug Ineffective256.8%
4. 4Nausea256.8%
5. 5Product Dose Omission215.8%
6. 6Headache174.7%
7. 7Diarrhoea133.6%
8. 8Hyperhidrosis133.6%
9. 9Product Availability Issue123.3%
10. 10Withdrawal Syndrome123.3%
11. 11Anxiety113.0%
12. 12Dizziness113.0%
13. 13Inappropriate Schedule Of Drug Administration113.0%
14. 14Vomiting113.0%
15. 15Constipation92.5%

Recent PubMed references pinned to Levorphanol as a MeSH major topic. Citations link to pubmed.ncbi.nlm.nih.gov.

• Tapentadol, Buprenorphine, and Levorphanol for the Treatment of Neuropathic Pain: a Systematic Review.
  Current pain and headache reports · 2021 · Erosa SC, Haffey PR, Mehta N, et al.
  PMID 33630185DOI 10.1007/s11916-020-00934-z
• Levorphanol versus methadone use: safety considerations.
  Annals of palliative medicine · 2020 · Haider A, Reddy A
  PMID 32156130DOI 10.21037/apm.2020.02.01
• Pharmacological Characterization of Levorphanol, a G-Protein Biased Opioid Analgesic.
  Anesthesia and analgesia · 2019 · Le Rouzic V, Narayan A, Hunkle A, et al.
  PMID 29649035DOI 10.1213/ANE.0000000000003360
• Identifying Levorphanol Ingestion Using Urine Biomarkers in Health Care Patients.
  Pain physician · 2018 · Watson AR, Roberts A
  PMID 29565959
• Levorphanol for Treatment of Intractable Neuropathic Pain in Cancer Patients.
  Journal of palliative medicine · 2018 · Reddy A, Ng A, Mallipeddi T, et al.
  PMID 29377758DOI 10.1089/jpm.2017.0475
• Levorphanol use: past, present and future.
  Postgraduate medicine · 2016 · Gudin J, Fudin J, Nalamachu S, et al.
  PMID 26635068DOI 10.1080/00325481.2016.1128308
• Is levorphanol a better option than methadone?
  Pain medicine (Malden, Mass.) · 2015 · Pham TC, Fudin J, Raffa RB, et al.
  PMID 26307179DOI 10.1111/pme.12795
• Levorphanol #240.
  Journal of palliative medicine · 2011 · Loitman JE
  PMID 21699425DOI 10.1089/jpm.2011.9673

The 2 most recently updated of 2 ClinicalTrials.gov registrations naming Levorphanol as an intervention. Registration is not evidence of efficacy or safety — reference crosswalk only.

• Levorphanol as a Second Line Opioid in Reducing Pain in Patients With Cancer
  Terminated · Early phase 1 · Interventional · 43 enrolled · M.D. Anderson Cancer Center
  NCT03579446updated 2025-08-03
• Evolution of Analgesic Tolerance With Opioids
  Completed · Interventional · 60 enrolled · University of California, San Francisco
  NCT00275249updated 2011-04-14

Frequently asked questions

How does Levorphanol work?

Levorphanol is a full opioid agonist and is relatively selective for the mu-opioid receptor, although it can bind to other opioid receptors at higher doses. The principal therapeutic action of levorphanol is analgesia.

What is Levorphanol used for?

According to FDA labeling, Levorphanol carries indications including: Levorphanol Tartrate Tablets are indicated for the management of pain severe enough to require an opioid analgesic and for which alternative treatments are inadequate. Limitations of Use Because of the risks of addiction, abuse, and misuse with opioids, which can occur at any dosage or duration [see WARNINGS ], reserve Levorphanol Tartrate Tablets for use in patients for whom alternative treatment options (e.g., non-opioid analgesics): • Have not been tolerated or are not expected to be tolerated, • Have not provided adequate analgesia or are not expected to provide adequate analgesia Levorphanol Tartrate Tablets should not be used for an extended period of time unless the pain remains severe enough to require an opioid analgesic and for which alternative treatment options continue to be inadequate.. This is a reference summary of labeled uses, not medical advice or a treatment recommendation.

What class of drug is Levorphanol?

Levorphanol is classified as Opioid Agonist, Full Opioid Agonists, Opioid mu-Receptor Agonists, Analgesia, Decreased Medullary Respiratory Drive, Decreased Organized Electrical Activity.

What are the brand names for Levorphanol?

Levorphanol is marketed under brand names including Xyvona.

What are the contraindications for Levorphanol?

Levorphanol labeling lists contraindications including: Levorphanol Tartrate Tablets are contraindicated in patients with: • Significant respiratory depression [see WARNINGS ] • Acute or severe bronchial asthma in an unmonitored setting or in the absence of resuscitative equipment [see WARNINGS ] • Known or suspected gastrointestinal obstruction, including paralytic ileus [see WARNINGS ] • Hypersensitivity to levorphanol or any of the formulation excipients (e.g., anaphylaxis) [see WARNINGS ]. Always consult the full prescribing information and a clinician.