section name header

Introduction ⬇

VA Class:CN101

AHFS Class:

Generic Name(s):

Associated Monographs

Notification

REMS:

FDA approved a REMS for levorphanol tartrate to ensure that the benefits outweigh the risk. The REMS may apply to one or more preparations of levorphanol tartrate and consists of the following: medication guide and elements to assure safe use. See the FDA REMS page ([Web]).

  • FDA drug safety communication (4/13/2023):500 As part of its ongoing efforts to address the nation's opioid crisis, FDA is requiring several updates to the prescribing information of opioid pain medicines. The changes are being made to provide additional guidance for safe use of these drugs while also recognizing the important benefits when used appropriately. The changes apply to both immediate-release (IR) and extended-release/long-acting preparations (ER/LA).
  • Updates to the IR opioids state that these drugs should not be used for an extended period unless the pain remains severe enough to require an opioid pain medicine and alternative treatment options are insufficient, and that many acute pain conditions treated in the outpatient setting require no more than a few days of an opioid pain medicine.
  • Updates to the ER/LA opioids recommend that these drugs be reserved for severe and persistent pain requiring an extended period of treatment with a daily opioid pain medicine and for which alternative treatment options are inadequate.
  • A new warning is being added about opioid-induced hyperalgesia (OIH) for both IR and ER/LA opioid pain medicines. This includes information describing the symptoms that differentiate OIH from opioid tolerance and withdrawal.
  • Information in the boxed warning for all IR and ER/LA opioid pain medicines will be updated and reordered to elevate the importance of warnings concerning life-threatening respiratory depression, and risks associated with using opioid pain medicines in conjunction with benzodiazepines or other medicines that depress the central nervous system (CNS).
  • Other changes will also be required in various other sections of the prescribing information to educate clinicians, patients, and caregivers about the risks of these drugs.

Levorphanol tartrate is an opiate agonist.

Uses ⬆ ⬇

Levorphanol tartrate is a strong analgesic used in relief of moderate to severe pain. The drug is also used to relieve severe, intractable pain (e.g., in terminally ill patients). For further information on the role of opiate analgesics in the management of acute or chronic pain, see Uses: Pain, in the Opiate Agonists General Statement 28:08.08.

Dosage and Administration ⬆ ⬇

[Section Outline]

Administration !!navigator!!

Levorphanol tartrate is administered orally.

Dosage !!navigator!!

Levorphanol tartrate should be given at the lowest effective dosage and for the shortest duration of therapy consistent with the treatment goals of the patient.411,413,431,432,435 Reduced dosage is indicated in poor-risk patients and in very old patients. If concomitant therapy with other CNS depressants is required, the lowest effective dosages and shortest possible duration of concomitant therapy should be used.700,703 The initial dose of levorphanol tartrate should be reduced by 50% or more in patients with compromised respiratory function and in those receiving other drugs that depress respiration.

The usual oral adult dosage of levorphanol tartrate is 2 mg every 6-8 hours as needed; the dosage may be increased to 3 mg every 6-8 hours if necessary.

When an “around-the-clock” dosing regimen is used, at least 72 hours should elapse between dosage adjustments.

For acute pain not related to trauma or surgery, the prescribed quantity should be limited to the amount needed for the expected duration of pain severe enough to require opiate analgesia (generally 3 days or less and rarely more than 7 days).411,433,434,435 When opiate analgesics are used for the management of chronic noncancer pain, the US Centers for Disease Control and Prevention (CDC) recommends that primary care clinicians carefully reassess individual benefits and risks before prescribing dosages equivalent to 50 mg or more of morphine sulfate daily and avoid dosages equivalent to 90 mg or more of morphine sulfate daily or carefully justify their decision to titrate the dosage to such levels.411 Other experts recommend consulting a pain management specialist before exceeding a dosage equivalent to 80-120 mg of morphine sulfate daily.423,431 For further information on the management of opiate analgesic therapy, see Dosage and Administration: Dosage, in the Opiate Agonists General Statement 28:08.08.

Cautions ⬆ ⬇

Levorphanol tartrate shares the toxic potentials of the opiate agonists, and the usual precautions of opiate agonist therapy should be observed. (See Cautions in the Opiate Agonists General Statement 28:08.08.)

Safe use of levorphanol tartrate in pregnancy and children has not been established.

Other Information ⬆ ⬇

[Section Outline]

Pharmacology

Although levorphanol tartrate may produce less nausea, vomiting, and constipation, it appears to produce more sedation and smooth muscle stimulation than do equianalgesic doses of morphine sulfate.

Pharmacokinetics

Levorphanol tartrate is well absorbed following oral administration. Following oral administration, peak plasma concentrations are achieved in about 1 hour. With multiple oral dosing, steady-state plasma concentrations usually are achieved in 3 days. Levorphanol's duration of analgesic effect (6-8 hours) is longer than that produced by morphine or meperidine.

Levorphanol tartrate is metabolized primarily in the liver where it undergoes conjugation with glucuronic acid and is excreted primarily in urine as the glucuronide conjugate. Following IV administration (parenteral preparation no longer commercially available in the US), a terminal half-life of levorphanol of 11-16 hours has been reported.

Chemistry and Stability

Chemistry !!navigator!!

Levorphanol tartrate is an opiate agonist. The drug is a synthetic morphinan derivative which is structurally related to the phenanthrene-derivative opiate agonists. Levorphanol tartrate occurs as a practically white, crystalline powder and is sparingly soluble in water and slightly soluble in alcohol.

Stability !!navigator!!

Levorphanol tartrate tablets should be stored in well-closed, light-resistant containers at 15-30°C.

Additional Information

For further information on chemistry, pharmacology, uses, cautions, chronic toxicity, acute toxicity, drug interactions, and dosage and administration of levorphanol tartrate, see the Opiate Agonists General Statement 28:08.08.

Preparations ⬆ ⬇

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.

Levorphanol tartrate is subject to control under the Federal Controlled Substances Act of 1970 as a schedule II (C-II) drug.

Levorphanol Tartrate

Routes

Dosage Forms

Strengths

Brand Names

Manufacturer

Oral

Tablets

2 mg*

Levorphanol Tartrate Tablets (C-II; scored)

* available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name

Copyright ⬆ ⬇

AHFS® Drug Information. © Copyright, 1959-2024, Selected Revisions April 19, 2023. American Society of Health-System Pharmacists, Inc., 4500 East-West Highway, Suite 900, Bethesda, MD 20814.

References ⬆

Only references cited for selected revisions after 1984 are available electronically.

410. Nuckols TK, Anderson L, Popescu I et al. Opioid prescribing: a systematic review and critical appraisal of guidelines for chronic pain. Ann Intern Med . 2014; 160:38-47. [PubMed 24217469]

411. Dowell D, Haegerich TM, Chou R. CDC Guideline for Prescribing Opioids for Chronic Pain - United States, 2016. MMWR Recomm Rep . 2016; 65:1-49. [PubMed 26987082]

412. Chou R, Fanciullo GJ, Fine PG et al. Clinical guidelines for the use of chronic opioid therapy in chronic noncancer pain. J Pain . 2009; 10:113-30. [PubMedCentral][PubMed 19187889]

413. Management of Opioid Therapy for Chronic Pain Working Group, US Department of Veterans Affairs and Department of Defense. VA/DoD clinical practice guideline for management of opioid therapy for chronic pain. 2010 May. [Web]

414. Chou R, Cruciani RA, Fiellin DA et al. Methadone safety: a clinical practice guideline from the American Pain Society and College on Problems of Drug Dependence, in collaboration with the Heart Rhythm Society. J Pain . 2014; 15:321-37. [PubMed 24685458]

415. Manchikanti L, Abdi S, Atluri S et al. American Society of Interventional Pain Physicians (ASIPP) guidelines for responsible opioid prescribing in chronic non-cancer pain: Part 2--guidance. Pain Physician . 2012; 15(3 Suppl):S67-116.

416. Park TW, Saitz R, Ganoczy D et al. Benzodiazepine prescribing patterns and deaths from drug overdose among US veterans receiving opioid analgesics: case-cohort study. BMJ . 2015; 350:h2698. [PubMedCentral][PubMed 26063215]

417. Jones CM, McAninch JK. Emergency Department Visits and Overdose Deaths From Combined Use of Opioids and Benzodiazepines. Am J Prev Med . 2015; 49:493-501. [PubMed 26143953]

418. Dasgupta N, Funk MJ, Proescholdbell S et al. Cohort Study of the Impact of High-Dose Opioid Analgesics on Overdose Mortality. Pain Med . 2016; 17:85-98. [PubMed 26333030]

419. Prescription Drug Monitoring Program Training and Technical Assistance Center (PDMP TTAC). Criteria for mandatory enrollment or query of PDMP. From PDMP TTAC website. Accessed 2016 Sep 14. [Web]

420. National Alliance for Model State Drug Laws (NAMSLD). Overview of state pain management and prescribing policies. From NAMSLD webiste. Accessed 2016 Sep 14. [Web]

421. Bennett A (Maine Office of Governor). Augusta, ME: 2016 Apr 19. Governor signs major opioid prescribing reform bill. Press release. [Web]

422. American Academy of Pain Medicine (AAPM). Use of opioids for the treatment of chronic pain. A statement from the American Academy of Pain Medicine. From AAPM website. 2013 Feb. [Web]

423. Franklin GM, American Academy of Neurology. Opioids for chronic noncancer pain: a position paper of the American Academy of Neurology. Neurology . 2014; 83:1277-84. [PubMed 25267983]

424. Dunn KM, Saunders KW, Rutter CM et al. Opioid prescriptions for chronic pain and overdose: a cohort study. Ann Intern Med . 2010; 152:85-92. [PubMedCentral][PubMed 20083827]

425. Gomes T, Mamdani MM, Dhalla IA et al. Opioid dose and drug-related mortality in patients with nonmalignant pain. Arch Intern Med . 2011; 171:686-91. [PubMed 21482846]

426. Bohnert AS, Valenstein M, Bair MJ et al. Association between opioid prescribing patterns and opioid overdose-related deaths. JAMA . 2011; 305:1315-21. [PubMed 21467284]

429. Paice JA, Portenoy R, Lacchetti C et al. Management of Chronic Pain in Survivors of Adult Cancers: American Society of Clinical Oncology Clinical Practice Guideline. J Clin Oncol . 2016; 34:3325-45. [PubMed 27458286]

430. Chou R, Gordon DB, de Leon-Casasola OA et al. Management of Postoperative Pain: A Clinical Practice Guideline From the American Pain Society, the American Society of Regional Anesthesia and Pain Medicine, and the American Society of Anesthesiologists' Committee on Regional Anesthesia, Executive Committee, and Administrative Council. J Pain . 2016; 17:131-57. [PubMed 26827847]

431. Washington State Agency Medical Directors' Group (AMDG). Interagency guideline on prescribing opioids for pain, 3rd ed. From Washington State AMDG website. 2015 Jun. [Web]

432. Hegmann KT, Weiss MS, Bowden K et al. ACOEM practice guidelines: opioids for treatment of acute, subacute, chronic, and postoperative pain. J Occup Environ Med . 2014; 56:e143-59.

433. Cantrill SV, Brown MD, Carlisle RJ et al. Clinical policy: critical issues in the prescribing of opioids for adult patients in the emergency department. Ann Emerg Med . 2012; 60:499-525. [PubMed 23010181]

434. Thorson D, Biewen P, Bonte B et al, for Institute for Clinical Systems Improvement (ICSI). Acute pain assessment and opioid prescribing protocol. From ICSI website. 2014 Jan. [Web]

435. New York City Department of Health and Mental Hygiene. New York City emergency department discharge opioid prescribing guidelines. From NYC Health website. 2013 Jan. [Web]

436. Chou R, Deyo R, Devine B et al. The effectiveness and risks of long-term opioid treatment of chronic pain. Evidence report/technology assessment No. 218. Rockville, MD: Agency for Healthcare Research and Quality (AHRQ); 2014 Sep. [Web]

500. FDA drug safety communication . FDA updates prescribing information for all opioid pain medicines to provide additional guidance for safe use Includes updates to help reduce unnecessary prescribing; issued Apr 13 2023. From FDA website. [Web]

700. US Food and Drug Administration. Drug safety communication: FDA warns about serious risks and death when combining opioid pain or cough medicines with benzodiazepines; requires its strongest warning. Silver Spring, MD; 2016 Aug 31. From FDA website. [Web]

701. Jones CM, Mack KA, Paulozzi LJ. Pharmaceutical overdose deaths, United States, 2010. JAMA . 2013; 309:657-9. [PubMed 23423407]

702. Jones CM, Paulozzi LJ, Mack KA et al. Alcohol involvement in opioid pain reliever and benzodiazepine drug abuse-related emergency department visits and drug-related deaths - United States, 2010. MMWR Morb Mortal Wkly Rep . 2014; 63:881-5. [PubMedCentral][PubMed 25299603]

703. Hertz S. Letter to manufacturers of opioid analgesics: safety labeling change notification. Silver Spring, MD: US Food and Drug Administration. Accessed 2017 Mar 20. [Web]

704. Sentynl Therapeutics. Levorphanol tartrate tablets prescribing information. Solana Beach, CA; 2016 Dec.

750. Food and Drug Administration. FDA Drug Safety Communication: FDA recommends health care professionals discuss naloxone with all patients when prescribing opioid pain relievers or medicines to treat opioid use disorder; consider prescribing naloxone to those at increased risk of opioid overdose. 2020 Jul 23. From FDA website. Accessed 2020 Jul 28. [Web]