Class: Opiate Agonists
VA Class: CN101
CAS Number: 5985-38-6
Brands: Levo-Dromoran
Introduction
Opiate agonist; phenanthrene derivative.a b c
Uses for Levorphanol Tartrate
Pain
Relief of moderate to severe pain.a b
Usually, temporary relief of moderate to severe pain such as that associated with acute and some chronic medical disorders including renal or biliary colic, acute trauma, postoperative pain, and cancer.c
Consider around-the-clock dosing of analgesics in the initial stages of acute pain to avoid wide swings in pain and sedation often associated with as-needed dosing regimens.c
In the management of chronic pain associated with a terminal illness such as cancer, the principal goal of analgesic therapy is to make the patient relatively pain-free while maintaining as good a quality of life as possible.c
Analgesic therapy must be individualized and titrated according to patient response and tolerance.c
Levorphanol Tartrate Dosage and Administration
Administration
Administer orally.b
Dosage
Available as levorphanol tartrate; dosage expressed in terms of the salt.b
Give the smallest effective dose as infrequently as possible to minimize the development of tolerance and physical dependence.a
Individualize dosage according to clinical status of the patient, desired therapeutic effect, degree of existing opiate tolerance, and age and weight; assess dosage at periodic intervals.b
Reduce dosage in poor-risk patients, in geriatric patients, in patients receiving other CNS depressants.a b
Reduce initial dose ≥50% in patients with compromised respiratory function and in those receiving other drugs that depress respiration.b (See Specific Drugs under Interactions.)
Reduce initial dose in patients with hypothyroidism, Addison's disease, toxic psychosis, prostatic hypertrophy, urethral strictures, acute alcoholism, or delirium tremens.b
In patients who are tolerant to opiate agonists and who require high dosages (e.g., patients with severe chronic pain associated with cancer), individualize dosage of highly potent preparations based on response and tolerance.b
Avoid abrupt withdrawal from relatively high dosages (e.g., in chronic pain patients) since precipitation of severe abstinence syndrome is likely.b
Assess patients for signs of hypoventilation or excessive sedation during therapy.b
Adults
Pain
Oral
Usually, initiate with 2 mg every 6–8 hours as needed.b May increase to 3 mg every 6–8 hours.b Adjust according to response and tolerance.b
Initial dosages >6–12 mg in 24 hours not recommended in non-opiate-tolerant patients; lower dosages may be appropriate.b
If a patient is placed on an “around-the-clock” dosing regimen, allow at least 72 hours to elapse between dosage adjustments; this is needed to avoid excessive sedation.b (See Half-life under Pharmacokinetics.)
Switching from Morphine to Levorphanol
Oral
The manufacturer states that the initial total daily dose of oral levorphanol should be 1/15 to 1/12 of the total daily dose of oral morphine; adjust subsequent dosage based on clinical response.b
Prescribing Limits
Adults
Pain
Oral
Maximum initial daily dose in non-opiate-tolerant patients: 6–12 mg in 24 hours.b
Special Populations
Hepatic Impairment
Reduce initial dose in patients with severe hepatic impairment.b
Renal Impairment
Reduce initial dose in patients with severe renal impairment.b
Geriatric Patients
Reduce initial dose by ≥50% in debilitated geriatric patients.b
Respiratory Impairment
Reduce initial dose by ≥50% in patients with any condition affecting respiratory reserve.b Titrate subsequent doses according to patient's response.b
Cautions for Levorphanol Tartrate
Contraindications
Known hypersensitivity to levorphanol or any ingredient in the formulation.b
Warnings/Precautions
Warnings
Respiratory Depression
Causes dose-related respiratory depression.b
Occurs most frequently in debilitated patients and following large and/or frequent doses.b
Use with extreme caution in patients with impaired respiratory reserve or respiratory depression (e.g., individuals with uremia, severe infection, obstructive respiratory conditions, restrictive respiratory diseases, intrapulmonary shunting, or chronic asthma).b
Use not recommended in patients with acute or severe asthma.b
Dependence and Abuse
Physical and psychologic dependence and tolerance may develop with repeated administration; abuse potential exists.b Use with caution.b
Use with careful surveillance in patients with a history of drug or alcohol dependence or abuse.b
Abrupt cessation of therapy or sudden reduction in dosage after prolonged use may result in withdrawal symptoms.b After prolonged exposure to opiate analgesics, if withdrawal is necessary, it must be undertaken gradually.b
Head Injury and Increased Intracranial Pressure
Respiratory depressant effects of levorphanol (with CO2 retention and secondary elevation of CSF pressure) may be markedly exaggerated in the presence of head injury, other intracranial lesions, or preexisting increase in intracranial pressure.b
Adverse effects of opiates may obscure the existence, extent, or course of intracranial pathology.b
Hypotensive Effects
Possible severe hypotension in individuals whose ability to maintain their BP is compromised by depleted blood volume or concomitant drugs that compromise vasculature tone (e.g., phenothiazines, general anesthetics).b
May produce orthostatic hypotension in ambulatory patients.b
Cardiovascular Effects
Limit use in patients with acute MI, myocardial dysfunction, or coronary insufficiency.b Manufacturer states effect of levorphanol on the cardiac function unknown.b
Biliary Tract Surgery
Moderate to marked increases in biliary tract pressure reported.b Use not recommended in patients undergoing biliary tract surgery.b
General Precautions
Acute Abdominal Conditions
May obscure diagnosis or clinical course of patients with acute abdominal conditions.b
Debilitated and Special-Risk Patients.
Use with caution in debilitated patients or in patients with hypothyroidism, Addison’s disease, prostatic hypertrophy, urethral stricture, toxic psychosis, acute alcoholism, or delirium tremens.b
Specific Populations
Pregnancy
Category C.b
Use not recommended during labor and delivery.b
Infants born to women regularly taking opiates during pregnancy may be physically dependent.b
Lactation
Not known whether levorphanol is distributed into human milk.b Discontinue nursing or the drug.b
Pediatric Use
Safety and efficacy not established in pediatric patients <18 years age.b
Geriatric Use
Use with caution.b Dosage adjustment recommended in debilitated geriatric patients.b (See Geriatric Patients under Dosage and Administration.)
Hepatic Impairment
Use with caution.b Extensive liver disease may predispose to excessive sedation, probably due to increased pharmacodynamic sensitivity or decreased hepatic metabolism of the drug.b Reduce initial dose in patients with severe hepatic impairment.b
Renal Impairment
Use with caution in patients with severe renal impairment; reduce initial dose in these patients.b
Common Adverse Effects
Nausea, vomiting, altered mood/mentation, flushing, urinary retention, pruritus, constipation, biliary spasm.b
Interactions for Levorphanol Tartrate
Specific Drugs
Drug | Interaction | Comments |
|---|---|---|
CNS depressants (e.g., opiate agonists, general anesthetics, tricyclic antidepressants, antihistamines, tranquilizers, phenothiazines, sedatives/hypnotics, alcohol) | Additive CNS effectsb | Reduce dosage of one or both agentsb |
MAO inhibitors | Concomitant use not recommendedb | |
Opiate partial agonists (butorphanol, buprenorphine, nalbuphine, pentazocine) | Possible reduced analgesic effect and/or withdrawal symptomsb | Avoid concomitant useb |
Respiratory depressants | Additive depressant effects on respirationb | Reduce initial dose of levorphanol by ≥50%b |
Skeletal muscle relaxants | May enhance the neuromuscular-blocking action of skeletal muscle relaxantsc Additive CNS effectsb | Reduce dosage of one or both agentsb |
Levorphanol Tartrate Pharmacokinetics
Absorption
Bioavailability
Well absorbed from the GI tract.a b Following oral administration, peak plasma concentration achieved in about 1 hour.b Steady-state plasma concentrations expected to be achieved by the third day of continuous dosing.b
Duration
6–8 hours.a
Distribution
Plasma Protein Binding
40%.b
Elimination
Metabolism
Extensively metabolized in the liver; undergoes conjugation with glucuronic acid.a b
Elimination Route
Primarily in urine as the glucuronide conjugate.a b
Half-life
IV administration: 11–16 hours.b
Stability
Storage
Oral
Tablets
Tight, light-resistant containers at 15–30°C.a b
ActionsActions
A potent analgesic; shares actions of the opiate agonists.b
Precise mechanism of action has not been fully elucidated; opiate agonists act at several CNS sites, involving several neurotransmitter systems to produce analgesia.c
Pain perception is altered in the spinal cord and higher CNS levels (e.g., substantia gelatinosa, spinal trigeminal nucleus, periaqueductal gray, periventricular gray, medullary raphe nuclei, hypothalamus).c
Opiate agonists do not alter the threshold or responsiveness of afferent nerve endings to noxious stimuli, nor peripheral nerve impulse conduction.c
Opiate agonists act at specific receptor binding sites in the CNS and other tissues; opiate receptors are concentrated in the limbic system, thalamus, striatum, hypothalamus, midbrain, and spinal cord.c
Agonist activity at the opiate μ- or κ-receptor can result in analgesia, miosis, and/or decreased body temperature.c
Agonist activity at the μ-receptor also can result in suppression of opiate withdrawal (and antagonist activity can result in precipitation of withdrawal).c
Respiratory depression may be mediated by μ-receptors, possibly μ2-receptors (which may be distinct from μ1-receptors involved in analgesia); κ- and δ-receptors may also be involved in respiratory depression.c
Advice to Patients
Importance of informing patients that levorphanol may impair mental and/or physical ability required for performance of potentially hazardous tasks; avoid driving or operating heavy machinery until effects on individual are known.b
Advise patients that levorphanol should not be combined with alcohol or other CNS depressants (e.g., sleep medications, tranquilizers).b
Risk of hypotension, dizziness, and syncope.b
Importance of informing patients that this is a drug of potential abuse and should be protected from theft.b
Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs, as well as any concomitant illnesses.b
Importance of women informing clinicians if they are or plan to become pregnant or plan to breast-feed.b
Importance of informing patients of other important precautionary information.b (See Cautions.)
Preparations
Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.
Levorphanol tartrate is subject to control under the Federal Controlled Substances Act of 1970 as a schedule II (C-II) drug.
* available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name
Routes | Dosage Forms | Strengths | Brand Names | Manufacturer |
|---|---|---|---|---|
Oral | Tablets | 2 mg* | Levo-Dromoran (C-II; scored) | Valeant |
Levorphanol Tartrate Tablets (C-II; scored) | Roxane |
Disclaimer
This report on medications is for your information only, and is not considered individual patient advice. Because of the changing nature of drug information, please consult your physician or pharmacist about specific clinical use.
The American Society of Health-System Pharmacists, Inc. and Drugs.com represent that the information provided hereunder was formulated with a reasonable standard of care, and in conformity with professional standards in the field. The American Society of Health-System Pharmacists, Inc. and Drugs.com make no representations or warranties, express or implied, including, but not limited to, any implied warranty of merchantability and/or fitness for a particular purpose, with respect to such information and specifically disclaims all such warranties. Users are advised that decisions regarding drug therapy are complex medical decisions requiring the independent, informed decision of an appropriate health care professional, and the information is provided for informational purposes only. The entire monograph for a drug should be reviewed for a thorough understanding of the drug's actions, uses and side effects. The American Society of Health-System Pharmacists, Inc. and Drugs.com do not endorse or recommend the use of any drug. The information is not a substitute for medical care.
AHFS Drug Information. © Copyright, 1959-2011, Selected Revisions September 2007. American Society of Health-System Pharmacists, Inc., 7272 Wisconsin Avenue, Bethesda, Maryland 20814.
References
a. AHFS drug information 2007. McEvoy GK, ed. Levorphanol. Bethesda, MD: American Society of Health-System Pharmacists; 2007:2137.
b. Roxane Laboratories. Levorphanol tartrate tablets prescribing information. Columbus, OH; 2004 Dec.
c. AHFS drug information 2007. McEvoy GK, ed. Opiod Agonists General Statement. Bethesda, MD: American Society of Health-System Pharmacists; 2007:2123-8.
More Levorphanol Tartrate resources
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