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Keep container tightly closed in a dry and well-ventilated place. Light sensitive. Keep in a dry place. /Levorphanol tartrate dihydrate/

Store at 20 deg to 25 °C (68 deg to 77 °F)

Personal precautions: Wear respiratory protection. Avoid dust formation. Avoid breathing vapors, mist or gas. Ensure adequate ventilation. Evacuate personnel to safe areas. Avoid breathing dust. Environmental precautions: Prevent further leakage or spillage if safe to do so. Do not let product enter drains. Methods and materials for containment and cleaning up: Pick up and arrange disposal without creating dust. Sweep up and shovel. Keep in suitable, closed containers for disposal. /Levorphanol tartrate dihydrate/

SRP: Expired or waste pharmaceuticals shall carefully take into consideration applicable DEA, EPA, and FDA regulations. It is not appropriate to dispose by flushing the pharmaceutical down the toilet or discarding to trash. If possible return the pharmaceutical to the manufacturer for proper disposal being careful to properly label and securely package the material. Alternatively, the waste pharmaceutical shall be labeled, securely packaged and transported by a state licensed medical waste contractor to dispose by burial in a licensed hazardous or toxic waste landfill or incinerator.

SRP: At the time of review, regulatory criteria for small quantity disposal are subject to significant revision, however, household quantities of waste pharmaceuticals may be managed as follows: Mix with wet cat litter or coffee grounds, double bag in plastic, discard in trash.

Product: Offer surplus and non-recyclable solutions to a licensed disposal company. Contact a licensed professional waste disposal service to dispose of this material. Dissolve or mix the material with a combustible solvent and burn in a chemical incinerator equipped with an afterburner and scrubber. Contaminated packaging: Dispose of as unused product. /Levorphanol tartrate dihydrate/

SRP: Local exhaust ventilation should be applied wherever there is an incidence of point source emissions or dispersion of regulated contaminants in the work area. Ventilation control of the contaminant as close to its point of generation is both the most economical and safest method to minimize personnel exposure to airborne contaminants. Ensure that the local ventilation moves the contaminant away from the worker.

Avoid contact with skin and eyes. Avoid formation of dust and aerosols. Provide appropriate exhaust ventilation at places where dust is formed. Normal measures for preventive fire protection. /Levorphanol tartrate dihydrate/

Avoid contact with skin, eyes and clothing. Wash hands before breaks and immediately after handling the product. /Levorphanol tartrate dihydrate/

Gloves must be inspected prior to use. Use proper glove removal technique (without touching glove's outer surface) to avoid skin contact with this product. Dispose of contaminated gloves after use in accordance with applicable laws and good laboratory practices. Wash and dry hands. /Levorphanol tartrate dihydrate/

Hand protection: Handle with gloves. /Levorphanol tartrate dihydrate/

Respiratory protection: Where risk assessment shows air-purifying respirators are appropriate use a full-face particle respirator type N100 (US) or type P3 (EN 143) respirator cartridges as a backup to engineering controls. If the respirator is the sole means of protection, use a full-face supplied air respirator. Use respirators and components tested and approved under appropriate government standards such as NIOSH (US) or CEN (EU). /Levorphanol tartrate dihydrate/

Skin and body protection: Complete suit protecting against chemicals, The type of protective equipment must be selected according to the concentration and amount of the dangerous substance at the specific workplace. /Levorphanol tartrate dihydrate/

Eye protection: Face shield and safety glasses Use equipment for eye protection tested and approved under appropriate government standards such as NIOSH (US) or EN 166(EU). /Levorphanol tartrate dihydrate/

The specific treatment of suspected levorphanol tartrate overdosage is immediate establishment of an adequate airway and ventilation, followed (if necessary) by intravenous naloxone. The respiratory and cardiac status of the patient should be continuously monitored and appropriate supportive measures instituted, such as oxygen, intravenous fluids and/or vasopressors, if required. Physicians are reminded that the duration of levorphanol action far exceeds the duration of action of naloxone, and repeated dosing with naloxone may be required. Naloxone should be administered cautiously to persons known or suspected to be physically dependent on Levorphanol. In such cases an abrupt and complete reversal of opioid effects may precipitate an acute abstinence syndrome. If necessary to administer naloxone to the physically dependent patient, the antagonist should be administered with extreme care and by titration with smaller than usual doses of the antagonist. (L1712)

Concurrent use of levorphanol with all central nervous system depressants (e.g., alcohol, sedatives, hypnotics, other opioids, general anesthetics, barbiturates, tricyclic antidepressants, phenothiazines, tranquilizers, skeletal muscle relaxants and antihistamines) may result in additive central nervous system depressant effects. Respiratory depression, hypotension, and profound sedation or coma may occur. When such combined therapy is contemplated, the dose of one or both agents should be reduced. Although no interaction between MAO inhibitors and levorphanol has been observed, it is not recommended for use with MAO inhibitors.

Agonist/antagonist analgesics (e.g., pentazocine, nalbuphine, butorphanol, dezocine and buprenorphine) should NOT be administered to a patient who has received or is receiving a course of therapy with a pure agonist opioid analgesic such as levorphanol. In opioid-dependent patients, mixed agonist/antagonist analgesics may precipitate withdrawal symptoms.

Concurrent use of levorphanol with central nervous system depressants (e.g., alcohol, sedatives, hypnotics, other opioids, barbiturates, tricyclic antidepressants, phenothiazines, tranquilizers, skeletal muscle relaxants and antihistamines) may result in additive central nervous system depressant effects.

TERRESTRIAL FATE: Based on a classification scheme(1), an estimated Koc value of 560(SRC), determined from a log Kow of 3.11(2) and a regression-derived equation(3), indicates that levorphanol is expected to have low mobility in soil(SRC). The pKa of levorphanol is 9.58(4), indicating that this compound will exist almost entirely in the cation form in the environment and cations generally adsorb more strongly to soils containing organic carbon and clay than their neutral counterparts(5). Volatilization from moist soil is not expected because the compound exists as a cation and ions do not volatilize. Levorphanol is not expected to volatilize from dry soil surfaces(SRC) based upon an estimated vapor pressure of 2.2X10-7 mm Hg at 25 °C(SRC), determined from a fragment constant method(3). Biodegradation data in soil were not available(SRC, 2014).

AQUATIC FATE: Based on a classification scheme(1), an estimated Koc value of 560(SRC), determined from a log Kow of 3.11(2) and a regression-derived equation(3), indicates that levorphanol is expected to adsorb to suspended solids and sediment(SRC). A pKa of 9.58(4) indicates levorphanol will exist almost entirely in the cation form at pH values of 5 to 9 and, therefore, volatilization from water surfaces and bioconcentration are not expected to be an important fate processes(SRC). Biodegradation data in water were not available(SRC, 2014).

ATMOSPHERIC FATE: According to a model of gas/particle partitioning of semivolatile organic compounds in the atmosphere(1), levorphanol, which has an estimated vapor pressure of 2.2X10-7 mm Hg at 25 °C(SRC), determined from a fragment constant method(2), will exist in both the vapor and particulate phases in the ambient atmosphere. Vapor-phase levorphanol is degraded in the atmosphere by reaction with photochemically-produced hydroxyl radicals(SRC); the half-life for this reaction in air is estimated to be 0.08 days(SRC), calculated from its rate constant of 2.1X10-10 cu cm/molecule-sec at 25 °C(SRC) that was derived using a structure estimation method(3). Particulate-phase levorphanol may be removed from the air by wet and dry deposition(SRC). Levorphanol contains chromophores that absorb at wavelengths >290 nm(4) and, therefore, may be susceptible to direct photolysis by sunlight(SRC).

The Koc of levorphanol is estimated as 560(SRC), using a log Kow of 3.11(1) and a regression-derived equation(2). According to a classification scheme(3), this estimated Koc value suggests that levorphanol is expected to have low mobility in soil. The pKa of levorphanol is 9.58(4), indicating that this compound will exist almost entirely in the cation form in the environment and cations generally adsorb more strongly to soils containing organic carbon and clay than their neutral counterparts(5).

/SIGNS AND SYMPTOMS/ As with all opioids, overdose can occur due to accidental or intentional misuse of this product, especially in infants and children who may gain access to the drug in the home. Based on its pharmacology, levorphanol overdosage would be expected to produce signs of respiratory depression, cardiovascular failure (especially in predisposed patients), and/or central nervous system depression. Serious overdosage with levorphanol is characterized by respiratory depression (a decrease in respiratory rate and/or tidal volume, periodic breathing, cyanosis), extreme somnolence progressing to stupor or coma, skeletal muscle flaccidity, cold and clammy skin, constricted pupils, and sometimes bradycardia and hypotension. In severe overdosage, apnea, circulatory collapse, cardiac arrest and death may occur.

/SIGNS AND SYMPTOMS/ Discontinuation of levorphanol after chronic use has been reported to result in withdrawal syndromes, and some reports of overuse and self-reported addiction have been received. Neither withdrawal nor withdrawal symptoms are usually expected in postoperative patients who used the drug for less than a week or in patients who are gradually tapered off the drug after longer use.

/SIGNS AND SYMPTOMS/ Levorphanol, like morphine, may be expected to produce serious or potentially fatal respiratory depression if given in an excessive dose, too frequently, or if given in full dosage to compromised or vulnerable patients. This is because the doses required to produce analgesia in the general clinical population may cause serious respiratory depression in vulnerable patients. Safe usage of this potent opioid requires that the dose and dosage interval be individualized to each patient based on the severity of the pain, weight, age, diagnosis and physical status of the patient, and the kind and dose of concurrently administered medication. The initial dose of levorphanol should be reduced by 50% or more when the drug is given to patients with any condition affecting respiratory reserve or in conjunction with other drugs affecting the respiratory center. Subsequent doses should then be individually titrated according to the patient's response. Respiratory depression produced by levorphanol tartrate can be reversed by naloxone, a specific antagonist

Schedule II shall consist of the drugs and other substances, by whatever official name, common or usual name, chemical name, or brand name designated, listed in this section. Each drug or substance has been assigned the DEA Controlled Substances Code Number set forth opposite it. Unless specifically excepted or unless in another schedule any of the following opiates, including its isomers, esters, ethers, salts and salts of isomers, esters and ethers whenever the existence of such isomers, esters, ethers, and salts is possible within the specific chemical designation, dextrorphan and levopropoxyphene excepted. Levorphanol (DEA Code Number: 9220) is included on this list.

The Approved Drug Products with Therapeutic Equivalence Evaluations identifies currently marketed prescription drug products, including levorphanol tartrate, approved on the basis of safety and effectiveness by FDA under sections 505 of the Federal Food, Drug, and Cosmetic Act. /Levorphanol tartrate/

Levorphanol is a Schedule II controlled substance.

Schedule II Controlled Substance: (A) The drug or other substance has a high potential for abuse; (B) The drug or other substance has a currently accepted medical use in treatment in the United States or a currently accepted medical use with severe restrictions; and (C) Abuse of the drug or other substances may lead to severe psychological or physical dependence.

MEDICATION

Analgesics, Opioid; Narcotics

THERAPEUTIC CATEGORY: Analgesic

For the management of moderate to severe pain or as a preoperative medication where an opioid analgesic is appropriate

5,6,7,8,-Tetrahydro-2-methylisoquinolinium bromide is metathesized with p-methoxybenzyl magnesium bromide, and the product rearranges at the expense of the 1,2-double bond to form 1-(p-methoxybenzyl)-2-methyl-1,2,5,6,7,8-hexahydroisoquinoline. ... A solution of the hydrochloride of 1-(p-methoxybenzyl)-2-methyl-1,2,5,6,7,8-hexahydroisoquinoline is then hydrogenated at the 3,4-positions with the aid of platinized charcoal, and subsequent treatment with ammonia liberates the dl-1,2,3,4,5,6,7,8-octahydro compound, which may be resolved into its (+)- and (-)-enantiomers by the usual procedures. The final step in the preparation of the base involves heating the (-)-enantiomer with phosphoric acid at 150 °C whereby cyclization between the isoquinoline residue and the benzene ring occurs at the expense of the remaining double bond of the isoquinoline. During the treatment with phosphoric acid, the methoxy group simultaneously is converted to hydroxy, thus producing levorphanol. The tartrate may be produced by dissolution of the base in aqueous tartaric acid solution and recrystallizing.

Oral: Tablets: 2 mg Levo-Dromoran, C-II; scored (Valeant) /Levorphanol tartrate; Discontinued/

Oral: Tablets: 2 mg Levorphanol Tartrate Tablets, C-II; scored (Roxane) /Levorphanol tartrate/

LEVORPHANOL IS ONLY COMMERCIALLY AVAIL OPOID AGONIST MORPHINAN SERIES. D ISOMER (DEXTRORPHAN) IS RELATIVELY DEVOID OF ANALGESIC ACTION.

Orally active synthetic morphine analog.