Levorphanol Tartrate Tablets contains levorphanol, a Schedule II controlled substance.
Levorphanol Tartrate Tablets contains levorphanol, a substance with a high potential for abuse similar to other opioids including fentanyl, hydrocodone, hydromorphone, methadone, morphine, oxycodone, oxymorphone and tapentadol. Levorphanol can be abused and is subject to misuse, addiction, and criminal diversion [see WARNINGS].
All patients treated with opioids require careful monitoring for signs of abuse and addiction, because use of opioid analgesic products carries the risk of addiction even under appropriate medical use.
Prescription drug abuse is the intentional nontherapeutic use of a prescription drug, even once, for its rewarding psychological or physiological effects.
Drug addiction is a cluster of behavioral, cognitive, and physiological phenomena that develop after repeated substance use and includes: a strong desire to take the drug, difficulties in controlling its use, persisting in its use despite harmful consequences, a higher priority given to drug use than to other activities and obligations, increased tolerance, and sometimes a physical withdrawal.
“Drug-seeking” behavior is very common in persons with substance use disorders. Drug- seeking tactics include emergency calls or visits near the end of office hours, refusal to undergo appropriate examination, testing, or referral, repeated “loss” of prescriptions, tampering with prescriptions, and reluctance to provide prior medical records or contact information for other treating health care provider(s). “Doctor shopping” (visiting multiple prescribers to obtain additional prescriptions is common among drug abusers and people suffering from untreated addiction. Preoccupation with achieving adequate pain relief can be appropriate behavior in a patient with poor pain control.
Abuse and addiction are separate and distinct from physical dependence and tolerance. Health care providers should be aware that addiction may not be accompanied by concurrent tolerance and symptoms of physical dependence in all addicts. In addition, abuse of opioids can occur in the absence of true addiction.
Levorphanol Tartrate Tablets, like other opioids, can be diverted for non-medical use into illicit channels of distribution. Careful record-keeping of prescribing information, including quantity, frequency, and renewal requests, as required by state and federal law, is strongly advised.
Proper assessment of the patient, proper prescribing practices, periodic reevaluation of therapy, and proper dispensing and storage are appropriate measures that help to limit abuse of opioid drugs.
Risks Specific to Abuse of Levorphanol Tartrate Tablets
Levorphanol Tartrate Tablets are for oral use only. Abuse of Levorphanol Tartrate Tablets poses a risk of overdose and death. The risk is increased with concurrent abuse of Levorphanol Tartrate Tablets with alcohol and other central nervous system depressants.
Parenteral drug abuse is commonly associated with transmission of infectious diseases such as hepatitis and HIV.
Both tolerance and physical dependence can develop during chronic opioid therapy. Tolerance is the need for increasing doses of opioids to maintain a defined effect such as analgesia (in the absence of disease progression or other external factors). Tolerance may occur to both the desired and undesired effects of drugs, and may develop at different rates for different effects.
Physical dependence is a physiological state in which the body adapts to the drug after a period of regular exposure, resulting in withdrawal symptoms after abrupt discontinuation or a significant dosage reduction of a drug. Withdrawal also may be precipitated through the administration of drugs with opioid antagonist activity (e.g., naloxone, nalmefene), mixed agonist/antagonist analgesics (e.g., pentazocine, butorphanol, nalbuphine), or partial agonists (e.g., buprenorphine). Physical dependence may not occur to a clinically significant degree until after several days to weeks of continued opioid usage.
Do not abruptly discontinue Levorphanol Tartrate Tablets in a patient physically dependent on opioids. Rapid tapering of Levorphanol Tartrate Tablets in a patient physically dependent on opioids may lead to serious withdrawal symptoms, uncontrolled pain, and suicide. Rapid discontinuation has also been associated with attempts to find other sources of opioid analgesics, which may be confused with drug-seeking for abuse.
When discontinuing Levorphanol Tartrate Tablets, gradually taper the dosage using a patient- specific plan that considers the following: the dose of Levorphanol Tartrate Tablets the patient has been taking, the duration of treatment, and the physical and psychological attributes of the patient. To improve the likelihood of a successful taper and minimize withdrawal symptoms, it is important that the opioid tapering schedule is agreed upon by the patient. In patients taking opioids for a long duration at high doses, ensure that a multimodal approach to pain management, including mental health support (if needed), is in place prior to initiating an opioid analgesic taper [see DOSAGE AND ADMINISTRATION, WARNINGS]. Infants born to mothers physically dependent on opioids will also be physically dependent and may exhibit respiratory difficulties and withdrawal signs [see PRECAUTIONS; Pregnancy].
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, 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 patent 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 techniques.
The opioid antagonists, naloxone or nalmefene, are specific antidotes to respiratory depression resulting from opioid overdose. For clinically significant respiratory or circulatory depression secondary to resulting from opioid overdose. For clinically significant respiratory or circulatory depression secondary to Levorphanol Tartrate Tablets overdose, administer an opioid antagonist. Opioid antagonists should not be administered in the absence of clinically significant respiratory or circulatory depression secondary to Levorphanol Tartrate Tablets overdose.
Because the duration of opioid reversal is expected to be less than the duration of action of levorphanol in Levorphanol Tartrate Tablets, carefully monitor the patient until spontaneous respiration is reliably reestablished. If the response to an opioid antagonist is suboptimal or only brief in nature, administer additional antagonist as directed by the product’s prescribing information.
In an individual physically dependent on opioids, administration of the recommended usual dosage of the antagonist will precipitate an acute withdrawal syndrome. The severity of the withdrawal symptoms experienced will depend on the degree of physical dependence and the dose of the antagonist administered. If a decision is made to treat serious respiratory depression in the physically dependent patient, administration of the antagonist should be initiated with care and by titration with smaller than usual doses of the antagonist.
Important Dosage and Administration Instructions
Use the lowest effective dosage for the shortest duration consistent with individual patient treatment goals [see WARNINGS].
Initiate the dosing regimen for each patient individually, taking into account the patient’s severity of pain, patient response, prior analgesic treatment experience, and risk factors for addiction, abuse, and misuse [see WARNINGS].
Monitor patients closely for respiratory depression, especially within the first 24-72 hours of initiating therapy and following dosage increases with Levorphanol Tartrate Tablets and adjust the dosage accordingly [see WARNINGS].
Use of Levorphanol Tartrate Tablets as the First Opioid Analgesic
Initiate treatment with Levorphanol Tartrate Tablets in a dosing range of 1 to 2 mg every 6 to 8 hours as needed for pain, provided the patient is assessed for signs of hypoventilation and excessive sedation. If necessary, the dose may be increased to up to 3 mg every 6 to 8 hours, after adequate evaluation of the patient’s response. Higher doses may be appropriate in opioid tolerant patients. Dosage should be adjusted according to the severity of the pain; age, weight and physical status of the patient; the patient’s underlying diseases; use of concomitant medications; and other factors [see INDIVIDUALIZATION OF DOSAGE, WARNINGS AND PRECAUTIONS].
Conversion from Other Opioids to Levorphanol Tartrate Tablets
There is inter-patient variability in the potency of opioid drugs and opioid formulations. Therefore, a conservative approach is advised when determining the total daily dosage of Levorphanol Tartrate Tablets. It is safer to underestimate a patient’s 24-hour Levorphanol Tartrate Tablets dosage than to overestimate the 24-hour Levorphanol Tartrate Tablets dosage and manage an adverse reaction due to overdose.
The dosage of levorphanol in patients with cancer or with other conditions for which chronic opioid therapy is indicated must be individualized. Levorphanol is 4 to 8 times as potent as morphine and has a longer half-life. Because there is incomplete cross-tolerance among opioids, when converting a patient from morphine to levorphanol, the total daily dose of levorphanol should begin at approximately 1/15 to 1/12 of the total daily dose of oral morphine that such patients had previously required and then the dose should be adjusted to the patient’s clinical response. If a patient is to be placed on fixed-schedule dosing (round-the-clock) with this drug, care should be taken to allow adequate time after each dose change (approximately 72 hours) for the patient to reach a new steady-state before a subsequent dose adjustment to avoid excessive sedation due to drug accumulation.
Note: As with all controlled substances, abuse by health care personnel is possible and the drug should be handled accordingly.
Elderly patients (aged 65 years or older) may have increased sensitivity to levorphanol. In general, use caution when selecting a dosage for an elderly patient, usually starting at the low end of the dosing range, reflecting the greater frequency of decreased hepatic, renal, or cardiac function and of concomitant disease or other drug therapy. The initial dose of Levorphanol Tartrate Tablets should be reduced by 50% or more in the infirm elderly patient. [see PRECAUTIONS].
Titration and Maintenance of Therapy
Individually titrate the dose of Levorphanol Tartrate Tablets that provides adequate analgesia and minimizes adverse reactions. Continually reevaluate patients receiving Levorphanol Tartrate Tablets to assess the maintenance of pain control and the relative incidence of adverse reactions, as well as monitoring for the development of addiction, abuse, or misuse [see WARNINGS].
Frequent communication is important among the prescriber, other members of the healthcare team, the patient, and the caregiver/family during periods of changing analgesic requirements, including initial titration.
If a patient is to be placed on fixed-schedule dosing (round-the-clock) with this drug, care should be taken to allow adequate time after each dose change (approximately 72 hours) for the patient to reach a new steady state before a subsequent dose adjustment to avoid excessive sedation due to drug accumulation.
If the level of pain increases after dosage stabilization, attempt to identify the source of increased pain before increasing Levorphanol Tartrate Tablets dosage. If unacceptable opioid- related adverse reactions are observed, consider reducing the dosage. Adjust the dosage to obtain an appropriate balance between management of pain and opioid-related adverse reactions.
Levorphanol has a long half-life. The duration of pain relief after a single dose cannot always be predicted from pharmacokinetic principles, and the inter-dose interval may have to be adjusted to suit the patient’s individual pharmacodynamic response.
Safe Reduction or Discontinuation of Levorphanol Tartrate Tablets
Do not abruptly discontinue Levorphanol Tartrate Tablets in patients who may be physically dependent on opioids. Rapid discontinuation of opioid analgesics in patients who are physically dependent on opioids has resulted in serious withdrawal symptoms, uncontrolled pain, and suicide. Rapid discontinuation has also been associated with attempts to find other sources of opioid analgesics, which may be confused with drug-seeking for abuse. Patients may also attempt to treat their pain or withdrawal symptoms with illicit opioids, such as heroin, and other substances.
When a decision has been made to decrease the dose or discontinue therapy in an opioid dependent patient taking Levorphanol Tartrate Tablets, there are a variety of factors that should be considered, including the dose of Levorphanol Tartrate Tablets the patient has been taking, the duration of treatment, the type of pain being treated, and the physical and psychological attributes of the patient. It is important to ensure ongoing care of the patient and to agree on an appropriate tapering schedule and follow-up plan so that patient and provider goals and expectations are clear and realistic. When opioid analgesics are being discontinued due to a suspected substance use disorder, evaluate and treat the patient, or refer for evaluation and treatment of the substance use disorder. Treatment should include evidence-based approaches, such as medication assisted treatment of opioid use disorder. Complex patients with co-morbid pain and substance use disorders may benefit from referral to a specialist.
There are no standard opioid tapering schedules that are suitable for all patients. Good clinical practice dictates a patient-specific plan to taper the dose of the opioid gradually. For patients on Levorphanol Tartrate Tablets who are physically opioid-dependent, initiate the taper by a small enough increment (e.g., no greater than 10% to 25% of the total daily dose) to avoid withdrawal symptoms, and proceed with dose- lowering at an interval of every 2 to 4 weeks. Patients who have been taking opioids for briefer periods of time may tolerate a more rapid taper.
It may be necessary to provide the patient with lower dosage strengths to accomplish a successful taper. Reassess the patient frequently to manage pain and withdrawal symptoms, should they emerge. Common withdrawal symptoms include restlessness, lacrimation, rhinorrhea, yawning, perspiration, chills, myalgia, and mydriasis. Other signs and symptoms also may develop, including irritability, anxiety, backache, joint pain, weakness, abdominal cramps, insomnia, nausea, anorexia, vomiting, diarrhea, or increased blood pressure, respiratory rate, or heart rate. If withdrawal symptoms arise, it may be necessary to pause the taper for a period of time or raise the dose of the opioid analgesic to the previous dose, and then proceed with a slower taper. In addition, monitor patients for any changes in mood, emergence of suicidal thoughts, or use of other substances.
When managing patients taking opioid analgesics, particularly those who have been treated for a long duration and/or with high doses for chronic pain, ensure that a multimodal approach to pain management, including mental health support (if needed), is in place prior to initiating an opioid analgesic taper. A multimodal approach to pain management may optimize the treatment of chronic pain, as well as assist with the successful tapering of the opioid analgesic [see WARNINGS/ Withdrawal, DRUG ABUSE AND DEPENDENCE].
Levorphanol Tartrate Tablets, USP 2 mg for oral administration are supplied as –
White, round tablet debossed with “N” above “236” on one side and score on other side.
NDC 0527-3236-37 Bottle of 100 Tablets
Levorphanol Tartrate Tablets, USP 3 mg for oral administration are supplied as –
White, oval shaped tablet debossed with “N237” on one side and plain on other side.
NDC 0527-3237-37 Bottle of 100 Tablets
Store at 20° to 25°C (68° to 77°F). [See USP Controlled Room Temperature.] Dispense in an amber airtight container as defined in the USP.
Store Levorphanol Tartrate Tablets securely and dispose of properly [see PRECAUTIONS/ Information for Patients].
Lannett Company, Inc.
Philadelphia, PA 19136
Levorphanol Tartrate (lee vor’ fa nol tar’ trate) Tablets, CII
Levorphanol Tartrate Tablets are:
- A strong prescription pain medicine that contains an opioid (narcotic) that is used to manage pain, severe enough to require an opioid pain medicine when other pain treatments such as non-opioid pain medicines do not treat your pain well enough or you cannot tolerate them.
- An opioid pain medicine that can put you at risk for overdose and death. Even if you take your dose correctly as prescribed you are at risk for opioid addiction, abuse, and misuse that can lead to death.
Important information about Levorphanol Tartrate Tablets:
- Get emergency help right away if you take too much Levorphanol Tartrate Tablets (overdose). When you first start taking Levorphanol Tartrate Tablets, when your dose is changed, or if you take too much (overdose), serious or life-threatening breathing problems that can lead to death may occur.
- Taking Levorphanol Tartrate Tablets with other opioid medicines, benzodiazepines, alcohol, or other central nervous system depressants (including street drugs) can cause severe drowsiness, decreased awareness, breathing problems, coma and death.
- Never give anyone else your Levorphanol Tartrate Tablets. They could die from taking it. Selling or giving away Levorphanol Tartrate Tablets is against the law.
- Store Levorphanol Tartrate Tablets securely, out of sight and reach of children, and in a location not accessible by others, including visitors to the home.
Do not take Levorphanol Tartrate Tablets if you have:
- severe asthma trouble breathing, or other lung problems
- a bowel blockage or have narrowing of the stomach or intestines.
- previously had an allergic reaction to levorphanol
Before taking Levorphanol Tartrate Tablets, tell your healthcare provider if you have a history of:
- head injury, seizures • liver, kidney, thyroid problems
- problems urinating • pancreas or gallbladder problems
- abuse of street or prescription drugs, alcohol addiction, or mental health problems.
Tell your healthcare provider if you are:
- pregnant or planning to become pregnant. Prolonged use of Levorphanol Tartrate Tablets during pregnancy can cause withdrawal symptoms in your newborn baby that could be life- threatening if not recognized and treated.
- breast feeding. Levorphanol passes into breast milk and may harm your baby.
- taking prescription or over-the-counter medicines, vitamins, or herbal supplements. Taking Levorphanol Tartrate Tablets with certain other medicines can cause serious side effects that could lead to death.
When taking Levorphanol Tartrate Tablets:
- Do not change your dose. Take Levorphanol Tartrate Tablets exactly as prescribed by your healthcare provider. Use the lowest dose possible for the shortest time needed.
- Take your prescribed dose every 6 to 8 hours as needed for pain. Do not take more than your prescribed dose. If you miss a dose, take your next dose at your usual time.
- Call your healthcare provider if the dose you are taking does not control your pain.
- If you have been taking Levorphanol Tartrate Tablets regularly, do not stop taking without talking to your healthcare provider.
- Dispose of expired, unwanted, or unused Levorphanol Tartrate Tablets by promptly flushing down the toilet if a drug take-back option is not readily available. Visit www.fda.gov/drugdisposal for additional information on disposal of unused medicines.
While taking Levorphanol Tartrate Tablets DO NOT:
- Drive or operate heavy machinery, until you know how Levorphanol Tartrate Tablets affects you. Levorphanol Tartrate Tablets can make you sleepy, dizzy, or lightheaded.
- Drink alcohol or use prescription or over-the-counter medicines that contain alcohol. Using products containing alcohol during treatment with Levorphanol Tartrate Tablets may cause you to overdose and die.
The possible side effects of Levorphanol Tartrate Tablets:
- constipation, nausea, sleepiness, vomiting, tiredness, headache, dizziness, abdominal pain. Call your healthcare provider if you have any of these symptoms and they are severe.
Get emergency medical help if you have:
- trouble breathing, shortness of breath, fast heartbeat, chest pain, swelling of your face, tongue, or throat, extreme drowsiness, light-headedness when changing positions, feeling faint, agitation, high body temperature, trouble walking, stiff muscles, or mental changes such as confusion.
These are not all the possible side effects of Levorphanol Tartrate Tablets. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088. For more information go to dailymed.nlm.nih.gov
Lannett Company, Inc.
Philadelphia, PA 19136
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