LEVORPHANOL TARTRATE- levorphanol tartrate tablet
Revised: April 2021
WARNING: ADDICTION, ABUSE, AND MISUSE; RISK EVALUATION AND MITIGATION STRATEGY (REMS); LIFE-THREATENING RESPIRATORY DEPRESSION; ACCIDENTAL INGESTION; NEONATAL OPIOID WITHDRAWAL SYNDROME; and RISKS FROM CONCOMITANT USE WITH BENZODIAZEPINES OR OTHER CNS DEPRESSANTS
Addiction, Abuse, and Misuse
Levorphanol Tartrate Tablets expose patients and other users to the risks of opioid addiction, abuse, and misuse, which can lead to overdose and death. Assess each patient’s risk prior to prescribing Levorphanol Tartrate Tablets, and monitor all patients regularly for the development of these behaviors and conditions (see WARNINGS).
Opioid Analgesic Risk Evaluation and Mitigation Strategy (REMS)
To ensure that the benefits of opioid analgesics outweigh the risks of addiction, abuse, and misuse,
the Food and Drug Administration (FDA) has required a REMS for these products (see WARNINGS).
Under the requirements of the REMS, drug companies with approved opioid analgesic products
must make REMS-compliant education programs available to healthcare providers. Healthcare
providers are strongly encouraged to
- Complete a REMS-compliant education program,
- counsel patients and/or their caregivers, with every prescription, on safe use, serious risks,
storage, and disposal of these products,
- emphasize to patients and their caregivers the importance of reading the Medication Guide every
time it is provided by their pharmacist, and
- consider other tools to improve patient, household, and community safety.
Life-Threatening Respiratory Depression
Serious, life-threatening, or fatal respiratory depression may occur with use of Levorphanol Tartrate Tablets. Monitor for respiratory depression, especially during initiation of Levorphanol Tartrate Tablets or following a dose increase (see WARNINGS).
Accidental ingestion of Levorphanol Tartrate Tablets, especially by children, can result in a fatal overdose of Levorphanol Tartrate Tablets (see WARNINGS).
Neonatal Opioid Withdrawal Syndrome
Prolonged use of Levorphanol Tartrate Tablets during pregnancy can result in neonatal opioid withdrawal syndrome, which may be life-threatening if not recognized and treated, and requires management according to protocols developed by neonatology experts. If opioid use is required for a prolonged period in a pregnant woman, advise the patient of the risk of neonatal opioid withdrawal syndrome and ensure that appropriate treatment will be available (see WARNINGS).
Risks from Concomitant Use with Benzodiazepines or Other CNS DepressantsConcomitant use of opioids with benzodiazepines or other central nervous system (CNS) depressants, including alcohol, may result in profound sedation, respiratory depression, coma, and death (see WARNINGS).
- Reserve concomitant prescribing of Levorphanol Tartrate Tablets and benzodiazepines or other CNS depressants for use in patients for whom alternative treatment options are inadequate.
- Limit dosages and durations to the minimum required.
- Follow patients for signs and symptoms of respiratory depression and sedation.
Levorphanol Tartrate Tablets contain levorphanol, an opioid agonist with a molecular formula of
C17 H23 NO • C4 H6 O6 • 2H2 O and molecular weight 443.5. Each milligram of levorphanol tartrate is equivalent to 0.58 mg levorphanol base. Levorphanol’s chemical name is levo-3-hydroxy-N-methylmorphinan. The USP nomenclature is 17- methylmorphinan 3-ol tartrate (1:1)(Salt) dihydrate. The material has 3 asymmetric carbon atoms. The chemical structure is:
Levorphanol tartrate is a white crystalline powder, soluble in water and ether, but insoluble in chloroform.
Levorphanol Tartrate Tablets, for oral administration, is available in one strength, distinguishable by the shape, size and debossing on the tablet surface:
2 mg tablet: white to off white, round, flat faced tablet, debossed logo “M” inside square on one side and a score on the opposite side of the tablet.
In addition, each tablet contains lactose anhydrous, pregelatinized corn starch, and magnesium stearate.
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. Like all full opioid agonists, there is no ceiling effect for analgesia with levorphanol. Clinically, dosage is titrated to provide adequate analgesia and may be limited by adverse reactions, including respiratory and CNS depression.
The precise mechanism of the analgesic action is unknown. However, specific CNS opioid receptors for endogenous compounds with opioid-like activity have been identified throughout the brain and spinal cord and are thought to play a role in the analgesic effects of this drug.
The principal therapeutic action of levorphanol is analgesia.
Levorphanol produces respiratory depression by direct action on brain stem respiratory centers. The respiratory depression involves a reduction in the responsiveness of the brain stem respiratory centers to both increases in carbon dioxide retention and electrical stimulation.
Levorphanol causes miosis, even in total darkness. Pinpoint pupils are a sign of opioid overdose but are not pathognomonic (e.g., pontine lesions of hemorrhagic or ischemic origins may produce similar findings). Marked mydriasis rather than miosis may be seen due to hypoxia in overdose situations.
Levorphanol causes a reduction in motility associated with an increase in smooth muscle tone in the antrum of the stomach and duodenum. Digestion of food in the small intestine is delayed and propulsive contractions are decreased. Propulsive peristaltic waves in the colon are decreased, while tone may be increased to the point of spasm, resulting in constipation. Other opioid-induced effects may include a reduction in biliary and pancreatic secretions, spasm of sphincter of Oddi, and transient elevations in serum amylase.
Levorphanol produces peripheral vasodilation which may result in orthostatic hypotension or syncope. Manifestations of histamine release and/or peripheral vasodilation may include pruritus, flushing, red eyes, sweating, and/or orthostatic hypotension.
Opioids inhibit the secretion of adrenocorticotropic hormone (ACTH), cortisol, and luteinizing hormone (LH) in humans (see ADVERSE REACTIONS). They also stimulate prolactin, growth hormone (GH) secretion, and pancreatic secretion of insulin and glucagon.
Chronic use of opioids may influence the hypothalamic-pituitary-gonadal axis, leading to androgen deficiency that may manifest as low libido, impotence, erectile dysfunction, amenorrhea, or infertility. The causal role of opioids in the clinical syndrome of hypogonadism is unknown because the various medical, physical, lifestyle, and psychological stressors that may influence gonadal hormone levels have not been adequately controlled for in studies conducted to date (see ADVERSE REACTIONS).
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