Pentazocine

INDICATIONS AND USAGE Pentazocine and Naloxone Tablets are indicated for the management of pain severe enough to require an opioid analgesic and for which alternative treatments are inadequate. Limitations of Use Because of the risks of addiction, abuse, misuse, overdose, and death, which can occur at any dosage or duration, and persist over the course of therapy, reserve opioid analgesics, including Pentazocine and Naloxone Tablets for use in patients for whom alternative treatment options are ineffective, not tolerated, or would be otherwise inadequate to provide sufficient management of pain.

DOSAGE AND ADMINISTRATION Important Dosage and Administration Instructions Pentazocine and Naloxone Tablets should be prescribed only by healthcare professionals who are knowledgeable about the use of opioids and how to mitigate the associated risks. Use the lowest effective dosage for the shortest duration of time consistent with individual patient treatment goals [see Warnings and Precautions ] . Reserve titration to higher doses of Pentazocine and Naloxone Tablets for patients in whom lower doses are insufficiently effective and in whom the expected benefits of using a higher dose opioid clearly outweigh the substantial risks. Many acute pain conditions (e.g., the pain that occurs with a number of surgical procedures or acute musculoskeletal injuries) require no more than a few days of an opioid analgesic. Clinical guidelines on opioid prescribing for some acute pain conditions are available. There is variability in the opioid analgesic dose and duration needed to adequately manage pain due both to the cause of pain and to individual patient factors. Initiate the dosing regimen for each patient individually, taking into account the patient's underlying cause and severity of pain, prior analgesic treatment and response, and risk factors for addiction, abuse, and misuse [ see Warnings ]. Respiratory depression can occur at any time during opioid therapy, especially when initiating and following dosage increases with Pentazocine and Naloxone Tablets. Consider this risk when selecting an initial dose and when making dose adjustments [ see Warnings ]. Patient Access to an Opioid Overdose Reversal Agent for the Emergency Treatment of Opioid Overdose Inform patients and caregivers about opioid overdose reversal agents (e.g., naloxone, nalmefene). Discuss the importance of having access to an opioid overdose reversal agent, especially if the patient has risk factors for overdose (e.g., concomitant use of CNS depressants, a history of opioid use disorder, or prior opioid overdose) or if there are household members (including children) or other close contacts at risk for accidental ingestion or opioid overdose. The presence of risk factors for overdose should not prevent the management of pain in any patient [see WARNINGS, Addiction, Abuse and Misuse; Life-Threatening Respiratory Depression; Risks from Concomitant Use with Benzodiazepines or Other CNS Depressants]. Discuss the options for obtaining an opioid overdose reversal agent (e.g., prescription, over-the-counter, or as part of a community-based program). There are important differences among the opioid overdose reversal agents, such as route of administration, product strength, approved patient age range, and pharmacokinetics. Be familiar with these differences, as outlined in the approved labeling for those products, prior to recommending or prescribing such an agent. Initial Dosage Use of Pentazocine and Naloxone Tablets as the First Opioid Analgesic Initiate treatment with Pentazocine and Naloxone Tablets, USP in a dosing range of 1 tablet every 3 to 4 hours as needed for pain, at the lowest dose necessary to achieve adequate analgesia. Titrate the dose based upon the individual patient's response to their initial dose of Pentazocine and Naloxone Tablets. This may be increased to 2 tablets when needed. Total daily dosage should not exceed 12 tablets. Conversion from Other Opioids to Pentazocine and Naloxone 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 Pentazocine and Naloxone Tablets. It is safer to underestimate a patient's 24-hour Pentazocine and Naloxone Tablets dosage than to overestimate the 24-hour Pentazocine and Naloxone Tablets dosage and manage an adverse reaction due to overdose. Titration and Maintenance of Therapy Individually titrate Pentazocine and Naloxone Tablets to a dose that provides adequate analgesia and minimizes adverse reactions. Continually reevaluate patients receiving Pentazocine and Naloxone Tablets to assess the maintenance of pain control, signs and symptoms of opioid withdrawal, and other adverse reactions, as well as assessing 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 the level of pain increases after dosage stabilization, attempt to identify the source of increased pain before increasing the Pentazocine and Naloxone Tablets dosage. If after increasing the dosage, unacceptable opioid- related adverse reactions are observed (including an increase in pain after dosage increase), consider reducing the dosage. Adjust the dosage to obtain an appropriate balance between management of pain and opioid-related adverse reactions. Safe Reduction or Disco

ADVERSE REACTIONS The following adverse reactions associated with the use of Pentazocine and Naloxone were identified in clinical studies or postmarketing reports. Because some of these reactions were reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure. Cardiovascular - Hypertension, hypotension, circulatory depression, tachycardia, syncope. Respiratory - Rarely, respiratory depression. Acute CNS Manifestations - Hallucinations (usually visual), disorientation, and confusion. Other CNS Effects - Grand mal convulsions, increase in intracranial pressure, dizziness, lightheadedness, hallucinations, sedation, euphoria, headache, confusion, disorientation; infrequently weakness, disturbed dreams, insomnia, syncope, and depression; and rarely tremor, irritability, excitement, tinnitus. Autonomic - Sweating; infrequently flushing; and rarely chills. Gastrointestinal - Nausea, vomiting, constipation, diarrhea, anorexia, dry mouth, biliary tract spasm, and rarely abdominal distress. Allergic - Edema of the face; anaphylactic shock; dermatitis, including pruritus; flushed skin, including plethora; infrequently rash, and rarely urticaria. Ophthalmic - Visual blurring and focusing difficulty, miosis. Hematologic - Depression of white blood cells (especially granulocytes), with rare cases of agranulocytosis, which is usually reversible, moderate transient eosinophilia. Dependence and Withdrawal Symptoms - (See WARNINGS , PRECAUTIONS , and DRUG ABUSE AND DEPENDENCE Sections). Other - Urinary retention, paresthesia, serious skin reactions, including erythema multiforme, Stevens-Johnson syndrome toxic epidermal necrolysis, and alterations in rate or strength of uterine contractions during labor. Serotonin syndrome : Cases of serotonin syndrome, a potentially life-threatening condition, have been reported during concomitant use of opioids with serotonergic drugs. Adrenal insufficiency : Cases of adrenal insufficiency have been reported with opioid use, more often following greater than one month of use. Anaphylaxis : Anaphylaxis has been reported with ingredients contained in Pentazocine and Naloxone Tablets. Androgen deficiency : Cases of androgen deficiency have occurred with use of opioids for an extended period of time [see Clinical Pharmacology ]. Hyperalgesia and Allodynia: Cases of hyperalgesia and allodynia have been reported with opioid therapy of any duration [see Warnings ]. Hypoglycemia : Cases of hypoglycemia have been reported in patients taking opioids. Most reports were in patients with at least one predisposing risk factor (e.g., diabetes). Opioid-induced esophageal dysfunction (OIED): Cases of OIED have been reported in patients taking opioids, and may occur more frequently in patients taking higher doses of opioid, and/or in patients taking opioids longer term [see WARNINGS]. Adverse Reactions from Observational Studies A prospective, observational cohort study estimated the risks of addiction, abuse, and misuse in patients initiating long-term use of Schedule II opioid analgesics between 2017 and 2021. Study participants included in one or more analyses had been enrolled in selected insurance plans or health systems for at least one year, were free of at least one outcome at baseline, completed a minimum number of follow-up assessments, and either: 1) filled multiple extended-release/long-acting opioid analgesic prescriptions during a 90 day period (n=978); or 2) filled any Schedule II opioid analgesic for at least 70 of 90 days (n=1,244). Those included also had no dispensing of the qualifying opioids in the previous 6 months. Over 12 months: approximately 1% to 6% of participants across the two cohorts newly met criteria for addiction, as assessed with two validated interview based measures of moderate-to-severe opioid use disorder based on Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) criteria, and approximately 9% and 22% of participants across the two cohorts newly met criteria for prescription opioid abuse and misuse [defined in DRUG ABUSE AND DEPENDENCE], respectively, as measured with a validated self-reported instrument. A retrospective, observational cohort study estimated the risk of opioid involved overdose or opioid overdose-related death in patients with new long-term use of Schedule II opioid analgesics from 2006 through 2016 (n=220,249). Included patients had been enrolled in either one of two commercial insurance programs, one managed care program, or one Medicaid program for at least 9 months. New long-term use was defined as having Schedule II opioid analgesic prescriptions covering at least 70 days' supply over the 3 months prior to study entry and none during the preceding 6 months. Patients were excluded if they had an opioid-involved overdose in the 9 months prior to study entry. Overdose was measured using a validated medical code-

DRUG INTERACTIONS Benzodiazepines and Other Central Nervous System (CNS) Depressants Due to additive pharmacologic effect, the concomitant use of benzodiazepines or other CNS depressants including alcohol, benzodiazepines and other sedative hypnotics, anxiolytics, and tranquilizers, muscle relaxants, general anesthetics, antipsychotics, and other opioids, can increase the risk of hypotension, respiratory depression, profound sedation, coma, and death. Reserve concomitant prescribing of these drugs for use in patients for whom alternative treatment options are inadequate. Limit dosages and durations to the minimum required. Inform patients and caregivers of this potential interaction, educate them on the signs and symptoms of respiratory depression (including sedation). If concomitant use is warranted, consider prescribing an opioid overdose reversal agent [see WARNINGS, DOSAGE AND ADMINISTRATION]. Serotonergic Drugs The concomitant use of opioids with other drugs that affect the serotonergic neurotransmitter system, such as selective serotonin reuptake inhibitors (SSRIs), serotonin and norepinephrine reuptake inhibitors (SNRIs), tricyclic antidepressants (TCAs), triptans, 5-HT3 receptor antagonists, drugs that affect the serotonin neurotransmitter system (e.g., mirtazapine, trazodone, tramadol), certain muscle relaxants (i.e., cyclobenzaprine, metaxalone), monoamine oxidase (MAO) inhibitors (those intended to treat psychiatric disorders and also others, such as linezolid and intravenous methylene blue), has resulted in serotonin syndrome. [see PRECAUTIONS; Information for Patients ]. If concomitant use is warranted, carefully observe the patient, particularly during treatment initiation and dose adjustment. Discontinue Pentazocine and Naloxone Tablets if serotonin syndrome is suspected. Monoamine Oxidase Inhibitors (MAOIs) Concomitant use of monoamine oxidase inhibitors (MAOIs) with Pentazocine and Naloxone Tablets may cause CNS excitation and hypertension through their respective effects on catecholamines. Caution should therefore be observed in administering Pentazocine and Naloxone Tablets to patients who are currently receiving MAOIs or who have received them within the preceding 14 days Mixed Agonist/Antagonist and Partial Agonist Opioid Analgesics Mixed Agonist/Antagonist and Partial Agonist Opioid Analgesics such as butorphanol, nalbuphine, pentazocine, buprenorphine, may reduce the analgesic effect of Pentazocine and Naloxone Tablets and/or precipitate withdrawal symptoms. Avoid concomitant use of these drugs. Muscle Relaxants The Concomitant use of opioids and muscle relaxants may enhance the neuromuscular blocking action of skeletal muscle relaxants and produce an increased degree of respiratory depression. Because respiratory depression may be greater than otherwise expected, decrease the dosage of Pentazocine and Naloxone Tablets and/or the muscle relaxant as necessary. Due to the risk of respiratory depression with concomitant use of skeletal muscle relaxants and opioids, consider prescribing an opioid overdose reversal agent [see WARNINGS, DOSAGE AND ADMINISTRATION]. Diuretics Opioids can reduce the efficacy of diuretics by inducing the release of antidiuretic hormone. Evaluate patients for signs of diminished diuresis and/or effects on blood pressure and increase the dosage of the diuretic as needed Anticholinergic Drugs The concomitant use of anticholinergic drugs may increase risk of urinary retention and/or severe constipation, which may lead to paralytic ileus. Evaluate patients for signs of urinary retention or reduced gastric motility when Pentazocine and Naloxone Tablets is used concomitantly with anticholinergic drugs. Tobacco Smoking tobacco could enhance the metabolic clearance rate of pentazocine reducing the clinical effectiveness of a standard dose of pentazocine. Carcinogenesis, Mutagenesis, Impairment of Fertility Carcinogenesis Long-term animal studies have not been completed to evaluate the carcinogenic potential of the combination or individual components of Pentazocine and Naloxone Tablets. Mutagenesis Studies to evaluate the mutagenic potential of the components of Pentazocine and Naloxone Tablets have not been conducted. Impairment of Fertility Studies in animals to evaluate the impact of Pentazocine and Naloxone Tablets on fertility have not been completed. The daily administration of 4 mg/kg to 20 mg/kg pentazocine subcutaneously to female rats during a 14 day pre-mating period and until the 13th day of pregnancy did not have any adverse effects on the fertility rate. Infertility Chronic Use of opioids for an extended period of time may cause reduced fertility in females and males of reproductive potential. It is not known whether these effects on fertility are reversible [see Adverse Reactions ].