1 ML meperidine hydrochloride 25 MG/ML Cartridge

INDICATIONS AND USAGE Meperidine hydrochloride tablets are indicated for the management of acute 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 [see Warnings and Precautions (5.2) ], reserve opioid analgesics, including meperidine hydrochloride 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. Meperidine hydrochloride tablets should not be used for treatment of chronic pain. Use of meperidine hydrochloride tablets for an extended period of time may increase the risk of toxicity (e.g., seizures) from the accumulation of the meperidine metabolite, normeperidine. Meperidine hydrochloride tablets are opioid agonists indicated for the management of pain, severe enough to require an opioid analgesic and for which alternative treatments are inadequate. ( 1 ) 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 meperidine hydrochloride 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. ( 1 , 5.2 ) Meperidine hydrochloride tablets should not be used for the treatment of chronic pain. Use of meperidine hydrochloride tablets for an extended period of time may increase the risk of toxicity (e.g., seizures) from the accumulation of the meperidine metabolite, normeperidine.

DOSAGE AND ADMINISTRATION • Meperidine Hydrochloride Tablets and Oral Solution should be prescribed only by healthcare professionals who are knowledgeable about the use of opioids and how to mitigate the associated risks. ( 2.1 ) • Use the lowest effective dosage for the shortest duration of time consistent with individual patient treatment goals. Reserve titration to higher doses of Meperidine Hydrochloride Tablets and Oral Solution 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. ( 2.1 , 5 ) • 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. ( 2.1 ) • 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. ( 2.1 , 5.2 ) • Respiratory depression can occur at any time during opioid therapy, especially when initiating and following dosage increases with Meperidine Hydrochloride Tablets and Oral Solution. Consider this risk when selecting an initial dose and when making dose adjustments. ( 2.1 , 5.3 ) • Discuss opioid overdose reversal agents and options for acquiring them with the patient and/or caregiver, both when initiating and renewing treatment with Meperidine Hydrochloride Tablets and Oral Solution, especially if the patient has additional risk factors for overdose, or close contacts at risk for exposure and overdose. ( 2.2 , 5.2 , 5.3 , 5.4 ) • Adult Patients : Initiate treatment in adults with 50 mg to 150 mg orally, every 3 to 4 hours as needed for pain, and at lowest dose necessary to achieve adequate analgesia ( 2.3 ). Titrate the dose based upon the individual patient’s response to their initial dose of Meperidine Hydrochloride Tablets and Oral Solution. • Pediatric Patients : Initiate treatment in pediatric patients with 1.1 mg/kg to 1.8 mg/kg orally, up to the adult dose, every 3 or 4 hours as needed and at the lowest dose necessary to achieve adequate analgesia ( 2.3 ). Titrate the dose based upon the individual patient’s response to their initial dose of Meperidine Hydrochloride Tablets and Oral Solution. • Periodically reassess patients receiving Meperidine Hydrochloride Tablets and Oral Solution to evaluate the continued need for opioid analgesics to maintain pain control, for the signs or symptoms of adverse reactions, and for the development of addiction, abuse, or misuse. ( 2.5 ) • Do not rapidly reduce or abruptly discontinue Meperidine Hydrochloride Tablets and Oral Solution in a physically-dependent patient because rapid reduction or abrupt discontinuation of opioid analgesics has resulted in serious withdrawal symptoms, uncontrolled pain, and suicide. ( 2.5 , 5.17 ) 2.1 Important Dosage and Administration Instructions Meperidine Hydrochloride Oral Solution Ensure accuracy when prescribing, dispensing, and administering Meperidine Hydrochloride Oral Solution to avoid dosing errors due to confusion between mg and mL, and with other meperidine solutions of different concentrations, which could result in accidental overdose and death. Ensure the proper dose is communicated and dispensed. When writing prescriptions, include both the total dose in mg and the total dose in volume. Instruct patients and caregivers on how to accurately measure and take or administer the correct dose of Meperidine Hydrochloride Oral Solution. Strongly advise patients and caregivers to always use a graduated oral syringe or measuring cup, with metric units of measurements (i.e., mL), to correctly measure the prescribed amount of medication. Inform patients and caregivers that oral dosing devices may be obtained from their pharmacy and to never use household teaspoons or tablespoons to measure Meperidine Hydrochloride Oral Solution. Meperidine Hydrochloride Tablets and Oral Solution Meperidine Hydrochloride Tablets and Oral Solution 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 ( 5 )]. Because the risk of overdose increases as opioid doses increase, reserve titration to higher doses of Meperidine Hydrochloride Tablets and Oral Solution 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 to both to the cause of pain and to individual patient factors. Initiate the dosing regimen for each patient individually, taking into account that patient’s underlying cause and severity of pain, prior analgesic treatment and response, and risk factors for addiction, abuse, and misuse [see Warnings and Precautions ( 5.1 )]. Respiratory depression can occur at any time during opioid therapy, especially when initiating and following dosage increases with Meperidine Hydrochloride Tablets and Oral Solution. Consider this risk when selecting an initial dose and when making dose adjustments [see Warnings and Precautions ( 5 )]. 2. 2 Patient Access to an Opioid Overdose Reversal Agent for the Emergency Treatment of Opioid Ov erdose 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 and Precautions ( 5.2 , 5.3 , 5.4 )]. Discuss the options for obtaining an opioid overdose reversal agent (e.g., prescription, over-the-counter, or as part of a community-based program) [see Warnings and Precautions ( 5.3 )]. 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. 2.3 Initial Dosage Adults Initiate treatment with Meperidine Hydrochloride Tablets or Oral Solution in a dosing range of 50 mg to 150 mg orally, every 3 or 4 hours as needed for pain, and at the lowest dose necessary to achieve adequate analgesia. Titrate the dose based upon the individual patient’s response to their initial dose of Meperidine Hydrochloride Tablets and Oral Solution. Pediatric Patients Initiate treatment with Meperidine Hydrochloride Tablets or Oral Solution in a dosing range of 1.1 mg/kg to 1.8 mg/kg orally, up to the adult dose, every 3 or 4 hours as needed, and at the lowest dose necessary to achieve adequate analgesia. Titrate the dose based upon the individual patient’s response to their initial dose of Meperidine Hydrochloride Tablets and Oral Solution. 2.4 Dosage Modification with Concomitant Use with Phenothiazines The dose of Meperidine Hydrochloride Tablets or Oral Solution should be reduced by 25 to 50% wh

WARNINGS AND PRECAUTIONS • Opioid-Induced Hyperalgesia and Allodynia: Opioid-Induced Hyperalgesia (OIH) occurs when an opioid analgesic paradoxically causes an increase in pain, or an increase in sensitivity to pain. If OIH is suspected, carefully consider appropriately decreasing the dose of the current opioid analgesic, or opioid rotation. ( 5.9 ) • Serotonin Syndrome: Potentially life-threatening condition could result from concomitant serotonergic drug administration. Discontinue Meperidine Hydrochloride Tablets or Oral Solution if serotonin syndrome is suspected. ( 5.10 ) • Life-Threatening Respiratory Depression in Patients with Chronic Pulmonary Disease or in Elderly, Cachectic, or Debilitated Patients: Regularly evaluate closely, particularly during initiation and titration. ( 5.11 ) • Adrenal Insufficiency: If diagnosed, treat with physiologic replacement of corticosteroids, and wean patient off of the opioid. ( 5.12 ) • Severe Hypotension: Regularly evaluate during dosage initiation and titration. Avoid use of Meperidine Hydrochloride Tablets or Oral Solution in patients with circulatory shock. ( 5.13 ) • Risks of Use in Patients with Increased Intracranial Pressure, Brain Tumors, Head Injury, or Impaired Consciousness: Regularly evaluate for sedation and respiratory depression. Avoid use of Meperidine Hydrochloride Tablets or Oral Solution in patients with impaired consciousness or coma. ( 5.14 ) 5.1 Risks of Accidental Overdose and Death Due to Medication Errors Dosing errors can result in accidental overdose and death. Avoid dosing errors that may result from confusion between mg and mL and confusion with meperidine solutions of different concentrations, when prescribing, dispensing, and administering Meperidine Oral Solution. Ensure that the dose is communicated clearly and dispensed accurately. Instruct patients and caregivers on how to measure and take or administer the correct dose of Meperidine Oral Solution and to use extreme caution when measuring the dose. Strongly advise patients to obtain and always use a graduated device that can measure and deliver the prescribed dose accurately, and to never use household teaspoons or tablespoons to measure a dose because these are not accurate measuring devices [see Dosage and Administration ( 2.1 )]. 5.2 Addiction, Abuse, and Misuse Meperidine Hydrochloride Tablets and Oral Solution contain meperidine, a Schedule II controlled substance. As an opioid, Meperidine Hydrochloride Tablets and Oral Solution expose users to the risks of addiction, abuse and misuse [see Drug Abuse and Dependence ( 9 )] . Although the risk of addiction in any individual is unknown, it can occur in patients appropriately prescribed Meperidine Hydrochloride Tablets or Oral Solution. Addiction can occur at recommended doses and if the drug is misused or abused. The risk of opioid-related overdose or overdose-related death is increased with higher opioid doses, and the risk persists over the course of therapy. In postmarketing studies, addiction, abuse, misuse, and fatal and non-fatal opioid overdose were observed in patients with long-term opioid use [see Adverse Reactions ( 6 )]. Assess each patient’s risk for opioid addiction, abuse, or misuse prior to prescribing Meperidine Hydrochloride Tablets and Oral Solution, and reassess all patients receiving Meperidine Hydrochloride Tablets or Oral Solution for the development of these behaviors and conditions. Risks are increased in patients with a personal or family history of substance abuse (including drug or alcohol abuse or addiction) or mental illness (e.g., major depression). The potential for these risks should not, however, prevent the proper management of pain in any given patient. Patients at increased risk may be prescribed opioids such as Meperidine Hydrochloride Tablets or Oral Solution, but use in such patients necessitates intensive counseling about the risks and proper use of Meperidine Hydrochloride Tablets and Oral Solution along with frequent reevaluation for signs of addiction, abuse, and misuse. Consider prescribing an opioid overdose reversal agent [see Dosage and Administration ( 2.2 ), Warnings and Precautions ( 5.4 )] . Opioids are sought for nonmedical use and are subject to diversion from legitimate prescribed use. Consider these risks when prescribing or dispensing Meperidine Hydrochloride Tablets or Oral Solution. Strategies to reduce these risks include prescribing the drug in the smallest appropriate quantity and advising the patient on careful storage of the drug during the course of treatment and proper disposal of unused drug. Contact local state professional licensing board or state-controlled substances authority for information on how to prevent and detect abuse or diversion of this product. Meperidine Hydrochloride Tablets have been reported as being abused by crushing, chewing, snorting, or injecting the dissolved product. These practices will result in the uncontrolled delivery of the opioid and pose a significant risk to the abuser that could result in overdose or death. 5.3 Life-Threatening Respiratory Depression Serious, life-threatening, or fatal respiratory depression has been reported with the use of opioids, even when used as recommended. Respiratory depression, if not immediately recognized and treated, may lead to respiratory arrest and death. Management of respiratory depression may include close observation, supportive measures, and use of opioid overdose reversal agents , depending on the patient’s clinical status [see Overdosage ( 10 )] . Carbon dioxide (CO 2 ) retention from opioid-induced respiratory depression can exacerbate the sedating effects of opioids. While serious, life-threatening, or fatal respiratory depression can occur at any time during the use of Meperidine Hydrochloride Tablets or Oral Solution, the risk is greatest during the initiation of therapy or following a dosage increase of Meperidine Hydrochloride Tablets or Oral Solution. To reduce the risk of respiratory depression, proper dosing and titration of Meperidine Hydrochloride Tablets and Oral Solution are essential [see Dosage and Administration ( 2 )]. Overestimating the meperidine dosage when converting patients from another opioid product can result in a fatal overdose with the first dose. Accidental ingestion of Meperidine Hydrochloride Tablets or Oral Solution, especially by children, can result in respiratory depression and death due to an overdose of meperidine. Educate patients and caregivers on how to recognize respiratory depression and emphasize the importance of calling 911 or getting emergency medical help right away in the event of a known or suspected overdose. Opioids can cause sleep-related breathing disorders including central sleep apnea (CSA) and sleep-related hypoxemia. Opioid use increases the risk of CSA in a dose-dependent fashion. In patients who present with CSA, consider decreasing the opioid dosage using best practices for opioid taper [see Dosage and Administration ( 2.6 )]. 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 and Precautions ( 5.2 , 5.4 )]. 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 adminis

CONTRAINDICATIONS Meperidine Hydrochloride Tablets and Oral Solution are contraindicated in patients with: • Significant respiratory depression [see Warnings and Precautions ( 5.3 )] • Acute or severe bronchial asthma in an unmonitored setting or in the absence of resuscitative equipment [see Warnings and Precautions ( 5.11 )] • Concomitant use of monoamine oxidase inhibitors (MAOIs) or within 14 days of having taken an MAOI [see Drug Interactions ( 7 )] • Known or suspected gastrointestinal obstruction, including paralytic ileus [see Warnings and Precautions ( 5.15 )] • Hypersensitivity to meperidine or to any of the other ingredients of the product (e.g., anaphylaxis) [see Adverse Reactions ( 6 )] • Significant respiratory depression. ( 4 ) • Acute or severe bronchial asthma in an unmonitored setting or in absence of resuscitative equipment. ( 4 ) • Concomitant use of monoamine oxidase inhibitors (MAOIs) or within 14 days of having taken an MAOI. ( 4 ) • Known or suspected gastrointestinal obstruction, including paralytic ileus. ( 4 ) • Hypersensitivity to meperidine or to any other ingredients of the product. ( 4 )

Mechanism of Action Meperidine hydrochloride is an opioid agonist with multiple actions qualitatively similar to those of morphine; the most prominent of these involve the central nervous system and organs composed of smooth muscle. The principal actions of therapeutic value are analgesia and sedation.