DEMEROL- meperidine hydrochloride injection, solution
WARNING: ADDICTION, ABUSE, AND MISUSE; LIFE-THREATENING RESPIRATORY DEPRESSION; NEONATAL OPIOID WITHDRAWAL SYNDROME; CYTOCHROME P450 3A4 INTERACTION; RISKS FROM CONCOMITANT USE WITH BENZODIAZEPINES OR OTHER CNS DEPRESSANTS; and MONOAMINE OXIDASE (MOA) INHIBITORS INTERACTIONS
Addiction, Abuse, and Misuse
DEMEROL Injection exposes 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 DEMEROL Injection, and monitor all patients regularly for the development of these behaviors and conditions [see Warnings and Precautions (5.1)].
Life-Threatening Respiratory Depression
Serious, life-threatening, or fatal respiratory depression may occur with use of DEMEROL Injection. Monitor for respiratory depression, especially during initiation of DEMEROL Injection or following a dose increase [see Warnings and Precautions (5.2)].
Neonatal Opioid Withdrawal Syndrome
Prolonged use of DEMEROL Injection 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 and Precautions (5.3)].
Cytochrome P450 3A4 Interaction
The concomitant use of DEMEROL Injection with all cytochrome P450 3A4 inhibitors may result in an increase in meperidine plasma concentrations, which could increase or prolong adverse reactions and may cause potentially fatal respiratory depression. In addition, discontinuation of a concomitantly used cytochrome P450 3A4 inducer may result in an increase in meperidine plasma concentration. Monitor patients receiving DEMEROL Injection and any CYP3A4 inhibitor or inducer [see Warnings and Precautions (5.4), Drug Interactions (7)].
Risks From Concomitant Use with Benzodiazepines Or Other CNS Depressants
Concomitant 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 and Precautions (5.5), Drug Interactions (7)].
- Reserve concomitant prescribing of DEMEROL Injection and benzodiazepines or other CNS depressants for use in patients for whom alternative treatment options are inadequate.
- Limit dosage and duration to the minimum required.
- Follow patients for signs and symptoms of respiratory depression and sedation.
Concomitant Use of DEMEROL Injection with Monoamine Oxidase (MAO) Inhibitors
Concomitant use of DEMEROL Injection with monoamine oxidase (MAO) inhibitors can result in coma, severe respiratory depression, cyanosis, and hypotension. Use of DEMEROL Injection with MAO inhibitors within last 14 days is contraindicated [see Contraindications (4), Warnings and Precautions (5.6), Drug Interactions (7)].
DEMEROL Injection is indicated for preoperative medication, support of anesthesia, and obstetrical analgesia.
DEMEROL Injection is 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, and misuse with opioids, even at recommended doses [see Warnings and Precautions (5.1)] , reserve DEMEROL Injection for use in patients for whom alternative treatment options [e.g., non-opioid analgesics or opioid combination products]:
- Have not been tolerated, or are not expected to be tolerated
- Have not provided adequate analgesia, or are not expected to provide adequate analgesia
DEMEROL Injection should not be used for treatment of chronic pain. Prolonged DEMEROL Injection use may increase the risk of toxicity (e.g. seizures) from the accumulation of the meperidine metabolite, normeperidine.
Use the lowest effective dosage for the shortest duration consistent with individual patient treatment goals [see Warnings and Precautions (5)].
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 and Precautions (5.1)].
Monitor patients closely for respiratory depression, especially within the first 24–72 hours of initiating therapy and following dosage increases with DEMEROL Injection and adjust the dosage accordingly [see Warnings and Precautions (5.2)].
Parenteral drug products should be inspected visually for particulate and discoloration prior to administration whenever solution and container permit.
Dosage should be adjusted according to the severity of the pain and the response of the patient. While subcutaneous administration is suitable for occasional use, intramuscular administration is preferred when repeated doses are required. If intravenous administration is required, dosage should be decreased and the injection made very slowly, preferably utilizing a diluted solution.
Adults: The usual dosage is 50 mg to 150 mg intramuscularly or subcutaneously every 3 or 4 hours as needed for pain. Elderly patients should usually be given meperidine at the lower end of the dose range and observed closely.
Children: The usual dosage is 0.5 mg/lb to 0.8 mg/lb intramuscularly or subcutaneously up to the adult dose, every 3 or 4 hours as necessary.
Titration and Maintenance of Therapy
Individually titrate DEMEROL Injection to a dose that provides adequate analgesia and minimizes adverse reactions. Continually reevaluate patients receiving DEMEROL Injection 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 and Precautions (5.1)]. Frequent communication is important among the prescriber, other members of the health and care 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 DEMEROL Injection 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.
Discontinuation of DEMEROL Injection
When a patient who has been taking DEMEROL Injection regularly and may be physically dependent no longer requires therapy with DEMEROL Injection, taper the dose gradually, by 25% to 50% every 2 to 4 days, while monitoring carefully for signs and symptoms of withdrawal. If the patient develops these signs or symptoms, raise the dose to the previous level and taper more slowly, either by increasing the interval between decreases, decreasing the amount of change in dose, or both. Do not abruptly discontinue DEMEROL Injection in a physically-dependent patient [see Warnings and Precautions (5.13), Drug Abuse and Dependence (9.3)].
Adults: The usual dosage is 50 mg to 100 mg intramuscularly or subcutaneously, 30 to 90 minutes before the beginning of anesthesia. Elderly patients should usually be given meperidine at the lower end of the dose range and observed closely.
Children: The usual dosage is 0.5 mg/lb to 1 mg/lb intramuscularly or subcutaneously up to the adult dose, 30 to 90 minutes before the beginning of anesthesia.
Repeated slow intravenous Injections of fractional doses (e.g., 10 mg/mL) or continuous intravenous infusion of a more dilute solution (e.g., 1 mg/mL) should be used. The dose should be titrated to the needs of the patient and will depend on the premedication and type of anesthesia being employed, the characteristics of the particular patient, and the nature and duration of the operative procedure. Elderly patients should usually be given meperidine at the lower end of the dose range and observed closely.
The usual dosage is 50 mg to 100 mg intramuscularly or subcutaneously when pain becomes regular, and may be repeated at 1- to 3-hour intervals.
The dose of DEMEROL Injection should be proportionately reduced (usually by 25 to 50 percent) when administered concomitantly with phenothiazines and many other tranquilizers since they potentiate the action of DEMEROL Injection.
Instructions for using the Carpuject Syringe are available with the reusable Carpuject Holder. Carpuject Single-dose cartridges are to be used ONLY with Carpuject Holders.
To prevent needlestick injuries, needles should not be recapped, purposely bent, or broken by hand.
Blunt cannulas should not be recapped, purposely bent or broken by hand.
DEMEROL Injection is a clear, colorless, sterile aqueous solution, available in the following dosage forms and strengths:
- Single-dose Carpuject cartridge with Luer Lock for the Carpuject Syringe System, available in the following strengths: 25 mg/mL, 50 mg/mL, 75 mg/mL, and 100 mg/mL.
- Multiple-dose vials containing 0.1% metacresol as a preservative, available in the following strength: 1,500 mg/30 mL (50 mg/mL).
- Single-dose NexJectTM Prefilled Syringe with Luer Lock, available in the following strengths: 25 mg/mL, 50 mg/mL, 75 mg/mL, and 100 mg/mL.
DEMEROL Injection is contraindicated in patients with:
- Significant respiratory depression [see Warnings and Precautions (5.2)]
- Acute or severe bronchial asthma in an unmonitored setting or in the absence of resuscitative equipment [see Warnings and Precautions (5.2)]
- Concomitant use of monoamine oxidase inhibitors (MAOIs) or within 14 days of having taken an MAOI [see Warnings and Precautions (5.6), Drug Interactions (7)]
- Known or suspected gastrointestinal obstruction, including paralytic ileus [see Warnings and Precautions (5.12)]
- Hypersensitivity to meperidine (e.g., anaphylaxis) [see Adverse Reactions (6)]
DEMEROL Injection contains meperidine, a Schedule II controlled substance. As an opioid, DEMEROL Injection exposes 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 DEMEROL Injection. Addiction can occur at recommended dosages and if the drug is misused or abused.
Assess each patient’s risk for opioid addiction, abuse, or misuse prior to prescribing DEMEROL Injection, and monitor all patients receiving DEMEROL Injection 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 DEMEROL Injection, but use in such patients necessitates intensive counseling about the risks and proper use of DEMEROL Injection along with intensive monitoring for signs of addiction, abuse, and misuse.
Opioids are sought by drug abusers and people with addiction disorders and are subject to criminal diversion. Consider these risks when prescribing or dispensing DEMEROL Injection. Strategies to reduce these risks include prescribing the drug in the smallest appropriate quantity.
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.
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 antagonists, depending on the patient’s clinical status [see Overdosage (10)]. Carbon dioxide (CO2 ) 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 DEMEROL Injection, the risk is greatest during the initiation of therapy or following a dosage increase. Monitor patients closely for respiratory depression, especially within the first 24 to 72 hours of initiating therapy with and following dosage increases of DEMEROL Injection.
To reduce the risk of respiratory depression, proper dosing and titration of DEMEROL Injection are essential [see Dosage and Administration (2.3)]. Overestimating the DEMEROL Injection dosage when converting patients from another opioid product can result in a fatal overdose with the first dose.
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 (2.1)].
Prolonged use of DEMEROL Injection during pregnancy can result in withdrawal in the neonate. Neonatal opioid withdrawal syndrome, unlike opioid withdrawal syndrome in adults, may be life-threatening if not recognized and treated, and requires management according to protocols developed by neonatology experts. Observe newborns for signs of neonatal opioid withdrawal syndrome and manage accordingly. Advise pregnant women using opioids of neonatal opioid withdrawal syndrome and ensure that appropriate treatment will be available [see Use in Specific Populations (8.1), Patient Counseling Information (17)].
Concomitant use of DEMEROL Injection with a CYP3A4 inhibitor, such as macrolide antibiotics (e.g., erythromycin), azole-antifungal agents (e.g., ketoconazole), and protease inhibitors (e.g., ritonavir), may increase plasma concentrations of meperidine and prolong opioid adverse reactions, which may cause potentially fatal respiratory depression [see Warnings and Precautions (5.4)] , particularly when an inhibitor is added after a stable dose of DEMEROL Injection is achieved. Similarly, discontinuation of a CYP3A4 inducer, such as rifampin, carbamazepine, and phenytoin, in DEMEROL-Injection treated patients may increase meperidine plasma concentrations and prolong opioid adverse reactions. When using DEMEROL Injection with CYP3A4 inhibitors or discontinuing CYP3A4 inducers in DEMEROL-Injection treated patients, monitor patients closely at frequent intervals and consider dosage reduction of DEMEROL Injection until stable drug effects are achieved [Drug Interactions (7)].
Concomitant use of DEMEROL Injection with CYP3A4 inducers or discontinuation of a CYP3A4 inhibitor could decrease meperidine plasma concentrations, decrease opioid efficacy or, possibly, lead to a withdrawal syndrome in a patient who had developed physical dependence to meperidine. When using DEMEROL Injection with CYP3A4 inducers or discontinuing CYP3A4 inhibitors, monitor patients closely at frequent intervals and consider increasing the opioid dosage if needed to maintain adequate analgesia or if symptoms of opioid withdrawal occur [see Drug Interactions (7)].
DrugInserts.com provides trustworthy package insert and label information about marketed drugs as submitted by manufacturers to the US Food and Drug Administration. Package information is not reviewed or updated separately by DrugInserts.com. Every individual package label entry contains a unique identifier which can be used to secure further details directly from the US National Institutes of Health and/or the FDA.