Usual Adult Dose for Pain

Oral:
50 to 150 mg orally every 3 to 4 hours as needed
Maximum dose: 600 mg per day

Parenteral:
50 to 150 mg IM or subcutaneously every 3 to 4 hours as needed; IM administration is preferred when repeated dose are required

• May be administered IV, however, lower doses are advised and administration should be very slow, preferably using a diluted solution

Patient Controlled Analgesia (PCA):

• Initial dose: 10 mg with a range of 1 to 5 mg per incremental dose; Lockout interval: 6 to 10 minutes; adjust dose based on patient response

For continuous IV infusion, the usual adult dose is 15 to 35 mg per hour

Comments:

• Due to the risks of addiction, abuse, and misuse, this drug should be reserved for use in patients for whom alternative treatment options have not been tolerated or are not expected to be tolerated or have not provided adequate analgesia, or are not expected to provide adequate analgesia.
• If adequate pain management cannot be achieved with a daily oral dose of 600 mg, alternative treatment is recommended.
• IV use should be restricted to settings in which a narcotic antagonist and facilities for assisted or controlled respiration are immediately available.
• The American Pain Society does not recommend use of this drug as an analgesic due to the accumulation of its toxic metabolite; this drug should not be used for the treatment of chronic pain.

Use: For the management of pain severe enough to require an opioid analgesic and for which alternative treatments are inadequate.

Usual Adult Dose for Anesthesia

For Preoperative Medication:
Usual dose: 50 to 100 mg IM or subcutaneously 30 to 90 minutes before the beginning of anesthesia

For Obstetrical Analgesia:
Usual dose: 50 to 100 mg IM or subcutaneously when pain becomes regular; may repeat at 1 to 3 hour intervals

For Support of Anesthesia:

• Slow IV fractional doses or continuous IV infusion of a dilute (e.g. 1 mg/mL) solution; titrate to needs of patients

Comment:

• This drug should not be administered IV unless a narcotic antagonist and facilities for assisted or controlled respiration are immediately available.

Uses: As a preoperative medication and for support of anesthesia and obstetrical analgesia.

Usual Pediatric Dose for Pain

Oral:
Initial dose: 1.1 to 1.8 mg/kg orally every 3 to 4 hours as needed
Maximum single dose: 50 to 150 mg
Maximum daily dose: 600 mg

Parenteral:
Initial dose: 1.1 to 1.8 mg/kg IM or subcutaneously every 3 to 4 hours as needed; IM administration is preferred when repeated doses are required
Maximum single dose: 50 to 150 mg

• May be administered IV, however, lower doses are advised and administration should be very slow, preferably using a diluted solution

Comments:

• The American Pain Society (APS) does not recommend this drug be used as an analgesic in infants, children, and those with acute vaso-occlusive crisis pain associated with sickle-cell disease.
• Due to the risks of addiction, abuse, and misuse, this drug should be reserved for use in patients for whom alternative treatment options have not been tolerated or are not expected to be tolerated or have not provided adequate analgesia, or are not expected to provide adequate analgesia.
• This drug should not be used for the treatment of chronic pain.

Use: For the management of pain severe enough to require an opioid analgesic and for which alternative treatments are inadequate.

Usual Pediatric Dose for Anesthesia

For Preoperative Medication:
Usual dose: 1.1 to 2.2 mg/kg IM or subcutaneously 30 to 90 minutes before the beginning of anesthesia
Maximum dose: 50 to 100 mg

For Support of Anesthesia:

• Slow IV fractional doses or continuous IV infusion of a dilute (e.g. 1 mg/mL) solution; titrate to needs of patients

Comment:

• This drug should not be administered IV unless a narcotic antagonist and facilities for assisted or controlled respiration are immediately available.

Uses: As a preoperative medication and for support of anesthesia.

Renal Dose Adjustments

Use with caution; accumulation of drug or active metabolite may occur

• Monitor closely for signs of CNS and respiratory depression

The American Pain Society recommends avoiding use of this drug for analgesia in patients with renal impairment.

Liver Dose Adjustments

Use with caution; accumulation of drug or active metabolite may occur

• Monitor closely for signs of CNS and respiratory depression

The American Pain Society recommends avoiding use of this drug for analgesia in patients with hepatic impairment.

Dose Adjustments

Elderly, Cachectic, or Debilitated Patients:

• Start at the low end of the dosing range; titrate slowly, and consider monitoring renal function
• Consider use of non-opioid analgesics

Concomitant Use with Phenothiazine or Other Tranquilizers:

• Meperidine dose should be reduced 25% to 50%

Do not abruptly discontinue in physically-dependent patient

• Taper gradually by 25% to 50% every 2 to 4 days
• If patient develops signs and symptoms of withdrawal, raise dose to previous level and taper more slowly.

Precautions

The US FDA requires a Risk Evaluation and Mitigation Strategy (REMS) for all opioids intended for outpatient use. The new FDA Opioid Analgesic REMS is a designed to assist in communicating the serious risks of opioid pain medications to patients and health care professionals. It includes a medication guide and elements to assure safe use. For additional information: www.accessdata.fda.gov/scripts/cder/rems/index.cfm

US BOXED WARNINGS: RISK OF MEDICATION ERRORS; ADDICTION, ABUSE AND MISUSE; RISK EVALUATION AND MITIGATION STRATEGY (REMS); LIFE-THREATENING RESPIRATORY DEPRESSION; ACCIDENTAL INGESTION; NEONATAL OPIOID WITHDRAWAL SYNDROME; CYP450 3A4 INTERACTION; RISKS FROM CONCOMITANT USE WITH BENZODIAZEPINES OR OTHER CNS DEPRESSANTS; and MONAMINE OXIDASE INHIBITORS (MAOIs) INTERACTIONS:

• Risk of Medication Errors: Ensure accuracy when prescribing, dispensing, and administering oral solution as confusion between mg and mL, and oral solutions of different concentrations can result in accidental overdose and death.
• Addiction, Abuse, and Misuse: This drug 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 and monitor all patients regularly for the development of these behaviors or conditions.
• Opioid Analgesic REMS: To ensure that the benefits of opioid analgesics outweigh the risks of addiction, abuse, and misuse, a REMS is required for these products. 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. Monitor for respiratory depression, especially during initiation or following a dose increase.
• Accidental Ingestion: Accidental ingestion, especially by children, can result in a fatal overdose.
• Neonatal Opioid Withdrawal Syndrome: Prolonged use 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 appropriate treatment be available.
• CYP450 3A4 Interaction: Concomitant use with all CYP450 3A4 inhibitors may result in an increase in plasma concentrations, which could increase or prolong adverse drug effects and may cause potentially fatal respiratory depression. Additionally, discontinuation of a concomitantly used CYP450 3A4 inducer may result in an increase in plasma concentrations. Monitor patients receiving any CYP450 3A4 inhibitor or inducer.
• 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. Reserve concomitant prescribing of meperidine 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; and follow patients for signs and symptoms of respiratory depression and sedation.
• Concomitant use with Monoamine Oxidase Inhibitors (MAOIs): Concomitant use with MAOIs can result in coma, severe respiratory depression, cyanosis, and hypotension. Use of meperidine with MAOIs within last 14 days is contraindicated.

CONTRAINDICATIONS:

• Hypersensitivity to the active substance or any of the product ingredients (e.g. anaphylaxis)
• Significant respiratory depression
• Acute or severe bronchial asthma in unmonitored setting or the absence of resuscitative equipment
• Known or suspected gastrointestinal obstruction, including paralytic ileus
• Concomitant use of monoamine oxidase inhibitors (MAOIs) or within 14 days

Safety and efficacy have not been established in patients younger than 18 years.

Consult WARNINGS section for additional precautions.

US Controlled Substance: Schedule II

Dialysis

Data not available

Other Comments

Administration advice:
Parenteral Use:

• IV use should be restricted to settings in which a narcotic antagonist and facilities for assisted or controlled respiration are immediately available
• For IV administration: Inject very slowly and preferably in the form of a diluted solution; patient should be lying down when receiving drug parenterally, especially IV
• Subcutaneous administration is suitable for occasional use; however, IM administration is preferred when repeated doses are required

Oral:

• For oral solution, ensure dose is communicated clearly to patients (both mg and mL) and a calibrated measuring device is provided to measure dose accurately.
• Oral solution should be diluted in one-half glass of water prior to administration as the undiluted solution may exert a slight topical anesthetic effect on mucous membranes.

Reconstitution/preparation techniques:

• Carpuject(R): Single use syringes to be used only with Carpuject(R) holders

Incompatibilities: Soluble barbiturates, aminophylline, heparin, morphine sulfate, methicillin, phenytoin, sodium bicarbonate, iodide, sulfadiazine, and sulfisoxazole.

General:

• The American Pain Society (APS) does not recommend use of oral meperidine as an analgesic agent due to the extensive amount of neurotoxic metabolite produced relative to the analgesic dose delivered; APS recommends avoiding analgesic use in infants, children, those with acute vaso-occlusive crisis pain associated with sickle-cell disease, and patients with renal impairment.
• Dosing regimens should be individualized taking into account pain severity, prior analgesic treatment experience, and risk factors for addiction, abuse, and misuse; the goal of therapy should be the lowest effective dose for the shortest duration consistent with individual patient goals; this drug is not indicated for the treatment of chronic pain.
• Black box warning includes warnings on addiction, abuse, and misuse; life-threatening respiratory depression; accidental ingestion, neonatal opioid withdrawal syndrome; CYP450 3A4 interaction; risks from concomitant use with benzodiazepines or other CNS depressants, and MAOI inhibitor interactions.

Monitoring:

• Assess risks for addiction, abuse, and misuse prior to therapy and regularly assess for development of these behaviors during therapy.
• Monitor for respiratory depression, especially within the first 24 to 72 hours of initiating therapy and following dose increases.
• Monitor for signs of hypotension upon initiating therapy and following dose increases, especially if blood pressure is already compromised.
• Monitor patients with biliary tract disease, including pancreatitis, for worsening symptoms

Patient advice:

• Patients should be instructed to read the US FDA-approved Medication Guide each time this drug is dispensed; they should understand the safe use, serious risks, and proper storage and disposal of this drug.
• Advise patients to store this drug safely out of the sight and reach of children; accidental use by a child is a medical emergency and can result in death.
• Patients should understand that this drug, even when taken as recommended can result in addiction, abuse, and misuse; instruct patients not to share their drug with others and protect their drug from theft or misuse.
• Patients should understand the risks of life-threatening respiratory depression, and be informed as to when this risk is greatest; patients should be made aware that crushing, chewing, or dissolving tablets may result in uncontrolled delivery of, and can lead to overdose or death.
• Patients should be informed about the risks of severe constipation or serotonin syndrome, and when to seek prompt medical help.
• Patients should be instructed to check with their healthcare provider before taking any new medications, including alcohol, herbal supplements and over the counter products.
• This drug may cause drowsiness, dizziness, or impair thinking or motor skills; patients should avoid driving or operating machinery until adverse effects are determined.
• Women of child bearing potential should understand that prolonged use during pregnancy can result in neonatal opioid withdrawal syndrome and that prompt recognition and treatment will be necessary.

Frequently asked questions

• What is pethidine used for?