meperidine

Meperidine is a synthetic opioid medication used for the management of acute pain severe enough to require an opioid pain reliever (analgesic) and for which alternative treatments are inadequate.

Meperidine depresses the central nervous system (CNS), has sedative and analgesic effects, and also causes respiratory depression. Meperidine inhibits the transmission of pain signals in the ascending pain pathways, altering pain perception and the body’s response to pain signals.

Meperidine works by binding to opioid receptors in the central nervous system. Opioid receptors are protein molecules on nerve cell (neurons) membranes that mediate the body’s response to most hormones and their functions include modulating pain, stress response, respiration, digestion, mood, and emotion. In addition to analgesia and sedation, meperidine has many other effects on the body’s systems which include:

• Central nervous system: Works on the brain stem respiratory centers and causes respiratory depression. Also causes constriction of pupils (miosis) even in complete darkness.
• Gastrointestinal system: Reduces gastric motility and peristalsis, the smooth muscle contractions that move the gastrointestinal contents, which can result in constipation. Also reduces pancreatic and biliary secretions.
• Cardiovascular system: Causes dilation of peripheral blood vessels which may result in low blood pressure (hypotension), including from change in position (orthostatic hypotension) and fainting, and histamine release that can cause opioid-induced itching, flushing, sweating and red eyes.
• Endocrine system: Inhibits secretion of luteinizing hormone by the pituitary gland and cortisol by the adrenal gland. Chronic opioid use can have deleterious effects on the reproductive system, including sexual dysfunction and infertility.
• Immune system: Animal studies indicate that meperidine has a variety of effects on components of the immune system, and overall, a modest immunosuppressive effect.

Opioid medications including meperidine have a high risk for addiction and must be used with great caution. Meperidine should be used for short-term acute severe episodes of pain, and not for chronic pain. Treatment is individualized based on the severity of pain, patient’s response to the drug and risk factors for addiction, abuse, or misuse.

FDA-approved uses of meperidine include:

• Acute pain severe enough to require opioid analgesic and no alternative option is adequate
• Preoperative analgesia before starting anesthesia
• Obstetrical anesthesia

Off-label uses include:

• Postoperative shivering
• Rigors from amphotericin B
• Targeted temperature management-related shivering

• Do not use meperidine in patients with:
  • Hypersensitivity to meperidine or any of the drug’s components
  • Significant respiratory depression
  • Acute or severe bronchial asthma, in the absence of resuscitative equipment
  • Suspected or confirmed gastrointestinal obstruction, or paralysis of the intestinal muscles (paralytic ileus)
• Do not use meperidine concurrently or within 14 days of monoamine oxidase inhibitor (MAOI) antidepressant therapy. Concurrent use with MAOs can cause severe respiratory depression and hypotension.
• Do not use meperidine concurrently with drugs that can increase serotonin levels. It can lead to serotonin syndrome, a potentially life-threatening condition.
• Meperidine should be used only in patients who cannot have alternate therapy or do not have effective pain relief from other therapies, because of the risks of addiction, abuse, and misuse with opioids, even at recommended doses.
• Ensure accuracy when prescribing, dispensing, and administering oral solution; dosing errors due to confusion between mg and mL, and other oral solutions of different concentrations can result in accidental overdose and death.
• Administer intravenous (IV) injections very slowly, preferably in the form of a diluted solution with the patient lying down. Do not administer IV unless an opioid antagonist and the facilities for assisted or controlled respiration are immediately available.
• Serious life-threatening or fatal respiratory depression can occur and the risk is greatest during initiation of therapy and increase of dosage. Monitor the patient closely.
• Advise patients and caregivers on how to recognize respiratory depression and to seek medical attention if breathing difficulties develop.
• Do not administer meperidine simultaneously with other central nervous system (CNS) depressants such as benzodiazepines. If no alternate drug is effective, limit dosages and durations to minimum required, and monitor the patient closely.
• Concomitant use with cytochrome P450 3A4 inhibitors or discontinuation of inducers can result in fatal overdose of meperidine.
• Meperidine addiction, abuse, and misuse can lead to overdose and death. Prescribe after carefully assessing the patient’s risk, and monitor regularly.
• Concurrent use with alcohol or other drugs of abuse that depress the central nervous system increases the risk for serious respiratory depression, coma and death.
• Tolerance to and physical dependence on meperidine can develop, with need for increased doses for pain relief.
• Prolonged opioid use during pregnancy can cause opioid withdrawal syndrome in the newborn, which may be life-threatening if not recognized and treated. If prolonged opioid treatment is required during pregnancy, advise the patient of the risks to the fetus and ensure appropriate treatment is available.
• Accidental consumption, especially in children, can result in fatal overdose.
• Meperidine can further reduce cardiac output and cause severe hypotension, positional (orthostatic) hypotension and loss of consciousness (syncope) in patients with already compromised circulation including reduced blood volume (hypovolemia) or circulatory shock; use with caution.
• Use with caution in patients with irregular heart rhythm (cardiac arrhythmia).
• Patients with bronchial asthma, chronic obstructive pulmonary disease (COPD) or other conditions with reduced lung capacity are at higher risk for serious respiratory depression. Use the lowest effective dose with extreme caution, under medical supervision.
• Avoid use in patients with impaired consciousness or coma. Patients are susceptible to intracranial effects of carbon dioxide retention.
• Use with caution in patients with head injury, brain tumors or high intracranial pressure. Meperidine can further increase intracranial pressure.
• Use with caution in patients with biliary tract diseases such as acute pancreatitis and monitor for worsening of symptoms. Meperidine may cause sphincter of Oddi spasms and increase serum amylase.
• Use with caution in acute abdominal conditions such as pseudomembranous colitis and toxin-mediated diarrhea. Meperidine may obscure diagnosis or clinical course of patient.
• Use meperidine with caution in patients with sickle cell anemia, hypothyroidism, myxedema, kyphoscoliosis with respiratory compromise, prostatic hypertrophy, urethral stricture, or biliary tract dysfunction.
• Event therapeutic doses of meperidine can cause serious, life-threatening, or fatal respiratory depression in elderly and debilitated patients. Use with extreme caution.
• Use with caution in patients with kidney impairment, meperidine metabolite normeperidine may accumulate and precipitate anxiety, tremors, or seizures.
• Cumulative dose or prolonged use for longer than 48 hours can cause accumulation of normeperidine, which can increase the frequency of seizures in patients with seizure disorders.
• Use with caution in patients with liver impairment.
• Use with caution in patients with alcohol intoxication, alcohol withdrawal syndrome, delirium tremens, or toxic psychoses.
• Opioids (dose-dependent) can cause sleep-related breathing disorders including central sleep apnea (CSA) and sleep-related hypoxemia. Taper and reduce if required.
• Use with caution in patients who are morbidly obese.
• In patients with pheochromocytoma, a type of adrenal tumor, meperidine has been reported to provoke hypertension.
• Meperidine may cause less smooth muscle spasm and constipation than equipotent doses of morphine.
• Meperidine can cause adrenal insufficiency, more often after one month of use; monitor the patient for symptoms and treat appropriately.
• When discontinuing meperidine therapy, particularly in physically-dependent patients, gradually taper dosage; do not abruptly discontinue.
• Avoid use of mixed opioid agonist/antagonist (e.g., pentazocine, nalbuphine, and butorphanol) or partial agonist (e.g., buprenorphine) analgesics in patients who are receiving meperidine, a full opioid agonist analgesic. May reduce analgesic effect and precipitate withdrawal symptoms.
• Discuss the availability of the opioid antagonist naloxone with all patients who are prescribed opioid analgesics, as well as their caregivers. Consider prescribing it to patients who are at increased risk of opioid overdose.
• Some formulations may contain sodium benzoate/benzoic acid, which have been associated with potentially fatal toxicity (gasping syndrome) in newborns.
• Some formulations contain sulfites, which may cause allergic reactions in sulfite sensitive patients.
• Healthcare workers are strongly encouraged to complete opioid analgesic risk evaluation and mitigation strategy (REMS) education program to be able to counsel patients and caregivers appropriately on safe use and disposal of opioid analgesics.

Common side effects of meperidine include:

• Lightheadedness
• Dizziness
• Sedation
• Sweating (diaphoresis)
• Flushing of the face
• Low blood pressure (hypotension)
• Palpitations
• Chest pain (angina)
• Abnormal ECG readings such as:
  • QT-interval elongation
  • ST-segment elevation
• Slow or rapid heart rate (bradycardia or tachycardia)
• Irregular heart rhythm (arrhythmia)
• Circulatory depression
• Fainting (syncope)
• Nausea
• Vomiting
• Dry mouth (xerostomia)
• Constipation
• Abdominal pain
• Spasm of sphincter of Oddi
• Agitation
• Restlessness
• Nervousness
• Confusion
• Delirium
• Disorientation
• Hallucination
• Mood changes
• Sedation
• Drug addiction, abuse and misuse
• Drug dependence (physical and psychological)
• Headache
• Increased intracranial pressure
• Involuntary muscle movements
• Weakness
• Tremor
• Convulsions
• Visual disturbances
• Shortness of breath (dyspnea)
• Respiratory depression
• Urinary retention
• Skin rash
• Hives (urticaria)
• Itching (pruritus)
• Local injection site reactions such as:
  • Pain
  • Wheal
  • Flare
• Hypersensitivity reactions
• Histamine release
• Adrenal insufficiency
• Reduced reproductive gland function (hypogonadism)
• Androgen insufficiency
• Withdrawal symptoms with discontinuation of drug

Serious side effects of meperidine include:

• Shock
• Seizure
• Cardiac arrest
• Life-threatening respiratory depression
• Respiratory arrest
• Neonatal opioid withdrawal syndrome
• Severe allergic reaction (anaphylaxis)
• Serotonin syndrome, a life-threatening drug reaction, with concurrent use of other serotonergic drugs

Call your doctor immediately if you experience any of the following symptoms or serious side effects while using this drug:

• Serious heart symptoms include fast or pounding heartbeats, fluttering in your chest, shortness of breath, and sudden dizziness;
• Severe headache, confusion, slurred speech, severe weakness, vomiting, loss of coordination, feeling unsteady;
• Severe nervous system reaction with very stiff muscles, high fever, sweating, confusion, fast or uneven heartbeats, tremors, and feeling like you might pass out; or
• Serious eye symptoms include blurred vision, tunnel vision, eye pain or swelling, or seeing halos around lights.

This is not a complete list of all side effects or adverse reactions that may occur from the use of this drug. Call your doctor for medical advice about serious side effects or adverse reactions. You may also report side effects or health problems to the FDA at 1-800-FDA-1088.

Syrup: Schedule II

• 50 mg/5 mL

Tablet: Schedule II

• 50 mg
• 100 mg

Injectable Solution: Schedule II

• 25 mg/mL
• 50 mg/mL
• 75 mg/mL
• 100 mg/mL

Adult:

Pain

• Meperidine is not recommended as a first choice analgesic by The American Pain Society and ISMP (2007); if no other options, limit use in acute pain to 48 hours or less; doses should not exceed 600 mg/24 hours; oral route is not recommended for treatment of acute or chronic pain
• Pain: 50-150 mg oral/intramuscular (IM)/subcutaneous (SC) every 3 to 4 hours as needed; adjust dose based degree of response
• Preoperatively: 50-100 mg IM/SC 30-90 minutes before beginning anesthesia
• Continuous infusion: 15-35 mg/hour
• Obstetrical analgesia: 50-100 mg IM/SC; repeated every 1-3 hours as needed

Dosing Modifications

• Renal impairment: Avoid use
• Hepatic impairment: Consider lower initial dose initially; increased opioid effect possible in cirrhosis

Dosing Considerations

Access to naloxone for opioid overdose

• Assess need for naloxone upon initiating and renewing treatment
• Consider prescribing naloxone based on:
  • Patient’s risk factors for overdose (e.g., concomitant use of central nervous system [CNS] depressants, a history of opioid use disorder, prior opioid overdose); presence of risk factors should not prevent proper pain management
  • Household members (including children) or other close contacts at risk for accidental ingestion or overdose
• Consult patients and caregivers on the following:
  • Availability of naloxone for emergency treatment of opioid overdose
  • Ways differ on how to obtain naloxone as permitted by individual state dispensing and prescribing requirements or guidelines (e.g., by prescription, directly from a pharmacist, as part of a community-based program)

Limitations of Use

• Because of risks of addiction, abuse, and misuse with opioids, even at recommended doses, reserve therapy for use in patients for whom alternative treatment options [e.g., non-opioid analgesics] have not been tolerated, or are not expected to be tolerated, have not provided adequate analgesia, or are not expected to provide adequate analgesia

Geriatric:

Pain

• 50 mg orally every 4 hours or 25 mg IM every 4 hours; treatment for acute pain should be limited to 1-2 doses

Dosing Considerations

• Not drug of choice in elderly patients, because of accumulation of metabolite normeperidine, causing increased CNS effects
• Reduce total daily dose in elderly patients

Pediatric:
Pain

• Meperidine is not recommended as a first choice analgesic by The American Pain Society and ISMP (2007); if no other options, limit use in acute pain to 48 hours or less; doses should not exceed 600 mg/24 hours; oral route is not recommended for treatment of acute or chronic pain
• 1-1.8 mg/kg oral/IM/SC every 3 to 4 hours as needed; individual dose not to exceed 100 mg  
• Preoperatively: 1.1-2.2 mg/kg IM/SC 30-90 minutes before initiation of anesthesia

Oral Solution Administration

• Ensure accuracy when prescribing, dispensing, and administrating oral solution to avoid dosing errors due to confusion between mg and mL with other meperidine hydrochloride oral solutions of different concentrations, which could result in accidental overdose and death; ensure proper dose is communicated and dispensed; when writing prescriptions, include both the total dose in mg and the total dose in volume
• Do not use household teaspoons or tablespoons to measure oral solution, as using a tablespoon instead of a teaspoon could lead to overdosage
• Use the lowest effective dosage for the shortest duration consistent with individual patient treatment goals
• Dilute each dose of oral solution in one-half glass of water because undiluted solution may exert a slight topical anesthetic effect on mucous membranes.

• Meperidine has a high potential for addiction, abuse, and misuse and can lead to overdose. Physical tolerance and dependence can also develop with chronic opioid use and cause withdrawal symptoms upon discontinuation of the drug.
• Meperidine overdose can cause respiratory depression, constricted pupils, cold and clammy skin, skeletal muscle flaccidity, extreme drowsiness leading to stupor or coma, pulmonary edema, hypotension, slow heart rate, airway obstruction and death.
• Accumulation of normeperidine, the active metabolite of meperidine, with chronic use can cause hallucinations, tremors, muscle twitches, dilated pupils, hyperactive reflexes, and convulsions.
• Opioid overdose treatment includes:
  • Supportive care to maintain respiration with assisted ventilation, oxygen, intravenous fluids and medication to increase arterial pressure.
  • Advanced life-support techniques if irregular heart rhythms or cardiac arrest occur.
  • Administration of an opioid antagonist such as naloxone hydrochloride, the antidote used to reverse opioid effects, if there is significant respiratory and circulatory depression.
  • The duration of opioid antagonist is usually shorter than the duration of meperidine. Patient is monitored till spontaneous respiration is established. Additional naloxone doses may be administered, if necessary.
  • Patients with physical dependence may have severe withdrawal symptoms and opioid antagonist should be initiated and titrated with care.

Inform your doctor of all medications you are currently taking, who can advise you on any possible drug interactions. Never begin taking, suddenly discontinue, or change the dosage of any medication without your doctor’s recommendation.

• Severe interactions of meperidine include:
  • alvimopan
  • isocarboxazid
  • linezolid
  • nirmatrelvir
  • nirmatrelvir/ritonavir
  • phenelzine
  • procarbazine
  • rasagiline
  • safinamide
  • selegiline
  • selegiline transdermal
  • tranylcypromine
• Meperidine has serious interactions with at least 59 different drugs.
• Meperidine has moderate interactions with at least 223 different drugs.
• Mild interactions of meperidine include:
  • brimonidine
  • bupropion
  • dextroamphetamine
  • ethotoin
  • eucalyptus
  • fosphenytoin
  • lidocaine
  • metoclopramide
  • phenytoin
  • ritonavir
  • sage
  • ziconotide

The drug interactions listed above are not all of the possible interactions or adverse effects. For more information on drug interactions, visit the RxList Drug Interaction Checker.

It is important to always tell your doctor, pharmacist, or health care provider of all prescription and over-the-counter medications you use, as well as the dosage for each, and keep a list of the information. Check with your doctor or health care provider if you have any questions about the medication.

• Chronic use of opioids may reduce fertility in both men and women of reproductive potential; it is not known whether these effects are reversible.
• Meperidine may cause fetal harm. Use meperidine in pregnancy only if benefits clearly outweigh potential risks to the fetus.
• Chronic opioid use by the mother during pregnancy can result in physical dependence and opioid withdrawal syndrome in the newborn.
• Opioid analgesics may prolong labor by temporarily reducing the strength, duration, and frequency of uterine contractions; however, this effect is not consistent and may be offset by the increased rate of cervical dilation.
• Maternal use of meperidine during labor and delivery may produce respiratory depression and other effects in the newborn; monitor newborn closely; keep an opioid antagonist, such as naloxone, available for reversal of opioid-induced respiratory depression in the newborn.
• Meperidine is present in breast milk. The decision to use opioids in breastfeeding women should be made after considering the mother’s clinical need and potential risks to the breastfeeding infant. If opioids are required in nursing mothers, the lowest effective dose for the shortest possible duration should be used.
• The breastfeeding infant should be monitored for adverse effects such as feeding difficulties, drowsiness, sedation or limpness. When maternal opioid use is discontinued or breastfeeding is stopped, the infant may have withdrawal symptoms.

• Meperidine is a Schedule II controlled substance; diversion of Schedule II products is subject to criminal penalty.
• Meperidine exposes users to the risks of addiction, abuse, misuse and dependence, even with prescribed dose, and can lead to fatal overdose. Use with great caution.
• Take meperidine exactly as prescribed; do not take a higher or more frequent dosage. Use the lowest possible dose for the shortest possible time.
• Never use a kitchen teaspoon or tablespoon to measure meperidine solution. Always use a calibrated measuring device. Dilute solution in half a glass water to avoid topical anesthetic effects in the mouth and throat.
• In case of known or suspected overdose, seek emergency medical help.
• Do not drink alcohol or take other drugs that can depress the central nervous system, while taking meperidine. It increases the risk for sedation, respiratory depression, coma and death.
• Meperidine can impair mental and physical ability. Avoid driving, operating heavy machinery or performing other potentially hazardous tasks while on meperidine therapy.
• Store meperidine well out of reach of children in a safe location not accessible to others. Accidental consumption, especially in children, can result in a fatal overdose.
• Dispose of expired, unwanted, or unused meperidine tablets and syrup by promptly flushing down the toilet, if a drug take-back option is not readily available.