Meperidine (Pethidine) - Uses, Dose, Side effects, MOA, Brands

Meperidine (Pethidine) is an opioid analgesic similar to morphine. It is used in the management of moderate to severe pain and for perioperative management of pain.

Meperidine (Pethidine) Uses:

  • Pain management:

    • Used in the management of acute pain severe enough to require an opioid analgesic and for which alternative treatments are inadequate; obstetrical analgesia, preoperative medication (IV only).
  • Limitations of use:
    • The American Pain Society and Institute for Safe Medication Practices do not recommend meperidine’s use as an analgesic.
    • If use in acute pain (in patients without renal or CNS disease) cannot be restricted, treatment should be limited to 48 or less than 48 hours and doses should not exceed 600 mg per 24 hours.
  • Off Label Use of Meperidine in Adults:

    • Used in postoperative shivering
    • Used in rigors from amphotericin B (conventional)
    • Used in targeted temperature management-related shivering

Meperidine (Pethidine) Dose in Adults:


  • The American Pain Society and ISMP do not allow meperidine’s use as an analgesic.
  • If use in acute pain (in sufferers without renal or CNS disease) cannot be avoided, treatment should be limited to 48 hours or less than 48 hours and doses should not exceed 600 mg per 24 hours.
  • Oral consideration is not necessary for the treatment of acute or chronic pain.
  • If IV consideration is necessary, consider a reduced dose.
  • When treating pain, patients with prior opioid exposure may require higher initial doses.

Meperidine (Pethidine) Dose in the management of Pain:

  • Acute pain:

    • IM, SubQ: 50 to 150 mg every 3 to 4 hours as required.
  • Discontinuation of therapy:

    • When stopping chronic opioid therapy, the dose should be gradually tapered down.
    • An optimal universal tapering schedule for all patients has not been established. Schedules range from slow (eg, 10 percent reductions per week) to rapid (e.g, 25 percent to 50 percent reduction every few days).
    • Tapering schedules should be individualized to minimize opioid withdrawal while considering patient-specific goals and concerns as well as the pharmacokinetics of the opioid being tapered.
    • An even taper slower may be appropriate in patients who have been accepting opioids for a long duration (e.g, years), particularly in the final stage of tapering, whereas more rapid tapers may be appropriate in patients experiencing severe adverse events.
    • Monitor carefully for signs or symptoms of withdrawal.
    • If the sufferer displays withdrawal symptoms, consider slowing the taper schedule; alterations may include increasing the interval between dose reductions, decreasing the amount of daily dose reduction, pausing the taper and restarting when the sufferer is ready, and coadministration of an alpha-2 agonist (eg, clonidine) to blunt withdrawal symptoms.
    • Continue to offer nonopioid analgesics as required for pain management during the taper; consider nonopioid adjunctive treatments for withdrawal symptoms (eg, muscle spasm, GI complaints) as required.
  • Obstetrical analgesia:

    • IM, SubQ: 50 to 100 mg when the pain becomes regular; may repeat at 1to 3-hour intervals.
  • Preoperative:

    • IM, SubQ: 50 to 100 mg administered 30 to 90 minutes before the beginning of anesthesia.
  • Dosage adjustment for concomitant therapy:

    • Concomitant phenothiazines/tranquilizers:
      • Reduce meperidine dose by 25% to 50% when administered concomitantly with phenothiazines and other tranquilizers.

Meperidine (Pethidine) Dose for postoperative shivering (off-label):

  • IV: 12.5 - 50 mg once or 0.2 mg per kg with adjunctive dexamethasone.

Meperidine (Pethidine) Dose in Rigors from conventional amphotericin B (off-label):

  • IV: 25 - 50 mg once.

Meperidine (Pethidine) Dose in Children:

Doses should be titrated to appropriate analgesic effect; when changing the route of administration, note that oral doses are about half as effective as parenteral dose.


  • The American Pain Society and ISMP advise against the use of meperidine as an analgesic.
  • If use for acute pain (in patients without CNS disease or renal ) cannot be restricted, treatment should be limited to 48 or less than 48  hours and doses should not exceed 600 mg per 24 hours in adults.
  • The oral route is not recommended for the treatment of acute or chronic pain.
  • If an IV route is needed, consider a reduced dose. Patients with prior opioid exposure may need higher initial doses.

Meperidine (Pethidine) Dose in the treatment of Acute pain (analgesic): Initial:

  • Infants ≤6 months:

    • IM, IV, SubQ: 0.2 to 0.25 mg/kg/dose every 2 to 3 hours
    • Oral: 0.5 to 0.75 mg per kg per dose every 3 to 4 hours
  • Infants >6 months, Children, and Adolescents:

    • IM, IV, or SubQ; intermittent dosing:

      • Patient weight <50 kg:
        • 0.8 to 1 mg/kg/dose every 2 to 3 hours as needed;
        • The maximum dose: 75 mg/dose
      • Patient weight ≥50 kg:
        • 50 to 75 mg every 2 to 3 hours as needed
    • Oral:

      • Patient weight <50 kg:
        • 2 to 3 mg/kg/dose every 3 to 4 hours as needed;
        • The maximum dose: 150 mg/dose
      • Patient weight ≥50 kg:
        • 100 to 150 mg every 3 to 4 hours as needed

Meperidine (Pethidine) Dose as preoperative in the treatment of Analgesia for minor procedures/ sedation:

  • Infants, Children, and Adolescents:

    • IM, IV, SubQ:
      • 0.5 to 1 mg per kg given 30 to 90 minutes before the starting of anesthesia;
      • The maximum dose: 2 mg per kg or 150 mg per dose.
    • Oral:
      • 2 to 4 mg per kg given 30 to 90 minutes before the beginning of anesthesia;
      • maximum dose: 150 mg per dose

Meperidine (Pethidine) Dose in the treatment of acute crisis in sickle cell disease; opioid naïve patients:

  • Infants ≥6 months, Children, and Adolescents:

Note: Not recommended for use unless it is the only opioid effective for the patient. Initial:

  • Patient weight <50 kg:
    • IV: 0.75 to 1 mg/kg every 3 to 4 hours as needed;
    • maximum dose: 1.75 mg/kg/dose or 100 mg/dose
  • Patient weight ≥50 kg:
    • IV: 50 to 150 mg every 3 hours as needed.

Meperidine (Pethidine) Pregnancy Category: B

  • Opioids can cross the placenta.
  • Some studies have shown that opioid use by mothers may cause birth defects such as congenital heart defects and neural tube defects.
  • [US Boxed Warning]Neonatal opioid withdrawal syndrome can develop from prolonged meperidine use during pregnancy. This condition is life-threatening and must be treated according to neonatology experts' protocols.
  • Pregnant women who are required to use opioids for prolonged periods of time should be advised and treated.
  • A pregnant woman who has been exposed to chronic opioids during pregnancy may experience withdrawal symptoms in her newborn.
  • Symptoms of neonatal Abstinence Syndrome (NAS) may include autonomic symptoms (eg. fever, temperature instability), gastrointestinal symptoms (eg. diarrhea, vomiting), or neurologic (eg. high-pitched crying and hyperactivity, increased muscle tone/abnormal wakefulness/sleep pattern, irritability/sneezing), seizure/tremor, yawning).
  • Opioid-dependent mothers may give birth to children who are also dependent.
  • Opioids can cause respiratory depression in neonates and psychophysiological effects in newborns.
  • Mothers who have given opioids to their babies during labor need to be closely monitored.
  • Meperidine was approved for use in obstetrical pain relief. However, it is not recommended for peripartum pain relief due to its prolonged half-life in the mother and neonate. It is also not recommended to be used to treat non-cancer chronic pain in pregnant women and those who might become pregnant.
  • Long-term opioid abuse can cause secondary hypogonadism. This could lead to infertility or sexual dysfunction in both men and women.

Meperidine use during breastfeeding:

  • Breast milk contains meperidine.
  • Exposure to meperidine or normeperidine in breast milk is associated with neonatal sedation, and can interfere with breastfeeding.
  • Breastfeeding females who need pain control during pregnancy or after surgery are advised to use nonopioid analgesics. Meperidine is not recommended for opioid-dependent patients.
  • Even though a single dose may be acceptable, it is important to monitor the infant after multiple doses.
  • To limit adverse reactions in mother and baby when opioids are required for breastfeeding, it is important to use the lowest dose of opioids for the shortest time.
  • Breastfeeding mothers who use opioids to treat postpartum pain must monitor their infants for signs of drowsiness or sedation, feeding difficulties, and/or limpness.
  • When breastfeeding is stopped or maternal use is cut off, withdrawal symptoms can occur.
  • According to the manufacturer breastfeeding during therapy is a decision that should be made after considering the risks to infants and the benefits to mothers.

Dose in Kidney Disease:

Avoid use as an analgesic in renal impairment.

Meperidine (Pethidine) Dose in Liver disease:

  • There are no dosage adjustments provided in the manufacturer's labeling; use with caution and titrate slowly; monitor closely for signs of CNS excitation (eg, seizure activity) and CNS and respiratory depression.
  • In patients with severe impairment, consider a lower dose when initiating therapy; an increased opioid effect may be seen in patients with cirrhosis; dose reduction is more important for the oral (route not recommended) than IV route.

Meperidine (Pethidine) Side effects:

  • Cardiovascular:

    • Syncope
    • Tachycardia
  • Central Nervous System:

    • Agitation
    • Confusion
    • Delirium
    • Disorientation
    • Dizziness
    • Drug Dependence (Physical Dependence)
    • Habituation
    • Hallucination
    • Headache
    • Increased Intracranial Pressure
    • Involuntary Muscle Movements (Including Muscle Twitching, Myoclonus)
    • Mood Changes (Including Euphoria, Dysphoria)
    • Sedation
    • Seizure (Associated With Metabolite Accumulation)
    • Serotonin Syndrome
  • Dermatologic:

    • Diaphoresis
    • Pruritus
    • Skin Rash
    • Urticaria
  • Gastrointestinal:

    • Biliary Colic
    • Constipation
    • Nausea
    • Spasm Of Sphincter Of Oddi
    • Vomiting
    • Xerostomia
  • Genitourinary:

    • Urinary Retention
  • Hypersensitivity:

    • Anaphylaxis
    • Histamine Release
    • Hypersensitivity Reaction
  • Local:

    • Injection Site Reaction (Including Pain, Wheal, And Flare)
  • Neuromuscular & Skeletal:

    • Tremor
    • Weakness
  • Ophthalmic:

    • Visual Disturbance
  • Respiratory:

    • Dyspnea
    • Respiratory Arrest
    • Respiratory Depression

Contraindications to Meperidine (Pethidine):

  • Hypersensitivity to meperidine and any other component of the formulation (eg, anaphylaxis);
  • Use within 14 days of MAO inhibitors
  • Significant respiratory depression
  • Acute or severe bronchial asthma in unmonitored settings or without resuscitative devices;
  • Paralytic ileus, known or suspected, GI obstruction

Canadian labeling: Additional contraindications not in US labeling

  • Known or suspected mechanical GI obstruction (eg bowel obstruction or strictures), or any diseases/conditions affecting bowel transit (eg ileus of any kind).
  • Acute respiratory depression
  • Mild pain can be managed by other pain medication;
  • Status asthmatics, acute or severe bronchial asthma, chronic obstruction of the airway, status asthmatics
  • Suspected surgical abdomen (eg acute appendicitis, pancreatitis);
  • Hypoxia
  • CNS depression severe, elevated cerebrospinal and intracranial pressures, head injury
  • hypercapnia
  • Cor pulmonale
  • acute alcoholism, delirium tremens,
  • convulsive disorders and
  • Concurrent use or use within two weeks of an MAOI

There is not much evidence of cross-reactivity between opioids and allergenic opioids. Cross-sensitivity is possible due to similarities in chemical structure or pharmacologic effects.

Warnings and precautions

  • CNS depression:

    • CNS depression can result, which could impair mental or physical abilities.
    • Patients should be cautious about driving or operating machinery that requires mental alertness.
  • Events of the CNS

    • Normeperidine, a CNS stimulant and active metabolite, can cause anxiety, tremors and seizures.
    • The risk is increased if there are preexisting conditions such as CNS dysfunction or prolonged use (>48hrs), cumulative dose (>600mg/24 hours for adults), or long-term use (>48hrs).
    • Oral meperidine should be avoided as the first-pass metabolism reduces efficacy and increases normeperidine concentrations.
    • Notification: Naloxone can not reverse or worsen neurotoxicity.
  • Constipation

    • Constipation can be a problem in patients with unstable angina or post-myocardial injury (MI) patients.
    • To reduce constipation, consider preventive measures such as stimulant laxative.
  • Hypotension

    • It can cause severe hypotension, including syncope or orthostatic hypotension. Patients with hypovolemia, heart disease (including acute MI), and drugs that may exaggerate hypotensive effect (including phenothiazines and general anesthetics) are strongly advised to be cautious.
    • After dose titration or initiation, monitor for hypotension symptoms.
    • Patients with circulatory shock should not use this product.
  • Respiratory depression [US Boxed Warning]

    • It is possible to develop severe, life-threatening or fatal respiratory depression.
    • Pay attention to respiratory depression during dose escalation or initiation. 
    • The sedating effects of opioid-induced respiratory depression may be exacerbated by carbon dioxide retention.
  • Serotonin syndrome:

    • May occur with concomitant use of serotonergic agents (eg, selective serotonin reuptake inhibitors, serotonin-norepinephrine reuptake inhibitors, triptans, tricyclic antidepressants), lithium, St. John's wort, agents that impair metabolism of serotonin (eg, monoamine oxidase inhibitors [MAOIs]), or agents that impair metabolism of tramadol (eg, CYP2D6 and 3A4 inhibitors).
    • Monitor patients for serotonin symptoms such as mental changes (eg. agitation, hallucinations and coma); autonomic instability, (eg. tachycardias, labile pressure, hyperthermia); neuromuscular modifications (eg. hyperreflexia or incoordination); and/or GI signs (eg. nausea, vomiting, diarrhea).
  • Conditions abdominales:

    • A patient with acute abdominal problems may have a questionable diagnosis or follow-up.
  • Adrenocortical Insufficiency

    • Patients with adrenal insufficiency (Addison disease) should be cautious and decrease the initial dose.
    • Long-term opioid abuse can lead to secondary hypogonadism. This could cause infertility, sexual dysfunction, mood disorders, and osteoporosis.
  • Insufficiency of the biliary tract:

    • Patients with biliary dysfunction (including acute pancreatitis) should be cautious. Opioids may cause constriction to the sphincter.
  • CNS depression/coma:

    • Patients with impaired consciousness and coma should not be used as they are more susceptible to the intracranial effects carbon dioxide retention.
  • Delirium tremens:

    • Patients with delirium-tremens should be taken with caution
  • Head trauma

    • Patients who have suffered a head injury, intracranial lesion, or elevated intracranial Pressure (ICP), are strongly advised to avoid it. Exaggerated elevations of ICP could occur.
  • Hepatic impairment

    • Patients with liver disorders should be cautious; meperidine, and in a lesser extent normeperidine, can accumulate and cause CNS depression (eg anxiety, tremors or seizures).
  • Obesity:

    • Patients who are severely obese should be taken with caution
  • Pheochromocytoma:

    • Patients with pheochromocytoma should be cautious.
  • Prostatic hyperplasia/urinary restriction:

    • Patients with prostatic hyperplasia or urinary stricture should be cautious and reduced the initial dose.
  • Psychosis:

    • Patients with toxic psychosis should be treated with caution.
  • Renal impairment

    • Patients with impaired renal function should not take normeperidine. It can cause anxiety, tremors or seizures and may lead to a buildup.
  • Respiratory disease

    • Patients with severe chronic obstructive lung disease (or cor pulmonale) and patients with significantly decreased respiratory reserve, hypoxia or hypercapnia or preexisting respiratory depression should be cautious.
    • Monitor for signs of respiratory depression when initiating or titrating therapy. Critical respiratory depression can occur even at therapeutic doses.
    • These patients should be prescribed nonopioid analgesics.
  • Seizure disorders:

    • Patients with seizure disorders should be cautious when using this medication. High doses or prolonged use can cause seizures or worsen them.
  • Sickle-cell Disease:

    • Patients with sickle cell disease should be cautious and reduce the initial dose.
    • Notice:The American Pain Society does not recommend Meperidine for sickle cell patients. It should be used only in patients suffering from a vasoocclusive crisis.
  • Sleep-related disorders

    • Dose-dependently, opioid use can increase the risk of sleep-related disorders (eg central sleep apnea and hypoxemia). Use with caution.
  • Tachycardia

    • Patients with supraventricular tachycardias or atrial flutter should be cautious. The vagolytic effect may cause an increase in the ventricular response rate.
  • Thyroid dysfunction:

    • Patients with hypothyroidism or thyroid dysfunction should be cautious.

Monitoring parameters:

  • Mental status and respiratory,blood pressure, Pain relief;
  • bowel function;
  • signs or symptoms of misuse, abuse and addiction;
  • signs or symptoms of hypoadrenalism or hypogonadism or serotonin syndrome in patient receiving other medications that enhance serotonergic activity.

How to administer Meperidine (Pethidine)?


  • Administration of IM, SubQ or IV (patient must be lying down during administration).
  • IV Push should be administered slowly with a diluted solution. A 10 mg/mL concentration is recommended.
  • When repeated doses are required, IM consideration is preferable.

Oral solution

  • Each dose should be taken in 1/2 glass water. Undiluted solutions may cause a local anesthetic effect to the mucous membranes.
  • To measure the dosage, use a calibrated measuring instrument; don't use a teaspoon nor a tablespoon.
  • High caution is advised. Dosing mistakes can lead to accidental overdose and even death.

Mechanism of action of Meperidine (Pethidine):

The CNS binds to opioid receptors, which affect inhibition of ascending pain pathways. This alters the perception and response to pain.

The onset of action: Analgesic:

  • Oral, IM, SubQ: 10 to 15 minutes;
  • IV: ~5 minutes

Peak effect:

  • IV: 5 to 7 minutes;
  • IM, SubQ: ~1 hour;
  • Oral: 2 hours


  • Oral, IM, SubQ: 2 to 4 hours;
  • IV: 2 to 3 hours

Absorption: IM, Oral:

  • Erratic and highly variable

Protein binding (to alpha 1-acid glycoprotein):

  • Neonates: 52 percent ;
  • Infants: 3 to 18 months: 85 percent;
  • Adults: 65 percent to 75 percent.


  • Hepatic; hydrolyzed to meperidinic acid (inactive) or undergoes N-demethylation to normeperidine (active; has 1/2 the analgesic effect and 2 to 3 times the CNS effects of meperidine)


  • ~50 percent  to 60 percent; increased with liver disease

Half-life elimination:

Parent drug: Terminal phase:

  • Preterm infants 3.6 to 65 days of age:
    • 11.9 hours (range: 3.3 to 59.4 hours)
  • Term infants:
    • 0.3 to 4 days of age: 10.7 hours (range: 4.9 to 16.8 hours);
    • 26 to 73 days of age: 8.2 hours (range: 5.7 to 31.7 hours)
  • Neonates:
    • 23 hours (range: 12 to 39 hours)
  • Infants 3 to 18 months:
    • 2.3 hours
  • Children 5 to 8 years:
    • 3 hours
  • Adults: 2.5 to 4 hours, Liver disease:
    • 7 to 11 hours

Normeperidine (active metabolite):

  • Neonates: 30 to 85 hours;
  • Adults: 8 to 16 hours; normeperidine half-life is dependent on renal function and can accumulate with high doses or in patients with decreased renal function; normeperidine may precipitate tremors or seizures


  • Urine (as metabolites; ~5% as unchanged drug)

International Brand Names of Meperidine:

  • Demerol
  • Aldolan
  • Alodan "Gerot"
  • Cluyer
  • Deme
  • Demero
  • Demerol HCl
  • Dolantin
  • Dolantina
  • Doloblok
  • Dolosal
  • Dolsin
  • Dornot
  • Lydol
  • Meperdol
  • Meperidol
  • Pethidin
  • Pethidine
  • Pethidine Injection
  • Pethidine Roche
  • Pethidine Tablet
  • Pethidine-Hameln
  • Petidin
  • Petidina
  • Verpat

Meperidine Brand Names in Pakistan:

Meperidine (Pethidine) (HCl) Injection 50 mg/ml

Pethidine Lahore Chemical & Pharmaceutical Works (Pvt) Ltd
Pethiscot Scotmann Pharmaceuticals