Brand name: Demerol
Drug class: Opiate Agonists
VA class: CN101
CAS number: 50-13-5

Medically reviewed by Drugs.com on Apr 19, 2023. Written by ASHP.

Introduction

Opiate agonist; a synthetic phenylpiperidine derivative.^b

Uses for Meperidine

Acute Pain

A strong analgesic used in the relief of moderate to severe pain.^b

Usually, temporary relief of moderate to severe pain such as that associated with acute and some chronic medical disorders including renal or biliary colic, acute trauma, postoperative pain, and cancer.^e

Used to provide analgesia during diagnostic and orthopedic procedures and during labor.^{246 e}

For preoperative sedation and as a supplement to anesthesia.^e

Use as first-line opiate therapy is discouraged because of central excitatory toxicity of metabolite (normeperidine).^{247 245}

Because of extensive first-pass metabolism in the liver to normeperidine, the risk of excitatory toxicity is increased with oral administration of meperidine; therefore, oral therapy is discouraged.^{246 247 245}

Has been used to relieve the pain of MI, although probably not as effective as morphine sulfate.^b

In symptomatic treatment of acute pain, reserve opiate analgesics for pain resulting from severe injuries, severe medical conditions, or surgical procedures, or when nonopiate alternatives for relieving pain and restoring function are expected to be ineffective or are contraindicated.^{431 432 433 435} Use smallest effective dosage for shortest possible duration since long-term opiate use often begins with treatment of acute pain.^{411 431 434 435} Optimize concomitant use of other appropriate therapies.^{432 434 435} (See Managing Opiate Therapy for Acute Pain under Dosage and Administration.)

Chronic Pain

Use for chronic pain is discouraged because of short duration of effect and risk of accumulation of normeperidine metabolite and resultant central excitatory toxicity with repeated or large doses.^{e 248}

Surgery

Used parenterally for preoperative sedation and as a supplement to anesthesia.^b

Pulmonary Edema

Used in patients with acute pulmonary edema^{† [off-label]} for its cardiovascular effects and to allay anxiety.^b

Do not use in the treatment of pulmonary edema resulting from a chemical respiratory irritant.^b

Meperidine Dosage and Administration

General

• Generally limit to short-term use (a few days) because of risk of accumulation of toxic normeperidine metabolite with repeated or large doses.^{e 247 245 248}

Managing Opiate Therapy for Acute Pain

• Optimize concomitant use of other appropriate therapies.^{432 434 435}

• When opiate analgesia required, use conventional (immediate-release) opiates in smallest effective dosage and for shortest possible duration, since long-term opiate use often begins with treatment of acute pain.^{411 431 434 435}

• When sufficient for pain management, use lower-potency opiate analgesics given in conjunction with acetaminophen or an NSAIA on as-needed (“prn”) basis.⁴³²

• For acute pain not related to trauma or surgery, limit prescribed quantity to amount needed for expected duration of pain severe enough to require opiate analgesia (generally ≤3 days and rarely >7 days).^{411 433 434 435} Do not prescribe larger quantities for use in case pain continues longer than expected;^{411 432} instead, reevaluate patient if severe acute pain does not remit.^{411 431 435}

• For moderate to severe postoperative pain, provide opiate analgesic as part of a multimodal regimen that also includes acetaminophen and/or NSAIAs and other pharmacologic (e.g., certain anticonvulsants, regional local anesthetic techniques) and nonpharmacologic therapy as appropriate.^{430 431 432}

• Oral administration of conventional opiate analgesics generally preferred over IV administration in postoperative patients who can tolerate oral therapy.^{430 431}

• Scheduled (around-the-clock) dosing frequently is required during immediate postoperative period or following major surgery.^{430 432} When repeated parenteral administration is required, IV patient-controlled analgesia (PCA) generally is recommended.^{430 431}

• Consider prescribing naloxone concomitantly for patients who are at increased risk of opiate overdosage^{411 431 750} or who have household members, including children, or other close contacts who are at risk for accidental ingestion or overdosage.⁷⁵⁰ (See Respiratory Depression under Cautions.)

Administration

Administer orally; by sub-Q, IM, or slow IV injection; or by slow, continuous IV infusion.^b

Oral Administration

Least effective when given orally.^{b 246 247 245} Higher dosages may be necessary for pain relief, but the risk of toxicity from metabolite normeperidine is increased.^{247 248}

Oral therapy is discouraged because of extensive first-pass metabolism in the liver and resultant increased formation of the toxic metabolite (normeperidine).^{246 247 245 248}

Dilution

Dilute each dose of oral solution in ½ glassful of water, since undiluted solution may produce slight topical anesthesia on mucous membranes.^b

IV Administration

For solution and drug compatibility information, see Compatibility under Stability.

Administer by direct IV injection, IV infusion, or IV via a controlled-delivery device for patient-controlled analgesia (PCA).^{b c 246}

If IV administration is required, decrease dosage and administer injections very slowly, preferably as a 10-mg/mL injection.^{b HID}

Alternatively, may use the commercially available injection containing 10 mg/mL intended for use with a compatible infusion device (does not require further dilution); this 10-mg/mL injection is for single use only, and unused portions should be discarded appropriately.^b

When given parenterally, especially by the IV route, the patient should be lying down.^b

During and immediately following IV administration, an opiate antagonist and facilities for administration of oxygen and control of respiration should be available.^b

Dilution

May dilute in a compatible IV solution for infusion, usually to a concentration of 1 mg/mL.^{b HID} (See Solution Compatibility under Compatibility.)

Rate of Administration

Direct IV injection: Usually, very slowly, preferably as a 10-mg/mL injection.^{246 HID}

IV injection for PCA: Self-administered intermittently as needed (“prn”) via controlled-delivery device, with usual lockout intervals (minimum time between self-administered doses programmed into device) of 6–12 minutes.²⁴⁶

IV infusion, adults: Usually, 15–35 mg/hour.^b

IM Administration

Inject into a large muscle mass, taking care to avoid nerve trunks.^b (See IM Injection under Cautions.)

IM administration of opiate analgesics is discouraged; IM injections can cause pain and are associated with unreliable absorption, resulting in inconsistent analgesia.^{246 247 248 430}

When repeat parenteral doses are necessary and IV therapy is not used, IM is preferred over sub-Q administration because of occurrence of local tissue irritation and induration following sub-Q injection.^b

Epidural Administration

Preservative-free injections have been injected or infused epidurally^{† [off-label]}; specialized techniques are required for administration of the drug by this route, and such administration should be performed only by qualified individuals familiar with the techniques of administration, dosages, and special patient management problems associated with epidural meperidine hydrochloride administration.^b

Dosage

Orally, 300 mg is approximately equianalgesic with 30 mg morphine sulfate.^{c 245 248} Parenterally, 75–100 mg is approximately equianalgesic with 10 mg morphine sulfate.^{c 245 248} (For specific patient dosages, see dosage recommendations in Dosage and also see Prescribing Limits under Dosage and Administration.)

Use lowest effective dosage and shortest duration of therapy consistent with treatment goals of the patient.^{411 413 431 432 435}

Reduced dosage is indicated initially in poor-risk patients, geriatric and very young patients, and patients with renal (particularly) or hepatic impairment.^{b 246 247 245}

When used concomitantly with other CNS depressants, use lowest effective dosages and shortest possible duration of concomitant therapy.^{700 703} (See Specific Drugs under Interactions.) Reduce meperidine dose by 25–50% when used in conjunction with phenothiazines or other tranquilizers.^b

Pediatric Patients

Some experts discourage use in children.²⁴⁵

Usual Dosage

Oral, IM, or Sub-Q

May receive 1.1–1.8 mg/kg (up to adult dose) orally, IM, or sub-Q every 3–4 hours as needed.^{b c 246}

Alternatively, 175 mg/m² daily in 6 divided doses orally, IM, or sub-Q.^b

Single pediatric doses should not exceed 100 mg.^b

IV

Do not use for PCA when analgesic consumption is expected to be high; risk of CNS excitatory toxicity from normeperidine.²⁴⁷

PCA (usually IV) via controlled-delivery device: Loading doses of 0.5–1.5 mg/kg, preferably titrated by clinician or nurse at bedside.²⁴⁶

PCA (usually IV) via controlled-delivery device: Maintenance doses (administered intermittently) of 0.1–0.2 mg/kg, self-administered usually no more frequently than every 6–12 minutes as a device-programmed lockout period.²⁴⁶

Preoperative Dosage

IM or Sub-Q

May receive 1–2.2 mg/kg (maximum up to the adult dose) IM or sub-Q 30–90 minutes before the beginning of anesthesia.^b

Adjunct to Anesthesia

IV Injection or IV Infusion

May be given by repeated slow IV injections of a dilute solution (e.g., containing 10 mg/mL) or by continuous IV infusion of a more dilute solution (e.g., containing 1 mg/mL).^b

Adults

Usual Dosage

Oral, IM, or Sub-Q

Usually, 50–150 mg every 3–4 hours as needed.^{b c 246}

IV infusion

Usually, 15–35 mg/hour.^b

IV

Do not use for PCA when analgesic consumption is expected to be high; risk of CNS excitatory toxicity from normeperidine.²⁴⁷

PCA (usually IV) via controlled-delivery device: Loading doses of 12.5–25 mg every 10 minutes, preferably titrated by clinician or nurse at bedside, up to 50–125 mg total.²⁴⁶

PCA (usually IV) via controlled-delivery device: Maintenance doses (self-administered intermittently) of 5–10 mg, self-administered usually no more frequently than every 6–12 minutes as a device-programmed lockout period.²⁴⁶

Preoperative Dosage

IM or Sub-Q

Usually, 50–100 mg IM or sub-Q 30–90 minutes before the beginning of anesthesia.^b

Adjunct to Anesthesia

IV Injection or IV Infusion

May be given by repeated slow IV injections of a dilute solution (e.g., containing 10 mg/mL) or by continuous IV infusion of a more dilute solution (e.g., containing 1 mg/mL).^b

Analgesia during Labor

IM or Sub-Q

50–100 mg when labor pains become regular; repeat at 1- to 3-hour intervals as needed.^b

Prescribing Limits

Pediatric Patients

Oral, IM, or Sub-Q

Single pediatric doses should not exceed 100 mg.^b

Adults

Oral, IV, IM, or Sub-Q

Increased risk of toxicity from the active metabolite, normeperidine, when given for >48 hours or in total dosages exceeding 600 mg/24 hours.²⁴⁵ (See Elimination under Pharmacokinetics.)

Special Populations

Hepatic Impairment

Adjustment in the dose, frequency, and/or duration of therapy may be necessary because accumulation of the drug and/or its toxic metabolite, normeperidine, can occur.^{200 204 205 206 207 208 209 210 211 212 213}

Certain adverse effects secondary to CNS stimulation (e.g., seizures, agitation, irritability, nervousness, tremors, twitches, myoclonus) have been attributed to accumulation of normeperidine.^{200 201 204 205 206 209 210 211 240}

Oral bioavailability may be increased substantially in these patients.^{212 213} (See Pharmacokinetics.)

Renal Impairment

Generally avoid in renal impairment, particularly repeated or high doses.^{246 247 245}

If used, adjustment in the dose, frequency, and/or duration of meperidine therapy is likely to be necessary because accumulation of the drug and/or its toxic metabolite, normeperidine, can occur.^{200 204 205 206 207 208 209 210 211 212 213}

Certain adverse effects secondary to CNS stimulation (e.g., seizures, agitation, irritability, nervousness, tremors, twitches, myoclonus) have been attributed to accumulation of normeperidine.^{200 201 204 205 206 209 210 211 240}

End-stage Renal Failure

Avoid because of the risk of accumulation of the toxic metabolite, normeperidine.^{200 205 207 208 211 220}

Cautions for Meperidine

Contraindications

• Current or recent (within 14 days) use of MAO inhibitor.^{b e 244}

• Known hypersensitivity to meperidine or any ingredient in the respective formulation.²⁴⁴

Warnings/Precautions

Warnings

Shares the toxic potentials of the opiate agonists; observe the usual precautions of opiate agonist therapy.^e

Respiratory Depression

Causes dose-related respiratory depression.^{e 244}

Respiratory depression is most common in geriatric or debilitated patients, or in conditions accompanied by hypoxia or hypercapnia; even moderate therapeutic opiate dosages may dangerously decrease pulmonary ventilation.^{e 244}

Use with extreme caution, if at all, in anoxia, hypercapnia, respiratory depression, or in those who are especially prone to respiratory depression such as comatose patients or those with head injury, brain tumor, or elevated CSF pressure.^e

Also use with extreme caution, if at all, in cor pulmonale, acute asthma exacerbation, or COPD and in others with substantially decreased respiratory reserve as in emphysema, hypoxia, hypercapnia, kyphoscoliosis, or severe obesity.^{e 244}

Routinely discuss the availability of the opiate antagonist naloxone with all patients receiving new or reauthorized prescriptions for opiate analgesics, including meperidine.⁷⁵⁰

Consider prescribing naloxone for patients receiving opiate analgesics who are at increased risk of opiate overdosage (e.g., those receiving concomitant therapy with benzodiazepines or other CNS depressants, those with history of opiate or substance use disorder, those with medical conditions that could increase sensitivity to opiate effects, those who have experienced a prior opiate overdose)^{411 431 750} or who have household members, including children, or other close contacts who are at risk for accidental ingestion or overdosage.⁷⁵⁰ Even if patients are not receiving an opiate analgesic, consider prescribing naloxone if the patient is at increased risk of opiate overdosage (e.g., those with current or past diagnosis of opiate use disorder [OUD], those who have experienced a prior opiate overdose).⁷⁵⁰

Concomitant Use with Benzodiazepines or Other CNS Depressants

Concomitant use of opiates, including meperidine, and benzodiazepines or other CNS depressants (e.g., anxiolytics, sedatives, hypnotics, tranquilizers, muscle relaxants, general anesthetics, antipsychotics, other opiate agonists, alcohol) may result in profound sedation, respiratory depression, coma, and death.^{416 417 418 700 701 702 703} Substantial proportion of fatal opiate overdoses involve concurrent benzodiazepine use.^{416 417 418 435 700 701}

Reserve concomitant use of meperidine and other CNS depressants for patients in whom alternative treatment options are inadequate.^{700 703} (See Specific Drugs under Interactions.)

Serotonin Syndrome

Serotonin syndrome may occur in patients receiving meperidine in conjunction with other serotonergic drugs or drugs that impair serotonin metabolism (e.g., MAO inhibitors).^{249 250 251 252 254 400} (See Interactions.)

Serotonin syndrome may occur at usual dosages.⁴⁰⁰ Manifestations may include mental status changes (e.g., agitation, hallucinations, coma), autonomic instability (e.g., tachycardia, labile BP, hyperthermia), neuromuscular aberrations (e.g., hyperreflexia, incoordination, rigidity), and/or GI symptoms (e.g., nausea, vomiting, diarrhea).⁴⁰⁰

Concomitant use with an MAO inhibitor has resulted in excitatory effects (e.g., agitation, bizarre behavior, headache, hypertension, hypotension, rigidity, seizures, hyperpyrexia, coma) associated with serotonin syndrome.^{249 250 251 252 253 254}

Adrenal Insufficiency

Adrenal insufficiency reported in patients receiving opiate agonists or opiate partial agonists.⁴⁰⁰ Manifestations are nonspecific and may include nausea, vomiting, anorexia, fatigue, weakness, dizziness, and hypotension.⁴⁰⁰

If adrenal insufficiency is suspected, perform appropriate laboratory testing promptly and provide physiologic (replacement) dosages of corticosteroids; taper and discontinue the opiate agonist or partial agonist to allow recovery of adrenal function.⁴⁰⁰ If the opiate agonist or partial agonist can be discontinued, perform follow-up assessment of adrenal function to determine if corticosteroid replacement therapy can be discontinued.⁴⁰⁰ In some patients, switching to a different opiate improved symptoms.⁴⁰⁰

Head Injury and Increased Intracranial Pressure

Respiratory depression effects and ability of opiates to increase CSF pressure may be markedly exaggerated in patients with head injury, other intracranial lesions, or preexisting elevation in intracranial pressure; opiate effects may produce cerebral hypoxia and obscure clinical course of patients with head injuries.²⁴⁴ Use with extreme caution, if at all.²⁴⁴

May interfere with evaluation of CNS function, and respiratory depression produced by the drug may produce cerebral hypoxia and elevated CSF pressure not caused by the injury itself.^{e 246}

Ambulatory Patients

Performance of activities requiring mental alertness and physical coordination may be impaired (e.g., operating a motor vehicle or machinery).²⁴⁴

Hypotension

May cause severe hypotension postoperatively or when ability to maintain blood pressure is compromised (e.g., depleted blood volume, concurrent phenothiazine or general anesthetic use).²⁴⁴

May produce orthostatic hypotension in ambulatory patients.²⁴⁴

IM Injection

Inadvertent IM injection into or near nerve trunks can result in sensory-motor paralysis, which may or may not be transient.^b

Dependence

Physical and psychic dependence and tolerance may develop with repeated administration, and abuse potential exists; use with caution.^e

Sensitivity Reactions

Sulfite Sensitivity

Some commercially available formulations contain sodium metabisulfite, a sulfite that may cause allergic-type reactions, including anaphylaxis and life-threatening or less severe asthmatic episodes, in certain susceptible individuals.^b

Overall prevalence of sulfite sensitivity in the general population is unknown but probably low; such sensitivity appears to occur more frequently in asthmatic than in nonasthmatic individuals.^b

General Precautions

Toxic Psychosis and Special Populations

Care should be exercised and the initial dosage of the opiate agonist should be reduced in patients with toxic psychosis and in geriatric or debilitated patients.^e

Cardiac Arrhythmias

May increase ventricular response rate through a vagolytic action, therefore use with caution in patients with atrial flutter and other supraventricular tachycardias.^{b 244}

Acute Abdominal Conditions

May obscure diagnosis or clinical course of patients with acute abdominal conditions.²⁴⁴

Seizure Risk

May aggravate preexisting seizure disorders.

Accumulation of toxic normeperidine metabolite can stimulate the CNS and precipitate seizures in patients without a preexisting seizure disorder.^{246 247 245 248}

Normeperidine Accumulation

Use with caution in patients at risk for accumulation of normeperidine (e.g., those with renal or hepatic impairment) and during prolonged therapy and/or with high dosages in other patients (e.g., those with sickle cell anemia or CNS disease, burn patients, cancer patients) at risk for neurotoxic effects of the metabolite.^{200 204 205 206 207 208 209 210 211 212 213 220 240 245}

Observe these patients closely for potential manifestations of CNS stimulation (e.g., seizures, agitation, irritability, nervousness, tremors, twitches, myoclonus) associated with accumulation of the metabolite.^{246 247 248 200 204 205 206 208 209 210 211 220 240}

Hypogonadism

Hypogonadism or androgen deficiency reported in patients receiving long-term opiate agonist or opiate partial agonist therapy;^{400 401 402 403 404} causality not established.⁴⁰⁰ Manifestations may include decreased libido, impotence, erectile dysfunction, amenorrhea, or infertility.⁴⁰⁰ Perform appropriate laboratory testing in patients with manifestations of hypogonadism.⁴⁰⁰

Specific Populations

Pregnancy

Category C.^PDH

Lactation

Distributed into milk.^{246 244} Discontinue nursing or the drug.²⁴⁴

Pediatric Use

Should not be given to infants <6 months of age;^PDH neonatal elimination is greatly reduced.²⁴⁶

Some experts discourage use in children of any age.²⁴⁵

Geriatric Use

Elimination is slower in geriatric patients than in younger patients.²⁴⁴

Geriatric patients, especially those with decreased renal and hepatic function, may be at greater risk for adverse CNS effects secondary to accumulation of the toxic metabolite normeperidine.^{242 243 244}

Use with caution in geriatric patients, taking into account the potential risks and benefits to the patient, and dosage adjustment should be considered.^{246 242 243 244}

Hepatic Impairment

Adjustment in the dose, frequency, and/or duration of therapy may be necessary because accumulation of the drug and/or its toxic metabolite, normeperidine, can occur.^{200 204 205 206 207 208 209 210 211 212 213} (See Hepatic Impairment under Dosage and Administration.)

Renal Impairment

Generally avoid in renal impairment, particularly repeated or high doses.^{246 247 245} (See Renal Impairment under Dosage and Administration.)

Common Adverse Effects

Adverse CNS effects include dizziness, visual disturbances, mental clouding or depression, sedation, coma, euphoria, dysphoria, weakness, faintness, agitation, restlessness, nervousness, seizures, and, rarely, delirium and insomnia.^e

Adverse GI effects of opiate agonists include nausea, vomiting, and constipation.^e

Opiate agonists may interfere with evaluation of CNS function, especially relative to consciousness levels, pupillary changes, and respiratory depression, thereby masking the patient’s clinical course.^e

May increase the risk of water intoxication in postoperative patients because of stimulation of the release of vasopressin.^e

Drug Interactions

Drugs Associated with Serotonin Syndrome

Risk of serotonin syndrome when used with other serotonergic drugs.^{255 400} May occur at usual dosages.⁴⁰⁰ Symptom onset generally occurs within several hours to a few days of concomitant use, but may occur later, particularly after dosage increases.⁴⁰⁰ (See Advice to Patients.)

Do not use meperidine concomitantly with other serotonergic drugs.²⁵⁵

If serotonin syndrome is suspected, discontinue meperidine, other opiate therapy, and/or any concurrently administered serotonergic agents.⁴⁰⁰

Specific Drugs

Meperidine Pharmacokinetics

Absorption

Bioavailability

Oral: Undergoes extensive first-pass metabolism in the liver, with approximately 50–60% of a dose reaching systemic circulation unchanged.^{246 246 207 212 213 214}

Oral: Bioavailability increases to approximately 80–90% in patients with hepatic impairment.^{212 213}

Less than half as effective when given orally as when given parenterally.^{b 247}

IM: Approximately 80–85% of a dose of the drug is absorbed within 6 hours after intragluteal injection.²¹⁷

Onset

Oral, peak analgesia: Within 1 hour and declines gradually over 2–4 hours.^b

Sub-Q, peak analgesia: In about 40–60.^b

IM, peak analgesia: In about 30–50 minutes.^b

Duration

Sub-Q or IM: Analgesia is maintained for 2–4 hours.^b

Plasma Concentrations

Oral, peak: About 1 hour.²⁴⁶

IM, peak: Within 5–15 minutes..²⁴⁶

Distribution

Extent

Crosses the placenta; may accumulate in fetus.^{246 207 218}

Distributes into breast milk.^{b 244}

Plasma Protein Binding

Approximately 60–80%;^{246 212} principally albumin and α₁-acid glycoprotein.^{246 212}

Elimination

Metabolism

Principally in the liver.^{b 246}

Normeperidine is the active metabolite and exhibits about half the analgesic potency of meperidine but twice the CNS stimulant (e.g., seizure-inducing) potency.^{200 201 202 203 204 205 206 207 208 209 210 211}

Various toxic effects secondary to CNS stimulation (e.g., seizures, agitation, irritability, nervousness, tremors, twitches, myoclonus) have been attributed to accumulation of normeperidine.^{200 201 204 205 206 209 210 211 240}

Elimination Route

Excreted in urine as metabolites and unchanged drug.^{b 246}

Acidifying the urine enhances excretion of the unchanged drug and normeperidine.^b

Half-life

Distribution phase half-life, meperidine: 2–11 minutes^{207 215 219}

Terminal elimination half-life, meperidine: 3–5 hours.^{246 200 204 205 207 213 214 215 216 217 219}

Terminal elimination half-life, normeperidine: Approximately 8–21 hours.^{246 200 204 205 207 208 210}

Special Populations

Elimination half-life in hepatic dysfunction, meperidine: Prolonged.²⁰⁷

Cirrhosis^{207 213 215} or active viral hepatitis:^{207 216} Averages about 7–11 hours.^b

Terminal elimination half-life in renal impairment, normeperidine: May be prolonged (e.g., 30–40 hours).^{200 204 205 207 208 210 211}

Renal or hepatic impairment: Accumulation of normeperidine may occur with repeated, high doses of the drug.^{200 204 205 206 207 212 213 240}

Stability

Storage

Protect from light and store at a temperature <40°C.^b

Oral

Tablets

Well-closed containers^b at 25°C (may be exposed to 15–30°C).²⁴⁴

Oral Solution

Tight containers^b at 25°C (may be exposed to 15–30°C).²⁴⁴

Avoid freezing.^b

Parenteral

Injection

15–25°C.^b

Avoid freezing.^b

Compatibility

Parenteral

Solution CompatibilityHID

Drug Compatibility

Actions

• Opiate agonists alter perception of and emotional response to pain.²⁴⁶

• Precise mechanism of action has not been fully elucidated; opiate agonists act at several CNS sites, involving several neurotransmitter systems to produce analgesia.²⁴⁶

• Pain perception is altered in the spinal cord and higher CNS levels (e.g., substantia gelatinosa, spinal trigeminal nucleus, periaqueductal gray, periventricular gray, medullary raphe nuclei, hypothalamus).²⁴⁶

• Opiate agonists do not alter the threshold or responsiveness of afferent nerve endings to noxious stimuli, nor peripheral nerve impulse conduction.²⁴⁶

• Opiate agonists act at specific receptor binding sites in the CNS and other tissues; opiate receptors are concentrated in the limbic system, thalamus, striatum, hypothalamus, midbrain, and spinal cord.²⁴⁶

• Agonist activity at the opiate μ- or κ-receptor can result in analgesia, miosis, and/or decreased body temperature.²⁴⁶

• Agonist activity at the μ-receptor can also result in suppression of opiate withdrawal (and antagonist activity can result in precipitation of withdrawal).²⁴⁶

• Respiratory depression may be mediated by μ-receptors, possibly μ₂-receptors (which may be distinct from μ₁-receptors involved in analgesia); κ- and δ-receptors may also be involved in respiratory depression.²⁴⁶

• Equianalgesic doses of meperidine hydrochloride and morphine sulfate produce the same degree of respiratory depression.^b

• Sedative and euphoric effects of equianalgesic doses of meperidine may be greater than those of morphine but reports are conflicting.^b

• Causes little or no constipation and has antitussive activity only in analgesic doses.^b

• Exhibits some anticholinergic properties.^e

• Systemic administration: May cause corneal anesthesia which can abolish the corneal reflex.^b

• Topical application: Produces considerable local anesthesia, but meperidine is not utilized for local anesthesia because it also produces local irritation.^b

• Overdosage may produce mydriasis rather than miosis.^e

• Toxic effects may be excitatory.^e

Advice to Patients

• Potential for drug to impair mental alertness or physical coordination; avoid driving or operating machinery until effects on individual are known.²⁴⁴

• Risk of respiratory depression following overdosage.⁷⁵⁰ Advise patients of the benefits of naloxone following opiate overdose and of their options for obtaining the drug.⁷⁵⁰

• Risk of potentially fatal additive effects (e.g., profound sedation, respiratory depression, coma) if used concomitantly with benzodiazepines or other CNS depressants, including alcohol and other opiates, either therapeutically or illicitly; avoid concomitant use unless such use is supervised by clinician.^{700 703} Importance of informing patients that meperidine should not be combined with alcohol.⁷⁰⁰

• Advise patients of risk of postural hypotension during ambulation.²⁴⁴

• Potential risk of serotonin syndrome with concurrent use of meperidine and other serotonergic agents.⁴⁰⁰ Importance of immediately contacting clinician if manifestations of serotonin syndrome (e.g., agitation, hallucinations, tachycardia, labile BP, fever, excessive sweating, shivering, shaking, muscle stiffness, twitching, loss of coordination, nausea, vomiting, diarrhea) develop.⁴⁰⁰

• Potential risk of adrenal insufficiency.⁴⁰⁰ Importance of contacting clinician if manifestations of adrenal insufficiency (e.g., nausea, vomiting, loss of appetite, fatigue, weakness, dizziness, hypotension) develop.⁴⁰⁰

• Possible risk (although causality not established) of hypogonadism or androgen deficiency with long-term opiate agonist or partial agonist use.⁴⁰⁰ Importance of informing clinician if decreased libido, impotence, erectile dysfunction, amenorrhea, or infertility occurs.⁴⁰⁰

• Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs as well as any concomitant illnesses.

• Importance of women informing clinicians if they are or plan to become pregnant or plan to breast-feed.

• Importance of informing patients of other important precautionary information. (See Cautions.)

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.

Meperidine hydrochloride preparations are subject to control under the Federal Controlled Substances Act of 1970 as schedule II (C-II) drugs.

* available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name

Frequently asked questions

• What is pethidine used for?

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