meperidine (Rx)

Brand and Other Names:Demerol, pethidine
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Dosing & Uses

AdultPediatricGeriatric

Dosage Forms & Strengths

syrup: Schedule II

  • 50mg/5mL

tablet: Schedule II

  • 50mg
  • 100mg

injectable solution: Schedule II

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

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 ≤48hr; doses should not exceed 600 mg/24hr; oral route is not recommended for treatment of acute or chronic pain

Pain: 50-150 mg PO/IM/SC q3-4hr PRN; adjust dose based degree of response

Preoperatively: 50-150 mg IM/SC q3-4hr PRN

Continuous infusion: 15-35 mg/hr

Obstetrical analgesia: 50-100 mg IM/SC; repeated q1-3hr PRN

Dosing Modifications

Renal impairment: Avoid use

Hepatic impairment: Consider lower initial dose intially; increased opioid effect possible in cirrhosis

Dosage Forms & Strengths

syrup: Schedule II

  • 50mg/5mL

tablet: Schedule II

  • 50mg
  • 100mg

injectable solution: Schedule II

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

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 ≤48hr; doses should not exceed 600 mg/24hr; oral route is not recommended for treatment of acute or chronic pain

1-1.8 mg/kg PO/IM/SC q3-4hr PRN; individual dose not to exceed 100 mg  

Preoperatively: 1.1-2.2 mg/kg IM/SC 30-90 minutes before initiation of anesthesia

Pain

50 mg PO q4hr or 25 mg IM q4hr; 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 central nervous system (CNS) effects

Reduce total daily dose in elderly patients

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Interactions

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            Adverse Effects

            Frequency Not Defined

            Agitation

            Angina

            Bradycardia

            Cardiac arrest

            Coma

            Constipation

            Dizziness

            Dry mouth

            Dysphoria

            Euphoria

            Faintness

            Hypotension

            Mental clouding or depression

            Myocardial infarction

            Nausea

            Nervousness

            Palpitation

            Physical and psychological dependence

            Pruritus, urticaria

            QT-interval prolongation

            Respiratory arrest

            Respiratory/circulatory depression

            Restlessness

            Sedation

            Seizures

            Severe cardiac arrhythmias

            Shock

            ST-segment elevation

            Sweating, flushing, warmness of face/neck/upper thorax

            Syncope

            Tachycardia

            Urinary retention

            Visual disturbances

            Vomiting

            Weakness

            Postmarketing Reports

            Life-threatening respiratory depression

            Neonatal opioid withdrawal syndrome

            Adrenal insufficiency

            Severe hypotension

            Abdominal pain

            Serotonin syndrome

            Anaphylaxis

            Androgen deficiency

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            Warnings

            Black Box Warnings

            Addiction, abuse, and misuse

            • Risk 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

            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

            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 that appropriate treatment will be available

            Interactions with Drugs Affecting Cytochrome P450 Isoenzymes

            • Concomitant use with cytochrome P450 3A4 inhibitors or discontinuation of inducers can result in fatal overdose of meperidine

            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 for use in patients for whom alternative treatment options are inadequate; limit dosages and durations to minimum required; follow patients for signs and symptoms of respiratory depression and sedation

            Concomitant Use of Meperidine with Monoamine Oxidase (MAO) Inhibitors

            • Concomitant use of with Monoamine oxidase (MAO) inhibitors can result in coma, severe respiratory depression, cyanosis and hypotension; use with MAO inhibitors is contraindicated

            Contraindications

            Hypersensitivity to drug or component of the formulation

            Acute or severe bronchial asthma in an unmonitored setting or in absence of resuscitative equipment

            Known or suspected gastrointestinal obstruction, including paralytic ileus

            Within 14 days of taking MAO inhibitors; if linezolid or IV methylene blue (MAOIs) must be administered, discontinue serotonergic drug immediately and monitor for CNS toxicity; may resume 24 hr after last linezolid or methylene blue dose, or after 2 weeks of monitoring, whichever comes first

            Cautions

            Therapy exposes users to the risks of addiction, abuse and misuse; because extended-release products deliver opioid over extended period of time, there is a greater risk for overdose and death due to the larger amount of tramadol present; addiction can occur at recommended dosages and if drug is misused or abused; assess each patient’s risk for opioid addiction, abuse or misuse prior to prescribing therapy; risks are increased in patients with personal or family history of substance abuse (including drug or alcohol abuse or addiction) or mental illness (e.g., major depression); patients at risk may be prescribed opioids but use in such patients necessitates intensive counseling about risks and proper use along with intensive monitoring for signs of addiction, abuse and misuse; strategies to reduce these risks include prescribing drug in smallest appropriate quantity and advising patient on proper disposal of unused drug

            Therapy may cause severe hypotension including orthostatic hypotension and syncope in ambulatory patients; there is increased risk in patients whose ability to maintain blood pressure has already been compromised by a reduced blood volume or concurrent administration of certain CNS depressant drugs (e.g., phenothiazines or general anesthetics); monitor patients for signs of hypotension after initiating or titrating dosage; in patients with circulatory shock, therapy may cause vasodilation that can further reduce cardiac output and blood pressure; avoid therapy in patients with circulatory shock

            In patients who may be susceptible to intracranial effects of CO2 retention (e.g., those with evidence of increased intracranial pressure or brain tumors), therapy may reduce respiratory drive, and resultant CO2 retention can further increase intracranial pressure; monitor such patients for signs of sedation and respiratory depression, particularly when initiating therapy; opioids may obscure clinical course in a patient with a head injury; avoid the use in patients with impaired consciousness or coma

            Contraindicated in patients with known or suspected gastrointestinal obstruction, including paralytic ileus; may cause spasm of sphincter of Oddi; opioids may cause increases in serum amylase; monitor patients with biliary tract disease, including acute pancreatitis, for worsening symptoms

            Use in patients with acute or severe bronchial asthma in unmonitored setting or in absence of resuscitative equipment is contraindicated; patients with significant chronic obstructive pulmonary disease or cor pulmonale, and those with a substantially decreased respiratory reserve, hypoxia, hypercapnia, or pre-existing respiratory depression are at increased risk of decreased respiratory drive including apnea, even at recommended dosages

            Caution in acute abdominal conditions (may obscure diagnosis or clinical course of patient), pseudomembranous colitis, toxin-mediated diarrhea

            Narrow therapeutic index in certain patient populations, particularly in combination with CNS-depressant drugs

            Cardiac arrhythmias, drug abuse or dependence, emotional lability, gallbladder disease, head injury, increased intracranial pressure, benign prostatic hyperplasia, hepatic or renal impairment, seizures with epilepsy, urethral stricture, urinary tract surgery

            Use with caution in following conditions: Sickle cell anemia; acute alcoholism; adrenocortical insufficiency (eg, Addison disease); CNS depression or coma; delirium tremens; debilitated patients; kyphoscoliosis associated with respiratory depression; myxedema or hypothyroidism; prostatic hypertrophy or urethral stricture; head trauma; billiary tract impairment; severe impairment of hepatic, pulmonary, or renal function; toxic psychosis

            Warn patients not to drive or operate dangerous machinery unless they are tolerant to therapy and know how they will react to medication

            While serious, life-threatening, or fatal respiratory depression can occur at any time during therapy, the risk is greatest during the initiation of therapy or following a dosage increase; monitor patients closely for respiratory depression, especially within the first 24-72 hours of initiating therapy with and following dosage increases; to reduce risk of respiratory depression, proper dosing and titration are essential; overestimating dosage when converting patients from another opioid product can result in a fatal overdose with the first dose

            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 that appropriate treatment will be available

            In patients with pheochromocytoma, meperidine has been reported to provoke hypertension

            If necessary, meperidine may be given intravenously, but injection should be given very slowly, preferably as diluted solution; rapid intravenous injection of narcotic analgesics, including meperidine, increases incidence of adverse reactions; severe respiratory depression, apnea, hypotension, peripheral circulatory collapse, and cardiac arrest have occurred; meperidine should not be administered intravenously unless a narcotic antagonist and facilities for assisted or controlled respiration are immediately available; when meperidine is given parenterally, especially intravenously, the patient should be lying down

            Chronic use of opioids may cause reduced fertility in females and males of reproductive potential; it is not known whether effects on fertility are reversible

            Avoid use of mixed agonist/antagonist (e.g., pentazocine, nalbuphine, and butorphanol) or partial agonist (e.g., buprenorphine) analgesics in patients who are receiving a full opioid agonist analgesic; mixed agonist/antagonist and partial agonist analgesics may reduce analgesic effect and/or may precipitate withdrawal symptoms; when discontinuing therapy, gradually taper dosage; do not abruptly discontinue therapy

            May cause less smooth muscle spasm and constipation than equipotent doses of morphine

            Cases of adrenal insufficiency reported with opioid use, more often following greater than one month of use; symptoms may include nausea, vomiting, anorexia, fatigue, weakness, dizziness, and low blood pressure; if adrenal insufficiency is diagnosed, treat with physiologic replacement doses of corticosteroids; wean patient off of opioid to allow adrenal function to recover and continue corticosteroid treatment until adrenal function recovers; other opioids may be tried as some cases reported use of a different opioid without recurrence of adrenal insufficiency

            Chronic high-dose therapy or administration to patients with renal impairment may result in accumulation of active metabolite normeperidine, leading to agitation and seizures

            Drug interaction overview

            • Concomitant use 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, particularly when an inhibitor is added after a stable dose of meperidine injection is achieved; similarly, discontinuation of a CYP3A4 inducer, such as rifampin, carbamazepine, and phenytoin, in meperidine-injection treated patients may increase meperidine plasma concentrations and prolong opioid adverse reactions; when using meperidine Injection with CYP3A4 inhibitors or discontinuing CYP3A4 inducers in meperidine-Injection treated patients, monitor patients closely at frequent intervals and consider dosage reduction of meperidine injection until stable drug effects are achieved
            • Concomitant use of meperidine 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 meperidine injection with CYP3A4 inducers or discontinuing CYP3A4 inhibitors, monitor patients closely at frequent intervals and consider increasing opioid dosage if needed to maintain adequate analgesia or if symptoms of opioid withdrawal occur
            • 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 for use in patients for whom alternative treatment options are inadequate; limit dosages and durations to minimum required; follow patients for signs and symptoms of respiratory depression and sedation
            • Cases of serotonin syndrome, a potentially life-threatening condition, reported, particularly during concomitant use with serotonergic drugs. Serotonergic drugs include selective serotonin reuptake inhibitors (SSRIs), serotonin and norepinephrine reuptake inhibitors (SNRIs), tricyclic antidepressants (TCAs), triptans, 5-HT3 receptor antagonists, drugs that affect the serotonergic neurotransmitter system (e.g., mirtazapine, trazodone, tramadol), and drugs that impair metabolism of serotonin (including MAO inhibitors, both those intended to treat psychiatric disorders and also others, such as linezolid and intravenous methylene blue); may occur within recommended dosage range; symptoms may include mental status changes (e.g., agitation, hallucinations, coma), autonomic instability (e.g., tachycardia, labile blood pressure, hyperthermia), neuromuscular aberrations (e.g., hyperreflexia, incoordination, rigidity), and/or gastrointestinal symptoms (e.g., nausea, vomiting, diarrhea); onset of symptoms generally occurs within several hours to a few days of concomitant use, but may occur later than that; discontinue therapy if serotonin syndrome is suspected
            • Meperidine is contraindicated in patients who have received MAO inhibitors within the last 14 days; therapeutic doses of meperidine have occasionally precipitated unpredictable, severe, and occasionally fatal reactions in patients who have received such agents within 14 days; intravenous hydrocortisone or prednisolone have been used to treat severe reactions, with the addition of intravenous chlorpromazine in those cases exhibiting hypertension and hyperpyrexia
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            Pregnancy & Lactation

            Pregnancy: Prolonged use of opioid analgesics during pregnancy for medical or nonmedical purposes can result in physical dependence in neonate and neonatal opioid withdrawal syndrome shortly after birth; the onset, duration, and severity of neonatal opioid withdrawal syndrome vary based on specific opioid used, duration of use, timing and amount of last maternal use, and rate of elimination of drug by newborn; observe newborns for symptoms of neonatal opioid withdrawal syndrome and manage accordingly

            Prolonged use of opioid analgesics during pregnancy for medical or nonmedical purposes can result in physical dependence in neonate and neonatal opioid withdrawal syndrome shortly after birth; the onset, duration, and severity of neonatal opioid withdrawal syndrome vary based on specific opioid used, duration of use, timing and amount of last maternal use, and rate of elimination of drug by newborn; observe newborns for symptoms of neonatal opioid withdrawal syndrome and manage accordingly

            Lactation: Meperidine appears in milk of nursing mothers receiving drug; developmental and health benefits of breastfeeding should be considered along with mother’s clinical need for therapy and any potential adverse effects on breastfed infant or from underlying maternal condition

            Pregnancy Categories

            A:Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.

            B:May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.

            C:Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.

            D:Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.

            X:Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.

            NA:Information not available.

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            Pharmacology

            Mechanism of Action

            Narcotic agonist-analgesic of opiate receptors; inhibits ascending pain pathways, thus altering response to pain; produces analgesia, respiratory depression, and sedation

            Absorption

            Bioavailability: 50-60%; hepatic impairment, 80-90%

            Onset: Rapid

            Duration: PO/SC, 2-4 hr

            Peak plasma time: SC, 40-60 min; IM, 30-50 min

            Distribution

            Protein bound: 65-75%

            Metabolism

            Metabolized in liver via hydrolysis, partial conjugation with glucuronic acid, N-demethylation

            Metabolites: Meperidinic acid, normeperidine (active)

            Elimination

            Half-life: 2.5-4 hr (adults); 7-11 hr (liver disease)

            Excretion: Urine (primarily)

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            Administration

            IV Incompatibilities

            Additive: Aminophylline, amobarbital, floxacillin, furosemide, heparin, morphine, phenobarbital, phenytoin, sodium bicarbonate(?)

            Syringe: Heparin, morphine, pentobarbital

            Y-site: Acyclovir(?), allopurinol, amphotericin B cholesteryl sulfate, cefepime, cefoperazone, doxorubicin, furosemide (may be compatible at lower concentrations), idarubicin, imipenem-cilastatin, minocycline, nafcillin(?)

            Not specified: Diazepam

            IV Compatibilities

            Solution: Most common solvents

            Additive: Cefazolin, dobutamine, metoclopramide, ondansetron, scopolamine, triflupromazine, verapamil

            Syringe: Atropine, butorphanol, chlorpromazine, cimetidine, dimenhydrinate, diphenhydramine, droperidol, fentanyl, glycopyrrolate, hydroxyzine, ketamine, metoclopramide, midazolam, ondansetron, papaveretum, pentazocine, pentazocine with perphenazine, perphenazine, prochlorperazine, promazine, promethazine, promethazine with atropine, ranitidine, scopolamine

            Y-site: Amifostine, amikacin, ampicillin, ampicillin-sulbactam, atenolol, aztreonam, bivalirudin, bumetanide, cefamandole, cefazolin, cefotaxime, cefotetan, cefoxitin, ceftazidime, ceftizoxime, ceftriaxone, cefuroxime, chloramphenicol, cisatracurium, cladribine, clindamycin, dexamethasone, dexmedetomidine, diltiazem, diphenhydramine, dobutamine, docetaxel, dopamine, doxycycline, droperidol, erythromycin, etoposide phosphate, famotidine, fenoldopam, filgrastim, fluconazole, fludarabine, gatifloxacin, gemcitabine, gentamicin, granisetron, heparin, 6% hetastarch in lactated electrolyte injection (Hextend), hydrocortisone, insulin, kanamycin, labetalol, lidocaine, linezolid, magnesium sulfate, melphalan, methyldopate, methylprednisolone, metoclopramide, metoprolol, metronidazole, ondansetron, oxacillin, oxytocin, paclitaxel, penicillin G, piperacillin, piperacillin-tazobactam, potassium chloride, propofol, propranolol, ranitidine, remifentanyl, sargramostim, teniposide, thiotepa, ticarcillin, ticarcillin-clavulanate, tobramycin, trimethoprim, vancomycin, verapamil, vinorelbine

            Not specified: Epinephrine

            IV/IM Administration

            IM: Inject into large muscle mass; when repeated injection is needed, IM is preferred to SC

            IV injection: Inject 10 mg/mL very slowly; opiate antagonist and facilities for administration of oxygen and control of respiration should be available during and immediately after administration

            Continuous IV infusion: 15-35 mg/hr

            Drug has been injected or infused epidurally

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            Formulary

            FormularyPatient Discounts

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            • View the formulary and any restrictions for each plan.
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            The above information is provided for general informational and educational purposes only. Individual plans may vary and formulary information changes. Contact the applicable plan provider for the most current information.

            Tier Description
            1 This drug is available at the lowest co-pay. Most commonly, these are generic drugs.
            2 This drug is available at a middle level co-pay. Most commonly, these are "preferred" (on formulary) brand drugs.
            3 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs.
            4 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
            5 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
            6 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
            NC NOT COVERED – Drugs that are not covered by the plan.
            Code Definition
            PA Prior Authorization
            Drugs that require prior authorization. This restriction requires that specific clinical criteria be met prior to the approval of the prescription.
            QL Quantity Limits
            Drugs that have quantity limits associated with each prescription. This restriction typically limits the quantity of the drug that will be covered.
            ST Step Therapy
            Drugs that have step therapy associated with each prescription. This restriction typically requires that certain criteria be met prior to approval for the prescription.
            OR Other Restrictions
            Drugs that have restrictions other than prior authorization, quantity limits, and step therapy associated with each prescription.
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