meperidine

me-PER-i-deen

Therapeutic Classification: opioid analgesics

Pharmacologic Classification: opioid agonists

BEERS REMS, High Alert

Moderate or severe pain (as monotherapy or in combination with nonopioid agents).
Anesthesia adjunct.
Analgesic during labor.
Preoperative sedation.

Unlabeled Use:

Rigors.

Binds to opiate receptors in the CNS. Alters the perception of and response to painful stimuli while producing generalized CNS depression.

Therapeutic effects:

Reduction in severity of pain.

Absorption: 50% from the GI tract; well absorbed from IM sites. Oral doses are about half as effective as parenteral doses. IV administration results in complete bioavailability.

Distribution: Widely distributed to tissues.

Metabolism/Excretion: Mostly metabolized by the liver; some converted to normeperidine, which may accumulate and cause seizures. 5% excreted unchanged by the kidneys.

Half-Life: Neonates: 12–39 hr; Infants 3–18 mo: 2.3 hr; Children 5–8 yr: 3 hr; Adults: 2.5–4 hr (↑ in impaired renal or hepatic function [7–11 hr]).

(analgesia)

ROUTE	ONSET	PEAK	DURATION
PO	15 min	60 min	2–4 hr
IM	10–15 min	30–50 min	2–4 hr
SUBQ	10–15 min	40–60 min	2–4 hr
IV	immediate	5–7 min	2–3 hr

Contraindicated in:

Hypersensitivity;
Hypersensitivity to bisulfites (some injectable products);
Recent (within 14 days) MAO inhibitor therapy;
Severe respiratory impairment;
OB: Labor and delivery;
Lactation: Lactation.

Use Cautiously in:

Personal or family history of substance use disorder or mental illness;
Head trauma;
↑intracranial pressure;
Severe renal or hepatic impairment;
Acute asthma attack, COPD, hypoxia, or hypercapnea;
Hypothyroidism;
Adrenal insufficiency;
Debilitated patients (dose ↓ suggested);
Undiagnosed abdominal pain or prostatic hyperplasia;
Extensive burns;
High-dose or prolonged therapy (>600 mg/day or >2 days; ↑ risk of CNS stimulation and seizures due to accumulation of normeperidine);
Sickle cell anemia (may require ↓ initial doses);
OB: Avoid chronic use during pregnancy as can result in neonatal opioid withdrawal syndrome;
Pedi: Syrup contains benzyl alcohol, which can cause gasping syndrome in neonates. Children have ↑ risk of seizures due to accumulation of normeperidine;
Geri: Appears on Beers list. ↑ risk of delirium in older adults. Avoid use in older adults.

CV: hypotension, bradycardia

Derm: flushing, sweating

EENT: blurred vision, diplopia, miosis

Endo: adrenal insufficiency

GI: constipation, nausea, vomiting

GU: urinary retention

Neuro: confusion, sedation, dysphoria, euphoria, floating feeling, hallucinations, headache, SEIZURES, unusual dreams

Resp: RESPIRATORY DEPRESSION (INCLUDING CENTRAL SLEEP APNEA OR SLEEP-RELATED HYPOXEMIA)

Misc: allodynia, HYPERSENSITIVITY REACTIONS (INCLUDING ANAPHYLAXIS), opioid-induced hyperalgesia, physical dependence, psychological dependence, tolerance

Drug-drug:

Do not use in patients receiving MAO inhibitors or procarbazine (may cause fatal reaction; contraindicated within 14 days of MAO inhibitor therapy).
Use with benzodiazepines or other CNS depressants, including other opioids, nonbenzodiazepine sedative/hypnotics, anxiolytics, general anesthetics, muscle relaxants, antipsychotics, and alcohol, may cause profound sedation, respiratory depression, coma, and death; reserve concurrent use for when alternative treatment options are inadequate.
Administration of mixed agonist/antagonist analgesics, including nalbuphine or butorphanol, or partial agonist analgesics, including buprenorphine, may ↓ meperidine's analgesic effects and/or precipitate opioid withdrawal in physically dependent patients.
Concurrent use of CYP3A4 inhibitors, including ritonavir, ketoconazole, itraconazole, fluconazole, clarithromycin, erythromycin, nefazodone, diltiazem, verapamil, nelfinavir, and fosamprenavir, ↑ levels and risk of opioid toxicity; careful monitoring during initiation, dose changes, or discontinuation of the inhibitor is recommended.
Concurrent use with CYP3A4 inducers, including barbiturates, carbamazepine, efavirenz, corticosteroids, modafinil, nevirapine, oxcarbazepine, phenobarbital, phenytoin, rifabutin, or rifampin, may ↓ levels and analgesia; if inducers are discontinued or dosage ↓, patients should be monitored for signs of opioid toxicity and necessary dose adjustments should be made.
Chlorpromazine and thioridazine may ↑ the risk of adverse reactions (concurrent use should be avoided).
May aggravate side effects of isoniazid.
Acyclovir may ↑ levels of meperidine and normeperidine.
Drugs that affect serotonergic neurotransmitter systems, including tricyclic antidepressants, SSRIs, SNRIs, MAO inhibitors, TCAs, tramadol, trazodone, mirtazapine, 5-HT3 receptor antagonists, linezolid, methylene blue, and triptans, ↑ risk of serotonin syndrome.

Drug-Natural Products:

Concomitant use of kava-kava, valerian, or chamomile can ↓ CNS depression.
St. John's wort may ↑ serious side effects; concurrent use is not recommended.

PO (Adults ): Analgesia: 50–150 mg every 3–4 hr; may ↑ as needed (not to exceed 600 mg/24 hr).
IM SC (Adults ): Analgesia: 50–150 mg every 3–4 hr; may ↑ as needed (not to exceed 600 mg/24 hr). Analgesia during labor: 50–100 mg when contractions become regular; may repeat every 1–3 hr. Preoperative sedation: 50–100 mg 30–90 min before anesthesia.
PO (Children ): Analgesia: 1.1–1.8 mg/kg every 3–4 hr (max = 100 mg/dose).
IM SC (Children ): Analgesia: 1.1–1.8 mg/kg every 3–4 hr (max = 100 mg/dose). Preoperative sedation: 1.1–2.2 mg/kg 30–90 min before anesthesia (not to exceed adult dose).
IV (Adults ): 15–35 mg/hr as a continuous infusion; PCA: 10 mg initially; with a range of 1–5 mg/incremental dose, recommended lockout interval is 6–10 min (minimum 5 min).
IV (Children ): Continuous infusion: 0.5–1 mg/kg loading dose followed by 0.3 mg/kg/hr, titrate to effect up to 0.5–0.7 mg/kg/hr.

(Generic available)

Tablets: 50 mg; 100 mg
Oral solutionbanana flavor: 50 mg/5 mL
Solution for injection : 25 mg/mL; 50 mg/mL; 75 mg/mL; 100 mg/mL

Assess type, location, and intensity of pain prior to and 1 hr following PO, SUBQ, and IM doses and 5 min (peak) following IV administration. When titrating opioid doses, ↑ of 25–50% should be administered until there is either a 50% ↓ in the patient’s pain rating on a numerical or visual analogue scale or the patient reports satisfactory pain relief. A repeat dose can be safely administered at the time of the peak if previous dose is ineffective and side effects are minimal.
An equianalgesic chart (see Equianalgesic Dosing Guidelines) should be used when changing routes or when changing from one opioid to another.
Assess BP, HR, and respiratory rate before and periodically during administration. If respiratory rate <10/min, assess level of sedation. Dose may need to be ↓ by 25–50%. Initial drowsiness will ↓ with continued use. Monitor for respiratory depression, especially during initiation or following dose ↑; serious, life-threatening, or fatal respiratory depression may occur. May cause sleep-related breathing disorders (central sleep apnea, sleep-related hypoxemia).
Assess bowel function routinely. Institute prevention of constipation with ↑ intake of fluids and bulk and laxatives to minimize constipating effects. Administer stimulant laxatives routinely if opioid use exceeds 2–3 days, unless contraindicated. Consider drugs for opioid-induced constipation.
Prolonged use may lead to physical and psychological dependence and tolerance, which should not prevent patient from receiving adequate analgesia. Patients who receive meperidine for pain rarely develop psychological dependence. Progressively higher doses may be required to relieve pain with long-term therapy.
Monitor patients on chronic or high-dose therapy for CNS stimulation (restlessness, irritability, seizures) due to accumulation of normeperidine metabolite. Risk of toxicity ↑ with doses >600 mg/24 hr, chronic administration (>2 days), and renal impairment.
Assess risk for opioid addiction, abuse, or misuse prior to administration.
Geri: Meperidine has been reported to cause delirium in the elderly; older adults are at ↑ risk for normeperidine toxicity. Monitor frequently.
Pedi: Assess pediatric patient frequently; neonates, infants, and children are more sensitive to the effects of opioid analgesics and may experience respiratory complications, excitability, and restlessness more frequently.
Assess for opioid-induced hyperalgesia, which can appear as ↑ levels of pain upon increasing the dose of the opioid, ↓ levels of pain on decreasing the dose of the opioid, or pain from ordinarily nonpainful stimuli (allodynia). This condition is different from tolerance. If a patient is suspected to be experiencing opioid-induced hyperalgesia, consider ↓ the dose of the current opioid or switching to a different opioid analgesic.

Lab Test Considerations:

May ↑ plasma amylase and lipase concentrations.

Toxicity and Overdose:

If an opioid antagonist is required to reverse respiratory depression or coma, naloxone is the antidote to improve respiratory function without reversing analgesia. Dilute the 0.4-mg ampule of naloxone in 10 mL of 0.9% NaCl and administer 0.5 mL (0.02 mg) by IV push every 2 min. For children and patients weighing <40 kg, dilute 0.1 mg of naloxone in 10 mL of 0.9% NaCl for a concentration of 10 mcg/mL and administer 0.5 mcg/kg every 2 min. Titrate dose to avoid withdrawal, seizures, and severe pain. In patients receiving meperidine chronically, naloxone may precipitate seizures by eliminating the CNS depressant effects of meperidine, allowing the convulsant activity of normeperidine to predominate. Monitor patient closely.

High Alert: Accidental overdose of opioid analgesics has resulted in fatalities. Before administering, clarify all ambiguous orders; have second practitioner independently check original order, dose calculations, and infusion pump settings. Medication errors with opioid analgesics are common in the pediatric population and include misinterpretation or miscalculation of doses and use of inappropriate measuring devices.
Explain therapeutic value of medication prior to administration to enhance the analgesic effect.
- Regularly administered doses may be more effective than as needed administration. Analgesic is more effective if given before pain becomes severe.
- Coadministration with nonopioid analgesics may have additive analgesic effects and permit lower doses.
- Oral dose is <50% as effective as parenteral dose. When changing to oral administration, dose may need to be ↑ (see Equianalgesic Dosing Guidelines).
- Medication should be discontinued gradually after long-term use to prevent withdrawal symptoms. For patients who are physically opioid dependent, initiate the taper by a small enough increment (no greater than 25–50% of total daily dose) to avoid withdrawal symptoms, and proceed with dose-lowering at an interval of every 2–4 days. Patients who have been taking opioids for briefer periods of time may tolerate a more rapid taper. Monitor frequently to manage pain and withdrawal symptoms (restlessness; lacrimation; rhinorrhea; yawning; perspiration; chills; myalgia; mydriasis; irritability; anxiety; backache; joint pain; weakness; abdominal cramps; insomnia; nausea; anorexia; vomiting; diarrhea; or ↑ BP, respiratory rate, or HR). If withdrawal symptoms occur, pause the taper for a period of time or ↑ dose of opioid analgesic to previous dose, and then proceed with a slower taper. Also, monitor patients for changes in mood, emergence of suicidal thoughts, or use of other substances. A multimodal approach to pain management may optimize the treatment of chronic pain and assist with the successful tapering of the opioid analgesic.
- May be administered via PCA pump.
PO: Doses may be administered with food or milk to minimize GI irritation. Dilute syrup in half-full glass of water.
IM: Patient should be lying down when administered; IM is the preferred route for repeated doses. SUBQ administration may cause tissue irritation.
REMS: FDA strongly encourages health care professionals to complete a REMS-compliant education program that includes all the elements of the FDA Education Blueprint for Health Care Providers Involved in the Management or Support of Patients with Pain, available at www.fda.gov/OpioidAnalgesicREMSBlueprint. Information on programs can be found at 1-800-503-0784 or www.opioidanalgesicrems.com.
Discuss availability of naloxone for emergency treatment of opioid overdose with the patient and caregiver and assess the potential need for access to naloxone, both when initiating and renewing therapy, especially if patient has household members (including children) or other close contacts at risk for accidental exposure or overdose. Consider prescribing naloxone, based on the patient’s risk factors for overdose, such as concomitant use of CNS depressants, a history of opioid use disorder, or prior opioid overdose. However, the presence of risk factors for overdose should not prevent the proper management of pain in any patient.

IV Administration:

IV Push: Administer undiluted.
Rate: High Alert: Administer slowly over at least 5 min. Rapid administration may lead to ↑ respiratory depression, hypotension, and circulatory collapse.
Intermittent Infusion: Diluent: Dilute with D5W, D10W, dextrose/saline combinations, dextrose/Ringer’s or LR injection combinations, 0.45% NaCl, 0.9% NaCl, or LR. Administer via infusion pump.Concentration: 1 mg/mL.
Y-Site Compatibility:
- acetaminophen
- alemtuzumab
- amifostine
- amikacin
- aminocaproic acid
- aminophylline
- amiodarone
- amphotericin B lipid complex
- anidulafungin
- argatroban
- arsenic trioxide
- ascorbic acid
- atracurium
- atropine
- azithromycin
- aztreonam
- benztropine
- bivalirudin
- bleomycin
- bumetanide
- buprenorphine
- busulfan
- butorphanol
- calcium chloride
- calcium gluconate
- cangrelor
- carboplatin
- carmustine
- caspofungin
- cefazolin
- cefotaxime
- cefoxitin
- ceftaroline
- ceftazidime
- ceftolozane/tazobactam
- ceftriaxone
- cefuroxime
- chlorpromazine
- ciprofloxacin
- cisatracurium
- cisplatin
- cladribine
- clindamycin
- cyanocobalamin
- cyclophosphamide
- cyclosporine
- cytarabine
- dacarbazine
- dactinomycin
- daptomycin
- daunorubicin
- dexmedetomidine
- dexrazoxane
- digoxin
- diltiazem
- diphenhydramine
- dobutamine
- docetaxel
- dopamine
- doxorubicin hydrochloride
- doxycycline
- droperidol
- enalaprilat
- ephedrine
- epinephrine
- epirubicin
- epoetin alfa
- eptifibatide
- ertapenem
- erythromycin
- esmolol
- etoposide
- etoposide phosphate
- famotidine
- fentanyl
- filgrastim
- fluconazole
- fludarabine
- fluorouracil
- folic acid
- foscarnet
- fosphenytoin
- gemcitabine
- gentamicin
- glycopyrrolate
- granisetron
- hetastarch
- hydrocortisone
- ifosfamide
- insulin, regular
- irinotecan
- isavuconazonium
- isoproterenol
- ketamine
- ketorolac
- labetalol
- LR
- leucovorin calcium
- levofloxacin
- lidocaine
- linezolid
- mannitol
- melphalan
- meropenem/vaborbactam
- mesna
- methotrexate
- metoclopramide
- metoprolol
- metronidazole
- midazolam
- milrinone
- mitomycin
- mitoxantrone
- morphine
- multivitamins
- mycophenolate
- naloxone
- nicardipine
- nitroglycerin
- nitroprusside
- norepinephrine
- octreotide
- ondansetron
- oxaliplatin
- oxytocin
- paclitaxel
- palonosetron
- pamidronate
- papaverine
- pemetrexed
- penicillin G
- pentamidine
- phentolamine
- phenylephrine
- phytonadione
- piperacillin/tazobactam
- plazomicin
- potassium acetate
- potassium chloride
- procainamide
- prochlorperazine
- promethazine
- propofol
- propranolol
- protamine
- pyridoxine
- remifentanil
- rituximab
- rocuronium
- sargramostim
- sodium acetate
- succinylcholine
- sufentanil
- tacrolimus
- tedizolid
- theophylline
- thiamine
- thiotepa
- tigecycline
- tirofiban
- tobramycin
- topotecan
- trastuzumab
- vancomycin
- vasopressin
- vecuronium
- verapamil
- vinblastine
- vincristine
- vinorelbine
- voriconazole
- zidovudine
- zoledronic acid
Y-Site Incompatibility:
- allopurinol
- amphotericin B deoxycholate
- amphotericin B liposomal
- azathioprine
- cefepime
- dantrolene
- diazepam
- ganciclovir
- gemtuzumab ozogamicin
- idarubicin
- indomethacin
- lorazepam
- micafungin
- minocycline
- nafcillin
- pantoprazole
- pentobarbital
- phenobarbital
- phenytoin
- sodium bicarbonate
- thiopental

Explain purpose and side effects of meperidine to patient. Advise patient to not share medication with others, even if they have similar symptoms; may be harmful. Advise patient to read Patient Informationbefore starting and with each Rx refill in case of changes.
REMS: Instruct patient to take meperidine as directed. If dose is less effective after a few wk, do not dose without consulting health care professional. Discuss safe use, risks, and proper storage and disposal of opioid analgesics with patients and caregivers with each Rx. The Patient Counseling Guide is available at www.fda.gov/OpioidAnalgesicREMSPCG.Pedi: Teach parents or caregivers how to accurately measure liquid medication and to use only the measuring device dispensed with the medication.
Advise patient that meperidine is a drug with known abuse potential. Protect it from theft, and never give to anyone other than the individual for whom it was prescribed. Store out of sight and reach of children and in a location not accessible by others.
May cause drowsiness or dizziness. Advise patient to call for assistance when ambulating and to avoid driving or other activities that require alertness until response to the medication is known.
Educate patients and caregivers on how to recognize respiratory depression and emphasize the importance of calling 911 or getting emergency medical help right away in the event of a known or suspected overdose. Inform patients and caregivers about various ways to obtain naloxone as permitted by individual state naloxone-dispensing and prescribing requirements or guidelines (Rx, direct from pharmacist, or state programs). OTC naloxone nasal spray is available at pharmacies nationwide for overdose or accidental ingestion.
Advise patient to change positions slowly to minimize orthostatic hypotension.
Instruct patient to avoid concurrent use of alcohol or other CNS depressants, may lead to overdose.
Instruct patient to notify health care professional of all Rx or OTC medications, vitamins, or herbal products being taken and consult health care professional before taking any new medications.
Advise ambulatory patients that nausea and vomiting may be ↓ by lying down.
Encourage patient to turn, cough, and breathe deeply every 2 hr to prevent atelectasis.
Rep: May cause fetal harm. Advise females with reproductive potential to notify health care professional if pregnancy is planned or suspected and to avoid breastfeeding. Inform patient of potential for neonatal opioid withdrawal syndrome with prolonged use during pregnancy. Monitor neonate for signs and symptoms of withdrawal symptoms (irritability, hyperactivity and abnormal sleep pattern, high-pitched cry, tremor, vomiting, diarrhea, failure to gain weight); usually occur the first days after birth. Monitor infants exposed to meperidine through breast milk for excess sedation and respiratory depression. Chronic use may ↓ fertility in females and males.

Decrease in severity of pain without a significant alteration in level of consciousness or respiratory status.
Resolution of rigors.

Demerol

Schedule II (C-II)

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