meperidine hydrochloride (pethidine hydrochloride)
Demerol

Available forms
Available by prescription only
Injection: 10 mg/ml, 25 mg/ml, 50 mg/ml, 75 mg/ml, 100 mg/ml
Liquid: 50 mg/5 ml
Tablets: 50 mg, 100 mg

Indications and dosages
 Moderate to severe pain. Adults: 50 to 150 mg P.O., I.M., or S.C. q 3 to 4 hours; or continuous infusion of 15 to 35 mg/hour.
Children: 1.1 to 1.8 mg/kg P.O., I.M., or S.C. q 3 to 4 hours or 175 mg/m² daily in six divided doses. Maximum single dose for children shouldn’t exceed 100 mg.
 Preoperatively. Adults: 50 to 100 mg I.M. or S.C. 30 to 90 minutes before surgery.
Children: 1 to 2 mg/kg I.M. or S.C. 30 to 90 minutes before surgery. Don’t exceed adult dose.
 Support of anesthesia. Adults: Repeated slow I.V. injections of fractional doses (10 mg/ml) or continuous I.V. infusion of 1 mg/ml. Titrate dose to meet patient’s needs.
 Obstetric analgesia. Adults: 50 to 100 mg I.M. or S.C. when pain becomes regular; may repeat at 1- to 3-hour intervals.

Pharmacodynamics
Analgesic action: Meperidine is a narcotic agonist with actions and potency similar to those of morphine, with principal actions at the opiate receptors. It’s recommended for the relief of moderate to severe pain.

Pharmacokinetics
Absorption: Given orally, drug is only half as effective as when given parenterally.
Distribution: Distributed widely throughout the body and is 60% to 80% bound to plasma proteins.
Metabolism: Metabolized primarily by hydrolysis in the liver to an active metabolite, normeperidine.
Excretion: About 30% is excreted in urine as the N-demethylated derivative; about 5% is excreted unchanged. Excretion is enhanced by acidifying the urine. Half-life of parent compound is 3 to 5 hours and the half-life of metabolite is 8 to 21 hours.

Contraindications and precautions
Contraindicated in patients hypersensitive to drug and in those who have received MAO inhibitors within the past 14 days.
  Use cautiously in geriatric or debilitated patients and in those with increased intracranial pressure, head injury, asthma, other respiratory conditions, supraventricular tachycardia, seizures, acute abdominal conditions, renal or hepatic disease, hypothyroidism, Addison’s disease, urethral stricture, or prostatic hyperplasia.

Interactions
Drug-drug. Anticholinergics: May cause paralytic ileus. Monitor patient closely.
Cimetidine: May increase respiratory and CNS depression, causing confusion, disorientation, apnea, or seizures. Reduce meperidine dosage.
CNS depressants, such as antihistamines, barbiturates, benzodiazepines, general anesthetics, muscle relaxants, narcotic analgesics, phenothiazines, sedative-hypnotics, and tricyclic antidepressants: Potentiate respiratory and CNS depression, sedation, and hypotensive effects of drugs. Use together cautiously.
General anesthetics: May cause severe CV depression. Use together cautiously.
Isoniazid: May potentiate adverse effects of isoniazid. Avoid use together.
MAO inhibitors: May precipitate unpredictable and occasionally fatal reactions, even in patients who may receive MAO inhibitors within 14 days of receiving meperidine. Avoid use together.
Narcotic antagonist: Patients who become physically dependent on drug may experience acute withdrawal syndrome if given a narcotic antagonist. Avoid use together.
Drug-herb. Parsley: May promote or produce serotonin syndrome. Discourage use together.
Drug-lifestyle. Alcohol use: Potentiates respiratory and CNS depression, sedation, and hypotensive effects of drug. Discourage alcohol use.

Adverse reactions
CNS: sedation, somnolence, clouded sensorium, euphoria, dizziness, paradoxical excitement, tremor, seizures (with large doses), headache, hallucinations, syncope, light-headedness.
CV: hypotension, bradycardia, tachycardia, cardiac arrest, shock.
GI: constipation, ileus, dry mouth, nausea, vomiting, biliary tract spasms.
GU: urine retention.
Respiratory: respiratory depression, respiratory arrest.
Skin: pruritus, urticaria, diaphoresis, pain (at injection site); local tissue irritation, induration (after S.C. injection).
Other: physical dependence, muscle twitching, phlebitis (after I.V. delivery).

Effects on lab test results
• May increase amylase and lipase levels.

Overdose and treatment
The most common signs and symptoms of meperidine overdose are CNS depression, respiratory depression, skeletal muscle flaccidity, cold and clammy skin, mydriasis, bradycardia, and hypotension. Other acute toxic effects include hypothermia, shock, apnea, cardiopulmonary arrest, circulatory collapse, pulmonary edema, and seizures.
 To treat acute overdose, first establish adequate respiratory exchange via a patent airway and ventilation as needed; give a narcotic antagonist (naloxone) to reverse respiratory depression. (Because the duration of action of meperidine is longer than that of naloxone, repeated dosing is needed.) Don’t give naloxone unless the patient has clinically significant respiratory or CV depression. Monitor vital signs.
 If within 2 hours of ingestion of an oral overdose, empty patient’s stomach immediately by inducing emesis (ipecac syrup) or using gastric lavage. Use cautiously to avoid risk of aspiration. Give activated charcoal via nasogastric tube for further removal of meperidine, and acidify urine to help remove drug.
 Provide symptomatic and supportive treatment (continued respiratory support, correction of fluid or electrolyte imbalance). Monitor laboratory values, vital signs, and neurologic status closely.

Special considerations
• Drug may be given to patients allergic to morphine.
• Commercial preparations contain sodium metabisulfite, which may cause allergic reactions in susceptible individuals.
• Question patient carefully regarding possible use of MAO inhibitors within the past 14 days.
• Use concentration of 10 mg/ml only with compatible infusion device; doesn’t require further dilution.
• Because drug toxicity commonly appears after several days of treatment, this drug isn’t recommended for treatment of chronic pain.
• Meperidine may be given slowly through an I.V. line, preferably as a diluted solution. S.C. injection is very painful. During I.V. administration, tachycardia may occur, possibly as a result of atropine-like effects of the drug.
• Oral dose is less than half as effective as parenteral dose. Give I.M. if possible. When changing from parenteral to oral route, increase dosage.
• Syrup has local anesthetic effect. Give with water.
• Alternating meperidine with a peripherally active nonopioid analgesic, such as aspirin, acetaminophen, or an NSAID, may improve pain control while allowing lower opioid dosages.
• Injectable meperidine is compatible with saline and D₅W solutions and their combinations, and with lactated Ringer’s and sodium lactate solutions.
• Drug increases plasma amylase or lipase levels through increased biliary tract pressure; levels may be unreliable for 24 hours after meperidine administration.
• Meperidine and its active metabolite normeperidine accumulate. Monitor patient for neurotoxic effects, especially in burn patients and those with poor renal function, sickle cell anemia, or cancer.
Breast-feeding patients
• Drug appears in breast milk. Use cautiously in breast-feeding women.
Pediatric patients
• Don’t give drug to infants younger than age 6 months.
Geriatric patients
• Lower doses are usually indicated for geriatric patients because they may be more sensitive to therapeutic and adverse effects of drug.

Patient education
• Caution patient about CNS drug effects. Warn patient to avoid driving and other potentially hazardous activities that require mental alertness until CNS effects of drug are known.
• Advise patient to avoid alcohol.
• Tell patient to take drug before pain becomes intense.

Reactions may be common, uncommon, life-threatening, or COMMON AND LIFE THREATENING.
◆ Canada only
◇ Unlabeled clinical use