Meperidine, also known as pethidine, is in the class of phenylpiperidine as a hydrochloride salt synthetic form of the opioid, which is a white crystalline with a melting point of 186 degrees C. This medication has calcium sulfate, dibasic calcium phosphate, starch, stearic acid, and talc as inactive ingredients. Clinicians use meperidine is used for the treatment of moderate to severe pain. It has intramuscular, subcutaneous, intravenous injection, syrup, and tablet forms. In the 20th century, it was the drug of choice amongst the opioids in the management of acute pain by most of the physicians and the management of some patients with chronic pain. Meperidine is also being used as an adjunct to preoperative medications to reduce shivering.[1][2][3]

Meperidine appeared to be safer with a lower risk of addiction when compared to other opioids and because of the anticholinergic effects associated with less biliary spasm or renal colic. However, it appears that risks of addiction, biliary spasm, and renal colic are equal to other opioids. Additionally, due to its toxic metabolite is known as normeperidine, which has serotonergic properties, it correlates with an increased risk of serotonin syndrome and seizure. These issues have led to the removal of meperidine from the World Health Organization’s list of essential medicines, the list of most effective and safe medicines in the health system in 2003.[4][5][6]

Meperidine has the same mechanism of action as morphine, which is acting as an agonist to the mu-opioid receptor. The anti-shivering effect may involve the stimulation of k-opioid receptors.[7]

Meperidine also has some local anesthetic effects because of interactions with sodium ion channels. Also, meperidine has stimulant effects by inhibition of the dopamine transporter (DAT) and norepinephrine transporter (NET).

Oral form: (not recommended for acute pain control)

• Tablet form: 50 mg to 100 mg
• Syrup form: 50 mg/5 ml

Injectable solution form: 25 mg/ml, 50 mg/ml, 75 mg/ml, 100 mg/ml 

Intravenous (IV) injection: inject the dose of 10 mg/ml slowly. The injection should be a consideration only when an opiate antagonist and the administration of oxygen and respiratory monitoring facilities are available.

For continuous IV infusion: 15 to 35 mg/hr

Intramuscular: Injection should be into large muscle mass, and it is preferable to subcutaneous injection.

Using Meperidine for pain control should be considered if no other options are available, in which case duration of medication use should be limited to less than 48 hours, and the total dosage administered should not exceed 600 mg in 24 hours.

For pain management:

• In adults: 50 mg to 150 mg orally, IM, subcutaneously (SC) every 3 to 4 hours as needed.
• In pediatrics: 1 mg/kg to1.8 mg/kg orally, IM, subcutaneously (SC) every 3 to 4 hours as needed. (each dose should not exceed 100mg)

Continuous infusion: 15 mg to 35 mg per hour

Obstetrical pain management: 50 mg to 100 mg IM/SC, every 1 to 3 hours as needed

Preoperatively:

• In adults: 50 mg to 150 mg IM/SC every 3 to 4 hours as needed.
• In pediatrics: 1.1 mg/kg to 2.2 mg/kg SC/IM 30 to 90 minutes before anesthesia

Serious Reactions

Shock, seizure, syncope, hallucination (especially among the geriatric population), potential opioid dependency, withdrawal symptoms if discontinued without tapering down, opioid-induced androgen deficiency (chronic use), bradycardia, cardiac arrest, severe hypotension, apnea, respiratory failure.

Common Reactions

Tachycardia, urinary retention, tremor, involuntary movements, xerostomia, constipation, dysphoria, weakness, palpitation, headache, rash, pruritus, urticaria, visual disturbances, involuntary movements, confusion, dysphoria, delirium (especially in geriatric population), nausea, vomiting, lightheadedness, diaphoresis, agitation, orthostatic hypotension, weakness, bradycardia, flushing.

Meperidine is contraindicated in patients that are actively receiving or have been exposed during the past 14 days to monoamine oxidase inhibitors (MAOI) because of unpredictable severe, and occasionally fatal reactions such as coma, severe respiratory depression, hypotension, cyanosis, and acute narcotic overdose. Also, convulsion, hyper-excitability, tachycardia, hyperpyrexia, and hypertension have been reported. Intravenous hydrocortisone or prednisone have been used to treat severe reactions. In those cases exhibiting hypertension and hyperpyrexia, intravenous chlorpromazine is added.

Meperidine has respiratory depressant effects and capacity to elevate cerebrospinal fluid pressure especially in patients with head injury or other intracranial lesions. In this group of patients using Meperidine should be with extreme caution. Like other narcotics, using meperidine in patients having an acute asthma attack and chronic obstructive pulmonary disease should be with caution, and these patients should be monitored for any signs of increased airway resistance or apnea.

Meperidine has several Black Box warnings:

1. The potential risk of opioid addiction which can cause overdose and death. Physicians should evaluate their patients continuously for developing these conditions.
2. Life-threatening respiratory failure may occur, therefore monitoring for respiratory depression during the initiation and following dose increase should be considered.
3. Parallel use with cytochrome P450 3A4 inhibitors or discontinuation of P450 inducers causes the increase of the meperidine concentration that can result in a fatal overdose.
4. Concomitant use of meperidine and monoamine oxidase inhibitors (MAOI) can cause coma, severe respiratory failure, cyanosis, and hypotension.
5. Chronic use of meperidine during pregnancy can cause neonatal opioid withdrawal syndrome, which needs to be diagnosed and managed by guidelines of neonatology, which otherwise can be fatal.
6. Concomitant use of another central nervous system (CNS) depressant like benzodiazepines or alcohol with meperidine may cause profound sedation, respiratory depression, coma, and death.
7. There is a risk of medication errors, which can be prevented by ensuring accuracy when prescribing, dispensing, and administrating. This is especially important as confusing mg and ml when dosing can result in an accidental fatal overdose.