Meperidine Hydrochloride — Veterinary Vademecum Drug Reference

Dosage & Administration Guidelines

Species	Route	Dose	Frequency	Duration & Clinical Notes
Dog	IM, SC	2-5 mg/kg	q2-4h	Duration: As needed for acute pain (usually <24-48 hours) Notes: Use lowest effective dose. Not recommended for prolonged use due to risk of normeperidine accumulation.
Cat	IM, SC	2-4 mg/kg	q2-4h	Duration: As needed for acute pain (usually <24-48 hours) Notes: Cats may exhibit excitement at higher doses. Use with caution.
Horse	IV, IM	0.5-1 mg/kg	q4-6h	Duration: As needed for acute pain (e.g., colic) Notes: IV administration should be slow. May cause transient excitement.
Cattle	IM, SC	2-4 mg/kg	q4-6h	Duration: As needed for acute pain Notes: Extra-label use; observe withdrawal times.
Small Ruminants (Sheep, Goats)	IM, SC	2-4 mg/kg	q4-6h	Duration: As needed for acute pain Notes: Extra-label use; observe withdrawal times.
Rabbit	IM, SC	5-10 mg/kg	q2-4h	Duration: As needed for acute pain Notes: Limited data; use with caution.
Birds (e.g., Psittacines)	IM	1-2 mg/kg	q2-4h	Duration: As needed for acute pain Notes: Limited data; use with caution.

Clinical Indications & Species Uses

General Indications

Short-term management of moderate to severe pain
Preanesthetic medication to reduce anesthetic requirements

Dog (Canine)

Analgesia for acute pain (e.g., postoperative, trauma)
Preanesthetic medication
Relief of pain associated with gastrointestinal or biliary colic

Cat (Feline)

Analgesia for acute pain (e.g., postoperative, trauma)
Preanesthetic medication

Horse (Equine)

Analgesia for acute pain (e.g., colic)
Preanesthetic medication

Cattle (Bovine)

Analgesia for acute pain (e.g., surgery, trauma)
Preanesthetic medication

Small Ruminants (Sheep / Goat)

Analgesia for acute pain (e.g., surgery, trauma)
Preanesthetic medication

Rabbit & Small Mammals

Analgesia for acute pain (e.g., surgery, trauma)

Avian & Poultry

Analgesia for acute pain (e.g., surgery, trauma)

Exotic & Other Species

Analgesia for acute pain (e.g., surgery, trauma) in small mammals and reptiles

Pharmacology & Mechanism of Action

Drug Class: Opioid Analgesic | Pharmacological Group: Phenylpiperidine Opioid

Mechanism of Action: Meperidine is a synthetic opioid agonist that primarily acts on mu-opioid receptors in the central nervous system (CNS) and peripheral tissues. It produces analgesia by mimicking endogenous endorphins and enkephalins, leading to activation of G-protein coupled receptors, inhibition of adenylate cyclase, decreased cAMP production, and modulation of ion channels (increased potassium efflux, decreased calcium influx). This results in reduced neurotransmitter release (e.g., substance P, glutamate) and hyperpolarization of neurons, thereby inhibiting pain transmission. Additionally, meperidine has local anesthetic-like effects and weak anticholinergic activity. Its metabolite, normeperidine, has CNS stimulant properties and can cause seizures at high concentrations.

Pharmacodynamics: Meperidine produces dose-dependent analgesia, sedation, euphoria, and respiratory depression. It has a faster onset but shorter duration of action compared to morphine. It also causes histamine release, leading to vasodilation, hypotension, and bronchoconstriction. Unlike morphine, meperidine has minimal effects on biliary smooth muscle and may cause less constipation. It can cause mydriasis in dogs and cats (due to CNS stimulation) and has antitussive effects. In veterinary patients, it is used primarily for short-term pain management, especially in gastrointestinal or biliary colic due to its spasmolytic effects on smooth muscle.

⚡ Pharmacokinetics Summary

Absorption: Meperidine is well absorbed after oral, subcutaneous, and intramuscular administration. Oral bioavailability is approximately 50-60% due to first-pass metabolism. Onset of action after oral administration is 15-30 minutes, and after parenteral administration is 5-10 minutes. Peak plasma concentrations occur within 1-2 hours after oral dosing and 30-60 minutes after IM/SC injection.

Distribution: Meperidine is widely distributed throughout the body, including the CNS. It crosses the blood-brain barrier and placenta. It has a volume of distribution of approximately 3-4 L/kg in dogs. It is approximately 60-70% bound to plasma proteins, primarily albumin and alpha-1-acid glycoprotein.

Metabolism: Meperidine is extensively metabolized in the liver via hydrolysis and N-demethylation. The primary metabolic pathway is N-demethylation to normeperidine, which is pharmacologically active and has a longer half-life. Normeperidine can accumulate with repeated dosing, leading to CNS excitation and seizures. Other metabolites include meperidinic acid and normeperidinic acid, which are conjugated and excreted renally.

Excretion: Meperidine and its metabolites are primarily excreted in the urine. Approximately 5-10% of the drug is excreted unchanged. Renal excretion is pH-dependent; acidic urine increases excretion of the ionized form. Biliary excretion also occurs, with some enterohepatic recirculation.

Half-Life: Dog: 1-2 hours; Cat: 1-2 hours; Horse: 1-2 hours; Human: 2-4 hours. Normeperidine half-life is 15-30 hours in dogs and cats.

Bioavailability: Oral: 50-60%; IM/SC: 100% (assumed)

Protein Binding: 60-70%

Available Formulations & Strengths

Injectable Solution 50 mg/mL (as hydrochloride) (IM, SC, IV)

Oral Tablet 50 mg, 100 mg (PO)

Oral Syrup 50 mg/5 mL (PO)

Contraindications & Clinical Warnings

Contraindications:

Hypersensitivity to meperidine or other opioids
Severe respiratory depression
Concurrent use with MAO inhibitors (within 14 days)
Severe hepatic or renal impairment (use with caution)
Head trauma or increased intracranial pressure (may worsen)
Use in patients with seizure disorders (normeperidine may precipitate seizures)
Use in patients with cardiovascular instability (may cause hypotension)

Warnings & Clinical Precautions:

Use with caution in patients with hypothyroidism, adrenal insufficiency, or prostatic hypertrophy
May cause respiratory depression; monitor respiratory rate and depth
May cause hypotension, especially in hypovolemic patients
May cause CNS excitation or seizures, especially with high doses or prolonged use due to normeperidine accumulation
Use with caution in geriatric or debilitated patients
May cause ileus or constipation; monitor gastrointestinal motility
In cats, may cause mydriasis and excitement
In horses, may cause transient ataxia or excitement
Use with caution in animals with biliary colic (may cause sphincter of Oddi spasm)
Avoid extravasation at injection site (may cause tissue irritation)
Do not administer intravenously rapidly; may cause severe hypotension and respiratory arrest

Adverse Effects & Reactions

Common:

Sedation
Dysphoria (especially in cats and horses)
Vomiting
Constipation
Respiratory depression (dose-dependent)
Hypotension
Bradycardia or tachycardia
Miosis or mydriasis (species-dependent)

Serious / Severe:

Seizures (due to normeperidine accumulation)
Severe respiratory depression
Cardiovascular collapse
Anaphylactoid reactions
Ileus
Urinary retention

Rare:

Hyperthermia
Muscle rigidity
Pruritus
Allergic reactions

Key Drug Interactions

Interacting Drug / Class	Clinical Effect & Mechanism	Severity
MAO inhibitors (e.g., selegiline)	Severe serotonin syndrome, hyperthermia, hypotension, respiratory depression, coma, and death. Avoid concurrent use or within 14 days.	High
CNS depressants (e.g., barbiturates, benzodiazepines, phenothiazines, anesthetics)	Additive CNS and respiratory depression. Reduce doses of both agents.	High
Other opioids	Additive analgesic and respiratory depressant effects. Use with caution.	Moderate
Anticholinergic agents (e.g., atropine)	May increase risk of tachycardia and urinary retention.	Moderate
Cimetidine	May decrease meperidine metabolism, increasing plasma levels and toxicity.	Moderate
Phenytoin	May increase meperidine metabolism, reducing efficacy and increasing normeperidine levels.	Moderate
Ritonavir	May increase meperidine levels and risk of toxicity.	Moderate

Overdose & Toxicity Management

Signs of Toxicity:

Severe respiratory depression (bradypnea, apnea)
CNS depression progressing to coma
Hypotension
Bradycardia
Hypothermia
Muscle flaccidity
Pulmonary edema
Seizures (especially with normeperidine accumulation)

Emergency Treatment Protocol: Maintain airway and provide respiratory support (mechanical ventilation if necessary). Administer naloxone (opioid antagonist) at 0.01-0.04 mg/kg IV, IM, or SC; may repeat as needed. Monitor for seizures; treat with diazepam or barbiturates if they occur. Provide supportive care including fluids, vasopressors for hypotension, and temperature management. Note: Naloxone may precipitate withdrawal in animals physically dependent on opioids.

Food Animal Withdrawal Times

🥩 Meat: 7 days🥛 Milk: 72 days

Withdrawal times are not established for meperidine in food animals. Use is extra-label in the US; consult FARAD for specific recommendations. The values provided are conservative estimates based on limited data; actual withdrawal times may vary.

Storage, Handling & Regulatory Information

Storage Temperature: Store at controlled room temperature 15-30°C (59-86°F). Protect from light.

Light Sensitivity: Light-sensitive — protect from direct exposure.

Handling & Special Conditions: Store in a tightly closed container. Protect from freezing. Keep out of reach of children and animals. Dispose of unused medication properly.

Dispensing Status: Prescription Required (Rx Only)

Approval Status: Approved for human use; not FDA-approved for veterinary use, but can be used legally in animals under the Animal Medicinal Drug Use Clarification Act (AMDUCA) for non-food animals.

Extra-Label (Off-Label) Use: In the US, extra-label use of meperidine in food animals is prohibited under AMDUCA because it is a controlled substance and not approved for food animals. Use in food animals is not permitted. In non-food animals, extra-label use is allowed under veterinary supervision.

Clinical Pearls & Practice Notes

💡 Clinical Insights: Meperidine is a short-acting opioid analgesic that is less commonly used in veterinary medicine due to the availability of safer and more effective opioids (e.g., morphine, hydromorphone, fentanyl). It has a rapid onset but short duration, making it suitable for brief painful procedures or as a preanesthetic. However, its metabolite normeperidine can accumulate with repeated dosing, causing CNS excitation and seizures, especially in patients with renal impairment. Therefore, it is not recommended for prolonged pain management. In dogs and cats, it can cause dysphoria and excitement, particularly at higher doses. In horses, it may cause transient excitement and ataxia. Due to its potential for abuse, it is a Schedule II controlled substance. Always use with caution, monitor respiratory and cardiovascular status, and have naloxone available. For food animals, meperidine is not approved and its use is prohibited; alternative analgesics should be considered.

References & Literature

📚 Plumb's Veterinary Drug Handbook
📚 Papich Veterinary Pharmacology and Therapeutics
📚 Compendium of Veterinary Products (CVP)