Metamizole Sodium

Non-opioid analgesic, antipyretic, spasmolytic Pyrazolone derivative (NSAID-like)

Dosage & Administration Guidelines

Species Route Dose Frequency Duration & Clinical Notes
Dog IV, IM, SC, PO 25-50 mg/kg (IV/IM/SC); 25-50 mg/kg (PO) q8-12h Duration: Up to 3-5 days depending on clinical response
Notes: IV administration should be slow to avoid hypotension. Use lowest effective dose.
Cat IV, IM, SC, PO 25 mg/kg (IV/IM/SC); 25 mg/kg (PO) q12-24h Duration: Short-term use (1-3 days) due to limited safety data
Notes: Off-label use; monitor for adverse effects.
Horse IV 10-25 mg/kg q8-12h Duration: Up to 3 days
Notes: Slow IV administration; avoid extravasation.
Cattle IV, IM, SC 20-30 mg/kg q12-24h Duration: Up to 3 days
Notes: For food animals, observe withdrawal times.
Small Ruminants (sheep, goats) IV, IM, SC 20-30 mg/kg q12-24h Duration: Up to 3 days
Notes: Off-label; use with caution.

Clinical Indications & Species Uses

General Indications
  • Acute pain management
  • Fever reduction
  • Visceral pain and smooth muscle spasms
Dog (Canine)
  • Analgesia for acute pain (visceral, colic, postoperative)
  • Antipyresis
  • Spasmolytic for gastrointestinal and urinary tract spasms
Cat (Feline)
  • Analgesia (off-label use)
  • Antipyresis (off-label use)
Horse (Equine)
  • Analgesia for colic
  • Antipyresis
  • Musculoskeletal pain (off-label)
Cattle (Bovine)
  • Analgesia for pain associated with surgery, trauma, or mastitis
  • Antipyresis
  • Spasmolytic for gastrointestinal disorders
Small Ruminants (Sheep / Goat)
  • Analgesia (off-label)
  • Antipyresis (off-label)

Pharmacology & Mechanism of Action

Drug Class: Non-opioid analgesic, antipyretic, spasmolytic | Pharmacological Group: Pyrazolone derivative (NSAID-like)

Mechanism of Action: Metamizole (dipyrone) is a prodrug that is hydrolyzed in the gastrointestinal tract to its active metabolite 4-methyl-amino-antipyrine (4-MAA). The exact mechanism of action is not fully understood, but it is believed to involve inhibition of cyclooxygenase (COX) enzymes, particularly COX-3, and activation of the endocannabinoid system. It also modulates the endogenous opioid system and the descending pain pathways, providing analgesic, antipyretic, and spasmolytic effects. Unlike traditional NSAIDs, metamizole has minimal anti-inflammatory activity and less gastrointestinal toxicity.

Pharmacodynamics: Metamizole produces potent analgesia and antipyresis. It relieves visceral pain and spasms of smooth muscle. Its antipyretic effect is mediated by inhibition of prostaglandin synthesis in the hypothalamus. It does not have significant anti-inflammatory or antiplatelet effects at therapeutic doses. The onset of action is rapid, and the duration is dose-dependent.

⚑ Pharmacokinetics Summary

Absorption: Rapidly absorbed after oral administration; bioavailability is nearly 100% in most species. After IV administration, effects are immediate.
Distribution: Widely distributed in tissues and body fluids; crosses the blood-brain barrier and placenta. Volume of distribution is moderate.
Metabolism: Extensively metabolized in the liver, primarily to 4-MAA, which is further metabolized to other active and inactive metabolites. Metabolism involves CYP450 enzymes and non-enzymatic hydrolysis.
Excretion: Metabolites are excreted primarily via the kidneys (urine) and to a lesser extent in bile. Renal excretion is the main route of elimination.
Half-Life: Dog: approximately 4-5 hours; Horse: approximately 2-3 hours; Cattle: approximately 1-2 hours; Cat: approximately 2-3 hours (limited data).
Bioavailability: Oral bioavailability is high (near 100%) in dogs and horses; in cattle, oral bioavailability is lower (around 50-60%) due to rumen degradation.
Protein Binding: Moderate protein binding, approximately 50-60% in most species.

Available Formulations & Strengths

Injectable Solution 500 mg/mL (50% solution) (IV, IM, SC)
Oral Tablet 500 mg, 1000 mg (PO)
Oral Solution/Drops 500 mg/mL (PO)

Contraindications & Clinical Warnings

Contraindications:
  • Hypersensitivity to metamizole or other pyrazolones (e.g., phenylbutazone)
  • Known blood dyscrasias (e.g., agranulocytosis, aplastic anemia)
  • Severe hepatic or renal impairment
  • Gastrointestinal ulceration or bleeding
  • Pregnancy (especially first and last trimester) unless benefit outweighs risk
  • Concurrent use with other NSAIDs or anticoagulants
Warnings & Clinical Precautions:
  • Use with caution in animals with cardiovascular disease, hypotension, or dehydration.
  • Monitor for signs of blood dyscrasias (e.g., fever, sore throat, bruising) during prolonged therapy.
  • In horses, rapid IV injection may cause transient hypotension and collapse.
  • In cats, use only when no alternatives are available due to potential toxicity.
  • In food animals, observe withdrawal times to avoid residues.
  • Avoid extravasation during IV administration as it may cause tissue irritation.
  • Use with caution in neonates and geriatric animals.

Adverse Effects & Reactions

Common:

  • Injection site pain or swelling
  • Hypotension (especially after rapid IV)
  • Gastrointestinal upset (nausea, vomiting, diarrhea)
  • Salivation

Serious / Severe:

  • Blood dyscrasias (agranulocytosis, leukopenia, thrombocytopenia)
  • Anaphylactic shock
  • Renal toxicity (especially with dehydration)
  • Hepatotoxicity
  • Gastrointestinal ulceration and bleeding

Rare:

  • CNS stimulation or depression
  • Allergic skin reactions
  • Bone marrow suppression

Key Drug Interactions

Interacting Drug / Class Clinical Effect & Mechanism Severity
Other NSAIDs (e.g., flunixin, carprofen) Increased risk of gastrointestinal ulceration and renal toxicity High
Corticosteroids Increased risk of gastrointestinal ulceration High
Anticoagulants (e.g., warfarin, heparin) Increased risk of bleeding High
ACE inhibitors (e.g., enalapril) Reduced antihypertensive effect and increased renal risk Moderate
Furosemide Reduced diuretic effect and increased risk of renal toxicity Moderate
Phenobarbital or other enzyme inducers May increase metabolism of metamizole, reducing efficacy Mild

Overdose & Toxicity Management

Signs of Toxicity:

  • Hypotension
  • Tachycardia
  • Vomiting
  • Abdominal pain
  • CNS depression or seizures
  • Respiratory depression
  • Hypothermia
  • Renal failure
  • Hepatic damage

Emergency Treatment Protocol: There is no specific antidote. Treatment is symptomatic and supportive. Induce emesis if recent oral ingestion and animal is conscious. Administer activated charcoal to reduce absorption. Provide IV fluids to maintain blood pressure and renal perfusion. Monitor vital signs, ECG, and organ function. Use anticonvulsants (e.g., diazepam) for seizures. In severe cases, consider hemodialysis or hemoperfusion.

Food Animal Withdrawal Times

πŸ₯© Meat: 15 daysπŸ₯› Milk: 3 days

Withdrawal times vary by country and formulation. In the US, metamizole is not approved for food animals; extra-label use requires extended withdrawal periods. Consult regulatory guidelines.

Storage, Handling & Regulatory Information

Storage Temperature: Store at controlled room temperature (20-25Β°C), protect from light.

Light Sensitivity: Light-sensitive β€” protect from direct exposure.

Handling & Special Conditions: Keep container tightly closed. Do not freeze. Protect from moisture.

Dispensing Status: Prescription Required (Rx Only)

Approval Status: Not FDA-approved for veterinary use in the US. Approved in some European and other countries for veterinary use.

Extra-Label (Off-Label) Use: In the US, metamizole is not approved for veterinary use in food animals. Extra-label use in animals is permitted under AMDUCA only with a valid veterinarian-client-patient relationship and extended withdrawal times. In some countries, it is approved for use in dogs, cats, and horses. Check local regulations.

Clinical Pearls & Practice Notes

πŸ’‘ Clinical Insights: Metamizole is a valuable analgesic and antipyretic in veterinary medicine, particularly for visceral pain and colic in horses. It is often used as an alternative to NSAIDs when gastrointestinal safety is a concern. However, its use is limited in some countries due to the risk of agranulocytosis in humans, but this risk is not well-documented in animals. In dogs and cats, it is used off-label; in horses, it is commonly used for colic pain. In cattle, it is used for pain management but requires strict adherence to withdrawal times. Always use the lowest effective dose for the shortest duration. Monitor for adverse effects, especially hematological and renal. Avoid concurrent use with other NSAIDs or corticosteroids. In food animals, ensure compliance with regulatory requirements.

References & Literature

  • πŸ“š Plumb's Veterinary Drug Handbook
  • πŸ“š Papich Veterinary Pharmacology and Therapeutics
  • πŸ“š Compendium of Veterinary Products (CVP)