Tilmicosin Phosphate

Macrolide antibiotic Antibacterial

Dosage & Administration Guidelines

Species Route Dose Frequency Duration & Clinical Notes
Cattle SC 10 mg/kg Single dose Duration: Single administration
Notes: Do not inject more than 10 mL per injection site. Administer subcutaneously only. Not for IV or IM use.
Sheep SC 10 mg/kg Single dose Duration: Single administration
Notes: Extra-label use. Use with caution; observe withdrawal times.
Swine PO (in feed or water) 200-400 mg/L drinking water or 15-20 mg/kg feed Continuous administration for 5-7 days Duration: 5-7 days
Notes: Not approved in all countries. Ensure adequate water intake.

Clinical Indications & Species Uses

General Indications
  • Treatment of respiratory tract infections caused by susceptible organisms in cattle and sheep.
Cattle (Bovine)
  • Treatment of bovine respiratory disease (BRD) associated with Mannheimia haemolytica, Pasteurella multocida, and Histophilus somni.
  • Control of respiratory disease in cattle at high risk of developing BRD.
Small Ruminants (Sheep / Goat)
  • Treatment of respiratory disease in sheep associated with Mannheimia haemolytica and Pasteurella multocida (extra-label).

Pharmacology & Mechanism of Action

Drug Class: Macrolide antibiotic | Pharmacological Group: Antibacterial

Mechanism of Action: Tilmicosin is a semi-synthetic macrolide antibiotic that acts by binding to the 50S ribosomal subunit of susceptible bacteria, thereby inhibiting protein synthesis. It is primarily bacteriostatic but can be bactericidal at higher concentrations. It exhibits activity against Gram-positive bacteria, some Gram-negative bacteria, and mycoplasmas. The drug also has immunomodulatory effects, including stimulation of neutrophil function and reduction of inflammation.

Pharmacodynamics: Tilmicosin has a prolonged post-antibiotic effect and concentrates in phagocytes, delivering high drug levels to sites of infection. It is effective against Mannheimia haemolytica, Pasteurella multocida, Histophilus somni, Mycoplasma spp., and some other respiratory pathogens. It is not effective against enterobacteriaceae due to intrinsic resistance.

⚡ Pharmacokinetics Summary

Absorption: After subcutaneous injection, tilmicosin is rapidly absorbed with peak plasma concentrations reached within 1-2 hours. Oral absorption is variable and less predictable.
Distribution: Tilmicosin is extensively distributed, with high concentrations in lung tissue, bronchial secretions, and alveolar macrophages. It has a large volume of distribution.
Metabolism: Tilmicosin is minimally metabolized; the majority is excreted unchanged.
Excretion: Excretion is primarily via the biliary route into feces, with some renal excretion. In cattle, the elimination half-life is approximately 1-2 days.
Half-Life: Cattle: ~1-2 days; Sheep: ~1-2 days; Swine: ~8-12 hours (oral)
Bioavailability: Subcutaneous injection: ~100% bioavailable. Oral: variable, approximately 20-30% in swine.
Protein Binding: Approximately 20-30% protein bound in cattle.

Available Formulations & Strengths

Injectable Solution 300 mg/mL (SC)
Premix (for feed) Various concentrations (e.g., 20%, 40%) (PO)
Soluble Powder (for water) Various concentrations (PO)

Contraindications & Clinical Warnings

Contraindications:
  • Do not administer intravenously or intramuscularly to cattle or sheep.
  • Do not use in horses, dogs, cats, or other non-target species due to severe toxicity.
  • Do not use in animals with known hypersensitivity to macrolides.
  • Do not use in lactating dairy cattle if milk withdrawal time cannot be met.
  • Do not use in calves less than 2 weeks of age unless directed by a veterinarian.
Warnings & Clinical Precautions:
  • Tilmicosin is highly toxic to humans; avoid accidental self-injection. Seek medical attention immediately if injected.
  • Use with caution in animals with hepatic impairment.
  • Do not exceed the recommended dose or duration.
  • In cattle, do not inject more than 10 mL per site to minimize tissue irritation.
  • In sheep, use extra-label with caution; observe withdrawal times.
  • Keep out of reach of children and unauthorized personnel.
  • Wear protective gloves and eyewear when handling.

Adverse Effects & Reactions

Common:

  • Injection site swelling and pain
  • Local tissue irritation
  • Transient pyrexia
  • Decreased appetite

Serious / Severe:

  • Cardiotoxicity (especially in non-target species)
  • Respiratory distress
  • Collapse
  • Death (in horses, dogs, cats)
  • Anaphylaxis

Rare:

  • Hepatotoxicity
  • Nephrotoxicity
  • Blood dyscrasias

Key Drug Interactions

Interacting Drug / Class Clinical Effect & Mechanism Severity
Other macrolides (e.g., erythromycin, tylosin) Additive effects and potential increased toxicity. Moderate
Chloramphenicol Antagonistic effect due to competition for binding site. Moderate
Lincomycin Antagonistic effect; avoid concurrent use. Moderate
Beta-lactam antibiotics (e.g., penicillin) Potential antagonism due to bacteriostatic vs bactericidal action. Mild

Overdose & Toxicity Management

Signs of Toxicity:

  • In cattle: tachycardia, dyspnea, pulmonary edema, collapse.
  • In non-target species: severe cardiotoxicity, hypotension, cardiac arrest.
  • In humans: nausea, vomiting, tachycardia, hypotension.

Emergency Treatment Protocol: There is no specific antidote. Treatment is symptomatic and supportive. In case of accidental injection in humans, seek immediate medical attention. For animals, provide supportive care, monitor cardiac function, and administer fluids and electrolytes as needed. In severe cases, consider antiarrhythmics and respiratory support.

Food Animal Withdrawal Times

🥩 Meat: 28 days🥛 Milk: 36 days

Withdrawal times are for cattle and sheep. For swine, meat withdrawal is 7 days. Milk withdrawal for sheep is 36 days. Always follow local regulations.

Storage, Handling & Regulatory Information

Storage Temperature: Store at controlled room temperature 20-25°C (68-77°F), excursions permitted between 15-30°C (59-86°F).

Handling & Special Conditions: Protect from freezing. Keep container tightly closed. Store in a dry place.

Dispensing Status: Prescription Required (Rx Only)

Approval Status: Approved for use in cattle and sheep in the US (e.g., Micotil 300). Not approved for swine in the US, but approved in some other countries.

Extra-Label (Off-Label) Use: In the US, extra-label use in food animals is permitted under AMDUCA with a valid veterinary-client-patient relationship, but must adhere to withdrawal times and residue avoidance. Not approved for use in minor species.

Clinical Pearls & Practice Notes

💡 Clinical Insights: Tilmicosin is a valuable antibiotic for the control and treatment of bovine respiratory disease complex. It is characterized by excellent lung tissue penetration and a long half-life, allowing single-dose therapy. However, its use is limited by significant toxicity in non-target species, particularly horses, dogs, and cats, and by the risk of fatal cardiovascular effects in humans if accidentally injected. Therefore, strict adherence to label directions and safety precautions is essential. In cattle, subcutaneous administration is the only approved route; intravenous or intramuscular injection can be fatal. In sheep, extra-label use requires careful consideration of withdrawal times. For swine, oral administration via feed or water is used in some countries, but it is not approved in the US. Always monitor animals for adverse reactions, and ensure proper handling to prevent human exposure.

References & Literature

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