Melatonin

Hormone Pineal hormone / Chronobiotic

Dosage & Administration Guidelines

Species Route Dose Frequency Duration & Clinical Notes
Dog PO 0.1-0.2 mg/kg (anxiety); 0.1-0.5 mg/kg (alopecia); 0.1 mg/kg (estrus suppression) q12h or q24h (depending on indication) Duration: Variable; for anxiety as needed or long-term; for alopecia 2-3 months
Notes: For anxiety, administer 30-60 minutes before stressful event. For alopecia, may require 3-6 months for hair regrowth.
Cat PO 0.5-1 mg per cat (anxiety); 0.1-0.2 mg/kg (sleep) q12h or q24h Duration: As needed or long-term
Notes: Start with low dose and titrate. Use caution in cats with hepatic disease.
Horse PO 10-30 mg per horse (hair growth); 10-20 mg per horse (reproductive) q24h Duration: Seasonal or as needed
Notes: For PPID adjunct, use in conjunction with pergolide. Administer in feed.
Cattle PO Not established; experimental doses 0.1-0.5 mg/kg q24h Duration: Variable
Notes: Not approved for use in food animals; withdrawal times must be considered.
Small Ruminants PO Not established; experimental doses 0.1-0.5 mg/kg q24h Duration: Variable
Notes: Not approved for use in food animals; withdrawal times must be considered.
Rabbit PO 0.5-1 mg per rabbit q12h or q24h Duration: As needed
Notes: Use with caution in rabbits with hepatic disease.
Bird/Poultry PO Not established; experimental doses 0.1-0.5 mg/kg q24h Duration: Variable
Notes: Not approved for use in food animals; withdrawal times must be considered.
Exotic/Other PO Varies by species; consult exotic animal formulary q24h Duration: Variable
Notes: Use with caution; limited safety data.

Clinical Indications & Species Uses

General Indications
  • Circadian rhythm disorders
  • Antioxidant support
  • Adjunct in cancer therapy (melanoma, mammary tumors)
Dog (Canine)
  • Anxiety and phobias (noise, separation)
  • Sleep disorders
  • Alopecia X (hair loss)
  • Seasonal alopecia
  • Estrus suppression (mild)
  • Cognitive dysfunction syndrome (adjunct)
  • Melanoma (adjunctive therapy)
Cat (Feline)
  • Anxiety and stress reduction
  • Sleep cycle regulation
  • Hair growth disorders (feline psychogenic alopecia adjunct)
Horse (Equine)
  • Seasonal hair growth regulation (hirsutism in PPID adjunct)
  • Reproductive cycle manipulation (seasonal breeding)
  • Sedation for handling (mild)
Cattle (Bovine)
  • Stress reduction during transport (experimental)
Rabbit & Small Mammals
  • Anxiety reduction
  • Hair growth disorders (fur chewing adjunct)
Exotic & Other Species
  • Reptiles: regulation of seasonal reproductive cycles
  • Small mammals (ferrets, guinea pigs): anxiety and hair loss

Pharmacology & Mechanism of Action

Drug Class: Hormone | Pharmacological Group: Pineal hormone / Chronobiotic

Mechanism of Action: Melatonin is a hormone synthesized from serotonin in the pineal gland, primarily regulating circadian rhythms and seasonal reproductive cycles. It acts on MT1 and MT2 G-protein coupled receptors in the suprachiasmatic nucleus and peripheral tissues, modulating neuronal firing and vasomotor responses. In veterinary medicine, it is used to influence photoperiod-dependent behaviors, induce sedation, and affect hair growth cycles. It also has antioxidant and immunomodulatory properties.

Pharmacodynamics: Melatonin influences the sleep-wake cycle, reduces anxiety, and has a calming effect. In dogs, it can suppress estrus cycles and treat separation anxiety and noise phobias. In horses, it affects seasonal hair growth and reproductive function. It also has oncostatic and antioxidant effects, and may modulate immune responses. Its effects are dose-dependent and vary by species.

⚑ Pharmacokinetics Summary

Absorption: Melatonin is rapidly absorbed after oral administration, with peak plasma concentrations occurring within 30-60 minutes in most species. Bioavailability is variable due to extensive first-pass metabolism, ranging from 15-50% depending on formulation and species.
Distribution: Melatonin is lipophilic and distributes widely throughout the body, crossing the blood-brain barrier and placenta. It accumulates in the pineal gland, retina, and other tissues. Volume of distribution is moderate.
Metabolism: Melatonin is primarily metabolized in the liver by cytochrome P450 enzymes (CYP1A2, CYP2C19) to 6-hydroxymelatonin, which is then conjugated with sulfate or glucuronide. Some metabolism occurs in the gut and brain.
Excretion: Metabolites are excreted primarily in urine (about 90%) and feces. The renal clearance of melatonin itself is low, with less than 1% excreted unchanged.
Half-Life: Dog: 15-30 minutes; Cat: 20-40 minutes; Horse: 30-60 minutes; Cattle: 20-40 minutes (estimated).
Bioavailability: Oral bioavailability is low and variable (15-50%) due to first-pass metabolism. Sublingual and transdermal routes may improve bioavailability.
Protein Binding: Approximately 60-70% bound to plasma proteins, mainly albumin.

Available Formulations & Strengths

Oral Tablet 0.5 mg, 1 mg, 3 mg, 5 mg, 10 mg (PO)
Oral Capsule 1 mg, 3 mg, 5 mg (PO)
Oral Liquid 1 mg/mL (PO)
Injectable Solution 1 mg/mL (compounded) (IM, SC)
Implant (compounded) Various (e.g., 12 mg, 18 mg) (SC)

Contraindications & Clinical Warnings

Contraindications:
  • Hypersensitivity to melatonin or any component
  • Autoimmune diseases (potential immunomodulation)
  • Severe hepatic disease (metabolism impairment)
  • Pregnancy (use with caution; may affect reproductive cycles)
  • Lactation (safety not established)
  • Concurrent use with immunosuppressive drugs
Warnings & Clinical Precautions:
  • Use with caution in animals with renal or hepatic impairment
  • May cause drowsiness; monitor when used with other CNS depressants
  • In food animals, extra-label use requires withdrawal time estimation
  • Not for use in animals intended for breeding unless directed by veterinarian
  • May affect reproductive cycles; avoid in pregnant animals unless benefits outweigh risks
  • Compounded formulations may vary in stability and potency
  • In horses with PPID, melatonin is adjunctive; do not replace primary therapy

Adverse Effects & Reactions

Common:

  • Drowsiness
  • Lethargy
  • Gastrointestinal upset (vomiting, diarrhea)
  • Changes in appetite

Serious / Severe:

  • Reproductive cycle disruption
  • Immune suppression (with prolonged use)
  • Hepatotoxicity (rare, with high doses)

Rare:

  • Allergic reactions (urticaria, angioedema)
  • Seizures (in predisposed animals)
  • Blood dyscrasias

Key Drug Interactions

Interacting Drug / Class Clinical Effect & Mechanism Severity
Benzodiazepines Additive sedation and CNS depression Moderate
Opioids Additive sedation and respiratory depression Moderate
Corticosteroids May antagonize effects of melatonin on immune function Mild
NSAIDs Potential increased risk of gastrointestinal bleeding (theoretical) Mild
Fluvoxamine Increased melatonin levels due to CYP inhibition Moderate
Warfarin Potential increased anticoagulant effect Moderate

Overdose & Toxicity Management

Signs of Toxicity:

  • Excessive sedation
  • Ataxia
  • Disorientation
  • Vomiting
  • Diarrhea
  • Hypothermia (in severe cases)

Emergency Treatment Protocol: Treatment is symptomatic and supportive. Induce vomiting if recent ingestion and animal is stable. Administer activated charcoal to reduce absorption. Provide IV fluids for dehydration. Monitor vital signs and neurological status. In severe cases, provide respiratory support and temperature regulation. No specific antidote exists.

Food Animal Withdrawal Times

πŸ₯© Meat: 0 daysπŸ₯› Milk: 0 daysπŸ₯š Eggs: 0 days

Melatonin is not approved for use in food animals. Extra-label use requires a veterinarian to establish appropriate withdrawal times based on pharmacokinetic data and withdrawal interval guidelines. A conservative withdrawal time of at least 24 hours for meat and milk is often recommended, but official withdrawal times are not established.

Storage, Handling & Regulatory Information

Storage Temperature: Store at room temperature (20-25Β°C) in a dry place.

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

Handling & Special Conditions: Protect from light and moisture. Keep container tightly closed. Compounded formulations may have specific storage requirements; follow label instructions.

Dispensing Status: Over-The-Counter (OTC)

Approval Status: Not FDA-approved for veterinary use; available as a dietary supplement for humans and animals.

Extra-Label (Off-Label) Use: In the US, melatonin is a dietary supplement and not FDA-approved as a veterinary drug. Extra-label use in animals is permitted under AMDUCA for non-food animals. For food animals, extra-label use is prohibited unless a veterinarian establishes a valid veterinary-client-patient relationship and sets appropriate withdrawal times.

Clinical Pearls & Practice Notes

πŸ’‘ Clinical Insights: Melatonin is a versatile agent used in veterinary medicine for behavioral, dermatological, and reproductive conditions. It is generally well-tolerated with a wide safety margin. Dosing is often empirical and may require titration. For anxiety, it is best used as an adjunct to behavior modification. For alopecia X, response may take months. In horses with PPID, it is not a substitute for pergolide. Always consider potential drug interactions and underlying health conditions. In food animals, use is limited due to lack of approval and withdrawal data. Compounded formulations should be used with caution due to variability.

References & Literature

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