Amantadine HCl
Adamantanamine hydrochloride
Also known as: Symmetrel · Adekin · Amantagamma · Amantrel · Amixx · Antiflu-DES · Atarin · Atenegine · Cerebramed · Endantadine · Infectoflu · Influ-A · Lysovir · Mantadix · Mantidan · Padiken · Symadine · Viroifral · Virucid · Adamantanamine HCl · Amantadine HCl · Amantadini hydrochloridum
Reviewed by the VetSheet Veterinary TeamUpdated Apr 5, 2026Evidence-based veterinary reference
Doses are a clinical reference for licensed veterinary professionals. Always confirm against the current label and the individual patient.
Dosing by species
🌎 NA — North America🌍 EU — Europe
Dogs
| Indication | Dose | Route | Frequency | Duration | Region |
|---|---|---|---|---|---|
| Osteoarthritis pain when NSAIDs alone are not effective | 3-5 mg/kg PO once daily in addition to an NSAID | PO | q24h | — | 🌎 NA |
| Adjunctive therapy for chronic pain | 3-5 mg/kg PO once daily | PO | q24h | — | 🌎 NA |
| To decrease wind-up | 3-5 mg/kg PO once daily for one week | PO | q24h | 1 week | 🌎 NA |
| Analgesia (adjunct for chronic pain) | 3-5 mg/kg | PO | sid to bid | Chronic | 🌍 EU |
- Osteoarthritis pain when NSAIDs alone are not effective: Meloxicam at approved doses was used for this study.
- Analgesia (adjunct for chronic pain): Potentiates the effects of other analgesics. Often combined with NSAIDs.
Cats
| Indication | Dose | Route | Frequency | Duration | Region |
|---|---|---|---|---|---|
| Adjunctive therapy for chronic pain | 3 mg/kg PO once daily | PO | q24h | — | 🌎 NA |
| Adjunctive therapy for chronic pain | 3-5 mg/kg PO once daily | PO | q24h | — | 🌎 NA |
| Adjunctive therapy for chronic pain | 3 mg/kg PO once daily | PO | q24h | — | 🌎 NA |
| Analgesia (adjunct for chronic pain) | 3-5 mg/kg | PO | sid | Chronic | 🌍 EU |
- Adjunctive therapy for chronic pain: May be useful addition to NSAIDs; has not been evaluated for toxicity. May need to be compounded.
- Analgesia (adjunct for chronic pain): Liquid formulations may be bitter and difficult to administer.
Horses
| Indication | Dose | Route | Frequency | Duration | Region |
|---|---|---|---|---|---|
| Acute treatment of equine-2 influenza | 5 mg/kg IV q4h | IV | q4h | — | 🌎 NA |
- Acute treatment of equine-2 influenza: Not commonly used due to expense, PK variability, and seizure risk.
Doses are a clinical reference for licensed veterinary professionals. Always confirm against the current label and the individual patient.
Overview
Amantadine is an antiviral agent originally developed for the prophylaxis and treatment of Influenza A, but in modern veterinary medicine, it is primarily utilized for its NMDA (N-methyl-D-aspartate) receptor antagonist properties.
Key clinical applications include:
- Adjunctive Analgesia: Used primarily in dogs and cats to treat chronic, neuropathic, or opioid-tolerant pain (e.g., severe osteoarthritis, osteosarcoma). It is rarely effective as a sole analgesic but shines when combined with NSAIDs, opioids, or gabapentin to combat central sensitization.
- Equine Influenza: Investigated for equine-2 influenza virus, though clinical use is limited by high cost, erratic oral absorption, and the risk of seizures with IV administration.
Clinical Pearl: Amantadine is a crucial tool for treating "wind-up" pain (allodynia and hyperalgesia) where the nervous system has become hypersensitive to pain signals.
Mechanism of action
Amantadine has distinct mechanisms depending on the therapeutic target:
- Analgesia (NMDA Antagonism): Chronic pain causes excessive release of excitatory neurotransmitters (glutamate and aspartate). These bind to the NMDA receptor on postsynaptic neurons in the dorsal horn of the spinal cord. Amantadine acts as a non-competitive antagonist, blocking the open ion channel of the NMDA receptor → prevents calcium (Ca2+) influx → reduces central sensitization and "wind-up" pain.
- Antiviral: Interferes with the influenza A virus M2 transmembrane protein → blocks the uncoating of the virus particle and prevents viral replication.
- Antiparkinsonian (Human): Potentiates dopaminergic neurotransmission in the CNS and exhibits mild anticholinergic activity.
Safety & warnings
Contraindications
- Known hypersensitivity to amantadine or rimantadine
- Untreated angle-closure glaucoma
- Extra-label use in chickens, turkeys, and ducks (Prohibited by FDA)
Adverse effects
- Agitation or restlessness (especially early in therapy)
- Loose stools, flatulence, or diarrhea
- Narrow safety margin in cats (potential for neurotoxicity)
- Seizures (reported in horses given IV)
Precautions
Use with caution in patients with liver disease, renal disease (dosage adjustment may be required as it is primarily renally excreted), congestive heart failure, active psychoses, eczematoid dermatitis, or seizure disorders.
Warning: The FDA strictly prohibits the extra-label use of amantadine and other influenza antivirals in poultry (chickens, turkeys, ducks).
Drug interactions
May enhance the anticholinergic effects of amantadine.
Concomitant use may increase the CNS stimulatory effects of amantadine.
May decrease the renal excretion of amantadine, yielding higher and potentially toxic blood levels.
May increase the renal excretion of amantadine, potentially decreasing its efficacy.
Decreased renal clearance of amantadine, potentially leading to toxicity
Increased anticholinergic side effects (e.g., dry mouth, urine retention)
Increased risk of agitation, restlessness, or seizures
Monitoring
- Adverse effects (especially GI upset and agitation/behavioral changes)
- Clinical efficacy (reduction in pain scores, improved mobility)
Pharmacokinetics
Half-life
Absorption
Horses: Wide interpatient variability after oral dosing; bioavailability ranges from 40-60%. Humans: Well absorbed orally with peak plasma concentrations at ~3 hours.
Distribution
Horses: Steady state volume of distribution is approximately 5 L/kg. Humans: Vd is 3-8 L/kg.
Metabolism
Not well described in veterinary species.
Elimination
Humans: Primarily eliminated via renal mechanisms. Oral clearance is ~0.28 L/hr/kg.
Overdose
Overdoses are potentially very serious due to a fairly narrow therapeutic index.
- Cats: Toxic dose reported is 30 mg/kg. Behavioral effects may be noted at 15 mg/kg.
- Dogs: Behavioral effects noted at 15 mg/kg.
- Humans: Overdoses as low as 2 grams have been fatal. Signs include cardiac dysfunction (arrhythmias, hypertension, tachycardia), pulmonary edema, CNS toxicity (tremors, seizures, psychosis, agitation, coma), hyperthermia, and renal dysfunction.
Treatment: No specific antidote. Empty the gut if possible. Provide intensive monitoring and supportive therapy. Forced urine acidifying diuresis may increase renal excretion. Physostigmine has been suggested for cautious use in treating CNS effects.
Available products
Formulations
- Oral Tablets
- Oral Capsules
- Oral Syrup/Solution
Human-labeled
- Amantadine HCl Oral Tablets & Capsules: 100 mg (Symmetrel®, generic)
- Amantadine HCl Oral Syrup: 10 mg/mL in 480 mL (Symmetrel®, generic)
Regulatory status
POM. Used off-label under the prescribing cascade.
POM. Used off-label under the prescribing cascade.
No regulatory data for: 🇺🇸 US · 🇭🇰 HK · 🇹🇼 TW · 🇯🇵 JP · 🇰🇷 KR · 🇦🇺 AU
Storage & stability
Tablets, capsules, and oral solution should be stored in tight containers at room temperature. Limited exposures to temperatures as low as 15°C and as high as 30°C are permitted. Avoid freezing the liquid.
Client information
- Patience is Key: When used for chronic pain, this medication must be given consistently as prescribed. It may take a week or more to see noticeable improvements in your pet's comfort.
- Side Effects: Mild gastrointestinal effects (loose stools, gas, diarrhea) or mild agitation/restlessness may occur, especially during the first few days of treatment. Contact your veterinarian if these signs become severe or persist.
- Taste: If using the liquid formulation, be aware that it has a very bitter taste. Your veterinarian or a compounding pharmacy may be able to provide a flavored version.
- Safety Warning: Overdoses can be life-threatening. Keep this medication strictly out of reach of children and all pets.
VetSheet drug reference is intended for licensed veterinary professionals as a clinical decision-support aid, not a substitute for professional judgement or the manufacturer’s current label.