Amantadine HCl
**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: 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** โ prevents calcium (Ca2+) influx โ reduces central sensitization and "wind-up" pain. * **Antiviral**: Interferes with the **influenza A virus M2 transmembrane protein** โ blocks the uncoating of the virus particle and prevents viral replication. * **Antiparkinsonian (Human)**: Potentiates dopaminergic neurotransmission in the CNS and exhibits mild anticholinergic activity.
Dosing by species
- Osteoarthritis pain when NSAIDs alone are not effective ยท 3-5 mg/kg PO once daily in addition to an NSAID ยท PO ยท q24h ยท Meloxicam at approved doses was used for this study.
- Adjunctive therapy for chronic pain ยท 3-5 mg/kg PO once daily ยท PO ยท q24h
- To decrease wind-up ยท 3-5 mg/kg PO once daily for one week ยท PO ยท q24h ยท 1 week
- Analgesia (adjunct for chronic pain) ยท 3-5 mg/kg ยท PO ยท sid to bid ยท Chronic ยท Potentiates the effects of other analgesics. Often combined with NSAIDs.
- Adjunctive therapy for chronic pain ยท 3 mg/kg PO once daily ยท PO ยท q24h ยท May be useful addition to NSAIDs; has not been evaluated for toxicity. May need to be compounded.
- Adjunctive therapy for chronic pain ยท 3-5 mg/kg PO once daily ยท PO ยท q24h
- Adjunctive therapy for chronic pain ยท 3 mg/kg PO once daily ยท PO ยท q24h
- Analgesia (adjunct for chronic pain) ยท 3-5 mg/kg ยท PO ยท sid ยท Chronic ยท Liquid formulations may be bitter and difficult to administer.
- Acute treatment of equine-2 influenza ยท 5 mg/kg IV q4h ยท IV ยท q4h ยท 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.
Routes of administration
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)
Drug interactions
- Anticholinergic drugs ยท May enhance the anticholinergic effects of amantadine.
- CNS Stimulants (e.g., selegiline) ยท Concomitant use may increase the CNS stimulatory effects of amantadine.
- Trimethoprim/sulfa, quinidine, quinine, thiazide diuretics, triamterene ยท May decrease the renal excretion of amantadine, yielding higher and potentially toxic blood levels.
- Urinary acidifiers (e.g., methionine, ammonium chloride, ascorbic acid) ยท May increase the renal excretion of amantadine, potentially decreasing its efficacy.
- Trimethoprim/Sulfamethoxazole ยท Decreased renal clearance of amantadine, potentially leading to toxicity ยท moderate
- Anticholinergics ยท Increased anticholinergic side effects (e.g., dry mouth, urine retention) ยท minor
- CNS stimulants ยท Increased risk of agitation, restlessness, or seizures ยท moderate
Monitoring
- Adverse effects (especially GI upset and agitation/behavioral changes)
- Clinical efficacy (reduction in pain scores, improved mobility)
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.
VetSheet drug reference is intended for licensed veterinary professionals as a clinical decision-support aid, not a substitute for professional judgement or the manufacturerโs current label.