Tramadol
Tramadol is a synthetic, centrally acting **opiate-like analgesic** used primarily for the management of mild to moderate pain and occasionally as an antitussive. **Key Clinical Highlights:** * Acts as a weak **mu-opioid receptor agonist** and inhibits the reuptake of **serotonin** and **norepinephrine**. * Highly useful as part of a **multimodal analgesic protocol** (e.g., combined with NSAIDs, gabapentin, or amantadine) for chronic pain conditions like osteoarthritis or cancer. * May take up to **two weeks** to reach full analgesic efficacy in chronic pain states. * **Clinical Pearl:** While the monograph notes it is not a controlled substance, **tramadol was reclassified as a Schedule IV controlled substance by the DEA in the USA in 2014** due to human abuse potential. * Generally well-tolerated in dogs, with sedation being the most common side effect. Cats may experience dysphoria and find the medication highly unpalatable.
Mechanism: Tramadol provides analgesia through a dual mechanism of action: 1. **Opioid Activity:** Tramadol and its active metabolite **O-desmethyltramadol (M1)** bind to **mu-opioid receptors** in the central nervous system. 2. **Monoaminergic Activity:** It inhibits the synaptic reuptake of **serotonin (5-HT)** and **norepinephrine (NE)** โ enhancing descending inhibitory pathways of pain transmission in the spinal cord. **Pharmacologic Pearl:** The M1 metabolite is 6 times more potent as an analgesic and has 20 times greater affinity for mu-receptors than the parent drug. Dogs produce very little of the M1 metabolite compared to cats and humans, which explains why tramadol's opioid-mediated efficacy in dogs is often erratic and heavily reliant on its serotonin/norepinephrine reuptake inhibition. Naloxone only partially antagonizes tramadol's analgesic effects.
Dosing by species
- Starting dose ยท 2 mg/kg twice daily ยท PO ยท q12h ยท Based upon the pharmacokinetics of tramadol and ODT in cats.
- Current dosing recommendations ยท 1-2 mg/kg PO q12h ยท PO ยท q12h ยท Maximum analgesic effects may be delayed up to 14 days for chronic pain.
- Chronic pain ยท 1-4 mg/kg PO 2-3 times a day ยท PO ยท q8-12h ยท Reasonable for mild pain; dose and interval may need adjustment for more severe pain.
- Analgesia ยท 2-4 mg/kg ยท PO ยท q8h ยท Oral preparations are highly unpalatable to cats. Watch for dysphoria.
- Analgesia ยท 1-2 mg/kg ยท IV ยท as needed
- Analgesia ยท 1-2 mg/kg ยท SC ยท as needed
- Chronic laminitis pain ยท 5 mg/kg PO twice daily for seven days, alone or with ketamine at 0.6 mg/kg/hr IV during six hours each day for the first 3 days of treatment ยท PO/IV ยท q12h ยท 7 days ยท Pain relief was enhanced.
- General/Non-responsive pain ยท 5 mg/kg PO q6-8h and up to 10 mg/kg PO q6-8h ยท PO ยท q6-8h ยท Maximum analgesic effects may not occur immediately and may be delayed up to 14 days for chronic pain conditions.
- Analgesic ยท 2-5 mg/kg four times daily ยท PO ยท q6h ยท Suggested starting dose.
Routes of administration
Contraindications
- Hypersensitivity to tramadol or other opioids
- Combination products containing acetaminophen (e.g., Ultracet) are STRICTLY CONTRAINDICATED in cats
- Concurrent use with MAOIs (e.g., selegiline, amitraz) due to risk of serotonin syndrome
- Patients with a history of epilepsy or seizure disorders
- Concurrent use with MAOIs
Adverse effects
- Dogs: Excessive sedation, agitation, anxiety, tremor, dizziness
- Dogs: Inappetence, vomiting, constipation, diarrhea
- Cats: Dysphoria, mydriasis, dose avoidance (unpalatability)
- Humans: Pruritus (approx. 10%)
- Injectable form: Respiratory and cardiac depression
- Sedation (especially at high doses in dogs)
- Dysphoria (more likely in cats)
- Nausea
- Behavioral changes
- Increased risk of seizures
Drug interactions
- Digoxin ยท Rarely linked to digoxin toxicity in humans.
- MAO Inhibitors (amitraz, selegiline) ยท Potential for fatal serotonin syndrome; concurrent use should be avoided.
- Ondansetron ยท May reduce the effectiveness of both drugs.
- Quinidine ยท May increase tramadol concentrations and decrease M1 (active metabolite) concentrations.
- SAMe (S-adenosylmethionine) ยท Theoretically could cause additive serotonergic effects.
- Sevoflurane ยท Pretreatment with tramadol reduced MAC values by approximately 30% in dogs and 40% in cats.
- SSRI Antidepressants (fluoxetine, sertraline, paroxetine) ยท Can inhibit the metabolism of tramadol to its active metabolites, decreasing efficacy and increasing the risk of toxicity (serotonin syndrome, seizures).
- Tricyclic Antidepressants (clomipramine, amitriptyline) ยท Increased risk for seizures; amitriptyline may inhibit tramadol metabolism.
- Warfarin ยท Increased PT and INR reported in humans (relatively rare).
- Amitriptyline ยท Increased risk of serotonin syndrome ยท major
- Selegiline ยท Increased risk of serotonin syndrome ยท major
- SSRIs (e.g., Fluoxetine) ยท Increased risk of serotonin syndrome ยท major
Monitoring
- Clinical efficacy (pain scoring, mobility, comfort levels)
- Adverse effects (excessive sedation, GI upset, dysphoria, agitation)
- Pain scores to assess efficacy
- Signs of sedation or dysphoria
- Signs of serotonin syndrome (hyperthermia, hypertension, agitation, tremors)
- Seizure activity in susceptible individuals
Overdose
Acute oral overdoses may cause either **CNS depressive signs** or **serotonin syndrome**. * **Clinical Signs:** Lethargy, mydriasis, ataxia, and vomiting are most common. Stimulatory signs such as tachycardia, tremors, vocalization, agitation, and seizures may also occur. Cats frequently show mydriasis, hypersalivation, and tachycardia. * **Treatment:** Primarily supportive (maintaining respiration, treating seizures with benzodiazepines or barbiturates). * > **Important:** Naloxone may **NOT** be useful in tramadol overdoses. It only partially reverses effects and may actually **increase the risk of seizures**. Cyproheptadine and phenothiazines can be used to treat stimulatory signs (serotonin syndrome).
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.