Amitriptyline HCL (Elavil)

By | 2013-07-18

Tricyclic Behavior Modifier; Anti-Pruritic; Neuropathic Pain Modifier

Highlights Of Prescribing Information

Tricyclic “antidepressant” used primarily for behavior disorders & neuropathic pain/pruritus in small animals

May reduce seizure thresholds in epileptic animals

Sedation & anticholinergic effects most likely adverse effects

Overdoses can be very serious in both animals & humans

What Is Amitriptyline HCL Used For?

Amitriptyline has been used for behavioral conditions such as separation anxiety or generalized anxiety in dogs, and excessive grooming, spraying and anxiety in cats. Amitriptyline may be useful for adjunctive treatment of pruritus, or chronic pain of neuropathic origin in dogs and cats. In cats, it potentially could be useful for adjunctive treatment of lower urinary tract disease. Amitriptyline has been tried to reduce feather plucking in birds.

Pharmacology / Actions

Amitriptyline (and its active metabolite, nortriptyline) has a complicated pharmacologic profile. From a slightly oversimplified viewpoint, it has 3 main characteristics: blockage of the amine pump, thereby increasing neurotransmitter levels (principally serotonin, but also norepinephrine), sedation, and central and peripheral anticholinergic activity. Other pharmacologic effects include stabilizing mast cells via H-l receptor antagonism, and antagonism of glutamate receptors and sodium channels. In animals, tricyclic antidepressants are similar to the actions of phenothiazines in altering avoidance behaviors.

Pharmacokinetics

Amitriptyline is rapidly absorbed from both the GI tract and from parenteral injection sites. Peak levels occur within 2-12 hours. Amitriptyline is highly bound to plasma proteins, enters the CNS, and enters maternal milk in levels at, or greater than those found in maternal serum. The drug is metabolized in the liver to several metabolites, including nortriptyline, which is active. In humans, the terminal half-life is approximately 30 hours. Half-life in dogs has been reported to be 6-8 hours.

Before you take Amitriptyline HCL

Contraindications / Precautions / Warnings

These agents are contraindicated if prior sensitivity has been noted with any other tricyclic. Concomitant use with monoamine oxidase inhibitors is generally contraindicated. Use with extreme caution in patients with seizure disorders as tricyclic agents may reduce seizure thresholds. Use with caution in patients with thyroid disorders, hepatic disorders, KCS, glaucoma, cardiac rhythm disorders, diabetes, or adrenal tumors.

Adverse Effects

The most predominant adverse effects seen with the tricyclics are related to their sedating and anticholinergic (constipation, urinary retention) properties. Occasionally, dogs exhibit hyperexcitability and, rarely, develop seizures. However, adverse effects can run the entire gamut of systems, including cardiac (dysrhythmias), hematologic (bone marrow suppression), GI (diarrhea, vomiting), endocrine, etc. Cats may demonstrate the following adverse effects: sedation, hypersalivation, urinary retention, anorexia, thrombocytopenia, neutropenia, unkempt hair coat, vomiting, ataxia, dis-orientation and cardiac conductivity disturbances.

Reproductive / Nursing Safety

Isolated reports of limb reduction abnormalities have been noted; restrict use to pregnant animals only when the benefits clearly outweigh the risks. In humans, the FDA categorizes this drug as category D for use during pregnancy (There is evidence of human fetal risk, hut the potential benefits from the use of the drug in pregnant women may he acceptable despite its potential risks.)

Overdosage / Acute Toxicity

Overdosage with tricyclics can be life-threatening (arrhythmias, cardiorespiratory collapse). Because the toxicities and therapies for treatment are complicated and controversial, it is recommended to contact a poison control center for further information in any potential overdose situation.

There were 25 exposures to amitriptyline reported to the ASPCA Animal Poison Control Center (APCC; www.apcc.aspca.org) during 2005-2006. In these cases, 21 were cats with 5 showing clinical signs. Common findings recorded in decreasing frequency included: anorexia, mydriasis and adipsia. The remaining 4 cases were dogs with no reported clinical signs.

How to use Amitriptyline HCL

Amitriptyline HCL dosage for dogs:

For adjunctive treatment of pruritus:

a) 1-2 mg/kg PO q12h ()

b) For acral pruritic dermatitis: 2.2 mg/kg PO twice daily; only occasionally effective. A 2-4 week trial is recommended ()

For behavior disorders amenable to tricyclics:

a) For separation anxiety or generalized anxiety: 1-2 mg/kg PO q12h; with behavior modification ()

b) 1-4 mg/kg PO q12h. Begin at 1-2 mg/kg PO q12h for 2 weeks, increase by 1 mg/kg up to maximum dosage (4 mg/ kg) as necessary. If no clinical response, decrease by 1 mg/kg PO q12h for 2 weeks until at initial dosage. ()

c) 2.2-4.4 mg/kg PO q12h ()

d) 0.25-1.5 mg/kg PO every 12-24h ()

For neuropathic pain:

a) 1-2 mg/kg PO ql2-24h ()

b) For adjunctive treatment of pain associated with appendicular osteosarcoma: 1-2 mg/kg PO ql2-24h ()

Amitriptyline HCL dosage for cats:

For adjunctive treatment of behavior disorders amenable to tricyclics:

a) 5-10 mgper cat PO once daily ()

b) 0.5-2 mg/kg PO ql2-24h; start at 0.5 mg/kg PO q12h ()

c) 0.5-1 mg/kg PO ql2-24h ()

d) 0.5-1 mg/kg PO ql2-24h. Allow 3-4 weeks for initial trial. ()

For self-mutilation behaviors associated with anxiety:

a) 5-10 mg per cat PO once to twice daily; with behavior modification ()

b) 1-2 mg/kg PO q12h ()

For pruritus (after other more conventional therapies have failed):

a) 5-10 mg per cat PO once daily or 2.5-7.5 mg/cat once to twice daily. When discontinuing, taper dose over 1-3 weeks. ()

For symptomatic therapy of idiopathic feline lower urinary tract disease:

a) 2.5-12.5 mg (total dose) PO once daily at night ()

b) 5-10 mg (total dose) PO once daily at night; the drug is in popular use at present and further studies are needed ()

c) Reserved for cases with severe, recurrent signs; 2.5-12.5 mg (total dose) PO at the time the owner retires for the night. Dosage is adjusted to produce a barely perceptible calming effect on the cat. If no improvement is seen within 2 months, the medication may be gradually tapered and then stopped. ()

For neuropathic pain:

a) 2.5-12.5 mg/cat PO once daily ()

b) 0.5-2 mg/kg PO once daily; may be a useful addition to NSAIDs for chronic pain. ()

Amitriptyline HCL dosage for birds:

For adjunctive treatment of feather plucking:

a) 1-2 mg/kg PO ql2-24 hours. Anecdotal reports indicate some usefulness. Barring side effects, may be worth a more prolonged course of therapy to determine efficacy. ()

Monitoring

■ Efficacy

■ Adverse effects; it is recommended to perform a cardiac evaluation, CBC and serum chemistry panel prior to therapy

■ For cats, some clinicians recommend that liver enzymes be measured prior to therapy, one month after initial therapy, and yearly, thereafter

Client Information

■ All tricyclics should be dispensed in child-resistant packaging and kept well away from children or pets.

■ Several weeks may be required before efficacy is noted and to continue dosing as prescribed. Do not abruptly stop giving medication without veterinarian’s advice.

Chemistry / Synonyms

A tricyclic dibenzocycloheptene-derivative antidepressant, amitriptyline HCL occurs as a white or practically white, odorless or practically odorless crystalline powder that is freely soluble in water or alcohol. It has a bitter, burning taste and a pKa of 9.4.

Amitriptyline may also be known as amitriptylini hydrochloridum; many trade names are available.

Storage / Stability

Amitriptyline tablets should be stored at room temperature. The injection should be kept from freezing and protected from light.

Dosage Forms / Regulatory Status

Veterinary-Labeled Products: None

The ARCI (Racing Commissioners International) has designated this drug as a class 2 substance. See the appendix for more information.

Human-Labeled Products:

Amitriptyline HCL Tablets: 10,25, 50, 75,100,150 mg; generic; (Rx)

There are also fixed dose oral combination products containing amitriptyline and chlordiazepoxide, and amitriptyline and perphenazine.