Alprazolam (Xanax)

By | 2013-06-08

Benzodiazepine Sedative / Tranquilizer

Highlights Of Prescribing Information

Oral benzodiazepine that may be useful for unwanted behaviors in dogs or cats

Contraindications: Aggressive animals (controversial), benzodiazepine hypersensitivity

Caution: Hepatic or renal disease

Adverse Effects: Sedation, behavior changes, & contradictory responses; physical dependence is a possibility; may impede training

C-IV controlled substance

What Is Alprazolam Used For?

Alprazolam may be useful for adjunctive therapy in anxious, aggressive dogs or in those demonstrating panic reactions. (Note: Some clinicians believe that benzodiazepines are contraindicated in aggressive dogs as anxiety may actually restrain the animal from aggressive tendencies). It may be useful in cats to treat anxiety disorders.

Alprazolam may have less effect on motor function at low doses than does diazepam.


Subcortical levels (primarily limbic, thalamic, and hypothalamic) of the CNS are depressed by alprazolam and other benzodiazepines thus producing the anxiolytic, sedative, skeletal muscle relaxant, and anticonvulsant effects seen. The exact mechanism of action is unknown, but postulated mechanisms include: antagonism of serotonin, increased release of and/or facilitation of gamma-aminobutyric acid (GABA) activity, and diminished release or turnover of acetylcholine in the CNS. Benzodiazepine specific receptors have been located in the mammalian brain, kidney, liver, lung, and heart. In all species studied, receptors are lacking in the white matter.


The pharmacokinetics of alprazolam have not been described for either dogs or cats. In humans, alprazolam is well absorbed and is characterized as having an intermediate onset of action. Peak plasma levels occur in 1-2 hours.

Alprazolam is highly lipid soluble and widely distributed throughout the body. It readily crosses the blood-brain barrier and is somewhat bound to plasma proteins (80%).

Alprazolam is metabolized in the liver to at least two metabolites, including alpha-hydroxyalprazolam which is pharmacologically active. Elimination half-lives range from 6-27 hours in people.

Before you take Alprazolam

Contraindications / Precautions / Warnings

Some clinicians believe that benzodiazepines are contraindicated in aggressive dogs as anxiety may actually restrain the animal from aggressive tendencies. This remains controversial. Alprazolam is contraindicated in patients with known hypersensitivity to the drug. Use cautiously in patients with hepatic or renal disease, narrow angle glaucoma and debilitated or geriatric patients. Benzodiazepines may impair the abilities of working animals.

Adverse Effects

Benzodiazepines can cause sedation, increased appetite, and transient ataxia. Cats may exhibit changes in behavior (irritability, increased affection, depression, aberrant demeanor) after receiving benzodiazepines.

Dogs may rarely exhibit a contradictory response (CNS excitement) following administration of benzodiazepines.

Chronic usage of benzodiazepines may induce physical dependence. Animals appear to be less likely than humans to develop physical dependence.

Benzodiazepines may impede the ability of the animal to learn and may retard training.

Reproductive / Nursing Safety

Diazepam and other benzodiazepines have been implicated in causing congenital abnormalities in humans if administered during the first trimester of pregnancy. Infants born of mothers receiving large doses of benzodiazepines shortly before delivery have been reported to suffer from apnea, impaired metabolic response to cold stress, difficulty in feeding, hyperbilirubinemia, hypotonia, etc. Withdrawal symptoms have occurred in infants whose mothers chronically took benzodiazepines during pregnancy. The veterinary significance of these effects is unclear, but the use of these agents during the first trimester of pregnancy should only occur when the benefits clearly outweigh the risks associated with their use. 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

When administered alone, alprazolam overdoses are generally limited to significant CNS depression (confusion, coma, decreased reflexes, etc.). Hypotension, respiratory depression, and cardiac arrest have been reported in human patients but apparently, are quite rare. The reported LD50 in rats for alprazolam is >330 mg/kg, but cardiac arrest occurred at doses as low as 195 mg/kg.

There were 935 exposures to alprazolam reported to the ASPCA Animal Poison Control Center (APCC; during 2005-2006. In these cases 863 were dogs with 208 showing clinical signs, 63 were cats with 20 showing clinical signs, 3 were rodents with 1 reported as having clinical signs, and 2 cases were rabbits with 1 reported as having clinical signs. Common findings in dogs recorded in decreasing frequency included ataxia, lethargy, hyperactivity, disorientation, depression. Common findings in cats recorded in decreasing frequency included ataxia disorientation, sedation, hyperactivity and restlessness. Common findings in rodents recorded in decreasing frequency included ataxia, somnolence and vomiting. Common findings in lagomorphs recorded in decreasing frequency included ataxia and lethargy.

Treatment of acute toxicity consists of standard protocols for removing and/or binding the drug in the gut if taken orally and supportive systemic measures. Flumazenil (see separate monograph) may be employed to reverse the sedative effects of alprazolam, but only if the patient has significant CNS or respiratory depression. Seizures may be precipitated in patients physically dependent. The use of analeptic agents (CNS stimulants such as caffeine) is generally not recommended.

How to use Alprazolam

Alprazolam dosage for dogs:

a) For treatment of canine anxiety disorders: 0.01-0.1 mg/kg PO as needed for panic, not to exceed 4 mg/dog/day. Start with 1-2 mg (total dose) for a medium-sized dog. ()

b) For separation anxiety: 0.25 mg-2 mg (total dose) once daily to three times daily PO. ()

c) For storm phobias: 0.02 – 0.4 mg/kg PO q4h as needed; helps to minimize impact of experiencing a severe storm ();

0.02 mg/kg PO as needed one hour before anticipated storm and every 4 hours as needed; used as an adjunct after behavior modification and prior clomipramine treatment (see clomipramine monograph for further information) ()

d) For phobias, night waking: 0.01-0.1 mg/kg or 0.25-2 mg (total dose) per dog PO q6- 12h PO ()

Alprazolam dosage for cats:

a) For treatment of feline anxiety disorders: 0.125-0.25 mg/kg PO q12h (Start at 0.125 mg/kg PO) ()

b) For refractory house soiling: 0.1 mg/kg or 0.125-0.25 mg (total dose) per cat PO q8- 12h ()

c) For urine marking: 0.05-0.2 mg/kg PO ql2-24h ()

d) For fears/phobias/anxieties: 0.125-0.25 mg (total dose) PO once to three times a day. ()


■ Efficacy

■ Adverse Effects

■ Consider monitoring hepatic enzymes particularly when treating cats chronically

Client Information

■ Try to dose approximately one hour in advance of storms or other anticipated stimuli that evokes negative responses

■ If difficulty with pilling the medication occurs, consider using the orally-disintegrating tablets; hands must be dry before handling

■ If excessive sedation or yellowing of the whites of eyes (especially in cats) occurs, contact veterinarian

Chemistry / Synonyms

A benzodiazepine, alprazolam occurs as a white to off-white, crystalline powder. It is soluble in alcohol and insoluble in water.

Alprazolam may also be known as D65 MT, U 31889, or alprazolamum; many trade names available internationally.

Storage / Stability

Alprazolam tablets should be stored at room temperature in tight, light-resistant containers. The orally disintegrating tablets should be stored at room temperature and protected from moisture.

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:

Alprazolam Tablets: 0.25 mg, 0.5 mg, 1 mg & 2 mg; Xanax (Pfizer); generic; (Rx; C-IV)

Alprazolam Extended-release Tablets: 0.5 mg, 1 mg, 2 mg, & 3 mg; Xanax XR (Pfizer); generic; (Rx; C-IV)

Alprazolam Orally Disintegrating Tablets: 0.25 mg, 0.5 mg, 1 mg, & 2 mg; Niravam (Pfizer); (Rx; C-IV)

Alprazolam Oral Solution: 1 mg/mL in 30 mL; Alprazolam Inten-sol (Roxane); (Rx; C-IV)