Tolazine (Tolazoline HCl) Injection

By | 2016-03-15

TOLAZOLINE HCL (Tolazine)

ALPHA- ADRENERGIC BLOCKER

Highlights of Prescribing Information

  • Alpha-adrenergic blocker used primarily as a reversal agent for xylazine
  • Contraindications: Horses exhibiting signs of stress, debilitation, cardiac disease, sympathetic blockage, hypovolemia or shock, hypersensitivity, or with coronary artery or cerebrovascular disease
  • Adverse Effects: HORSES: Transient tachycardia; peripheral vasodilatation presenting as sweating & injected mucous membranes of the gingiva & conjunctiva; hyperalgesia of the lips (licking, flipping of lips); piloerection; clear lacrimal & nasal discharge; muscle fasciculations; apprehensiveness

What Is Drug Used For?

Tolazoline is approved and indicated for the reversal of effects associated with xylazine in horses. It has also been used for this purpose in a variety of other species as well, but less safety and efficacy data is available.

In humans, the primary uses for tolazoline are: treatment of persistent pulmonary hypertension in newborns, adjunctive treatment and diagnosis of peripheral vasospastic disorders, and as a provocative test for glaucoma after subconjunctival injection.

Pharmacology / Actions

By directly relaxing vascular smooth muscle, tolazoline has peripheral vasodilating effects and decreases total peripheral resistance. Tolazoline also is a competitive alphai and alpha2-adrenergic blocking agent, explaining its mechanism for reversing the effects of xylazine. Tolazoline is rapid acting (usually within 5 minutes of IV administration), but has a short duration of action and repeat doses maybe required.

Pharmacokinetics

After IV injection in horses, tolazoline is widely distributed. Animal studies have demonstrated that tolazoline is concentrated in the liver and kidneys. Half-life in horses at recommended doses is approximately 1 hour.

Before you take Drug

Contraindications / Precautions / Warnings

The manufacturer does not recommend use in horses exhibiting signs of stress, debilitation, cardiac disease, sympathetic blockage, hypovolemia, or shock. Safe use for foals has not been established and some believe it should not be used in foals, as adverse reactions and fatalities have been reported.

Tolazoline should be considered contraindicated in patients known to be hypersensitive to it, or with coronary artery or cerebrovascular disease. Humans having any of the above-contraindicated conditions should use extra caution when handling the agent.

Adverse Effects

In horses adverse effects that may occur include: transient tachycardia; peripheral vasodilatation presenting as sweating and injected mucous membranes of the gingiva and conjunctiva; hyperalgesia of the lips (licking, flipping of lips); piloerection; clear lacrimal and nasal discharge; muscle fasciculations; apprehensiveness. Adverse effects should diminish with time and generally disappear within 2 hours of dosing. The potential for adverse effects increases if tolazoline is given at higher than recommended dosages or if xylazine has not be previously administered.

Reproductive / Nursing Safety

Safety during pregnancy, in breeding or lactating animals has not been established. It is unknown if the drug enters maternal milk.

Overdosage / Acute Toxicity

In horses given tolazoline alone (no previous xylazine), doses of 5X recommended resulted in gastrointestinal hypermotility with resultant flatulence and defecation or attempt to defecate. Some horses exhibited mild colic and transient diarrhea. Intraventricular conduction may be slowed when horses are overdosed, with a prolongation of the QRS-complex noted. Ventricular arrhythmias may occur resulting in death with higher overdoses (5X). In humans, ephedrine (NOT epinephrine or norepinephrine) has been recommended to treat serious tolazoline-induced hypotension.

A llama that received 4.3 mg/kg IV and again 45 minutes later (approximately a 5X overdose) developed signs of anxiety, hyperesthesia, profuse salivation, GI tract hypermotility, diarrhea, convulsions, hypotension, and tachypnea. Treatment including IV diazepam, phenylephrine, IV fluids, and oxygen was successful. ().

Drug Interactions

The following drug interactions have either been reported or are theoretical in humans or animals receiving tolazoline and may be of significance in veterinary patients:

■ ALCOHOL: Accumulation of acetaldehyde can occur if tolazoline and alcohol are given simultaneously

■ EPINEPHRINE, NOREPINEPHRINE: If large doses of tolazoline are given with either norepinephrine or epinephrine, a paradoxical drop in blood pressure can occur followed by a precipitous increase in blood pressure

How to use Drug

Drug dosage for horses:

For reversal of xylazine effects:

  1. a) 4 mg/kg slow IV (4 mL/220 lb. of body weight); administration rate should approximate 1 mL/second (Package Insert; Tolazine — Lloyd Laboratories)

Drug dosage for dogs & cats:

For reversal of xylazine effects:

  1. a) 4 mg/kg slow IV (4 mL/220 lb. of body weight); administration rate should approximate 1 mL/second (Package Insert; Tolazine — Lloyd Laboratories; New Zealand) Note: If reversal is warranted, the high concentration (100 mg/mL) of the veterinary drug may make accurate dosing difficult; yohimbine or the human-labeled tolazoline product (25 mg/mL) maybe safer alternatives than Tolazine (100 mg/mL). Note: Tolazoline is not approved for use in dogs and cats in the USA and the US manufacturer does not recommend its use

Drug dosage for llamas/alpacas:

For reversal of xylazine/ketamine effects:

  1. a) 2 mg/kg IM ()
  2. b) 1-2 mg/kg IV or IM; Caution: acute death has been reported after rapid IV administration of tolazoline at high dosages. ()

Drug dosage for birds:

As a reversal agent for alpha2-adrenergic agonists (e.g., xylazine, detomidine, etc.):

  1. a) 15 mg/kg IV ()

Drug dosage for deer:

Note: Not approved in the USA for use in food animals

For reversal of xylazine effects:

  1. a) 2-4 mg/kg slow IV; titrate to effect; Slaughter withdrawal: 30 days (Label Directions; Tolazine — Lloyd Laboratories; New Zealand)

Drug dosage for cattle:

Note: Not approved in the USA for use in food animals

For reversal of xylazine effects:

  1. a) 2-4 mg/kg slow IV; titrate to effect; Slaughter withdrawal: 30 days (Label Directions; Tolazine — Lloyd Laboratories; New Zealand)

Drug dosage for sheep and goats:

Note: Not approved in the USA for use in food animals For reversal of xylazine effects:

  1. a) 2-4 mg/kg slow IV; titrate to effect; Slaughter withdrawal: 30 days (Label Directions; Tolazine — Lloyd Laboratories; New Zealand)
  2. b) Goats: 1-2 mg/kg IV, inject slowly to effect ()
  3. c) Sheep: 2.2 mg/kg slowly IV ()

Monitoring/Client Information

■ Reversal effects (efficacy)

■ Adverse effects (see above). Because of the risks associated with the use of xylazine and reversal by tolazoline, these drugs should be administered and monitored by veterinary professionals only.

Chemistry / Synonyms

An alpha-adrenergic blocking agent, tolazoline HCl is structurally related to phentolamine. It occurs as a white to off-white, crystalline powder possessing a bitter taste and a slight aromatic odor. Tolazoline is freely soluble in ethanol or water. The commercially available (human) injection has pH between 3-4.

Tolazoline HCl may also be known as: benzazoline hydrochlo-ride, tolazolinium chloratum, Priscol, Priscoline, Tolazine or Vaso-Dilatan.

Storage / Stability / Compatibility

Commercially available injection products should be stored between 15-30°C and protected from light. The drug is reportedly physically compatible with the commonly used IV solutions.

Dosage Forms / Regulatory Status

Veterinary-Labeled Products:

Tolazoline HCl Injection: 100 mg/mL in 100 mL multi-dose vials; Tolazine* (Lloyd); (Rx). Approved for use in horses; not to be used in food-producing animals.

Human-Labeled Products: None

 

Plumb’s Veterinary Drug Handbook. 2008