Tolazoline HCl CAS NO 59-97-2 Inquire about Tolazoline HCl 

Tecoland supplies Tolazoline HCl bulk active pharmaceutical ingredient (API) to the pharmaceutical industry. Our Tolazoline HCl is manufactured by cGMP compliant facility. Welcome to contact us for further details including current DMF status for the product and up to date regulatory status of the manufacturing facility. We look forward to assisting you with your research and development projects.

Category:

Antihypertensive (pulmonary)—

Indications

Note: Products containing tolazoline were withdrawn from the U.S. market by Novartis in July 2002. {17}

Accepted

Hypertension, persistent pulmonary (treatment)— Tolazoline is indicated in the treatment of persistent pulmonary hypertension in the newborn (persistent fetal circulation) when systemic arterial oxygenation cannot be maintained by supplemental oxygen and/or mechanical ventilation. {01}

Unaccepted
Tolazoline is not considered to be effective for previously labeled indications, which included spastic peripheral vascular disorders.

Pharmacology/Pharmacokinetics

Physicochemical characteristics:
Molecular weight—
196.68 {01} {04}

pKa—
10.5 {09}

Mechanism of action/Effect:

Vasodilation by means of a direct effect on peripheral vascular smooth muscle and indirect effects produced, in part, by release of endogenous histamine {12}; tolazoline has moderate alpha-adrenergic blocking activity and has histamine agonist activity. {01} {06} Tolazoline usually reduces pulmonary arterial pressure and vascular resistance. {01}

Other actions/effects:

Sympathomimetic (cardiac stimulation, both inotropic and chronotropic); parasympathomimetic (stimulation of gastrointestinal tract that is blocked by atropine); histamine-like (stimulation of gastric secretion). {01}

Half-life:

Neonates—3 to 10 hours; {01} {08} however, reportedly as long as 40 hours, varying inversely with urine flow. {05}

Onset of action:

Within 30 minutes after initial dose. {01}

Elimination:
Renal, primarily unchanged. {05}

Precautions to Consider

Carcinogenicity

Studies have not been done in either humans or animals.

Pregnancy/Reproduction

Pregnancy—
Studies have not been done in humans. {01}

Studies in fetal sheep have shown that tolazoline crosses the placenta. Following maternal tolazoline infusions in sheep, fetal tolazoline concentrations averaged 20% of maternal concentrations. {14}

FDA Pregnancy Category C. {01}

Breast-feeding

It is not known whether tolazoline is excreted in breast milk. {01} However, problems in humans have not been documented.

Geriatrics

No information is available on the relationship of age to the effects of tolazoline in geriatric patients.

Drug interactions and/or related problems
The following drug interactions and/or related problems have been selected on the basis of their potential clinical significance (possible mechanism in parentheses where appropriate)—not necessarily inclusive (» = major clinical significance):

Note: Combinations containing any of the following medications, depending on the amount present, may also interact with this medication.

Dopamine (tolazoline antagonizes the peripheral vasoconstriction produced by high doses of dopamine)

Ephedrine (alpha-adrenergic blocking agents such as tolazoline may decrease the pressor response to ephedrine)

Epinephrine or
Norepinephrine (concurrent use with large doses of tolazoline may cause a paradoxical reduction in blood pressure followed by an exaggerated rebound increase; these medications are not recommended for treatment of tolazoline overdose)

Metaraminol (concurrent use with tolazoline usually decreases, but does not reverse or completely block, the pressor effect of metaraminol)

Methoxamine or
Phenylephrine (prior administration of tolazoline may block the pressor response to methoxamine or phenylephrine, possibly resulting in severe hypotension)

Laboratory value alterations
The following have been selected on the basis of their potential clinical significance (possible effect in parentheses where appropriate)—not necessarily inclusive (» = major clinical significance):

With physiology/laboratory test values
Blood pressure (may be increased or decreased, depending on the relative contribution of cardiac-stimulating effects and peripheral vasodilation; pulmonary arterial pressure is usually reduced)

Medical considerations/Contraindications
The medical considerations/contraindications included have been selected on the basis of their potential clinical significance (reasons given in parentheses where appropriate)— not necessarily inclusive (» = major clinical significance).

Except under special circumstances, this medication should not be used when the following medical problem exists:
» Hypotension, systemic (may be exacerbated)

Risk-benefit should be considered when the following medical problems exist
Acidosis (increases pulmonary vasoconstriction; effect of tolazoline may be decreased; should be corrected before initiation of tolazoline therapy)

» Mitral stenosis (parenteral tolazoline may cause an increase or decrease in pulmonary artery pressure and total pulmonary resistance)

» Renal function impairment, reduced urine flow (decreases tolazoline elimination; may require dosage reduction {05})

Sensitivity to tolazoline

Patient monitoring
The following may be especially important in patient monitoring (other tests may be warranted in some patients, depending on condition; » = major clinical significance):

Blood counts, complete, and
» Blood gases (PO 2, PCO 2), arterial, and
Blood pH, arterial, and
Blood pressure, arterial, and
Electrocardiogram (ECG) and
Electrolyte concentrations, serum, especially chloride and potassium, and
Heart rate (recommended at regular intervals throughout tolazoline treatment)

(if adequate systolic blood pressure cannot be maintained, tolazoline should be withdrawn)

(if hypochloremic metabolic alkalosis occurs, patient should be weaned from tolazoline therapy and replacement chloride and potassium administered)

Hematest of gastric aspirates (recommended at periodic intervals to detect gastrointestinal bleeding)

Renal function, including urine flow, determinations (recommended periodically during tolazoline therapy {16})

Side/Adverse Effects
The following side/adverse effects have been selected on the basis of their potential clinical significance (possible signs and symptoms in parentheses where appropriate)—not necessarily inclusive:

Those indicating need for medical attention
Incidence more frequent

Gastrointestinal hemorrhage{01}{07} —detected by hematest of gastric aspirates; may be fatal

hypochloremic alkalosis —secondary to gastric hypersecretion{01}

systemic hypotension{01}{07}

acute renal failure, especially oliguria{01}{07}

thrombocytopenia{01}{07}

Note: Hypotension may be very common in neonates; may occur suddenly in some cases. {15}

Incidence less frequent

Diarrhea or nausea and vomiting{01}

increased pilomotor activity (goose flesh)

peripheral vasodilation (flushing)

tachycardia{01}

Note: Tachycardia is a reflex response to vasodilation and a result of direct cardiac stimulation.

Incidence rare

Mydriasis{02}

General Dosing Information
See also Patient monitoring.

It is recommended that tolazoline be administered in an area with trained personnel and facilities necessary to provide pediatric or neonatal intensive care. Respiratory support should be immediately available.

To achieve optimal dosage control, it is recommended that tolazoline be administered intravenously by means of an infusion pump, a micro-drip regulator, or a similar device to allow precise adjustment of the flow rate.

Pretreatment with antacids may prevent gastrointestinal bleeding in infants.

For treatment of adverse effects and/or overdose
Hypotension is treated by:

• Keeping the patient’s head low and administering intravenous fluids.
• Use of epinephrine or norepinephrine is not recommended because of the risk of a further decrease in blood pressure followed by an exaggerated rebound increase.
• If fluid expansion fails to maintain blood pressure, an intravenous dopamine infusion (high doses may be needed to obtain adequate vasoconstrictor effect) may be used simultaneously with the tolazoline infusion. {11} {12} {13}

Parenteral Dosage Forms

TOLAZOLINE HYDROCHLORIDE INJECTION USP

Usual pediatric dose
Antihypertensive (pulmonary)

Initial:
Intravenous, 1 to 2 mg per kg of body weight via scalp vein {01} over a five- to ten-minute period.

Note: Alternatively, the initial dose may be infused into any vein that drains into the superior vena cava to maximize delivery to the pulmonary artery. {15} {16}

Maintenance:
Intravenous infusion, 0.2 mg (200 mcg) per kg of body weight per hour for each 1 mg per kg of body weight loading dose. {12} {13} May be withdrawn gradually when arterial blood gases remain stable.

Note: If necessary, the initial bolus dose may be repeated during the maintenance infusion {03}.
A decreased infusion rate may be necessary in patients with renal tubular dysfunction and oliguria less than 0.9 mL per kg of body weight per hour. {12}

Strength(s) usually available
U.S.—
Not commercially available.{17}

Canada—
Not commercially available.

Packaging and storage:
Store below 40 °C (104 °F), preferably between 15 and 30 °C (59 and 86 °F), unless otherwise specified by manufacturer. Protect from light (according to manufacturer’s labeling).

Preparation of dosage form:
Caution—Use of diluents containing benzyl alcohol is not recommended for preparation of medications for use in neonates. A fatal toxic syndrome consisting of metabolic acidosis, central nervous system (CNS) depression, respiratory problems, renal failure, hypotension, and possibly seizures and intracranial hemorrhages has been associated with the use of benzyl alcohol.

Disclaimer:

Information on this page is provided for general information purposes. You should not make a clinical treatment decision based on information contained in this page without consulting other references including the package insert of the drug, textbooks and where relevant, expert opinion. We cannot be held responsible for any errors you make in administering drugs mentioned on this page, nor for use of any erroneous information contained on this page.

External Link

Tolazoline (Parenteral-Systemic). (n.d.). Drugs.Com. https://www.drugs.com/mmx/tolazoline-hydrochloride.html