Phentolamine

- 10mg/1ml ampules (subcutaneous)
- 5mg lyophilized powder (subcutaneous)

Emergency Medicine Executive Summary

(Extended Version, Updated July 2021)

Phentolamine is a vasodilator used to prevent tissue necrosis caused by extravasated catecholamine infusions (epinephrine, norepinephrine, dopamine, etc). Available in the US. Limited stock in Canada. Unavailable in Chile.

  • Adult dose:
    5-10mg diluted in 10-20ml of NaCl 0.9% subcutaneous immediately after extravasation (use within 12 hours).

Mechanism of Action and Usage

Mechanism of Action

Phentolamine is a potent and short-acting non-selective alpha blocker (alpha-1 and alpha-2). Alpha-1 blockade reduces peripheral resistance, and alpha-2 blockade causes cardiac stimulation due to an enhanced release of norepinephrine from sympathetic nerves, with subsequent inotropic and chronotropic effects.

Usage
It is used to prevent tissue ischemia caused by extravasation of norepinephrine and other alpha agonists (1, 3), obtaining the FDA approval in 1998 (2). From the safety patient perspective it is recommended to have an extravasation protocol in the hospital services where vasopressors are used (3), and in retrospective studies phentolamine use is associated with favorable outcomes (4, 5). It is also indicated to diagnose pheochromocytoma disease and to prevent and treat pheochromocytoma-related hypertensive crises (1).

Adult dose

Injection site vasopressor extravasation

Phentolamine 5 to 10mg in 10mL of normal saline, subcutaneous within 12 hours into the area of extravasation. Any visible hyperemia and increased tissue warmth at the site of extravasation are signs of effective treatment.

Pediatric dose

Injection site vasopressor extravasation

  • Infants, children and adolescents: Infiltrate the area with 1 to 5 mL (in 5 divided doses) of a 0.5 to 1 mg/mL solution (made by diluting 5 to 10 mg in 10 mL 0.9% Sodium Chloride injection). Inject into the affected area within 12 hours of extravasation. Do not exceed 0.1 to 0.2 mg/kg or 5 mg total.

  • Neonates: Infiltrate the area with 1 mL of solution made by diluting 2.5 to 5 mg in 10 mL of 0.9% Sodium Chloride injection. Give 5 divided doses subcutaneously around the site. Inject into the affected area within 12 hours of extravasation. Do not exceed 0.1 mg/kg or 2.5 mg total.

Renal, hepatic, or other adjustments

No adjustments required.

Dosage Forms and brand names

  • Phentolamine mesylate (US): 5mg lyophilized powder

  • Rogitine® (Canada): 10mg/1ml ampules

Contraindications, Adverse effects, Warnings, and Major drug interactions

The following issues of concern are related mostly to endovenous administration of phentolamine. Consider that subcutaneous use in extravasation is intended to cause local effects rather than systemic effects. The following issues of concern are related to IV administration.

  • Contraindications: hypersensitivity to drug or related compounds, acute or chronic coronary artery disease.

  • Adverse effects: hypotension, tachycardia, dysrhythmias.

  • Warnings: myocardial infarction and cerebrovascular spasms usually in association with marked hypotensive episodes have been reported.

  • Major drug interactions: enhance effect with other alpha blockers (urapidil), and diminish effect with alpha agonists. Caution when combined with other antihypertensive or vasodilator medications.

Pregnancy and Lactation

Consider that subcutaneous use in extravasation is intended to cause local effects rather than systemic effects, with an hypothetical low risk for the fetus or infant.

  • Pregnancy Risk Factor Category (FDA): C.

  • Lactation: not known if excreted in milk.

Pharmacology

Alpha-adrenergic block of relatively short duration. Also direct but less marked positive inotropic and chronotropic effects. The pharmacokinetics of phentolamine are largely unknown.


Following specifications are not applicable to subdermic administration:

  • Onset of action: 1-2 min IV, 15-20 min IM.

  • Half-life elimination: 19 minutes IV.

  • Time to peak, plasma: unknown.

References

  1. NIH-NLM (National Institutes of Health National Library of Medicine). DailyMed. Label: Phentolamine mesylate injection, powder, for solution. Updated in december 2018. Visited in July 2021.
    DailyMed

  1. FDA (United States Food and Drug Administration), CDER (Center for Drug Evaluation and Research), Application Number 40235, Phentolamine Mesylate for Injection USP 5mg/vial, Bedford Laboratories, march 1998. Visited in July 2021.
    US-FDA

  1. Lewis T, Merchan C, Altshuler D, Papadopoulos J. Safety of the Peripheral Administration of Vasopressor Agents. J Intensive Care Med. 2019;34(1):26-33. doi:10.1177/0885066616686035.
    Pubmed

  1. Cardenas-Garcia J, Schaub KF, Belchikov YG, Narasimhan M, Koenig SJ, Mayo PH. Safety of peripheral intravenous administration of vasoactive medication. J Hosp Med. 2015;10(9):581-585. doi:10.1002/jhm.2394.
    Pubmed

  1. Pancaro C, Shah N, Pasma W, et al. Risk of Major Complications After Perioperative Norepinephrine Infusion Through Peripheral Intravenous Lines in a Multicenter Study. Anesth Analg. 2020;131(4):1060-1065. doi:10.1213/ANE.0000000000004445.
    Pubmed

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