Extravasation of norepinephrine, management: Local infiltration: Inject 5 to 10 mg (diluted in 10 mL 0.9% sodium chloride) into extravasation area (as soon as possible after extravasation is noted but within 12 hours of extravasation).
Extravasation of other sympathomimetic vasopressors, management (off-label use): Infiltrate extravasation site with 5 to 10 mg diluted in 10 to 20 mL 0.9% sodium chloride as soon as possible after extravasation; may readminister if patient remains symptomatic (Reynolds 2014).
Diagnosis of pheochromocytoma (phentolamine-blocking test): Note: The phentolamine-blocking test for the diagnosis of pheochromocytoma has largely been supplanted by the measurement of catecholamine concentrations and catecholamine metabolites (eg, metanephrine) in the plasma and urine; reserve phentolamine for cases when additional confirmation is necessary to determine diagnosis: IM, IV: 5 mg
Perioperative hypertensive episodes associated with pheochromocytoma, prevention and management: Note: In the perioperative period, the use of other agents may be preferred due to slow onset of action and prolonged duration of phentolamine in comparison to the other agents (eg, nitroprusside) (Miller 2010).
Preoperative: IM, IV: 5 mg given 1 to 2 hours before surgery and repeat if needed.
Intraoperative: IV: Administer 5 mg as indicated to prevent or control paroxysms of hypertension, tachycardia, respiratory depression, seizure, or other effects associated with epinephrine intoxication resulting from tumor manipulation or other stressor (eg, intubation). In practice, others have used intraoperative continuous infusion of 1 to 6 mcg/kg/minute or intermittent boluses of 10 mg, as indicated, to control blood pressure (Yu 2018).
Hypertensive crisis (off-label use): Note: Generally used in the setting of catecholamine excess (eg, pheochromocytoma) (Marik 2007): IV: 1 to 5 mg bolus; maximum single dose: 15 mg. A continuous infusion may be administered after initial bolus dosing (eg, 1 mg/hour titrated to blood pressure response) to a maximum infusion rate of 40 mg/hour (McMillian 2011).
Reversal of oral soft tissue (lip, tongue) anesthesia (OraVerse): Infiltration or block technique: Submucosal oral injection: Note: Dose is based upon the number of cartridges of local anesthetic administered. Infiltration or block injection:
0.1 mg if one-quarter cartridge of anesthesia was administered
0.2 mg if one-half cartridge of anesthesia was administered
0.4 mg if 1 cartridge of anesthesia was administered
0.8 mg if 2 cartridges of anesthesia were administered
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
There are no dosage adjustments provided in the manufacturer’s labeling.
There are no dosage adjustments provided in the manufacturer’s labeling.
(For additional information see "Phentolamine: Pediatric drug information")
Diagnosis of pheochromocytoma (phentolamine blocking test): Note: The phentolamine-blocking test for the diagnosis of pheochromocytoma has largely been supplanted by the measurement of catecholamine concentrations and catecholamine metabolites (eg, metanephrine) in the plasma and urine; reserve phentolamine for cases when additional confirmation is necessary to determine diagnosis.
Children and Adolescents:
IM: 3 mg.
IV: 1 mg.
Extravasation of sympathomimetic vasopressors (eg, dopamine, epinephrine, norepinephrine, phenylephrine), treatment: Limited data available for infants:
Infants, Children, and Adolescents: SUBQ: Infiltrate area of extravasation with a small amount (eg, 1 mL given in 0.2 mL aliquots) of a 0.5 to 1 mg/mL solution within 12 hours of extravasation (Flemmer 1993; Hackenberg 2021; Hill 1991; MacCara 1983; Montgomery 1999; Park 2021; manufacturer's labeling). Total dose required depends on the size of extravasation; dose may be repeated if required. When reported, the total dose needed was 1 to 5 mL of a 1 mg/mL solution; however, other concentrations could be used (Montgomery 1999).
Hypertensive episodes associated with pheochromocytoma, prevention and treatment: Note: In the perioperative period, the use of other agents may be preferred due to slow onset of action and prolonged duration of phentolamine in comparison to the other agents (eg, nitroprusside) (Kiefer 2020).
Preoperative: Children and Adolescents: IM, IV: 1 mg given 1 to 2 hours before surgery and repeat if needed.
Intraoperative:
Manufacturer's labeling: Children and Adolescents: IV: 1 mg as indicated to prevent or control paroxysms of hypertension, tachycardia, respiratory depression, seizure, or other effects associated with epinephrine intoxication resulting from tumor manipulation.
Alternate dosing: Limited data available: Infants, Children, and Adolescents: IV, IM: 0.05 to 0.1 mg/kg/dose, repeated every 5 minutes until hypertension is controlled, then every 2 to 4 hours as needed (Park 2021; Schure 2019). Note: Usual adult dose is 5 mg/dose (Park 2021).
Reversal of oral soft tissue (lip, tongue) anesthesia (OraVerse): Note: Dose is based upon the number of cartridge(s) of local anesthetic administered; location and administration technique (infiltration or block injection) should be the same as used for local anesthetic administration.
Children ≥3 years weighing ≥15 kg and Adolescents: Submucosal oral injection: Infiltration or block technique:
|
Amount of Local Anesthetic Administered |
Dose of OraVerse |
|
1/4 cartridge |
1/4 cartridge (0.1 mg) |
|
1/2 cartridge |
1/2 cartridge (0.2 mg) |
|
1 cartridge |
1 cartridge (0.4 mg) |
|
2 cartridges |
2 cartridges (0.8 mg) |
Maximum dose:
15 to <30 kg: 0.2 mg/dose.
≥30 kg: 0.8 mg/dose. Note: A dose of >0.4 mg has not been studied in children <4 years of age.
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
There are no dosage adjustments provided in manufacturer's labeling.
There are no dosage adjustments provided in manufacturer's labeling.
Refer to adult dosing.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling. [DSC] = Discontinued product
Solution, Injection, as mesylate [preservative free]:
OraVerse: 0.4 mg/1.7 mL (1.7 mL) [contains edetate disodium; dental cartridge]
Solution Reconstituted, Injection, as mesylate [preservative free]:
Generic: 5 mg (1 ea)
Yes
Extravasation management (treatment), sympathomimetic vasopressors: Stop vesicant infusion immediately and disconnect IV line (leave needle/cannula in place); gently aspirate extravasated solution from the IV line (do NOT flush the line); remove needle/cannula; elevate extremity. Inject small amounts of phentolamine 5 to 10 mg in 10 to 20 mL saline into extravasation site (as soon as possible but within 12 hours of extravasation). Apply dry warm compresses (Hurst 2004; Reynolds 2014).
Pheochromocytoma diagnosis: Patient should be supine throughout test, preferable in a quiet, dark room. Blood pressure should be monitored every 10 minutes for at least 30 minutes, delay phentolamine administration until after blood pressure is stable (at an untreated, hypertensive level). A drop in blood pressure >35 mm Hg (systolic) and >25 mm Hg (diastolic) is considered a positive response. If blood pressure is elevated, unchanged, or decrease is <35 mm Hg (systolic) and <25 mm Hg (diastolic), then response is negative. Confirm positive response with other diagnostic measure. Negative responses do not exclude a pheochromocytoma diagnosis, particularly in patients with paroxysmal hypertension where an incidence of false negatives is high.
IM: After IM injection, monitor blood pressure every 5 minutes for 35 to 40 minutes. Blood pressure drops to above parameters within 20 minutes are considered positive.
IV: Inject rapidly (after venous response to venipuncture has subsided); then monitor blood pressure immediately after injection, every 30 seconds for 3 minutes, then every minute for 7 minutes. Maximum response is generally achieved within 2 minutes; duration may last 15 to 30 minutes (although return to prior blood pressure may be sooner).
Pheochromocytoma-associated hypertensive episode: Administer IM or IV 1 to 2 hours prior to surgery and repeat during surgery (IV) if necessary.
Reversal of oral soft tissue (lip, tongue) anesthesia (OraVerse): Submucosal oral injection: Use the same location and dental technique employed for administration of the local anesthetic.
Hypertensive crisis (off-label use): Administer as an IV bolus (Marik 2007); may follow with a continuous IV infusion (McMillian 2011).
Parenteral: Route varies with indication.
Extravasation treatment: SUBQ: Stop vesicant infusion immediately and disconnect IV line (leave needle/cannula in place); gently aspirate extravasated solution from the IV line (do NOT flush the line); remove needle/cannula; elevate extremity. Infiltrate area of extravasation with multiple small injections of a diluted phentolamine solution (as soon as possible but within 12 hours of extravasation); use 25- or 30-gauge 1/2-inch needles; insert at a 15° angle, bevel up and change needle between each skin entry (Hill 1991; Siwy 1987) (see Management of Drug Extravasations). Apply dry warm compresses (Hurst 2004; Reynolds 2014).
Pheochromocytoma diagnosis (Phentolamine block test): Note: Patient should be supine throughout test, preferable in a quiet, dark room. Blood pressure should be monitored every 10 minutes for at least 30 minutes, delay phentolamine administration until after blood pressure is stable (at an untreated, hypertensive level).
IM: After IM injection, monitor blood pressure every 5 minutes for 35 to 40 minutes. Blood pressure drops to target parameters - within 20 minutes are considered positive (see Note).
IV: Inject rapidly (after venous response to venipuncture has subsided); then monitor blood pressure immediately after injection, every 30 seconds for 3 minutes, then every minute for 7 minutes. Maximum response is generally achieved within 2 minutes; duration may last 15 to 30 minutes (although return to prior blood pressure may be sooner).
Note: A drop in blood pressure >35 mm Hg systolic and >25 mm Hg diastolic is considered a positive response. If blood pressure is elevated, unchanged, or decrease is <35 mm Hg systolic and <25 mm Hg diastolic, then response is negative. Confirm positive response with other diagnostic measure. Negative responses do not exclude a pheochromocytoma diagnosis, particularly in patients with paroxysmal hypertension where an incidence of false negatives is high.
Pheochromocytoma-associated hypertensive episode: IM, IV: Administer 1 to 2 hours prior to surgery and repeat during surgery (as rapid IV injection) if necessary.
Reversal of oral soft tissue (lip, tongue) anesthesia (OraVerse): Submucosal oral injection: Use the same location and dental technique employed for administration of the local anesthetic.
Pheochromocytoma: Diagnosis of pheochromocytoma via the phentolamine-blocking test (see "Note"); prevention and management of hypertensive episodes associated with pheochromocytoma resulting from stress or manipulation during the perioperative period
Extravasation management: Prevention and treatment of dermal necrosis/sloughing after extravasation of norepinephrine
Local anesthesia reversal (OraVerse): Reversal of soft tissue (lip, tongue) anesthesia and the associated functional deficits resulting from an intraoral submucosal injection of a local anesthetic containing a vasoconstrictor in adult and pediatric patients ≥3 years.
Note: The phentolamine-blocking test for the diagnosis of pheochromocytoma has largely been supplanted by the measurement of catecholamine concentrations and catecholamine metabolites (eg, metanephrine) in the plasma and urine; reserve phentolamine for cases when additional confirmation is necessary to determine diagnosis.
Hypertensive crisis; Extravasation of sympathomimetic vasopressors
Phentolamine may be confused with phentermine, Ventolin
Regitine may be confused with Reglan
The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified. Frequency not always defined.
Cardiovascular: Bradycardia (OraVerse 2% to 4%), hypertension (OraVerse <3%), cerebrovascular occlusion, hypotension, myocardial infarction
Central nervous system: Mouth pain (OraVerse ≤19%), headache (OraVerse 6%), paresthesia (OraVerse <3%; mild, transient), cerebrovascular spasm
Dermatologic: Facial swelling (OraVerse <3%), pruritus (OraVerse <3%)
Gastrointestinal: Diarrhea (OraVerse <3%), upper abdominal pain (OraVerse <3%), vomiting (OraVerse <3%), nausea
Local: Pain at injection site (OraVerse 6%)
Neuromuscular & skeletal: Jaw pain (OraVerse <3%)
Miscellaneous: Postinjection pain (10%)
Postmarketing and/or case reports: Cardiac arrhythmia, dizziness, flushing, nasal congestion, orthostatic hypotension, weakness
Hypersensitivity to phentolamine, any component of the formulation, or related compounds; MI (or history of MI), coronary insufficiency, angina, or other evidence suggestive of coronary artery disease (excluding OraVerse)
Canadian labeling: Additional contraindications (not in the US labeling): Hypotension
Concerns related to adverse effects:
• Cardiovascular effects: MI, cerebrovascular spasm, and cerebrovascular occlusion have been reported following administration, usually associated with hypotensive episodes producing shock-like states. Tachycardia and cardiac arrhythmias may occur. Use with caution in patients with a history of cardiovascular disease. Discontinue if symptoms of angina occur or worsen.
Other warnings/precautions:
• Appropriate use: The use of phentolamine as a blocking agent in the screening of patients with hypertension has predominantly been replaced with urinary/biochemical assays; phentolamine use should be reserved for situations where additional confirmation is necessary and after risks associated with use have been considered.
None known.
Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the Lexicomp drug interactions program by clicking on the “Launch drug interactions program” link above.
Alpha-/Beta-Agonists: Alpha1-Blockers may diminish the vasoconstricting effect of Alpha-/Beta-Agonists. Similarly, Alpha-/Beta-Agonists may antagonize Alpha1-Blocker vasodilation. Risk C: Monitor therapy
Alpha1-Agonists: Alpha1-Blockers may diminish the vasoconstricting effect of Alpha1-Agonists. Similarly, Alpha1-Agonists may antagonize Alpha1-Blocker vasodilation. Risk C: Monitor therapy
Alpha1-Blockers: May enhance the antihypertensive effect of other Alpha1-Blockers. Risk X: Avoid combination
Amifostine: Blood Pressure Lowering Agents may enhance the hypotensive effect of Amifostine. Management: When used at chemotherapy doses, hold blood pressure lowering medications for 24 hours before amifostine administration. If blood pressure lowering therapy cannot be held, do not administer amifostine. Use caution with radiotherapy doses of amifostine. Risk D: Consider therapy modification
Amphetamines: May diminish the antihypertensive effect of Antihypertensive Agents. Risk C: Monitor therapy
Antipsychotic Agents (Second Generation [Atypical]): Blood Pressure Lowering Agents may enhance the hypotensive effect of Antipsychotic Agents (Second Generation [Atypical]). Risk C: Monitor therapy
Barbiturates: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy
Benperidol: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy
Beta-Blockers: May enhance the orthostatic hypotensive effect of Alpha1-Blockers. The risk associated with ophthalmic products is probably less than systemic products. Risk C: Monitor therapy
Brigatinib: May diminish the antihypertensive effect of Antihypertensive Agents. Brigatinib may enhance the bradycardic effect of Antihypertensive Agents. Risk C: Monitor therapy
Brimonidine (Topical): May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy
Bromperidol: May diminish the hypotensive effect of Blood Pressure Lowering Agents. Blood Pressure Lowering Agents may enhance the hypotensive effect of Bromperidol. Risk X: Avoid combination
Calcium Channel Blockers: Alpha1-Blockers may enhance the hypotensive effect of Calcium Channel Blockers. Risk C: Monitor therapy
Dapoxetine: May enhance the orthostatic hypotensive effect of Alpha1-Blockers. Risk C: Monitor therapy
Dexmethylphenidate: May diminish the therapeutic effect of Antihypertensive Agents. Risk C: Monitor therapy
Diazoxide: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy
DULoxetine: Blood Pressure Lowering Agents may enhance the hypotensive effect of DULoxetine. Risk C: Monitor therapy
Flunarizine: May enhance the therapeutic effect of Antihypertensive Agents. Risk C: Monitor therapy
Herbal Products with Blood Pressure Increasing Effects: May diminish the antihypertensive effect of Antihypertensive Agents. Risk C: Monitor therapy
Herbal Products with Blood Pressure Lowering Effects: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy
Hypotension-Associated Agents: Blood Pressure Lowering Agents may enhance the hypotensive effect of Hypotension-Associated Agents. Risk C: Monitor therapy
Levodopa-Containing Products: Blood Pressure Lowering Agents may enhance the hypotensive effect of Levodopa-Containing Products. Risk C: Monitor therapy
Loop Diuretics: May enhance the hypotensive effect of Antihypertensive Agents. Risk C: Monitor therapy
Lormetazepam: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy
Methylphenidate: May diminish the antihypertensive effect of Antihypertensive Agents. Risk C: Monitor therapy
Molsidomine: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy
Nicorandil: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy
Nitroprusside: Blood Pressure Lowering Agents may enhance the hypotensive effect of Nitroprusside. Risk C: Monitor therapy
Obinutuzumab: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Management: Consider temporarily withholding blood pressure lowering medications beginning 12 hours prior to obinutuzumab infusion and continuing until 1 hour after the end of the infusion. Risk D: Consider therapy modification
Pentoxifylline: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy
Pholcodine: Blood Pressure Lowering Agents may enhance the hypotensive effect of Pholcodine. Risk C: Monitor therapy
Phosphodiesterase 5 Inhibitors: May enhance the hypotensive effect of Alpha1-Blockers (Nonselective). Management: Ensure patient is stable on one agent prior to initiating the other, and always initiate combination using the lowest possible dose of the drug being added. When tadalafil is used for treatment of BPH, concurrent alpha 1-blockers are not recommended. Risk D: Consider therapy modification
Prostacyclin Analogues: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy
Quinagolide: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy
Rilmenidine: Alpha1-Blockers may enhance the hypotensive effect of Rilmenidine. Risk C: Monitor therapy
Adverse events have been observed in some oral animal reproduction studies. Diagnosing and treating pheochromocytoma is critical for favorable maternal and fetal outcomes (Schenker 1971; Schenker 1982).
It is not known if phentolamine is present in breast milk. Due to the potential for serious adverse reaction in the breastfed infant, the decision to discontinue phentolamine or discontinue breastfeeding during treatment should take in account the benefits of treatment to the mother. The manufacturer of OraVerse recommends the developmental and health benefits of breastfeeding be considered along with the mother's clinical need for phentolamine and any potential adverse effects on the breastfed infant from phentolamine, or from the underlying maternal condition.
Blood pressure, heart rate; monitor and document extravasation site; monitor patient for orthostasis; assist patient with ambulation
Competitively blocks alpha-adrenergic receptors (nonselective) to produce brief antagonism of circulating epinephrine and norepinephrine to reduce hypertension caused by alpha effects of these catecholamines and minimizes tissue injury due to extravasation of these and other sympathomimetic vasoconstrictors (eg, dopamine, phenylephrine); also has a positive inotropic and chronotropic effect on the heart thought to be due to presynaptic alpha-2 receptor blockade which results in release of presynaptic norepinephrine (Hoffman 1980)
OraVerse: Causes vasodilation and increased blood flow in injection area via alpha-adrenergic blockade to accelerate reversal of soft tissue anesthesia
Onset of action: IM: 15 to 20 minutes; IV: 1 to 2 minutes (Chobanian 2003)
Peak effect: OraVerse: 10 to 20 minutes
Duration: IM: 30 to 45 minutes; IV: 10 to 30 minutes (Chobanian 2003)
Metabolism: Hepatic
Half-life elimination: IV: 19 minutes; Submucosal injection: ~2 to 3 hours
Excretion: Urine (~13% as unchanged drug)
Pediatric: OraVerse Cmax ~3.5-fold higher in children weighing 15 to 30 kg compared with children weighing >30 kg.
Solution (reconstituted) (Phentolamine Mesylate Injection)
5 mg (per each): $501.60 - $587.95
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