Phentolamine

The mechanism by which OraVerse accelerates reversal of soft-tissue anesthesia and the associated functional deficits is not fully understood. Phentolamine mesylate, the active ingredient in OraVerse, produces an alpha-adrenergic block of relatively short duration resulting in vasodilatation when applied to vascular smooth muscle.

• 1. INDICATONS AND USAGE OraVerse an alpha adrenergic blocker, is indicated for adult and pediatric patients ages 3 years and older for the reversal of soft-tissue anesthesia, i.e., anesthesia of the lip and tongue, and the associated functional deficits resulting from an intraoral submucosal injection of a local anesthetic containing a vasoconstrictor.

• 4. CONTRAINDICATIONS OraVerse is contraindicated in patients with: Hypersensitivity to the active substance or to any ingredients in the formulation OraVerse is contraindicated in patients with: Hypersensitivity to the active substance or to any ingredients in the formulation.contraindicated

2. DOSAGE AND ADMINISTRATION Amount of Local Anesthetic Administered Dose of OraVerse 1 / 4 Cartridge 1 / 4 Cartridge (0.1 mg) ½ Cartridge ½ Cartridge (0.2 mg) 1 Cartridge 1 Cartridge (0.4 mg) 2 Cartridges 2 Cartridges (0.8 mg) OraVerse is administered using the same location(s) and same technique(s) (infiltration or block injection) used for the administration of local anesthetic. ( 2.1 ) 2.1 General Dosing information The recommended dose of OraVerse is based on the number of cartridges of local anesthetic with vasoconstrictor administered: Amount of Local Anesthetic Administered Dose of OraVerse [mg] Dose of OraVerse [Cartridge(s)] 1 / 4 Cartridge 0.1 1 / 4 ½ Cartridge 0.2 ½ 1 Cartridge 0.4 1 2 Cartridges 0.8 2 OraVerse should be administered following the dental procedure using the same location(s) and technique(s) (infiltration or block injection) employed for the administration of the local anesthetic. Chemically disinfect the carpule cap by wiping with either isopropyl alcohol (91%) or ethyl alcohol (70%). Many commercially available brands of isopropyl (rubbing) alcohol, as well as solutions of ethyl alcohol not of U.S.P. grade, contain denaturants that are injurious to rubber and therefore are not to be used. Inspect carpules visually prior to administration and do not use if particulate matter, discoloration, cracks in the glass, protruding plungers or other defects are observed. Note: Do not administer OraVerse if particulate matter, discoloration, cracks in the glass, protruding plungers or other defects are observed.

5. WARNINGS AND PRECAUTIONS Myocardial infarction, cerebrovascular spasm, and cerebrovascular occlusion have been reported to occur following the intravenous or intramuscular administration of phentolamine, usually in association with marked hypotensive episodes or shock-like states which occasionally follow parenteral administration. Tachycardia and cardiac arrhythmiasmay occur with the use of phentolamine or other alpha-adrenergic blocking agents. ( 5.1 ) 5.1 Cardiovascular Events Myocardial infarction, cerebrovascular spasm, and cerebrovascular occlusion have been reported to occur following the parenteral administration of phentolamine. These events usually occurred in association with marked hypotensive episodes producing shock-like states. Tachycardia and cardiac arrhythmias may occur with the use of phentolamine or other alpha-adrenergic blocking agents. Although such effects are uncommon after administration of OraVerse, clinicians should be alert to the signs and symptoms of these events, particularly in patients with a prior history of cardiovascular disease.

6. ADVERSE REACTIONS In clinical trials, the most common adverse reaction with OraVerse that was greater than the control group was injection site pain. The most common adverse reaction with OraVerse (incidence ≥5% and > control) is injection-site pain. ( 6 ) To report SUSPECTED ADVERSE REACTIONS, contact Septodont at 1-888-888-1441 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch . 6.1 Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. Dental patients were administered a dose of either 0.2, 0.4 or 0.8mg of OraVerse. The majority of adverse reactions were mild and resolved within 48 hours. There were no serious adverse reactions and no discontinuations due to adverse reactions. Table 1 lists adverse reactions where the frequency was greater than or equal to 3% in any OraVerse dose group and was equal to or exceeded that of the control group.

8. USE IN SPECIFIC POPULATIONS Use in pediatric patients less than 3 years of age or <15 kg (33 lbs) has not been established. ( 8.4 ) In pediatric patients weighing at least 10 kg (22 lbs), the maximum dose of OraVerse recommended is 1/4cartridge (0.1 mg). ( 8.4 ) 8.1 Pregnancy Pregnancy Category C Risk summary There are no available data with OraVerse in pregnant women to inform a drug-associated risk for major birth defects and miscarriage. In animal toxicology studies, phentolamine administered orally to pregnant mice and rats during the period of organogenesis resulted in skeletal immaturity and decreased growth in the offspring at doses at least 24-times the recommended dose. Additionally, a lower rate of implantation was seen in pregnant rats treated with phentolamine at least 60-times the recommended dose. No malformations or embryofetal deaths were observed in the offspring of pregnant mice, rats, and rabbits administered phentolamine during the period of organogenesis at doses 24-, 60-, and 20-times, respectively, the recommended dose [see Data]. The estimated background risk of major birth defects and miscarriage for the indicated population is unknown. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2-4% and 15-20%, respectively.

Metabolism

Following OraVerse administration, phentolamine is 100% available from the submucosal injection site and peak concentrations are achieved 10-20 minutes after injection. Phentolamine systemic exposure increased linearly after 0.8 mg compared to 0.4 mg OraVerse intraoral submucosal injection.

10. OVERDOSAGE No deaths due to acute poisoning with phentolamine have been reported. Overdosage with parenterally administered phentolamine is characterized chiefly by cardiovascular disturbances, such as arrhythmias, tachycardia, hypotension, and possibly shock. In addition, the following might occur: excitation, headache, sweating, pupillary contraction, visual disturbances, nausea, vomiting, diarrhea, or hypoglycemia. There is no specific antidote; treatment consists of appropriate monitoring and supportive care. Substantial decreases in blood pressure or other evidence of shock-like conditions should be treated vigorously and promptly.

• Mar 11, 1998ANDAANDA040235Hikma
• May 9, 2008NDANDA022159Septodont Holding
• Jul 14, 2017ANDAANDA207686Precision Dose Inc
• Sep 25, 2023NDANDA217064Famygen Life Sci

1. 1Ocular Hyperaemia2013%
2. 2Blood Urea Increased149.1%
3. 3Blood Glucose Increased138.4%
4. 4Headache138.4%
5. 5Neutrophil Count Increased138.4%
6. 6Anaemia127.8%
7. 7Diarrhoea127.8%
8. 8Lymphocyte Count Decreased127.8%
9. 9Drug Ineffective117.1%
10. 10Hypertension117.1%
11. 11Dizziness106.5%
12. 12Abdominal Distension95.8%
13. 13Eye Pain95.8%
14. 14Haemoglobin Decreased95.8%
15. 15Hypoaesthesia95.8%

Recent PubMed references pinned to Phentolamine as a MeSH major topic. Citations link to pubmed.ncbi.nlm.nih.gov.

• Adjunctive treatment of symmetrical peripheral gangrene with phenolamine wet compress.
  Medicine · 2025 · Zhu Y, Zhou T, Qian H, et al.
  PMID 40859539DOI 10.1097/MD.0000000000044099
• Inhibition Molecular Mechanism of α(2) Adrenergic Receptor Activation by Antagonist.
  FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2025 · Li Y, Jiao H, Hu H, et al.
  PMID 40444459DOI 10.1096/fj.202403409R
• Intracavernosal injection of aviptadil and phentolamine for refractory erectile dysfunction.
  The journal of sexual medicine · 2025 · Al-Mitwalli A, Holden F, Di Giovanni A, et al.
  PMID 40192471DOI 10.1093/jsxmed/qdaf067
• Phentolamine Infusion for the Treatment of Norepinephrine Extravasation in a Dog.
  Journal of veterinary emergency and critical care (San Antonio, Tex. : 2001) · 2025 · Flynn GE, Riffe CI, Aicher KM, et al.
  PMID 40127428DOI 10.1111/vec.13461
• α-Adrenoreceptor blocker phentolamine inhibits voltage-gated sodium channels via the local anaesthetic binding site.
  British journal of pharmacology · 2025 · Toklucu I, Sudha Bhagavath Eswaran V, Bott RA, et al.
  PMID 39888002DOI 10.1111/bph.17450
• Effectiveness of phentolamine mesylate, vibration and photobiomodulation in reducing pain and the reversal of local anesthesia: A systematic review.
  Advances in clinical and experimental medicine : official organ Wroclaw Medical University · 2025 · Olszewska A, Forszt D, Szymczak A, et al.
  PMID 39503279DOI 10.17219/acem/190202
• The administration of a phentolamine infusion into the basolateral amygdala enhances long-term memory and diminishes anxiety-like behavior in stressed rats.
  Behavioural pharmacology · 2024 · Dehghani A, Meftahi GH, Sahraei H, et al.
  PMID 39436284DOI 10.1097/FBP.0000000000000796
• Reversal of Pharmacologically Induced Mydriasis with Phentolamine Ophthalmic Solution.
  Ophthalmology · 2025 · Pepose JS, Wirta D, Evans D, et al.
  PMID 39293681DOI 10.1016/j.ophtha.2024.09.010

The 10 most recently updated of 51 ClinicalTrials.gov registrations naming Phentolamine as an intervention. Registration is not evidence of efficacy or safety — reference crosswalk only.

• Adrenergic System in Islet Transplantation
  Completed · Early phase 1 · Interventional · 9 enrolled · University of Pennsylvania
  NCT03079921updated 2026-04-27
• Oraverse Versus Laser
  Recruiting · Phase 3 · Interventional · 36 enrolled · sara nabil
  NCT05473858updated 2026-04-06
• Safety and Efficacy of Nyxol Eye Drops as a Single Agent and With Adjunctive Low-Dose Pilocarpine Eye Drops in Subjects With Presbyopia
  Completed · Phase 3 · Interventional · 333 enrolled · Ocuphire Pharma, Inc.
  NCT05646719updated 2026-03-12
• Evaluate Efficacy and Safety of POS to Improve Distance-corrected Near Visual in Participants With Presbyopia
  Completed · Phase 3 · Interventional · 569 enrolled · Ocuphire Pharma, Inc.
  NCT06542497updated 2026-03-12
• Safety and Efficacy of 0.75% Phentolamine Ophthalmic Solution in Subjects With Post-refractive Surgery Visual Disturbances
  Completed · Phase 3 · Interventional · 200 enrolled · Ocuphire Pharma, Inc.
  NCT06349759updated 2026-03-12
• Role of Sympathetic Vasoconstriction on Insulin-Mediated Microvascular Recruitment and Glucose Uptake in Obesity
  Active not recruiting · Phase 1 · Interventional · 36 enrolled · Vanderbilt University Medical Center
  NCT03318094updated 2026-03-02
• Sympathetic Neurovascular Transduction: Role of Adrenergic Receptors and Sex Differences
  Recruiting · Phase 4 · Interventional · 30 enrolled · University of Alberta
  NCT05997732updated 2026-01-08
• Comparison Between the Use of Phentolamine Versus Glyceryl Trinitrate for Their Effect on Renal Function in Pre-eclampsia Patients in ICU
  Completed · Phase 4 · Interventional · 170 enrolled · Assiut University
  NCT05687669updated 2025-12-26
• Safety and Efficacy of Nyxol (0.75% Phentolamine Ophthalmic Solution) in Subjects With Dim Light Vision Disturbances
  Completed · Phase 3 · Interventional · 144 enrolled · Ocuphire Pharma, Inc.
  NCT04638660updated 2025-10-14
• Safety and Efficacy of Nyxol With Pilocarpine Eye Drops in Subjects With Presbyopia
  Completed · Phase 2 · Interventional · 150 enrolled · Ocuphire Pharma, Inc.
  NCT04675151updated 2025-10-10

Frequently asked questions

How does Phentolamine work?

The mechanism by which OraVerse accelerates reversal of soft-tissue anesthesia and the associated functional deficits is not fully understood. Phentolamine mesylate, the active ingredient in OraVerse, produces an alpha-adrenergic block of relatively short duration resulting in vasodilatation when applied to vascular smooth muscle.

What is Phentolamine used for?

According to FDA labeling, Phentolamine carries indications including: 1. INDICATONS AND USAGE OraVerse an alpha adrenergic blocker, is indicated for adult and pediatric patients ages 3 years and older for the reversal of soft-tissue anesthesia, i.e., anesthesia of the lip and tongue, and the associated functional deficits resulting from an intraoral submucosal injection of a local anesthetic containing a vasoconstrictor.. This is a reference summary of labeled uses, not medical advice or a treatment recommendation.

What class of drug is Phentolamine?

Phentolamine is classified as Antidotes, Imidazoline derivatives, alpha-Adrenergic Blocker, Adrenergic alpha-Antagonists, Arterial Vasodilation, Decreased Blood Pressure, Positive Chronotropy, Positive Inotropy.

What are the brand names for Phentolamine?

Phentolamine is marketed under brand names including OraVerse, Ryzumvi.

What are the contraindications for Phentolamine?

Phentolamine labeling lists contraindications including: 4. CONTRAINDICATIONS OraVerse is contraindicated in patients with: Hypersensitivity to the active substance or to any ingredients in the formulation OraVerse is contraindicated in patients with: Hypersensitivity to the active substance or to any ingredients in the formulation.. Always consult the full prescribing information and a clinician.