Revoferin-zdorovya

INSTRUCTIONS FOR MEDICAL USE OF THE MEDICINAL PRODUCT REVOFRIN-ZDOROVYE (REVOPHRIN-ZDOROVYE)

Composition:

active substance: phentolamine;

1 ml contains phentolamine mesylate 0.235 mg;

excipients: disodium edetate, mannitol (E 421), sodium acetate trihydrate, glacial acetic acid, sodium hydroxide, water for injections.

Pharmaceutical form. Solution for injection.

Main physicochemical properties: clear, colorless solution.

Pharmacotherapeutic group. Various. Other therapeutic agents. Antidotes. Phentolamine. ATC code V03A B36.

Pharmacological Properties

Pharmacodynamics

Phentolamine mesylate is a non-selective alpha-adrenergic blocker.

The mechanism by which the drug accelerates the resolution of soft tissue anesthesia and related functional deficits is not fully understood. Phentolamine mesylate, the active ingredient of the drug, induces a relatively short-duration alpha-adrenergic blockade, resulting in vasodilation when administered to vascular smooth muscles. In an animal model, phentolamine mesylate increased local blood flow in the submucosal tissue of dogs when administered after an injection of 2% lidocaine with epinephrine 1:100,000 into the oral mucosa.

Pharmacokinetics

After administration of the drug, phentolamine is 100% available at the site of injection into the oral mucosa, with maximum concentration achieved within 10–20 minutes after injection. Systemic exposure to phentolamine increased linearly following oral mucosal injection of 0.8 mg compared to 0.4 mg of the drug. The terminal elimination half-life of phentolamine in blood was approximately 2–3 hours.

Children. After administration of the drug, Cmax of phentolamine was higher (approximately 3.5 times) in children with body weight between 15 and 30 kg compared to children with body weight above 30 kg. However, AUC of phentolamine was similar between the two groups. For children with body weight of 15–30 kg, the maximum recommended dose of the drug should be limited to ½ cartridge (0.2 mg) (see "Method of administration and dosage").

The pharmacokinetics of the drug in adults and children weighing over 30 kg are similar following oral mucosal injection.

Clinical Characteristics

Indications. The drug, an alpha-adrenergic blocker, is indicated in adults and children aged 3 years and older for the reversal of soft tissue anesthesia, i.e., anesthesia of the lips and tongue, and associated functional disturbances caused by injection of a local anesthetic containing a vasoconstrictor, administered submucosally in the oral cavity.

Contraindications. Hypersensitivity to the active substance or to any of the excipients of the drug.

Interaction with other medicinal products and other forms of interaction. Interaction is unknown.

Lidocaine and epinephrine. When phentolamine was administered as a submucosal injection in the oral cavity 30 minutes after injection of the local anesthetic – 2% lidocaine hydrochloride with epinephrine 1:100,000, the concentration of lidocaine increased immediately after phentolamine injection into the oral mucosa. Administration of phentolamine did not affect the AUC and Cmax values of lidocaine. Administration of phentolamine had no effect on the pharmacokinetics of epinephrine.

Special precautions for use

Cases of myocardial infarction, cerebral vasospasm, and cerebrovascular occlusion have been reported following parenteral administration of phentolamine. These events usually occurred in association with pronounced episodes of hypotension leading to shock-like conditions.

Tachycardia and cardiac arrhythmias may occur during treatment with phentolamine or other alpha-adrenergic blockers. Although such effects are rare following phentolamine administration, physicians should remain vigilant for signs and symptoms of these events, particularly in patients with a history of cardiovascular disease.

No overall differences in safety or efficacy have been observed between patients aged 65 years and older and younger patients, but greater sensitivity in some elderly individuals cannot be ruled out.

Patients should be advised not to eat or drink until normal sensation has returned.

The product contains less than 1 mmol (23 mg)/dose of sodium, i.e., it is practically sodium-free.

Use during pregnancy or breastfeeding

Pregnancy

Data on the use of phentolamine in pregnant women are limited. Although animal studies have not demonstrated teratogenic effects of phentolamine, there is insufficient data regarding its reproductive toxicity in humans. The medicinal product is not recommended for use during pregnancy.

Lactation

There are no available data on the presence of phentolamine in human milk, its effects on the breastfed infant, or its impact on milk production.

The decision to temporarily discontinue breastfeeding in favor of treatment with the medicinal product should be made by considering the benefits of breastfeeding for the child versus the benefits of treatment for the woman.

Fertility

The effect of phentolamine on human fertility has not been studied.

Ability to affect reaction speed when driving or operating machinery

Only the dentist can determine, based on the information provided in the section "Adverse reactions," when a patient may resume driving or operating machinery after administration of the product.

Method of administration and dosage.

The recommended dose of the medicinal product is based on the number of cartridges of local anesthetic with vasoconstrictor administered:

The medicinal product should be administered after a dental procedure using the same site and technique (infiltration or block injection) as used for the local anesthetic.

Chemically disinfect the cartridge cap by wiping with isopropyl alcohol (91%) or ethyl alcohol (70%). Many commercially available brands of isopropyl alcohol, as well as ethyl alcohol solutions, contain denaturants that are harmful to rubber and therefore should not be used.

The preparation should be inspected visually before administration and should not be used if particulate matter, discoloration, cracks in the glass, or other defects are observed.

Dosing in Special Patient Populations

In pediatric patients with body weight from ≥15 kg to <30 kg, the recommended maximum dose of the medicinal product is ½ cartridge (0.2 mg). Use in children under 3 years of age or with body weight less than 15 kg is not recommended. Doses exceeding 1 cartridge (0.4 mg) have not been studied in children under 4 years of age.

Children

The safety and efficacy of the medicinal product in patients under 3 years of age have not been established. Dosing in pediatric patients may depend on body weight (see "Instructions for Use and Dosage").

Overdose. There have been no reported fatal cases due to acute poisoning with phentolamine.

Overdose of parenterally administered phentolamine is characterized primarily by cardiovascular disturbances such as arrhythmias, tachycardia, arterial hypotension, and possibly shock. In addition, the following may occur: restlessness, headache, sweating, miosis, visual disturbances, nausea, vomiting, diarrhea, or hypoglycemia.

There is no specific antidote; treatment consists of appropriate monitoring and supportive therapy. Significant reduction in arterial blood pressure or other signs of shock-like conditions should be treated intensively and immediately.

Adverse Reactions

In clinical studies, the most common adverse reaction of phentolamine that occurred more frequently than in the control group was injection site pain.

Clinical Trial Experience. Because clinical trials are conducted under widely varying conditions, the adverse reaction rates observed in clinical trials of a drug cannot be directly compared to those of another drug, and may not reflect the rates observed in practice.

Dental patients were administered doses of 0.2, 0.4, or 0.8 mg of phentolamine. Most adverse reactions were mild and resolved within 48 hours. There were no serious adverse reactions, and no treatment discontinuations due to adverse reactions.

The table below lists adverse reactions with an incidence rate of ≥3% in any phentolamine dose group and equal to or greater than that of the control group.

Subgroup analyses did not reveal differences in the frequency of adverse reactions based on age, gender, or race.

Results of pain assessment in Study 1 and Study 2, which included mandibular and maxillary procedures respectively, showed that the majority of dental patients in both the phentolamine and control groups experienced no pain or only mild oral pain, with less than 10% of patients in each group reporting moderate oral pain, and a similar distribution between the phentolamine and control groups. In these studies, no patient experienced severe pain.

Study 4 included 150 children aged 2 to 5 years who received a dose of ¼ cartridge (0.1 mg), ½ cartridge (0.2 mg), or 1 cartridge (0.4 mg) of phentolamine or a placebo injection (placebo). The safety profile in Study 4 was similar to that observed in older patients, as described above. Post-procedure assessment revealed that oral pain was reported more frequently in the phentolamine group (10.1%) compared to the placebo group (3.9%). The proportion of patients in the phentolamine and placebo groups was comparable regarding the highest pain severity: 30.4% of patients in the phentolamine group and 30% in the placebo group reported no pain; 43.1% of patients in the phentolamine group and 45% in the placebo group reported mild pain; 19% of patients in the phentolamine group and 17.5% in the placebo group reported moderate pain; and 15.2% of patients in the phentolamine group and 15% in the placebo group reported severe pain.

Adverse reactions reported in less than 3% but in at least 2 dental patients receiving phentolamine and occurring more frequently than in the control group included diarrhea, facial swelling, increased blood pressure / hypertension, injection site reactions, jaw pain, oral pain, paresthesia, pruritus, weakness, upper abdominal pain, and vomiting. Most of these adverse reactions were mild and resolved within 48 hours. In several reports, paresthesia was mild and transient, resolving within the same time period.

Post-marketing adverse reactions reported from literature and other sources. The following adverse reactions have been identified during parenteral use of phentolamine mesylate. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.

Acute and prolonged hypotensive episodes and cardiac arrhythmias have been reported with the use of phentolamine. In addition, weakness, dizziness, flushing, orthostatic hypotension, and nasal congestion have been observed.

Reporting of adverse reactions following drug registration is of significant importance. It enables ongoing monitoring of the benefit-risk balance of the drug. Healthcare and pharmaceutical professionals, as well as patients or their legal representatives, should report all suspected adverse reactions and lack of efficacy through the Automated Pharmacovigilance Information System at the following link: https://aisf.dec.gov.ua.

Shelf life. 2 years.

Storage conditions. Store in the original packaging at a temperature of 25 °C. Keep out of reach of children.

Incompatibilities. Should not be mixed with other medicinal products.

Packaging. 1.7 mL in a cartridge, pack of 10 (10x1), pack of 50 (10x5) in blister packs in a cardboard box.

Prescription status. Prescription only.

Manufacturer. Limited liability company "FARMEKS GROUP".

Manufacturer's address and location of business activity. Ukraine, 08301, Kyiv region, Boryspil, Shevchenko Street, 100.