美国FDA批准Novalar制药公司上市的药物是OraVerse,这是一种α-adrenoceptor拮抗剂和血管舒张剂酚妥拉明甲磺酰基的新制剂,在美国用于齿科麻醉后的恢复。
DOSAGE FORMS AND STRENGTHS 0.4mg/1.7mL solution per cartridge (3) CONTRAINDICATIONS None (4) 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) ADVERSE REACTIONS 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. USE IN SPECIFIC POPULATIONS Use in pediatric patients less than 6 years of age or <15 kg (33 lbs) is not recommended. (8.4) In pediatric patients weighing less than 30 kg (66 lbs), the maximum dose of OraVerse recommended is 1/2 cartridge (0.2mg). (8.4) See 17 for PATIENT COUNSELING INFORMATION. Revised: 5/2011
Note: Do not administer OraVerse if the product is discolored or contains particulate matter. 2.2 Dosing in Special PopulationsIn pediatric patients weighing 15-30 kg, the maximum dose of OraVerse recommended is 1/2 cartridge (0.2 mg). (Note: Use in pediatric patients under 6 years of age or weighing less than15 kg (33 lbs) is not recommended. A dose of more than 1 cartridge [0.4 mg] of OraVerse has not been studied in children less than 12 years of age.) 3. DOSAGE FORMS AND STRENGTHS 0.4 mg/1.7 mL solution per cartridge 4. CONTRAINDICATIONS(What is this) None. 5. WARNINGS AND PRECAUTIONS 5.1 Cardiovascular EventsMyocardial 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. 6.1 Clinical Trials ExperienceBecause 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. Table 1: Adverse Reactions with Frequency Greater Than or Equal to 3% and Equal to or Exceeding Control
Results from the pain assessments in Study 1 and Study 2, involving mandibular and maxillary procedures, respectively, indicated that the majority of dental patients in both OraVerse and control groups experienced no or mild oral pain, with less than 10% of patients in each group reporting moderate oral pain with a similar distribution between the OraVerse and control groups. No patient experienced severe pain in these studies. 6.2 Adverse Reactions in Clinical TrialsAdverse reactions reported by less than 3% but at least 2 dental patients receiving OraVerse and occurring at a greater incidence than those receiving control, included diarrhea, facial swelling, increased blood pressure/hypertension, injection site reactions, jaw pain, oral pain, paresthesia, pruritus, tenderness, upper abdominal pain and vomiting. The majority of these adverse reactions were mild and resolved within 48 hours. The few reports of paresthesia were mild and transient and resolved during the same time period. 6.3 Post Marketing Adverse Reactions Reports from Literature and Other SourcesThe following adverse reactions have been identified during postapproval 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 stuffiness have occurred. 7. DRUG INTERACTIONS There are no known drug interactions with OraVerse. 7.1 Lidocaine and EpinephrineWhen OraVerse was administered as an intraoral submucosal injection 30 minutes after injection of a local anesthetic, 2% lidocaine HCl with 1:100,000 epinephrine, the lidocaine concentration increased immediately after OraVerse intraoral injection. Lidocaine AUC and Cmax values were not affected by administration of OraVerse. OraVerse administration did not affect the PK of epinephrine. 8. USE IN SPECIFIC POPULATIONS 8.1 Pregnancy Pregnancy Category C There are no adequate and well-controlled studies in pregnant women. OraVerse should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus. Oral administration of phentolamine to pregnant rats and mice at doses at least 24 times the recommended dose (based on a 60 kg human) resulted in slightly decreased growth and slight skeletal immaturity of the fetuses. Immaturity was manifested by increased incidence of incomplete or unossified calcaneal and phalangeal nuclei of the hind limb and of incompletely ossified sternebrae. At oral phentolamine doses at least 60 times the recommended dose (based on a 60 kg human), a slightly lower rate of implantation was found in the rat. Phentolamine did not affect embryonic or fetal development in the rabbit at oral doses at least 20 times the recommended dose (based on a 60 kg human). No teratogenic or embryotoxic effects were observed in the rat, mouse, or rabbit studies. 8.3 Nursing MothersIt is not known whether OraVerse is excreted in human milk. Because many drugs are excreted in human milk, caution should be exercised when OraVerse is administered to a nursing woman. The unknown risks of limited infant exposure to phentolamine through breast milk following a single maternal dose should be weighed against the known benefits of breastfeeding. 8.4 Pediatric UseIn clinical studies, pediatric patients between the ages of 3 and 17 years received OraVerse. The safety and effectiveness of OraVerse have been established in the age group 6-17 years. Effectiveness in pediatric patients below the age of 6 years has not been established. Use of OraVerse in patients between the ages of 6 and 17 years old is supported by evidence from adequate and well-controlled studies of OraVerse in adults, with additional adequate and well-controlled studies of OraVerse in pediatric patients ages 12-17 years old [Studies 1 (mandibular procedures) and 2 (maxillary procedures)] and ages 6-11 years old [Study 3 (mandibular and maxillary procedures)]. The safety, but not the efficacy, of OraVerse has been evaluated in pediatric patients under the age of 6 years old. Dosages in pediatric patients may need to be limited based on body weight. [see Dosage and Administration (2)] 8.5 Geriatric UseOf the total number of patients in clinical studies of OraVerse, 55 were 65 and over, while 21 were 75 and over. No overall differences in safety or effectiveness were observed between these patients and younger patients, and other reported clinical experience has not identified differences in responses between the elderly and younger patients, but greater sensitivity of some older individuals cannot be ruled out. 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. 11. DESCRIPTION Phentolamine mesylate is phenol,3-[[(4,5-dihydro-1H-imidazol-2-yl)methyl](4-methyl-phenyl)amino]-,methanesulfonate (salt), a non-specific alpha adrenergic blocker. Phentolamine mesylate USP is a white to off-white, odorless crystalline powder with a molecular weight of 377.46. It is sparingly soluble in water, soluble in alcohol, and slightly soluble in chloroform. The empirical formulation is C17H19N3O•CH4O3S, and the chemical structure is: OraVerse (phentolamine mesylate) Injection is a clear, colorless, sterile, non pyrogenic, isotonic, preservative free solution. Each 1.7 mL cartridge contains 0.4 mg phentolamine mesylate, D-mannitol, edetate disodium, and sodium acetate. Either acetic acid or sodium hydroxide is used as necessary to adjust the pH.
Septodont, Inc
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OraVerse Injection(phentolamine mesylate)甲磺酸酚妥拉明注射液简介:
美国FDA批准Novalar制药公司上市的药物是OraVerse,这是一种α-adrenoceptor拮抗剂和血管舒张剂酚妥拉明甲磺酰基的新制剂,在美国用于齿科麻醉后的恢复。美国每年约有3亿多齿科局部麻醉案例。虽然应用广 ... 责任编辑:admin |
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