氢溴酸加兰他敏 Galantamine Hydrobromide
作用与用途:本品为抗胆碱酯酶药,有较弱的抗胆碱酯酶作用,能透过血脑屏障,故对中枢神经系统作用比较强。使受阻碍的神经肌肉传导恢复,改善各种末梢神经肌肉障碍的麻痹状态。其治疗范围广,毒性较小,病人较易耐受。临床主要用于治疗脊髓灰质炎(小儿麻痹症)后遗症、肌肉萎缩及重症肌无力等。也可用于儿童脑型麻痹、外伤性感觉运动障碍、多发性神经炎及脊神经根炎等。 剂量与用法:口服,成人10mg/次,3次/日;小儿每日0.5mg~1mg/kg,分3次。皮下或肌注,成人2.5mg~10mg/次,1次/日。小儿每次0.05mg~0.1mg/kg,1次/日。对脊髓灰质炎后遗症可连续用药40~50日,一般20~40日为1个疗程,间隔30~45日后开始第二个疗程。经1~2个疗程后,病情仍未改善者,应停止使用。有效者可连续3个疗程。 副作用: 【原产地英文商品名】RAZADYNE TABLET 12mg/tab 60tabs/bottle Razadyne® ER Razadyne® DRUG DESCRIPTION RAZADYNE® ER is available in opaque hard gelatin extended-release capsules of 8 mg (white), 16 mg (pink), and 24 mg (caramel) containing galantamine hydrobromide, equivalent to respectively 8, 16 and 24 mg galantamine base. Inactive ingredients include gelatin, diethyl phthalate, ethylcellulose, hypromellose, polyethylene glycol, titanium dioxide and sugar spheres (sucrose and starch).The 16 mg capsule also contains red ferric oxide. The 24 mg capsule also contains red ferric oxide and yellow ferric oxide. RAZADYNE® for oral use is available in circular biconvex film-coated immediate-release tablets of 4 mg (off-white), 8 mg (pink), and 12 mg (orange-brown). Each 4, 8, and 12 mg (base equivalent) tablet contains 5.126, 10.253, and 15.379 mg of galantamine hydrobromide, respectively. Inactive ingredients include colloidal silicon dioxide, crospovidone, hypromellose, lactose monohydrate, magnesium stearate, microcrystalline cellulose, propylene glycol, talc, and titanium dioxide. The 4 mg tablets contain yellow ferric oxide. The 8 mg tablets contain red ferric oxide. The 12 mg tablets contain red ferric oxide and FD&C yellow #6 aluminum lake. RAZADYNE® is also available as a 4 mg/mL oral solution. The inactive ingredients for this solution are methyl parahydroxybenzoate, propyl parahydroxybenzoate, sodium saccharin, sodium hydroxide and purified water. ---------------------------------------------------------- INDICATIONS ---------------------------------------------------------- DOSAGE AND ADMINISTRATION The recommended starting dose of RAZADYNE® ER is 8 mg/day. The dose should be increased to the initial maintenance dose of 16 mg/day after a minimum of 4 weeks. A further increase to 24 mg/day should be attempted after a minimum of 4 weeks at 16 mg/day. Dose increases should be based upon assessment of clinical benefit and tolerability of the previous dose. RAZADYNE® ER should be administered once daily in the morning, preferably with food. Patients currently being treated with RAZADYNE® tablets can convert to RAZADYNE® ER by taking their last dose of RAZADYNE® tablets in the evening and starting RAZADYNE® ER once daily treatment the next morning. Converting from RAZADYNE® to RAZADYNE® ER should occur at the same total daily dose. RAZADYNE® Immediate-Release Tablets and Oral Solution The recommended starting dose of RAZADYNE® Tablets and Oral Solution is 4 mg twice a day (8 mg/day). The dose should be increased to the initial maintenance dose of 8 mg twice a day (16 mg/day) after a minimum of 4 weeks. A further increase to 12 mg twice a day (24 mg/day) should be attempted after a minimum of 4 weeks at 8 mg twice a day (16 mg/day). Dose increases should be based upon assessment of clinical benefit and tolerability of the previous dose. RAZADYNE® Tablets and Oral Solution should be administered twice a day, preferably with morning and evening meals. Patients and caregivers should be advised to ensure adequate fluid intake during treatment. If therapy has been interrupted for several days or longer, the patient should be restarted at the lowest dose and the dose escalated to the current dose. Caregivers should be instructed in the correct procedure for administering RAZADYNE® Oral Solution. In addition, they should be informed of the existence of an Instruction Sheet (included with the product) describing how the solution is to be administered. They should be urged to read this sheet prior to administering RAZADYNE® Oral Solution. Caregivers should direct questions about the administration of the solution to either their physician or pharmacist. The abrupt withdrawal of RAZADYNE® ER/RAZADYNE® in those patients who had been receiving doses in the effective range was not associated with an increased frequency of adverse events in comparison with those continuing to receive the same doses of that drug. The beneficial effects of RAZADYNE® ER/RAZADYNE® are lost, however, when the drug is discontinued. Doses in Special Populations For patients with moderate renal impairment the dose should generally not exceed 16 mg/day. In patients with severe renal impairment (creatinine clearance < 9 mL/min), the use of RAZADYNE® ER/RAZADYNE® is not recommended. ---------------------------------------------------------- HOW SUPPLIED 8 mg white opaque, size 4 hard gelatin capsules with the inscription "GAL 8." The capsules are supplied as follows: RAZADYNE® Tablets are imprinted "JANSSEN" on one side, and "G" and the strength "4", "8", or "12" on the other. 4 mg off-white tablet: bottles of 60 NDC 50458-396-60 RAZADYNE® 4 mg/mL oral solution (NDC 50458-490-10) is a clear colorless solution supplied in 100 mL bottles with a calibrated (in milligrams and milliliters) pipette. The minimum calibrated volume is 0.5 mL, while the maximum calibrated volume is 4 mL. Storage and Handling RAZADYNE® Tablets should be stored at 25°C (77°F); excursions permitted to 15-30°C (59-86°F) [see USP Controlled Room Temperature]. RAZADYNE® Oral Solution should be stored at 25°C (77°F); excursions permitted to 15-30°C (59-86°F) [see USP Controlled Room Temperature]. DO NOT FREEZE. ---------------------------------------------------------- SIDE EFFECTS Adverse Events Leading to Discontinuation Adverse Events Reported in Controlled Trials The majority of these adverse events occurred during the dose-escalation period. In those patients who experienced the most frequent adverse event, nausea, the median duration of the nausea was 5-7 days. Administration of RAZADYNE® with food, the use of anti-emetic medication, and ensuring adequate fluid intake may reduce the impact of these events. Adverse events occurring with an incidence of at least 2% in RAZADYNE®-treated patients that was either equal to or greater than with placebo treatment were constipation, agitation, confusion, anxiety, hallucination, injury, back pain, peripheral edema, asthenia, chest pain, urinary incontinence, upper respiratory tract infection, bronchitis, coughing, hypertension, fall, and purpura. There were no important differences in adverse event rates related to dose or sex. There were too few non-Caucasian patients to assess the effects of race on adverse event rates. No clinically relevant abnormalities in laboratory values were observed. Other Adverse Events Observed During Clinical Trials To establish the rate of adverse events, data from all patients receiving any dose of galantamine in 8 placebo-controlled trials and 6 open-label extension trials were pooled.The methodology to gather and codify these adverse events was standardized across trials, using WHO terminology. All adverse events occurring in approximately 0.1% are included, except for those already listed elsewhere in labeling, WHO terms too general to be informative, or events unlikely to be drug caused. Events are classified by body system and listed using the following definitions: frequent adverse events - those occurring in at least 1/100 patients; infrequent adverse events - those occurring in 1/100 to 1/1000 patients; rare adverse events - those occurring in fewer than 1/1000 patients. These adverse events are not necessarily related to RAZADYNE® treatment and in most cases were observed at a similar frequency in placebo-treated patients in the controlled studies. Additional adverse events observed in other clinical trials are also included below. Body As a Whole – General Disorders: Frequent: chest pain, asthenia, fever, malaise Cardiovascular System Disorders: Infrequent: postural hypotension, hypotension, dependent edema, cardiac failure, myocardial ischemia or infarction Central & Peripheral Nervous System Disorders: Infrequent: vertigo, hypertonia, convulsions, involuntary muscle contractions, paresthesia, ataxia, hypokinesia, hyperkinesia, apraxia, aphasia, leg cramps, tinnitus, transient ischemic attack or cerebrovascular accident Gastrointestinal System Disorders: Frequent: flatulence; Infrequent: gastritis, melena, dysphagia, rectal hemorrhage, dry mouth, saliva increased, diverticulitis, gastroenteritis, hiccup; Rare: esophageal perforation Heart Rate & Rhythm Disorders: Infrequent: A V block, palpitation, atrial arrhythmias including atrial fibrillation and supraventricular tachycardia, QT prolonged, bundle branch block, T-wave inversion, ventricular tachycardia; Rare: severe bradycardia Metabolic & Nutritional Disorders: Infrequent: hyperglycemia, alkaline phosphatase increased Platelet, Bleeding & Clotting Disorders: Infrequent: purpura, epistaxis, thrombocytopenia Psychiatric Disorders: Infrequent: apathy, paroniria, paranoid reaction, libido increased, delirium; Rare: suicidal ideation, suicide Urinary System Disorders: Frequent: incontinence; Infrequent: hematuria, micturition frequency, cystitis, urinary retention, nocturia, renal calculi Post-Marketing Experience Body as a Whole – General Disorders: dehydration (including rare, severe cases leading to renal insufficiency and renal failure) Psychiatric Disorders: aggression Gastrointestinal System Disorders: upper and lower GI bleeding, stomach discomfort, abdominal discomfort Hepatobiliary Disorders: elevated liver enzymes, hepatitis Metabolic & Nutritional Disorders: hypokalemia Nervous System Disorders: lethargy, dysgeusia, hypersomnia Eye Disorders: vision blurred These adverse events may or may not be causally related to the drug. ---------------------------------------------------------- DRUG INTERACTIONS Use With Anticholinergics Use With Cholinomimetics and Other Cholinesterase Inhibitors Effect of Other Drugs on Galantamine In vivo Ketoconazole: Ketoconazole, a strong inhibitor of CYP3A4 and an inhibitor of CYP2D6, at a dose of 200 mg BID for 4 days, increased the AUC of galantamine by 30%. Erythromycin: Erythromycin, a moderate inhibitor of CYP3A4 at a dose of 500 mg QID for 4 days, affected the AUC of galantamine minimally (10% increase). Paroxetine: Paroxetine, a strong inhibitor of CYP2D6, at 20 mg/day for 16 days, increased the oral bioavailability of galantamine by about 40%. Memantine: Memantine, an N-methyl-D-aspartate receptor antagonist, at a dose of 10 mg BID, had no effect on the pharmacokinetics of galantamine (16 mg/day) at steady state. Effect of Galantamine on Other Drugs In vivo Digoxin: Galantamine at 24 mg/day had no effect on the steady-state pharmacokinetics of digoxin (0.375 mg once daily) when they were coadministered. In this study, however, one healthy subject was hospitalized for 2nd and 3rd degree heart block and bradycardia. ---------------------------------------------------------- WARNINGS Cardiovascular Conditions In randomized controlled trials, bradycardia was reported more frequently in galantamine-treated patients than in placebo-treated patients, but was rarely severe and rarely led to treatment discontinuation. The overall frequency of this event was 2-3% for galantamine doses up to 24 mg/day compared with < 1% for placebo. No increased incidence of heart block was observed at the recommended doses. Patients treated with galantamine up to 24 mg/day using the recommended dosing schedule showed a dose-related increase in risk of syncope (placebo 0.7% [2/286]; 4 mg BID 0.4% [3/692]; 8 mg BID 1.3% [7/552]; 12 mg BID 2.2% [6/273]). Gastrointestinal Conditions RAZADYNE® ER/RAZADYNE®, as a predictable consequence of its pharmacological properties, has been shown to produce nausea, vomiting, diarrhea, anorexia, and weight loss (see ADVERSE REACTIONS). Genitourinary Neurological Conditions Pulmonary Conditions ---------------------------------------------------------- PRECAUTIONS Deaths in Subjects with Mild Cognitive Impairment (MCI) Although the difference in mortality between RAZADYNE® and placebo-treated groups in these two studies was significant, the results are highly discrepant with other studies of RAZADYNE®. Specifically, in these two MCI studies, the mortality rate in the placebo-treated subjects was markedly lower than the rate in placebo-treated patients in trials of RAZADYNE® in Alzheimer's disease or other dementias (0.7 per 1000 person years compared to 22-61 per 1000 person years, respectively). Although the mortality rate in the RAZADYNE®-treated MCI subjects was also lower than that observed in RAZADYNE®-treated patients in Alzheimer's disease and other dementia trials (10.2 per 1000 person years compared to 23-31 per 1000 person years, respectively), the relative difference was much less. When the Alzheimer's disease and other dementia studies were pooled (n=6000), the mortality rate in the placebo group numerically exceeded that in the RAZADYNE® group. Furthermore, in the MCI studies, no subjects in the placebo group died after 6 months, a highly unexpected finding in this population. Individuals with mild cognitive impairment demonstrate isolated memory impairment greater than expected for their age and education, but do not meet current diagnostic criteria for Alzheimer's disease. Special Populations Renal Impairment Carcinogenesis, Mutagenesis and Impairment of Fertility Galantamine was not carcinogenic in a 6-month oral carcinogenicity study in transgenic (P 53-deficient) mice up to 20 mg/kg/day, or in a 24-month oral carcinogenicity study in male and female mice up to 10 mg/kg/day (2 times the MRHD on a mg/m2 basis and equivalent on an AUC basis). Galantamine produced no evidence of genotoxic potential when evaluated in the in vitro Ames S. typhimurium or E. coli reverse mutation assay, in vitro mouse lymphoma assay, in vivo micronucleus test in mice, or in vitro chromosome aberration assay in Chinese hamster ovary cells. No impairment of fertility was seen in rats given up to 16 mg/kg/day (7 times the MRHD on a mg/m2 basis) for 14 days prior to mating in females and for 60 days prior to mating in males. Pregnancy There are no adequate and well-controlled studies of RAZADYNE® in pregnant women. RAZADYNE® should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus. Nursing Mothers Pediatric Use ---------------------------------------------------------- OVERDOSE As in any case of overdose, general supportive measures should be utilized. Signs and symptoms of significant overdosing of galantamine are predicted to be similar to those of overdosing of other cholinomimetics. These effects generally involve the central nervous system, the parasympathetic nervous system, and the neuromuscular junction. In addition to muscle weakness or fasciculations, some or all of the following signs of cholinergic crisis may develop: severe nausea, vomiting, gastrointestinal cramping, salivation, lacrimation, urination, defecation, sweating, bradycardia, hypotension, respiratory depression, collapse and convulsions. Increasing muscle weakness is a possibility and may result in death if respiratory muscles are involved. Tertiary anticholinergics such as atropine may be used as an antidote for RAZADYNE® (galantamine hydrobromide) overdosage. Intravenous atropine sulfate titrated to effect is recommended at an initial dose of 0.5 to 1.0 mg i.v. with subsequent doses based upon clinical response. Atypical responses in blood pressure and heart rate have been reported with other cholinomimetics when coadministered with quaternary anticholinergics. It is not known whether RAZADYNE® and/or its metabolites can be removed by dialysis (hemodialysis, peritoneal dialysis, or hemofiltration). Dose-related signs of toxicity in animals included hypoactivity, tremors, clonic convulsions, salivation, lacrimation, chromodacryorrhea, mucoid feces, and dyspnea. In one postmarketing report, one patient who had been taking 4 mg of galantamine daily for a week inadvertently ingested eight 4 mg tablets (32 mg total) on a single day. Subsequently, she developed bradycardia, QT prolongation, ventricular tachycardia and torsades de pointes accompanied by a brief loss of consciousness for which she required hospital treatment. Two additional cases of accidental ingestion of 32 mg (nausea, vomiting, and dry mouth; nausea, vomiting, and substernal chest pain) and one of 40 mg (vomiting), resulted in brief hospitalizations for observation with full recovery. One patient, who was prescribed 24 mg/day and had a history of hallucinations over the previous two years, mistakenly received 24 mg twice daily for 34 days and developed hallucinations requiring hospitalization. Another patient, who was prescribed 16 mg/day of oral solution, inadvertently ingested 160 mg (40 mL) and experienced sweating, vomiting, bradycardia, and near-syncope one hour later, which necessitated hospital treatment. His symptoms resolved within 24 hours. ---------------------------------------------------------- CONTRAINDICATIONS |
氢溴酸加兰他敏片剂|RAZADYNE(GALANTAMINE HYDROBROMIDE)简介:
氢溴酸加兰他敏 Galantamine Hydrobromide
作用与用途:本品为抗胆碱酯酶药,有较弱的抗胆碱酯酶作用,能透过血脑屏障,故对中枢神经系统作用比较强。使受阻碍的神经肌肉传导恢复,改善各种末梢神 ... 责任编辑:admin |
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