| 英文药名: Mirapex (pramipexole tablets)
中文药名: 米拉帕（普拉克索片） 生产厂家: Boehringer Ingelheim 药品名称 药理毒性 药代动力学 适应症 用法用量 不良反应 禁忌 注意事项 孕妇和哺乳期妇女用药 MIRAPEX® ER™ DRUG DESCRIPTION Pramipexole dihydrochloride is a white to off-white powder substance. Melting occurs in the range of 296°C to 301°C, with decomposition. Pramipexole dihydrochloride is more than 20% soluble in water, about 8% in methanol, about 0.5% in ethanol, and practically insoluble in dichloromethane. MIRAPEX ER tablets, for oral administration, contain 0.375 mg, 0.75 mg, 1.5 mg, 3 mg, or 4.5 mg of pramipexole dihydrochloride monohydrate. Inactive ingredients are hypromellose, corn starch, carbomer homopolymer, colloidal silicon dioxide, and magnesium stearate. ----------------------------------------------------- INDICATIONS ----------------------------------------------------- DOSAGE AND ADMINISTRATION MIRAPEX ER tablets must be swallowed whole and must not be chewed, crushed, or divided. If a significant interruption in therapy with MIRAPEX ER tablets has occurred, re-titration of therapy may be warranted. Dosing for Parkinson's Disease In clinical trials, dosage was initiated at 0.375 mg/day and gradually titrated based on individual therapeutic response and tolerability. Doses greater than 4.5 mg/day have not been studied in clinical trials. Patients should be assessed for therapeutic response and tolerability at a minimal interval of 5 days or longer after each dose increment [see Clinical Studies]. Due to the flexible dose design used in clinical trials, specific dose-response information could not be determined [see Clinical Studies]. When discontinuing therapy with MIRAPEX ER, taper the dose gradually over a period of one week. In some studies with immediate-release pramipexole tablets, however, abrupt discontinuation was uneventful. Dosing in Patients with Renal Impairment In patients with moderate renal impairment (creatinine clearance between 30 and 50 mL/min), MIRAPEX ER tablets should initially be taken every other day. Caution should be exercised and careful assessment of therapeutic response and tolerability should be made before increasing to daily dosing after one week, and before any additional titration in 0.375 mg increments up to 2.25 mg per day. Dose adjustment should occur no more frequently than at weekly intervals. MIRAPEX ER tablets have not been studied in patients with severe renal impairment (creatinine clearance < 30 mL/min) or patients on hemodialysis, and are not recommended in these patients. Switching from Immediate-Release Pramipexole Tablets to MIRAPEX ER ----------------------------------------------------- HOW SUPPLIED 0.75 mg white to off-white, round, bevel-edged, extended-release tablets debossed with “ER” on one side and “0.75” on the other side 1.5 mg white to off-white, oval, extended-release tablets debossed with “ER” on one side and “1.5” on the other side 3 mg white to off-white, oval, extended-release tablets debossed with “ER” on one side and “3.0” on the other side 4.5 mg white to off-white, oval, extended-release tablets debossed with “ER” on one side and “4.5” on the other side Storage And Handling 0. 375 mg: white to off-white, round, bevel-edged, extended-release tablets debossed with “ER” on one side and “0.375” on the other side. 0.75 mg: white to off-white, round, bevel-edged, extended-release tablets debossed with “ER” on one side and “0.75” on the other side. 1.5 mg: white to off-white, oval, extended-release tablets debossed with “ER” on one side and “1.5” on the other side. 3 mg: white to off-white, oval, extended-release tablets debossed with “ER” on one side and “3.0” on the other side. 4.5 mg: white to off-white, oval, extended-release tablets debossed with “ER” on one side and “4.5” on the other side. Storage ----------------------------------------------------- SIDE EFFECTS Clinical Trials Experience During the premarketing development of MIRAPEX ER tablets, patients with early Parkinson's disease were treated with MIRAPEX ER tablets, placebo, or immediate-release pramipexole tablets. In addition, a randomized, double-blind, parallel group trial was conducted in 156 early Parkinson's disease patients (Hoehn & Yahr Stages I-III) to assess overnight switching of immediate-release pramipexole tablets to MIRAPEX ER tablets. In this latter study, concomitant treatment with stable doses of levodopa, monoamine oxidase B inhibitor (MAOB-I) drugs, anticholinergics, or amantadine, individually or in combination, was allowed. In a third trial, advanced Parkinson's disease patients received MIRAPEX ER tablets, placebo, or immediate-release pramipexole tablets as adjunctive therapy to levodopa. Early Parkinson's Disease Twenty four of 223 (11%) patients treated with MIRAPEX ER tablets for 33 weeks discontinued treatment due to adverse events compared to 4 of 103 (4%) patients who received placebo and approximately 20 of 213 (9%) patients who received immediate-release pramipexole tablets. The adverse event most commonly causing discontinuation of treatment with MIRAPEX ER tablets was nausea (2%). Because this study used a flexible dose titration design, it was not possible to assess the effects of dose on the incidence of adverse events. Adverse events can initially occur in either the titration or maintenance phase. Some adverse events developed in MIRAPEX ER-treated patients during the titration phase and persisted ( ≥ 7 days) into the maintenance phase (i.e., MIRAPEX ER % - placebo % = treatment difference ≥ 2%); persistent adverse events were somnolence, nausea, constipation, fatigue, and dry mouth. A double-blind, randomized, parallel group trial evaluated the tolerability of an overnight switch from immediate-release pramipexole tablets to MIRAPEX ER tablets at the same daily dose in 156 early Parkinson's disease patients with or without levodopa. One of 104 patients switched from immediate-release pramipexole tablets to MIRAPEX ER tablets discontinued due to adverse events (vertigo and nausea). Advanced Parkinson's Disease Eight of 164 (5%) patients treated with MIRAPEX ER tablets for 18 weeks discontinued treatment due to adverse events compared to 7 of 178 (4%) patients who received placebo and 8 of 175 (5%) patients who received immediate-release pramipexole tablets. The most common adverse events leading to discontinuation of treatment with MIRAPEX ER tablets were nausea (1%) and hallucination (1%). Because this flexible dose study used a titration design, it was not possible to assess the effects of dose on the incidence of adverse events. Adverse events can initially occur in either the titration or maintenance phase. Some adverse events developed in MIRAPEX ER-treated patients during the titration phase and persisted ( ≥ 7 days) into the maintenance phase (i.e., MIRAPEX ER % - placebo % = treatment difference ≥ 2%); persistent adverse events were dyskinesia and insomnia. Laboratory Testing Other adverse events observed during clinical trials of immediate-release pramipexole tablets Adverse events not listed above but reported on at least two occasions (one occasion if the event was serious) in clinical studies involving 2509 individuals who received pramipexole immediate-release tablets are listed below. The reported events are included without regard to determination of a causal relationship to pramipexole immediate-release tablets. Blood and lymphatic system disorders: anemia, iron deficiency anemia, leukocytosis, leukopenia, lymphadenitis, lymphadenopathy, thrombocythaemia, thrombocytopenia Cardiac disorders: angina pectoris, arrhythmia supraventricular, atrial fibrillation, atrioventricular block first degree, atrioventricular block second degree, bradycardia, bundle branch block, cardiac arrest, cardiac failure, cardiac failure congestive, cardiomegaly, coronary artery occlusion, cyanosis, extrasystoles, left ventricular failure, myocardial infarction, nodal arrhythmia, sinus arrhythmia, sinus bradycardia, sinus tachycardia, supraventricular extrasystoles, supraventricular tachycardia, tachycardia, ventricular fibrillation, ventricular extrasystoles, ventricular hypertrophy Congenital, familial, and genetic disorders: atrial septal defect, congenital foot malformation, spine malformation Ear and labyrinth disorders: deafness, ear pain, hearing impaired, hypoacusis, motion sickness, vestibular ataxia Endocrine disorders: goiter, hyperthyroidism, hypothyroidism Eye disorders: accommodation abnormalities, amaurosis fugax, blepharitis, blepharospasm, cataract, dacryostenosis acquired, diplopia, dry eye, eye hemorrhage, eye irritation, eye pain, eyelid edema, eyelid ptosis, glaucoma, keratitis, macular degeneration, myopia, photophobia, retinal detachment, retinal vascular disorder, scotoma, vision abnormalities, vision blurred, visual acuity reduced, vitreous floaters Gastrointestinal disorders: abdominal distension, aphthous stomatitis, ascites, cheilitis, colitis, colitis ulcerative, dyspepsia, dysphagia, duodenal ulcer, duodenal ulcer hemorrhage, enteritis, eructation, fecal incontinence, gastric ulcer, gastric ulcer hemorrhage, gastritis, gastrointestinal hemorrhage, gastroesophageal reflux disease, gingivitis, haematemesis, haematochezia, hemorrhoids, hiatus hernia, hyperchlorhydria, ileus, inguinal hernia, intestinal obstruction, irritable bowel syndrome, esophageal spasm, esophageal stenosis, esophagitis, pancreatitis, periodontitis, rectal hemorrhage, reflux esophagitis, tongue edema, tongue ulceration, toothache, umbilical hernia General disorders: chest discomfort, chills, death, drug withdrawal syndrome, face edema, feeling cold, feeling hot, feeling jittery, fever, gait disturbance, impaired healing, influenza-like illness, irritability, localized edema, edema, malaise, pitting edema, thirst Hepatobiliary disorders: biliary colic, cholecystitis, cholecystitis chronic, cholelithiasis Immune system disorders: drug hypersensitivity Infections and infestations: abscess, acute tonsillitis, appendicitis, bronchiolitis, bronchitis, bronchopneumonia, cellulitis, cystitis, dental caries, diverticulitis, ear infection, eye infection, folliculitis, fungal infection, furuncle, gangrene, gastroenteritis, gingival infection, herpes simplex, herpes zoster, hordeolum, influenza, intervertebral discitis, laryngitis, lobar pneumonia, nail infection, onychomycosis, oral candidiasis, orchitis, osteomyelitis, otitis externa, otitis media, paronychia, pyelonephritis, pyoderma, sepsis, skin infection, tonsillitis, tooth abscess, tooth infection, upper respiratory tract infection, urethritis, vaginal candidiasis, vaginal infection, viral infection, wound infection Injury, poisoning, and procedural complications: accidental falls, drug toxicity epicondylitis, road traffic accident, sunburn, tendon rupture Metabolism and nutrition disorders: cachexia, decreased appetite, decreased weight, dehydration, diabetes mellitus, fluid retention, gout, hypercholesterolemia, hyperglycemia, hyperlipidemia, hyperuricemia, hypocalcemia, hypoglycemia, hypokalemia, hyponatremia, hypovitaminosis, increased creatine PK, metabolic alkalosis Musculoskeletal and connective tissue disorders: bone pain, bursitis, fasciitis, flank pain, intervertebral disc disorder, intervertebral disc protrusion, joint effusion, joint stiffness, joint swelling, monarthritis, muscle rigidity, musculoskeletal stiffness, myasthenia, myopathy, myositis, nuchal rigidity, osteoarthritis, osteonecrosis, osteoporosis, pain in extremity, polymyalgia, rheumatoid arthritis, shoulder pain, spinal osteoarthritis, tendonitis, tenosynovitis, twitching Neoplasms benign, malignant, and unspecified: abdominal neoplasm, adenocarcinoma, adenoma benign, basal cell carcinoma, bladder cancer, breast cancer, breast neoplasm, chronic lymphocytic leukemia, colon cancer, colorectal cancer, endometrial cancer, gallbladder cancer, gastric cancer, gastrointestinal neoplasm, hemangioma, hepatic neoplasm, hepatic neoplasm malignant, lip and/or oral cavity cancer, lung neoplasm malignant, lung cancer metastatic, lymphoma, malignant melanoma, melanocytic naevus, metastases to lung, multiple myeloma, oral neoplasm benign, neoplasm, neoplasm malignant, neoplasm prostate, neoplasm skin, neuroma, ovarian cancer, prostate cancer, prostatic adenoma, pseudo lymphoma, renal neoplasm, skin cancer, skin papilloma, squamous cell carcinoma, thyroid neoplasm, uterine leiomyoma Nervous system disorders: ageusia, akinesia, amnesia, akathisia, anticholinergic syndrome, aphasia, brain edema, carotid artery occlusion, carpal tunnel syndrome, cerebral artery embolism, cerebral hemorrhage, cerebral infarction, cerebral ischemia, chorea, cognitive disorder, coma, convulsion, coordination abnormal, dementia, depressed level of consciousness, disturbance in attention, dizziness postural, dysarthria, dysgraphia, dystonia, extrapyramidal syndrome, facial palsy, grand mal convulsion, hemiplegia, hyperaesthesia, hyperkinesia, hyperreflexia, hyporeflexia, hypertonia, hypesthesia, hypotonia, lethargy, loss of consciousness, memory impairment, migraine, muscle contractions involuntary, myoclonus, narcolepsy, neuralgia, neuropathy, nystagmus, parosmia, psychomotor hyperactivity, sciatica, sedation, sensory disturbance, sleep phase rhythm disturbance, sleep talking, stupor, syncope vasovagal, tension headache, thinking abnormalities Psychiatric disorders: affect lability, aggression, agitation, bradyphrenia, bruxism, suicide, delirium, delusions, delusional disorder persecutory type, disorientation, dissociation, emotional distress, euphoric mood, initial insomnia, libido increased, mania, middle insomnia, mood altered, nightmare, obsessive thoughts, obsessive-compulsive disorder, panic reaction, paranoid reaction, parasomnia, personality disorder, psychotic disorder, restlessness, sleep walking, suicidal ideation Renal and urinary disorders: chromaturia, dysuria, glycosuria, hematuria, urgency, nephrolithiasis, neurogenic bladder, nocturia, oliguria, pollakiuria, proteinuria, renal artery stenosis, renal colic, renal cyst, renal failure, renal impairment, urinary frequency, urinary incontinence, urinary retention, urinary tract infection Reproductive system and breast disorders: amenorrhea, breast pain, dysmenorrhea, epididymitis, gynaecomastia, impotence, menopausal symptoms, menorrhagia, metrorrhagia, ovarian cyst, priapism, prostatitis, sexual dysfunction, uterine hemorrhage, vaginal discharge, vaginal hemorrhage Respiratory, thoracic, and mediastinal disorders: apnea, aspiration, asthma, choking, chronic obstructive pulmonary disease, dry throat, dysphonia, dyspnea exertional, epistaxis, haemoptysis, hiccups, hyperventilation, increased bronchial secretion, laryngospasm, nasal congestion, nasal dryness, nasal polyps, obstructive airways disorder, pharyngolaryngeal pain, pleurisy, pneumonia, pneumonia aspiration, pneumothorax, postnasal drip, productive cough, pulmonary embolism, pulmonary edema, respiratory alkalosis, respiratory distress, respiratory failure, respiratory tract congestion, rhinitis allergic, rhinorrhea, sinus congestion, sleep apnoea syndrome, sneezing, snoring, tachypnea, wheezing Skin and subcutaneous tissue disorders: acne, alopecia, cold sweat, dermal cyst, dermatitis, dermatitis bullous, dermatitis contact, dry skin, ecchymosis, eczema, erythema, hyperkeratosis, livedo reticularis, night sweats, periorbital edema, petechiae, photosensitivity allergic reaction, psoriasis, purpura, rash erythematous, rash maculo-papular, rash papular, rosacea, seborrhea, seborrheic dermatitis, skin burning sensation, skin discoloration, skin disorders, skin exfoliation, skin hyperpigmentation, skin hypertrophy, skin irritation, skin nodule, skin odor abnormal, skin ulcer, urticaria Vascular disorders: aneurysm, angiopathy, arteriosclerosis, circulatory collapse, deep vein thrombosis, embolism, hematoma, hot flush, hypertensive crisis, lymphoedema, pallor, phlebitis, Raynaud's phenomenon, shock, thrombophlebitis, thrombosis, varicose vein Postmarketing Experience ----------------------------------------------------- DRUG INTERACTIONS Dopamine Antagonists Drug/Laboratory Test Interactions Drug Abuse And Dependence Abuse and Dependence ----------------------------------------------------- WARNINGS ----------------------------------------------------- PRECAUTIONS In early Parkinson's disease, somnolence was reported in 36% of 223 patients treated with MIRAPEX ER, median dose 3.0 mg/day, compared to 15% of 103 patients on placebo. In advanced Parkinson's disease, somnolence was reported in 15% of 164 patients treated with MIRAPEX ER tablets, median dose 3 mg/day, compared to 16% of 178 patients on placebo. Many clinical experts believe that falling asleep while engaged in activities of daily living always occurs in a setting of preexisting somnolence, although patients may not give such a history. For this reason, prescribers should continually reassess patients for drowsiness or sleepiness, especially since some of the events occur well after the start of treatment. Prescribers should also be aware that patients may not acknowledge drowsiness or sleepiness until directly questioned about drowsiness or sleepiness during specific activities. Before initiating treatment with MIRAPEX ER tablets, advise patients of the potential to develop drowsiness, and specifically ask about factors that may increase the risk such as the use of concomitant sedating medications or alcohol, the presence of sleep disorders, and concomitant medications that increase pramipexole plasma levels (e.g., cimetidine) [see CLINICAL PHARMACOLOGY]. If a patient develops significant daytime sleepiness or episodes of falling asleep during activities that require active participation (e.g., conversations, eating, etc.), MIRAPEX ER tablets should ordinarily be discontinued. If a decision is made to continue MIRAPEX ER tablets, advise patients not to drive and to avoid other potentially dangerous activities. While dose reduction reduces the degree of somnolence, there is insufficient information to establish that dose reduction will eliminate episodes of falling asleep while engaged in activities of daily living. Symptomatic Orthostatic Hypotension Impulse Control/Compulsive Behaviors Hallucinations Age appears to increase the risk of hallucinations attributable to pramipexole. In placebo-controlled clinical trials in Parkinson's disease, hallucinations were reported in 15 of 162 (9%)patients ≥ 65 years of age taking MIRAPEX ER tablets compared to 10 of 225 (4%)patients < 65 years of age taking MIRAPEX ER tablets. Dyskinesia Renal Impairment Rhabdomyolysis Advise patients to contact a physician if they experience any unexplained muscle pain, tenderness, or weakness, as these may be symptoms of rhabdomyolysis. Retinal Pathology in Rat Events Reported with Dopaminergic Therapy Withdrawal-Emergent Hyperpyrexia and Confusion Fibrotic Complications Although these adverse events are believed to be related to the ergoline structure of these compounds, whether other, non-ergot derived dopamine agonists can cause them is unknown. Cases of possible fibrotic complications, including peritoneal fibrosis, pleural fibrosis, and pulmonary fibrosis have been reported in the postmarketing experience with immediate-release pramipexole tablets. While the evidence is not sufficient to establish a causal relationship between pramipexole and these fibrotic complications, a contribution of pramipexole cannot be completely ruled out. Melanoma For the reasons stated above, patients and providers are advised to monitor for melanomas frequently and on a regular basis when using MIRAPEX ER tablets for any indication. Ideally, periodic skin examinations should be performed by appropriately qualified individuals (e.g., dermatologists). Patient Counseling Information Dosing Instructions MIRAPEX ER tablets can be taken with or without food. If patients develop nausea, advise that taking MIRAPEX ER tablets with food may reduce the occurrence of nausea. MIRAPEX ER tablets should be swallowed whole. They should not be chewed, crushed, or divided [see DOSAGE AND ADMINISTRATION]. Pramipexole is the active ingredient that is in both MIRAPEX ER tablets and immediate-release pramipexole tablets. Ensure that patients do not take both immediate-release pramipexole and MIRAPEX ER. Sedating Effects Impulse Control Symptoms Including Compulsive Behaviors Hallucinations Postural (Orthostatic) Hypotension Pregnancy Nursing Mothers Nonclinical Toxicology Pramipexole was not mutagenic or clastogenic in a battery of in vitro (bacterial reverse mutation, V79/HGPRT gene mutation, chromosomal aberration in CHO cells) and in vivo (mouse micronucleus) assays. In rat fertility studies, pramipexole at a dose of 2.5 mg/kg/day (5 times the MRHD on a mg/m² basis) prolonged estrus cycles and inhibited implantation. These effects were associated with reductions in serum levels of prolactin, a hormone necessary for implantation and maintenance of early pregnancy in rats. Use In Specific Populations When pramipexole was given to female rats throughout pregnancy, implantation was inhibited at a dose of 2.5 mg/kg/day [5 times the maximum recommended human dose (MRHD) on a mg/m² basis]. Administration of 1.5 mg/kg/day of pramipexole to pregnant rats during the period of organogenesis (gestation days 7 through 16) resulted in a high incidence of total resorption of embryos. The plasma AUC in rats at this dose was 4 times the AUC in humans at the MRHD. These findings are thought to be due to the prolactin-lowering effect of pramipexole, since prolactin is necessary for implantation and maintenance of early pregnancy in rats (but not rabbits or humans). Because of pregnancy disruption and early embryonic loss in these studies, the teratogenic potential of pramipexole could not be adequately evaluated. There was no evidence of adverse effects on embryo-fetal development following administration of up to 10 mg/kg/day to pregnant rabbits during organogenesis (plasma AUC was 70 times that in humans at the MRHD). Postnatal growth was inhibited in the offspring of rats treated with 0.5 mg/kg/day (approximately equivalent to the MRHD on a mg/m² basis) or greater during the latter part of pregnancy and throughout lactation. Nursing Mothers Studies have shown that pramipexole treatment resulted in an inhibition of prolactin secretion in humans and rats. It is not known whether this drug is excreted in human milk. Because many drugs are excreted in human milk and because of the potential for serious adverse reactions in nursing infants from pramipexole, a decision should be made as to whether to discontinue nursing or to discontinue the drug, taking into account the importance of the drug to the mother. Pediatric Use Geriatric Use Patients with Renal Impairment ----------------------------------------------------- OVERDOSE There is no known antidote for overdosage of a dopamine agonist. If signs of central nervous system stimulation are present, a phenothiazine or other butyrophenone neuroleptic agent may be indicated; the efficacy of such drugs in reversing the effects of overdosage has not been assessed. Management of overdose may require general supportive measures along with gastric lavage, intravenous fluids, and electrocardiogram monitoring. ----------------------------------------------------- CONTRAINDICATIONS 注：以下产品不同规格和不同价格，购买时请以下面电话咨询为准！ --------------------------------------------------------------- |
盐酸普拉克索缓释片|MIRAPEX ER(Pramipexole Dihydrochloride)简介：
英文药名: Mirapex (pramipexole tablets)
中文药名: 米拉帕（普拉克索片）
生产厂家: Boehringer Ingelheim
药品名称药品名：盐酸普拉克索片 英文名：Pramipexole Dihydrochloride Tablets 性状: 本品 ... 责任编辑：admin
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