topamax::用法 注意事項

TOPIRAMATE

托吡酯

<< 商品名 >>

美國 - Topamax

加拿大 - Apo-Topiramate; CO Topiramate; Dom-Topiramate; Mint-Topiramate; Mylan-Topiramate; Novo-Topiramate; PHL-Topiramate; Epitomax ( 芬蘭 , 法國 ); Topamac ( 阿根廷 , 印度 , 秘魯 , 烏拉圭 ); Topamax ( 阿拉伯 , 奧地利 , 澳大利亞 , 比利時 , 巴西 , 瑞士 , 智利 , 德國 , 西班牙 , 芬蘭 , 香港 , 愛爾蘭 , 以色列 , 義大利 , 墨西哥 , 馬來西亞 , 荷蘭 , 紐西蘭 ) 菲律賓 , 巴基斯坦 , 波蘭 , 葡萄牙 , 俄羅斯 , 新加坡 , 泰國 , 土耳其 , 委內瑞拉 , 南非 ); Topamax Sprinkle ( 香港 , 以色列 , 紐西蘭 ) ; Topimax ( 丹麥 , 挪威 , 巴拿馬 , 瑞典 )

<< 藥物作用 >>

Topiramate是一種「治療癲癇」的藥物。 腦部是由許多神經細胞所組成的並透過電子信號彼此聯络。通常這些信號是由一些腦神經傳導物質或電離子所調控，如果調控失常，腦神經會產生不正常放電，造成腦神經過度刺激而造成癲癇。

Topiramate 可單獨使用或與其它藥物一起合用以預防或控制癲癇的發作。目前為止，此藥物的作用機制不是很明確，但相信是藉著增強腦內神經傳導物 GABA 的活動，以及防止鈉離子進入神經细胞，因而防止腦神經不正常放電，達到預防癲癇發作的作用。

此藥物也可以用於防止或減少偏頭痛發生的頻率，使偏頭痛發生次數減少或停止。但是它不具有止痛作用，因此不可當作急性偏頭疼發作時的止痛藥使用。此藥其中之一的副作用是會造成體重減輕，因此許多醫師利用此一副作用，幫助病患達到減肥的目地。

<< 用法 >>

此藥可以空腹或與食物一起服用，通常一天服用兩次。由於藥物有苦味，因此最好整粒吞服，不要在嘴內咀嚼或壓碎服用。為了防止腎結石的形成，除非醫生指示外，服藥時應該飲用額外的流體。使用膠囊時，如有必要，可打開膠囊，將裡面的小顆粒灑在柔軟的食物上使用，但切忌在嘴中咀嚼，應該直接吞服入口。

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<< 注意事項 >>

如果懷孕，對藥物過敏，或者有腎臟疾病﹑腎結石﹑青光眼﹑電解質代謝不平衡﹑骨質疏鬆症等等，醫師需要針對這些情況謹慎用藥，因此在使用此藥之前，應該先通知醫師。

美衛生署曾發出警訊，要求醫藥人員及病患密切注意T opiramate 可能引起眼睛方面的副作用，尤其在服藥的第一個月發生的機率最高。其症狀包括視覺模糊，淚流不止，眼睛充血，眼痛，眼壓增高等，甚至可能造成短暫或永久性的失明。以上的副作用如果及早發現，停藥及治療後，視力通常可恢復回原有狀態。病患服用此藥時需留意視力的變化，如果眼睛四周感覺疼痛，視覺突然模糊，必須立即通知醫師。

此藥可能會讓您覺得眩暈或嗜睡，除非已經適應了藥物的作用，當開車或操作危險機械時，應該格外小心謹慎。如果感覺眩暈，緩慢站立或坐起，應該會減少此一現象。酒精會增加藥物嗜睡的副作用，應當避免或限制酒量。感冒(流感)藥，止痛劑，肌肉鬆弛劑，抗抑劑，癲癇藥會增加此藥的嗜睡作用，應該特別留意。

此藥物的處方劑量根據病患健康狀況或適應症有所不同。對於兒童，藥物劑量也許需要根據体重而調整，並經過幾個星期的時間，逐漸增加劑量，以降低藥物可能產生的副作用如如嗜睡和記憶等問題，病患在服藥時﹑應完全遵循醫師指示使用。

如果您服此藥的目的是預防癲癇發作，應該養成定時服藥的習慣，以免忘記服藥而觸發癲癇的發作。服用藥物一段時期後，也不可未經醫師許可下突然地停藥，突然停藥有可能會使癲癇病況轉壞或發作。如有停藥的必要時，醫師也許會要求服用另一種取代藥物，並且經過一段時間後，逐漸地將此藥的劑量降低，然後再停。

此藥對少許病患，可能會降底身體排汗散熱的能力，尤其在大熱天中從事激烈運動後，對於小孩的影響更為明顯。為了避免中暑，在運動時應穿著透氣性好及輕便宽鬆易透風的衣服，並隨時補充水分。病患如果覺得體溫過高應該立即停止運動，並在陰凉通風或有冷氣的房間休息，待體溫恢復正常後，再回復運動。

服用此藥後，有可能會降低口服避孕藥的作用。女性患者如果在服藥期間有任何不正常月經出血或變化，此代表避孕藥的藥效減弱，病患最好能同時併用其它有效的避孕方法。此藥也有可能造成皮膚不正常反應如皮膚發紅，脫皮，發癢等。如果有以上症狀或其它皮膚不正常反應，請告知醫師。

<< 副作用 >>

Topiramate 最常見的副作用為：頭暈（ 4 ％至 25 ％）﹑疲勞（ 9 ％至 16 ％）﹑神經質（ 9 ％至 18 ％）﹑記憶困難（ 2 ％至 12 ％）﹑行為問題（兒童 11 ％）﹑食慾不振（ 4 ％至 24 ％）﹑味覺改變（ 3 ％至 15 ％）﹑噁心（ 6 ％至 10 ％）﹑感覺異常（ 1 ％至 11 ％）﹑視覺異常（ 2 ％至 13 ％）。其它可能副作用包括：臉部發紅發熱﹑腹瀉﹑體重下降﹑嗜睡﹑ 經期改變﹑腸胃不適﹑腹痛﹑厭食﹑頭痛及體重減輕等。這些副作用﹑通常在服用藥物一陣子後﹑應該會漸漸消失。如果這些副作用達到困擾你的程度﹑或者經過一段時間後﹑這些症狀還不能完全消除﹑就應該通知醫師。

此藥較嚴重的副作用為 : 尿液顏色變紅或混濁﹑下背部痛﹑血尿﹑尿液變紅﹑心情或行為異常﹑憂鬱﹑手麻﹑出血﹑皮疹﹑行為改變﹑視力模糊﹑突然間眼睛痛﹑眼球跳動﹑ 精神混亂﹑ 運動失調﹑焦慮﹑發作次數遽增﹑喉嚨痛﹑發燒﹑腎結石﹑語言障礙﹑顫抖等。通常這些副作用發生的機率較低﹑但是如果發生時﹑此可能是藥物造成的不良反應﹑或者是劑量需要調整﹑應該盡快通知醫師。

<< 懷孕及哺乳 >

美國藥管局 (FDA) 將此藥歸類為 D 級： D 級表示從以往研究或銷售經驗中﹑已有足夠證據顯示藥物會對胎兒產生危險性。盡管有潛在風險﹑但在用藥利益大於危險性的前提下﹑(在醫師的監測下) 仍然可以考慮使用。

動物實驗顯示，孕婦服用此藥可能會造成胎兒出生後骨骼或脊柱方面的問題。不過，也有報告指出此可能與癲癇病症本身有關。藥物治療對預防癲癇的發作相當重要，而且在醫師的特別照顧下，絕大部分的孕婦都會生出正常的嬰兒。如果停止服藥，可能會導致母體及胎兒更大的危險，在利弊得失之間，醫師可能會要求繼續服藥，而將劑量及副作用降到最低程度。

Micromedex公司哺乳評級結論﹕ 對嬰兒的風險性還無法排除 。

( 由於現有資料不足或專家結論不同情況下﹑無法充分證明哺乳期間使用藥物是否會增加嬰兒的風險。婦女若考慮使用母奶哺乳嬰兒﹑應該權衡藥物的優點或藥物對嬰兒潛在的風險性。 )

此药会经由母乳到达婴儿体内 ﹑ 對嬰兒的影響還未知。 为了避免药物可能造成新生儿的不良影响，餵奶的母亲应该考虑使用其它乳制品，以取代母乳。

<< 忘記用藥 >>

如果忘記服藥，應該在記得時，立即服用。但是，如果距離下次服藥的時間太近，就應該捨棄此次的藥物，恢復到下次正常服藥的時間，千萬不可一次服用雙倍的劑量。

Topiramate (brand name Topamax ) is an anticonvulsant (antiepilepsy) drug. In late 2012, topiramate was approved by the United States Food & Drug Administration (FDA) in combination with phentermine for weight loss . The drug had previously been used off-label for this purpose. Topiramate was originally produced by Ortho-McNeil Neurologics and Noramco, Inc., both divisions of the Johnson & Johnson Corporation. This medication was discovered in 1979 by Bruce E. Maryanoff and Joseph F. Gardocki during their research work at McNeil Pharmaceutical. [ 1 ] [ 2 ] [ 3 ] Topiramate was first approved in the US in 1996. [ 4 ] Generic versions are available in Canada and these were approved by the FDA in September 2006. Mylan Pharmaceuticals was recently granted final approval for generic topiramate 25, 100, and 200 mg tablets and sprinkle capsules by the FDA for sale in the United States . 50 mg tablets were granted tentative approval. [ 5 ] The last patent for topiramate in the U.S. was for pediatric use; this patent expired on February 28, 2009. [ 6 ]

Topiramate is used to treat epilepsy in children and adults, and it was originally used as an anticonvulsant . In children, it is indicated for the treatment of Lennox-Gastaut syndrome , a disorder that causes seizures and developmental delay. It is also Food and Drug Administration (FDA) approved for, and most frequently prescribed for, the prevention of migraines . Psychiatrists have used topiramate to treat bipolar disorder , [ 7 ] and they sometimes use topiramate to augment psychotropics, or to counteract the weight gain associated with numerous antidepressants. In 2006, a Cochrane review concluded that there is insufficient evidence on which to base any recommendations regarding the use of topiramate in any phase of bipolar illness. [ 8 ] A more recent Cochrane review , published in 2010, suggested a benefit of topiramate in the treatment of symptoms of borderline personality disorder , however the authors note that this was based only on one randomized controlled trial and requires replication. Also the Authors noted that the long-term effects have not been studied. [ 9 ]

This drug has been investigated for use in treating alcoholism, [ 10 ] [ 11 ] methamphetamine addiction, [ 12 ] and obesity, [ 13 ] [ 14 ] especially to reduce binge eating . [ 15 ] [ 16 ]

This drug is also widely used to treat migraines due to the effect it has on the blood vessels in the brain. It is used as a preventative for atypical migraine sufferers. It widens the blood vessels in the brain which become restricted by increased serotonin levels. It has been found to be increasingly effective for migraine sufferers with very few side effects.

The drug is also used in clinical trials to treat post traumatic stress disorder . [ 17 ] A pilot study suggested that topiramate is effective against infantile spasms. [ 18 ] Another study recommends topiramate as an effective treatment in the prevention of periventricular leukomalacia in preterm infants after an hypoxic - ischemic injury. [ 19 ]

Recent clinical reports indicate that it may have mood stabilizing properties. [ 20 ] Other off-label and investigational uses of topiramate include the treatment of essential tremor , bulimia nervosa , [ 21 ] obsessive-compulsive disorder , alcoholism , [ 11 ] smoking cessation , [ 22 ] idiopathic intracranial hypertension , [ 23 ] cluster headache , [ 24 ] migraine headache, treatment-resistant depression , cocaine dependence, and Borderline Personality Disorder . [ 25 ] [ 26 ] Topiramate is also being studied with a mixture of phentermine to form a drug called Qsymia for the treatment of obesity . Topiramate has not been shown to work as a pain medicine in diabetic neuropathy, the only neuropathic condition in which it has been adequately tested. [ 27 ]

On May 21, 2010, Ortho-McNeil pled guilty and was fined $6.14 million by the FDA for promoting Topamax to treat psychiatric disorders without applying for any Federal government approval. Also, there were no data from any well-controlled clinical trial to demonstrate that Topamax was safe and/or effective to treat any psychiatric conditions at all. [ 28 ]

A GlaxoSmithKline -sponsored Phase IV study suggested that cognitive side effects may be more common with topiramate than with lamotrigine . [ 29 ] In studies of healthy volunteers, therapeutic doses of topiramate for bipolar disorder produced greater cognitive deficits than lamotrigine, including short term memory loss and word-finding difficulty.

Side-effects reported by > 10% of subjects in at least one clinical study [ 30 ] (listed by prevalence):

Side-effects most frequently leading to discontinuation of therapy with topiramate:

That same study also reported that in adult patients with Bipolar 1 disorder who were already receiving either lithium or valproate , the addition of topiramate did not produce a statistically significant improvement versus placebo, while adding the above adverse reactions.

Rarely, the inhibition of carbonic anhydrase may be strong enough to cause metabolic acidosis of clinical importance. [ 31 ]

The U.S. Food and Drug Administration (FDA) has notified prescribers that topiramate can cause acute myopia and secondary angle closure glaucoma in a small subset of people who take topiramate regularly. [ 32 ] The symptoms, which typically begin in the first month of use, include blurred vision and eye pain. Discontinuation of topiramate may halt the progression of the ocular damage, and may reverse the visual impairment.

Preliminary data suggests that, as with several other anti-epileptic drugs, topiramate carries an increased risk of congenital malformations. [ 33 ] This might be particularly important for women who take topiramate to prevent migraine attacks. In March 2011 the FDA notified healthcare professionals and patients of an increased risk of development of cleft lip and/or cleft palate (oral clefts) in infants born to women treated with Topamax (topiramate) during pregnancy and placed it in Pregnancy Category D. [ 34 ]

Topiramate has been associated with a statistically significant increase in suicidality , [ 35 ] and "suicidal thoughts or actions" is now listed as one of the possible side effects of the drug "in a very small number of people, about 1 in 500." [ 36 ]

Topiramate has many drug-drug interactions. Some of the most common are listed below:

Overdose is rare. In most cases, acute exposure produced only minimal to moderate effects. Fatalities have occurred, but were the result of polydrug exposure.

Symptoms of overdose may include but are not limited to: [ citation needed ]

A specific antidote is not available. Treatment is entirely supportive.

Blood, serum or plasma topiramate concentrations may be measured using immunoassay or chromatographic methods to monitor therapy, confirm a diagnosis of poisoning in hospitalized patients or to assist in a medicolegal death investigation. Plasma levels are usually less than 10 mg/L during therapeutic administration, but can range from 10–150 mg/L in overdose victims. [ 39 ] [ 40 ] [ 41 ]

People taking topiramate should be aware of the following risks:

Chemically, topiramate is a sulfamate -substituted monosaccharide , related to fructose , a rather unusual chemical structure for an anticonvulsant.

Topiramate is quickly absorbed after oral use. Most of the drug (70%) is excreted in the urine unchanged. The remainder is extensively metabolized by hydroxylation , hydrolysis , and glucuronidation . Six metabolites have been identified in humans, none of which constitutes more than 5% of an administered dose.

The exact mechanism of action is unknown, [ 42 ] but four properties that may contribute to topiramate's antiepileptic and antimigraine efficacy include a blockage of voltage-dependent sodium channels, an augmentation of gamma-aminobutyric acid activity at some subtypes of the GABA- A receptors, antagonism of AMPA/kainate subtype of the glutamate receptor, and inhibition of the carbonic anhydrase enzyme, particularly isozymes II and IV .

Its possible effect as a mood stabilizer seems to occur before anticonvulsant qualities at lower dosages. Topiramate inhibits maximal electroshock and pentylenetetrazol -induced seizures as well as partial and secondarily generalized tonic-clonic seizures in the kindling model, findings predictive of a broad spectrum of activities clinically. Its action on mitochondrial permeability transition pores has been proposed as a mechanism. [ 44 ]

While many anticonvulsants have been associated with apoptosis in young animals, animal experiments have found that topiramate is the only anticonvulsant that does not induce apoptosis in young animals at doses needed to produce an anticonvulsant effect. [ 45 ]

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