英文药名: Cerebyx(Fosphenytoin Injections)

中文药名: 磷苯妥英钠注射液

药品简介

通用名: 磷苯妥英钠

用法用量
按本品75mg相当于苯妥英钠50mg等效剂量计算，在非紧急情况时静注或肌注苯妥英钠10～20mg/kg，最初苯妥英钠维持剂量为4～6mg/(kg.d)。静注治疗癫痫发作的苯妥英钠剂量15～20mg/kg。静脉输注前以5%葡萄糖液或0.9%氯化钠注射液稀释本品制剂，稀释后本品浓度范围为1.5～25mg/ml（苯妥因钠），稀释液置室温8h或2～8℃24h是稳定的。

药理作用
本品是在全世界第一个被批准上市的苯妥英钠前体药，具有高效抗惊厥作用。通过小鼠抗电休克试验测得本品腹腔注射或口服给药的抗惊厥作用（抗最大电休克发作）半数有效剂量ED50（mg/kg）各为10.3、11.8，苯妥英的腹腔注射或口服给药ED50（mg/kg）各为9.5、0.4，表明本品与苯妥英具有同等程度的抗惊厥作用。但是小鼠腹腔注射给红色的旋转毒性TD50(mg/kg)本品为42.1苯妥英为65.4，本品旋转毒性较苯妥英大些，这是由于本品是苯妥英的前体，容易被机体吸收所致。给大鼠腹腔注射高半胱氨酸5.5mmol/kg引起大鼠癫发作，将动物分组，每组9只大鼠，分别腹腔给本品130mg/kg和苯妥英120mg/kg，用脑电图监察给药结果。给药后30min，本品在大鼠脑内浓度几乎与苯妥英相同，60min时未测得本品血药浓度峰值，但是在给药后1~2h期间苯妥英给药组大鼠的血药浓度及脑内浓度变化较本品组显著接收本品的大鼠没有1只中止癫发作，而苯妥英组大鼠有4只中止发作，此结果差异在于本品注射后转化为苯妥英需要一定时间。
本品与苯妥英相似具有抗心律失常作用。本品为苯妥因前体药，在豚鼠动脉的体外试验中，因本品未转化为苯妥因而无抗心律失常作用，而苯妥英显示抗心律失常作用。可是在动物体内本品与苯妥英等效地拮抗哇巴因引起的心律失常。以麻醉狗进行试验评价本品对心血管作用。分别静注本品27mg/kg、苯妥英18mg/kg（两药为等分子剂量）。迅速静注苯妥英的狗立即发生及明显降低左心室压力增高率、降低平均动脉压和心率，然后反射性地加快心率。而本品仅引起较小的血流动力学变化。这与本品不引起临床上明显的心血管系统的不良反应是一致的。

适应症
本品用于控制原发性癫痫病人的痉挛症状，预防并治疗神经外科手术中惊厥的发作。

不良反应
常见不良反应为眼球震颤、眩晕、瘙痒、感觉异常、头痛、嗜睡和运动失调。除了感觉异常和瘙痒外，其余的不良反应静注较肌注为常见。按折算为苯妥英钠剂量计，以150mg/min速率静注，剂量为≥15mg/kg时约有2/3病人发生不舒适感。

注意事项
对本品或其制剂成分、苯妥英或其他乙内酰脲药物过敏者禁用，心功能异常者禁用。紫质症病人慎用本品，因苯妥英可使其症状加重。与苯妥英有相互作用的药物也可与本品发生作用，如影响血浆蛋白结合或细胞色素P450酶系统的药物，使用时需注意。
抗癫痫药物苯妥英和磷苯妥英钠可能导致患者严重皮肤不良反应.
近日，FDA发布抗癫痫药苯妥英（Phenytoin）和磷苯妥英钠（Fosphenytoin Sodium）可能导致相同严重皮肤不良反应的信息。2007年度，FDA曾发布的药物信息中指出携带HLA-B*1502等位基因的患者在服用抗癫痫药卡马西平（Carbamazepine）时可能导致致命的皮肤反应，包括史蒂文斯-约翰逊综合征（Stevens Johnson syndrome，SJS）和中毒性表皮坏死松解症（toxic epidermal necrolysis，TEN），这一特殊基因大多出现在亚裔人群中。
磷苯妥英钠是一个前体药物，在体内转化为苯妥英，因此任何与苯妥英相关的信息都适用于磷苯妥英钠。而苯妥英与卡马西平均属于二苯并氮卓类抗癫痫药物，结构相近，作用机理也类似。目前的数据显示，苯妥英与SJS/ TEN之间的关联性已被证实，而HLA-B*1502等位基因与苯妥英导致SJS/ TEN之间可能存在某种关联，证实这一关联性的研究尚在进行。在这项研究结束以前，FDA建议医护人员在为携带HLA-B*1502等位基因的患者提供苯妥英和磷苯妥英钠时应充分考虑使用该药的风险利益信息，同时应避免为这类患者提供苯妥英和磷苯妥英作为卡马西平的替代药物。

包装规格：
·75mg/ml (50mg PE)  20支 x 2ml  
·75mg/ml (50mg PE)  5支 x 10ml

Brand names: Cerebyx®
Chemical formula:

 
Fosphenytoin injection

What is fosphenytoin injection?
FOSPHENYTOIN (Cerebyx®) helps to control seizures (convulsions) in certain types of epilepsy. Fosphenytoin can help to prevent seizures occurring during or after surgery. Generic fosphenytoin injections are not available.

What should I tell my health care provider before I take this medicine?

They need to know if you have any of these conditions:
• an alcohol abuse problem
• blood disorders or disease
• depression
• diabetes
• fever
• heart problems, low blood pressure
• kidney disease
• liver disease
• porphyria
• receiving intramuscular injections
• receiving radiation therapy
• skin problems
• suicidal thoughts, plans, or attempt; a previous suicide attempt by you or a family member
• thyroid disease
• an unusual or allergic reaction to phenytoin, other medicines, foods, dyes, or preservatives
• pregnant or trying to get pregnant
• breast-feeding

How should I use this medicine?

Fosphenytoin is for injection into a vein or muscle or for infusion into a vein. It is given by a health-care professional in a hospital or clinic setting.

What if I miss a dose?

This does not apply. Your condition will be closely monitored to maintain adequate seizure control.

What drug(s) may interact with fosphenytoin?

Many medicines can interact with fosphenytoin; check with your prescriber or health care professional if you regularly take other medications or over-the-counter products. Some of the medicines that can interact with fosphenytoin are listed:
• alcohol
• amphetamines
• aspirin and aspirin-like medicines
• barbiturate medicines for inducing sleep or treating seizures (convulsions)
• bosentan
• carbamazepine
• cimetidine
• ciprofloxacin
• clopidogrel
• cyclosporine
• disulfiram
• ethosuximide
• felbamate
• female hormones, including contraceptive or birth control pills
• fluconazole
• folic acid, vitamin B9
• heart medicines such as digoxin or digitoxin
• chloramphenicol
• corticosteroid hormones such as prednisone or cortisone
• isoniazid
• itraconazole
• kava kava
• ketoconazole
• leucovorin
• levodopa
• lidocaine
• medicines for diabetes
• medicines for hay fever and other allergies
• medicines for mental depression, anxiety or other mood problems
• medicines to control heart rhythm
• medicines used to treat HIV infection or AIDS
• methadone or other medicines for pain
• methsuximide
• modafinil
• omeprazole
• oxcarbazepine
• rifampin, rifabutin or rifapentine
• sirolimus
• St. John's wort
• tacrolimus
• theophylline
• tiagabine
• ticlopidine
• tramadol
• valproic acid
• voriconazole
• warfarin
• zonisamide

Tell your prescriber or health care professional about all other medicines you are taking, including non-prescription medicines, nutritional supplements, or herbal products. Also tell your prescriber or health care professional if you are a frequent user of drinks with caffeine or alcohol, if you smoke, or if you use illegal drugs. These may affect the way your medicine works. Check with your health care professional before stopping or starting any of your medicines.

What should I watch for while taking fosphenytoin?

Visit your prescriber or health care professional for regular checks on your progress. Your prescriber or health care professional may schedule regular blood tests. Do not stop using fosphenytoin suddenly; this increases the risk of seizures. Because your condition and the use of fosphenytoin carry some risk, it is a good idea to carry an identification card, necklace or bracelet with details of your condition, medications and prescriber or health care professional.

You may feel dizzy or drowsy. Do not drive, use machinery, or do anything that needs mental alertness until you know how fosphenytoin affects you. To reduce the risk of dizzy or fainting spells, do not sit or stand up quickly, especially if you are an older patient. Alcohol can make you more dizzy, increase flushing and may cause rapid heartbeats. Avoid alcoholic drinks while receiving fosphenytoin.

The use of this medicine may increase the chance of suicidal thoughts or actions. Pay special attention to how you are responding while on this medicine. Any worsening of mood, or thoughts of suicide or dying should be reported to your health care professional right away.

Fosphenytoin can cause unusual growth of gum tissues; visit your dentist regularly. Problems can arise if you need dental work, and in the day to day care of your teeth. Try to avoid damage to your teeth and gums when you brush or floss your teeth.

What side effects may I notice from receiving fosphenytoin?

Side effects that you should report to your prescriber or health care professional as soon as possible:
• confusion, nervousness, hostility, or other behavioral changes (especially in children or elderly patients)
• difficulty breathing, wheezing or shortness of breath
• double vision or uncontrollable and rapid eye movement
• fever, sore throat
• headache
• loss of seizure control
• mouth ulcers
• pain, redness, swelling or irritation at the injection site
• poor control of body movements or difficulty walking
• sexual problems (painful erections, loss of sexual desire)
• redness, blistering, peeling or loosening of the skin, including inside the mouth
• skin rash, itching
• stomach pain
• swollen or painful glands
• unusual bleeding or bruising, pinpoint red spots on skin
• unusual tiredness or weakness
• unusual swelling
• worsening of mood, thoughts or actions of suicide or dying
• yellowing of the eyes or skin

Side effects that usually do not require medical attention (report to your prescriber or health care professional if they continue or are bothersome):
• clumsiness or unsteadiness
• constipation
• difficulty sleeping
• dizziness or drowsiness
• dry mouth
• excessive hair growth on the face or body
• nausea, vomiting
• unusual growth of gum tissue

Where can I keep my medicine?

Keep out of the reach of children.

Store in a refrigerator between 2 and 8 degrees C (36 and 46 degrees F); do not freeze. Throw away any unused medicine after the expiration date.