部分中文溴吡斯的明处方资料（仅供参考）

分类名称
一级分类：神经系统药物 二级分类：作用于自主神经系统的药物 三级分类：抗胆碱酯酶药 
 
药品英文名
Pyridostigmine Bromide
 
药品别名
吡斯的明、吡啶斯的明、溴化吡啶斯的明、美斯的侬、美定隆、溴吡啶斯的明、Bromurede、Mestinon、Regonol、Pyridostigmine bromide
 
药物剂型
1.片剂：60mg；
2.注射剂(粉)：1mg，5mg，10mg；
3.糖浆剂：12mg(1ml)；
4.缓释片：180mg。
 
药理作用
本品为季铵化合物。作用类似新斯的明。作用开始较迟，而持续时间较长。
 
药动学
本品难从胃肠道吸收。既被胆碱酯酶水解，也在肝内代谢。本品主要以原药和代谢物随尿排出。本品极少进入CSF，但可透过胎盘，少量进入乳汁。
 
适应证
重症肌无力、麻痹性肠梗阻，也可用于逆转非除极肌松药产生的神经肌肉阻滞，但一般认为其效力不如新斯的明。虽然也可用于术后尿潴留，但当前常被导尿管所取代。
 
禁忌证
1.对本品过敏者、孕妇和哺乳者禁用。
2.机械性肠梗阻和尿路梗阻者禁用。
 
注意事项
1.慎用：(1)支气管哮喘患者；(2)术后肺不张或肺炎患者；(3)心律失常尤其是房室传导阻滞者。
2.药物对妊娠的影响：孕妇给药后，由于子宫肌收缩，可引起早产。FDA妊娠分类为C类。
3.药物对哺乳的影响：少量可分泌入乳汁中。常用剂量时，婴儿通过乳汁摄入的药物量极少，乳母可安全用药。
4.重症肌无力患者：重症肌无力患者用药须谨慎，过量时可造成神经肌接头的除极型阻滞，出现肌无力现象，即“胆碱能危象”。
5.注射给药限用于拮抗非除极肌松药，注射给药后应作严密观察。
6.口服用的糖浆或缓释片一般仅供重症肌无力治疗用。因缓释片的用量大，毒性反应也较多发生，小儿一般不用。
7.本药的某些不良反应(如心动过缓，唾液多和胃肠道症状等)比新斯的明轻。
8.使用本药应严格遵守医嘱用药，并按时做记录；漏服药后不可服用双倍量；重症肌无力患者用量要恰到好处，过量时可发生胆碱能危象。
9.本药过量的特征有：视物模糊、恶心、呕吐或(和)腹泻，严重时可导致低血钾、呼吸短促、呼吸困难、喘鸣或(和)胸闷、唾液和气管支气管黏液分泌增多，甚至可引起肺不张、胃痉挛性疼痛、脉搏减慢等，由于毒蕈样作用，可导致上肢、颈、肩、舌等处肌肉出现麻痹状态，言语不清、行动不便、步态不稳、神志不清、抽搐或阵挛等。本药中毒量时出现胆碱能危象，临床表现系胆碱样和毒蕈样毒性反应的混合。使用阿托品或东莨菪碱均能予以解除。
 
不良反应
1.长期口服可出现溴化物的反应，如皮疹、乏力、恶心和呕吐等，且比溴新斯的明严重。
2.可出现轻度的抗胆碱酯酶的毒性反应，如腹痛、腹泻、唾液增多、气管内黏液分泌增加、出汗、缩瞳、血压下降和心动过缓等，一般均能自行消失。
3.凡是对溴化物过敏者，对本品也过敏。
 
用法用量
1.治疗重症肌无力：每天总量为0.3～1.2g，也有专家认为日总量不应超过720mg。全日用量，应分次给予，包括夜间；如有必要，在明显乏力的时候，应给予较大部分的药量。儿童用量为每天7mg/kg，5～6次分服。每天可逐步增加剂量15～30mg，总用量为每天30～360mg。也可采用肌内注射，严重病例还可很缓慢静脉注射。不过，静脉注射有一定的危险性，应备好阿托品，以抵消严重的毒蕈碱反应。
2.新生儿肌无力：可肌内注射50～150μg/kg，或口服5～10mg，每4～6小时1次。不过，临床更愿意使用新斯的明。
3.逆转由非除极肌松药产生的神经肌肉阻滞：可静脉给予本品10～20mg，此前，先给予阿托品0.6～1.2mg，以抵消任何毒蕈碱作用。格隆溴铵可用来替代阿托品。
4.治疗麻痹性肠梗阻和术后尿潴留：可口服本品60～240mg。
 
专家点评
本品起效缓慢，作用较溴化新斯的明弱但持续时间较久，引起的心动缓慢、唾液分泌和消化道反应较轻。一般认为本品对抗非除极化型肌松药过量的效果不如新斯的明好。

REGONOL - pyridostigmine bromide injection, solution 
Sandoz Inc

Regonol®
(Pyridostigmine Bromide Injection USP)

CONTAINS BENZYL ALCOHOL

THIS DRUG SHOULD BE ADMINISTERED BY ADEQUATELY TRAINED INDIVIDUALS FAMILIAR WITH ITS ACTIONS, CHARACTERISTICS, AND HAZARDS.

DESCRIPTION

REGONOL® (pyridostigmine bromide injection USP) is an active cholinesterase inhibitor chemically designated as 3-hydroxy-1-methylpyridinium bromide dimethyl-carbamate.

Its structural formula is:

REGONOL® is supplied as a sterile, isotonic, nonpyrogenic solution for injection. Each mL contains 5 mg of pyridostigmine bromide with 1% BENZYL ALCOHOL, WHICH IS NOT INTENDED FOR USE IN NEWBORNS, as the preservative. The pH is buffered with sodium citrate and citric acid and adjusted with sodium hydroxide if necessary.

CLINICAL PHARMACOLOGY

REGONOL® (pyridostigmine bromide injection USP), an analogue of neostigmine, facilitates the transmission of impulses across the myoneural junction by inhibiting the destruction of acetylcholine by cholinesterase. Currently available data indicate that pyridostigmine may have a significantly lower degree and incidence of bradycardia, salivation and gastrointestinal stimulation than does neostigmine. Animal studies using the injectable form of pyridostigmine and human studies using the oral preparation have indicated that pyridostigmine has a longer duration of action than does neostigmine measured under similar circumstances.1,2 REGONOL® is effective in reversing the neuromuscular blocking effects of nondepolarizing muscle relaxants.

Anticholinesterase agents such as REGONOL® and neostigmine may produce depolarization block when administered at doses above their recommended therapeutic ranges. The therapeutic index of REGONOL® (ratio of reversal dose to blocking dose) is approximately 1:6 (see OVERDOSAGE).3

The antagonism of neuromuscular blockade by anticholinesterase agents may be influenced by the degree of spontaneous recovery achieved when the reversal agent is administered, by the particular relaxant administered, acid-base balance, body temperature, electrolyte imbalance, concomitant medications such as potent inhalational anesthetics, antibiotics or other drugs which enhance or antagonize the action of nondepolarizing muscle relaxants.4 The use of peripheral nerve stimulation to determine the degree of neuromuscular blockade is recommended in evaluating the effects of the reversal agents.

Failure of anticholinesterase agents to produce prompt (within 30 minutes) reversal of neuromuscular blockade may occur in the presence of extreme debilitation, carcinomatosis, and with concomitant use of certain broad-spectrum antibiotics, or anesthetic agents and other drugs which enhance neuromuscular blockade or cause respiratory depression through their own pharmacologic actions.

As with other anticholinesterase agents, the administration of REGONOL® may be associated with muscarinic and nicotinic side effects, notably bradycardia and excessive bronchial secretions; the use of glycopyrrolate or atropine sulfate simultaneously with or prior to administration of REGONOL® is recommended to counteract these side effects (see DOSAGE AND ADMINISTRATION).5

Pharmacokinetics

It has been postulated that the clearance of pyridostigmine is almost equally dependent on metabolism and on urinary elimination of the unchanged drug.6 Other studies in man indicated that approximately 75 percent of the plasma clearance of pyridostigmine is dependent on renal excretion and the remainder on nonrenal mechanisms.7

INDICATIONS AND USAGE

REGONOL® (pyridostigmine bromide injection USP) is indicated as a reversal agent or antagonist to the neuromuscular blocking effects of nondepolarizing muscle relaxants.

CONTRAINDICATIONS

Known hypersensitivity to anticholinesterase agents; intestinal and urinary obstructions of mechanical type.

WARNINGS

NOT FOR USE IN NEONATES

REGONOL® (pyridostigmine bromide injection USP) should be used with particular caution in patients with bronchial asthma or cardiac dysrhythmias. Transient bradycardia may occur and be relieved by atropine sulfate. Atropine sulfate should also be used with caution in patients with cardiac dysrhythmias. When large doses of pyridostigmine bromide are administered, as during reversal of muscle relaxants, prior or simultaneous injection of atropine sulfate or an equipotent dose of glycopyrrolate is advisable. Because of the possibility of hypersensitivity in an occasional patient, atropine and antishock medication should always be readily available.

When used as an antagonist to nondepolarizing muscle relaxants, adequate recovery of voluntary respiration and neuromuscular transmission must be obtained prior to discontinuation of respiratory assistance, and there should be continuous patient observation. Satisfactory recovery may be judged by adequacy of skeletal muscle tone, respiratory measurements, and by observation of the response to peripheral nerve stimulation. A patent airway should be maintained and manual or mechanical ventilation should be continued until complete recovery of normal respiration is assured.

Exposure to excessive amounts of benzyl alcohol has been associated with toxicity (hypotension, metabolic acidosis), particularly in neonates, and an increased incidence of kernicterus, particularly in small preterm infants. There have been rare reports of deaths, primarily in preterm infants, associated with exposure to excessive amounts of benzyl alcohol. The amount of benzyl alcohol from medications is usually considered negligible compared to that received in flush solutions containing benzyl alcohol. Administration of high dosages of medications containing this preservative must take into account the total amount of benzyl alcohol administered. The amount of benzyl alcohol at which toxicity may occur is not known. If the patient requires more than the recommended dosages or other medications containing this preservative, the practitioner must consider the daily metabolic load of benzyl alcohol from these combined sources (see PRECAUTIONS: Pediatric Use).

PRECAUTIONS

THE USE OF A PERIPHERAL NERVE STIMULATOR TO MONITOR RECOVERY OF NEUROMUSCULAR FUNCTION WILL MINIMIZE THE POSSIBILITY OF EXCESS DOSING OR INADEQUATE REVERSAL.

Inadequate reversal of the neuromuscular blockade induced by nondepolarizing (curariform) muscle relaxants is possible. This can be managed by manual or mechanical ventilation until recovery is judged adequate. The administration of additional doses of anticholinesterase reversal agents is not recommended since excessive dosages of such drugs may produce depolarizing block through their own pharmacologic actions.

Pyridostigmine is mainly excreted unchanged by the kidney.2,7,8 Therefore, lower doses may be required in patients with renal disease, and treatment should be based on titration of drug dosage to effect.2,7

Drug Interactions

Concomitant administration of REGONOL® (pyridostigmine bromide injection USP) and 4-aminopyridine has been reported to delay the onset of action of REGONOL®.9

Antibiotics

Parenteral administration of high doses of certain antibiotics may intensify or produce neuromuscular block through their own pharmacologic actions. The following antibiotics have been associated with various degrees of paralysis: aminoglycosides (such as neomycin, streptomycin, kanamycin, gentamicin, and dihydrostreptomycin); tetracyclines; bacitracin; polymyxin B; colistin; and sodium colistimethate. If these or other newly introduced antibiotics are used in conjunction with nondepolarizing neuromuscular blocking drugs during surgery, unexpected prolongation of neuromuscular block or resistance to its reversal should be considered a possibility.

Other

Experience concerning injection of quinidine during recovery from use of nondepolarizing muscle relaxants suggest that recurrent paralysis may occur. This possibility must be considered when administering anticholinesterase agents to antagonize neuromuscular blockade induced by nondepolarizing muscle relaxants.

Electrolyte imbalance and diseases which lead to electrolyte imbalance, such as adrenal cortical insufficiency, have been shown to alter neuromuscular blockade. Depending on the nature of the imbalance, either enhancement or inhibition may be expected. Magnesium salts, administered for the management of toxemia of pregnancy, may enhance the neuromuscular blockade. The possibility that such circumstances may interfere with the restoration of neuromuscular function should be considered when administering REGONOL®.

Interactions with Laboratory Tests

None known.

Carcinogenesis, Mutagenesis, Impairment of Fertility

Long-term studies in animals have not been performed to evaluate carcinogenic or mutagenic potential or impairment of fertility.

Pregnancy

Pregnancy Category C

It is not known whether REGONOL® (pyridostigmine bromide injection USP) can cause fetal harm when administered to a pregnant woman or can affect reproductive capacity. REGONOL® should be given to a pregnant woman only if the administering clinician decides that the benefits outweigh the risks.

Pediatric Use

Safety and efficacy in pediatric patients have not been established.

Benzyl alcohol, a component of this drug product, has been associated with serious adverse events and death, particularly in pediatric patients. The “gasping syndrome”, (characterized by central nervous system depression, metabolic acidosis, gasping respirations, and high levels of benzyl alcohol and its metabolites found in the blood and urine) has been associated with benzyl alcohol dosages >99 mg/kg/day in neonates and low-birth-weight neonates. Additional symptoms may include gradual neurological deterioration, seizures, intracranial hemorrhage, hematologic abnormalities, skin breakdown, hepatic and renal failure, hypotension, bradycardia, and cardiovascular collapse. Although normal therapeutic doses of this product deliver amounts of benzyl alcohol that are substantially lower than those reported in association with the “gasping syndrome”, the minimum amount of benzyl alcohol at which toxicity may occur is not known. Premature and low-birth-weight infants, as well as patients receiving high dosages, may be more likely to develop toxicity. Practitioners administering this and other medications containing benzyl alcohol should consider the combined daily metabolic load of benzyl alcohol from all sources.

ADVERSE REACTIONS

The side effects of pyridostigmine bromide are most commonly related to overdosage and generally are of two varieties, muscarinic and nicotinic. Among those in the former group are nausea, vomiting, diarrhea, abdominal cramps, increased peristalsis, increased salivation, increased bronchial secretions, miosis, and diaphoresis. Nicotinic side effects are comprised chiefly of muscle cramps, fasciculation, and weakness. Muscarinic side effects can usually be counteracted by atropine. As with any compound containing the bromide radical, a skin rash may be seen in an occasional patient. Such reactions usually subside promptly upon discontinuance of the medication. Thrombophlebitis has been reported subsequent to intravenous administration.

OVERDOSAGE

THE POSSIBILITY OF IATROGENIC OVERDOSAGE CAN BE MINIMIZED BY CAREFULLY MONITORING THE MUSCLE TWITCH RESPONSE TO PERIPHERAL NERVE STIMULATION. Should overdosage occur, ventilation should be supported by artificial means until the adequacy of spontaneous respiration is assured, and cardiac function should be monitored.

Respiratory depression following administration of nondepolarizing neuromuscular blocking agents may be due either wholly or in part to other drugs used during the conduct of general anesthesia, such as narcotics, thiobarbiturates and other central nervous system depressants. A peripheral nerve stimulator may be used to assess the degree of residual neuromuscular blockade and to help differentiate residual neuromuscular blockade from other causes of decreased respiratory reserve.

DOSAGE AND ADMINISTRATION

REGONOL® (pyridostigmine bromide injection USP) is for intravenous use only. This drug should be administered by or under the supervision of experienced clinicians familiar with the use of agents which reverse or antagonize the effects of neuromuscular blocking agents. Dosage must be individualized in each case. The dosage information which follows is derived from studies based upon units of drug per unit of body weight and is intended to serve as a guide only. Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit.

NOTE: CONTAINS BENZYL ALCOHOL (see PRECAUTIONS).

Reversal doses of REGONOL® range from 0.1 to 0.25 mg/kg.5,10,11,12,13 The onset time to peak effect is dose-dependent; return of twitch height to 90% of control occurs within approximately 6 minutes following administration of a 0.25 mg/kg dose of REGONOL®.5,12 At lower doses, full recovery usually occurs within 15 minutes in most patients, although others may require a half-hour or more.

When REGONOL® is given intravenously to reverse the action of muscle relaxant drugs, it is recommended that atropine sulfate (0.6 to 1.2 mg) or an equipotent dose of glycopyrrolate be given immediately prior to or simultaneously with the administration of REGONOL®. Side effects, notably excessive secretions and bradycardia are thereby minimized. Please refer to the appropriate prescribing information prior to the use of glycopyrrolate or atropine sulfate.

To obtain maximum clinical benefits of REGONOL® and to minimize the possibility of overdosage, the monitoring of muscle twitch response to peripheral nerve stimulation is advised. REGONOL® should be administered after spontaneous recovery of neuromuscular function has begun.

Satisfactory reversal can be evident by adequate voluntary respiration, respiratory measurements and use of a peripheral nerve stimulator device. It is recommended that the patient be well-ventilated and a patent airway maintained until complete recovery of normal respiration is assured. Once satisfactory reversal has been attained following administration of REGONOL®, recurrence of paralysis is unlikely to occur.

Inadequate reversal of neuromuscular blockade by anticholinesterase drugs is possible with all curariform drugs, and is managed by manual or mechanical ventilation until recovery is judged adequate. The administration of additional doses of anticholinesterase reversal agents is not recommended since excessive dosages of such drugs may produce depolarizing block through their own pharmacological actions.

Use in Pediatrics

The safety and efficacy of REGONOL® (pyridostigmine bromide injection USP) in pediatric patients have not been established, therefore no dosing recommendations can be made (see PRECAUTIONS).

HOW SUPPLIED

REGONOL® (pyridostigmine bromide injection USP) for injection is available as:

REGONOL® 2 mL ampules containing 10 mg pyridostigmine bromide injection (5 mg/mL) and supplied as:

NDC 0781-3040-95 boxes of 10

CONTAINS BENZYL ALCOHOL.

Store at 25°C (77°F); excursions permitted to 15°-30°C (59°-86°F) (see USP Controlled Room Temperature). Protect from light.

PRINCIPAL DISPLAY PANEL
10 mg 2 mL Ampule
NDC 0781-3040-72
Regonol® Pyridostigmine
Bromide Injection, USP
10 mg/2 mL
Sterile
IV ONLY
(5 mg/mL) 2 mL Rx only
Contains Benzyl Alcohol.
Not for use in neonates.
Store at 25°C (77°F).

10 mg 2 mL Carton
NDC 0781-3040-95
Regonol®
Pyridostigmine Bromide Injection USP
Sterile
FOR INTRAVENOUS USE ONLY
(5 mg/mL)
Contains Benzyl Alcohol. Not for use in neonates.
Rx only 5 x 2 mL Ampules