Regonol

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.

DOSAGE AND ADMINISTRATION REGONOL ® (pyridostigmine bromide injection, USP) 2 mL single-dose ampule 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 ).

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 ).

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 ® .

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.

Pregnancy 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.