Prescription Required
In stock
Manufacturer
OCEANSIDE PHARM
SKU
68682030130

pyridostigmine er 180 mg tab

Generic
$8.19 / tablet
$24.84 / tablet
$16.65 / tablet
+ -
1,000 tablets Available
Total Price:

Uses

Myasthenia Gravis

Pyridostigmine is used mainly to improve muscle strength in the symptomatic treatment of myasthenia gravis. Because of its longer duration of action, smoother and steadier effects, and reportedly lower incidence of adverse muscarinic effects, most clinicians prefer pyridostigmine to neostigmine for oral therapy. In addition, pyridostigmine may be more effective than neostigmine in relieving ptosis, diplopia, dysarthria, and weakness in bulbar muscles. Pyridostigmine is not effective in patients who are resistant to other anticholinesterase drugs.

Pyridostigmine is used parenterally for symptomatic treatment of acute exacerbations of myasthenia gravis and when oral therapy is impractical. However, the injectable preparation that was used for this indication no longer is commercially available in the US, and the parenteral injection that is commercially available does not include this use in its prescribing information. Some clinicians prefer neostigmine to pyridostigmine for IM therapy since it has a shorter duration of action and therefore dosage can be adjusted more frequently as needed. Neostigmine is usually preferred for treatment of neonatal myasthenia gravis, although pyridostigmine has been used.

Surgery

Parenteral pyridostigmine is useful for reversal of the effects of nondepolarizing neuromuscular blocking agents (e.g., tubocurarine, metocurine, gallamine [no longer commercially available in the US], pancuronium) after surgery. When used for this purpose, pyridostigmine has been reported to produce less oropharyngeal secretion, bradycardia, and cardiac arrhythmia than neostigmine. Anticholinesterase drugs do not antagonize the phase I block of depolarizing neuromuscular blocking agents such as succinylcholine; therefore, pyridostigmine should not be given in an attempt to reverse the neuromuscular block produced by these agents.

Chemical Warfare Agent Poisoning

Pyridostigmine bromide is used in military combat personnel for preexposure prophylaxis against the lethal effects of soman nerve agent poisoning. Pyridostigmine is used in conjunction with standard treatment of nerve agent poisoning (i.e., atropine and pralidoxime chloride) and other protective measures such as specifically designed masks, hoods, and overgarments. Use of pyridostigmine alone will not be protective against the effects of soman; efficacy of pyridostigmine is dependent on the rapid administration of atropine and pralidoxime following exposure to the nerve agent. Pyridostigmine is administered orally prior to an expected exposure to soman (i.e., when under the threat of a nerve agent attack); the drug must be discontinued immediately at the first indication of nerve agent poisoning. In addition, pyridostigmine should not be taken after exposure to soman. If pyridostigmine is taken immediately before exposure or at the same time as soman poisoning, the drug is not likely to be effective and may exacerbate the effects of a sublethal exposure to soman.

The most toxic of the known chemical warfare agents are the nerve agents. Most nerve agents are liquid at room temperature (although most are volatile at ambient temperatures, the term nerve gas is a misnomer); nerve agents are readily absorbed after inhalation of aerosols (e.g., following an explosion), ingestion, or dermal contact. Nerve agents (e.g., sarin, soman, tabun, VX [metylphosphonothionic acid]) are chemically similar to the organophosphate pesticides and exert their biologic effects by inhibiting acetylcholinesterase enzymes. Nerve agents alter cholinergic synaptic transmission at neuroeffector junctions (muscarinic effects), at skeletal myoneural junctions and autonomic ganglia (nicotinic effects), and in the CNS.

Pyridostigmine was approved for preexposure prophylaxis against effects of soman under the US Food and Drug Administration's (FDA's) animal efficacy rule that allows use of animal data of effectiveness for certain conditions when a drug cannot be ethically tested in humans. Studies in animals indicate that administration of pyridostigmine prior to exposure to soman reduces lethality of soman provided that atropine and pralidoxime are given immediately after exposure to the nerve agent. Administration of pyridostigmine in conjunction with atropine and pralidoxime increases survival after lethal exposures to soman above that provided by atropine and pralidoxime alone.

Dosage and Administration

Administration

Pyridostigmine bromide is administered orally or by very slow IV injection. The drug also has been administered by IM injection, but the manufacturer of the currently available injectable preparation states that this injection is for IV injection only.

When pyridostigmine is administered as conventional tablets or syrup for the symptomatic treatment of myasthenia gravis, the dosage should be adjusted so the patient takes larger doses at times of greatest fatigue (e.g., 30-45 minutes before meals to assist patients who have difficulty eating).

Pyridostigmine oral solution is especially useful for children and patients who have difficulty swallowing, and the solution may be administered through a nasogastric tube, if necessary.

Dosage

Oral dosage requirements of pyridostigmine bromide are approximately 30 times those required for parenteral therapy. When pyridostigmine is used in the symptomatic treatment of myasthenia gravis, dosage, route, and frequency of administration depend on the requirements and clinical response of the patient.

Myasthenia Gravis

In patients with myasthenia gravis, dosage requirements may vary from day to day, according to remissions and exacerbations of the disease and the physical and emotional stress suffered by the patient. Complete restoration of muscle strength is rare in myasthenia gravis, and patients should be cautioned not to increase their dosage above the maximum response level in an attempt to relieve all symptoms. Mild exacerbations may be treated under medical supervision by increasing the dosage of anticholinesterase medication, as long as the increase produces symptomatic improvement. When anticholinesterase therapy has been stabilized, patients can be taught to recognize adverse muscarinic effects and modify their dosage of pyridostigmine bromide accordingly, or take atropine if necessary.

In the initial treatment of myasthenia gravis, oral pyridostigmine bromide should be started at a dosage smaller than that required to produce maximum strength (usually 60 mg 3 times daily for adults), and daily dosage is gradually increased at intervals of 48 hours or more.

The usual oral adult daily maintenance dosage of pyridostigmine bromide in myasthenia gravis ranges from 60 mg to 1.5 g, with an average of 600 mg. Although the manufacturer states that adults may receive 180-540 mg of pyridostigmine bromide in extended-release tablets once or twice daily (with at least 6 hours between doses), most clinicians agree that this dosage form should be used only at bedtime for patients who are very weak upon awakening.

Although the manufacturers state that safety and efficacy in children have not been established, some clinicians have suggested that children may be started on 7 mg/kg daily, divided into 5 or 6 oral doses.

Changes in oral dosage may take several days to show results. When a further increase in dosage produces no corresponding increase in muscle strength, dosage should be reduced to the previous level, so that the patient receives the smallest dosage necessary to produce maximum strength.

In patients with myasthenia gravis who require parenteral therapy, approximately /30 of the usual oral dose of pyridostigmine bromide may be given by IM or very slow IV injection. The patient should be closely observed for cholinergic reactions, especially if the IV route were used. Myasthenic mothers may be given /30 of their usual oral dose by IM or slow IV injection 1 hour before completion of the second stage of labor to provide adequate strength during labor and protection to the neonate. Neonatal myasthenia gravis may be treated with 5 mg of pyridostigmine bromide orally every 4-6 hours or 0.05-0.15 mg/kg IM every 4-6 hours. Because of the self-limiting nature of the disease in neonates, the daily dosage of anticholinesterase medication should be gradually reduced until the drug can be withdrawn. Children may be given 0.05-0.15 mg/kg of pyridostigmine bromide every 4-6 hours up to a maximum single IV or IM dose of 10 mg.

Surgery

For reversal of the effects of nondepolarizing neuromuscular blocking agents after surgery in adults, doses of 0.1-0.25 mg/kg (approximately 10-20 mg) of pyridostigmine bromide may be given IV, shortly after or simultaneously with 0.6-1.2 mg of atropine sulfate IV (or an equipotent dose of glycopyrrolate). The effect of each dose of pyridostigmine bromide on respiration should be carefully observed before additional doses are given, and assisted ventilation should always be employed.

The patient's muscle twitch response to peripheral nerve stimulation should be monitored, and pyridostigmine bromide should be administered after spontaneous recovery of neuromuscular function has begun. Satisfactory reversal is evident by adequate voluntary respiration, respiratory measurements, and use of a peripheral nerve stimulator device. The patient must be well-ventilated and a patent airway and manual or mechanical ventilation should be maintained until complete recovery of normal respiration is assured. Recurrence of paralysis is unlikely after satisfactory reversal of the effects of nondepolarizing neuromuscular blocking agents has been attained. The patient should be closely observed to ensure that respiratory depression does not recur. Full recovery usually occurs within 15-30 minutes, but may be delayed in the presence of extreme debilitation, hypokalemia, carcinomatosis, or with concomitant use of certain broad spectrum antibiotics (e.g., aminoglycosides) or anesthetic agents, notably ether. Satisfactory recovery of respiration and neuromuscular transmission must be assured before respiratory assistance is discontinued.

Chemical Warfare Agent Poisoning

For preexposure prophylaxis against the lethal effects of soman nerve agent poisoning, the recommended dosage of pyridostigmine bromide is 30 mg orally every 8 hours. Administration of pyridostigmine bromide should be started several hours prior to anticipated exposure to the nerve agent. At the first sign of nerve agent poisoning, pyridostigmine should be discontinued and treatment with atropine and pralidoxime instituted immediately.

The effects of continued administration of pyridostigmine for longer than 14 consecutive days for this indication have not been definitively established. Administration of the drug for longer than 14 consecutive days should be evaluated in the context of the likelihood of exposure to soman.

Dosage in Renal Impairment

Since pyridostigmine is excreted predominantly by the kidneys, the manufacturer of Mestinon states that lower dosages of pyridostigmine bromide may be required in patients with renal disease. In such patients, the dosage should be titrated carefully to produce the desired effect.

Cautions

Adverse Effects

Adverse effects of pyridostigmine are chiefly those of exaggerated response to parasympathetic stimulation and include adverse muscarinic effects such as nausea, vomiting, diarrhea, increased peristalsis, miosis, excessive salivation and sweating, increased bronchial secretions, abdominal cramps, bradycardia, and bronchospasm. Weakness, muscle cramps, fasciculation, and, rarely, hypotension may also occur. Thrombophlebitis has been reported after IV administration. Pyridostigmine reportedly produces fewer severe adverse muscarinic effects than does neostigmine, but in high doses is more likely to produce headache. As with other drugs containing bromide, skin rash may occasionally occur during therapy; however, the rash usually subsides promptly following discontinuance of pyridostigmine bromide. Overdosage of pyridostigmine can cause cholinergic crisis and death. (See Acute Toxicity: Manifestations.)

Adverse effects of pyridostigmine may be minimized by precise dosage adjustment. Adverse muscarinic effects can be reduced or eliminated by concomitant administration of atropine; however, these symptoms may be the first indication of pyridostigmine overdose, and masking them with atropine may prevent early detection of cholinergic crisis.

The most frequently reported adverse effects associated with pyridostigmine administration in 41,650 soldiers (the 18th Airborne Corps) who received the drug at the onset of hostilities of Operation Desert Storm (Jan 1991) were GI and urinary tract symptoms. Adverse GI effects (increased flatus, loose stools, abdominal cramps, nausea) occurred in 50% or more of soldiers; urinary urgency and frequency occurred in 5-30% of soldiers; headache, rhinorrhea, diaphoresis, or tingling of the extremities was reported in less than 5% of soldiers. Other adverse effects reported in these soldiers include bad dreams, worsening of acute bronchitis, slurred speech, rash, vertigo, asthma exacerbation, hypertension, or bleeding episode. Approximately 1% of soldiers experiencing an adverse effect sought medical attention; less than 0.1% of soldiers discontinued the drug on medical advice. While most soldiers were aware that pyridostigmine altered their normal physiology, these changes did not interfere with their daily lives. Soldiers taking pyridostigmine under combat conditions reportedly were able to perform at full effectiveness.

The possible association between chronic illness in Persian Gulf War veterans (Jan 1991 war) and pyridostigmine has been evaluated. Data from a 1996-1997 survey in 700 reserve male veterans indicated that use of pyridostigmine during the Gulf War was associated with a decline in self-reported health status after the war. Reactions to vaccines and other medications also were associated with a decline in self-reported health status. Results from this survey and other data suggest that pyridostigmine alone or in combination with other factors such as stress or other toxic exposures may play a role in some of the symptoms experienced by many Gulf War veterans.

Precautions and Contraindications

Patients who are hyperreactive to pyridostigmine experience a severe cholinergic reaction to the drug. Therefore, atropine sulfate injection should always be readily available as an antagonist for the muscarinic effects of pyridostigmine. Patients who are hypersensitive to bromides may develop skin reactions such as acneiform rash during pyridostigmine bromide therapy; however, these reactions usually disappear when the drug is discontinued. Ambenonium chloride may be used for oral anticholinesterase therapy in myasthenia gravis patients who are sensitive to bromides.

When pyridostigmine is used to treat myasthenia gravis, it should be kept in mind that individual muscle groups may respond differently to the same dose of an anticholinesterase agent, producing weakness in one muscle group while increasing strength in another. The muscles of the neck and of chewing and swallowing are usually the first muscles weakened by overdosage, followed by the muscles of the shoulder girdle and upper extremities, and finally the pelvic girdle and extraocular and leg muscles. Vital capacity should be routinely measured whenever dosage is increased, so that the dosage of the anticholinesterase medication can be adjusted to ensure good respiratory function. Adequate facilities for cardiopulmonary resuscitation, cardiac monitoring, endotracheal intubation, and assisting respiration should be available during dosage adjustment.

When pyridostigmine is used for preexposure prophylaxis against the lethal effects of soman, efficacy of pyridostigmine depends on the rapid use of atropine and pralidoxime following exposure to the nerve agent. Use of pyridostigmine alone will not be protective against the effects of soman. The primary means of protection against exposure to nerve agents is wearing protective garments including masks, hoods, and overgarments specifically designed for this use. Individuals should not solely rely on pyridostigmine, atropine, and pralidoxime to provide complete protection against the effects of soman. Pyridostigmine should not be administered after exposure to soman. If pyridostigmine is taken immediately before exposure (e.g., when the attack alarm is given), at the same time as soman poisoning, or after such exposure, the drug is not likely to be effective and may exacerbate the effects of a sublethal exposure to soman.

If military personnel receiving pyridostigmine experience serious adverse effects such as difficult breathing, severe dizziness, or loss of consciousness, they should be advised to temporarily discontinue the drug and immediately seek medical care.

Caution should be observed when pyridostigmine is used in patients with renal impairment. Since pyridostigmine is excreted predominantly by the kidneys, the manufacturer of Mestinon states that lower dosages of pyridostigmine bromide may be required in patients with renal disease. In such patients, the dosage should be titrated carefully to produce the desired effect.

Pyridostigmine should be used with caution in patients with bronchial asthma, chronic obstructive pulmonary disease, bradycardia, or cardiac arrhythmias. In addition, pyridostigmine should be used with caution in patients receiving concomitant therapy with a β-adrenergic blocking agent for the treatment of hypertension or glaucoma.

Pyridostigmine bromide is contraindicated in patients with mechanical obstruction of the intestinal or urinary tracts and in patients who are known to be hypersensitive to anticholinesterase agents.

Pediatric Precautions

The manufacturers state that safety and efficacy of pyridostigmine bromide in children have not been established.

Regonol injection contains benzyl alcohol as a preservative. Although a causal relationship has not been established, administration of injections preserved with benzyl alcohol has been associated with toxicity in neonates. Toxicity appears to have resulted from administration of large amounts (i.e., 100-400 mg/kg daily) of benzyl alcohol in these neonates. Although use of drugs preserved with benzyl alcohol should be avoided in neonates whenever possible, the American Academy of Pediatrics states that the presence of small amounts of the preservative in a commercially available injection should not proscribe its use when indicated in neonates. The manufacturer recommends that clinicians administering the drug in neonates take into account the total daily metabolic load of benzyl alcohol from all sources.

Geriatric Precautions

Clinical studies of pyridostigmine did not include sufficient numbers of patients 65 years of age and older to determine whether geriatric patients respond differently than younger individuals. Drug dosage should be selected carefully in geriatric individuals taking into consideration the greater frequency of decreased hepatic, renal, and/or cardiac function and of concomitant disease and drug therapy observed in the elderly. Because patients with renal impairment may be at increased risk of pyridostigmine-induced toxicity and geriatric individuals may have decreased renal function, the pyridostigmine bromide dosage should be selected carefully in patients in this age group. It may be advisable to monitor renal function in geriatric patients.

Pregnancy and Lactation

Pregnancy

Few data are available regarding the effects of cholinesterase inhibitors, including pyridostigmine, on the fetus because of the rarity of maternal conditions requiring the use of these drugs during pregnancy. Transient muscular weakness has occurred in 10-20% of neonates whose mothers received anticholinesterase drugs for the treatment of myasthenia gravis, although similar symptoms have also been reported in infants whose mothers were not treated with these drugs. Anticholinesterase drugs may cause uterine irritability and induce premature labor when given IV to pregnant women near term. Use of pyridostigmine in pregnant women requires that the possible benefits be weighed against the potential risks.

Lactation

Since it is not known whether pyridostigmine is distributed into milk, the drug should be used with caution in nursing women.

Drug Interactions

Neuromuscular Blocking Agents

Pyridostigmine does not antagonize, and may in fact prolong, the phase I block of depolarizing muscle relaxants such as succinylcholine. Fully established phase II (desensitization) block can be reversed by pyridostigmine, but the individual variation in transition time between phases I and II and difficulty in accurately determining the stage of depolarizing neuromuscular block at any given time often make anticholinesterase administration ineffective or dangerous under these circumstances. Parenteral pyridostigmine effectively antagonizes the effect of nondepolarizing muscle relaxants (e.g., tubocurarine, metocurine, gallamine [no longer commercially available in the US], pancuronium), and this interaction is used to therapeutic advantage to reverse muscle relaxation after surgery. (See Uses: Surgery.)

Particular caution is advised in soldiers who have received pyridostigmine if a depolarizing neuromuscular blocking agent (i.e., succinylcholine) is administered during surgery since the degree of neuromuscular blockage may be enhanced by pyridostigmine. Conversely, doses of nondepolarizing neuromuscular blocking agents (e.g., pancuronium) may need to be increased in soldiers who have received pyridostigmine.

β-Adrenergic Blocking Agents

Pyridostigmine should be used with caution in patients receiving concomitant therapy with a β-adrenergic blocking agent. Military personnel receiving therapy with a β-adrenergic blocking agent are likely to be receiving such therapy for the treatment of hypertension or glaucoma; the prescribing information for military combat use of pyridostigmine advises that the drug be used with caution in patients receiving concomitant therapy with a β-adrenergic blocking agent for the treatment of hypertension or glaucoma. While no difference in heart rate, plasma catecholamine concentrations, or resting blood pressure was observed in military personnel receiving a β-adrenergic blocker for the treatment of mild to moderate hypertension and pyridostigmine bromide 30 mg every 8 hours for 5 doses relative to those receiving a β-adrenergic blocker and placebo, the effect of pyridostigmine in patients receiving a β-adrenergic blocker who have borderline heart failure or atrioventricular conduction disturbances has not been determined.

Topical Miotics

Pyridostigmine may produce additive effects (i.e., cause or exacerbate problems with night vision) in patients receiving ophthalmic anticholinesterases (e.g., physostigmine) for the treatment of glaucoma.

Opiate Agonists

Bradycardia associated with the administration of opiate agonists may exacerbate pyridostigmine-induced bradycardia.

Mefloquine

The potential exists that pyridostigmine and mefloquine may have additive effects on the GI tract since the most frequently reported adverse effect of each drug is loose stools. Additive effects on atrial rate have been reported when pyridostigmine and mefloquine were used concomitantly.

Atropine

Atropine antagonizes the muscarinic effects of pyridostigmine, and this interaction is utilized to counteract the muscarinic symptoms of pyridostigmine toxicity. However, atropine may mask manifestations of pyridostigmine overdose if used concomitantly, possibly increasing the risk of inadvertent induction of cholinergic crisis. (See Acute Toxicity: Manifestations.)

Dexpanthenol

Theoretically, drugs such as dexpanthenol, which are converted to pantothenic acid in vivo, may have additive effects with pyridostigmine by increasing production of acetylcholine.

Other Drugs

Anticholinesterase agents are sometimes effective in reversing neuromuscular block induced by aminoglycoside antibiotics. However, aminoglycoside antibiotics, local and some general anesthetics, antiarrhythmic agents, and other drugs that interfere with neuromuscular transmission should be used cautiously, if at all, in patients receiving pyridostigmine.

Pharmacokinetics

Absorption

Pyridostigmine bromide is poorly absorbed from the GI tract. The bioavailability of orally administered pyridostigmine bromide is 10-20%. Extended-release tablets reportedly release one-third of the total 180-mg dose immediately after ingestion and the remainder over 8-12 hours; however, release of the drug from this dosage form may be erratic and unpredictable. Pyridostigmine has a variable duration of action in patients with myasthenia gravis, depending on the physical and emotional stress suffered by the patient and the severity of the disease. However, it generally has a shorter duration of action than ambenonium and a slower onset and a longer duration of action than neostigmine. After oral administration, pyridostigmine generally has an onset of action of 30-45 minutes and a duration of action of 3-6 hours. After IV injection, muscle strength is increased in 2-5 minutes and the improvement may continue for 2-3 hours in most patients. Following IM administration, the drug has an onset of action within about 15 minutes.

Following oral administration of a single 30-mg dose of pyridostigmine bromide in fasting individuals, peak plasma concentration is achieved in 2.2 hours. Following oral administration of pyridostigmine bromide 30 mg every 8 hours for 21 days, steady-state trough plasma concentrations average about 25% of the peak plasma concentration following a single oral 30-mg dose. The pharmacokinetics of pyridostigmine bromide are linear over a dose range of 30-60 mg. Pharmacodynamic parameters of pyridostigmine have been determined using red blood cell acetylcholinesterase activity. This pharmacodynamic end point was selected because red blood cell acetylcholinesterase activity has been shown to correlate with survival in nerve agent exposure in some animal models. The maximal effect of pyridostigmine bromide 30 mg on red blood cell acetylcholinesterase occurs shortly after the peak plasma concentration of pyridostigmine and returns to baseline within 8 hours.

Distribution

Pyridostigmine has been reported to cross the placenta and to decrease fetal plasma cholinesterase activity after large oral doses. Following oral administration of radiolabeled pyridostigmine to animals, radioactivity was present in most tissues except brain, intestinal wall, fat, and thymus. A volume of distribution of approximately 19 L has been reported. Information on protein binding is not available.

Elimination

The elimination half-life of pyridostigmine is 1.05-1.86 or 3 hours following IV administration or oral administration of conventional tablets, respectively, in patients with normal renal function. A prolonged elimination half-life of approximately 6.3 hours has been reported in anephric patients.

Pyridostigmine undergoes hydrolysis by cholinesterases; the drug also is metabolized by microsomal enzymes in the liver. Patients with severe myasthenia gravis seem to metabolize and excrete pyridostigmine faster than patients with a milder form of the disease; this may be one explanation for the resistance to anticholinesterase medication which occurs in some severely ill patients. Approximately 80-90% of a dose of pyridostigmine is excreted unchanged by the kidneys; the drug and its metabolites are excreted in urine by tubular secretion and glomerular filtration. Following IV administration, total body clearance of pyridostigmine is about 8.5-9.7 mL/minute per kg. In anephric patients, clearance was decreased to 0.21 mL/minute per kg. Although patients with myasthenia gravis may show considerable individual variation in urinary excretion patterns, pyridostigmine and 7 metabolites, including the major metabolite 3-hydroxy-N-methylpyridinium, have been detected in urine up to 72 hours after a single IV dose.

Write Your Own Review
You're reviewing:PYRIDOSTIGMINE ER 180 MG TAB
Your Rating