Mestinon (pyridostigmine bromide tablets, USP) is an orally active cholinesterase inhibitor. Chemically, pyridostigmine bromide is 3-hydroxy-1-methylpyridinium bromide dimethylcarbamate. Its structural formula is:

Mestinon is available in the following forms: Syrup containing 60 mg pyridostigmine bromide per teaspoonful in a vehicle containing 5% alcohol, glycerin, lactic acid, sodium benzoate, sorbitol, sucrose, FD&C Red No. 40, FD&C Blue No. 1, flavors and water. Tablets containing 60 mg pyridostigmine bromide; each tablet also contains lactose, silicon dioxide and stearic acid. Timespan Tablets containing 180 mg pyridostigmine bromide; each tablet also contains carnauba wax, corn-derived proteins, magnesium stearate, silica gel and tribasic calcium phosphate.

Mestinon is useful in the treatment of myasthenia gravis.

Mestinon is available in three dosage forms:

Syrup - raspberry-flavored, containing 60 mg pyridostigmine bromide per teaspoonful (5 mL). This form permits accurate dosage adjustment for children and "brittle" myasthenic patients who require fractions of 60 mg doses. It is more easily swallowed, especially in the morning, by patients with bulbar involvement.

Conventional Tablets - each containing 60 mg pyridostigmine bromide.

Timespan Tablets - each containing 180 mg pyridostigmine bromide. This form provides uniformly slow release, hence prolonged duration of drug action; it facilitates control of myasthenic symptoms with fewer individual doses daily. The immediate effect of a 180 mg Timespan Tablet is about equal to that of a 60 mg Conventional Tablet; however, its duration of effectiveness, although varying in individual patients, averages 2½ times that of a 60 mg dose.

Dosage: The size and frequency of the dosage must be adjusted to the needs of the individual patient.

Syrup and Conventional Tablets - The average dose is ten 60 mg tablets or ten 5 mL teaspoonfuls daily, spaced to provide maximum relief when maximum strength is needed. In severe cases as many as 25 tablets or teaspoonfuls a day may be required, while in mild cases one to six tablets or teaspoonfuls a day may suffice.

Timespan Tablets - One to three 180 mg tablets, once or twice daily, will usually be sufficient to control symptoms; however, the needs of certain individuals may vary markedly from this average. The interval between doses should be at least 6 hours. For optimum control, it may be necessary to use the more rapidly acting regular tablets or syrup in conjunction with Timespan therapy.

Note: For information on a diagnostic test for myasthenia gravis, and for the evaluation and stabilization of therapy, please see product literature on Tensilon® (edrophonium chloride).

Syrup, 60 mg pyridostigmine bromide per teaspoonful (5 mL) and 5% alcohol - bottles of 16 fluid ounces (1 pint) (NDC 0187-3012-20).

Tablets, are available as white, flat-faced tablets containing 60 mg pyridostigmine bromide in bottles of 100 (NDC 0187-3010-30) and 500 (NDC 0187-3010-40). Each tablet is engraved MESTINON 60 V" on one side and is quadrisect scored on the other.

Timespan Tablets are available as light straw-colored, capsule-shaped tablets containing 180 mg pyridostigmine bromide in bottles of 30 (NDC 0187-3013-30). Each tablet is engraved "MES V 180" on one side and is single-scored on the other.

Note: Because of the hygroscopic nature of the Timespan Tablets, mottling may occur. This does not affect their efficacy.

Store Mestinon Tablets, Timespan Tablets, and Syrup at 25°C (77°F); excursions permitted to 15°C-30°C (59°F-86°F). Keep Mestinon Tablets and Timespan Tablets in a dry place with the silica gel enclosed.

Valeant Pharmaceuticals North America, One Enterprise, Aliso Viejo, CA 92656 U.S.A. Rev.04.07. FDA Rev date: 07/26/01

The side effects of Mestinon 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, but for reasons shown in the preceding section the expedient is not without danger. 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.

No information provided.

Although failure of patients to show clinical improvement may reflect underdosage, it can also be indicative of overdosage. As is true of all cholinergic drugs, overdosage of Mestinon may result in cholinergic crisis, a state characterized by increasing muscle weakness which, through involvement of the muscles of respiration, may lead to death. Myasthenic crisis due to an increase in the severity of the disease is also accompanied by extreme muscle weakness, and thus may be difficult to distinguish from cholinergic crisis on a symptomatic basis. Such differentiation is extremely important, since increases in doses of Mestinon or other drugs of this class in the presence of cholinergic crisis or of a refractory or "insensitive" state could have grave consequences. Osserman and Genkins¹indicate that the differential diagnosis of the two types of crisis may require the use of Tensilon® (edrophonium chloride) as well as clinical judgment. The treatment of the two conditions obviously differs radically. Whereas the presence of myasthenic crisis suggests the need for more intensive anticholinesterase therapy, the diagnosis of cholinergic crisis, according to Osserman and Genkins,¹ calls for the prompt withdrawal of all drugs of this type. The immediate use of atropine in cholinergic crisis is also recommended.

Atropine may also be used to abolish or obtund gastrointestinal side effects or other muscarinic reactions; but such use, by masking signs of overdosage, can lead to inadvertent induction of cholinergic crisis.

For detailed information on the management of patients with myasthenia gravis, the physician is referred to one of the excellent reviews such as those by Osserman and Genkins,² Grob³ or Schwab^.4,5

Usage in Pregnancy: The safety of Mestinon during pregnancy or lactation in humans has not been established. Therefore, use of Mestinon in women who may become pregnant requires weighing the drug's potential benefits against its possible hazards to mother and child.

Pyridostigmine is mainly excreted unchanged by the kidney.^6,7,8 Therefore, lower doses may be required in patients with renal disease, and treatment should be based on titration of drug dosage to effect.^6,7

Pediatric Use: Safety and effectiveness in pediatric patients have not been established.

REFERENCES

1. Osserman KE, Genkins G. Studies in myasthenia gravis: Reduction in mortality rate after crisis. JAMA. Jan 1963; 183:97-101.

2. Osserman KE, Genkins G. Studies in myastheniagravis. NY State J Med. June 1961;61:2076-2085.

3. Grob D. Myasthenia gravis. A review of pathogenesis and treatment. Arch Intern Med. Oct 1961; 108:615-638.

4. Schwab RS. Management of myasthenia gravis. New Eng J Med. Mar 1963; 268:596-597.

5. Schwab RS. Management of myasthenia gravis. New Eng J Med. Mar 1963; 268:717-719.

6. Cronnelly R, Stanski DR, Miller RD, Sheiner LB. Pyridostigmine kinetics with and without renal function. Clin Pharmacol Ther. 1980; 28:No. 1, 78-81.

7. Miller RD. Pharmacodynamics and pharmacokinetics of anticholinesterase. In: Ruegheimer E, Zindler M, ed. Anaesthesiology. (Hamburg, Germany: Congress; Sep 14-21, 1980; 222-223.) (Int Congr. No. 538), Amsterdam, Netherlands: Excerpta Medica; 1981.

8. Breyer-Pfaff U, Maier U, Brinkmann AM, Schumm F. Pyridostigmine kinetics in healthy subjects and patients with myasthenia gravis. Clin Pharmacol Ther. 1985;5:495-501.

No information provided.

Mestinon is contraindicated in mechanical intestinal or urinary obstruction, and particular caution should be used in its administration to patients with bronchial asthma. Care should be observed in the use of atropine for counteracting side effects, as discussed below.

Mestinon inhibits the destruction of acetylcholine by cholinesterase and thereby permits freer transmission of nerve impulses across the neuromuscular junction. Pyridostigmine is an analog of neostigmine (Prostigmin®), but differs from it in certain clinically significant respects; for example, pyridostigmine is characterized by a longer duration of action and fewer gastrointestinal side effects.

No information provided. Please refer to the WARNINGS and PRECAUTIONS sections.

IMPORTANT NOTE: This is a summary and does not contain all possible information about this product. For complete information about this product or your specific health needs, ask your health care professional. Always seek the advice of your health care professional if you have any questions about this product or your medical condition. This information is not intended as individual medical advice and does not substitute for the knowledge and judgment of your health care professional. This information does not contain any assurances that this product is safe, effective, or appropriate for you.

PYRIDOSTIGMINE - ORAL

(pir-id-oh-STIG-meen)

COMMON BRAND NAME(S): Mestinon

USES: Pyridostigmine is used to improve muscle strength in patients with a certain muscle disease (myasthenia gravis). It works by preventing the breakdown of a certain natural substance (acetylcholine) in your body. Acetylcholine is needed for normal muscle function.

HOW TO USE: Take the regular-release tablet or liquid form of this medication by mouth with or without food as directed by your doctor. If taking the liquid, use a medication-measuring spoon or device to make sure you get the correct dose. Do not use a household spoon.

Take the slow-release tablet by mouth with or without food, usually 1 to 2 times daily (at least 6 hours apart) or as directed by your doctor. Swallow the slow-release tablets whole. Do not crush, chew, or break the tablets. Doing so can destroy the long action of the drug and may increase side effects.

Taking this medication with food or milk may help to decrease side effects.

Dosage is based on your medical condition and response to therapy. Talk with your doctor about how you respond to the medication and about when you feel the most tired or weak so that your doctor can make the proper dosage changes.

Do not increase your dose or take this medication more often than prescribed. Doing so may increase the risk of serious side effects.

The tablet forms of this medication may become discolored due to moisture. This does not affect how well the medication works.

Tell your doctor if your condition persists or worsens or if the medication stops working well.

SIDE EFFECTS: Nausea, vomiting, diarrhea, abdominal cramps, increased saliva/mucus, decreased pupil size, increased urination, or increased sweating may occur. If any of these effects persist or worsen, tell your doctor or pharmacist promptly.

Remember that your doctor has prescribed this medication because he or she has judged that the benefit to you is greater than the risk of side effects. Many people using this medication do not have serious side effects.

Tell your doctor immediately if any of these unlikely but serious side effects occur: new or increased muscle cramps/weakness/twitching, shortness of breath, new or increased difficulty swallowing, slow heartbeat, dizziness, headache.

A very serious allergic reaction to this drug is rare. However, seek immediate medical attention if you notice any symptoms of a serious allergic reaction, including: rash, itching, swelling, severe dizziness, trouble breathing.

This is not a complete list of possible side effects. If you notice other effects not listed above, contact your doctor or pharmacist.

Contact your doctor for medical advice about side effects. The following numbers do not provide medical advice, but in the US you may report side effects to the Food and Drug Administration (FDA) at 1-800-FDA-1088. In Canada, you may call Health Canada at 1-866-234-2345.

PRECAUTIONS: Before taking pyridostigmine, tell your doctor or pharmacist if you are allergic to it; or to other anticholinesterase medications (e.g., neostigmine); or to bromides; or if you have any other allergies.

This medication should not be used if you have certain medical conditions. Before using this medicine, consult your doctor or pharmacist if you have: stomach/intestinal blockage, urinary blockage.

Before using this medication, tell your doctor or pharmacist your medical history, especially of: lung disease (e.g., asthma, chronic obstructive pulmonary disease-COPD), kidney disease, slow/irregular heartbeat.

Before having surgery, tell your doctor or dentist that you are using this medication.

The liquid form of this product contains sugar and/or alcohol. Caution is advised if you have diabetes, alcohol dependence, or liver disease. Ask your doctor or pharmacist about using this product safely.

Kidney function declines as you grow older. This medication is removed by the kidneys. Therefore, elderly people may be at greater risk for side effects while using this drug.

During pregnancy, this medication should be used only when clearly needed. Discuss the risks and benefits with your doctor.

It is not known whether this medication passes into breast milk. Consult your doctor before breast-feeding.

DRUG INTERACTIONS: Your doctor or pharmacist may already be aware of any possible drug interactions and may be monitoring you for them. Do not start, stop, or change the dosage of any medicine before checking with your doctor or pharmacist first.

Before using this medication, tell your doctor or pharmacist of all prescription and nonprescription/herbal products you may use, especially of: aminoglycoside antibiotics (e.g., gentamicin), antiarrhythmic medications (e.g., quinidine), anticholinesterase eye medications (e.g., physostigmine), beta blockers (e.g., timolol, propranolol), mefloquine, narcotic pain medications (e.g., morphine, codeine).

This document does not contain all possible interactions. Therefore, before using this product, tell your doctor or pharmacist of all the products you use. Keep a list of all your medications with you, and share the list with your doctor and pharmacist.

OVERDOSE: If overdose is suspected, contact your local poison control center or emergency room immediately. US residents can call the US National Poison Hotline at 1-800-222-1222. Canada residents can call a provincial poison control center. Symptoms of overdose may include: nausea, vomiting, diarrhea, greatly increased saliva/sweat/tears, blurred vision, fast/slow heartbeat, confusion, agitation, muscle cramps/weakness, inability to move, trouble breathing, loss of consciousness.

NOTES: Do not share this medication with others.

MISSED DOSE: If you miss a dose, take it as soon as you remember. If it is near the time of the next dose, skip the missed dose and resume your usual dosing schedule. Do not double the dose to catch up.

STORAGE: Store at room temperature at 59-86 degrees F (15-30 degrees C) away from light and moisture. Do not store in the bathroom. Keep all medicines away from children and pets.

Do not flush medications down the toilet or pour them into a drain unless instructed to do so. Properly discard this product when it is expired or no longer needed. Consult your pharmacist or local waste disposal company for more details about how to safely discard your product.

MEDICAL ALERT: Your condition can cause complications in a medical emergency. For information about enrolling in MedicAlert, call 1-800-854-1166 (USA) or 1-800-668-1507 (Canada).

Information last revised July 2008 Copyright(c) 2008 First DataBank, Inc.