Mestinon®

MESTINON®
(pyridostigmine
bromide tablets, USP)
SYRUP
TABLETS
and
TIMESPAN® TABLETS
DESCRIPTION: 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.
CLINICAL PHARMACOLOGY: 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.
INDICATIONS AND USAGE: Mestinon is useful in the
treatment of myasthenia gravis.
CONTRAINDICATIONS: 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.
WARNINGS: 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 Genkins1 indicate 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.
PRECAUTIONS:
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.
ADVERSE REACTIONS: 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.
DOSAGE AND ADMINISTRATION: 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).
HOW SUPPLIED: 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.
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.
Valeant Pharmaceuticals North America One Enterprise Aliso Viejo, CA 92656 U.S.A. (949) 461-6000 Rev.04.07

Source: http://www.mestinon.com/Portals/25/Pdf/products/PI/Mestinon_Suspension_60mg-Tablet_60-180mg_PI_May01.pdf