PDR Descriptions for Use on Test #2
DESCRIPTION
Mestinon (pyridostigmine bromide) 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.
ACTIONS
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.
INDICATION
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.
Pediatric Use: Safety and effectiveness in pediatric patients have not been
established.
PRECAUTION
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
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 21/2 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 six
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, scored, 60 mg pyridostigmine bromide each--bottles of 100 (NDC
0187-3010-30) and 500 (NDC 0187-3010-40).
Timespan tablets, scored, 180 mg pyridostigmine bromide each--bottles of 30
(NDC 0187-3013-30).
Note: Because of the hygroscopic nature of the Timespan tablets, mottling may
occur. This does not affect their efficacy.
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 myasthenia gravis. 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.
Manufactured for ICN Pharmaceuticals, Inc.
Costa Mesa, CA 92626
by Hoffmann-La Roche Inc.
Nutley, N.J. 07110
Rev. 1/97
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CYSTOSPAZ® is a pale blue uncoated compressed tablet for oral
administration. It contains the parasympatholytic agent hyoscyamine as the
free base. Each tablet contains: hyoscyamine 0.15 mg.
CYSTOSPAZ-M® is a light blue timed-release capsule containing
hyoscyamine sulfate 0.375 mg.
CLINICAL PHARMACOLOGY
Through its parasympatholytic action, hyoscyamine relaxes smooth muscle
spasm resulting from parasympathetic stimulation. It inhibits gastrointestinal
propulsive motility and decreases gastric acid secretion. It also controls
excessive pharyngeal, tracheal and bronchial secretions. It is
the(lambda)-isomer of atropine and therefore exhibits the same clinical
effects as atropine. It is, however, approximately twice as active peripherally
as atropine, since the latter is the racemic (d(lambda)) form of hyoscyamine
and d-hyoscyamine possesses only a very weak anti-cholinergic action. Since
only one-half the atropine dose is required for (lambda)-hyoscyamine, it has
only one-half the unwanted central effects of atropine.
INDICATIONS AND USAGE
In the management of disorders of the lower urinary tract associated with
hypermotility. Although specific therapy is often required to remove the
underlying cause of spasm, CYSTOSPAZ Tablets and CYSTOSPAZ-M
Capsules are offered as antispasmodic agent dosage forms which may be
combined with other forms of therapy where indicated.
CYSTOSPAZ Tablets and CYSTOSPAZ-M capsules are effective as
adjunctive therapy in the treatment of peptic ulcer and irritable bowel
syndrome (irritable colon, spastic colon, mucous colitis), acute entercolitis and
other functional gastrointestinal disorders.
CYSTOSPAZ Tablets and CYSTOSPAZ-M Capsules can also be used to
control gastric secretion, visceral spasm and hypermotility in cystitis,
pylorospasm and associated abdominal cramps. May be used in functional
intestinal disorders to reduce symptoms such as those seen in mild
dysenteries and diverticulitis. They are indicated (along with appropriate
analgesics) in symptomatic relief of biliary and renal colic.
CONTRAINDICATIONS
Glaucoma, obstructive uropathy (for example, bladder neck obstruction due
to prostatic hypertrophy); obstructive disease of the gastrointestinal tract (as
in achalasia, pyloroduodenal stenosis); paralytic ileus, intestinal atony of
elderly or debilitated patients; unstable cardiovascular status in acute
hemorrhage; severe ulcerative colitis; toxic megacolon complicating
ulcerative colitis; myasthenia gravis. Hypersensitivity to any of the
ingredients.
WARNINGS
In the presence of high environmental temperature, heat prostration can
occur with drug use (fever and heat stroke due to decreased sweating).
Diarrhea may be an early symptom of incomplete intestinal obstruction,
especially in patients with ileostomy or colostomy. In this instance, treatment
with this drug would be inappropriate and possibly harmful. Like other
anticholinergic agents, these products may produce drowsiness or blurred
vision. In this event, the patient should be warned not to engage in activities
requiring mental alertness such as operating a motor vehicle or other
machinery or to perform hazardous work while taking this drug.
PRECAUTIONS
General: Use with caution in patients with autonomic neuropathy,
hyperthyroidism, coronary heart disease, congestive heart failure, cardiac
arrhythmias, and hypertension. Investigate any tachycardia before giving any
anticholinergic drug since they may increase the heart rate. Use with caution
in patients with hiatal hernia associated with reflux esophagitis.
Information for Patients: CYSTOSPAZ Tablets and CYSTOSPAZ-M
Capsules may cause drowsiness, dizziness or blurred vision; patients should
observe caution before driving, using machinery or performing other tasks
requiring mental alertness. Use of CYSTOSPAZ Tablets or
CYSTOSPAZ-M Capsules may decrease sweating resulting in heat
prostration, fever or heat stroke; febrile patients or those who may be
exposed to elevated environmental temperatures should use caution.
Prolonged use of CYSTOSPAZ Tablets or CYSTOSPAZ-M Capsules may
decrease or inhibit salivary flow, thus contributing to the development of
caries, periodontal disease, oral candidiasis, and discomfort.
DRUG INTERACTIONS
Additive adverse effects resulting from cholinergic blockade may occur
when CYSTOSPAZ® Tablets or CYSTOSPAZ-M Capsules are
administered concomitantly with other antimuscarinics, amantadine,
haloperidol, phenothiazines, monoamine oxidase (MAO) inhibitors, tricyclic
antidepressants or some antihistamines. Antacids may interfere with the
absorption of CYSTOSPAZ Tablets or CYSTOSPAZ-M Capsules; take
CYSTOSPAZ Tablets or CYSTOSPAZ-M Capsules before meals and
antacids after meals.
Carcinogenesis, Mutagenesis, Impairment Of Fertility: No long term
studies in animals have been performed to determine the carcinogenic,
mutagenic or impairment of fertility potential of CYSTOSPAZ Tablets or
CYSTOSPAZ-M Capsules.
Pregnancy Category C--Animal reproduction studies have not been
conducted with CYSTOSPAZ Tablets or CYSTOSPAZ-M Capsules. It is
also not known whether CYSTOSPAZ Tablets or CYSTOSPAZ-M
Capsules can cause fetal harm when administered to a pregnant woman or
can affect reproduction capacity. CYSTOSPAZ Tablets or
CYSTOSPAZ-M Capsules should be taken by a pregnant woman only if
clearly needed.
Nursing Mothers--Hyoscyamine is excreted in human milk. Caution should
be exercised when CYSTOSPAZ Tablets or CYSTOSPAZ-M Capsules are
administered to a nursing woman.
ADVERSE REACTIONS
Adverse reactions may include dryness of the mouth; urinary hesitancy and
retention; blurred vision; tachycardia; palpitations; mydriasis; cycloplegia;
increased ocular tension; headache; nervousness; drowsiness; weakness;
suppression of lactation; allergic reactions or drug idiosyncrasies; urticaria
and other dermal manifestations; and decreased sweating. Note: Slight
dryness of the mouth is an indication that parasympathetic blockage is
effective.
DRUG ABUSE AND DEPENDENCE
A dependence on the use of CYSTOSPAZ Tablets or CYSTOSPAZ-M
Capsules has not been reported and due to the nature of their ingredients,
abuse of CYSTOSPAZ Tablets or CYSTOSPAZ-M Capsules is not
expected.
OVERDOSAGE
Symptoms of overdosage include severe dryness of the mouth, nose, throat,
and hot dry flushed skin, hyperpyrexia (especially in children), difficulty or
inability to swallow, difficult speech, dilated pupils until iris almost disappears,
restlessness and garrulity indicating an irritability of the brain, marked
tremors, convulsions, respiratory failure, death. In adults, symptoms of
overdosage may begin in the range of ingestion of 0.6 to 1 mg with doses
exceeding 1-2 mg eliciting more profound toxicity. Measures to be taken are
immediate lavage of the stomach and injection of physostigmine 0.5 to 2 mg
intravenously and repeated as necessary up to a total of 5 mg. Fever may be
treated symptomatically (tepid water sponge baths, hypothermic blanket).
Excitement to a degree which demands attention may be managed with
sodium thiopental 2% solution given slowly intravenously or chloral hydrate
(100-200 ml. of a 2% solution) by rectal infusion.
DOSAGE AND ADMINISTRATION
Adults: CYSTOSPAZ Tablets--One or two tablets four times daily or
fewer if needed. CYSTOSPAZ-M Capsules--One capsule every twelve
hours.
Children (12 and under): Reduce dosage in proportion to age and weight.
HOW SUPPLIED
CYSTOSPAZ Tablets-- Bottles of 100 light blue tablets. Tablets are
imprinted with a "W 2225". CYSTOSPAZ-M Capsules--Bottles of 100 light
blue timed-release capsules. Capsules are identified with "W 2260" printed in
black.
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