ASPIRIN
DESCRIPTION:
PAIN RELIEVER
FOR ASPIRIN THERAPY USERS
INDICATIONS AND USAGE:
For the temporary relief of minor aches and pains associated with headaches,
muscle aches, toothaches, and menstrual cramps. ASPIRIN enteric also
provides relief from the minor aches and pains of arthritis.
PROFESSIONAL LABELING
ASPIRIN FOR RECURRENT TIA'S IN MEN
For reducing the risk of recurrent transient ischemic attacks (TIA's) or stroke
in men who have had transient ischemia of the brain due to fibrin platelet
emboli. There is inadequate evidence that aspirin or buffered aspirin is
effective in reducing TIA's in women at the recommended dosage. There is no
evidence that aspirin or buffered aspirin is of benefit in the treatment of
completed strokes in men or women.
ASPIRIN FOR MYOCARDIAL INFARCTION
Recurrent Myocardial Infarction (MI) (Reinfarction) Or Unstable Angina Pectoris
Aspirin is indicated to reduce the risk of death and/or nonfatal MI in patients
with a previous MI or unstable angina pectoris.
Suspected Acute MI
Aspirin is indicated to reduce the risk of vascular mortality in patients with a
suspected acute MI.
DOSAGE AND ADMINISTRATION:
REGULAR STRENGTH ASPIRIN
DIRECTIONS: ADULTS: Two tablets every four hours while symptoms persist, not to
exceed 12 tablets in 24 hours, or as directed by a doctor. CHILDREN UNDER 12
YEARS OF AGE: Consult a doctor. Drink a full glass of water with each dose.
ADULT LOW STRENGTH ASPIRIN ENTERIC
DIRECTIONS: ADULTS: 4-8 tablets every four hours while symptoms persist, not to
exceed 48 tablets in 24 hours, or as directed by a doctor. CHILDREN UNDER 12
YEARS OF AGE: Consult a doctor. Drink a full glass of water with each dose.
ASPIRIN FOR RECURRENT TIA'S IN MEN
Adult dosage for men is 1300 mg a day, in divided doses of 650 mg twice a day or
325 mg four times a day.
Recurrent MI (Reinfarction) And Unstable Angina Pectoris
Although most of the studies used dosages exceeding 300 milligrams, two trials
used only 300 milligrams, and pharmacologic data indicate that this dose
inhibits platelet function fully. Therefore, 300 milligrams or a conventional
325 milligram aspirin dose is a reasonable, routine dose that would minimize
gastrointestinal adverse reactions. This use of aspirin applies to both solid,
oral dosage forms (buffered and plain aspirin) and buffered aspirin in solution.
Suspected Acute MI
The recommended dose of aspirin to treat suspected acute MI is 160 to 162.5
milligrams taken as soon as the infarct is suspected and then daily for at least
30 days. (One-half of a conventional 325-milligram aspirin tablet or two 80- or
81-milligram aspirin tablets may be taken.) This use of aspirin applies to both
solid, oral dosage forms (buffered, plain, and enteric-coated aspirin) and
buffered aspirin in solution. If using a solid dosage form, the first dose
should be crushed, sucked or chewed. After the 30-day treatment, physicians
should consider further therapy based on the labeling for dosage and
administration of aspirin for prevention of recurrent MI (reinfarction).
WARNINGS:
CHILDREN AND TEENAGERS SHOULD NOT USE THIS MEDICINE FOR CHICKEN POX OR FLU
SYMPTOMS BEFORE A DOCTOR IS CONSULTED ABOUT REYE'S SYNDROME, A RARE BUT SERIOUS
ILLNESS REPORTED TO BE ASSOCIATED WITH ASPIRIN. KEEP THIS AND ALL DRUGS OUT OF
THE REACH OF CHILDREN. Do not take this product for pain for more than 10 days
or for fever for more than 3 days unless directed by a doctor. If pain or fever
persists or gets worse, if new symptoms occur, or if redness or swelling is
present, consult a doctor because these could be signs of a serious condition.
Do not take this product if you are allergic to aspirin or if you have asthma
unless directed by a doctor. Do not take this product if you have stomach
problems (such as heartburn, upset stomach, or stomach pain) that persist or
recur, or if you have ulcers or bleeding problems, unless directed by a doctor.
As with any drug, if you are pregnant or nursing a baby, seek the advice of a
health professional before using this product. IT IS ESPECIALLY IMPORTANT NOT TO
USE ASPIRIN DURING THE LAST 3 MONTHS OF PREGNANCY UNLESS SPECIFICALLY DIRECTED
TO DO SO BY A DOCTOR BECAUSE IT MAY CAUSE PROBLEMS IN THE UNBORN CHILD OR
COMPLICATIONS DURING DELIVERY. If ringing in the ears or loss of hearing occurs,
consult a doctor before taking any more of this product. IN CASE OF ACCIDENTAL
OVERDOSE, SEEK PROFESSIONAL ASSISTANCE OR CONTACT A POISON CONTROL CENTER
IMMEDIATELY.
DRUG INTERACTION PRECAUTION: Do not use if taking a prescription drug for
anticoagulation (blood thinning), diabetes, gout, or arthritis unless directed
by a doctor.
ALCOHOL WARNING: If you generally consume 3 or more alcohol-containing drinks
per day, you should consult your physician for advice on when and how you should
take ASPIRIN and other pain relievers.
IMPORTANT: See your doctor before taking this product for your heart or for
other new uses of aspirin, because serious side effects could occur with self
treatment.
DRUG INTERACTIONS:
DRUG INTERACTION PRECAUTION: Do not use if taking a prescription drug for
anticoagulation (blood thinning), diabetes, gout, or arthritis unless directed
by a doctor.
(See Also WARNINGS.)
CLINICAL STUDIES:
ASPIRIN FOR RECURRENT TIA'S IN MEN
CLINICAL TRIALS: The indication is supported by the results of a Canadian study
(REF. 1) in which 585 patients with threatened stroke were followed in a
randomized clinical trial for an average of 26 months to determine whether
aspirin or sulfinpyrazone, singly or in combination, was superior to placebo in
preventing transient ischemic attacks, stroke, or death. The study showed that,
although sulfinpyrazone had no statistically significant effect, aspirin reduced
the risk of continuing transient ischemic attacks, stroke, or death by 19
percent and reduced the risk of stroke or death by 31 percent. Another aspirin
study carried out in the United States with 178 patients showed a statistically
significant number of "favorable outcomes" including reduced transient ischemic
attacks, stroke, and death (REF. 2).
Recurrent MI (Reinfarction) And Unstable Angina Pectoris
CLINICAL TRIALS:
Recurrent MI (Reinfarction) And Unstable Angina Pectoris
The indication is supported by the results of six large, randomized multicenter,
placebo-controlled studies involving 10,816, predominantly male, post-MI
subjects and one randomized placebo- controlled study of 1,266 men with unstable
angina (REFS. 1-7). Therapy with aspirin was begun at intervals after the onset
of acute MI varying from less than 3 days to more than 5 years and continued for
periods of from less than 1 year to 4 years. In the unstable angina study,
treatment was started within 1 month after the onset of unstable angina and
continued for 12 weeks, and patients with complicating conditions such as
congestive heart failure were not included in the study.
Aspirin therapy in MI subjects was associated with about a 20-percent reduction
in the risk of subsequent death and/or nonfatal reinfarction, a median absolute
decrease of 3 percent from the 12- to 22-percent event rates in the placebo
groups. In aspirin-treated unstable angina patients the reduction in risk was
about 50 percent, a reduction in the event rate of 5-percent from the 10-percent
rate in the placebo group over the 12-weeks of the study.
Daily dosage of aspirin in the post-MI studies was 300 milligrams in one study
and 900 to 1,500 milligrams in five studies. A dose of 325 milligrams was used
in the study of unstable angina.
Suspected Acute MI
The use of aspirin in patients with a suspected acute MI is supported by the
results of a large, multicenter 2 X 2 factorial study of 17,187 subjects with
suspected acute MI (REF. 8). Subjects were randomized within 24 hours of the
onset of symptoms so that 8,587 subjects received oral aspirin (162.5
milligrams, enteric-coated) daily for 1 month (the first dose crushed, sucked,
or chewed) and 8,600 received oral placebo. Of the subjects, 8,592 were also
randomized to receive a single dose of streptokinase (1.5 million units) infused
intravenously for about 1 hour, and 8,595 received a placebo infusion. Thus,
4,295 subjects received aspirin plus placebo, 4,300 received streptokinase plus
placebo, 4,292 received aspirin plus streptokinase, and 4,300 received double
placebo.
Vascular mortality (attributed to cardiac, cerebral, hemorrhagic, other
vascular, or unknown causes) occurred in 9.4 percent of the subjects in the
aspirin group and in 11.8 percent of the subjects in the oral placebo group in
the 35-day followup. This represents an absolute reduction of 2.4 percent in the
mean 35-day vascular mortality attributable to aspirin and a 23-percent
reduction in the odds of vascular death (2p < 0.00001).
Significant absolute reductions in mortality and corresponding reductions in
specific clinical events favoring aspirin were found for reinfarction (1.5
percent absolute reduction, 45 percent odds reduction, 2p < 0.00001), cardiac
arrest (1.2 percent absolute reduction, 14.2 percent odds reduction,
2p < 0.01), and total stroke (0.4 percent absolute reduction, 41.5 percent odds
reduction, 2p < 0.01). The effect of aspirin over and above its effect on
mortality was evidenced by small, but significant, reductions in vascular
morbidity in those subjects who were discharged.
The beneficial effects of aspirin on mortality were present with or without
streptokinase infusion. Aspirin reduced vascular mortality from 10.4 to 8.0
percent for days 0 to 35 in subjects given streptokinase and reduced vascular
mortality from 13.2 to 10.7 percent in subjects given no streptokinase.
The effects of aspirin and thrombolytic therapy with streptokinase in this study
were approximately additive. Subjects who received the combination of
streptokinase infusion and daily aspirin had significantly lower vascular
mortality at 35 days than those who received either active treatment alone
(combination 8.0 percent, aspirin 10.7 percent, streptokinase 10.4 percent, and
no treatment 13.2 percent). While this study demonstrated that aspirin has an
additive benefit in patients given streptokinase, there is no reason to restrict
its use to that specific thrombolytic.
PRECAUTIONS:
ASPIRIN FOR RECURRENT TIA'S IN MEN
(1) Patients presenting with signs and symptoms of TIA's should have a complete
medical and neurologic evaluation. Consideration should be given to other
disorders which resemble TIA's. (2) Attention should be given to risk factors;
it is important to evaluate and treat, if appropriate, other diseases associated
with TIA's and stroke such as hypertension and diabetes. (3) Concurrent
administration of absorbable antacids at therapeutic doses may increase the
clearance of salicylates in some individuals. The concurrent administration of
nonabsorbable antacids may alter the rate of absorption of aspirin, thereby
resulting in a decreased acetylsalicylic acid/salicylate ratio in plasma. The
clinical significance on TIA's of these decreases in available aspirin is
unknown.
Aspirin at dosages of 1,000 milligrams per day has been associated with small
increases in blood pressure, blood urea nitrogen, and serum uric acid levels. It
is recommended that patients placed on long-term aspirin treatment be seen at
regular intervals to assess changes in these measurements.
ADVERSE REACTIONS:
At dosages of 1,000 milligrams or higher of aspirin per day, gastrointestinal
side effects include stomach pain, heartburn, nausea and/or vomiting, as well as
increased rates of gross gastrointestinal bleeding.
Gastrointestinal Reactions
Doses of 1,000 milligrams per day of aspirin caused gastrointestinal symptoms
and bleeding that in some cases were clinically significant. In the Aspirin
Myocardial Infarction Study (AMIS) (REF. 4) with 4,500 post-infarction subjects,
the percentage incidences of gastrointestinal symptoms for the aspirin (1,000
milligrams of a standard, solid-tablet formulation) and placebo- treated
subjects, respectively, were: stomach pain (14.5 percent, 4.4 percent);
heartburn (11.9 percent, 4.8 percent); nausea and/or vomiting (7.6 percent, 2.1
percent); hospitalization for gastrointestinal disorder (4.8 percent, 3.5
percent). Symptoms and signs of gastrointestinal irritation were not
significantly increased in subjects treated for unstable angina with 325
milligrams buffered aspirin in solution.
Bleeding
In the AMIS and other trials, aspirin-treated subjects had increased rates of
gross gastrointestinal bleeding. In the ISIS-2 study (REF. 8), there was no
significant difference in the incidence of major bleeding (bleeds requiring
transfusion) between 8,587 subjects taking 162.5 milligrams aspirin daily and
8,600 subjects taking placebo (31 versus 33 subjects). There were five confirmed
cerebral hemorrhages in the aspirin group compared with two in the placebo
group, but the incidence of stroke of all causes was significantly reduced from
81 to 47 for the placebo versus aspirin group (0.4 percent absolute change).
There was a small and statistically significant excess (0.6 percent) of minor
bleeding in people taking aspirin (2.5 percent for aspirin, 1.9 percent for
placebo). No other significant adverse effects were reported.
Cardiovascular And Biochemical
In the AMIS trial (REF. 4), the dosage of 1,000 milligrams per day of aspirin
was associated with small increases in systolic blood pressure (BP) (average 1.5
to 2.1 millimeters Hg) and diastolic BP (0.5 to 0.6 millimeters Hg), depending
upon whether maximal or last available readings were used. Blood urea nitrogen
and uric acid levels were also increased, but by less than 1.0 milligram
percent.
Subjects with marked hypertension or renal insufficiency had been excluded from
the trial so that the clinical importance of these observations for such
subjects or for any subjects treated over more prolonged periods is not known.
It is recommended that patients placed on long-term aspirin treatment, even at
doses of 160 milligrams per day, be seen at regular intervals to assess changes
in these measurements.
REFERENCES:
ASPIRIN FOR RECURRENT TIA'S IN MEN
(1) The Canadian Cooperative Study Group, "A Randomized Trial of Aspirin and
Sulfinpyrazone in Threatened Stroke," New England Journal Of Medicine, 299:53-
59, 1978.
(2) Fields, W.S., et al., "Controlled Trial of Aspirin in Cerebral Ischemia,"
Stroke, 8:301-316, 1977.
Recurrent MI (Reinfarction) And Unstable Angina Pectoris
(1) Elwood, P. C. et al., "A Randomized Controlled Trial of Acetylsalicylic Acid
in the Secondary Prevention of Mortality from Myocardial Infarction," British
Medical Journal, 1:436-440, 1974.
(2) The Coronary Drug Project Research Group, "Aspirin in Coronary Heart
Disease," Journal Of Chronic Diseases, 29:625-642, 1976.
(3) Breddin, K. et al., "Secondary Prevention of Myocardial Infarction: A
Comparison of Acetylsalicylic Acid, Phenprocoumon or Placebo," Homeostasis,
470:263-268, 1979.
(4) Aspirin Myocardial Infarction Study Research Group, "A Randomized,
Controlled Trial of Aspirin in Persons Recovered from Myocardial Infarction."
Journal Of The American Medical Association, 243:661-669, 1980.
(5) Elwood, P. C., and P. M. Sweetnam, "Aspirin and Secondary Mortality After
Myocardial Infarction," Lancet, II:1313-1315, December 22-29, 1979.
(6) The Persantine-Aspirin Reinfarction Study Research Group, "Persantine and
Aspirin in Coronary Heart Disease," Circulation, 62:449-461, 1980.
(7) Lewis, H. D. et al., "Protective Effects of Aspirin Against Acute Myocardial
Infarction and Death in Men with Unstable Angina, Results of a Veterans
Administration Cooperative Study," New England Journal Of Medicine, 309:396-403,
1983.
(8) ISIS-2 (Second International Study of Infarct Survival) Collaborative Group,
"Randomized Trial of Intravenous Streptokinase, Oral Aspirin, Both, or Neither
Among 17,187 Cases of Suspected Acute Myocardial Infarction: ISIS-2," Lancet,
2:349-360, August 13, 1988.
(9) "1984 Report of the Joint National Committee on Detection, Evaluation, and
Treatment of High Blood Pressure," United States Department of Health and Human
Services and United States Public Health Service, National Institutes of Health,
Publication No. NIH 84-1088, 1984.
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