aSPIRIN

Therapeutic uses

Headache

Aspirin is one of the first-line drugs used in the treatment of migraine, bringing relief in 50–60% of the cases.

It is as effective as a newer triptan medication sumatriptan (Imitrex)[27] and other painkillers such as paracetamol (acetaminophen)
[28]
or ibuprofen.[29] The combination of aspirin, paracetamol (acetaminophen) and caffeine (Excedrin) is even more potent. For
the treatment of migraine headache, this formulation works better than any of its three components taken separately, [28] better than
ibuprofen[30] and better than sumatriptan. Similarly to all other medications for migraine, it is recommended to take aspirin at the
first signs of the headache, and it is the way these medications were used in the comparative clinical trials. [31]

Aspirin alleviates pain in 60-75% of patients with episodic tension headaches.[32][33] It is equivalent to paracetamol
(acetaminophen) in that respect, except for the higher frequency of gastrointestinal side effects. [33] Comparative clinical trials
indicated that metamizole and ibuprofen may relieve pain faster than aspirin, although the difference becomes insignificant after
about 2 hours. The addition of Caffeine in a dose of 60 – 130 mg to aspirin increases the analgesic effect in headache. [32][34] The
combination of aspirin, paracetamol (acetaminophen) and caffeine (Excedrin) is still more effective, but at the cost of more
stomach discomfort, nervousness and dizziness.[35]

Pain

In general, aspirin works well for dull, throbbing pain; it is ineffective for pain caused by most muscle cramps, bloating, gastric
distension and acute skin irritation.[36] The most studied example is pain after surgery such as tooth extraction, for which the
highest allowed dose of aspirin (1 g) is equivalent to 1 g of paracetamol (acetaminophen), 60 mg of codeine and 5 mg of
oxycodone. Combination of aspirin and caffeine, generally, affords greater pain relief than aspirin alone. Effervescent aspirin
alleviates pain much faster than aspirin in tablets (15-30 min vs. 45-60 min). [37]

Nevertheless, as a post-surgery painkiller, aspirin is inferior to ibuprofen. Aspirin has higher gastrointestinal toxicity than
ibuprofen. The maximum dose of aspirin (1 g) provides weaker pain relief than an intermediate dose of ibuprofen (400 mg), and
this relief does not last as long.[37] A combination of aspirin and codeine may have a slightly higher analgesic effect than aspirin
alone; however, this difference is not clinically meaningful. [38] It appears that ibuprofen is at least equally, and possibly more,
effective than this combination.[39]

According to a meta-analysis of clinical trials for menstrual pain, aspirin demonstrated higher efficacy than placebo but lower
one than ibuprofen or naproxen, although maximum doses of aspirin were never used in these trials. The authors concluded that
ibuprofen has the best risk-benefit ratio.[40]

Aspirin did not ease pain during cycling exercise, [41] while caffeine, surprisingly, was very effective. [42][43] Similarly, aspirin,
codeine or paracetamol (acetaminophen) were not better than placebo for muscle soreness after exercise. [44]

Coronary and carotid arteries, bypasses and stents

The coronary arteries supply blood to the heart. Aspirin is recommended for 1 to 6 months after placement of stents in the
coronary arteries and for years after a coronary artery bypass graft.

The carotid arteries supply blood to the brain. Patients with mild carotid artery stenosis benefit from aspirin. Aspirin is
recommended after a carotid endarterectomy or carotid artery stent.

After vascular surgery of the lower legs using artificial grafts which are sutured to the arteries to improve blood supply, aspirin is
used to keep the grafts open.
Other uses

Although aspirin has been used to combat fever and pains associated with common cold for more than 100 years, only recently its
efficacy was confirmed in controlled clinical trials on adults. 1 g of aspirin, on average, reduced the oral body temperature from
39.0 °C (102.2 °F) to 37.6 °C (99.7 °F) after 3 hours. The relief began after 30 minutes, and after 6 hours the temperature still
remained below 37.8 °C (100.0 °F). Aspirin also helped with "achiness", discomfort and headache, [49] and with sore throat pain,
for those who had it.[50] Aspirin was indistinguishable from paracetamol (acetaminophen) in any respect, except for, possibly,
slightly higher rate of sweating and gastrointestinal side effects. [49]

Fever and joint pain of acute rheumatic fever respond extremely well, often within three days, to high doses of aspirin. The
therapy usually lasts for 1–2 weeks; and only in about 5% of the cases it has to continue for longer than six months. After fever
and pain have subsided, the aspirin treatment is unnecessary as it does not decrease the incidence of heart complications and
residual rheumatic heart disease.[51] In addition, the high doses of aspirin used cause liver toxicity in about 20% of the treated
children,[52][53] who are the majority of rheumatic fever patients, and increase the risk of them developing Reye's syndrome.[51]
Naproxen was shown to be as effective as aspirin and less toxic; however, due to the limited clinical experience, naproxen is
recommended only as a second-line treatment. [51][54]

Along with rheumatic fever, Kawasaki disease remains one of the few indications for aspirin use in children, although even this
use has been questioned by some authors.[55] In the United Kingdom, the only indications for aspirin use in children and
adolescents under 16 are Kawasaki disease and prevention of blood clot formation.

Aspirin is also used in the treatment of pericarditis, coronary artery disease, and acute myocardial infarction.[56][57][58]

Experimental

Aspirin has been theorized to reduce cataract formation in diabetic patients, but one study showed it was ineffective for this
purpose.[59] The role of aspirin in reducing the incidence of many forms of cancer has also been widely studied. In several studies,
aspirin use did not reduce the incidence of prostate cancer.[60][61] Its effects on the incidence of pancreatic cancer are mixed; one
study published in 2004 found a statistically significant increase in the risk of pancreatic cancer among women, [62] while a meta-
analysis of several studies, published in 2006, found no evidence that aspirin or other NSAIDs are associated with an increased
risk for the disease.[63] The drug may be effective in reduction of risk of various cancers, including those of the colon,[64][65][66][67]
lung,[68][69] and possibly the upper GI tract, though some evidence of its effectiveness in preventing cancer of the upper GI tract
has been inconclusive.[70][70][71] Its preventative effect against adenocarcinomas may be explained by its inhibition of PTGS2
(COX-2) enzymes expressed in them.[72]

In a 2009 article published by the Journal of Clinical Investigation, it was found that aspirin might prevent liver damage. In their
experiment, scientists from Yale University and The University of Iowa induced damage in certain liver cells called hepatocytes
using excessive doses of acetaminophen. This caused hepatoxicity and hepatocyte death which triggered an increase in the
production of TLR9. The expression of TLR9 caused an inflammatory cascade involving pro–IL-1β and pro-IL-18. Aspirin was
found to have a protective effect on hepatocytes because it led to the "downregulation of proinflammatory cytokines". [73]

In another 2009 article published by the Journal of the American Medical Association, it was found that men and women who
regularly took aspirin after colorectal cancer diagnosis had lower risk of overall and colorectal cancer death compared to patients
not using aspirin.[74][75]

A 2010 article in the Journal of Clinical Oncology has suggested that aspirin may reduce the risk of death from breast cancer [76].
While the information has been well-circulated by the media [77][78], official health bodies and medical groups have expressed
concern over the touting of aspirin as "miracle drug" [79].

Contraindications and resistance

Aspirin should not be taken by people who are allergic to ibuprofen or naproxen,[80][81] or who have salicylate intolerance[82][83] or a
more generalized drug intolerance to NSAIDs, and caution should be exercised in those with asthma or NSAID-precipitated
bronchospasm. Owing to its effect on the stomach lining, manufacturers recommend that people with peptic ulcers, mild diabetes,
or gastritis seek medical advice before using aspirin.[80][84] Even if none of these conditions are present, there is still an increased
risk of stomach bleeding when aspirin is taken with alcohol or warfarin.[80][81] Patients with hemophilia or other bleeding
tendencies should not take aspirin or other salicylates. [80][84] Aspirin is known to cause hemolytic anemia in people who have the
genetic disease glucose-6-phosphate dehydrogenase deficiency (G6PD), particularly in large doses and depending on the severity
of the disease.[85][86] Use of aspirin during dengue fever is not recommended owing to increased bleeding tendency. [87] People with
kidney disease, hyperuricemia, or gout should not take aspirin because aspirin inhibits the kidneys' ability to excrete uric acid and
thus may exacerbate these conditions. Aspirin should not be given to children or adolescents to control cold or influenza
symptoms as this has been linked with Reye's syndrome.[4]

For some people, aspirin does not have as strong an effect on platelets as for others, an effect known as aspirin resistance or
insensitivity. One study has suggested that women are more likely to be resistant than men [88] and a different, aggregate study of
2,930 patients found 28% to be resistant.[89] A study in 100 Italian patients found that of the apparent 31% aspirin resistant
subjects, only 5% were truly resistant, and the others were noncompliant.[90]

Dosage
Coated 325 mg aspirin tablets

For adults doses are generally taken four times a day for fever or arthritis, [100] with doses near the maximal daily dose used
historically for the treatment of rheumatic fever. [101] For the prevention of myocardial infarction in someone with documented or
suspected coronary artery disease, much lower doses are taken once daily. [100]

New recommendations from the US Preventive Services Task Force (USPSTF, March, 2009) on the use of aspirin for the
primary prevention of coronary heart disease encourage men aged 45–79 and women aged 55–79 to use aspirin when the
potential benefit of a reduction in myocardial infarction (MI) for men or stroke for women outweighs the potential harm of an
increase in gastrointestinal hemorrhage. Regular low dose (75 to 81 mg) aspirin users had a 25% lower risk of death from
cardiovascular disease and a 14% lower risk of death from any cause. Low dose aspirin use was also associated with a trend
toward lower risk of cardiovascular events, and lower aspirin doses (75 to 81 mg/day) may optimize efficacy and safety for
patients requiring aspirin for long-term prevention.[102]

In children with Kawasaki disease, aspirin is taken at dosages based on body weight, initially four times a day for up to two
weeks and then at a lower dose once daily for a further six to eight weeks. [103]

Overdose
Main article: Aspirin poisoning

Aspirin overdose can be acute or chronic. In acute poisoning, a single large dose is taken; in chronic poisoning, higher than
normal doses are taken over a period of time. Acute overdose has a mortality rate of 2%. Chronic overdose is more commonly
lethal with a mortality rate of 25%; chronic overdose may be especially severe in children. [104] Toxicity is managed with a number
of potential treatments including: activated charcoal, intravenous dextrose and normal saline, sodium bicarbonate, and dialysis.
[105]

Uses of This Medicine:

Aspirin, sodium bicarbonate, and citric acid combination is used to relieve pain occurring together with heartburn, sour stomach,
or acid indigestion.

The aspirin in this combination is the pain reliever. Aspirin belongs to the group of medicines known as salicylates and to the
group of medicines known as anti-inflammatory analgesics. The sodium bicarbonate in this medicine is an antacid. It neutralizes
stomach acid by combining with it to form a new substance that is not an acid.

Aspirin, sodium bicarbonate, and citric acid combination may also be used to lessen the chance of heart attack, stroke, or other
problems that may occur when a blood vessel is blocked by blood clots. The aspirin in this medicine helps prevent dangerous
blood clots from forming. However, this effect of aspirin may increase the chance of serious bleeding in some people. Therefore,
aspirin should be used for this purpose only when your doctor decides, after studying your medical condition and history, that the
danger of blood clots is greater than the risk of bleeding. Do not take aspirin to prevent blood clots or a heart attack unless it has
been ordered by your doctor.

This combination medicine is available without a prescription.

Older adults—
People 60 years of age and older are especially sensitive to the effects of aspirin. This may increase the chance of side effects
during treatment. Also, the sodium in this combination medicine can be harmful to some elderly people, especially if large
amounts of the medicine are taken regularly. Therefore, it is best that older people not use this medicine for more than 5 days in a
row, unless otherwise directed by their doctor.

Dosing—

The dose of this medicine will be different for different patients. Follow your doctor's orders or the directions on the label. The
following information includes only the average doses of this medicine. If your dose is different, do not change it unless your
doctor tells you to do so.

The amount of medicine that you take depends on the strength of the medicine. Also, the number of doses you take each day, the
time allowed between doses, and the length of time you take the medicine depend on the medical problem for which you are
using the medicine.

 For oral dosage forms (effervescent tablets):

o For pain and upset stomach:
 Adults and teenagers—One or two regular-strength (325-milligram [mg]) tablets every four to six
hours as needed, one extra-strength (500-mg) tablet every four to six hours as needed, or two extra-
strength (500-mg) tablets every six hours as needed, dissolved in water. Elderly people should not
take more than four regular-strength or extra-strength tablets a day. Other adults and teenagers
should not take more than 6 regular-strength flavored tablets, 8 regular-strength unflavored tablets,
or 7 extra-strength tablets a day.
 Children—The dose depends on the child's age.
 Children younger than 3 years of age: Use and dose must be determined by your doctor.
 Children 3 to 5 years of age: One-half of a regular-strength (325-mg) tablet, dissolved in
water, every four to six hours as needed.
 Children 6 to 12 years of age: One regular-strength (325-mg) tablet, dissolved in water,
every four to six hours as needed.
o For reducing the chance of heart attack, stroke, or other problems that may occur when a blood vessel is
blocked by blood clots:
 Adults—One regular-strength (325-mg) tablet a day, dissolved in water.
 Children and teenagers—Use and dose must be determined by your doctor.

Side Effects of This Medicine:

Any loss of hearing
bloody urine
confusion
convulsions (seizures)
diarrhea (severe or continuing)
difficulty in swallowing
dizziness, lightheadedness, or feeling faint (severe)
drowsiness (severe)
excitement or nervousness (severe)
fast or deep breathing
flushing, redness, or other change in skin color
hallucinations (seeing, hearing, or feeling things that are not there)
nausea or vomiting (severe or continuing)
shortness of breath, troubled breathing, tightness in chest, or wheezing
stomach pain (severe or continuing)
swelling of eyelids, face, or lips
unexplained fever
uncontrollable flapping movements of the hands (especially in elderly patients)
vision problems
Signs of overdose in children
Changes in behavior
drowsiness or tiredness (severe)
fast or deep breathing
Less common or rare
Bloody or black, tarry stools
frequent urge to urinate
headache (severe or continuing)
increased blood pressure
loss of appetite (continuing)
mood or mental changes
muscle pain or twitching
ringing or buzzing in ears (continuing)
skin rash, hives, or itching
slow breathing
swelling of face, fingers, ankles, feet, or lower legs
unpleasant taste
unusual tiredness or weakness
vomiting of blood or material that looks like coffee grounds
weight gain (unusual)

Some side effects may occur that usually do not need medical attention. These side effects may go away during treatment as your
body adjusts to the medicine. Also, your health care professional may be able to tell you about ways to prevent or reduce some of
these side effects. Check with your health care professional if any of the following side effects continue or are bothersome or if
you have any questions about them:

Heartburn or indigestion
increased thirst
nausea or vomiting
stomach pain (mild)

Other side effects not listed may also occur in some patients. If you notice any other effects, check with your healthcare
professional.

Call your doctor for medical advice about side effects. You may report side effects to the FDA at 1-800-FDA-1088.