US Pharm. 2013;38(2):9-15.
Millions of people have heard the message that a daily aspirin can help prevent heart attack and stroke.1 They may decide to self-medicate without first consulting a physician or other health care professional. However, the labels of nonprescription aspirin products do not mention these uses. What is behind this seeming discrepancy? The answer lies in the FDA and its role of protecting public health.
The FDA’s Patient Brochure
The FDA has published an explanatory brochure entitled, “Aspirin for Reducing Your Risk of Heart Attack and Stroke: Know the Facts.”2 The brochure explains daily aspirin use to patients. Although it is intended for patient use, a careful examination of its contents can guide pharmacists in counseling patients about daily aspirin use.
In the brochure, the FDA explored its rationale for advising against unsupervised aspirin use.2 The agency discusses the paradoxical situation in the United States wherein pharmacologically active and potentially dangerous medications such as aspirin are available in any retail location that wishes to sell them. The FDA then stresses that aspirin retains its dangers despite its nonprescription status.
Next, the FDA explains clearly that aspirin has two types of uses.2 First, it is marketed with full FDA approval as an analgesic/antipyretic for headache, pain, swelling, and/or fever. The exhaustive nature of the labeled directions for these approved uses allows patients to use aspirin safely and effectively for these indications. However, the FDA points out that using aspirin to prevent myocardial infarction (MI) or ischemic stroke is not an indication for which dosing appears on the label. Therefore, patients cannot use aspirin in an informed manner for those uses and must seek further advice from a health care professional before purchase.
What Does the FDA Suggest?
The FDA brochure contains an interesting twist. First, it instructs the consumer who wishes to use aspirin for prevention of heart attack or stroke to use it only as directed on the label, which does not speak to MI or stroke. The FDA brochure contains the following language: “Since you don’t have the labeling directions to help you, you need the medical knowledge of your doctor, nurse practitioner, or other health professional.”2 Although the FDA did not further clarify this rather vague wording, it appears to grant legitimacy to the role of the pharmacist in counseling on unlabeled uses of aspirin.
How Does the FDA Describe the Benefit-Risk Question?
The FDA provides consumers with a clear explanation of the manner in which prescribers must weigh the benefit to use of a medication against its potential risk when they ponder which drug to prescribe for a patient. The agency then applies this approach to aspirin, explaining that patients who may experience benefit to aspirin use are those who have such problems as cardiac or vessel disease, or those with evidence of compromised cerebral blood flow. The agency then stresses that aspirin is a drug and, as such, carries a risk of adverse effects and drug interactions.
The FDA introduces some ambiguities in a section on following directions. The brochure advises: “Once your doctor decides that daily use of aspirin is for you, safe use depends on following your doctor’s directions.” This section clearly reinforces the physician as the health care professional to direct the patient. However, in an explanatory subpara-graph, the FDA again says, “You may rely on your health professional to provide the correct information on dose and directions for use.”2
Professional Aspirin Dosing Information
In a Final Rule published by the FDA in the Federal Register on October 23, 1998, the FDA presented required aspirin labeling written for health care professionals (not for the general public).3 The labeling includes sections on clinical pharmacology, pharmacokinetics, clinical studies, animal toxicology, indications and usage, contra-indications, warnings, precautions, adverse reactions, drug abuse and dependence, overdosage, dosage, and administration. Pharmacists should peruse the document to be prepared when patients ask about aspirin. Some relevant sections are discussed below.
Dosage: Patients should take the aspirin with a full glass of water unless they are fluid restricted. For ischemic stroke and transient ischemic attack (TIA), the FDA recommends a dosage of 50 to 325 mg once daily, continued for an indefinite period. For prevention of recurrent MI, the dosage is 75 to 325 mg once daily, continued indefinitely.3
Precautions: The following precautions are listed by the FDA3:
1) Avoid recommending aspirin for patients with severe renal failure (glomerular filtration rate [GFR] <10 mL/min).
2) Avoid recommending aspirin for patients with severe hepatic insufficiency.
3) Patients with sodium-retaining conditions (e.g., congestive heart failure, renal failure) are often placed on sodium-restricted diets and must avoid high-sodium buffered aspirin products.
4) Aspirin can elevate hepatic enzymes, blood urea nitrogen, and serum creatinine. It can cause hyperkalemia, proteinuria, and prolonged bleeding time.
Drug Interactions: Aspirin may decrease the effect of angiotensin-converting enzyme (ACE) inhibitors, diuretics, beta-blockers, and uricosurics (probenecid and sulfinpyrazone); increase the toxicity of acetazolamide and methotrexate; prolong prothrombin time and bleeding time in patients taking warfarin; increase the anticoagulant activity of heparin; lower phenytoin blood levels; raise valproic acid serum levels; and increase the efficacy of oral hypo-glycemics to the point that the patient may experience hypoglycemia. If given concurrently with other nonsteroidal anti-inflammatory drugs (NSAIDs), aspirin can increase bleeding or reduce renal function.3
Contraindications: Aspirin is contraindicated in patients with known allergy to NSAIDs and in patients with asthma, rhinitis, and nasal polyps. It may cause anaphylaxis, laryngeal edema, severe urticaria, angioedema, or bronchospasm (asthma). All salicylate products also carry the traditional Reye’s syndrome warning to prevent use in children or teenagers who have any viral infection, with or without fever.3
Pregnancy and Nursing: Pharmacists should not recommend the use of aspirin in patients who are pregnant or nursing. Aspirin can cause alterations in maternal and neonatal homeostasis, decreased birth weight, and increased risk of perinatal mortality. Used during the last 3 weeks of pregnancy, it can lead to closure of the ductus arteriosus. If taken during the week prior to delivery, it can result in excessive blood loss during childbirth. Aspirin-induced prostaglandin inhibition can also prolong gestation and labor. When aspirin passes into breast milk, it can cause bleeding, rash, and platelet abnormalities in the infant.3
Warnings/Adverse Reactions: Aspirin can cause stomach pain, heartburn, nausea, vomiting, and ulceration, perforation, and gross gastrointestinal (GI) bleeding. Dyspepsia is common, but pharmacists should urge patients to immediately report manifestations of ulceration or bleeding. Patients with a history of active peptic ulcer disease should avoid aspirin. Aspirin may also cause hypoglycemia (or hyperglycemia) in children.3
Overdosage: Patients may administer an accidental or intentional acute overdose or experience chronic intoxication with aspirin. Early signs include tinnitus. However, if the patient has preexisting high-frequency hearing loss, tinnitus may not be perceptible and cannot be used as a reliable indicator of salicylism. Should a patient complain of tinnitus, the pharmacist should advise discontinuing aspirin.3
Aspirin and the Aging Brain
In October 2012, the National Institutes of Health (NIH) publicized a surprising new finding regarding aspirin.4 Investigators administered aspirin in doses of 75 to 160 mg daily to approximately 700 Swedish females aged 70 to 92 years. The majority of the subjects had preexisting heart disease, heightening their risk for heart attack or stroke. A total of 66 subjects completed the 5-year study. At the end of the study period, researchers administered tests of memory and verbal fluency, as well as other tests of mental capability. While many subjects demonstrated a natural age-related decline in their test results, those taking aspirin for 5 years or even a shorter period of time had less mental loss than subjects who never took aspirin and also did better than those who took other NSAIDs. Subjects who completed the entire 5-year regimen also tended to exhibit an actual improvement in their scores from baseline. The findings prompted one physician quoted by the NIH to state, “I have recommended 81 mg of baby aspirin for my patients with any vascular risk factors who are either at risk for developing cognitive decline or who currently have mild cognitive impairment or mild-to-moderate Alzheimer’s disease.”4
Aspirin and Recurrent Blood Clots
In November 2012, the NIH publicized the results of another aspirin study, this one involving venous thromboembolism (VTE).5 The purpose was to explore the usefulness of aspirin in preventing further deadly blood clots in the legs and lungs after patients are weaned from warfarin. Subjects were over 800 patients with a history of VTE of uncertain cause, half given low-dose aspirin (100 mg/day) and half given placebo. There was a trend demonstrating the utility of aspirin in preventing a recurrent VTE, but it was not statistically significant. However, the researchers then took the unusual step of combining the results of their study with an earlier 2012 study. After they explored the result of the combined studies, aspirin was found to confer a 30% reduction in risk of recurrent VTE. The NIH quoted a cardiologist, who stated that “the study was positive enough that physicians should consider adding aspirin when stopping warfarin in patients who are reasonable candidates for long-term aspirin.”
Is Aspirin Really a Drug?
People often believe that OTC drugs, herbals, dietary supplements, and homeopathics are far safer than prescription medications, since they can be purchased in any retail store. Although OTC drugs are easier to obtain, they still have dangers associated with them, and certain patients should not take them at all. This is the great challenge with nonprescription products. While the label provides a good deal of critical information about their use, a vast majority of people never read the labels at all. For this reason, you should always purchase these products from a pharmacist who can advise you on their use. Aspirin, in particular, is a potent and powerful drug, and it must only be taken under medical advice.
Speak to Your Physician First
It can be dangerous to start aspirin therapy without first checking with your physician. The labels of aspirin products in the United States will not have directions on them to allow you to safely take aspirin for prevention of heart attack or stroke. It is best to obtain complete use directions from your physician.
Further, aspirin can interact with other medications you are taking and cause serious medical problems. When you speak to your physician about future aspirin use, bring a complete list of all medications you are currently taking. This includes prescription and nonprescription drugs, as well as herbal products and dietary supplements. You should also provide the following:
1) A medical history (e.g., asthma, atopic dermatitis) for you and your family members
2) Whether you have been diagnosed with heart or circulatory disease
3) Any allergies or sensitivities, especially to aspirin or other analgesics
4) Adverse reactions you have experienced in the past from taking aspirin or other analgesics
5) Your daily alcohol intake.
Other Precautions in Aspirin Use
You should be aware of other aspirin label warnings. For instance, children and teenagers taking aspirin for chickenpox or flu may develop Reye’s syndrome, which can be a deadly illness. Further, those who drink 3 or more alcoholic beverages daily can experience severe stomach problems if they take aspirin. Patients with stomach problems (e.g., heartburn, upset stomach, stomach pain) that will not go away or comes and goes should not use aspirin without speaking to a physician. The same applies to patients with bleeding problems, ulcers, and asthma.
If you are pregnant or breast-feeding, it is important to speak to your physician before using aspirin, as it can be dangerous. Taking aspirin during the last 3 months of pregnancy can cause serious problems for the fetus. Taking aspirin shortly before delivery can cause bleeding problems for the mother and baby. If you are breastfeeding, you should not take aspirin, as it can cause problems for the baby if the drug gets into the breast milk.
Remember, if you have questions, Consult Your Pharmacist.
1. Pray WS. Nonprescription Product Therapeutics. 2nd ed. Baltimore, MD: Lippincott Williams & Wilkins; 2006.
2. Aspirin for reducing your risk of heart attack and stroke: know the facts. FDA. www.fda.gov/Drugs/ResourcesForYou/Consumers/BuyingUsingMedicineSafely/UnderstandingOver-the-CounterMedicines/SafeDailyUseofAspirin/ucm291433.htm. Accessed December 29, 2012.
3. Internal analgesic, antipyretic, and antirheumatic drug products for over-the-counter human use; final rule for professional labeling of aspirin, buffered aspirin, and aspirin in combination with antacid drug products. Fed Regist. 1998;63:56802-56817.
4. Daily aspirin may bolster aging brain, study shows. MedlinePlus. October 26, 2012. www.nlm.nih.gov/medlineplus/news/fullstory_130710.html. Accessed December 29, 2012.
5. Daily aspirin may help those at risk for recurrent blood clots. MedlinePlus. November 5, 2012. www.nlm.nih.gov/medlineplus/news/fullstory_131006.html. Accessed December 29, 2012.
6. Information for healthcare professionals: concomitant use of ibuprofen and aspirin. FDA. www.fda.gov/Drugs/DrugSafety/PostmarketDrugSafetyInformationforPatientsandProviders/ucm125222.htm. Accessed December 29, 2012.
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