Does CBD interact with aspirin and other antiplatelets, and if so, how? Is it safe to take with aspirin or other antiplatelets?
- Aspirin can help some people lower their risk of a heart attack or stroke. However, the antiplatelet can also cause severe bleeding, according to an article published by the University of Michigan Health System (UMHS)(1).
- Data from a 2012 study published in the British Journal of Clinical Pharmacology showed that CBD influenced platelet formation, which could support the ability of CBD to delay or prevent the development of cardiovascular disorders(2).
- However, CBD can inhibit the cytochrome P450 (CYP450) system’s ability to metabolize certain drugs, leading to an overall increase in processing times(3).
- In a study published by the American Society for Clinical Pharmacology and Therapeutics, researchers found that the effects of low-dose aspirin administration on CYP450 in healthy human subjects are enzyme-specific, meaning the effects depend on which type of enzymes(4).
- Given that the specific effects of combining CBD with aspirin have not been established in any longitudinal scientific study conducted on humans, using the two substances together is not recommended.
- Consulting with a trusted medical practitioner experienced with cannabis use is the best course of action for anyone looking to try CBD for the first time or include CBD in their current regimen.
Can CBD Be Taken with Aspirin?
The cytochrome P450 enzyme system, which is found within the liver, is responsible for metabolizing (breaking down) potentially toxic compounds, including over 60% percent of any drugs consumed(5).
Certain substances can affect processing times within this system, making drugs metabolize faster or slower than they would on their own.
Cannabidiol can inhibit the cytochrome P450 system’s ability to metabolize certain drugs, leading to an overall increase in processing times(6).
In a study published by the American Society for Clinical Pharmacology and Therapeutics, researchers illustrated the effect of low-dose aspirin administration on the activity of cytochrome P450 (CYP) in healthy human subjects(7).
Researchers of the said study found that the effects of aspirin on the CYP450 system of enzymes depend on the specific type of enzyme under the CYP450 family of enzymes.
Given that the specific effects of combining CBD with aspirin have not been established in any scientific study, using the two substances together is not recommended.
Can Another Antiplatelet Be a Substitute for Aspirin So CBD Oil Can Be Taken?
Ticlopidine (marketed as Ticlid), an effective inhibitor of platelet formation, is indicated for patients who cannot take aspirin or in whom aspirin has not worked to prevent a thrombotic stroke(8).
A thrombotic stroke is one that is caused by thrombosis, the formation or presence of a blood clot within a blood vessel.
However, ticlopidine inhibits multiple CYP450 types of enzymes, as data from a study published in the British Journal of Clinical Pharmacology showed(9).
According to the research findings, the plasma concentrations and/or toxicity of drugs whose elimination pathways involve the different types of CYP450 enzymes increased when ticlopidine is concomitantly administered.
Thus, ticlopidine may also interact with CBD in the same way that aspirin does.
Given that the specific effects of combining CBD with aspirin have not been established with scientific evidence, using ticlopidine is also not recommended to use with CBD.
It is interesting to note, however, that bleeding time was significantly prolonged by aspirin alone and by ticlopidine alone.
However, the most significant prolongation was produced by aspirin plus ticlopidine, according to results of a study published by the American Heart Association(10).
The results of the study also demonstrated that the combination of aspirin and ticlopidine is a potent antiplatelet strategy.
Can CBD replace Aspirin?
There is no scientific data to establish CBD as a treatment option in the same way that people use aspirin. The two drugs may interact with the heart in different ways.
An article on aspirin risks and benefits by Mark Fendrick, M.D., published by the University of Michigan Institute for Healthcare Policy and Innovation.
In the said article, Fendrick says that aspirin interferes with the blood’s clotting action and reduces the clumping action of platelets, possibly preventing a heart attack(11).
Still, he cautions that it is not advisable to take aspirin tablets, hoping to prevent a heart attack, without a doctor’s supervision.
Is CBD a safer alternative to aspirin in preventing heart attack?
Data from a 2012 study published in the British Journal of Clinical Pharmacology showed that CBD influenced platelet formation, which could support the ability of CBD to delay or prevent the development of cardiovascular disorders(12).
However, the study was done on animal subjects. Whether the responses to CBD would translate into the human cardiovascular system remains to be established.
In another study, which was first published by JCI Insight in 2017, results showed that CBD could lower blood pressure, which could help prevent hypertensive heart disease(13).
The study was done on healthy volunteers, however. The researchers noted that further research is required to establish whether CBD has a role in the treatment of cardiovascular disorders.
New Guidelines for Aspirin Use
According to an October 2019 article published by the American College of Physicians, recent research based on a 2017 National Health Interview Survey has found that, in certain groups of people, there are few advantages and a higher risk of bleeding from daily aspirin use(14).
In response to the results of the survey, the American Heart Association and American College of Cardiology updated their guidelines in March of 2019.
The two agencies no longer recommend aspirin for the prevention of cardiovascular disease in adults aged 70 and above or for those with a higher risk of bleeding, like those with stomach (peptic) ulcers.
Thus, medical experts advise that people speak with their health care providers before taking aspirin daily.
Two Types of Blood Thinners: Which Type is Aspirin?
There are two primary types of blood thinners. Anticoagulants, like heparin or warfarin (Coumadin), slow down the aggregation or formation of clots.
On the other hand, antiplatelet drugs, like aspirin, inhibit blood cells (platelets) from clumping together to form a clot(15).
Aspirin as Nonsteroidal Anti-Inflammatory Drug (NSAID)
Nonsteroidal anti-inflammatory drugs (NSAIDs) reduce fever and inflammation and relieve pain. Examples of NSAIDs include aspirin, ibuprofen, and naproxen.
Aspirin, unlike other NSAIDs, can help certain people lower their risk of a heart attack or stroke. However, taking aspirin is not recommended for everyone as the antiplatelet can cause severe bleeding, according to an article published by the University of Michigan Health System (UMHS)(16).
The article says that people who are over 65 years old or who have existing kidney, heart, liver, stomach, or intestinal disease are at increased risk for complications.
How NSAIDs Work
NSAIDs work by blocking enzymes called COX-1 and COX-2. These enzymes produce prostaglandins, a group of compounds made by the cells in the body(17).
Prostaglandins made by COX-1 enzymes actuate platelets and protect the lining of stomach and intestines. Prostaglandins produced by COX-2 enzymes are generated in response to injury or infection, controlling inflammation.
Most NSAIDs work non-selectively on both enzymes. However, this lack of selectivity becomes an issue given that pain and inflammation relief from NSAIDs come from blocking COX-2. When COX-1 is also blocked, unwanted adverse side effects emerge.
Aspirin, an NSAID, functions by blocking the production of prostaglandins, the on-off switch in cells that control pain and inflammation. Thus, aspirin prevents mild inflammation and pain(18).
“To the consumer, aspirin is almost a miracle drug,” says Nimita Thekkepat, assistant professor of pharmacy at St. Louis College of Pharmacy. “It helps inflammation, fever, and it can save your life from a heart attack.”
However, while aspirin blocks the type of prostaglandins that trigger pain or lead to clotting and narrowing of the blood vessels and inflammation, the drug also blocks a different kind of prostaglandins that protect the stomach lining.
Aspirin belongs to a group of nonsteroidal anti-inflammatory drugs, or NSAIDs, that include ibuprofen (Motrin, Advil), naproxen (Aleve) and ketoprofen (Orudis).
Among these NSAIDs, aspirin induces the most irritation and the most toxic (painkiller) to the stomach, says Dr Richard Brasington, head of the Division of Rheumatology at Washington University School of Medicine.
Medical experts, like Brasington, warn against taking a variety of nonsteroidal anti-inflammatory drugs at the same time as they neutralize each other, making neither drugs perform well. The remedy is to wait several hours after taking one medicine before taking the next.
Blood Thinners and NSAIDs, A Bad Mix
NSAIDs impact the way platelets work and could impede with healthy blood clotting, which could increase the risk of bleeding, especially in the digestive tract, says cardiologist Dr Deepak L. Bhatt, a Harvard Medical School professor, in an article published by Harvard Health(19).
Bhatt also adds that taking NSAIDs together with blood thinners raises the bleeding risk even more.
Medical marijuana, sometimes referred to as medical cannabis, is a term for derivatives of the Cannabis sativa plant(20).
CBD (cannabidiol) and THC (tetrahydrocannabinol) are common cannabinoids that are natural constituents of cannabis plants, which include marijuana and hemp. Thus, CBD can either be a hemp or cannabis extract.
Marijuana contains much more THC than hemp, while hemp contains excellent quantities of CBD. THC induces a euphoric high, while CBD helps promote relaxation and calmness.
In a study published in the Cerebrum Journal, researchers explained that the endocannabinoid system (ECS), which is comprised of cannabinoid receptors, endocannabinoid molecules, and their metabolic enzymes, is crucial in maintaining homeostasis, or balance, amongst physiological functions(21).
CBD Oil or Hemp Oil?
The term “hemp oil” is sometimes used to refer to the CBD-rich product extracted from the hemp plant’s flowers and leaves, which is essentially CBD oil. However, the term is also used to refer to hemp seed oil that contains no CBD.
Although hemp seed oil is not CBD oil, which is extracted from the flowers and leaves of the plant, note that oil pressed from hemp seed does not contain CBD, THC, and plant cannabinoids(22).
CBD oil is available in different varieties, such as full-spectrum (oil derived from the whole plant), THC-free distillate, and CBD isolates.
Cannabis and Aspirin
In a 2013 study published in the Rambam Maimonides Medical Journal, it was shown that the ECS is involved in numerous body functions, including the modulation of pain and inflammation(23).
In a 2008 study published in the Journal of Therapeutics and Clinical Risk Management, author Ethan Russo found that Tetrahydrocannabinol (THC) has twenty times the anti-inflammatory potency of aspirin(24).
Results from his research also suggest that cannflavin A, a flavone unique to cannabis, inhibits PGE-2 thirty times more potently than aspirin, although further examinations are needed(25).
PGE-2 (Prostaglandin E2) is a bioactive lipid that elicits a wide range of biological effects associated with cancer and inflammation(26).
Flavones are a sub-group of flavonoids shown to exhibit anti-inflammatory, antidiabetic, anticancer, anti-thrombogenic (prevents blood clot), and neuroprotective activities through different mechanisms of action outside a living organism and in animal models(27).
Cannabidiol and CYP2D6
Cannabidiol, a major phytocannabinoid, is a potent atypical inhibitor for CYP2D6, according to a study published in the Drug Metabolism and Disposition Journal(28).
Phytocannabinoids are cannabinoids that occur naturally in the cannabis plant. Cannabinoids are closely-related compounds naturally found in cannabis, like CBD and THC.
In the said study, the researchers investigated the inhibitory impacts of the primary phytocannabinoids on the activity of human CYP2D6. The results indicated that CBD caused directly blocked CYP2D6 potency.
Drug to Drug Interactions
In a 2016 study published in the Epilepsia Journal, the authors found that repeated administration of CBD may induce CYP2B enzymes in animal subjects, which may have implications for people with epilepsy as antiepileptic drugs (AEDs), such as valproate and clobazam, are metabolized via these enzymes(29).
Still, the antiepileptic mechanisms of CBD have not been known. The researchers noted that there is a lack of data from longitudinal double-blind, randomized, controlled studies on the efficacy of pure CBD for any disorder.
Recently, the U.S. Food and Drug Administration (FDA) approved Epidiolex as the first-ever cannabis-derived medicine for Lennox-Gastaut Syndrome (LGS) and Dravet Syndrome (DS), the symptoms of which do not typically respond to anti-seizure medications(30).
While CBD is the active ingredient in Epidiolex, it also contains inactive ingredients that include dehydrated alcohol, sesame seed oil, strawberry flavor, and sucralose(31).
Aspirin and Beta Blockers
Aspirin blunts the vasodilation (widening of blood vessels) caused by both angiotensin-converting enzyme (ACE) inhibitors and beta blockers in hypertensive patients and in patients with heart failure. This conclusion was derived from a study that was published in the Journal of the American College of Cardiology(32).
The specific mechanisms that cause this interaction are unknown, and further studies are needed. Until conclusive evidence is available, it is not advisable to use aspirin in conjunction with beta blockers.
Aspirin and Warfarin
A 2017 study published in the Cannabis and Cannabinoid Research Journal analyzed CBD safety and side effects(33).
Researchers of the said study noted that while CBD can raise the levels of concentration of certain medications in the blood, its adverse side effects can sometimes outweigh the advantages.
Based on the results of the study, the authors indicated that CBD could cause a surge in the level of the anticoagulant (blood thinner), warfarin (Coumadin), by accentuating aspirin’s blood-thinning property.
Aspirin is part of a group of painkillers and fever reducers called non-steroidal anti-inflammatory drugs (NSAIDs).
Meanwhile, CBD’s broad utility for pain relief may be partly explained by its anti-inflammatory effects.
Still, despite CBD’s potential therapeutic benefits, taking it together with aspirin is not recommended. Neither is it advised to use CBD products in any form (tincture, vape, or topical) with other antiplatelet prescription drugs.Although using aspirin and CBD may each have its advantages, it also comes with risks. As studies mentioned above demonstrate, the risks may outweigh the health benefits.
Healthwise. (2019, March 28). Nonsteroidal Anti-Inflammatory Drugs (NSAIDs). Retrieved from https://www.uofmhealth.org/health-library/sid7998.
Stanley CP, Hind WH, O’Sullivan SE. Is the cardiovascular system a therapeutic target for cannabidiol?. Br J Clin Pharmacol. 2013;75(2):313–322. doi:10.1111/j.1365-2125.2012.04351.x.
CBDOilReview.org. Drugs that May Interact with CBD Oil. Retrieved from https://cbdoilreview.org/cbd-cannabidiol/cbd-p-450-enzyme.
Chen XP, Tan ZR, Huang SL, Huang Z, Ou-Yang DS, Zhou HH. Isozyme-specific induction of low-dose aspirin on cytochrome P450 in healthy subjects. Clin Pharmacol Ther. 2003 Mar;73(3):264-71.
Project CBD. (2015, Sept. 8). CBD-Drug Interactions: Role of Cytochrome P450. Retrieved from https://www.projectcbd.org/medicine/cbd-drug-interactions/p450.
CBDOilReview.org. Op. cit.
Chen XP et al. op. cit.
Drugbank.ca, a project supported by the Canadian Institutes of Health Research. (2020, Feb 16). Retrieved from https://www.drugbank.ca/drugs/DB00208.
Ko JW, Desta Z, Soukhova NV, Tracy T, Flockhart DA. In vitro inhibition of the cytochrome P450 (CYP450) system by the antiplatelet drug ticlopidine: potent effect on CYP2C19 and CYP2D6. Br J Clin Pharmacol. 2000;49(4):343–351. doi:10.1046/j.1365-2125.2000.00175.x.
S Uchiyama, R Sone, T Nagayama, Y Shibagaki, I Kobayashi, S Maruyama, and K Kusakabe. Combination therapy with low-dose aspirin and ticlopidine in cerebral ischemia.
Mark Fendrick, M.D. (2018, March 15). An aspirin a day, or not? Understanding the risks & benefits. Retrieved from https://ihpi.umich.edu/news/aspirin-day-or-not-understanding-risks-benefits.
Stanley CP, Hind WH, O’Sullivan SE. Is the cardiovascular system a therapeutic target for cannabidiol?. Br J Clin Pharmacol. 2013;75(2):313–322. doi:10.1111/j.1365-2125.2012.04351.x.
Khalid A. Jadoon, Garry D. Tan, and Saoirse E. O’Sullivan. A single dose of cannabidiol reduces blood pressure in healthy volunteers in a randomized crossover study. JCI Insight. 2017;2(11):e93760. https://doi.org/10.1172/jci.insight.93760. Retrieved from https://insight.jci.org/articles/view/93760#FN.
Colin W. O’Brien, MD; Stephen P. Juraschek, MD, PhD; Christina C. Wee, MD, MPH. (2019, October 15). Prevalence of Aspirin Use for Primary Prevention of Cardiovascular Disease in the United States: Results From the 2017 National Health Interview Survey. Retrieved from https://annals.org/aim/article-abstract/2738925/prevalence-aspirin-use-primary-prevention-cardiovascular-disease-united-states-results.
(2015, April 2). Blood Thinners, Also called: Anti-platelet drugs, Anticoagulants. Medline Plus. Retrieved from https://medlineplus.gov/bloodthinners.html.
Healthwise. (2019, March 28). Nonsteroidal Anti-Inflammatory Drugs (NSAIDs). Retrieved from https://www.uofmhealth.org/health-library/sid7998.
Bonni Goldstein, MD On August 15, 2018 (Updated On May 6, 2019). Trade in Your Ibuprofen for Cannabis. Retrieved from https://www.projectcbd.org/wellness/trade-your-ibuprofen-cannabis.
Harry Jackson Jr. (2007, July 23). St. Louis Post-Dispatch. Retrieved from https://source.wustl.edu/2007/07/aspirin-the-mighty-drug/.
Harvard Health Publishing. Updated: December 16, 2019Published: October, 2013. Bad mix: Blood thinners and NSAIDs. Retrieved from https://www.health.harvard.edu/diseases-and-conditions/bad-mix-blood-thinners-and-nsaids.
Mayo Clinic.(2019, Nov. 27). Medical marijuana. Retrieved from https://www.mayoclinic.org/healthy-lifestyle/consumer-health/in-depth/medical-marijuana/art-20137855.
Alger BE. Getting high on the endocannabinoid system. Cerebrum. 2013;2013:14. Published 2013 Nov 1.
Martin A. Lee. Cannabis Oil vs. Hemp Oil. Retrieved from https://www.projectcbd.org/cbd-101/cannabis-oil-vs-hemp-oil.
Fine PG, Rosenfeld MJ. The endocannabinoid system, cannabinoids, and pain. Rambam Maimonides Med J. 2013;4(4):e0022. Published 2013 Oct 29. doi:10.5041/RMMJ.10129.
Russo EB. Cannabinoids in the management of difficult to treat pain. Ther Clin Risk Manag. 2008;4(1):245–259. doi:10.2147/tcrm.s1928.
Barrett ML, Scutt AM, Evans FJ. Cannflavin A and B, prenylated flavones from Cannabis sativa L. Experientia. 1986;42:452–3. DOI: 10.1007/bf02118655.
Nakanishi M, Rosenberg DW. Multifaceted roles of PGE2 in inflammation and cancer. Semin Immunopathol. 2013;35(2):123–137. doi:10.1007/s00281-012-0342-8.
Jane Higdon, Ph.D. (2005). Flavonoids. Retrieved from https://lpi.oregonstate.edu/mic/dietary-factors/phytochemicals/flavonoids.
Satoshi Yamaori, Yasuka Okamoto, Ikuo Yamamoto and Kazuhito Watanabe. Cannabidiol, a Major Phytocannabinoid, As a Potent Atypical Inhibitor for CYP2D6. Drug Metabolism and Disposition November 2011, 39 (11) 2049-2056; DOI: https://doi.org/10.1124/dmd.111.041384.
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U.S. Food and Drug Administration (FDA). (2018, June 25). FDA approves first drug comprised of an active ingredient derived from marijuana to treat rare, severe forms of epilepsy. Retrieved from https://www.fda.gov/news-events/press-announcements/fda-approves-first-drug-comprised-active-ingredient-derived-marijuana-treat-rare-severe-forms.
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Jadoon KA, Tan GD, O’Sullivan SE. A single dose of cannabidiol reduces blood pressure in healthy volunteers in a randomized crossover study. JCI Insight. 2017;2(12):e93760. Published 2017 Jun 15. doi:10.1172/jci.insight.93760.
A Closer Look at Aspirin
Aspirin is a safe over-the-counter drug that most people have been relying on for years to treat pain, fever, and headache. When administered in low doses, it can also reduce the risks of stroke, heart attack, and pre-eclampsia in pregnant mothers.
Aspirin therapy reduces the clumping action of platelets to help prevent heart attacks. As a blood thinner, aspirin prevents the formation of blood clots, which can quickly form and block the artery. Unfortunately, this blood-thinning property of aspirin is what could also cause an increased risk of bleeding.
CBD and Salicylate
Aspirin and CBD both help treat inflammation. Aspirin is part of a group of painkillers and fever reducers called non-steroidal anti-inflammatory drugs (NSAIDs). Meanwhile, CBD’s broad utility for pain relief may be partly explained by its anti-inflammatory effects.
Lke CBD, aspirin is derived from plant compounds. Salicylate, the active ingredient in aspirin, is salt derived from salicylic acid. Salicylate compounds are naturally present in some plants like white willow bark and wintergreen leaves. These compounds protect the plants are protected against insect damage and disease. Thousands of years ago, the salicylate compounds extracted from willow bark were used as a folk remedy.
Types of Aspirin and Their Uses
Baby Aspirin vs. Adult Aspirin
Low-dose aspirin has an aspirin content of 75 to 150 mg. A single pill of baby aspirin contains 81 milligrams of aspirin. It is called baby aspirin because of the small dose, but it is not safe for children. One should never give aspirin to children younger than 16 unless their doctor prescribes it.
An adult aspirin pill contains a 325-milligram dose. For individuals who have had a heart attack or have had a heart stent placed, it is crucial to take aspirin and other blood-thinning medications exactly as prescribed by a doctor.
Plain or Coated?
Enteric-coated aspirin is formulated to pass through the stomach and not dissolve until it reaches the small intestine. Hence, coated aspirins are gentler on the stomach and are appropriate for people who take aspirin daily, as well as those with a history of gastritis or ulcers. Although coated aspirins do not guarantee a decreased risk of gastrointestinal bleeding, they may be as effective as plain aspirin when taken at the time of a possible heart attack.
Why Some People Take Aspirin Daily
Every day, millions of Americans take aspirin to prevent another heart attack, or what doctors refer to as secondary prevention. Unless there is a particularly valid reason not to take aspirin, individuals with coronary artery disease should take an aspirin every day. Most experts recommend taking a baby aspirin daily for prevention.
To get aspirin into the bloodstream immediately, especially when the clotting process is underway, the patient should chew and swallow an uncoated 325 mg full adult-size tablet as soon as possible.
Meanwhile, if one is taking aspirin and needs to undergo a surgical procedure or dental work, he or she should inform the attending physician about the aspirin dose and frequency of intake. Otherwise, there could be complications that may arise from excessive bleeding during surgery. Also, one must not stop taking prescribed aspirin therapy unless advised by a doctor.
Drug Interactions Between Aspirin and Other Drugs
- Aspirin can severely weaken the body’s ability to prevent the formation of blood clots when taken with anticoagulants (blood thinners), such as warfarin (like Coumadin) or enoxaparin (like Lovenox). This combination of blood thinners and aspirin can result in spontaneous and excessive bleeding. Thus, patients who are taking aspirin while on warfarin or enoxaparin must be carefully managed and observed by a doctor.
- Aspirin can cause a substantial rise in uric acid levels in the blood. Patients who have problems related to increased uric acid levels or gout must refrain from taking aspirin.
- Aspirin may interact with prescription drugs used to lower blood sugar levels in patients with diabetes. The interaction may lead to a severe medical condition called hypoglycemia, which is characterized by an abnormal drop in blood sugar level. Blood sugar levels should be monitored closely.
- Some NSAIDs, such as ibuprofen (like Motrin and Advil), can lower the antiplatelet effects of aspirin if taken immediately before aspirin. In this situation, aspirin becomes less effective.
- Aspirin may cause allergic reactions in some people. Symptoms, such as flushing, hives (itchy rashes), blocked and runny nose, and severe asthma may occur within an hour of taking a tablet. The aspirin allergy of people who have hives, nasal polyps, or asthma is 10 to 30% greater compared to people without these conditions.
More Information on Aspirin and Salicylate Aspirin Use During Pregnancy
- Prospective studies of aspirin use during pregnancy have involved low doses (40-150 mg/day) rather than analgesic doses.
- Large retrospective studies of aspirin use in women during pregnancy have failed to demonstrate a teratogenic effect.
- Aspirin should be avoided during the third trimester due to possible bleeding complications and premature closure of the ductus arteriosus, which may lead to pulmonary vasculature abnormalities and pulmonary hypertension in the newborn.
- In pregnancies at risk for the development of pregnancy-induced hypertension and pre-eclampsia, and in fetuses with intrauterine growth retardation, low-dose aspirin (40-150 mg/day) may be beneficial.
- Use of low dose aspirin may reduce preeclampsia by approximately 25%, but study findings have been inconsistent.
Pregnancy-Induced Hypertension (PIH)
Imperiale and Petrulis performed a meta-analysis of six published, controlled trials (one nonrandomized, two non-placebo, three double-blind) of aspirin in PIH. They evaluated the degree of reduction in the incidence of PIH, the reduction in severe low birth weight infants, and adverse effects of low doses of aspirin during pregnancy. Of 394 women studied the relative risk of pregnancy-induced hypertension in women who took aspirin was found to be 0.35 (95% CI; 0.22-0.55).
Aspirin reduced the risk of severe low birth weight among newborns by 44% (RR 0.56; CI 0.36-0.88), and reduced the risk of caesarean section by 66% (RR 0.34; CI 0.25-0.48) overall, although the specific indications for caesarean section were generally not described. There was no effect on fetal and neonatal mortality and no maternal or neonatal adverse were associated with aspirin use.
In a randomized, double-blind, placebo-controlled trial, Sibai et al studied the effects of a daily aspirin dose of 60 mg on the incidence of pre-eclampsia in 3135 normotensive nulliparous women. Aspirin was started at 13 to 26 weeks gestation for the remainder of pregnancy.
There was no significant difference in birth weight or the incidence of fetal growth retardation, postpartum hemorrhage, or neonatal bleeding problems between groups in the 2985 women followed up. The incidence of pre-eclampsia was reduced in the treatment group (4.6% vs 6.3%), while abruptio placentae (premature separation of placenta from uterus) was increased by aspirin (11/1,570 Vs 2/1,565; p=0.01).
A multicenter study (CLASP) looked at aspirin administration for the prophylaxis of pre-eclampsia, prophylaxis and treatment of intrauterine growth retardation (IUGR), and treatment of pre-eclampsia in 9364 women. Women between 12- and 32-weeks’ gestation were randomly assigned 60 mg aspirin daily or placebo.
Aspirin was associated with a 12% reduction in the incidence of protein uric pre-eclampsia, which was not significant. There were no significant differences in the incidence of IUGR (1.4% with aspirin Vs 1.7% with placebo) or stillbirth and neonatal death (2.7% Vs 2.8%), but the likelihood of preterm delivery was significantly reduced (19.7% Vs 22.2%, p=0.003).
Aspirin was not associated with a significant increase in placental hemorrhage or in bleeding during preparation for epidural anesthesia (0.4% Vs 0.6%), but there was a slight increase in the use of blood transfusion after delivery 4.0% Vs 3.2%). Low-dose aspirin was generally safe for the fetus and newborn infant, with no evidence of an increase in bleeding.
Adverse Effects of Aspirin
Aspirin in therapeutic doses may induce hypersensitivity, asthma, urate kidney stones, chronic gastro-intestinal blood loss, tinnitus, nausea, vomiting, and Reyes syndrome.
Anticoagulants or NSAIDs – increased risk of bleeding
Methotrexate – reduced excretion
Diuretics – antagonism of spironolactone and reduced excretion acetazolamide
Corticosteroids – increased risk GI bleeding/ulceration
Antiepileptics – increased effect of phenytoin and valproate
The pharmacokinetic characteristics of salicylate taken in overdosage have important implications for the genesis and treatment of poisoning.
Salicylates are rapidly and completely absorbed from the jejunum and small bowel when administered in aqueous solutions. However, ingestion of excessive doses does not always occur in the fasting state, so absorption and the attainment of peak plasma salicylate concentrations may be delayed by the presence of food in the stomach and by prolonged gastric emptying.
It has also been suggested that salicylates cause pyloric spasm, thus delaying gastric emptying and absorption, but variability in the rates of disintegration and dissolution of different formulations are probably more important.
About 10 percent of adults who ingest overdoses show a rise in plasma salicylate concentrations after gastric lavage, almost certainly due to flushing salicylate from the stomach into the small bowel thus facilitating absorption.
Absorption of large, potentially lethal doses may be slower than therapeutic doses partly due to the inhibitory effect of aspirin on gastric emptying and the impaired dispersion of the drug in gastrointestinal fluids. In overdose, salicylate levels may rise for 12 hours or more.
When enteric-coated aspirin formulations are taken, the onset of toxic features and the attainment of peak plasma concentrations may be delayed for 12 or more hours.
Salicylates are rapidly hydrolyzed by first pass metabolism in the intestinal mucosa and liver. Acetylsalicylic acid can only be detected in the plasma for a few hours after an overdose while plasma concentrations of salicylic acid, the principal product of hydrolysis, decline slowly with a half-life of the order of 20 to 30 hours.
Kinetics in Children
Neonates absorb salicylate as rapidly as any other age group but metabolize it more slowly than young teenagers because of comparatively immature hepatic function. Renal excretion is also slower and neonates therefore attain higher plasma concentrations. Reduced plasma albumin concentrations in this age group may increase
Kinetics in the Elderly
Absorption of therapeutic doses of salicylate is not impaired in the elderly but the elimination half-life and volume of distribution may be significantly increased. These observations may be explained by impaired hepatic and renal function despite the normal results of conventional laboratory function tests.
Phil Young, BSc (Hons) Msc MRPharmS
National Poisons Information Service (Newcastle Centre)
Regional Drug & Therapeutics Centre
Newcastle upon Tyne
This monograph has been produced by staff of a National Poisons Information Service Centre in the United Kingdom. The work was commissioned and funded by the UK Departments of Health, and was designed as a source of detailed information for use by poisons information centres.
Peer review group: Directors of the UK National Poisons Information Service.