What are NSAIDs contraindicated with? Navigating Drug Interactions and Health Risks

October 14, 2025 •

4 min read

Over 111 million people in the U.S. take prescription nonsteroidal anti-inflammatory drugs (NSAIDs) annually, but they are not safe for everyone. This guide explains what are NSAIDs contraindicated with, detailing potential health risks and dangerous drug interactions that require careful consideration.

Quick Summary

NSAIDs are contraindicated in various medical conditions like severe heart failure, advanced kidney disease, and active gastrointestinal bleeding. They also interact dangerously with blood thinners, methotrexate, and certain blood pressure medications, increasing the risk of serious complications.

Key Points

Heart Failure: NSAIDs cause fluid retention and increase blood pressure, which can worsen heart failure and raise the risk of heart attacks and stroke.
Kidney Disease: By inhibiting renal prostaglandins, NSAIDs can severely restrict blood flow to the kidneys, potentially causing acute kidney injury or accelerating existing kidney disease.
Gastrointestinal Bleeding: A history of peptic ulcers or active bleeding is a major contraindication, as NSAIDs can irritate the stomach lining and cause or worsen dangerous GI bleeding.
Anticoagulant Therapy: The combination of NSAIDs and blood thinners significantly increases the risk of severe and potentially fatal bleeding, particularly in the gastrointestinal tract.
Late-Stage Pregnancy: Use of NSAIDs from 20 weeks of gestation onwards is strongly discouraged by the FDA due to the risk of fetal kidney problems and low amniotic fluid.
Methotrexate Interaction: Concomitant use with low-dose methotrexate can inhibit its excretion, leading to toxic levels and serious adverse events like liver or kidney damage.
Prior to Surgery: NSAIDs are typically stopped several days before elective surgery to reduce the risk of excessive bleeding during and after the procedure.

Nonsteroidal anti-inflammatory drugs (NSAIDs) are a class of medications commonly used for pain relief, reducing inflammation, and lowering fever. However, they are associated with notable risks and have specific contraindications for individuals with certain health conditions or those taking particular medications. Recognizing these contraindications is vital to avoid severe, potentially life-threatening adverse effects. NSAIDs primarily work by inhibiting cyclooxygenase (COX) enzymes, which can impact various systems in the body, including the cardiovascular, renal, and gastrointestinal.

Medical Conditions as Contraindications

NSAIDs should be avoided in patients with certain medical conditions to prevent worsening existing issues or causing significant harm.

Cardiovascular Disease

Patients with heart conditions such as severe heart failure, coronary artery disease, or a history of heart attack or stroke face an elevated risk of cardiovascular events when using NSAIDs. NSAIDs can lead to sodium and fluid retention, raising blood pressure and increasing the workload on the heart, potentially exacerbating heart failure. They are also contraindicated after coronary artery bypass graft (CABG) surgery.

Renal (Kidney) Disease

Individuals with pre-existing or advanced chronic kidney disease should generally not use NSAIDs. NSAIDs interfere with prostaglandins that maintain kidney blood flow, and this can significantly reduce flow in those with impaired kidney function, potentially leading to acute kidney injury or accelerating chronic kidney disease.

Gastrointestinal Issues

NSAIDs are known to cause gastrointestinal (GI) problems, from mild irritation to serious complications like peptic ulcers and bleeding. Individuals with a history of ulcers, active GI bleeding, or inflammatory bowel diseases like Crohn's or ulcerative colitis should avoid NSAIDs as they can trigger or worsen these conditions.

Dangerous Drug-Drug Interactions

Combining NSAIDs with certain medications can result in dangerous interactions.

Blood Thinners (Anticoagulants and Antiplatelets)

This is a critical interaction. NSAIDs have mild blood-thinning properties, and when combined with prescription blood thinners such as warfarin, apixaban, or clopidogrel, the risk of serious bleeding, especially in the GI tract, is significantly increased. Research shows a doubled bleeding risk when these medications are combined with NSAIDs.

Methotrexate

Using NSAIDs concurrently with low-dose methotrexate, used for autoimmune conditions, has been linked to increased methotrexate toxicity. NSAIDs can reduce the kidneys' ability to excrete methotrexate, leading to a dangerous buildup in the body and potential liver or kidney damage.

Blood Pressure Medications

NSAIDs can decrease the effectiveness of blood pressure medications, including ACE inhibitors and ARBs. They also increase the risk of kidney damage when combined with these drugs and diuretics. The combination of an NSAID, a diuretic, and an ACE inhibitor or ARB is a known risk factor for kidney problems.

Other Significant Interactions

Corticosteroids: Increased risk of GI ulcers and bleeding when combined with NSAIDs.
SSRIs and SNRIs: Elevated bleeding risk when combined with certain antidepressants.
Lithium: NSAIDs can increase lithium levels in the body, potentially leading to toxicity.

Special Patient Populations and Circumstances

Certain groups and situations require avoiding or using extreme caution with NSAIDs.

Pregnancy

NSAIDs are generally not advised during pregnancy, and the FDA recommends avoiding them from 20 weeks onward. This is due to potential kidney problems in the fetus, leading to low amniotic fluid. In the third trimester (after 30 weeks), there's a risk of premature closure of the fetal ductus arteriosus.

Older Adults

Adults aged 65 and over have a higher risk of serious NSAID side effects, such as GI bleeding, kidney damage, and heart issues. Due to changes in the body with age and the likelihood of other health conditions, they should use the lowest effective dose for the shortest time or consider alternatives.

Before and After Surgery

Patients are typically instructed to stop taking NSAIDs several days before surgery, especially procedures with a high bleeding risk. The antiplatelet effect can increase bleeding during and after the operation. There is also a risk of infection and complications with wound healing after surgery with some NSAID use.

Comparison of Contraindications


Condition / Drug	Primary Mechanism of Harm	Resulting Complication
Severe Heart Failure	Sodium and fluid retention; increased blood pressure	Worsened heart failure; higher risk of MI and stroke
Advanced Kidney Disease	Inhibited renal prostaglandins reducing blood flow to kidneys	Acute kidney injury; accelerated CKD progression
Active GI Ulcers/Bleeding	Gastric mucosa irritation; COX-1 inhibition	Exacerbated bleeding; perforation
Anticoagulants	Additive antiplatelet effects; increased bleeding risk	Severe gastrointestinal bleeding
Methotrexate	Reduced renal clearance of methotrexate	Methotrexate toxicity; liver/kidney damage
Late-Stage Pregnancy	Fetal renal dysfunction; premature ductus arteriosus closure	Low amniotic fluid; neonatal renal impairment

Conclusion

The potential harms associated with NSAIDs, affecting major organ systems and interacting with numerous medications, highlight the necessity of careful consideration before use. Despite their over-the-counter availability, NSAIDs are not universally safe. Individuals with existing heart, kidney, or gastrointestinal conditions, or those taking medications affecting blood clotting or excretion, often have contraindications for NSAID use. It is crucial to consult a healthcare provider for a personalized risk assessment before starting any NSAID, particularly for high-risk individuals like older adults and pregnant women. Understanding these restrictions is key for patient safety and effective pain management. Further information on the risks of NSAID use during pregnancy can be found on the FDA website.

Frequently Asked Questions

You should consult a healthcare professional before taking an NSAID if you have high blood pressure (hypertension). Many NSAIDs can raise blood pressure and may interfere with the effectiveness of your blood pressure medications, especially diuretics and ACE inhibitors.

The FDA recommends avoiding NSAID use at 20 weeks of pregnancy or later due to the risk of causing kidney problems in the unborn baby, which can lead to low amniotic fluid. Additionally, after 30 weeks, NSAIDs can cause premature closure of the ductus arteriosus in the fetus, leading to heart complications.

Acetaminophen (Tylenol) is generally a safer alternative for pain and fever relief for many people who cannot take NSAIDs due to heart, kidney, or bleeding risks. Topical NSAID gels or non-drug options like physical therapy might also be considered. Always consult your doctor for a personalized recommendation.

No, combining NSAIDs with blood thinners (anticoagulants or antiplatelets) is very dangerous and significantly increases the risk of serious bleeding. This combination should be avoided completely unless specifically directed by a medical professional under close supervision.

Yes, it is standard practice to stop taking NSAIDs before surgery to reduce the risk of bleeding. The exact timeframe varies depending on the specific NSAID and type of surgery, so you must follow your surgeon's specific instructions.

NSAIDs can damage the kidneys by inhibiting the production of protective prostaglandins, which help maintain proper blood flow to the kidneys. This can reduce kidney function and, in at-risk individuals, lead to acute kidney injury.

Older adults (over 65) are at a higher risk for serious NSAID side effects, including GI bleeding, kidney damage, and cardiovascular issues. While not always a total contraindication, caution is advised, and use should be limited to the lowest effective dose for the shortest duration possible under a doctor's supervision.