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?Cardiovascular system – Blood pressure may rise with use of NSAIDs. Control of treated hypertension may be adversely affected by the addition of either selective or nonselective NSAIDs.?Gastrointestinal system – Short-term use of NSAIDs can cause stomach upset (dyspepsia). Long-term use of NSAIDs, especially at high doses, can lead to peptic ulcer disease and bleeding from the stomach.

(See ‘Ulcer disease’ below.)?Liver toxicity – Long-term use of NSAIDs, especially at high doses, can rarely harm the liver. Monitoring the liver function with blood tests may be recommended in some cases.?Kidney toxicity – Use of NSAIDs, even for a short period of time, can harm the kidneys. This is especially true in people with underlying kidney disease. The blood pressure and kidney function should be monitored at least once per year but may need to be checked more often, depending on a person’s medical conditions. (See ‘Kidney disease’ below.

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)?Ringing in the ears – Ringing in the ears (tinnitus) is common in people who take high doses of aspirin, although it is very uncommon for this to occur in people who take other NSAIDs. The ringing usually resolves when the dose is decreased.MEDICAL CONDITIONS AND NONSTEROIDAL ANTIINFLAMMATORY DRUGSPeople with some medical problems and those taking various medications are at increased risk of complications related to NSAIDs. Potential complications of NSAIDs include the following:Hypertension — As noted above, the addition of either a selective or a nonselective NSAID to the medications taken by someone with hypertension can result in a loss of blood pressure control. If NSAIDs are required, they should be used at the lowest effective dose and for the shortest duration necessary for the given indication.

If chronic use of NSAIDs is anticipated, changes in blood pressure medications may be required.Cardiovascular disease — Anyone who is at risk for or who has cardiovascular disease (coronary artery disease) may have a further increase in risk of heart attacks when taking an NSAID. This includes people who have experienced a heart attack, angina (chest pain due to narrowed arteries in the heart), procedures to widen clogged arteries, a stroke, or narrowed arteries to the brain.

As a result, people who have or who are at high risk for coronary artery disease are generally advised to avoid NSAIDs or, if that is not possible, to take the lowest possible dose of NSAID for the shortest possible time.Although aspirin is an NSAID, the recommendation to avoid or limit the use of NSAIDs does NOT apply to people who have been advised to take low-dose aspirin to treat or prevent heart attacks or strokes. However, the use of any dose of aspirin plus an NSAID is associated with an increased risk of bleeding. There is also an increased risk of bleeding when NSAIDs are used in patients taking other drugs that reduce clotting, such as anticoagulants (eg, warfarin) or antiplatelet agents (eg, clopidogrel).

There is also some concern that nonselective NSAIDs may reduce the cardiovascular benefits of low-dose aspirin. (See ‘Interaction with other medications’ below.)Ulcer disease — Those who have had a stomach or intestinal ulcer are at an increased risk of another ulcer while taking an NSAID. People being treated for ulcers should consult their health care provider about the safety of taking NSAIDs or drugs containing aspirin. People over 65 years of age have an increased risk of developing ulcers when taking NSAIDs. (See “Patient education: Peptic ulcer disease (Beyond the Basics)”.)Reducing ulcer risk — The risk of developing ulcers can be reduced by taking an anti-ulcer medication in addition to an NSAID.

Anti-ulcer agents that reduce gastrointestinal damage from NSAIDs include:?Inhibitor of stomach acid production – High doses of antacid histamine blockers, such as famotidine (Pepcid), and ordinary doses of the acid production inhibitors, such as omeprazole (Prilosec) or lansoprazole (Prevacid), can reduce the risk of developing an ulcer (related to use of an NSAID).Bleeding — People who have had bleeding from the stomach, upper intestine, or esophagus have an increased risk of recurrent bleeding when taking NSAIDs.People with platelet disorders such as von Willebrand disease, abnormal platelet function from uremia, and a low platelet count (thrombocytopenia) are advised to avoid NSAIDs.Before surgery — Most clinicians recommend stopping all NSAIDs approximately one week before elective surgery to decrease the risk of excessive bleeding.

This usually includes aspirin, ibuprofen, naproxen, and most prescription NSAIDs. Specific instructions regarding NSAIDs and surgery should be discussed with the surgeon and with the clinician who prescribed the NSAID.Interaction with other medications?Warfarin and heparin – People using anticoagulant medications such as warfarin (brand names: Coumadin, Jantoven) and heparin; a newer anticoagulant such as dabigatran (brand name: Pradaxa), rivaroxaban (brand name: Xarelto), apixaban (brand name: Eliquis) or edoxaban (brand name: Savaysa); or an anti-platelet drug such as clopidogrel (brand name: Plavix), should generally not take NSAIDs or aspirin because of an increased risk of bleeding when both classes of drugs are used. (See “Patient education: Warfarin (Coumadin) (Beyond the Basics)”.

)Celecoxib may be safe in such instances but should be used with caution and under the guidance of a clinician.?Aspirin – As noted above, the combination of low-dose aspirin and an NSAID may increase the risk of bleeding. To preserve the benefit of low-dose aspirin for the heart, aspirin should be taken at least two hours before the NSAID.?Phenytoin – Taking an NSAID and phenytoin (Dilantin, Phenytek) can increase the phenytoin level. As a result, people who take phenytoin should have a blood test to monitor the phenytoin level when starting or increasing the dose of an NSAID.

?Cyclosporine – People who take cyclosporine (eg, to prevent rejection after an organ transplant or for a rheumatic disease, such as rheumatoid arthritis) should take particular care when taking an NSAID. There is a theoretical risk of kidney damage when cyclosporine and NSAIDs are taken together. To monitor for this complication, blood testing may be recommended.?People taking one NSAID should not take a second NSAID at the same time because of the increased risk of side effects.Fluid retention — People with medical conditions that require diuretics, including heart failure, liver disease, and kidney damage, are at increased risk of developing kidney damage while taking nonselective NSAIDs (eg, ibuprofen) as well as selective NSAIDs (eg, celecoxib Celebrex).


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